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1.
Asian J Androl ; 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39238320

RESUMEN

This study aimed to introduce a modified Byars staged procedure and investigate its application value in patients with severe hypospadias. We retrospectively analyzed the clinical data of patients with severe hypospadias admitted to the First Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) between October 2012 and October 2022. In total, 31 patients underwent the conventional Byars procedure (conventional group), and 45 patients underwent the modified Byars staged procedure (modified group). Our modified strategy was built upon the standard Byars procedure by incorporating glansplasty during the first stage and employing a Y-shaped flap in conjunction with a glandular tunnel for urethroplasty during the second stage. Notably, there were no statistically significant differences in the preoperative baseline characteristics, duration of surgery, amount of blood loss, or occurrence of postoperative complications, including urethral fistula, stricture and diverticulum, or penile curvature, between the conventional and modified groups. However, there was a significantly lower incidence of coronal sulcus fistula (0 vs 16.1%, P = 0.02) and glans dehiscence (0 vs 12.9%, P = 0.02) in the surgical group than that in the conventional group. In addition, the modified group exhibited a notably greater rate of normotopic urethral opening (100.0% vs 83.9%, P = 0.01) and a higher mean score on the Hypospadias Objective Penile Evaluation (HOPE; mean ± standard error of mean: 8.6 ± 0.2 vs 7.9 ± 0.3, P = 0.02) than did the conventional group. In conclusion, the modified Byars staged procedure significantly reduced the risks of glans dehiscence and coronal sulcus fistula. Consequently, it offers a promising approach for achieving favorable penile esthetics, thereby providing a reliable therapeutic option for severe hypospadias.

2.
Angew Chem Int Ed Engl ; : e202414905, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39266869

RESUMEN

Hybrid local and charge transfer (HLCT) excited state materials, which possess weak donor-acceptor (D-A) pure organic structures, deserve one of the most promising efficient and stable blue emitters. Through high-lying reverse intersystem crossing (hRISC) process, 75% triplet excitons generated by electrical excitation could be harvested and utilized in organic light-emitting diodes (OLEDs). However, there are still significant challenges to achieve high-efficiency ultra-deep-blue HLCT emitters with low Commission Internationale de l'Eclairage (CIE) 1931 chromaticity coordinate y values. Here, a series of novel blue HLCT emitters based on spiro[1,8-diazafluorene-9,2'-imidazole] structure were designed and synthesized by fine-tuning the spiro[fluorene-9,2'-imidazole] core structure in our previous work through heteroatom substitution and hyperconjugation effect. The target emitters were endowed with excellent photophysical and electrochemical merits, thermal stability and solution processibility. The solution-processed OLED device based on 4',5'-bis(4-(9H-carbazol-9-yl)phenyl)spiro[1,8-diazafluorene-9,2'-imidazole] (NFIP-CZ) achieved efficient ultra-deep-blue emission (CIEx,y = 0.1581, 0.0422) with the maximum external quantum efficiency (EQEmax), maximum current efficiency (CEmax) and maximum power efficiency (PEmax) of 11.94%, 4.07 cd·A-1 and 2.56 lm·W-1. The record EQE is a breakthrough in both solution-processed and vacuum vapor deposition ultra-deep-blue HLCT-OLEDs currently.

3.
J Med Case Rep ; 18(1): 441, 2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39272123

RESUMEN

BACKGROUND: Ogden type V tibial tubercle avulsion fracture is an unusual type of physial injury. Thus, little is known about its mechanism of injury and treatment. The type of osteosynthesis is variable and depends on the experience of the surgeon. We commonly used cancellous screws fixation combined with tension band wiring for displaced fracture of the anterior tibial tuberosity. CASE PRESENTATION: The present manuscript describes a case of a Han nationality 13-year-old boy who presented with severe pain of the left knee, which began after landing following a high jump. He had no significant past medical history apart from a high body mass index of 30.3. Radiographs revealed that he had an unusual Ogden type V tibial tubercle avulsion fracture. He was treated by open reduction and combined fixation with cannulated screws and tension-band wiring. After 3 months, the fracture healed without any complications or knee symptoms with full range of motion. He underwent reoperation for symptomatic hardware, which was removed at 5 months after initial surgery, and returned to his prior level of sporting activity at 1 year follow-up. CONCLUSION: Our case suggests that excellent functional outcome could be achievable by open reduction with the combination of internal fixation and tension-band wiring for Ogden type V tibial tubercle avulsion fracture. This type of osteosynthesis could not only achieve anatomical reduction and stable fixation for such fractures, but also avoid further damage to the proximal tibial epiphysis, which prevents serious complications, such difference in leg length.


