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1.
Int J Biol Macromol ; 277(Pt 3): 134300, 2024 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-39097069

RESUMEN

Extensive bodies of research are dedicated to the study of seed aging with a particular focus on the roles of reactive oxygen species (ROS), and the ensuing oxidative damage during storage, as a primary cause of seed vigor decreasing. ROS diffuse to the nucleus and damage the telomeres, resulting in a loss of genetic integrity. Protection of telomeres 1 (POT1) is a telomeric protein that binds to the telomere region, and plays an essential role in maintaining genomic stability in plants. In this study, there were totally four MsPOT1 genes obtained from alfalfa genome. Expression analysis of four MsPOT1 genes in germinated seed presented the different expressions. Four MsPOT1 genes displayed high expression levels at the early stage of seed germination, Among the four POT1 genes, it was found that MS. gene040108 was significantly up-regulated in the early germination stage of CK seeds, but down-regulated in aged seeds. RT-qPCR assays and RNA-seq data revealed that MsPOT1-X gene was significantly induced by seed aging treatment. Transgenic seeds overexpressing MsPOT1-X gene in Arabidopsis thaliana and Medicago trunctula exhibited enhanced seed vigor, telomere length, telomerase activity associated with reduced H2O2 content. These results would provide a new way to understand aging stress-responsive MsPOT1 genes for genetic improvement of seed vigor. Although a key gene regulating seed vigor was identified in this study, the specific mechanism of MsPOT1-X gene regulating seed vigor needs to be further explored.

2.
Clin Linguist Phon ; : 1-24, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39101257

RESUMEN

Echolalia, a prevalent feature of Autism Spectrum Disorders (ASD), has been extensively debated among behaviourists and developmental researchers for decades, long segmenting clinical work within the context of autism. This qualitative study aimed to explore the interactive underpinnings of immediate echolalia naturally occurring in dyadic conversation between autistic individuals and clinicians, employing turn-by-turn and sequence-by-sequence analysis within the framework of Conversation Analysis (CA). The results revealed that varying the complete-incomplete-transformed format, echolalia helped participants a) express their emotions, b) automatically associate conversation, c) organise their response, d) maintain conversational reciprocity, and e) assist with request initiation. Within the context of echolalia, the dynamics of conversation exhibited blocking, diverting, or affiliating patterns. The current study provides insights into the interactive traits of immediate echolalia and underscores the potential utility for clinical therapists to employ the echoic sources in clinical intervention.

3.
Zhongguo Gu Shang ; 37(7): 664-9, 2024 Jul 25.
Artículo en Chino | MEDLINE | ID: mdl-39104066

RESUMEN

OBJECTIVE: To analyze the differences of clinical features of acute gout flare and postoperative infection under arthroscopy of knee gouty arthritis patients to offer guiding opinions of clinical diagnosis and treatment. METHODS: Between January 2017 and December 2022, 235 patients with gouty knee osteoarthritis were admitted, and underwent arthroscopic debridement combined with synovectomy. Among them, 35 cases had fever with a temperature higher than 38 °C postoperatively while acute inflammatory appears under redness, swelling, heat and pain of the operated joints. There were 29 males and 6 females, with an average age of (41.48±13.90) years old. Among them 23 patients were diagnosed with acute gout attack, and recovered well after being given colchicine and prednisolone;12 patients were diagnosed with postoperative joint infection, and were cured after being given anti-infective treatments and cleaning and rinsing of the joint cavity. The two groups of patients were compared and analyzed in terms of preoperative general data, surgical conditions, hematology, joint fluid, limb function and other clinical characteristics. RESULTS: There were no significant difference in the preoperative general data between two groups. The onset of fever in the postoperative acute gout flare group occurred mostly within 48 hours, significantly earlier than that in the postoperative infection group(P=0.037). The visual analogue scale score was significantly higher in the acute gout flare group (5.32±1.38) score than in the postoperative infection group (2.45±0.68) score (P=0.000), while 14 patients with acute gout flare were accompanied by severe pain in other joints. Hematologically, indicators such as white blood cell counts and ratios were significantly higher in both groups. In terms of inflammatory indicators, IL-6, erythrocyte sedimentation rate, procalcitonin and other inflammatory indicators were significantly elevated in both groups, but there was no statistical difference between two groups. The C-reactive protein level in the postoperative infection group (220.97±116.30) mg·L-1 was higher than that in the postoperative acute gout attack group(120.67±82.45) mg·L-1(P=0.006). Blood uric acid (316.55±112.84) µmol·L-1 was higher in the acute postoperative gout flare group than in the postoperative infection group (159.14±126.92) µmol·L-1(P=0.001). In the joint fluid examination of the postoperative infection group, the glucose metabolism indicator was significantly lower than that of the acute gout flare group, and five of them had positive bacterial cultures. CONCLUSION: The symptoms of acute gout flare could be mistaken as postoperative infection due to their similarity, therefore requires careful differentiation. Differential diagnosis should be based on a combination of clinical signs, hematology and joint fluid findings, and targeted treatment should be given to avoid serious complications.


