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1.
Methods Mol Biol ; 2854: 143-151, 2025.
Artículo en Inglés | MEDLINE | ID: mdl-39192126

RESUMEN

Protein lysine acetylation involved in the antiviral innate immunity contributes to the regulation of antiviral inflammation responses, including type 1 interferon production and interferon-stimulated gene expression. Thus, investigation of acetylated antiviral proteins is vital for the complete understanding of inflammatory responses to viral infections. Immunoprecipitation (IP) assay with anti-targeted-protein antibody or with acetyl-lysine affinity beads followed by immunoblot provides a classical way to determine the potential modified protein in the antiviral innate pathways, whereas mass spectrometry can be utilized to identify the accurate acetylation lysine residues or explore the acetyl-proteomics. We demonstrate here comprehensive methods of protein lysine acetylation determination in virus-infected macrophages and embryonic fibroblast cells or proteins-overexpressed HEK 293 T cells in the context of antiviral innate immunity.


Asunto(s)
Inmunidad Innata , Lisina , Humanos , Acetilación , Lisina/metabolismo , Células HEK293 , Inmunoprecipitación/métodos , Macrófagos/inmunología , Macrófagos/metabolismo , Procesamiento Proteico-Postraduccional , Proteómica/métodos , Animales , Espectrometría de Masas/métodos , Ratones , Fibroblastos/metabolismo , Fibroblastos/inmunología , Fibroblastos/virología
2.
BMC Med ; 22(1): 402, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39300429

RESUMEN

BACKGROUND: The Medium and Long-Term Plan for the Prevention and Treatment of Chronic Diseases (2017-2025) in China has highlighted the importance of reducing fat, sodium, and sugar in foods. However, front-of-pack labeling, which enables consumers to assess the health levels of prepackaged foods, is lacking in China. In response to the Zhejiang Provincial Health Commission's request, we sought to develop a method for efficiently evaluating the health level of prepackaged foods. METHODS: Through a comprehensive literature review, we established a systematic framework: the Prepackaged Foods Healthiness Ranking Index (PHRI). We determined specific threshold values and grading criteria and conducted two rounds of Delphi survey to refine the index. Using a measurement dataset, we aimed to determine the optimal limit values for assessing the health level of prepackaged foods in real-world settings. RESULTS: After two rounds of Delphi surveys, the PHRI underwent multiple revisions until consensus among experts was reached. The final decision regarding the upper limit values set 30% Nutrient Reference Values as the limit for solid foods and 15% Nutrient Reference Values for liquid foods. The calculation of PHRI values was successfully implemented with the dataset, in accord with current nutrition awareness and real-world conditions. CONCLUSIONS: The PHRI provides a valuable tool for assessing the healthiness of prepackaged foods. This front-of-pack labeling system provides a convenient method for evaluating the nutritional quality of prepackaged foods. Ultimately, the PHRI has the potential to contribute to advancements in health policy, practice, and education in China.


Asunto(s)
Técnica Delphi , Etiquetado de Alimentos , China , Etiquetado de Alimentos/normas , Etiquetado de Alimentos/métodos , Humanos , Embalaje de Alimentos/normas , Valor Nutritivo
3.
Front Mol Biosci ; 11: 1409060, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39247207