Asunto(s)
Tornillos Óseos , Fijación Interna de Fracturas , Fracturas por Avulsión , Fracturas de la Tibia , Humanos , Masculino , Adolescente , Fijación Interna de Fracturas/métodos , Fracturas de la Tibia/cirugía , Fracturas de la Tibia/diagnóstico por imagen , Fracturas por Avulsión/cirugía , Fracturas por Avulsión/diagnóstico por imagen , Resultado del Tratamiento , Radiografía , Hilos Ortopédicos , Rango del Movimiento Articular , Reoperación , Reducción Abierta/métodos
4.
Acta Odontol Scand ; 83: 537-545, 2024 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-39324573

RESUMEN

OBJECTIVE: To elucidate cone-beam computed tomography (CBCT) referral profiles in Western Norway. MATERIALS AND METHODS: In all, 3,031 referrals to oral- and maxillofacial radiologist were reviewed. Patient data were retrieved retrospectively from electronic charts. The patient's age, gender, and perceived clinical indication were noted, as well as relevant medical and dental history and whether the referring clinician was a general dentist or held a clinical dental specialty. RESULTS: A total of 2,680 referrals fulfilled the inclusion criteria (UiB n = 1,471, and TkVestland, n = 1,209). The female:male ratio was 1,427:1,253. Mean age was 33 years - 35 years for females compared to 31 years for males (p < 0.001). The most common clinical indications were related to impacted teeth (29%), endodontic issues (17%), cleft lip palate (12%), and resorptions (10%). Less common were bone lesions, implant planning, trauma to the teeth or jaws, atypical orofacial pain, and temporo-mandibular joint (TMJ). The patient age-profiles mirrored differences in indications within the cohort. Most referrals were from specialist dentists such as orthodontists, oral surgeons, and endodontists. Interestingly, 543/2,680 (20%) referrals were from general dentists.  Conclusions: Specialist dentists such as orthodontists, oral surgeons, and endodontists refer most patients for clinical indications such as impacted teeth, endodontic issues, and resorptions.


Asunto(s)
Tomografía Computarizada de Haz Cónico , Derivación y Consulta , Humanos , Noruega , Tomografía Computarizada de Haz Cónico/estadística & datos numéricos , Tomografía Computarizada de Haz Cónico/métodos , Estudios Retrospectivos , Masculino , Femenino , Adulto , Derivación y Consulta/estadística & datos numéricos , Persona de Mediana Edad , Adolescente , Adulto Joven , Anciano , Niño
5.
Compr Rev Food Sci Food Saf ; 23(5): e13432, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39289792

RESUMEN

Storage is an important process involved in the postharvest treatment of grain-oilseed and is necessary for maintaining high quality and ensuring the long-term supply of these commodities in the food industry. Proper storage practices help prevent spoilage, maintain nutritional value, and preserve marketable quality. It is of great interest for storage to investigate flow, heat and mass transfer processes, and quality change for optimizing the operation parameters and ensuring the quality of grain-oilseed. This review discusses the mathematical models developed and applied to describe the physical field, biological field, and quality change during the storage of grain-oilseed. The advantages, drawbacks, and industrial relevance of the existing mathematical models were also critically evaluated, and an organic system was constructed by correlating them. Finally, the future research trends of the mathematical models toward the development of multifield coupling models based on biological fields to control quality were presented to provide a reference for further directions on the application of numerical simulations in this area. Meanwhile, artificial intelligence (AI) can greatly enhance our understanding of the coupling relationships within grain-oilseed storage. AI's strengths in both qualitative and quantitative analysis, as well as its effectiveness, make it an invaluable tool for this purpose.