Asunto(s)
Artritis Gotosa , Artroscopía , Humanos , Femenino , Masculino , Artritis Gotosa/cirugía , Artroscopía/efectos adversos , Adulto , Persona de Mediana Edad , Errores Diagnósticos , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Articulación de la Rodilla/cirugía , Enfermedad Aguda , Anciano
4.
Front Endocrinol (Lausanne) ; 15: 1217250, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39104815

RESUMEN

Background: Gallbladder mixed neuroendocrine-non-neuroendocrine neoplasm generally consists of a gallbladder neuroendocrine tumor and a non-neuroendocrine component. The World Health Organization (WHO) in 2019 established a guideline requiring each component, both neuroendocrine and non-neuroendocrine, to account for a minimum of 30% of the tumor mass. Methods: Patients after surgery resection and diagnosed at microscopy evaluation with pure gallbladder neuroendocrine carcinoma (GBNEC), gallbladder mixed adeno-neuroendocrine carcinoma (GBMANEC, GBNEC≥30%), and gallbladder carcinoma mixed with a small fraction of GBNEC (GBNEC <30%) between 2010 and 2022 at West China Hospital of Sichuan University were collated for the analyses. Demographic features, surgical variables, and tumor characteristics were evaluated for association with patients' overall and recurrence-free survival (OS and RFS). Results: The study included 26 GBNEC, 11 GBMANEC, 4 gallbladder squamous-cell carcinoma (GBSCC), and 7 gallbladder adenocarcinoma (GBADC) mixed with a small fraction of GBNEC. All patients had stage III or higher tumors (AJCC8th edition). The majority of included patients (79.17%) underwent curative surgical resection (R0), with only ten patients having tumoral resection margins. In the analysis comparing patients with GBNEC percentage (GBNEC≥30% vs. GBNEC<30%), the basic demographics and tumor characteristics of most patients were comparable. The prognosis of these patients was also comparable, with a median OS of 23.65 months versus 20.40 months (P=0.13) and a median RFS of 17.1 months versus 12.3 months (P=0.24). However, patients with GBADC or GBSCC mixed with GBNEC <30% had a statistically significant decreased OS and RFS (both P<0.0001)) compared with GBNEC and GBMANEC. Patients with GBNEC who exhibited advanced tumor stages and lymphovascular invasion had a higher risk of experiencing worse overall survival (OS) and recurrence-free survival (RFS). However, a 30% GBNEC component was not identified as an independent risk factor. Conclusion: Patients with GBNEC were frequently diagnosed at advanced stages and their prognosis is poor. The 30% percentage of the GBNEC component is not related to the patient's survival.


Asunto(s)
Carcinoma Neuroendocrino , Neoplasias de la Vesícula Biliar , Humanos , Neoplasias de la Vesícula Biliar/patología , Neoplasias de la Vesícula Biliar/mortalidad , Neoplasias de la Vesícula Biliar/cirugía , Femenino , Masculino , Persona de Mediana Edad , Pronóstico , Carcinoma Neuroendocrino/patología , Carcinoma Neuroendocrino/mortalidad , Carcinoma Neuroendocrino/cirugía , Carcinoma Neuroendocrino/diagnóstico , Anciano , Adulto , Estudios Retrospectivos , Adenocarcinoma/patología , Adenocarcinoma/mortalidad , Adenocarcinoma/cirugía , Tasa de Supervivencia
5.
Int J Biol Macromol ; 277(Pt 4): 134388, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39116978

