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Lactylation is a lactate-induced post-translational modification best known for its roles in epigenetic regulation. Herein, we demonstrate that MRE11, a crucial homologous recombination (HR) protein, is lactylated at K673 by the CBP acetyltransferase in response to DNA damage and dependent on ATM phosphorylation of the latter. MRE11 lactylation promotes its binding to DNA, facilitating DNA end resection and HR. Inhibition of CBP or LDH downregulated MRE11 lactylation, impaired HR, and enhanced chemosensitivity of tumor cells in patient-derived xenograft and organoid models. A cell-penetrating peptide that specifically blocks MRE11 lactylation inhibited HR and sensitized cancer cells to cisplatin and PARPi. These findings unveil lactylation as a key regulator of HR, providing fresh insights into the ways in which cellular metabolism is linked to DSB repair. They also imply that the Warburg effect can confer chemoresistance through enhancing HR and suggest a potential therapeutic strategy of targeting MRE11 lactylation to mitigate the effects.
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Proteínas de Unión al ADN , Proteína Homóloga de MRE11 , Reparación del ADN por Recombinación , Humanos , ADN , Roturas del ADN de Doble Cadena , Reparación del ADN , Proteínas de Unión al ADN/metabolismo , Epigénesis Genética , Recombinación Homóloga , Proteína Homóloga de MRE11/metabolismo , Ácido Láctico/metabolismoRESUMEN
The coupled relationship between carrier and phonon scattering severely limits the thermoelectric performance of n-type GeTe materials. Here, we provide an efficient strategy to enlarge grains and induce vacancy clusters for decoupling carrier-phonon scattering through the annealing optimization of n-type GeTe-based materials. Specifically, boundary migration is used to enlarge grains by optimizing the annealing time, while vacancy clusters are induced through the aggregation of Ge vacancies during annealing. Such enlarged grains can weaken carrier scattering, while vacancy clusters can strengthen phonon scattering, leading to decoupled carrier-phonon scattering. As a result, a ratio between carrier mobility and lattice thermal conductivity of â¼492.8 cm3 V-1 s-1 W-1 K and a peak ZT of â¼0.4 at 473 K are achieved in Ge0.67Pb0.13Bi0.2Te. This work reveals the critical roles of enlarged grains and induced vacancy clusters in decoupling carrier-phonon scattering and demonstrates the viability of fabricating high-performance n-type GeTe materials via annealing optimization.
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Despite extensive studies on the thermodynamic mechanism governing molecular adsorption at the solid-water interface, a comprehensive understanding of the crucial role of interface properties in mediating the entropy-enthalpy compensation during adsorption is lacking, particularly at a quantitative level. Herein, we employed two types of surface models (hydroxyapatite and graphene) along with a series of amino acids to successfully elucidate how distinct interfacial features dictate the delicate balance between entropy and enthalpy variations. The adsorption of all amino acids on the hydroxyapatite surface is an enthalpy-dominated process, where the water-induced enthalpic component of the free energy and the surface-adsorbate electrostatic interaction term alternatively act as the driving force for adsorption in different regions of the surface. Although favorable interactions are observed between amino acids and the graphene surface, the entropy-enthalpy compensation exhibits dependence on the molecular size of the adsorbates. For small amino acids, favorable enthalpy changes predominantly determine their adsorption behavior; however, larger amino acids tend to bind more tightly with the graphene surface, which is thermodynamically dominated by the entropy variations despite the structural characteristics of amino acids. This study reveals specific entropy-enthalpy mechanisms underlying amino acid adsorption at the solid-liquid interface, providing guidance for surface design and synthesis of new biomolecules.
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As the relative shortage of healthy tissue obviates the option of local soft tissue coverage, reconstruction of circumferential giant congenital melanocytic nevi (GCMN) on the upper extremity remains particularly challenging. Here the authors report a 3-stage procedure involving pre-expanded pedicled flap from the torso for the reconstruction of upper extremity after circumferential GCMN excision in pediatric patients. The giant nevus was completely removed and the size of the excised nevus was 31 × 14.5 cm. The donor site was primarily closed. No major complication was encountered. Reconstruction with expanded pedicled flap achieved satisfactory results, both functionally and cosmetically.
