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1.
J Colloid Interface Sci ; 678(Pt A): 703-712, 2025 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-39216397

RESUMO

Monitoring complex human movements requires the simultaneous detection of strain and pressure, which poses a challenge due to the difficulty in integrating high stretchability and compressive ability into a single material. Herein, a series of hyperbranched polysiloxane crosslinkers (HPSis) with self-floating abilities are designed and synthesized. Taking advantage of the self-floating capabilities of HPSis, ionogels with gradient composition distribution and conductivities are constructed by in situ one-step photopolymerization, and possess satisfactory stretchability, high compressibility and excellent resilience. The gradient-ionogel-based strain sensor exhibits extraordinary pressure sensitivity (19.33 kPa-1), high strain sensitivity (GF reaches 2.5) and temperature sensing ability, enabling the monitoring of the angles and direction of joint movements, transmitting Morse code and wirelessly detecting bioelectrical signals. This study may inspire the design of development of multi-function flexible electronics.


Assuntos
Géis , Géis/química , Humanos , Tecnologia sem Fio , Compostos de Organossilício/química , Reagentes de Ligações Cruzadas/química , Dispositivos Eletrônicos Vestíveis , Siloxanas/química , Tamanho da Partícula , Estrutura Molecular , Propriedades de Superfície , Temperatura , Monitorização Fisiológica/instrumentação , Monitorização Fisiológica/métodos
2.
Anal Chem ; 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39484990

RESUMO

Mitochondrial complex activity controls a multitude of physiological processes by regulating the cellular metabolism. Current methods for evaluating mitochondrial complex activity mainly focus on single metabolic reactions within mitochondria. These methods often require fresh samples in large quantities for mitochondria purification or intact mitochondrial membranes for real-time monitoring. Confronting these limitations, we shifted the analytical perspective toward interactive metabolic networks at the whole-cell level to reflect mitochondrial complex activity. To this end, we compiled a panel of mitochondrial respiratory chain-mapped metabolites (MRCMs), whose perturbations theoretically provide an overall reflection on mitochondrial complex activity. By introducing N-dimethyl-p-phenylenediamine and N-methyl-p-phenylenediamine as a pair of mass spectrometry probes, an ultraperformance liquid chromatography-tandem mass spectrometry method with high sensitivity (LLOQ as low as 0.2 fmol) was developed to obtain accurate quantitative data of MRCMs. Machine learning was then combined to capture the relationship between MRCMs and mitochondrial complex activity. Using Complex I as a proof-of-concept, we identified NADH, alanine, and phosphoenolpyruvate as metabolites associated with Complex I activity based on the whole-cell level. The effectiveness of using their concentrations to reflect Complex I activity was further validated in external data sets. Hence, by capturing the relationship between metabolites and mitochondrial complex activity at the whole-cell level, this study explores a novel analytical paradigm for the interrogation of mitochondrial complex activity, offering a favorable complement to existing methods particularly when sample quantities, type, and treatment timeliness pose challenges. More importantly, it shifts the focus from individual metabolic reactions within mitochondria to a more comprehensive view of an interactive metabolic network, which should serve as a promising direction for future research into the functional architecture between mitochondrial complexes and metabolites.

3.
Toxins (Basel) ; 16(10)2024 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-39453226

RESUMO

Recent studies have revealed that the coagulation system plays a role in mammalian innate defense by entrapping bacteria in clots and generating antibacterial peptides. So, it is very important for the survival of bacteria to defend against the host coagulation system, which suggests that bacterial exotoxins might be a new source of anticoagulants. In this study, we analyzed the genomic sequences of Acinetobacter baumannii and a new bacterial exotoxin protein, F6W77, with five Kunitz-domains, KABP1-5, was identified. Each Kunitz-type domain features a classical six-cysteine framework reticulated by three conserved disulfide bridges, which was obviously similar to animal Kunitz-domain peptides but different from plant Kunitz-domain peptides. Anticoagulation function evaluation showed that towards the intrinsic coagulation pathway, KABP1 and KABP5 had apparently inhibitory activity, KABP4 had weak inhibitory activity, and KBAP2 and KABP3 had no effect even at a high concentration of 20 µg/mL. All five Kunitz-domain peptides, KABP1-5, had no inhibitory activity towards the extrinsic coagulation pathway. Enzyme-inhibitor experiments showed that the high-activity anticoagulant peptide KABP1 had apparently inhibitory activity towards two key coagulation factors, Xa and XIa, which was further confirmed by pull-down experiments that showed that KABP1 can bind to coagulation factors Xa and XIa directly. Structure-function relationship analyses of five Kunitz-type domain peptides showed that the arginine of the P1 site of three new bacterial anticoagulants, KABP1, KABP4 and KABP5, might be the key residue for their anticoagulation activity. In conclusion, with bioinformatics analyses, peptide recombination, and functional evaluation, we firstly found bacterial-exotoxin-derived Kunitz-type serine protease inhibitors with selectively inhibiting activity towards intrinsic coagulation pathways, and highlighted a new interaction between pathogenic bacteria and the human coagulation system.