RESUMEN

Objective: This study aimed to investigate the value of a CT-enhanced scanning radiomics nomogram in distinguishing between early hepatic abscess (EHA) and intrahepatic cholangiocarcinoma (ICC) and to validate its diagnostic efficacy. Materials and Methods: Clinical and imaging data on 112 patients diagnosed with EHA and ICC who underwent double-phase CT-enhanced scanning at our hospital were collected. The contours of the lesions were delineated layer by layer across the three phases of CT scanning and enhancement using 3D Slicer software to define the region of interest (ROI). Subsequently, the contours were merged into 3D models, and radiomics features were extracted using the Radiomics plug-in. The data were randomly divided into training (n = 78) and validation (n = 34) cohorts at a 7:3 ratio, using the R programming language. Standardization was performed using the Z-score method, and LASSO regression was used to select the best λ-value for screening variables, which were then used to establish prediction models. The rad-score was calculated using the best radiomics model, and a joint model was constructed based on the rad-score and clinical scores. A nomogram was developed based on the joint model. The diagnostic efficacy of the models for distinguishing ICC and EHA was assessed using receiver operating characteristic (ROC) curve and area under the curve (AUC) analyses. Calibration curves were used to evaluate the reliability and accuracy of the nomograms, while decision curves and clinical impact curves were utilized to assess their clinical value. Results: Compared with the ICC group, significant differences were observed in clinical data and imaging characteristics in the EHA group, including age, centripetal enhancement, hepatic pericardial depression sign, arterial perfusion abnormality, arterial CT value, and arteriovenous enhancement (p < 0.05). Logistic regression analysis identified centripetal enhancement, hepatic pericardial depression sign, arterial perfusion abnormality, arterial CT value, and arteriovenous enhancement as independent influencing factors. Three, five, and four radiomics features were retained in the scanning, arterial, and venous phases, respectively. Single-phase models were constructed, with the radiomics model from the arterial phase demonstrating the best diagnostic efficacy. The rad-score was calculated using the arterial-phase radiomics model, and nomograms were drawn in conjunction with the clinical model. The nomogram based on the combined model exhibited the highest differential diagnostic efficacy between EHA and ICC (training cohort: AUC of 0.972; validation cohort: AUC of 0.868). The calibration curves indicated good agreement between the predicted and pathological results, while decision curves and clinical impact curves demonstrated higher clinical utility of the nomograms. Conclusion: The CT-enhanced scanning radiomics nomogram demonstrates high clinical value in distinguishing between EHA and ICC, thereby enhancing the accuracy of preoperative diagnosis.

4.
J Neuroimmunol ; 394: 578419, 2024 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-39088908

RESUMEN

Oxytocin can regulate immunological activity directly or indirectly; however, immunological functions and mechanisms of oxytocin actions under chronic stress like cesarean delivery (CD) are poorly understood. Our study found that abnormal oxytocin production and secretion in CD rats caused atrophy of thymic tissues. Neurotoxin kainic acid microinjected into the dorsolateral supraoptic nucleus in male rats selectively reduced hypothalamic oxytocin levels, increased corticotrophin-releasing hormone and plasma interleukin-1ß while reducing plasma oxytocin, thyroxine and testosterone levels and causing atrophy of immune tissues. Thus, plasma oxytocin is essential for immunological homeostasis, which involves oxytocin facilitation of thyroid hormone and sex steroid secretion.


Asunto(s)
Sistema Hipotálamo-Hipofisario , Oxitocina , Animales , Oxitocina/sangre , Oxitocina/metabolismo , Ratas , Masculino , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Sistema Hipotálamo-Hipofisario/metabolismo , Femenino , Ratas Sprague-Dawley , Ácido Kaínico/toxicidad , Interleucina-1beta/metabolismo , Interleucina-1beta/sangre , Testosterona/sangre , Hormona Liberadora de Corticotropina/metabolismo , Timo/efectos de los fármacos , Timo/metabolismo
5.
Acta Neurobiol Exp (Wars) ; 84(2): 203-217, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-39087835