RESUMEN

Numerous studies have investigated seed aging, with a particular emphasis on the involvement of reactive oxygen species. Reactive oxygen species diffuse into the nucleus and damage telomeres, resulting in loss of genetic integrity. Telomerase reverse transcriptase (TERT) plays an essential role in maintaining plant genomic stability. Genome-wide analyses of TERT genes in alfalfa (Medicago sativa) have not yet been conducted, leaving a gap in our understanding of the mechanisms underlying seed aging associated with TERT genes. In this study, four MsTERT genes were identified in the alfalfa genome. The expression profiles of the four MsTERT genes during seed germination indicated that MS. gene79077 was significantly upregulated by seed aging. Transgenic seeds overexpressing MS. gene79077 in Arabidopsis exhibited enhanced tolerance to seed aging by reducing the levels of H2O2 and increasing telomere length and telomerase activity. Furthermore, transcript profiling of aging-treated Arabidopsis wild-type and overexpressing seeds showed an aging response in genes related to glutathione-dependent detoxification and antioxidant defense pathways. These results revealed that MS. gene79077 conferred Arabidopsis seed-aging tolerance via modulation of antioxidant defense and telomere homeostasis. This study provides a new way to understand stress-responsive MsTERT genes for the potential genetic improvement of seed vigor.

6.
PNAS Nexus ; 3(8): pgae279, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39108304

RESUMEN

Inherited mutations in human beta-cardiac myosin (M2ß) can lead to severe forms of heart failure. The E525K mutation in M2ß is associated with dilated cardiomyopathy (DCM) and was found to stabilize the interacting heads motif (IHM) and autoinhibited super-relaxed (SRX) state in dimeric heavy meromyosin. However, in monomeric M2ß subfragment 1 (S1) we found that E525K enhances (threefold) the maximum steady-state actin-activated ATPase activity (k cat) and decreases (eightfold) the actin concentration at which ATPase is one-half maximal (K ATPase). We also found a twofold to fourfold increase in the actin-activated power stroke and phosphate release rate constants at 30 µM actin, which overall enhanced the duty ratio threefold. Loaded motility assays revealed that the enhanced intrinsic motor activity translates to increased ensemble force in M2ß S1. Glutamate 525, located near the actin binding region in the so-called activation loop, is highly conserved and predicted to form a salt bridge with another conserved residue (lysine 484) in the relay helix. Enhanced sampling molecular dynamics simulations predict that the charge reversal mutation disrupts the E525-K484 salt bridge, inducing conformations with a more flexible relay helix and a wide phosphate release tunnel. Our results highlight a highly conserved allosteric pathway associated with actin activation of the power stroke and phosphate release and suggest an important feature of the autoinhibited IHM is to prevent this region of myosin from interacting with actin. The ability of the E525K mutation to stabilize the IHM likely overrides the enhanced intrinsic motor properties, which may be key to triggering DCM pathogenesis.

7.
Cancer Cell Int ; 24(1): 288, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39143546

RESUMEN

BACKGROUND: Gastric cancer (GC) encompasses many different histological and molecular subtypes. It is a major driver of cancer mortality because of poor survival and limited treatment options. Personalised medicine in the form of patient-derived organoids (PDOs) represents a promising approach for improving therapeutic outcomes. The goal of this study was to overcome the limitations of current models by ameliorating organoid cultivation. METHODS: Organoids derived from cancer tissue were evaluated by haematoxylin and eosin staining, immunohistochemistry, mRNA, and whole-exome sequencing. Three representative chemotherapy drugs, 5-fluorouracil, docetaxel, and oxaliplatin, were compared for their efficacy against different subtypes of gastric organoids by ATP assay and apoptosis staining. In addition, drug sensitivity screening results from two publicly available databases, the Genomics of Drug Sensitivity in Cancer and Cancer Cell Line Encyclopaedia, were pooled and applied to organoid lines. Once key targeting genes were confirmed, chemotherapy was used in combination with poly (ADP ribose) polymerase (PARP)-targeted therapy. RESULTS: We successfully constructed GC PDOs surgically resected from GC patient tissue. PDOs closely reflected the histopathological and genomic features of the corresponding primary tumours. Whole-exosome sequencing and mRNA analysis revealed that changes to the original tumour genome were maintained during long-term culture. The drugs caused divergent responses in intestinal, poorly differentiated intestinal, and diffuse gastric cancer organoids, which were confirmed in organoid lines. Poorly differentiated intestinal GC patients benefited from a combination of 5-fluorouracil and veliparib. CONCLUSION: The present study demonstrates that combining chemotherapy with PARP targeting may improve the treatment of chemotherapy-resistant tumours.