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Nevo Pigmentado , Nevo , Neoplasias Cutáneas , Humanos , Niño , Expansión de Tejido/métodos , Colgajos Quirúrgicos/cirugía , Nevo Pigmentado/cirugía , Nevo Pigmentado/congénito , Neoplasias Cutáneas/cirugía , Neoplasias Cutáneas/congénito , Nevo/cirugía , Extremidad Superior/cirugíaRESUMEN
Accurate wind speed measurement in low-pressure conditions is crucial for the thermal performance validation and attitude control of stratospheric aircraft. As air density decreases, traditional wind speed measurement systems based on principles such as dynamic pressure, heat transfer, ultrasound, and particle velocimetry face significant challenges when applied in low-pressure environments, often failing to achieve the required measurement accuracy. This paper presents the development of a wind speed simulation system based on a rotation method designed to operate in low-pressure conditions, utilizing a space environment simulation chamber in conjunction with a high-precision turntable. The system was employed to conduct response tests on a constant heat flow thermal sphere anemometer within a stratospheric pressure range of 1 kPa to 30 kPa. The experimental results revealed that at extremely low Reynolds numbers, the probe signal exhibited increasing nonlinearity, significantly affecting the response curve at pressures below 15 kPa. While the sensitivity of the hot-sphere probe remained relatively stable at wind speeds above 5 m/s, it decreased nonlinearly as the pressure dropped when wind speeds fell below 5 m/s. Furthermore, this paper analyzes the impact of various interpolation methods on wind speed conversion errors, providing valuable data to support the future development and validation of stratospheric aircraft.
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BACKGROUND & AIMS: Most patients with gastric cancer (GCa) are diagnosed at an advanced stage. We aimed to investigate novel fecal signatures for clinical application in early diagnosis of GCa. METHODS: This was an observational study that included 1043 patients from 10 hospitals in China. In the discovery cohort, 16S ribosomal RNA gene analysis was performed in paired samples (tissues and feces) from patients with GCa and chronic gastritis (ChG) to determine differential abundant microbes. Their relative abundances were detected using quantitative real-time polymerase chain reaction to test them as bacterial candidates in the training cohort. Their diagnostic efficacy was validated in the validation cohort. RESULTS: Significant enrichments of Streptococcus anginosus (Sa) and Streptococcus constellatus (Sc) in GCa tumor tissues (P < .05) and feces (P < .0001) were observed in patients with intraepithelial neoplasia, early and advanced GCa. Either the signature parallel test SaâªSc or single signature Sa/Sc demonstrated superior sensitivity (Sa: 75.6% vs 72.1%, P < .05; Sc: 84.4% vs 64.0%, P < .001; and SaâªSc: 91.1% vs 81.4%, P < .01) in detecting early GCa compared with advanced GCa (specificity: Sa: 84.0% vs 83.9%, Sc: 70.4% vs 82.3%, and SaâªSc: 64.0% vs 73.4%). Fecal signature SaâªSc outperformed SaâªCEA/ScâªCEA in the discrimination of advanced GCa (sensitivity: 81.4% vs 74.2% and 81.4% vs 72.3%, P < .01; specificity: 73.4% vs 81.0 % and 73.4% vs 81.0%). The performance of SaâªSc in the diagnosis of both early and advanced GCa was verified in the validation cohort. CONCLUSION: Fecal Sa and Sc are noninvasive, accurate, and sensitive signatures for early warning in GCa. (ClinicalTrials.gov, Number: NCT04638959).