RESUMEN

Sleep deprivation (SD) is a prevalent sleep issue in modern society that significantly impairs neurological function and quality of life in affected individuals. This study seeks to investigate the involvement of the miR­155­5p/BDNF axis in SD mice, aiming to establish a theoretical foundation for potential treatment strategies. Male C57BL/6 mice were utilized in the construction of a SD model using the flower pot technique. HT22 cells were selected for cellular experiments. The Morris water maze was employed to assess the learning and memory capabilities of the mice. HE staining was utilized to observe pathological changes in hippocampal tissue. Levels of IL­1ß, IL­6, and TNF­α were analyzed using ELISA. The expression level of miR­155­5p was quantified via RT­qPCR. The binding between miR­155­5p and brain­derived neurotrophic factor (BDNF) was confirmed through a dual­luciferase reporter assay. Apoptosis of hippocampal neurons was assessed using TUNEL. Western blot analysis was conducted to evaluate the expression levels of BDNF, p65, and p­p65. The Morris water maze test revealed that the mice exhibited prolonged escape latency, decreased swimming velocity, and reduced time spent in the target platform quadrant, which are indicative of a successful construction of the SD model. The observed cognitive deficits in the mice were associated with SD­induced damage to the hippocampal tissue, leading to increased levels of miR­155­5p and decreased levels of BDNF. miR­155­5p was found to directly bind to BDNF, thereby suppressing its mRNA and protein expression. The upregulation of BDNF effectively mitigated hippocampal damage by attenuating cell apoptosis and reducing inflammation levels in SD mice. Additionally, the BDNF/NF­κB pathway was found to be suppressed in SD mice through the downregulation of miR­155­5p. Therefore, the silencing of miR­155­5p inhibited the activation of the NF­κB pathway by upregulating BDNF, which improved long­term memory and reduced neuronal damage in SD mice.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo , Hipocampo , Memoria a Largo Plazo , Ratones Endogámicos C57BL , MicroARNs , FN-kappa B , Transducción de Señal , Privación de Sueño , Animales , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/genética , Privación de Sueño/metabolismo , MicroARNs/metabolismo , MicroARNs/genética , Masculino , Ratones , Hipocampo/metabolismo , FN-kappa B/metabolismo , Transducción de Señal/fisiología , Memoria a Largo Plazo/fisiología , Neuronas/metabolismo , Aprendizaje por Laberinto/fisiología
6.
Opt Lett ; 49(15): 4246-4249, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39090905

RESUMEN

Ultrashort optical pulse manipulation is one of the key techniques for applications such as high-speed imaging and high-precision laser processing. In this study, we demonstrate the multidimensional manipulation of ultrashort optical pulses by integrating spatial dispersion and spatial light modulation. Specifically, by modulating the phase of each wavelength, we achieve arbitrary adjustments in multiple dimensions, including number of sub pulses, time interval, intensity, and pulse width simultaneously and independently with a simple setup and few calculations. The performance of the optical pulse manipulation method is verified through both numerical simulations and experiments.

7.
Am J Transl Res ; 16(7): 3231-3239, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39114676

RESUMEN

OBJECTIVE: To investigate the effects of enhanced recovery after surgery (ERAS) on the perioperative healing and stress response in patients with hip fractures. METHODS: A retrospective analysis was conducted on the medical records of 86 patients with hip fractures admitted to the Affiliated Hospital of Southwest Medical University between January 2022 and August 2023. Among them, 48 patients in the research group received ERAS, while 38 patients in the control group received conventional nursing. Hip joint function, pain levels, stress response, fracture healing time, incidence of complications, and nursing satisfaction were compared between the two groups. RESULTS: After nursing, the Harris scores notably increased in both groups, with the research group showing notably higher scores compared to the control group (P<0.05). The levels of cortisol and epinephrine, as well as the visual analog scale scores significantly decreased in both groups, with the research group showing significantly lower levels (P<0.05). In addition, the research group experienced significantly shorter fracture healing time (P<0.05), higher nursing satisfaction (P=0.014), and lower incidence of complications (P=0.028). Logistic regression analysis revealed that age, underlying diseases, nursing method, emotional disorders, and timing of surgery were independent factors influencing the post-nursing outcomes. CONCLUSION: The ERAS mode can effectively alleviate pain, improve hip joint function, reduce fracture healing time and complications, mitigate stress response, and accelerate postoperative recovery in patients with hip fractures. It is worthy of application and promotion in clinical practice.