9.
Curr Med Sci ; 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38967889

RESUMEN

OBJECTIVE: Colorectal cancer (CRC), a prevalent malignancy worldwide, has prompted extensive research into anticancer drugs. Traditional Chinese medicinal materials offer promising avenues for cancer management due to their diverse pharmacological activities. This study investigated the effects of Notopterygium incisum, a traditional Chinese medicine named Qianghuo (QH), on CRC cells and the underlying mechanism. METHODS: The sulforhodamine B assay and colony formation assay were employed to assess the effect of QH extract on the proliferation of CRC cell lines HCT116 and Caco-2. Propidium iodide (PI) staining was utilized to detect cell cycle progression, and PE Annexin V staining to detect apoptosis. Western blotting was conducted to examine the levels of apoptotic proteins, including B-cell lymphoma 2-interacting mediator of cell death (BIM), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (BAX) and cleaved caspase-3, as well as BIM stability after treatment with the protein synthesis inhibitor cycloheximide. The expression of BAX was suppressed using lentivirus-mediated shRNA to validate the involvement of the BIM/BAX axis in QH-induced apoptosis. The in vivo effects of QH extract on tumor growth were observed using a xenograft model. Lastly, APCMin+ mice were used to study the effects of QH extract on primary intestinal tumors. RESULTS: QH extract exhibited significant in vitro anti-CRC activities evidenced by the inhibition of cell proliferation, perturbation of cell cycle progression, and induction of apoptosis. Mechanistically, QH extract significantly increased the stability of BIM proteins, which undergo rapid degradation under unstressed conditions. Knockdown of BAX, the downstream effector of BIM, significantly rescued QH-induced apoptosis. Furthermore, the in vitro effect of QH extract was recapitulated in vivo. QH extract significantly inhibited the tumor growth of HCT116 xenografts in nude mice and decreased the number of intestinal polyps in the APCMin+ mice. CONCLUSION: QH extract promotes the apoptosis of CRC cells by preventing the degradation of BIM.

10.
Crit Care ; 28(1): 213, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38956604

RESUMEN

BACKGROUND: The multidimensional biological mechanisms underpinning acute respiratory distress syndrome (ARDS) continue to be elucidated, and early biomarkers for predicting ARDS prognosis are yet to be identified. METHODS: We conducted a multicenter observational study, profiling the 4D-DIA proteomics and global metabolomics of serum samples collected from patients at the initial stage of ARDS, alongside samples from both disease control and healthy control groups. We identified 28-day prognosis biomarkers of ARDS in the discovery cohort using the LASSO method, fold change analysis, and the Boruta algorithm. The candidate biomarkers were validated through parallel reaction monitoring (PRM) targeted mass spectrometry in an external validation cohort. Machine learning models were applied to explore the biomarkers of ARDS prognosis. RESULTS: In the discovery cohort, comprising 130 adult ARDS patients (mean age 72.5, 74.6% male), 33 disease controls, and 33 healthy controls, distinct proteomic and metabolic signatures were identified to differentiate ARDS from both control groups. Pathway analysis highlighted the upregulated sphingolipid signaling pathway as a key contributor to the pathological mechanisms underlying ARDS. MAP2K1 emerged as the hub protein, facilitating interactions with various biological functions within this pathway. Additionally, the metabolite sphingosine 1-phosphate (S1P) was closely associated with ARDS and its prognosis. Our research further highlights essential pathways contributing to the deceased ARDS, such as the downregulation of hematopoietic cell lineage and calcium signaling pathways, contrasted with the upregulation of the unfolded protein response and glycolysis. In particular, GAPDH and ENO1, critical enzymes in glycolysis, showed the highest interaction degree in the protein-protein interaction network of ARDS. In the discovery cohort, a panel of 36 proteins was identified as candidate biomarkers, with 8 proteins (VCAM1, LDHB, MSN, FLG2, TAGLN2, LMNA, MBL2, and LBP) demonstrating significant consistency in an independent validation cohort of 183 patients (mean age 72.6 years, 73.2% male), confirmed by PRM assay. The protein-based model exhibited superior predictive accuracy compared to the clinical model in both the discovery cohort (AUC: 0.893 vs. 0.784; Delong test, P < 0.001) and the validation cohort (AUC: 0.802 vs. 0.738; Delong test, P = 0.008). INTERPRETATION: Our multi-omics study demonstrated the potential biological mechanism and therapy targets in ARDS. This study unveiled several novel predictive biomarkers and established a validated prediction model for the poor prognosis of ARDS, offering valuable insights into the prognosis of individuals with ARDS.