Asunto(s)
Grano Comestible , Almacenamiento de Alimentos , Modelos Teóricos , Almacenamiento de Alimentos/métodos , Grano Comestible/química , Semillas/química , Inteligencia Artificial , Aceites de Plantas/química
6.
J Pharm Biomed Anal ; 251: 116447, 2024 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-39197205

RESUMEN

Cis-trans isomers of N-isobutyl-2E,4E,8Z,10E-dodecatetraenamide (DDA-E) and N-isobutyl-2E,4E,8Z,10Z-dodecatetraenamide (DDA-Z) are representative alkamides with numbness of tongue, anti-inflammatory and analgesic activities of Asari Radix et Rhizoma. However, their respective metabolic pathways and pharmacokinetic behaviors are still unknown. This study aim to investigate the metabolism of the two alkamides in vitro and in vivo using ultra-high-performance liquid chromatography-quadruple-time-of-flight mass spectrometry. Furthermore, a rapid, sensitive, and selective ultra-high-performance liquid chromatography-tandem mass spectrometry method was developed to quantify DDA-E/Z in rat plasma. Results indicated that DDA-E and DDA-Z showed significant differences in metabolism and pharmacokinetics. Across all samples, 24 metabolites of DDA-E and 21 metabolites of DDA-Z were detected. A variety of pathways were involved in the production of these metabolites, mainly hydroxylation and oxidation. The linear range of DDA-E/Z was 1-2500 ng/mL (R2 = 0.9984), and the lowest quantification limit was 1 ng/mL. Precision, accuracy, extraction recovery, matrix effect, and stability of DDA-E/Z were within acceptable limits. Pharmacokinetic research was conducted using male Sprague-Dawley rats receiving intravenous (1 mg/kg) or intragastric (40 mg/kg) administration of DDA-E or DDA-Z solution. There was a calculated absolute bioavailability of 15.67 % for DDA-E and 4.83 % for DDA-Z when consumed orally. The apparent volume of distribution of intravenous and intragastric administrations were 4.44 ± 0.41 L/kg and 5.18 ± 0.67 L/kg for DDA-E, and 1.56 ± 1.66 L/kg and 2.35 ± 0.42 L/kg for DDA-Z. The maximal plasma concentrations of DDA-E and DDA-Z were 599.84 ± 149.92 nM and 422.09 ± 69.17 nM, and the time to maximum peak were 4.33 ± 3.51 h and 0.70 ± 1.12 h, respectively. In conclusion, in subsequent pharmacodynamics and safety evaluation studies, great attention should be paid to the metabolic characteristics and pharmacokinetic differences between DDA-E and DDA-Z.


Asunto(s)
Medicamentos Herbarios Chinos , Ratas Sprague-Dawley , Espectrometría de Masas en Tándem , Animales , Espectrometría de Masas en Tándem/métodos , Cromatografía Líquida de Alta Presión/métodos , Masculino , Ratas , Medicamentos Herbarios Chinos/farmacocinética , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/análisis , Isomerismo , Rizoma/química , Microsomas Hepáticos/metabolismo , Administración Oral
7.
Pathol Res Pract ; 262: 155503, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39128411

RESUMEN

Gastric cancer (GC), a globally prevalent and lethal malignancy, continues to be a key research focus. However, due to its considerable heterogeneity and complex pathogenesis, the treatment and diagnosis of gastric cancer still face significant challenges. With the rapid development of spatial omics technology, which provides insights into the spatial information within tumor tissues, it has emerged as a significant tool in gastric cancer research. This technology affords new insights into the pathology and molecular biology of gastric cancer for scientists. This review discusses recent advances in spatial omics technology for gastric cancer research, highlighting its applications in the tumor microenvironment (TME), tumor heterogeneity, tumor genesis and development mechanisms, and the identification of potential biomarkers and therapeutic targets. Moreover, this article highlights spatial omics' potential in precision medicine and summarizes existing challenges and future directions. It anticipates spatial omics' continuing impact on gastric cancer research, aiming to improve diagnostic and therapeutic approaches for patients. With this review, we aim to offer a comprehensive overview to scientists and clinicians in gastric cancer research, motivating further exploration and utilization of spatial omics technology. Our goal is to improve patient outcomes, including survival rates and quality of life.