Assuntos
Acinetobacter baumannii , Anticoagulantes , Exotoxinas , Acinetobacter baumannii/efeitos dos fármacos , Anticoagulantes/farmacologia , Anticoagulantes/química , Exotoxinas/química , Exotoxinas/metabolismo , Humanos , Sequência de Aminoácidos , Peptídeos/farmacologia , Peptídeos/química , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Coagulação Sanguínea/efeitos dos fármacos , Domínios Proteicos
4.
Int J Endocrinol ; 2024: 2449037, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39411316

RESUMO

Objective: Polycystic ovary syndrome (PCOS) is one of the prevalent gynecological endocrine disorders encountered in clinical practice. Women diagnosed with PCOS demonstrate increased ovarian responsiveness, rendering them more prone to ovarian hyperstimulation syndrome (OHSS) during controlled ovarian stimulation (COS) procedures. The current study aimed at investigating whether CCL25/CCR9 plays a role in the pathological process of high ovarian response (HOR) during COS procedures. Design: Single-center retrospective cohort study. Patients. A total of 200 PCOS patients who received a fixed regimen of gonadotropin-releasing hormone (GnRH) antagonist were enrolled in this study. The cohort comprised 118 patients exhibiting HOR and 82 patients demonstrating a normal ovarian response (NOR). Results: The age and body mass index (BMI) variances across the two groups did not differ significantly. Similarly, the two groups observed no statistically significant differences in the baseline levels of luteinizing hormone (LH), progesterone (P), estradiol (E2), basal prolactin (PRL), and testosterone (T). Compared to the NOR group, HOR patients exhibit markedly elevated levels of anti-Müllerian hormone (AMH), antral follicle count (AFC), basal follicle-stimulating hormone (FSH), and HOMA-IR (all p < 0.05). Conversely, no statistically significant differences were observed between the two groups with respect to COS parameters, encompassing initial gonadotropin (Gn) dose, stimulation duration, and total Gn dose. During COS, the number of oocytes with diameter ≥14 mm, the levels of E2 on the HCG day, and the number of retrieved oocytes were significantly higher in the HOR group than in the NOR group (all p < 0.001). Additionally, the levels of CCL25/CCR9, matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinases (TIMPs), TNF-α, and IL-6 were significantly higher in the FF of the HOR group than in the NOR group (all p < 0. 001), while the variance in IL-1ß levels between the two cohorts did not reach statistical significance. The relevance analysis results indicated that the levels of CCL25/CCR9 in the FF of the HOR group are positively correlated with the number of retrieved oocytes and oocytes with diameters ≥14 mm during COS, AMH levels, and AFC. Concurrently, the CCL25 levels in the FF of the HOR group were positively correlated with HOMA-IR. Multivariable linear regression analysis revealed that the elevated AFC and HOMA-IR independently increase the CCL25 levels. Conclusion: The CCL25/CCR9 levels in FF are positively correlated with the clinical indicators of HOR, suggesting that CCL25/CCR9 may play a role in the pathogenesis of HOR in patients with PCOS.

5.
MAbs ; 16(1): 2415060, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39397258

RESUMO

The bispecific antibody tarperprumig (ALXN1820) was developed as a treatment option for diseases involving dysregulated complement alternative pathway (AP) activity that could be administered in small volumes, either subcutaneously or intravenously. Tarperprumig incorporates a C-terminal variable domain of a heavy chain only antibody (VHH) that binds properdin (FP) connected via a flexible linker to an N-terminal VHH that binds human serum albumin (HSA). The purified bispecific VHH antibody exhibits an experimental molecular weight average of 27.4 kDa and can be formulated at > 100 mg/mL. Tarperprumig binds tightly to FP and HSA with sub-nanomolar affinity at pH 7.4 and can associate simultaneously with FP and HSA to form a ternary complex. Tarperprumig potently and dose-dependently inhibits to completion in vitro AP-dependent complement C5b-9 formation, AP-dependent hemolysis, and the AP deposition of C3, FP and C9. X-ray crystallography revealed that the isolated FP-binding VHH recognizes the thrombospondin repeat 5 domain of FP, thereby preventing FP from binding to the AP convertase owing to severe steric hindrance. Tarperprumig cross-reacts with cynomolgus monkey FP and serum albumin. In summary, tarperprumig exhibits properties tailored for subcutaneous administration and is currently in clinical development for the treatment of complement AP-related disorders.


