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1.
Plant Cell ; 36(5): 2000-2020, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38299379

RESUMEN

The flower-infecting fungus Ustilaginoidea virens causes rice false smut, which is a severe emerging disease threatening rice (Oryza sativa) production worldwide. False smut not only reduces yield, but more importantly produces toxins on grains, posing a great threat to food safety. U. virens invades spikelets via the gap between the 2 bracts (lemma and palea) enclosing the floret and specifically infects the stamen and pistil. Molecular mechanisms for the U. virens-rice interaction are largely unknown. Here, we demonstrate that rice flowers predominantly employ chitin-triggered immunity against U. virens in the lemma and palea, rather than in the stamen and pistil. We identify a crucial U. virens virulence factor, named UvGH18.1, which carries glycoside hydrolase activity. Mechanistically, UvGH18.1 functions by binding to and hydrolyzing immune elicitor chitin and interacting with the chitin receptor CHITIN ELICITOR BINDING PROTEIN (OsCEBiP) and co-receptor CHITIN ELICITOR RECEPTOR KINASE1 (OsCERK1) to impair their chitin-induced dimerization, suppressing host immunity exerted at the lemma and palea for gaining access to the stamen and pistil. Conversely, pretreatment on spikelets with chitin induces a defense response in the lemma and palea, promoting resistance against U. virens. Collectively, our data uncover a mechanism for a U. virens virulence factor and the critical location of the host-pathogen interaction in flowers and provide a potential strategy to control rice false smut disease.


Asunto(s)
Quitina , Flores , Hypocreales , Oryza , Enfermedades de las Plantas , Oryza/microbiología , Oryza/metabolismo , Oryza/genética , Enfermedades de las Plantas/microbiología , Quitina/metabolismo , Flores/microbiología , Hypocreales/patogenicidad , Hypocreales/genética , Hypocreales/metabolismo , Transducción de Señal , Interacciones Huésped-Patógeno , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Virulencia , Factores de Virulencia/metabolismo , Factores de Virulencia/genética , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética
2.
Proc Natl Acad Sci U S A ; 121(9): e2320657121, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38386704

RESUMEN

To control net sodium (Na+) uptake, Arabidopsis plants utilize the plasma membrane (PM) Na+/H+ antiporter SOS1 to achieve Na+ efflux at the root and Na+ loading into the xylem, and the channel-like HKT1;1 protein that mediates the reverse flux of Na+ unloading off the xylem. Together, these opposing transport systems govern the partition of Na+ within the plant yet they must be finely co-regulated to prevent a futile cycle of xylem loading and unloading. Here, we show that the Arabidopsis SOS3 protein acts as the molecular switch governing these Na+ fluxes by favoring the recruitment of SOS1 to the PM and its subsequent activation by the SOS2/SOS3 kinase complex under salt stress, while commanding HKT1;1 protein degradation upon acute sodic stress. SOS3 achieves this role by direct and SOS2-independent binding to previously unrecognized functional domains of SOS1 and HKT1;1. These results indicate that roots first retain moderate amounts of salts to facilitate osmoregulation, yet when sodicity exceeds a set point, SOS3-dependent HKT1;1 degradation switches the balance toward Na+ export out of the root. Thus, SOS3 functionally links and co-regulates the two major Na+ transport systems operating in vascular plants controlling plant tolerance to salinity.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Transporte de Proteínas , Transporte Biológico , Proteolisis , Osmorregulación , Intercambiadores de Sodio-Hidrógeno/genética , Proteínas de Arabidopsis/genética
3.
J Neurosci ; 44(34)2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39019613