Asunto(s)
Biomarcadores de Tumor , Genómica , Neoplasias Gástricas , Microambiente Tumoral , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Neoplasias Gástricas/metabolismo , Humanos , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Medicina de Precisión , Proteómica/métodos
8.
J Cancer Res Ther ; 20(4): 1323-1333, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39206995

RESUMEN

BACKGROUND: Protein arginine deiminase 3 (PADI3) is involved in various biological processes of human disease. PADI3 has recently received increasing attention due to its role in tumorigenesis. In a previous study, we found that PADI3 plays a tumor suppressor role in colon cancer by inducing cell cycle arrest, but its critical role and mechanism in cancer metastasis remain obscure. In this study, we fully studied the role of PADI3 in colon cancer cell metastasis. METHODS: The expression levels of related proteins were detected by Western blotting, and Transwell and wound healing assays were used to examine the cell migration ability. Flow cytometry was used to measure and exclude cell apoptosis-affected cell migration. Both overexpression and rescue experiments were employed to elucidate the molecular mechanism of CKS1 in colon cancer cells. RESULTS: The expression levels of PADI3 and CKS1 are negatively related, and PADI3 can promote CKS1 degradation in a ubiquitin-dependent manner. PADI3 can suppress colon cancer cell migration and reduce the wound healing speed by inhibiting CKS1 expression. The molecular mechanism showed that CKS1 can promote EMT by increasing Snail and N-cadherin expression and suppressing E-cadherin expression. PADI3, as a suppressor of CKS1, can block the process of EMT by impairing CKS1-induced Snail upregulation and E-cadherin downregulation; however, the expression of N-cadherin cannot be rescued. CONCLUSIONS: CKS1 promotes EMT in colon cancer by regulating Snail/E-cadherin expression, and this effect can be reversed by PADI3 via the promotion of CKS1 degradation in a ubiquitylation-dependent manner.


Asunto(s)
Quinasas CDC2-CDC28 , Movimiento Celular , Neoplasias del Colon , Transición Epitelial-Mesenquimal , Transducción de Señal , Humanos , Neoplasias del Colon/patología , Neoplasias del Colon/metabolismo , Neoplasias del Colon/genética , Quinasas CDC2-CDC28/metabolismo , Quinasas CDC2-CDC28/genética , Hidrolasas/metabolismo , Hidrolasas/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Apoptosis , Cadherinas/metabolismo , Cadherinas/genética , Proliferación Celular , Antígenos CD
9.
Thorac Cancer ; 2024 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-39155057

RESUMEN

BACKGROUND: To evaluate the safety and efficacy of percutaneous biopsy and microwave ablation (B + MWA) in patients with pulmonary nodules (PNs) who are receiving antithrombotic therapy by rivaroxaban as bridging therapy. METHODS: The study comprised 187 patients with PNs who underwent 187 B + MWA sessions from January 1, 2020, to December 31, 2021. The enrolled patients were divided into two groups: Group A, who received antithrombotic therapy five days before the procedure and received rivaroxaban as a bridging drug during hospitalization, and group B, who had no antithrombotic treatment. Information about the technical success rate, positive biopsy rate, complete ablative rate, and major complications were collected and analyzed. RESULTS: Group A comprised 53 patients and group B comprised 134 patients. The technical success rate was 100% in both groups. The positive biopsy rates were 88.68% and 91.04%, respectively (p = 0.6211, X2 = 0.2443). In groups A and B, the complete ablative rates at 6, 12, and 24 months were 100.0% versus 99.25%, 96.23% versus 96.27%, and 88.68% versus 89.55%, respectively. There were no significant differences in bleeding and thrombotic complications between the two groups. No grade 5 complications occurred. CONCLUSIONS: It is generally considered safe and effective that patients who are on antithrombotic therapy by rivaroxaban as bridging to undergo B + MWA for treating PNs.