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Neoplasias Gástricas , Streptococcus constellatus , Detección Precoz del Cáncer , Heces , Humanos , Neoplasias Gástricas/diagnóstico , Streptococcus anginosus/genética , Streptococcus constellatus/genéticaRESUMEN
Methods allow the enhancement of nanofibers via self-assembly are potentially important for new disciplines with many advantages, including multi-anchor interaction, intrinsic mechanical properties and versatility. Herein, a microfluidic-assisted self-assembly process to construct hydroxyl functionalized boron nitride nanosheets (OH-BNNS)/graphene oxide (GO)/thermoplastic polyurethane (TPU) composite nanofiber film, in which stable and precisely controlled self-assembly is fulfilled by the confined ultra-small-volume chip is demonstrated. Multiple fine structural analyses alongside with the density-functional theory (DFT) calculations are implemented to confirm the synergistic effect of noncovalent interactions (hydrogen bonding interaction, π - π stacking interaction, and van der Waals attraction) plays a critical role in the robust micro-structure and a massive 700% enhancement of mechanical strength via adding only 0.3 wt% OH-BNNS and GO. Importantly, profiled from broadband optical absorption ability, robust mechanical properties and outstanding flexibility, the self-assembled 3D OH-BNNS/GO/TPU nanofiber film reveals an adorable evaporation rate of 4.04 kg m-2 h-1 under one sun illumination with stable energy transfer efficiency (93.2%) by accompanying hydrogen bonding interaction. This microfluidic-assisted self-assembly strategy will provide a constructive entry point for the rational design of nanofibers and beyond.
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Polycystic ovary syndrome (PCOS) is an endocrine disorder, affecting women of child-bearing age, and the incidence rate is growing and assuming epidemic proportions. The etiology of PCOS remains unknown and there is no cure. Some animal models for PCOS have been established which have enhanced our understanding of the underlying mechanisms, but omics data for revealing PCOS pathogenesis and for drug discovery are still lacking. In the present study, proteomics analysis was used to construct a protein profile of the ovaries in a PCOS mouse model. The result showed a clear difference in protein profile between the PCOS and control group, with 495 upregulated proteins and 404 downregulated proteins in the PCOS group. The GO term and KEGG pathway analyses of differentially expressed proteins mainly showed involvement in lipid metabolism, oxidative stress, and immune response, which are consistent with pathological characteristics of PCOS in terms of abnormal metabolism, endocrine disorders, chronic inflammation and imbalance between oxidant and antioxidant levels. Also, we found that inflammatory responses were activated in the PCOS ovarium, while lipid biosynthetic process peroxisome, and bile secretion were inhibited. In addition, we found some alteration in unexpected pathways, such as glyoxylate and dicarboxylate metabolism, which should be investigated. The present study makes an important contribution to the current lack of PCOS ovarian proteomic data and provides an important reference for research and development of effective drugs and treatments for PCOS.
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BACKGROUND: Surgical techniques and graft materials are important factors for short nose lengthening in both primary and revision rhinoplasty in Asian patients. Other subunit of the nose need to be improved as well to achieve aesthetic perfection. MATERIALS AND METHODS: A cohort of 98 patients who underwent primary and revision rhinoplasty for moderate to severe short nose deformity from January 1, 2019, to December 31, 2020, were enrolled. Nasal elongation was achieved via an open rhinoplasty approach using autologous costal cartilage exclusively for grafting. Aesthetic outcomes were evaluated by anthropometric measurement and satisfaction assessment from patients and physicians. RESULTS: The mean duration of follow-up was 10.6 months. In both primary and revision cases, nasal length relative to preoperative measurements increased significantly, while nasal tip projection did not differ significantly. Columellar-facial angle and nasofrontal angle decreased significantly in both groups. Both physicians and patients reported improvement in aesthetic outcomes. CONCLUSIONS: Aesthetic satisfaction was reported from both patients and physicians. Autologous costal cartilage is an ideal graft material that offers strong structural support. Caudal septal extension graft using autologous costal cartilage sandwiched by extended spreader grafts achieve satisfactory lengthening of the central compartment and also increase nasal tip projection and rotation.