RESUMEN

Although anesthesia provides favorable conditions for surgical procedures, recent studies have revealed that the brain remains active in processing noxious signals even during anesthesia. However, whether and how these responses affect the anesthesia effect remains unclear. The ventrolateral periaqueductal gray (vlPAG), a crucial hub for pain regulation, also plays an essential role in controlling general anesthesia. Hence, it was hypothesized that the vlPAG may be involved in the regulation of general anesthesia by noxious stimuli. Here, we found that acute noxious stimuli, including capsaicin-induced inflammatory pain, acetic acid-induced visceral pain, and incision-induced surgical pain, significantly delayed recovery from sevoflurane anesthesia in male mice, whereas this effect was absent in the spared nerve injury-induced chronic pain. Pretreatment with peripheral analgesics could prevent the delayed recovery induced by acute nociception. Furthermore, we found that acute noxious stimuli, induced by the injection of capsaicin under sevoflurane anesthesia, increased c-Fos expression and activity in the GABAergic neurons of the ventrolateral periaqueductal gray. Specific reactivation of capsaicin-activated vlPAGGABA neurons mimicked the effect of capsaicin and its chemogenetic inhibition prevented the delayed recovery from anesthesia induced by capsaicin. Finally, we revealed that the vlPAGGABA neurons regulated the recovery from anesthesia through the inhibition of ventral tegmental area dopaminergic neuronal activity, thus decreasing dopamine (DA) release and activation of DA D1-like receptors in the brain. These findings reveal a novel, cell- and circuit-based mechanism for regulating anesthesia recovery by nociception, and it is important to provide new insights for guiding the management of the anesthesia recovery period.


Asunto(s)
Anestésicos por Inhalación , Ratones Endogámicos C57BL , Nocicepción , Sustancia Gris Periacueductal , Sevoflurano , Sevoflurano/farmacología , Animales , Masculino , Ratones , Anestésicos por Inhalación/farmacología , Nocicepción/efectos de los fármacos , Nocicepción/fisiología , Sustancia Gris Periacueductal/efectos de los fármacos , Sustancia Gris Periacueductal/metabolismo , Mesencéfalo/efectos de los fármacos , Estado de Conciencia/efectos de los fármacos , Estado de Conciencia/fisiología , Periodo de Recuperación de la Anestesia , Capsaicina/farmacología , Neuronas GABAérgicas/efectos de los fármacos , Neuronas GABAérgicas/fisiología
4.
Mol Psychiatry ; 2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38454083

RESUMEN

Both peripheral and central corticotropin-releasing factor (CRF) systems have been implicated in regulating pain sensation. However, compared with the peripheral, the mechanisms underlying central CRF system in pain modulation have not yet been elucidated, especially at the neural circuit level. The corticoaccumbal circuit, a structure rich in CRF receptors and CRF-positive neurons, plays an important role in behavioral responses to stressors including nociceptive stimuli. The present study was designed to investigate whether and how CRF signaling in this circuit regulated pain sensation under physiological and pathological pain conditions. Our studies employed the viral tracing and circuit-, and cell-specific electrophysiological methods to label the CRF-containing circuit from the medial prefrontal cortex to the nucleus accumbens shell (mPFCCRF-NAcS) and record its neuronal propriety. Combining optogenetic and chemogenetic manipulation, neuropharmacological methods, and behavioral tests, we were able to precisely manipulate this circuit and depict its role in regulation of pain sensation. The current study found that the CRF signaling in the NAc shell (NAcS), but not NAc core, was necessary and sufficient for the regulation of pain sensation under physiological and pathological pain conditions. This process was involved in the CRF-mediated enhancement of excitatory synaptic transmission in the NAcS. Furthermore, we demonstrated that the mPFCCRF neurons monosynaptically connected with the NAcS neurons. Chronic pain increased the protein level of CRF in NAcS, and then maintained the persistent NAcS neuronal hyperactivity through enhancement of this monosynaptic excitatory connection, and thus sustained chronic pain behavior. These findings reveal a novel cell- and circuit-based mechanistic link between chronic pain and the mPFCCRF → NAcS circuit and provide a potential new therapeutic target for chronic pain.