Assuntos
Anticorpos Biespecíficos , Properdina , Anticorpos Biespecíficos/imunologia , Anticorpos Biespecíficos/química , Humanos , Animais , Properdina/imunologia , Anticorpos de Domínio Único/imunologia , Anticorpos de Domínio Único/química , Via Alternativa do Complemento/imunologia , Via Alternativa do Complemento/efeitos dos fármacos
6.
ACS Nano ; 18(40): 27393-27400, 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39344122

RESUMO

Detecting a microwave signal that is emitted or reflected by distant targets is a powerful tool in fundamental science and industrial technology. Solid-state spins provide an opportunity to realize quantum-enhanced remote sensing under ambient conditions. However, the weak interaction between the free-space signal and atomic size sensor limits the sensitivity. This hinders the realization of practical quantum remote sensing. Here, we demonstrate active microwave remote sensing with a diamond-based hybrid quantum receiver by combining electromagnetic field localization at nanoscale with quantum spin manipulation. A method of differential spin refocusing (DSR) is developed to overcome the challenge of reducing the impact of inhomogeneities in spin-signal interaction, while the strength of interaction is enhanced by more than 3 orders with nanostructure. It improves the coherent interaction time of quantum receiver by 30-fold, substantially enhancing the sensitivity and stability. By detecting the reflected microwave with picotesla sensitivity, diamond remote sensing monitors the real-time status of a centimeter-sized target at 2 m distance. Our method is general to various solid-state spins. The results will expand the applications of solid-state spin quantum sensors in areas ranging from medical imaging to resource survey.

7.
Biochem Biophys Res Commun ; 734: 150662, 2024 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-39245030

RESUMO

Lipid metabolism, particularly triglyceride (TG) metabolism, is crucial for liver regeneration. During the early phase of liver regeneration, the liver temporarily accumulates a substantial amount of TG-dominated lipids. However, the specific composition of the TG profile during this phase is not yet fully understood. Here, we showed that the TG molecular composition in the liver was significantly altered during liver regeneration following carbon tetrachloride (CCl4)-induced liver injury. Lipid accumulation in livers was observed as early as 12 hours after CCl4 treatment, with transient regeneration-associated steatosis (TRAS) lasting until 24 hours. Hepatocyte proliferation began only after liver lipid levels returned to baseline at 48 hours. Furthermore, the profile of TG species changed significantly during liver regeneration. During the TRAS period, the accumulated TGs in the liver were mainly long-chain triglycerides, with most of the fatty acids constituting these triglycerides having fewer than 20 carbon atoms. In the proliferation phase, the fatty acid composition of these triglycerides shifted from long-chain to ultra-long-chain fatty acids. Our results suggest a significant TRAS-related change in the TG lipid profile of the liver during liver regeneration.


Assuntos
Tetracloreto de Carbono , Regeneração Hepática , Fígado , Triglicerídeos , Regeneração Hepática/efeitos dos fármacos , Triglicerídeos/metabolismo , Animais , Tetracloreto de Carbono/toxicidade , Fígado/metabolismo , Fígado/patologia , Masculino , Metabolismo dos Lipídeos/efeitos dos fármacos , Hepatócitos/metabolismo , Hepatócitos/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Camundongos , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Ácidos Graxos/metabolismo
8.
Opt Lett ; 49(18): 5047-5050, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39270226

RESUMO

We report on the efficient generation of intense terahertz radiation from the organic crystal N-benzyl-2-methyl-4-nitroaniline pumped by chirped Ti:sapphire femtosecond laser pulses. The THz energy and spectrum as a function of the pump fluence and duration of the chirped laser pulses are studied systematically. For the appropriate positively chirped pump pulses, a significant boost in the THz generation efficiency by a factor of around 2.5 is achieved, and the enhancement of high-frequency components (>1 THz) shortens the THz pulse duration. Via complete characterization of THz properties and transmitted laser spectra, this nonlinear behavior is attributed to the extended effective interaction length for phase matching as a result of the self-phase modulation of the intense pump laser pulses. Numerical calculations well reproduce the experimental observation. Our results demonstrate a robust, efficient, strong-field (up to several MV/cm) THz source using the common sub-10 mJ and sub-100 fs Ti:sapphire laser systems without optical parametric amplifiers.