10.
J Cancer Res Ther ; 20(4): 1130-1140, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39206974

RESUMEN

ABSTRACT: Intestinal microecology (IM) is the largest and most important microecological system of the human body. Furthermore, it is the key factor for activating and maintaining the physiological functions of the intestine. Numerous studies have investigated the effects of the gut microbiota on the different tissues and organs of the human body as well as their association with various diseases, and the findings are gradually being translated into clinical practice. The gut microbiota affects the occurrence, progression, treatment response, and toxic side effects of tumors. The deepening of research related to IM and tumors has opened a new chapter in IM research driven by methods and technologies such as second-generation sequencing and bioinformatics. The IM maintains the function of the host immune system and plays a pivotal role in tumor-control drug therapy. Increasing evidence has proven that the efficacy of tumor-control drugs largely depends on the IM balance, and strategies based on the IM technology show promising application prospects in the diagnosis and treatment of tumor. The Tumor and Microecology Professional Committee of the Chinese Anti-cancer Association gathered relevant experts to discuss and propose the "Chinese guidelines for integrated diagnosis and treatment of IM technologies in tumor application (2024 Edition)," which was established based on the research progress of the application of the IM technology in tumor to provide a basis for the standardization of the diagnosis and treatment of the IM technology in the tumor.


Asunto(s)
Microbioma Gastrointestinal , Neoplasias , Humanos , China , Microbioma Gastrointestinal/efectos de los fármacos , Neoplasias/diagnóstico , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Neoplasias/patología
11.
Heliyon ; 10(14): e34302, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39104499

RESUMEN

Measuring the impact of project portfolio synergy (PPSI) is crucial for making informed decisions to improve the strategic realization of a project portfolio. However, the literature has failed to measure PPSI effectively from the perspective of project element flow and to explore the differences in synergy relationships between homogeneous and heterogeneous projects. Consequently, this study proposes a framework for measuring PPSI from the perspective of project element flow. First, based on analyzing the synergistic relationship between projects, the corresponding project element datum quantity is determined according to the different types of element flow forms. Second, the synergy degree between homogeneous and heterogeneous projects is quantified through project similarity and correlation. Third, a dynamic measurement model is constructed using System Dynamics to solve the complex interactive feedback and dynamics in the PPSI measurement system. Finally, the framework is demonstrated and validated by a numerical example of project management in Xi'an, Shaanxi Province. The results indicate that the model can effectively measure PPSI and identify the key factors generating it. In implementing the portfolio, managers must focus on sharing and integrating newly developed technologies and information, thus facilitating the generation of PPSI. This study extends the boundary of project portfolio synergy theory and contributes to the literature on measuring PPSI by focusing on the elements flow within portfolios. Additionally, the model provides an effective tool for managers to forecast PPSI and determine appropriate optimization strategies.

12.
Plant Cell Environ ; 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39101664
13.
PLoS One ; 19(7): e0303820, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39078856

RESUMEN

Although humans can recognize their body movements in point-light displays, self-recognition ability varies substantially across action types and participants. Are these variations primarily due to an awareness of visually distinct movement patterns, or to underlying factors related to motoric planning and/or individual differences? To address this question, we conducted a large-scale study in self-action recognition (N = 101). We motion captured whole-body movements of participants who performed 27 different actions across action goals and degree of motor planning. After a long delay period (~ 1 month), participants were tested in a self-recognition task: identifying their point-light action amongst three other point-light actors performing identical actions. We report a self-advantage effect from point-light actions, consistent with prior work in self-action recognition. Further, we found that self-recognition was modulated by the action complexity (associated with the degree of motor planning in performed actions) and individual differences linked to motor imagery and subclinical autism and schizotypy. Using dynamic time warping, we found sparse evidence in support of visual distinctiveness as a primary contributor to self-recognition, though speed distinctiveness negatively influenced self-recognition performance. Together, our results reveal that self-action recognition involves more than an awareness of visually distinct movements, with important implications for how the motor system may be involved.