5.
Nano Lett ; 24(10): 3221-3230, 2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38416582

RESUMEN

The hydrolysis of hydrides, represented by MgH2, delivers substantial capacity and presents an appealing prospect for an on-site hydrogen supply. However, the sluggish hydrolysis kinetics and low hydrogen yield of MgH2 caused by the formation of a passivation Mg(OH)2 layer hinder its practical application. Herein, we present a dual strategy encompassing microstructural design and compounding, leading to the successful synthesis of a core-shell-like nanostructured MgH2@Mg(BH4)2 composite, which demonstrates excellent hydrolysis performance. Specifically, the optimal composite with a low Ea of 9.05 kJ mol-1 releases 2027.7 mL g-1 H2 in 60 min, and its hydrolysis rate escalates to 1356.7 mL g-1 min-1 H2 during the first minute at room temperature. The nanocoating Mg(BH4)2 plays a key role in enhancing the hydrolysis kinetics through the release of heat and the formation of local concentration of Mg2+ field after its hydrolysis. This work offers an innovative concept for the design of hydrolysis materials.

6.
J Am Chem Soc ; 146(33): 23194-23204, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39115467

RESUMEN

Electrochemical hydrogenation reactions demand rapid proton-coupled electron transfer at the electrode surface, the kinetics of which depend closely on pH. Buffer electrolytes are extensively employed to regulate pH over a wide range. However, the specific role of buffer species should be taken into account when interpreting the intrinsic pH dependence, which is easily overlooked in the current research. Herein, we report the electrochemical hydrogenation of hydroxyacetone, derived from glycerol feedstock, to propylene glycol with a faradaic efficiency of 56 ± 5% on a polycrystalline Cu electrode. The reaction activities are comparable in citrate, phosphate, and borate buffer electrolytes, encompassing different buffer identities and pH. The electrokinetic profile reveals that citrate is a site-blocking adsorbate on the Cu surface, thereby decreasing buffer concentration and increasing pH will enhance the reaction rate; phosphate is an explicit proton donor, which promotes the interfacial rate by increasing buffer concentration and decreasing pH, while borate is an innocent buffer, which can be used to investigate the intrinsic pH effect. Combined with in situ SEIRAS, we demonstrate that water is the primary proton source in citrate and borate electrolytes, reiterating the rationality of the proposed mechanism based on the microkinetic modeling. Our results emphasize the intrinsic complexity of the buffer system on the kinetic activity for electrocatalysis. It calls for special care when we diagnose the mechanistic pathway in buffer electrolytes convoluted by different buffer identities and pH.

7.
Anal Chem ; 96(1): 347-354, 2024 01 09.
Artículo en Inglés | MEDLINE | ID: mdl-38153415

RESUMEN

Sorting single cells from a population was of critical importance in areas such as cell line development and cell therapy. Image-based sorting is becoming a promising technique for the nonlabeling isolation of cells due to the capability of providing the details of cell morphology. This study reported the focusing of cells using microwell arrays and the following automatic size sorting based on the real-time recognition of cells. The simulation first demonstrated the converged streamlines to the symmetrical plane contributed to the focusing effect. Then, the influence of connecting microchannel, flowing length, particle size, and the sample flow rate on the focusing effect was experimentally analyzed. Both microspheres and cells could be aligned in a straight line at the Reynolds number (Re) of 0.027-0.187 and 0.027-0.08, respectively. The connecting channel was proved to drastically improve the focusing performance. Afterward, a tapered microwell array was utilized to focus sphere/cell spreading in a wide channel to a straight line. Finally, a custom algorithm was employed to identify and sort the size of microspheres/K562 cells with a throughput of 1 event/s and an accuracy of 97.8/97.1%. The proposed technique aligned cells to a straight line at low Reynolds numbers and greatly facilitated the image-activated sorting without the need for a high-speed camera or flow control components with high frequency. Therefore, it is of enormous application potential in the field of nonlabeled separation of single cells.


Asunto(s)
Tamaño de la Partícula , Humanos , Microesferas , Células K562 , Simulación por Computador
8.
BMC Med ; 22(1): 176, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38664766