Asunto(s)
Biomarcadores , Síndrome de Dificultad Respiratoria , Humanos , Síndrome de Dificultad Respiratoria/sangre , Masculino , Femenino , Anciano , Biomarcadores/sangre , Biomarcadores/análisis , Pronóstico , Persona de Mediana Edad , Proteómica/métodos , Estudios de Cohortes , Anciano de 80 o más Años , Proteínas Sanguíneas/análisis , Metabolómica/métodos , Multiómica
11.
Cancer Med ; 13(13): e7342, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38967142

RESUMEN

OBJECTIVE: Our study aims to evaluate the predictive accuracy of functional liver remnant volume (FLRV) in post-hepatectomy liver failure (PHLF) among surgically-treated jaundiced patients with hilar cholangiocarcinoma (HCCA). METHODS: We retrospectively reviewed surgically-treated jaundiced patients with HCCA between June, 2000 and June, 2018. The correlation between FRLV and PHLF were analyzed. The optimal cut off value of FLRV in jaundiced HCCA patients was also identified and its impact was furtherly evaluated. RESULTS: A total of 224 jaundiced HCCA patients who received a standard curative resection (43 patients developed PHLF) were identified. Patients with PHLF shared more aggressive clinic-pathological features and were generally in a more advanced stage than those without PHLF. An obvious inconsistent distribution of FLRV in patients with PHLF and those without PHLF were detected. FLRV (continuous data) had a high predictive accuracy in PHLF. The newly-acquired cut off value (FLRV = 53.5%, sensitivity = 81.22%, specificity = 81.4%) showed a significantly higher predictive accuracy than conventional FLRV cut off value (AUC: 0.81 vs. 0.60, p < 0.05). Moreover, patients with FLRV lower than 53.5% also shared a significantly higher major morbidity rate as well as a worse prognosis, which were not detected for FLRV of 40%. CONCLUSION: For jaundiced patients with HCCA, a modified FLRV of 53.5% is recommended due to its great impact on PHLF, as well as its correlation with postoperative major morbidities as well as overall prognosis, which might help clinicians to stratify patients with different therapeutic regimes and outcomes. Future multi-center studies for training and validation are required for further validation.


Asunto(s)
Neoplasias de los Conductos Biliares , Hepatectomía , Ictericia , Tumor de Klatskin , Fallo Hepático , Humanos , Masculino , Hepatectomía/efectos adversos , Femenino , Persona de Mediana Edad , Tumor de Klatskin/cirugía , Tumor de Klatskin/patología , Estudios Retrospectivos , Neoplasias de los Conductos Biliares/cirugía , Neoplasias de los Conductos Biliares/patología , Fallo Hepático/etiología , Fallo Hepático/prevención & control , China/epidemiología , Ictericia/etiología , Hígado/cirugía , Hígado/patología , Anciano , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/epidemiología , Pronóstico , Adulto , Tamaño de los Órganos
12.
Front Physiol ; 15: 1394740, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39015225