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Deformidades Adquiridas Nasales , Rinoplastia , Humanos , Rinoplastia/métodos , Deformidades Adquiridas Nasales/cirugía , Estética Dental , Nariz/cirugía , Tabique Nasal/cirugía , ReoperaciónRESUMEN
Liver injury can lead to different hepatic diseases, which are the mainly causes of high global mortality and morbidity. Autophagy and Sirtuin type 1 (SIRT1) have been shown protective effects in response to liver injury. Previous studies have showed that Fibroblast growth factor 21 (FGF21) could alleviate acute liver injury (ALI), but the mechanism remains unclear. Here, we verified the relationship among FGF21, autophagy and SIRT1 in carbon tetrachloride (CCl4 )-induced ALI. We established CCl4 -induced ALI models in C57BL/6 mice and the L02 cell line. The results showed that FGF21 was robustly induced in response to stress during the development of ALI. After exogenous FGF21 treatment in ALI models, liver damage in ALI mice was significantly reduced, as well as serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Consistently, FGF21 also greatly reduced the levels of ALT, AST, pro-inflammatory cytokines interleukin 6 (IL6) and tumour necrosis factor-alpha (TNFα) in ALI cell lines. Mechanistically, exogenous FGF21 treatment efficiently upregulated the expression of autophagy marker microtubule-associated protein light chain-3 beta (LC3 II) and autophagy key molecule coiled-coil myosin-like BCL2-interacting protein (Beclin1), which was accompanied by alleviating hepatotoxicity in CCl4 -treated wild-type mice. Then, we examined how FGF21 induced autophagy expression and found that SIRT1 was also upregulated by FGF21 treatment. To further verify our results, we constructed an anti-SIRT1 lentit-RNAi to inhibit SIRT1 expression in mice and L02 cells, which reversed the protective effect of FGF21 on ALI. In summary, these results indicate that FGF21 alleviates ALI by enhancing SIRT1-mediated autophagy.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Sirtuina 1 , Animales , Autofagia , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Factores de Crecimiento de Fibroblastos , Hígado/metabolismo , Ratones , Ratones Endogámicos C57BL , Sirtuina 1/genética , Sirtuina 1/metabolismoRESUMEN
The ion association is widely believed to be dominated by the favorable entropy change arising from the release of water molecules from ion hydration shells. However, no direct thermodynamic evidence exists to validate the reliability and suitability of this view. Herein, we employ complicated free energy calculations to rigorously split the free energy including its entropic and enthalpic components into the water-induced contributions and ion-ion interaction terms for several ion pairs from monatomic to polyatomic ions, spanning the size range from small kosmotropes to large chaotropes (Na+ , Cs+ , Ca2+ , F- , I- , CO3 2- , and HPO4 2- ). Our results successfully reveal that though ion associations are indeed determined by a delicate balance between the favorable entropy variation and the repulsive enthalpy change, the entropy gain dominated by the solvent occurs only for the monatomic ion pairing. The water-induced entropic contribution significantly goes against the ion pairing between polyatomic anion and cation, which is, alternatively, dominated by the favorable entropy from the ion-ion interaction term, due to the configurational arrangement of polyatomic anions involved in ion association. The structural and dynamic analysis demonstrates that the entropy penalty from the water phase is primarily ascribed to the enhanced stability of water molecules around the cation imposed by the incoming anion. Our study successfully provides a fundamental understanding of water-mediated ion associations and highlights disparate lengthscale dependencies of the dehydration thermodynamics on the specific types of ions.