RESUMEN

BACKGROUND: There is an urgent unmet need for effective initial treatment for acute graft-versus-host disease (aGVHD) adding to the standard first-line therapy with corticosteroids after allogeneic haematopoietic stem cell transplantation (allo-HSCT). METHODS: We performed a multicentre, open-label, randomized, phase 3 study. Eligible patients (aged 15 years or older, had received allo-HSCT for a haematological malignancy, developed aGVHD, and received no previous therapies for aGVHD) were randomly assigned (1:1) to receive either 5 mg/m2 MTX on Days 1, 3, or 8 and then combined with corticosteroids or corticosteroids alone weekly. RESULTS: The primary endpoint was the overall response rate (ORR) on Day 10. A total of 157 patients were randomly assigned to receive either MTX plus corticosteroids (n = 78; MTX group) or corticosteroids alone (n = 79; control group). The Day 10 ORR was 97% for the MTX group and 81% for the control group (p = .005). Among patients with mild aGVHD, the Day 10 ORR was 100% for the MTX group and 86% for the control group (p = .001). The 1-year estimated failure-free survival was 69% for the MTX group and 41% for the control group (p = .002). There were no differences in treatment-related adverse events between the two groups. CONCLUSIONS: In conclusion, mini-dose MTX combined with corticosteroids can significantly improve the ORR in patients with aGVHD and is well tolerated, although it did not achieve the prespecified 20% improvement with the addition of MTX. TRIAL REGISTRATION: The trial was registered with clinicaltrials.gov (NCT04960644).


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Metotrexato , Metilprednisolona , Humanos , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Femenino , Masculino , Metotrexato/administración & dosificación , Metotrexato/uso terapéutico , Persona de Mediana Edad , Adulto , Metilprednisolona/uso terapéutico , Metilprednisolona/administración & dosificación , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Adulto Joven , Resultado del Tratamiento , Quimioterapia Combinada , Anciano , Adolescente , Enfermedad Aguda
9.
Cancer Cell Int ; 24(1): 47, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38291427

RESUMEN

BACKGROUND: Long noncoding RNAs (lncRNAs) are significant contributors to various human malignancies. The aberrant expression of lncRNA LINC00894 has been reported in various human malignancies. We aimed to illustrate the role of LINC00894 and its underlying mechanism in the development of papillary thyroid carcinoma (PTC). METHODS: We performed bioinformatics analysis of differentially expressed RNAs from TCGA and GEO datasets and selected the target lncRNA LINC00894. SRAMP analysis revealed abundant M6A modification sites in LINC00894. Further analysis of StarBase, GEPIA, and TCGA datasets was performed to identify the related differentially expressed genes METTL3. Colony formation and CCK-8 assays confirmed the relationship between LINC00894, METTL3, and the proliferative capacity of PTC cells. The analysis of AnnoLnc2, Starbase datasets, and meRIP-PCR and qRT‒PCR experiments confirmed the influence of METTL3-mediated m6A modification on LINC00894. The study employed KEGG enrichment analysis as well as Western blotting to investigate the impact of LINC00894 on the expression of proteins related to the Hippo signalling pathway. RESULTS: LINC00894 downregulation was detected in PTC tissues and cells and was even further downregulated in PTC with lymphatic metastasis. LINC00894 inhibits the lymphangiogenesis of vascular endothelial cells and the proliferation of cancer cells. METTL3 enhances PTC progression by upregulating LINC00894 by enhancing LINC00894 mRNA stability through the m6A-YTHDC2-dependent pathway. LINC00894 may inhibit PTC malignant phenotypes through the Hippo signalling pathway. CONCLUSION: The METTL3-YTHDC2 axis stabilizes LINC00894 mRNA in an m6A-dependent manner and subsequently inhibits tumour malignancy through the Hippo signalling pathway.

10.
Biotechnol Bioeng ; 121(7): 2163-2174, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38595326

RESUMEN

Pathogenic bacterial membrane proteins (MPs) are a class of vaccine and antibiotic development targets with widespread clinical application. However, the inherent hydrophobicity of MPs poses a challenge to fold correctly in living cells. Herein, we present a comprehensive method to improve the soluble form of MP antigen by rationally designing multi-epitope chimeric antigen (ChA) and screening two classes of protein-assisting folding element. The study uses a homologous protein antigen as a functional scaffold to generate a ChA possessing four epitopes from transferrin-binding protein A of Glaesserella parasuis. Our engineered strain, which co-expresses P17 tagged-ChA and endogenous chaperones groEL-ES, yields a 0.346 g/L highly soluble ChA with the property of HPS-positive serum reaction. Moreover, the protein titer of ChA reaches 4.27 g/L with >90% soluble proportion in 5-L bioreactor, which is the highest titer reported so far. The results highlight a timely approach to design and improve the soluble expression of MP antigen in industrially viable applications.