9.
Chem Sci ; 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39290593

RESUMO

Thiolate-protected metal nanoclusters (NCs) have been widely used in various electrocatalytic reactions, yet the dynamic evolution of metal NCs during electrocatalysis has been rarely explored and the activity origin remains largely ambiguous. Herein, using a PtAu24(SCH3)18 NC as a prototype model, we combined advanced first-principles calculations and attenuated total reflection surface-enhanced infrared spectroscopy (ATR-SEIRAS) to re-examine its active site and reaction dynamics in the hydrogen evolution reaction (HER). It has been previously assumed that the central Pt is the only catalytic center. However, differently, we observed the spontaneous desorption of thiolate ligands under moderate potential, and the dethiolated PtAu24 exhibits excellent HER activity, which is contributed not only by the central Pt atom but also by the exposed bridged Au sites. Particularly, the exposed Au exhibits high activity even comparable to Pt, and the synergistic effect between them makes dethiolated PtAu24 an extraordinary HER electrocatalyst, even surpassing the commercial Pt/C catalyst. Our predictions are further verified by electrochemical activation experiments and in situ FTIR (ATR-SEIRAS) characterization, where evident adsorption of Au-H* and Pt-H* bonds is monitored. This work detected, for the first time, the Au-S interfacial dynamics of the PtAu24 nanocluster in electrocatalytic processes, and quantitatively evaluated the essential catalytic role of the exposed Au sites that has been largely overlooked in previous studies.

10.
Int J Nanomedicine ; 19: 9487-9502, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39290860

RESUMO

Purpose: Photodynamic therapy (PDT) induces anti-tumor immune responses by triggering immunogenic cell death in tumor cells. Previously, we demonstrated that novel QDs-RGD nanoparticles exhibited high efficiency as photosensitizers in the treatment of pancreatic cancer. However, the underlying mechanism of the anti-tumor immune effects induced by the photosensitizer remains unknown. This study assessed the anticancer immune effect of QDs-RGD, as well as the conventional photosensitizer chlorine derivative, YLG-1, for comparison, against pancreatic cancer in support of superior therapeutic efficacy. Methods: The pancreatic cancer cell line, Panc02, was used for in vitro studies. C57BL/6 mice bearing pancreatic cancer cell-derived xenografts were generated for in vivo studies to assess the anti-tumor effects of QDs-RGD-PDT and YLG-1-PDT. The immunostimulatory ability of both photosensitizers was examined by measuring the expression of damage-associated molecular patterns (DAMP), such as calreticulin (CRT), assessing dendritic cell (DC) maturation, and analyzing cytokine expression. The specific immunity of QDs-RGD and YLG-1-PDT on distant tumor were determined by combining PDT with anti-CTLA-4 antibody. Results: QDs-RGD-PDT and YLG-1-PDT significantly inhibited pancreatic cancer cell growth in a dose- and time-dependent manner. While both photosensitizers significantly promoted CRT release, DC maturation, and interferon γ (IFN-γ) and tumor necrosis factor α (TNF-α) expression, QDs-RGD exerted a stronger immunostimulatory effect than YLG-1. Combination treatment with QDs-RGD and CTLA-4 blockade was able to significantly inhibit the growth of distant tumors. Conclusion: QDs-RGD is a novel and effective PDT strategy for treating pancreatic tumors by inducing anti-tumor immune responses.


Assuntos
Camundongos Endogâmicos C57BL , Oligopeptídeos , Neoplasias Pancreáticas , Fotoquimioterapia , Fármacos Fotossensibilizantes , Pontos Quânticos , Animais , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/imunologia , Fotoquimioterapia/métodos , Pontos Quânticos/química , Pontos Quânticos/administração & dosagem , Linhagem Celular Tumoral , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/administração & dosagem , Oligopeptídeos/química , Oligopeptídeos/farmacologia , Camundongos , Humanos , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto , Calreticulina , Modelos Animais de Doenças , Citocinas/metabolismo
11.
J Exp Bot ; 2024 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-39305212

RESUMO

Darkness is often used as an effective measure to induce leaf senescence. Although many senescence-related genes in rice have been reported, the genome-wide genetic architecture underlying leaf senescence remains poorly understood. In our study, indica and japonica rice showed contrasting responses to dark-induced leaf senescence (DILS). Genome-wide association studies (GWAS) combined with transcriptomic analyses revealed 57, 97, and 48 loci involved in the regulation of the onset, progression, and ending of DILS, respectively. Haplotype analyses showed that the senescence-related loci differentially accumulated in indica and japonica accessions and functioned additively to regulate DILS. A total of 357 candidate genes were identified that are involved in various senescence-related processes such as lipid and amino acid catabolism, photosynthesis, response to reactive oxygen species, and regulation of defense response. In addition, functional analyses of the two candidate genes, OsMYB21 and OsSUB1B, revealed that OsMYB21 positively regulates the onset of DILS, while OsSUB1B negatively regulates its progression. Thus, our results provide new insights into the genetic regulation of DILS in rice.