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Agua , Aniones , Cationes , Entropía , Reproducibilidad de los Resultados , Termodinámica , Agua/químicaRESUMEN
Caustic conditions are often employed for dissolution of a wide variety of minerals, where ion sorption, surface diffusion, and interfacial organization impact surface reactivity. In the case of gibbsite, γ-Al(OH)3, the chemistry at the NaOH(aq) interface is deeply intertwined with industrial processing of aluminum, including metal production and the disposition of Al-containing wastes. To date, little is known about the structure, speciation, and dynamic behavior of gibbsite interfaces (and that of many other minerals) with NaOH(aq)-particularly as a function of ionic strength. Yet concentration-dependent interfacial organization and dynamics are a critical starting point to develop a fundamental understanding of the factors that influence dissolution. This work reports equilibrium molecular dynamics simulations of the γ-Al(OH)3:NaOH(aq) interface, revealing the sorption behavior and speciation of ions from 0.5-10 M [NaOH]. As inner-sphere complexes, Na+ primarily coordinates to the side of the gibbsite hexagonal cavities, while OH- accepts hydrogen-bonding from the surface-OH groups. The mobility of inner-sphere Na+ and OH- ions is significantly reduced due to a strong surface affinity in comparison to previous reports of NaCl, CaCl2, or BaCl2 electrolytes. At high [NaOH], contact ion pairing that is observed in the bulk solution is partially disrupted upon sorption to the gibbsite surface by the individual ion-surface interactions. The molecular-scale changes to surface speciation and competition between ion-surface vs. ion-ion interactions influence surface characterization of gibbsite and potential dissolution processes, providing a valuable baseline for starting conditions needed within future reactive molecular simulations.
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Insulin, as a growth factor, can increase the risk of certain types of cancer. The present study showed that insulin promoted the proliferation of hepatocellular carcinoma cells in vitro and in vivo through pyruvate kinase M2 (PKM2), which is a rate-limiting enzyme in the process of glycolysis. Moreover, the expression of PKM2 was up-regulated by insulin at the posttranslational level in a nuclear orphan receptor TR3-dependent manner. In addition, insulin could enhance the interaction between PKM2 and TR3 and protect PKM2 from degradation. Our results identified a specific mechanism of insulin affecting cancer metabolism and thus promoting cancer progression, and they contribute to a better understanding of the observation that insulin is linked to an increased cancer risk under hyperinsulinemic conditions.
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Carcinoma Hepatocelular/genética , Proteínas Portadoras/genética , Insulina/genética , Neoplasias Hepáticas/genética , Proteínas de la Membrana/genética , Miembro 1 del Grupo A de la Subfamilia 4 de Receptores Nucleares/genética , Hormonas Tiroideas/genética , Carcinogénesis/genética , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica/genética , Glucólisis/genética , Humanos , Insulina/metabolismo , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Proteínas de Unión a Hormona TiroideRESUMEN
OBJECTIVES: Mesenchymal stem cells (MSCs) have become seed cells and basic elements for bone regeneration and bone tissue engineering. The aim of the present study was to investigate the roles and mechanisms of bone morphogenetic protein 2 (BMP-2) on osteogenic differentiation of MSCs. METHODS: Primary MSCs were isolated from the femur and tibia bone of rats and then transfected with BMP-2 and PGC-1α adenovirus vectors. Alkaline phosphatase (ALP) activity and alizarin red staining were used to measure osteogenic differentiation of MSCs. Real-time PCR and western blot assays were performed to assess osteogenic differentiation-related proteins levels. The activities of mitochondrial respiratory chain complexes I and II and mitochondrial fluorescence intensity were used to explore mitochondria status during osteogenic differentiation of MSCs. RESULTS: We found that the ability of BMP-2 overexpressed (OE) group osteogenic differentiation was significantly improved, compared with the negative control (NC) group. The results also indicated that BMP-2 can promote the activity of mitochondria. We further used the gain- and loss-of-function approaches to demonstrate that BMP-2 promotes mitochondrial activity by up-regulating PGC-1α to promote osteogenic differentiation of MSCs. CONCLUSIONS: These results explored the important role of BMP-2 in the osteoblast differentiation of MSCs from a new perspective, providing a theoretical and experimental basis for bone defect and repair.