Asunto(s)
Antígenos Bacterianos , Antígenos Bacterianos/genética , Antígenos Bacterianos/inmunología , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/metabolismo , Reactores Biológicos , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/química , Escherichia coli/genética , Escherichia coli/metabolismo , Clostridiales/genética , Clostridiales/metabolismo , Solubilidad
11.
J Org Chem ; 89(7): 4484-4495, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38470436

RESUMEN

Nickel-catalyzed carbonylation of alkenes is a stereoselective and regioselective method for the synthesis of amide compounds. Theoretical predictions with density functional theory calculations revealed the mechanism and origin of stereoselectivity and regioselectivity for the nickel-catalyzed carbonylation of norbornene. The carbonylation reaction proceeds through oxidative addition, migration insertion of alkenes, and subsequent reduction elimination to afford cis-carbonylation product. The C-N bond activation of amides is unfavorable because the oxidative addition ability of the C-C bond is stronger than that of the C-N bond. The determining step of stereoselectivity is the migratory insertion of the strained olefin. The structural analysis shows that steroselectivity is controlled by the steric hindrance of methyl groups to olefins and substituents to IMes in ligands.

12.
Inorg Chem ; 63(19): 8899-8907, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38695311

RESUMEN

Given the escalating significance of near-infrared (NIR) spectroscopy across industries, agriculture, and various domains, there is an imminent need to address the development of a novel generation of intelligent NIR light sources. Here, a series of Cr3+-doped BaLaMgNbO6 (BLMN) ultrabroadband NIR phosphor with a coverage range of 650-1300 nm were developed. The emission peak locates at 830 nm with a full width at half maximum of 210 nm. This ultrabroadband emission originates from the 4T2→4A2 transition of Cr3+ and the simultaneous occupation of [MgO6] and [NbO6] octahedral sites confirmed by low photoluminescence spectra (77-250 K), time-resolved photoluminescence spectra, and electron paramagnetic resonance spectra. The fluxing strategy improves the luminescence intensity and thermal stability of BLMN:0.02Cr3+ phosphors. The internal quantum efficiency (IQE) is 51%, external quantum efficiency (EQE) can reach 33%, and thermal stability can be maintained at 60%@100 °C. Finally, we successfully demonstrated the application of BLMN:Cr3+ ultrabroadband in the qualitative analysis of organic matter and food freshness detection.

13.
Avian Pathol ; : 1-10, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38887084

RESUMEN

Ascites syndrome (AS) in broiler chickens, also known as pulmonary arterial hypertension (PAH), is a significant disease in the poultry industry. It is a nutritional metabolic disease that is closely associated with hypoxia-inducible factors and rapid growth. The rise in pulmonary artery pressure is a crucial characteristic of AS and is instrumental in its development. Hypoxia-inducible factor 1α (HIF-1α) is an active subunit of a key transcription factor in the oxygen-sensing pathway. HIF-1α plays a vital role in oxygen homeostasis and the development of pulmonary hypertension. Studying the effects of HIF-1α on pulmonary hypertension in humans or mammals, as well as ascites in broilers, can help us understand the pathogenesis of AS. Therefore, this review aims to (1) summarize the mechanism of HIF-1α in the development of pulmonary hypertension, (2) provide theoretical significance in explaining the mechanism of HIF-1α in the development of pulmonary arterial hypertension (ascites syndrome) in broilers, and (3) establish the correlation between HIF-1α and pulmonary arterial hypertension (ascites syndrome) in broilers. HIGHLIGHTSExplains the hypoxic mechanism of HIF-1α.Linking HIF-1α to pulmonary hypertension in broilers.Explains the role of microRNAs in pulmonary arterial hypertension in broilers.