Asunto(s)
Individualidad , Humanos , Femenino , Masculino , Adulto , Adulto Joven , Movimiento/fisiología , Reconocimiento en Psicología/fisiología , Desempeño Psicomotor/fisiología , Adolescente
14.
J Pharm Biomed Anal ; 249: 116340, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-38986349

RESUMEN

Zuojin Pill (ZJP), a traditional Chinese medicine prescription composed of Rhizoma Coptidis and Euodiae Fructus in the ratio of 6:1 (w/w), has been widely used for the treatment of gastric disorders. However, an in-depth understanding of in vivo metabolism and distribution profiles of protoberberine alkaloids (PBAs) and indole alkaloids (IDAs) in ZJP is lacking. In this study, a method using ultra-high performance liquid chromatography coupled with quadruple time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) was developed to systematically screen the alkaloids and their metabolites in rat plasma and various tissues after oral administration of ZJP. Furthermore, bioinformatics and molecular docking analyses were conducted to elucidate the contribution of the alkaloids and metabolites enriched in the stomach to the therapeutic effect of ZJP on gastritis. A total of 33 compounds, including 7 prototype alkaloids and 26 metabolites, were chemically defined or tentatively identified in this work. The metabolic pathways of PBAs (hydroxylation, oxidation, reduction, demethylation, demethylenation, glucuronide conjugation, sulfate conjugation) and IDAs (hydroxylation, glucuronide conjugation) were revealed. Notably, 7 prototype alkaloids and 18 metabolites were detected in the stomach, indicating their propensity for gastric distribution. These alkaloids and metabolites showed strong affinities with the 7 hub targets associated with gastritis, such as CCR7, CXCR4, IL6, IFNG, CCL2, TNF, and PTPRC, and could be considered the potential active substances of ZJP for treating gastritis. In conclusion, this study clarified the gastric distribution propensity of PBAs and IDAs and their metabolites, as well as their favorable binding interactions with gastritis-related targets, which could provide essential data for the further study of the pharmacodynamic material basis and gastroprotective mechanism of ZJP.


Asunto(s)
Medicamentos Herbarios Chinos , Simulación del Acoplamiento Molecular , Ratas Sprague-Dawley , Animales , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/farmacocinética , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/análisis , Cromatografía Líquida de Alta Presión/métodos , Administración Oral , Ratas , Masculino , Biología Computacional/métodos , Espectrometría de Masas en Tándem/métodos , Alcaloides/administración & dosificación , Alcaloides/análisis , Alcaloides/química , Alcaloides/farmacocinética , Alcaloides Indólicos/farmacocinética , Alcaloides Indólicos/química , Alcaloides Indólicos/administración & dosificación , Alcaloides Indólicos/metabolismo , Alcaloides de Berberina/farmacocinética , Alcaloides de Berberina/análisis , Espectrometría de Masas/métodos
15.
Proc Natl Acad Sci U S A ; 121(29): e2323040121, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-38985761

RESUMEN

Stomata in leaves regulate gas (carbon dioxide and water vapor) exchange and water transpiration between plants and the atmosphere. SLow Anion Channel 1 (SLAC1) mediates anion efflux from guard cells and plays a crucial role in controlling stomatal aperture. It serves as a central hub for multiple signaling pathways in response to environmental stimuli, with its activity regulated through phosphorylation via various plant protein kinases. However, the molecular mechanism underlying SLAC1 phosphoactivation has remained elusive. Through a combination of protein sequence analyses, AlphaFold-based modeling and electrophysiological studies, we unveiled that the highly conserved motifs on the N- and C-terminal segments of SLAC1 form a cytosolic regulatory domain (CRD) that interacts with the transmembrane domain(TMD), thereby maintaining the channel in an autoinhibited state. Mutations in these conserved motifs destabilize the CRD, releasing autoinhibition in SLAC1 and enabling its transition into an activated state. Our further studies demonstrated that SLAC1 activation undergoes an autoinhibition-release process and subsequent structural changes in the pore helices. These findings provide mechanistic insights into the activation mechanism of SLAC1 and shed light on understanding how SLAC1 controls stomatal closure in response to environmental stimuli.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Estomas de Plantas , Transducción de Señal , Fosforilación , Estomas de Plantas/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Arabidopsis/metabolismo , Arabidopsis/genética , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Dominios Proteicos , Mutación
16.
Environ Pollut ; 360: 124580, 2024 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-39032549