8.
Proc Natl Acad Sci U S A ; 121(34): e2403392121, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39141356

RESUMEN

Cysteine palmitoylation or S-palmitoylation catalyzed by the ZDHHC family of acyltransferases regulates the biological function of numerous mammalian proteins as well as viral proteins. However, understanding of the role of S-palmitoylation in antiviral immunity against RNA viruses remains very limited. The adaptor protein MAVS forms functionally essential prion-like aggregates upon activation by viral RNA-sensing RIG-I-like receptors. Here, we identify that MAVS, a C-terminal tail-anchored mitochondrial outer membrane protein, is S-palmitoylated by ZDHHC7 at Cys508, a residue adjacent to the tail-anchor transmembrane helix. Using superresolution microscopy and other biochemical techniques, we found that the mitochondrial localization of MAVS at resting state mainly depends on its transmembrane tail-anchor, without regulation by Cys508 S-palmitoylation. However, upon viral infection, MAVS S-palmitoylation stabilizes its aggregation on the mitochondrial outer membrane and thus promotes subsequent propagation of antiviral signaling. We further show that inhibition of MAVS S-palmitoylation increases the host susceptibility to RNA virus infection, highlighting the importance of S-palmitoylation in the antiviral innate immunity. Also, our results indicate ZDHHC7 as a potential therapeutic target for MAVS-related autoimmune diseases.


Asunto(s)
Aciltransferasas , Proteínas Adaptadoras Transductoras de Señales , Inmunidad Innata , Lipoilación , Membranas Mitocondriales , Humanos , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Membranas Mitocondriales/metabolismo , Aciltransferasas/metabolismo , Células HEK293 , Mitocondrias/metabolismo , Animales , Cisteína/metabolismo , Transducción de Señal/inmunología , Agregado de Proteínas
9.
Biomimetics (Basel) ; 9(7)2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39056874

RESUMEN

The aerodynamic effects of wing corrugation on insect flight have received widespread attention. However, there has hardly been any specific focus on dynamic changes to corrugation angle in the models. The flexible vein joints containing resilin in the wings of dragonflies and damselflies enable the longitudinal veins to rotate and thereby change the corrugation angles throughout flapping cycles. Therefore, a two-dimensional corrugated airfoil with time-varying corrugation angles is proposed and the aerodynamic performance is evaluated in terms of aerodynamic force, power and efficiency. The results indicate that the airfoil with time-varying corrugations outperforms the rigid one in terms of enhancing thrust and reducing power consumption. The aerodynamic performance of time-varying corrugated airfoils is optimal when the angle varies in a specific range, and an excessively large angle variation may have negative effects. In addition, excessive height or a negative leading edge of the corrugation can lead to a reduction in the thrust. A design concept for the 2D airfoil with time-varying corrugations is provided and the findings are of significance for enhancing the aerodynamic performance of biomimetic flexible flapping-wing vehicles.

10.
Food Chem ; 456: 140007, 2024 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-38861864

RESUMEN

Developing an efficient method for screening Ochratoxin A (OTA) in agriculture products is vital to ensure food safety and human health. However, the complex food matrix seriously affects the sensitivity and accuracy. To address this issue, we designed a novel molecularly imprinted polymer (MIP) electrochemical sensor based on multiwalled carbon nanotube-modified niobium carbide (Nb2C-MWCNTs) with the aid of the density functional theory (DFT). In this design, a glassy carbon electrode (GCE) was first modified by Nb2C-MWCNTs heterostructure. Afterward, the MIP layer was prepared, with ortho-toluidine as a functional monomer selected via DFT and OTA acting as a template on the surface of Nb2C-MWCNTs/GCE using in-situ electropolymerization. Electrochemical tests and physical characterization revealed that Nb2C-MWCNTs improved the sensor's active surface area and electron transmission capacity. Nb2C-MWCNTs had a good synergistic effect on MIP, endowing the sensor with high sensitivity and specific recognition of OTA in complex food matrix systems. The MIP sensor showed a wide linear range from 0.04 to 10.0 µM with a limit of detection (LOD) of 3.6 nM. Moreover, it presented good repeatability and stability for its highly antifouling effect on OTA. In real sample analysis, the recoveries, ranging from 89.77% to 103.70%, agreed well with the results obtained by HPLC methods, suggesting the sensor has good accuracy and high potential in practical applications.