RESUMEN

Ischemic stroke, a significant threat to human life and health, refers to a class of conditions where brain tissue damage is induced following decreased cerebral blood flow. The incidence of ischemic stroke has been steadily increasing globally, and its disease mechanisms are highly complex and involve a multitude of biological mechanisms at various scales from genes all the way to the human body system that can affect the stroke onset, progression, treatment, and prognosis. To complement conventional experimental research methods, computational systems biology modeling can integrate and describe the pathogenic mechanisms of ischemic stroke across multiple biological scales and help identify emergent modulatory principles that drive disease progression and recovery. In addition, by running virtual experiments and trials in computers, these models can efficiently predict and evaluate outcomes of different treatment methods and thereby assist clinical decision-making. In this review, we summarize the current research and application of systems-level computational modeling in the field of ischemic stroke from the multiscale mechanism-based, physics-based and omics-based perspectives and discuss how modeling-driven research frameworks can deliver insights for future stroke research and drug development.

13.
Chem Sci ; 15(28): 11099-11107, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39027288

RESUMEN

Late-stage modification of peptides could potentially endow peptides with significant bioactivity and physicochemical properties, and thereby provide novel opportunities for peptide pharmaceutical studies. Since tryptophan (Trp) bears a unique indole ring residue and plays various critical functional roles in peptides, the modification methods for tryptophan were preliminarily developed with considerable progress via transition-metal mediated C-H activation. Herein, we report an unprecedented tertiary amine catalyzed peptide allylation via the SN2'-SN2' pathway between the N1 position of the indole ring of Trp and Morita-Baylis-Hillman (MBH) carbonates. Using this method that proceeds under mild conditions, we demonstrated an extremely broad scope of Trp-containing peptides and MBH carbonates to prepare a series of peptide conjugates and cyclic peptides. The reaction is amenable to either solid-phase (on resin) or solution-phase conditions. In addition, the modified peptides can be further conjugated with other biomolecules at Trp, providing a new handle for bioconjugation.

14.
Langmuir ; 40(31): 16538-16548, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39041610

RESUMEN

The theory of heat conduction paths has been widely recognized and widely studied in the research about the thermal conductivity of thermal conductive polymer composites at present. Encapsulating polymer pellets with thermally conductive fillers and processing them into thermally conductive polymer composites is a simple and effective method for constructing heat conduction paths. It is meaningful to investigate the related heat conduction mechanism of this method. Otherwise, this approach can significantly preserve the performance of the polymer substrate, making it highly valuable for practical material applications. In this work, polyethylene-octene elastomer (POE) pellets were encapsulated with thermal conductive fillers by physical absorption. Subsequently, the composite films containing heat conduction paths were fabricated using the encapsulated POE pellets through a heating press. Alumina (Al2O3), boron nitride (BN), and alumina/boron nitride hybrid (Al2O3/BN) fillers were used to prepare Al2O3@POE, BN@POE, and BN/Al2O3@POE composite films to investigate the influence of filler shapes on heat conduction path construction. The influence of the constitute and density of heat conduction paths on the thermal conductivity of composite films was analyzed by infrared thermal imaging, finite element analysis, and thermal resistance theory in detail. Owing to the reserved good adhesion and flexibility of the POE substrate, the composite films could be directly used as thermal interface materials for chip cooling, which presented a good heat dissipation effect. Furthermore, a series of integrated composite materials were prepared by the combination of encapsulated pellets with various functional films (copper foil, aluminum foil, and graphite sheet) through a one-pot heating press, exhibiting a good electromagnetic shielding effect. The performance of the composites and the corresponding preparation method demonstrate the strong significance of this research for practical applications.

15.
Acta Crystallogr C Struct Chem ; 80(Pt 8): 366-374, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38967632

RESUMEN

The structures of three 1:1 cocrystal forms of etoricoxib {ETR; systematic name: 5-chloro-2-(6-methylpyridin-3-yl)-3-[4-(methylsulfonyl)phenyl]pyridine, C18H15ClN2O2S} have been synthesized and characterized by single-crystal X-ray diffraction; these are etoricoxib-benzoic acid (1/1), C18H15ClN2O2S·C7H6O2 (ETR-Bz), etoricoxib-4-fluorobenzoic acid (1/1), C18H15ClN2O2S·C7H5FO2 (ETR-PFB), and etoricoxib-4-nitrobenzoic acid (1/1), C18H15ClN2O2S·C7H5NO4 (ETR-PNB). Powder X-ray diffraction and thermal differential scanning calorimetry-thermogravimetry (DSC-TG) techniques were also used to characterize these multicomponent systems. Due to the influence of the corresponding acids, ETR shows different conformations. Furthermore, the energetic contributions of the supramolecular motifs have been established by energy framework studies of the stabilizing interaction forces and are consistent with the thermal stability of the cocrystals.