RESUMEN

Published evidences have suggested that air pollutant benzo(a)pyrene (BaP) may modify the toxicity and adverse effects produced by other toxicants. However, the precise role of short-term exposure to low-dose BaP on acute lung injury (ALI) induced by crystalline silica (CS) and the underlying mechanisms remain to be clarified. To investigate this issue, a mouse co-exposure model was established by intratracheal instillation of 2.5 mg CS and BaP alone or in combination. Our data found that CS exposure resulted in ALI as evidenced by lung histological changes, elevated lactate dehydrogenase activity, increased level of pro-inflammatory markers and enhanced oxidative damage. Although exposure to BaP alone had little effect on the pathological changes of mice lung tissues except for occasionally mild inflammation, it could aggravate the CS-induced ALI in a dose-dependent manner. Bioinformatic analysis of transcriptome sequencing suggested that the expression changes of significantly differentially expressed genes were closely related to the severity of ALI. The joined analysis of STC and WGCNA found that "NOD-like receptor signaling pathway", "toll-like receptor signaling pathway", "TNF signaling pathway", and "NF-kappa B signaling pathway" associated with immune and inflammatory response were the most prominent significant pathways. TLR2/9 and Nod2 might be the key inflammation-related genes that were differentially expressed in the combined lung toxicity induced by CS and BaP exposure. All these findings suggest that co-exposure of CS and low-dose BaP can cause more severe lung inflammation and oxidative damage in mice than exposure alone, which may be useful in the management and prevention of silicosis. The roles of TLR2/9 and Nod2 as candidate targets in the combined toxicity need further exploration.


Asunto(s)
Lesión Pulmonar Aguda , Benzo(a)pireno , Dióxido de Silicio , Animales , Benzo(a)pireno/toxicidad , Ratones , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/genética , Lesión Pulmonar Aguda/metabolismo , Dióxido de Silicio/toxicidad , Transcriptoma/efectos de los fármacos , Masculino , Pulmón/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Contaminantes Atmosféricos/toxicidad , Estrés Oxidativo/efectos de los fármacos
17.
J Control Release ; 373: 201-215, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39004104

RESUMEN

Traditional bolus vaccines typically require multiple doses, which complicates the vaccination process and may cause missed shots, leading to sub-optimal immunity and reduced vaccine effectiveness. Herein, a gel-based long-acting vaccine system with self-adjuvant properties based on laponite was constructed to simplify vaccination procedures and improve vaccine effectiveness. Firstly, the gel system could recruit multiple types of immune cells to form immune niches. Secondly, it could achieve sustained delivery of antigens to lymph nodes by active transport and passive drainage. Then, the gel system triggered the formation of a large number of germinal centers, which elicited enhanced and durable humoral immune responses, as well as strong cellular immune responses. As a result, it eventually showed good prophylactic and therapeutic effects in a variety of tumor models including melanoma, colorectal cancer and peritoneal metastasis models. By further combining the immunoadjuvant CpG ODN and cytokine IL-12, the effect of the gel-vaccine could be further enhanced. In a murine peritoneal metastasis model of colorectal carcinoma, a single administration of the gel-vaccine resulted in complete tumor eradication in 8/9 mice. In summary, this study developed an immunologically active gel-vaccine system. And as a robust and versatile vaccine platform, by loading different antigens and adjuvants, this gel-vaccine system is expected to realize its better therapeutic potential.


Asunto(s)
Adyuvantes Inmunológicos , Vacunas contra el Cáncer , Geles , Ratones Endogámicos C57BL , Silicatos , Animales , Vacunas contra el Cáncer/administración & dosificación , Vacunas contra el Cáncer/inmunología , Silicatos/química , Silicatos/administración & dosificación , Femenino , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/química , Línea Celular Tumoral , Oligodesoxirribonucleótidos/administración & dosificación , Oligodesoxirribonucleótidos/química , Sistemas de Liberación de Medicamentos , Ratones Endogámicos BALB C , Interleucina-12/inmunología , Ratones , Neoplasias Colorrectales/inmunología
18.
Plant Cell ; 36(9): 2931-2975, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-38980154