Asunto(s)
Técnicas Electroquímicas , Contaminación de Alimentos , Límite de Detección , Impresión Molecular , Polímeros Impresos Molecularmente , Nanotubos de Carbono , Ocratoxinas , Ocratoxinas/análisis , Ocratoxinas/química , Nanotubos de Carbono/química , Técnicas Electroquímicas/instrumentación , Contaminación de Alimentos/análisis , Polímeros Impresos Molecularmente/química , Electrodos
11.
Int J Biol Macromol ; 274(Pt 1): 133393, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38917922

RESUMEN

Woody bamboo exhibits a unique flowering characteristic with a lengthy flowering cycle, often followed by death. In many plant species, alternative splicing (AS) is a common phenomenon involved in controlling flowering. In this study, a PeCOL13 gene in moso bamboo (Phyllostachys edulis) was characterized. It produced two isoforms: PeCOL13α and PeCOL13ß, due to an intron-retained AS. The PeCOL13α expressed in the vegetative phase and the reproductive phase, but the PeCOL13ß didn't express during the vegetative phase and showed only a weak expression from F1 to F3 during the reproductive phase. Overexpression of PeCOL13α in rice (Oryza sativa) resulted in a delayed heading time through inhibiting the expressions of Hd3a, OsFTL1, and Ehd1 and activating the expressions of Ghd7 and RCN1. However, the PeCOL13ß-overexpressed rice didn't show any significant differences in flowering compared with wild-type (WT), and the expressions of downstream flowering genes had no notable changes. Further analysis revealed that both PeCOL13α and PeCOL13ß can bind to the PeFT promoter. Meanwhile, PeCOL13α can inhibit the transcription of PeFT, but PeCOL13ß showed no effect. When PeCOL13α and PeCOL13ß coexist, the inhibitory effect of PeCOL13α on PeFT transcription was weakened by PeCOL13ß. This study provides new insights into the mechanism of bamboo flowering research.


Asunto(s)
Empalme Alternativo , Flores , Proteínas de Plantas , Poaceae , Flores/genética , Flores/crecimiento & desarrollo , Regulación de la Expresión Génica de las Plantas , Intrones , Oryza/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/genética , Poaceae/genética , Regiones Promotoras Genéticas , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
12.
Cytometry A ; 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38842356

RESUMEN

Optofluidic time-stretch imaging flow cytometry (OTS-IFC) provides a suitable solution for high-precision cell analysis and high-sensitivity detection of rare cells due to its high-throughput and continuous image acquisition. However, transferring and storing continuous big data streams remains a challenge. In this study, we designed a high-speed streaming storage strategy to store OTS-IFC data in real-time, overcoming the imbalance between the fast generation speed in the data acquisition and processing subsystem and the comparatively slower storage speed in the transmission and storage subsystem. This strategy, utilizing an asynchronous buffer structure built on the producer-consumer model, optimizes memory usage for enhanced data throughput and stability. We evaluated the storage performance of the high-speed streaming storage strategy in ultra-large-scale blood cell imaging on a common commercial device. The experimental results show that it can provide a continuous data throughput of up to 5891 MB/s.

13.
Dev Cell ; 59(15): 1954-1971.e7, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-38776924

RESUMEN

A significant variation in chromatin accessibility is an epigenetic feature of leukemia. The cause of this variation in leukemia, however, remains elusive. Here, we identify SMARCA5, a core ATPase of the imitation switch (ISWI) chromatin remodeling complex, as being responsible for aberrant chromatin accessibility in leukemia cells. We find that SMARCA5 is required to maintain aberrant chromatin accessibility for leukemogenesis and then promotes transcriptional activation of AKR1B1, an aldo/keto reductase, by recruiting transcription co-activator DDX5 and transcription factor SP1. Higher levels of AKR1B1 are associated with a poor prognosis in leukemia patients and promote leukemogenesis by reprogramming fructose metabolism. Moreover, pharmacological inhibition of AKR1B1 has been shown to have significant therapeutic effects in leukemia mice and leukemia patient cells. Thus, our findings link the aberrant chromatin state mediated by SMARCA5 to AKR1B1-mediated endogenous fructose metabolism reprogramming and shed light on the essential role of AKR1B1 in leukemogenesis, which may provide therapeutic strategies for leukemia.