12.
Biochim Biophys Acta Mol Basis Dis ; 1870(8): 167488, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39218272

RESUMO

BACKGROUND: Obesity-related hypertension is a major cardiovascular risk factor. Apigenin, a natural flavonoid in celery, induces vascular dilation via endothelial transient receptor potential channel vanilla 4 (TRPV4) channels. This study aimed to explore apigenin's potential to alleviate obesity-related hypertension in mice and its underlying mechanisms. METHODS: The C57BL/6 and TRPV4 knockout mice were fed a high-fat diet and subjected to dietary intervention with apigenin. Body weight and tail blood pressure of the mice were measured during the feeding. Vascular reactivity was assessed through a DMT wire myograph systems in vitro. The distribution and expression of adiponectin and pro-inflammatory markers in brown fat were detected. Injecting adeno-associated eight (AAV8) viruses into brown adipose tissue (BAT) to determine whether adiponectin is indispensable for the therapeutic effect of apigenin. Palmitic acid (PA) was used in mouse brown adipocytes to examine the detailed mechanisms regulating adiponectin secretion. RESULTS: Apigenin improved vasodilation and reduced blood pressure in obese mice, effects partly blocked in TRPV4 knockout. It also reduced weight gain independently of TRPV4. Apigenin increased adiponectin secretion from BAT; knockdown of adiponectin weakened its benefits. Apigenin downregulated Cluster of differentiation 38 (CD38), restoring Nicotinamide adenine dinucleotide+ (NAD+) levels and activating the NAD+/Sirtuin 1 (SIRT1) pathway, enhancing adiponectin expression. CONCLUSIONS: Our study indicates that dietary apigenin is suitable as a nonpharmaceutical intervention for obesity-related hypertension. In mechanism, in addition to improving vascular relaxation through the activation of endothelial TRPV4 channels, apigenin also directly alleviated adipose inflammation and increased adiponectin levels by inhibiting CD38.


Assuntos
Adiponectina , Apigenina , Dieta Hiperlipídica , Hipertensão , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade , Canais de Cátion TRPV , Vasodilatação , Animais , Adiponectina/metabolismo , Adiponectina/genética , Canais de Cátion TRPV/metabolismo , Canais de Cátion TRPV/genética , Obesidade/metabolismo , Obesidade/tratamento farmacológico , Obesidade/patologia , Apigenina/farmacologia , Camundongos , Hipertensão/metabolismo , Hipertensão/tratamento farmacológico , Hipertensão/patologia , Vasodilatação/efeitos dos fármacos , Masculino , Dieta Hiperlipídica/efeitos adversos , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Marrom/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos
13.
Org Lett ; 26(37): 7875-7879, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39238102

RESUMO

To increase solubility and decrease the lowest unoccupied molecular orbital (LUMO) energy levels of triphenodioxazine (TPDO), a novel series of imide-fused TPDO derivatives (TPDODIs) were designed, synthesized, and investigated. The introduction of alkyl diimide groups endows TPDODIs with high solubility and LUMO energy levels below -3.90 eV. TPDODIs also show strong absorption in the visible region with high maximum molar extinction coefficients and high fluorescence quantum yields (0.67 and 0.71, respectively). Moreover, TPDODIs display thermotropic liquid-crystalline behavior as indicated by spindly nematic or dendritic textures. Their high solubility and low LUMO levels suggest these materials are well-suited for solution-processable n-type electronic devices.