14.
Phys Chem Chem Phys ; 26(31): 21147-21154, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39072377

RESUMEN

Quasi-two-dimensional (quasi-2D) perovskites exhibit excellent performance in light-emitting diodes (LEDs). However, the quality of perovskite films prepared via the solution method is significantly impacted by the enormous number of defects that unavoidably form at the grain boundaries and interfaces during the precursor to the crystal formation process. Here, we propose a strategy to assist perovskite crystallization and defect passivation at the buried interface through interfacial modification. The organic ammonium salt, ethylamine chloride (EACl), is added to the hole transport material and modifies the buried interface of the perovskite film. EACl introduces the nucleation sites for perovskite precursors, and promotes the crystallization process of the perovskite grains, contributing to the formation of high-quality perovskite films. At the same time, the presence of Lewis base (-NH2) groups in EACl and their lone electron pairs effectively inactivate unlocated Pb2+ ions at the buried interface, thereby reducing non-radiative recombination. In addition, chloride ions help to mitigate defects and to improve the morphology of perovskite films. Devices with this modification show a higher performance than control devices on all metrics. This work proposes a facile but efficient way for improving quasi-2D pure blue perovskite crystallization and growth.

15.
Environ Res ; 260: 119508, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38945511

RESUMEN

Cyanobacterial blooms (CBs) and concomitant water quality issues in oligotrophic/mesotrophic waters have been recently reported, challenging the conventional understanding that CBs are primarily caused by eutrophication. To elucidate the underlying mechanism of CBs in nutrition-deficient waters, the changes in Chlorophyll a (Chl-a), cyanobacterial-bacterial community composition, and certain microbial function in Qingcaosha Reservoir, the global largest tidal estuary storage reservoir, were analyzed systematically and comprehensively after its pilot run (2011-2019) in this study. Although the water quality was improved and stabilized, more frequent occurrences of bloom level of Chl-a (>20 µg L-1) in warm seasons were observed during recent years. The meteorological changes (CO2, sunshine duration, radiation, precipitation, evaporation, and relative humidity), water quality variations (pH, total organic carbon content, dissolved oxygen, and turbidity), accumulated sediments as an endogenous source, as well as unique estuarine conditions collectively facilitated picocyanobacterial-bacterial coexistence and community functional changes in this reservoir. A stable and tight co-occurrence pattern was established between dominant cyanobacteria (Synechococcus, Cyanobium, Planktothrix, Chroococcidiopsis, and Prochlorothrix) and certain heterotrophic bacteria (Proteobacteria, Actinobacteria, and Bacteroidetes), which contributed to the remineralization of organic matter for cyanobacteria utilization. The relative abundance of chemoorganoheterotrophs and bacteria related to nitrogen transformation (Paracoccus, Rhodoplanes, Nitrosomonas, and Zoogloea) increased, promoting the emergence of CBs in nutrient-limited conditions through enhanced nutrient recycling. In environments with limited nutrients, the interaction between photosynthetic autotrophic microorganisms and heterotrophic bacteria appears to be non-competitive. Instead, they adopt complementary roles within their ecological niche over long-term succession, mutually benefiting from this association. This long-term study confirmed that enhanced nutrient cycling, facilitated by cyanobacterial-bacterial symbiosis following long-term succession, could promote CBs in oligotrophic aquatic environments devoid of external nutrient inputs. This study advances understanding of the mechanisms that trigger and sustain CBs under nutritional constraints, contributing to developing more effective mitigation strategies, ensuring water safety, and maintaining ecological balance.