Asunto(s)
Fructosa , Animales , Humanos , Ratones , Adenosina Trifosfatasas , Aldehído Reductasa/metabolismo , Aldehído Reductasa/genética , Carcinogénesis/metabolismo , Carcinogénesis/patología , Carcinogénesis/genética , Línea Celular Tumoral , Cromatina/metabolismo , Ensamble y Desensamble de Cromatina , Proteínas Cromosómicas no Histona/metabolismo , Proteínas Cromosómicas no Histona/genética , Fructosa/metabolismo , Leucemia/metabolismo , Leucemia/patología , Leucemia/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética
14.
J Craniofac Surg ; 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38810237

RESUMEN

BACKGROUND: Ptosis and upper eyelid depression were previously diagnosed as 2 separate diseases. The authors found that in patients with aponeurotic ptosis accompanied by upper eyelid depression, the main cause of upper eyelid depression was impaired dynamic transmission of the levator aponeurosis. OBJECTIVE: To analyze the causes of upper eyelid depression in patients with aponeurotic ptosis accompanied by upper eyelid depression and to introduce the best treatment methods. METHODS: The authors enrolled 15 eyes (11 patients) with aponeurotic ptosis accompanied by upper eyelid depression from October 2021 to August 2022. The authors analyzed the causes of upper eyelid depression in those patients and performed aponeurotic ptosis correction surgery and orbital septum fat release surgery. After 6 to 12 months of follow-up, the authors reviewed the patient's medical records and photographs to evaluate the treatment outcomes. RESULTS: After surgery, ptosis was corrected and upper eyelid depression significantly improved in all the patients. One patient had poor eyelid morphology and upper eyelid depression due to habitual brow lifting, which was relieved after an injection of botulinum toxin into the frontalis muscle. One patient had overcorrection of the upper eyelid depression on the affected side and no other complications. CONCLUSION: The main cause of upper eyelid depression in patients with aponeurotic ptosis is impaired dynamic transmission of the levator aponeurosis. Aponeurotic ptosis repair surgery and orbital septum fat release surgery are simple surgical procedures that restore the normal anatomy and physiology of the upper eyelid and maintain the normal structure of the eyelid, with good post-operative outcomes.

15.
Cell Rep ; 43(4): 114070, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38583156

RESUMEN

Nucleotide oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome hyperactivation contributes to many human chronic inflammatory diseases, and understanding how NLRP3 inflammasome is regulated can provide strategies to treat inflammatory diseases. Here, we demonstrate that NLRP3 Cys126 is palmitoylated by zinc finger DHHC-type palmitoyl transferase 7 (ZDHHC7), which is critical for NLRP3-mediated inflammasome activation. Perturbing NLRP3 Cys126 palmitoylation by ZDHHC7 knockout, pharmacological inhibition, or modification site mutation diminishes NLRP3 activation in macrophages. Furthermore, Cys126 palmitoylation is vital for inflammasome activation in vivo. Mechanistically, ZDHHC7-mediated NLRP3 Cys126 palmitoylation promotes resting NLRP3 localizing on the trans-Golgi network (TGN) and activated NLRP3 on the dispersed TGN, which is indispensable for recruitment and oligomerization of the adaptor ASC (apoptosis-associated speck-like protein containing a CARD). The activation of NLRP3 by ZDHHC7 is different from the termination effect mediated by ZDHHC12, highlighting versatile regulatory roles of S-palmitoylation. Our study identifies an important regulatory mechanism of NLRP3 activation that suggests targeting ZDHHC7 or the NLRP3 Cys126 residue as a potential therapeutic strategy to treat NLRP3-related human disorders.