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Células Madre Mesenquimatosas , Osteogénesis , Animales , Proteína Morfogenética Ósea 2 , Diferenciación Celular , Células Cultivadas , Células Madre Mesenquimatosas/metabolismo , Mitocondrias/metabolismo , Osteogénesis/fisiología , RatasRESUMEN
BACKGROUND: The multiple toothpick-shaped costal cartilage (MTCC) injection technique was introduced as an improvement based on the free diced costal cartilage (FDCC) injection technique for augmentation rhinoplasty. However, radix irregularities may occur when using the MTCC technique. Considering that the FDCC grafts are easier to shape at the nasal radix, we adopted a combination method of the 2 techniques to achieve natural and smooth contour. METHODS: Four patients accepted this method for augmentation rhinoplasty. Through a unilateral marginal incision, the costal cartilage grafts were injected for nasal augmentation at the subperiosteal plane. The FDCC grafts and the MTCC grafts were used for nasal radix and dorsum augmentation, respectively. Nasal contour was adjusted by external shaping. The follow-up ranged from 24 to 43 months. RESULTS: All patients were satisfied with the surgical outcome. There were no major complications occurred during the follow-up. One patient underwent rasping revision due to her own beauty-appreciation changes. CONCLUSIONS: The combination method can take advantages of the FDCC and MTCC injection techniques. It can effectively lower the incidence of contour irregularities and graft displacement. Meanwhile, it is easy to perform without special procedure, and is time-saving and cartilage-saving.
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Cartílago Costal , Rinoplastia , Humanos , Femenino , Cartílago Costal/trasplante , Rinoplastia/métodos , Estudios Retrospectivos , Nariz/cirugía , Cartílago/trasplanteRESUMEN
BACKGROUND: The free diced costal cartilage (FDCC) injection technique has been used in the augmentation rhinoplasty for a long time. In order to lower the incidence of nasal contour irregularities and graft displacement, we developed the multiple toothpick-shaped costal cartilage (MTCC) injection technique. This comparative study was conducted to introduce and assess this new technique. METHODS: This retrospective analysis included 51 patients who underwent augmentation rhinoplasty with either the FDCC or MTCC injection technique at the 17th Department of Plastic Surgery in the Plastic Surgery Hospital between July 2014 and May 2020. The patients were divided into the FDCC (n = 30, 58.82%) and MTCC (n = 21, 41.18%) groups. General data, postoperative patient satisfaction, complications and revision rate were compared between the groups. RESULTS: Except for the follow-up period, there were no significant differences in general data (age, sex, preoperative dorsum deformity, preoperative rhinoplasty history) between the groups. Postoperative patient satisfaction, complications and revision rate were similar between the two groups. CONCLUSIONS: The MTCC injection is a safe and effective technique for augmentation rhinoplasty. Like the FDCC injection technique, the new technique is relatively easy to perform and time-saving with concealed scarring and minimal postoperative edema. Most of its revision surgeries are also easy to perform by simple rasping and reinjection. According to our experience, the new technique may have wider indication as well as lower incidence of nasal contour irregularities and graft displacement. Therefore, we suggest that the MTCC injection technique is reliable and worthy of recommendation. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Cartílago Costal , Rinoplastia , Cartílago Costal/trasplante , Humanos , Nariz/cirugía , Reoperación , Estudios Retrospectivos , Rinoplastia/métodos , Resultado del TratamientoRESUMEN
Xuanfu Daizhe Decoction, first seen in Zhang Zhongjing's Treatise on Cold Damage Diseases, was composed of seven medicinal materials: Inulae Flos, Glycyrrhizae Radix, Ginseng Radix, Zingiberis Rhizoma Recens, Haematitum, Pinelliae Rhizoma and Jujubae Fructus. It was used to treat gastric fullness and hardness and belching due to the wrong treatment of typhoid fever and sweating. With detailed records and description in ancient medical books, Xuanfu Daizhe Decoction was widely adopted in clinical practice by physicians of later generations, which expanded its main therapeutic functions. By comprehensive collation of ancient and modern literature on Xuanfu Daizhe Decoction, this paper systematically explored the historical evolution of the prescription from the source, composition, dosage, processing, clinical application, function interpretation and decocting method. It was found that the composition and processing method of the prescription in the past dynasties were relatively consistent, and there was a gradual decrease in dosage in clinical application. In ancient times, Xuanfu Daizhe Decoction was mainly used to treat nausea, vomiting, hiccups, constipation, etc., while modern clinicians mainly used it for digestive diseases such as reflux esophagitis and gastritis. Through the analysis and textual research, the composition, dosage, processing, function evolution and decocting method of this prescription were determined, which provided reference for the research and development of compound preparations of Xuanfu Daizhe Decoction.