16.
Antioxidants (Basel) ; 13(7)2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-39061885

RESUMEN

Despite mounting evidence for dietary protease benefits, the mechanisms beyond enhanced protein degradation are poorly understood. This study aims to thoroughly investigate the impact of protease addition on the growth performance, intestinal function, and microbial composition of weaned piglets. Ninety 28-day-old weaned pigs were randomly assigned to the following three experimental diets based on their initial body weight for a 28-day experiment: (1) control (CC), a basic diet with composite enzymes without protease; (2) negative control (NC), a diet with no enzymes; and (3) dietary protease (PR), a control diet with protease. The results show that dietary proteases significantly enhanced growth performance and boosted antioxidant capacity, increasing the total antioxidant capacity (T-AOC) levels (p < 0.05) while reducing malonaldehyde levels (p < 0.05). Additionally, protease addition reduced serum levels of inflammatory markers TNF-α, IL-1ß, and IL-6 (p < 0.05), suppressed mRNA expression of pro-inflammatory factors in the jejunum (p < 0.01), and inhibited MAPK and NF-κB signaling pathways. Moreover, protease-supplemented diets improved intestinal morphology and barrier integrity, including zonula occludens protein 1(ZO-1), Occludin, and Claudin-1 (p < 0.05). Microbiota compositions were also significantly altered by protease addition with increased abundance of beneficial bacteria (Lachnospiraceae_AC2044_group and Prevotellaceae_UCG-001) (p < 0.05) and reduced harmful Terrisporobacter (p < 0.05). Further correlation analysis revealed a positive link between beneficial bacteria and growth performance and a negative association with inflammatory factors and intestinal permeability. In summary, dietary protease addition enhanced growth performance in weaned piglets, beneficial effects which were associated with improved intestinal barrier integrity, immunological response, and microbiota composition.

17.
Shanghai Kou Qiang Yi Xue ; 33(2): 180-185, 2024 Apr.
Artículo en Chino | MEDLINE | ID: mdl-39005096

RESUMEN

PURPOSE: To investigate the efficacy of a modified maxillary protraction appliance in patients of skeletal Class Ⅲ with crowding. METHODS: Forty patients with skeletal Class Ⅲ malocclusion were divided into two groups, with 20 patients in each group. The experimental group had molar in a neutral or distal relationship and applied a modified maxillary protraction appliance, while the control group had molar mesial relationship and applied a conventional maxillary protraction appliance. Lateral cephalometric radiographs were taken before and after treatment in both groups for comparison. SPSS 22.0 software package was used for data analysis. RESULTS: The angle measurements taken before and after treatment showed a significant increase in SNA, ANB, SN-MP and U4-SN(P<0.01), while SNB decreased(P<0.01) in both groups. SN-OL changes were statistically different before and after treatment in the experimental group(P<0.05). The sagittal measurements before and after treatment in both groups showed significant alterations in all(P<0.05) but the length of the maxillary arch in both groups. For vertical measurements, U1-PP, L1-MP, U4-SN, U6-SN, and ANS-ME all increased (P<0.05), while the changes of U4-PP and U6-PP in the two groups before and after treatment were statistically different(P<0.05). Compared with the control group, the experimental group had a significantly increased maxillary arch length, a more remote location at U6, and a less variable molar relationship after treatment(P<0.01). The two groups showed a variable amount of cephalometric measurements before and after treatment: the experimental group had a significant increase in maxillary arch length, a more remote position at U6, and a smaller change in molar relationship compared to the control group(P<0.01). CONCLUSIONS: The modified maxillary protraction appliance showed good results for maxillary protraction and pushing the molar distally in patients with skeletal Class Ⅲ with crowding at neutral or distal molar relationship.