14.
Hypertens Res ; 47(10): 2884-2894, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39117945

RESUMO

Mineralocorticoid receptor antagonists (MRAs) for bilateral primary aldosteronism (PA) are the mainstay option recommended by guidelines, but poor compliance occurs due to numerous side effects. We aimed to examine whether catheter-based adrenal ablation could be an alternative treatment for bilateral PA.644 PA patients were included from a total of 6054 hypertensive patients. Adrenal CT scan and adrenal venous sampling (AVS) were both performed for PA subtype classification. Clinical and biochemical outcomes were assessed at 6 months after treatment according to the Primary Aldosteronism Surgical Outcome (PASO) criteria.93 patients with PA were recruited to be treated by adrenal ablation, including 25 bilateral PA and 68 unilateral PA according to AVS results. Office SBP and DBP significantly decreased from baseline levels, serum potassium levels increased and ARR significantly decreased (p < 0.01) in both the bilateral and unilateral groups. In the bilateral group, complete, partial and absent clinical success was achieved in 6 (24.0%), 11 (44.0%) and 8(32.0%) patients, respectively. In the unilateral group, complete, partial and absent clinical success was achieved in 12 (17.6%), 37 (54.4%), and 19 (27.9%) patients, respectively. The numbers of patients achieving complete, partial, and absent biochemical success were 15 (60.0%), 6 (24.0%), and 4 (16.0%), respectively, in the bilateral group versus 37 (54.4%), 9 (13.2%), and 22 (32.3%), respectively, in the unilateral group. In conclusion, we provide evidence for the beneficial outcomes of unilateral adrenal ablation for patients with bilateral PA. Our findings provide insight into an alternative option for patients with bilateral excess aldosterone.


Assuntos
Glândulas Suprarrenais , Ablação por Cateter , Hiperaldosteronismo , Humanos , Hiperaldosteronismo/cirurgia , Hiperaldosteronismo/sangue , Feminino , Masculino , Pessoa de Meia-Idade , Glândulas Suprarrenais/cirurgia , Glândulas Suprarrenais/diagnóstico por imagem , Adulto , Ablação por Cateter/métodos , Resultado do Tratamento , Idoso , Adrenalectomia , Aldosterona/sangue , Hipertensão/cirurgia
15.
Front Endocrinol (Lausanne) ; 15: 1383706, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39175575

RESUMO

Background: Gestational diabetes mellitus (GDM) can result in adverse maternal and neonatal outcomes. Predicting those at high risk of GDM and early interventions can reduce the development of GDM. The aim of this study was to examine the associations between first-trimester prenatal screening biomarkers and maternal characteristics in relation to GDM in Chinese women. Methods: We conducted a retrospective cohort study of singleton pregnant women who received first-trimester aneuploidy and preeclampsia screening between January 2019 and May 2021. First-trimester prenatal screening biomarkers, including pregnancy-associated plasma protein A (PAPP-A), free beta-human chorionic gonadotropin, and placental growth factor (PLGF), along with maternal characteristics, were collected for analysis in relation to GDM. Receiver operating characteristic (ROC) curve and logistic regression analyses were used to evaluate variables associated with GDM. Results: Of the 1452 pregnant women enrolled, 96 developed GDM. PAPP-A (5.01 vs. 5.73 IU/L, P < 0.001) and PLGF (39.88 vs. 41.81 pg/mL, P = 0.044) were significantly lower in the GDM group than in the non-GDM group. The area under the ROC curve of combined maternal characteristics and biomarkers was 0.73 (95% confidence interval [CI] 0.68-0.79, P < 0.001). The formula for predicting GDM was as follows: P = 1/[1 + exp (-8.148 + 0.057 x age + 0.011 x pregestational body mass index + 1.752 x previous GDM history + 0.95 x previous preeclampsia history + 0.756 x family history of diabetes + 0.025 x chronic hypertension + 0.036 x mean arterial pressure - 0.09 x PAPP-A - 0.001 x PLGF)]. Logistic regression analysis revealed that higher pregestational body mass index (adjusted odds ratio [aOR] 1.03, 95% CI 1.01 - 1.06, P = 0.012), previous GDM history (aOR 9.97, 95% CI 3.92 - 25.37, P < 0.001), family history of diabetes (aOR 2.36, 95% CI 1.39 - 4.02, P = 0.001), higher mean arterial pressure (aOR 1.17, 95% CI 1.07 - 1.27, P < 0.001), and lower PAPP-A level (aOR 0.91, 95% CI 0.83 - 1.00, P = 0.040) were independently associated with the development of GDM. The Hosmer-Lemeshow test demonstrated that the model exhibited an excellent discrimination ability (chi-square = 3.089, df = 8, P = 0.929). Conclusion: Downregulation of first-trimester PAPP-A and PLGF was associated with the development of GDM. Combining first-trimester biomarkers with maternal characteristics could be valuable for predicting the risk of GDM.