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Medicamentos Herbarios Chinos , Triterpenos , Medicamentos Herbarios Chinos/uso terapéutico , Medicina Tradicional China , Extractos Vegetales , RizomaRESUMEN
New developments in artificial intelligence (AI) offer opportunities to enhance plastic surgery practice, research, and education. In this article, we review relevant AI tools and applications, including machine learning, reinforcement learning, and natural language processing. Our own Markov decision process for keloid treatment illustrates how these models are developed and can be used to enhance decision-making in clinical practice. Finally, we discuss challenges of implementing AI and knowledge gaps that must be addressed to successfully apply AI in plastic surgery. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Queloide , Procedimientos de Cirugía Plástica , Cirugía Plástica , Inteligencia Artificial , Medicina Basada en la Evidencia , HumanosRESUMEN
Fibroblast growth factor 21 (FGF21), a metabolic hormone with pleiotropic effects on glucose and lipid metabolism and insulin sensitivity, alleviates the process of acute pancreatitis (AP). However, its mechanism remains elusive. The pathological and physiological characteristics of FGF21 are observed in both patients with AP and cerulein-induced AP models, and the mechanisms of FGF21 in response to AP are investigated by evaluating the impact of autophagy in FGF21-treated mice and cultured pancreatic cells. Circulating levels of FGF21 significantly increase in both AP patients and cerulein-induced AP mice, which is accompanied by the change of pathology in pancreatic injury. Replenishment of FGF21 distinctly reverses cerulein-induced pancreatic injury and improves cerulein-induced autophagy damage in vivo and in vitro. Mechanically, FGF21 acts on pancreatic acinar cells to up-regulate Sirtuin-1 (Sirt1) expression, which in turn repairs impaired autophagy and removes damaged organs. In addition, blockage of Sirt1 accelerates cerulein-induced pancreatic injury and weakens the regulative effect in FGF21-activated autophagy in mice. These results showed that FGF21 protects against cerulein-induced AP by activation of Sirtuin-1-autophagy axis.
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Autofagia , Factores de Crecimiento de Fibroblastos/metabolismo , Pancreatitis/metabolismo , Pancreatitis/patología , Transducción de Señal , Sirtuina 1/metabolismo , Animales , Autofagosomas/metabolismo , Autofagosomas/ultraestructura , Células Cultivadas , Ceruletida , Factores de Crecimiento de Fibroblastos/sangre , Masculino , Ratones Endogámicos C57BL , Páncreas/patología , Pancreatitis/sangre , Sirtuina 1/sangreRESUMEN
MAIN CONCLUSION: NtALS1 is specifically expressed in glandular trichomes, and can improve the content of acylsugars in tobacco. ABTRACT: The glandular trichomes of many species in the Solanaceae family play an important role in plant defense. These epidermal outgrowths exhibit specialized secondary metabolism, including the production of structurally diverse acylsugars that function in defense against insects and have substantial developmental potential for commercial uses. However, our current understanding of genes involved in acyl chain biosynthesis of acylsugars remains poor in tobacco. In this study, we identified three acetolactate synthase (ALS) genes in tobacco through homology-based gene prediction using Arabidopsis ALS. Quantitative real-time PCR (qRT-PCR) and tissue distribution analyses suggested that NtALS1 was highly expressed in the tips of glandular trichomes. Subcellular localization analysis showed that the NtALS1 localized to the chloroplast. Moreover, in the wild-type K326 variety background, we generated two ntals1 loss-of-function mutants using the CRISPR-Cas9 system. Acylsugars contents in the two ntals1 mutants were significantly lower than those in the wild type. Through phylogenetic tree analysis, we also identified NtALS1 orthologs that may be involved in acylsugar biosynthesis in other Solanaceae species. Taken together, these findings indicate a functional role for NtALS1 in acylsugar biosynthesis in tobacco.