Asunto(s)
Acetiltransferasas , Aciltransferasas , Cisteína , Inflamasomas , Lipoilación , Proteína con Dominio Pirina 3 de la Familia NLR , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Aciltransferasas/metabolismo , Humanos , Animales , Cisteína/metabolismo , Ratones , Células HEK293 , Ratones Endogámicos C57BL , Red trans-Golgi/metabolismo , Macrófagos/metabolismo
16.
Proc Natl Acad Sci U S A ; 121(18): e2319833121, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38648480

RESUMEN

Sirt2 is a nicotinamide adenine dinucleotide (NAD+)-dependent protein lysine deacylase that can remove both acetyl group and long-chain fatty acyl groups from lysine residues of many proteins. It was reported to affect inflammatory bowel disease (IBD) symptoms in a mouse model. However, conflicting roles were reported, with genetic knockout aggravating while pharmacological inhibition alleviating IBD symptoms. These seemingly conflicting reports cause confusion and deter further efforts in developing Sirt2 inhibitors as a potential treatment strategy for IBD. We investigated these conflicting reports and elucidated the role of Sirt2 in the mouse model of IBD. We essentially replicated these conflicting results and confirmed that Sirt2 inhibitors' protective effect is not through off-targets as two very different Sirt2 inhibitors (TM and AGK2) showed similar protection in the IBD mouse model. We believe that the differential effects of inhibitors and knockout are due to the fact that the Sirt2 inhibitors only inhibit some but not all the activities of Sirt2. This hypothesis is confirmed by the observation that a PROTAC degrader of Sirt2 did not protect mice in the IBD model, similar to Sirt2 knockout. Our study provides an interesting example where genetic knockout and pharmacological inhibition do not align and emphasizes the importance of developing substrate-dependent inhibitors. Importantly, we showed that the effect of Sirt2 inhibition in IBD is through regulating the gut epithelium barrier by inhibiting Arf6-mediated endocytosis of E-cadherin, a protein important for the intestinal epithelial integrity. This mechanistic understanding further supports Sirt2 as a promising therapeutic target for treating IBD.


Asunto(s)
Colitis , Mucosa Intestinal , Sirtuina 2 , Animales , Humanos , Ratones , Cadherinas/metabolismo , Cadherinas/genética , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis/prevención & control , Modelos Animales de Enfermedad , Furanos , Enfermedades Inflamatorias del Intestino/metabolismo , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/patología , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/patología , Ratones Endogámicos C57BL , Ratones Noqueados , Quinolinas , Sirtuina 2/metabolismo , Sirtuina 2/antagonistas & inhibidores , Sirtuina 2/genética
17.
J Environ Manage ; 354: 120239, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38354607

RESUMEN

Most soil ammonia (NH3) emissions originate from soil nitrogen (N) that has been in the form of exchangeable ammonium. Emitted NH3 not only induces nutrient loss but also has adverse effects on the cycling of N and accelerates global warming. There is evidence that arbuscular mycorrhizal (AM) fungi can alleviate N loss by reducing N2O emissions in N-limited ecosystems, however, some studies have also found that global changes, such as warming and N deposition, can affect the growth and development of AM fungi and alter their functionality. Up to now, the impact of AM fungi on NH3 emissions, and whether global changes reduce the AM fungi's contribution to NH3 emissions reduction, has remained unclear. In this study, we examined how warming, N addition, and AM fungi alter NH3 emissions from high pH saline soils typical of a temperate meadow through a controlled microscopic experiment. The results showed that warming significantly increased soil NH3 emissions, but N addition and combined warming plus N addition had no impact. Inoculations with AM fungi strongly reduced NH3 emissions both under warming and N addition, but AM fungi effects were more pronounced under warming than following N addition. Inoculation with AM fungi reduced soil NH4+-N content and soil pH, and increased plant N content and soil net N mineralization rate while increasing the abundance of ammonia-oxidizing bacterial (AOB) gene. Structural equation modeling (SEM) shows that the regulation of NH3 emissions by AM fungi may be related to soil NH4+-N content and soil pH. These findings highlight that AM fungi can reduce N loss in the form of NH3 by increasing N turnover and uptake under global changes; thus, AM fungi play a vital role in alleviating the aggravation of N loss caused by global changes and in mitigating environmental pollution in the future.