RESUMEN

Proteolysis, including post-translational proteolytic processing as well as protein degradation and amino acid recycling, is an essential component of the growth and development of living organisms. In this article, experts in plant proteolysis pose and discuss compelling open questions in their areas of research. Topics covered include the role of proteolysis in the cell cycle, DNA damage response, mitochondrial function, the generation of N-terminal signals (degrons) that mark many proteins for degradation (N-terminal acetylation, the Arg/N-degron pathway, and the chloroplast N-degron pathway), developmental and metabolic signaling (photomorphogenesis, abscisic acid and strigolactone signaling, sugar metabolism, and postharvest regulation), plant responses to environmental signals (endoplasmic-reticulum-associated degradation, chloroplast-associated degradation, drought tolerance, and the growth-defense trade-off), and the functional diversification of peptidases. We hope these thought-provoking discussions help to stimulate further research.


Asunto(s)
Proteínas de Plantas , Plantas , Proteolisis , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Plantas/metabolismo , Plantas/genética , Transducción de Señal , Procesamiento Proteico-Postraduccional
19.
World J Methodol ; 14(2): 91889, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38983655

RESUMEN

BACKGROUND: However, the connection between smoking and the prognosis of patients with bladder cancer remains unclear. AIM: To determine whether smoking is linked to the recurrence and progression of bladder cancer. METHODS: As of July 20, 2022, relevant English-language research was identified by searching PubMed, the Web of Science, and the Cochrane Library. We pooled the available data from the included studies using a random effects model. Subgroup analysis and sensitivity analysis were also conducted. RESULTS: A total of 12 studies were included in this meta-analysis. The combined analysis revealed that tobacco exposure was associated with a significantly greater recurrence rate than nonsmoking status [odd ratios (OR) = 1.76, 95%CI: 1.84-2.93], and the progression of bladder cancer was significantly greater in smokers than in nonsmokers (OR = 1.21, 95%CI: 1.02-1.44). Stratified analysis further revealed that current smokers were more likely to experience relapse than never-smokers were (OR = 1.85, 95%CI: 1.11-3.07). Former smokers also had a greater risk of relapse than did never-smokers (OR = 1.73, 95%CI: 1.09-2.73). Subgroup analysis indicated that non-Caucasians may be more susceptible to bladder cancer recurrence than Caucasians are (OR = 2.13, 95%CI: 1.74-2.61). CONCLUSION: This meta-analysis revealed that tobacco exposure may be a significant risk factor for both the recurrence and progression of bladder cancer.

20.
Front Plant Sci ; 15: 1420649, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38947943

RESUMEN

Introduction: Targeted herbicide application refers to precise application of herbicides in weed-infested areas according to the location and density of farmland weeds. At present, targeted herbicide application in wheat fields generally faces problems including the low herbicide adhesion rate, leading to omission and excessive loss of herbicides. Methods: To solve these problems, changes in the impact force of herbicide and the weed leaves in the operation process of a spraying system were studied from the interaction between weeds and herbicides applied. A dynamic model of weed leaves was established. On this basis, the research indicated that the herbicide adhesion rate is highest under spraying pressure of 0.4 MPa and flow rate of 0.011 kg/s when the spray height is 300 mm. To study the dynamic deformation of weed leaves and the distribution of liquid herbicides in the external flow field under weed-herbicide interaction, a dynamic simulation model of herbicide application was built using the finite element method. Results and Discussion: The results show that when the spray height is 300 mm, the maximum weed leaf deformation index (LDI) is 0.43 and the velocity in the external flow field is 0 m/s under spraying pressure of 0.4 MPa and flow rate of 0.011 kg/s. This finding indicates that the herbicide is not splashed elsewhere and the turbulence intensity in the weed area is 2%, implying steady flow of the herbicide, most of which can be retained on weed leaves. Field test results of application quality of the herbicide show that the maximum LDI is 0.41 and the coverage of the herbicide in the sheltered area below the leaves is 19.02% when the spraying pressure is 0.4 MPa, flow rate is 0.011 kg/s, and spray height is 300 mm. This solves the problem of a low rate of utilization of herbicides because the herbicide passes through weed plants, and achieves the precision herbicide application in wheat fields.

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