Assuntos
Biomarcadores , Diabetes Gestacional , Primeiro Trimestre da Gravidez , Proteína Plasmática A Associada à Gravidez , Humanos , Feminino , Gravidez , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/epidemiologia , Diabetes Gestacional/sangue , Primeiro Trimestre da Gravidez/sangue , Adulto , Biomarcadores/sangue , Estudos Retrospectivos , Proteína Plasmática A Associada à Gravidez/metabolismo , Proteína Plasmática A Associada à Gravidez/análise , China/epidemiologia , Fator de Crescimento Placentário/sangue , Gonadotropina Coriônica Humana Subunidade beta/sangue , Diagnóstico Pré-Natal/métodos , Pré-Eclâmpsia/epidemiologia , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/sangue , População do Leste Asiático
16.
Front Immunol ; 15: 1379480, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39185418

RESUMO

Background: Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease characterized by progressive fibrosis, leading to impaired gas exchange and high mortality. The etiology of IPF is complex, with potential links to autoimmune disorders such as hypothyroidism. This study explores the relationship between hypothyroidism and IPF, focusing on the mediating role of plasma proteins. Methods: A two-sample Mendelian randomization (MR) approach was employed to determine the impact of hypothyroidism on IPF and the mediating role of 4,907 plasma proteins, all in individuals of European ancestry. Sensitivity analyses, external validation, and reverse causality tests were conducted to ensure the robustness of the findings. Additionally, the function of causal SNPs was evaluated through gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Conclusion: The findings suggest that hypothyroidism, through altered plasma protein expression, particularly CXCL10, may contribute to the pathogenesis of IPF. This novel insight highlights the potential of CXCL10 as a therapeutic target in IPF, especially in patients with hypothyroidism. The study emphasizes the need for further research into the complex interplay between autoimmune disorders and IPF, with a view towards developing targeted interventions for IPF management.


Assuntos
Quimiocina CXCL10 , Hipotireoidismo , Fibrose Pulmonar Idiopática , População Branca , Humanos , Quimiocina CXCL10/genética , Predisposição Genética para Doença , Hipotireoidismo/genética , Fibrose Pulmonar Idiopática/genética , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , População Branca/genética
17.
Front Genet ; 15: 1435793, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39119576

RESUMO

Introduction: To enhance the beef cattle industry, Heilongjiang Province has developed a new Crossbred beef cattle variety through crossbreeding with exotic commercial breeds. This new variety exhibits relatively excellent meat quality, and efficient reproductive performance, catering to market demands. Method: This study employed whole genome resequencing technology to analyze the genetic pedigree and diversity of 19 Heilongjiang Crossbred beef cattle, alongside 59 published genomes from East Asian, Eurasian, and European taurine cattle as controls. In addition, genes related to production traits were also searched by identifying Runs of Homozygosity (ROH) islands and important fragments from ancestors. Results: A total of 14,427,729 biallelic SNPs were discovered, with the majority located in intergenic and intron regions and a small percentage in exon regions, impacting protein function. Population genetic analyses including Principal Component Analysis (PCA), Neighbor-Joining (NJ) tree, and ADMIXTURE identified Angus, Holstein, and Mishima as the main ancestors of Crossbred beef cattle. In genetic diversity analysis, nucleotide diversity, linkage disequilibrium, and inbreeding coefficient analysis reveal that the genetic diversity of Crossbred beef cattle is at a moderate level, and a higher inbreeding coefficient indicates the need for careful breeding management. In addition, some genes related to economic traits are identified through the identification of Runs of Homozygosity (ROH) islands and important fragments from ancestors. Conclusion: This comprehensive genomic characterization supports the targeted improvement of economically important traits in Crossbred beef cattle, facilitating advanced breeding strategies.

18.
Sci Rep ; 14(1): 19358, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39169171

RESUMO

Global climate change and the collection of environmental protection taxes are accelerating the green transformation of thermal power enterprises. This study selected Chinese thermal power listed companies as samples and used a dynamic three-stage (operational, green transformation, and market performance) network DEA model to evaluate their transformation efficiency and corporate performance. This paper incorporates targeted indicators such as ESG (environment, society, governance) and stock prices into the model and conducts a comparative study on the basis of macro policies and the geographical location of the enterprise. A comparative analysis was conducted on the efficiency of enterprises before and after the adjustment of the environmental tax burden, using the environmental tax burden as an exogenous variable. Thus, the following conclusions can be drawn: there is a certain positive correlation between the collaborative efficiency of the two links of thermal power enterprises and the economic development of their respective regions. Moreover, the green transformation efficiency of most thermal power enterprises is superior to the market performance efficiency. The environmental tax burden mainly improves the overall efficiency of thermal power enterprises by improving their operational efficiency and efficiency in the green transformation stage without affecting market performance. To further improve efficiency, thermal power enterprises should actively communicate with stakeholders to strive for more financial relief.