Asunto(s)
Cefalometría , Maloclusión de Angle Clase III , Maxilar , Humanos , Maloclusión de Angle Clase III/terapia , Maloclusión/terapia
18.
J Org Chem ; 89(14): 10047-10053, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-38951997

RESUMEN

We have successfully synthesized a series of bidentate ligands by utilizing 2-(trimethylsilyl)phenyl trifluorosulfonate as a precursor for the benzyl group. This method proceeded by inserting a polythiourea into the C═S π-bond, intramolecular ring proton migration, and ring opening. Salient features of this strategy are mild reaction conditions, a novel product structure, excellent stereochemistry, and a good functional group tolerance. Furthermore, a series of density functional theory calculations were performed to gain insights into the transfer mechanism.

19.
Small ; : e2402669, 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38970544

RESUMEN

Sonodynamic therapy (SDT), featuring noninvasive, deeper penetration, low cost, and repeatability, is a promising therapy approach for deep-seated tumors. However, the general or only utilization of SDT shows low efficiency and unsatisfactory treatment outcomes due to the complicated tumor microenvironment (TME) and SDT process. To circumvent the issues, three feasible approaches for enhancing SDT-based therapeutic effects, including sonosensitizer optimization, strategies for conquering hypoxia TME, and combinational therapy are summarized, with a particular focus on the combination therapy of SDT with other therapy modalities, including chemodynamic therapy, photodynamic therapy, photothermal therapy, chemotherapy, starvation therapy, gas therapy, and immunotherapy. In the end, the current challenges in SDT-based therapy on tumors are discussed and feasible approaches for enhanced therapeutic effects are provided. It is envisioned that this review will provide new insight into the strategic design of high-efficiency sonosensitizer-derived nanotheranostics, thereby augmenting SDT and accelerating the potential clinical transformation.

20.
ACS Appl Mater Interfaces ; 16(27): 34819-34829, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38924763

RESUMEN

Sodium-ion batteries (SIBs) represent a promising energy storage technology with great safety. Because of their high operating potential, superior structural stability, and prominent thermal stability, polyanion-type phosphates have garnered significant interest in superior prospective cathode materials for SIBs. Nevertheless, the disadvantages of poor intrinsic electronic conductivity, sluggish kinetics, and volume variation during sodiation/desodiation remain great challenges for satisfactory rate performance and cycle stability, which severely hinder their further practical applications. In this work, by adjusting the amounts of pretreated multiwalled carbon nanotubes (CNT) added intentionally at the beginning of the preparation, biphasic polyanion-type phosphate materials (marked as NFC) are synthesized through a one-pot solid state reaction methodology, which are composed of CNT-interwoven Na3V2(PO4)2F3 (NVPF) and a small amount of Na3V2(PO4)3 (NVP). Benefiting from the improved electronic conductivity and unique composition and structure, the optimized sample (labeled as NFC-2) illustrates exceptional cycle stability and remarkable rate performance. The discharge capacities of the NFC-2 electrode are 114.8 and 78.6 mAh g-1 tested at 20 and 5000 mA g-1, respectively. Notably, such an electrode still gives out 75.7% capacity retention upon 10 000 cycles at 5000 mA g-1. In situ X-ray diffraction analysis demonstrates that the NFC-2 cathode has outstanding structural reversibility during charge/discharge cycles. More importantly, such a biphasic material has achieved impressive electrochemical performance within a wide operating temperature range of -20-50 °C. When temperature is decreased to -20 °C, the NFC-2 electrode still delivers an initial discharge capacity of 102.4 mAh g-1 and exhibits a remarkable capacity retention of 97.8% even after 500 cycles at 50 mA g-1. In addition, the sodium-ion full cell assembled by integrating NFC-2 cathode and hard carbon anode shows a satisfying energy density of 431.3 Wh kg-1 at 20 mA g-1 with a better long-term cycle performance. The synergistic effect among high energy NVPF, conductive CNT, and stable NVP may lead to the great improvement in the electrochemical sodium storage performance of the NFC-2 sample. Such biphasic polyanion-type phosphate materials will inject new ideas into the material design for SIBs with excellent electrochemical performance and further promote practical applications of this advanced energy storage technology.

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