16.
Appl Microbiol Biotechnol ; 108(1): 54, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38175240

RESUMEN

Hyaluronidases catalyze the degradation of hyaluronan (HA), which is finding rising applications in medicine, cosmetic, and food industries. Recombinant expression of hyaluronidases in microbial hosts has been given special attention as a sustainable way to substitute animal tissue-derived hyaluronidases. In this study, we focused on optimizing the secretion of hyaluronidase from Homo sapiens in Pichia pastoris by secretion pathway engineering. The recombinant hyaluronidase was first expressed under the control of a constitutive promoter PGCW14. Then, two endoplasmic reticulum-related secretory pathways were engineered to improve the secretion capability of the recombinant strain. Signal peptide optimization suggested redirecting the protein into co-translational translocation using the ost1-proα signal sequence improved the secretion level by 20%. Enhancing the co-translational translocation by overexpressing signal recognition particle components further enhanced the secretory capability by 48%. Then, activating the unfolded protein response by overexpressing a transcriptional factor ScHac1p led to a secreted hyaluronidase activity of 4.06 U/mL, which was 2.1-fold higher than the original strain. Finally, fed-batch fermentation elevated the production to 19.82 U/mL. The combined engineering strategy described here could be applied to enhance the secretion capability of other proteins in yeast hosts. KEY POINTS: • Improving protein secretion by enhancing co-translational translocation in P. pastoris was reported for the first time. • Overexpressing Hac1p homologous from different origins improved the rhPH-20 secretion. • A 4.9-fold increase in rhPH-20 secretion was achieved after fermentation optimization and fed-batch fermentation.


Asunto(s)
Hialuronoglucosaminidasa , Respuesta de Proteína Desplegada , Animales , Humanos , Hialuronoglucosaminidasa/genética , Transporte de Proteínas , Retículo Endoplásmico
17.
Plant Cell Rep ; 43(4): 88, 2024 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-38461436

RESUMEN

KEY MESSAGE: The homolog gene of the Growth Arrest and DNA Damage-inducible 45 (GADD45) in rice functions in the regulation of plant architecture, grain yield, and blast resistance. The Growth Arrest and DNA Damage-inducible 45 (GADD45) family proteins, well-established stress sensors and tumor suppressors in mammals, serve as pivotal regulators of genotoxic stress responses and tumorigenesis. In contrast, the homolog and role of GADD45 in plants have remained unclear. Herein, using forward genetics, we identified an activation tagging mutant AC13 exhibited dwarf characteristics resulting from the loss-of-function of the rice GADD45α homolog, denoted as OsGADD45a1. osgadd45a1 mutants displayed reduced plant height, shortened panicle length, and decreased grain yield compared to the wild-type Kitaake. Conversely, no obvious differences in plant height, panicle length, or grain yield were observed between wild-type and OsGADD45a1 overexpression plants. OsGADD45a1 displayed relatively high expression in germinated seeds and panicles, with localization in both the nucleus and cytoplasm. RNA-sequencing analysis suggested a potential role for OsGADD45a1 in the regulation of photosynthesis, and binding partner identification indicates OsGADD45a1 interacts with OsRML1 to regulate rice growth. Intriguingly, our study unveiled a novel role for OsGADD45a1 in rice blast resistance, as osgadd45a1 mutant showed enhanced resistance to Magnaporthe oryzae, and the expression of OsGADD45a1 was diminished upon blast fungus treatment. The involvement of OsGADD45a1 in rice blast fungus resistance presents a groundbreaking finding. In summary, our results shed light on the multifaceted role of OsGADD45a1 in rice, encompassing biotic stress response and the modulation of several agricultural traits, including plant height, panicle length, and grain yield.


Asunto(s)
Oryza , Proteínas de Plantas , Proteínas de Plantas/metabolismo , Grano Comestible/genética , Semillas/genética , Semillas/metabolismo , Oryza/metabolismo , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/microbiología , Regulación de la Expresión Génica de las Plantas
18.
BMC Pulm Med ; 24(1): 13, 2024 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-38178079

RESUMEN

BACKGROUND: This study was to establish and validate prediction models to predict the cancer-specific survival (CSS) and overall survival (OS) of small-cell lung cancer (SCLC) patients with liver metastasis. METHODS: In the retrospective cohort study, SCLC patients with liver metastasis between 2010 and 2015 were retrospectively retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were randomly divided into the training group and testing group (3: 1 ratio). The Cox proportional hazards model was used to determine the predictive factors for CSS and OS in SCLC with liver metastasis. The prediction models were conducted based on the predictive factors. The performances of the prediction models were evaluated by concordance indexes (C-index), and calibration plots. The clinical value of the models was evaluated by decision curve analysis (DCA). RESULTS: In total, 8,587 patients were included, with 154 patients experiencing CSS and 154 patients experiencing OS. The median follow-up was 3 months. Age, gender, marital status, N stage, lung metastases, multiple metastases surgery of metastatic site, chemotherapy, and radiotherapy were independent predictive factors for the CSS and OS of SCLC patients with liver metastasis. The prediction models presented good performances of CSS and OS among patients with liver metastasis, with the C-index for CSS being 0.724, whereas the C-index for OS was 0.732, in the training set. The calibration curve showed a high degree of consistency between the actual and predicted CSS and OS. DCA suggested that the prediction models provided greater net clinical benefit to these patients. CONCLUSION: Our prediction models showed good predictive performance for the CSS and OS among SCLC patients with liver metastasis. Our developed nomograms may help clinicians predict CSS and OS in SCLC patients with liver metastasis.