19.
Huan Jing Ke Xue ; 45(8): 4656-4669, 2024 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-39168685

RESUMO

It is of great significance to explore the regional differences of land use carbon emission (LUCE) in the Yangtze River Economic Belt and the path of coordinated emission reduction for regional sustainable development. Based on the LUCE estimation method, this study scientifically calculated the LUCE of the three major urban agglomerations of the Yangtze River Economic Belt (Yangtze River Delta, middle reaches of the Yangtze River, and Chengdu-Chongqing urban agglomeration) from 2010 to 2020. Kernel density estimation and the spatial convergence model were used to study the dynamic evolution, regional differences, and convergence characteristics of LUCE. The results showed that: ① The carbon absorption of forest land, water areas, grassland, and unused land were relatively small in terms of carbon emissions from cultivated land and construction land. The carbon emission of construction land increased gradually, whereas the carbon absorption of four carbon sinks fluctuated little during the study period. ② The core density curves of different urban agglomerations showed different distribution patterns, extensibility, and polarization characteristics but generally tended to be balanced. ③ From 2010 to 2020, the LUCE of the Yangtze River Economic Belt as a whole showed the spatio-temporal characteristics of increasing first and then decreasing and high in the east and low in the west. The LUCE of the central cities of the three urban agglomerations were at the highest level steadily, and stable coupling mechanisms had not been established between the economic development level and the ecological environment. ④ The LUCE of the three urban agglomerations in the Yangtze River Economic Belt all had absolute ß convergence and also had conditional ß convergence under the model control variables such as economic development level, urbanization level, industrial structure, population density, and environmental regulation, etc., and the conditional convergence speed was greater than the absolute convergence speed in each region. The convergence speed of the Yangtze River Delta urban agglomeration was the slowest. The above conclusions provide support for the coordinated emission reduction path of the three urban agglomerations in the Yangtze River Economic Belt and are also conducive to actively and steadily promoting the realization of the goals of carbon peak and carbon neutralization.

20.
PLoS One ; 19(8): e0308353, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39116046

RESUMO

As the number of foreign patients and the frequency of international academic exchanges increase, English proficiency has become increasingly essential for Chinese nurses in the treatment and nursing processes, clinical academic exchanges, and ongoing education. However, the overall English proficiency of Chinese nurses is generally inadequate, greatly depending on the English that they acquire during their nursing education. This study aims to explore the challenges encountered by Chinese EFL (English as a Foreign Language) nursing students in the process of learning Nursing English, along with the effective self-regulated learning strategies they adopt to overcome these challenges. Data were collected from nine Chinese EFL nursing students through their reflective journals and thematic analysis was applied. Data analysis revealed the variety of challenges EFL nursing students encountered, including language-related challenges, which are linguistic difficulties that relate to Nursing English learning itself, such as Nursing English vocabulary and terminology, English-to-English translation, limited listening comprehension, and the gap between textbook knowledge and its practical application; learner-related challenges, which are difficulties that affect students' emotional, affective, and mental state, primarily caused by uncertainty about the significance of Nursing English, the unexpected difficulty of Nursing English, and failing quizzes; and context-related challenges, which are difficulties relate to social, cultural, and educational context, such as insufficient learning resources, a lack of language environment, and peer pressure. To surmount these challenges, the participants adopted diverse self-regulated learning strategies, including setting goals, previewing in advance and reviewing in time, utilizing word roots, prefixes, and suffixes to facilitate vocabulary learning, repeating, practicing with sounds and writing systems, translating, highlighting and using imagery to overcome language-related challenges; believing in the usefulness and significance of Nursing English, keeping a growth mindset, enjoying Nursing English learning and teacher support and maintaining grit in learning Nursing English to overcome learner-related challenges; and integrating resources, creating supportive language environments and seeking assistance from teachers and cooperating with peers to overcome context-related challenges. Based on these findings, implications are drawn for Nursing English teachers, material designers, curriculum developers, and program designers. We suggest incorporating explicit strategy instruction into regular Nursing English education to enhance nursing students' self-regulated learning.


Assuntos
Idioma , Aprendizagem , Estudantes de Enfermagem , Estudantes de Enfermagem/psicologia , Humanos , China , Feminino , Adulto Jovem , Masculino , Educação em Enfermagem/métodos , Adulto , População do Leste Asiático
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