Asunto(s)
Micorrizas , Micorrizas/fisiología , Nitrógeno , Suelo/química , Ecosistema , Amoníaco , Pradera , Hongos , Microbiología del Suelo
18.
PLoS One ; 19(1): e0295633, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38232076

RESUMEN

In today's dynamic and competitive business landscape, innovation is paramount for companies striving to maintain a competitive edge. Among various innovation strategies, corporate green innovation has gained prominence as an efficient means of achieving sustainable growth. In response to the pressing need for sustainable development, this study investigates the bidirectional cointegration link between green innovation and overall corporate innovation in a panel dataset of Chinese-listed enterprises.As China emphasizes principles like "greening" and "innovation" for twenty-first-century development, this research aligns with the nation's goal of fostering sustainable industry growth through "green innovation". It employs panel cointegration tests, including the Westerlund test, dynamic panel ordinary least square (DOLS), and the panel vector error correction model (VECM), using data from Chinese A-listed firms spanning from 2008 to 2020. The study reveals a robust long-term, bidirectional relationship between corporate innovation and green innovation. Notably, it demonstrates that green innovation causally impacts corporate innovation in both the short and long term. This research also conducts subsample analysis, ensuring the robustness of the main findings across both non-polluted and polluted industries. These findings provide valuable insights into how corporate innovation factors influence corporate green innovation. Consequently, they offer valuable insights for policymakers and organizations, aiding in the formulation of policies that promote environmentally friendly innovation while elevating corporate innovation standards.

19.
Plants (Basel) ; 12(24)2023 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-38140417

RESUMEN

Albinism is a unique problem encountered in tissue culture experiments, but the underlying mechanism remains unclear in most bamboo species. In this study, we identified the putative regulatory genes in an albino mutant of Bambusa oldhamii using comparative physiology and transcriptome analysis. The degeneration of chloroplasts, low chlorophyll (Chl) content and reduced photosynthetic capacity were observed in albinotic B. oldhamii compared to normal lines. A total of 6191 unigenes were identified that were clearly differentially expressed between albino and normal lines by transcriptome sequencing. Most genes related to chloroplast development (such as Psa, Psb) and pigment biosynthesis (such as LHC, GUN4, ZEP) were downregulated significantly in albinotic lines, which might be responsible for the albino phenotype. Moreover, some transcription factors (TFs) such as PIF and GLK1 were identified to be involved in chloroplast development and Chl synthesis, indicating the involvement of putative regulatory pathways PIF-LHC and GLK1-LHC/Psa/Psb in albinotic B. oldhamii. Finally, the downregulation of some stress responsive TFs (like ICE1 and EREB1) suggested a reduction in stress resistance of albinotic B. oldhamii. The above findings provided new insights into the molecular mechanism of albinism in bamboo.

20.
Phys Chem Chem Phys ; 25(43): 29940-29950, 2023 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-37902029

RESUMEN

A new five-dimensional potential energy surface (PES) for H2O-Kr which explicitly includes the intramolecular 2OH overtone state of the H2O monomer is presented. The intermolecular potential energies were evaluated using explicitly correlated coupled cluster theory [CCSD(T)-F12] with a large basis set. Four vibrationally averaged analytical intermolecular PESs for H2O-Kr with H2O molecules in its |00+〉, |02+〉, |02-〉, and |11+〉 states are obtained by fitting to the multi-dimensional Morse/Long-Range potential function form. Each vibrationally averaged PES fitted to 578 points has root-mean-square (RMS) deviations smaller than 0.14 cm-1 and requires only 58 parameters. The combined radial discrete variable representation/angular finite basis representation method and the Lanczos algorithm were employed to calculate the rovibrational energy levels for |00+〉, |02+〉, |02-〉, and |11+〉 states of the H2O-Kr complexes. The calculated |02-〉Πf/e(101) ← |00+〉Σe(000) and |02+〉Πf/e(110) ← |00+〉Σe(101) infrared transitions are in excellent agreement with the experimental values with RMS discrepancies being only 0.007 and 0.016 cm-1, respectively. These analytical PESs can be used to provide reliable theoretical guidance for future infrared overtone spectroscopy of H2O-Kr.

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