Asunto(s)
Neoplasias Hepáticas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Neoplasias Hepáticas/terapia , Neoplasias Pulmonares/terapia , Pronóstico , Estudios Retrospectivos , Carcinoma Pulmonar de Células Pequeñas/terapia
19.
Postgrad Med J ; 100(1187): 671-678, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-38308654

RESUMEN

BACKGROUND: We compared total arterial revascularization (TAR) versus conventional revascularization (CR) in terms of left ventricular function recovery in patients with multivessel coronary artery disease (CAD) and reduced left ventricular ejection fraction (LVEF). METHODS: We conducted a retrospective cohort study of 162 consecutive patients with multivessel CAD and reduced LVEF who underwent isolated coronary artery bypass grafting at our institution between January 2013 and July 2022. We assessed left ventricular function by transthoracic echocardiography at admission, before discharge, and at follow-up of 3, 6, and 12 months, using LVEF, global longitudinal peak strain, end-diastolic volume index, and end-systolic volume index. We also evaluated mitral valve regurgitation and graft patency rate at 1 year. RESULTS: The TAR group had a significantly higher increase in LVEF and global longitudinal peak strain, and a significantly lower decrease in end-diastolic volume index and end-systolic volume index than the CR group at 6 and 12 months after surgery. The TAR group also had a significantly lower degree of mitral valve regurgitation than the CR group at all-time points within 12 months after surgery. The TAR group had a significantly higher graft patency rate than the CR group at 12 months. There was no significant difference in hospital mortality or repeat revascularization between the groups. CONCLUSIONS: TAR was associated with better recovery of left ventricular function than CR in patients with multivessel CAD and reduced LVEF. Further studies are needed to confirm these findings in this high-risk population.


Asunto(s)
Puente de Arteria Coronaria , Enfermedad de la Arteria Coronaria , Ecocardiografía , Volumen Sistólico , Humanos , Masculino , Femenino , Enfermedad de la Arteria Coronaria/cirugía , Enfermedad de la Arteria Coronaria/fisiopatología , Puente de Arteria Coronaria/métodos , Estudios Retrospectivos , Volumen Sistólico/fisiología , Persona de Mediana Edad , Anciano , Función Ventricular Izquierda/fisiología , Recuperación de la Función , Disfunción Ventricular Izquierda/fisiopatología , Disfunción Ventricular Izquierda/cirugía , Disfunción Ventricular Izquierda/diagnóstico por imagen , Resultado del Tratamiento , Insuficiencia de la Válvula Mitral/cirugía , Insuficiencia de la Válvula Mitral/fisiopatología , Insuficiencia de la Válvula Mitral/diagnóstico por imagen
20.
Sensors (Basel) ; 24(2)2024 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-38257432

RESUMEN

In this paper, the asymptotic consensus control of multi-agent systems with general linear agent dynamics is investigated. A neighbor-based adaptive event-triggering strategy with a dynamic triggering threshold is proposed, which leads to a fully distributed control of the multi-agent system, depending only on the states of the neighboring agents at triggering moments. By using the Lyapunov method, we prove that the states of the agents converge asymptotically. In addition, the proposed event-triggering strategy is proven to exclude Zeno behavior. The numerical simulation results illustrate that the agent states achieve consensus in sense of asymptotic convergence. Furthermore, the proposed strategy is shown to be scalable in case of variable agent numbers.

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