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Upadacitinib is an oral new selective JAK1 inhibitor that has been approved for treating adult patients with moderately to severely active ulcerative colitis. However, a growing number of studies are needed on the effectiveness of upadacitinib in the treatment of acute severe ulcerative colitis. This study was mainly aimed to describe the clinical and endoscopic effectiveness of upadacitinib 45 mg in Chinese acute severe ulcerative colitis patients following eight weeks of treatment. In this study, we examined all patients with acute severe ulcerative colitis from Xijing IBD Center, Xi'an, China, with acute severe ulcerative colitis. All patients were initially given oral upadacitinib 45 mg. Clinical indicators, C-reactive protein, and erythrocyte sedimentation rates were collected. Clinical response and clinical remission were assessed using modified Mayo. Endoscopic evaluation was performed carried out using the Mayo Endoscopic Score and Ulcerative colitis endoscopic index of severity score. A total of 14 patients who received upadacitinib were included in the study period. All patients exhibited a clinical response to 45 mg upadacitinib initially. All patients completed the 8-week induction. The clinical remission rate was 28.6% after eight weeks. Two patients revealed endoscopic remission at 14.3%. The pathology improved in 50.0% of patients. The 8-week surgical resection rate was 7.1%, with the 16-week surgical resection rate being 14.3%. Adverse events included herpes simplex virus infection and increased thrombin time. The results of our study support the short-term effectiveness and safety of upadacitinib in acute severe ulcerative colitis, providing new choices for patients' treatment. However, more extended investigation needs to be performed on the long-term effectiveness and safety.
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Colite Ulcerativa , Compostos Heterocíclicos com 3 Anéis , Humanos , Colite Ulcerativa/tratamento farmacológico , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Resultado do Tratamento , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , China , Adulto Jovem , Quinolizinas/uso terapêutico , Índice de Gravidade de Doença , População do Leste AsiáticoRESUMO
The developmental changes in the granular surface structure and functional properties of starch during the entire grain filling period of rice (around 40 days) were investigated. The specific surface area of rice starch significantly decreased firstly then stabilized during growth due to increasing granular size. The pore volume decreased from 5.40 cm3/g at 6th day after anthesis (DAA-6) to 3.02 cm3/g (DAA-46). More starch granule-associated proteins (SGAPs) accumulated on the surface and in channels. Swelling power decreased by 46 %, whereas the flow behavior index (n) decreased by 32 % in upward curve during starch development from DAA-6 to DAA-30. Tan δ first dropped then remained steady at DAA 22-34 and lightly rebounded at the final stage, indicating that starch in the middle stage tended to have greater viscoelastic gel behavior at all sweeps. Mature starch showed lower in vitro hydrolysis rate and exhibited stronger enzymatic resistance. The results showed that granular surface features of rice starch may be an essential factor in determining rheological behavior and resistance to hydrolysis.
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The degree of global soil salinization is gradually deepening, which will inevitably affect agricultural ecology. It has been found that salt stress induces the resistance of host plants to phytophagous pests. However, little is known about the effects of salt-stressed cotton plants on the fitness of cotton aphids (Aphis gossypii Glover). In this study, we investigated the differences between cotton metabolomes under mild (75 mM NaCl) and moderate (150 mM NaCl) salinity conditions and their effects on the fitness of cotton aphids. The results showed that 49 metabolites exhibited significant upregulation, while 86 metabolites were downregulated, with the increasing NaCl concentration. The duration of nymphal aphids under 150 mM NaCl significantly extended to 6.31 days when compared with the control (0 mM NaCl, 4.10 days). Meanwhile, the longevity of adult aphids decreased significantly under 75 and 150 mM NaCl, with an average of 10.38 days (0 mM NaCl) reduced to 8.55 and 4.89 days, respectively. Additionally, the total reproduction number of single females decreased from 31.31 (0 mM NaCl) to 21.13 (75 mM NaCl) and 10.75 (150 mM NaCl), whereas the survival rate of aphids decreased from 81.25% (0 mM NaCl) to 56.25% (75 mM NaCl) and 34.38% (150 mM NaCl) on the 12th day. These results support the hypothesis that plants growing under salt stress are better defended against herbivores. Furthermore, 49 differential metabolites were found to be negatively correlated with the longevity and fecundity of adult aphids, while 86 different metabolites showed the opposite trend. These results provide insights into the occurrence and control of cotton aphids amidst the escalating issue of secondary salinization.
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Aphis gossypii is one of the most economically important agricultural pests that cause serious crop losses worldwide, and the indiscriminate chemical application causes resistance development in A. gossypii, a major obstacle to successful control. In this study, we selected the up-regulated expression gene AgJHAMT, which was enriched into juvenile hormone pathway though transcriptome sequencing analysis of the cotton aphids that fed on transgenic cotton lines expressing dsAgCYP6CY3 (the TG cotton). The AgJHAMT gene was overexpressed in cotton aphids which fed on the TG cotton, and its expression profile during the nymphs was clarified. Then, silencing AgJHAMT could advance the developmental period of cotton aphids by 0.5 days compared with control groups. The T and t values of cotton aphids in the dsJHAMT treatment group (6.88 ± 0.15, 1.65 ± 0.06) were significantly shorter than that of the sprayed H2O control group (7.6 ± 0.14, 1.97 ± 0.09) (P < 0.05), respectively. The fast growth caused by AgJHAMT silencing was rescued by applying the JH analogue, methoprene. Overall, these findings clarified the function of AgJHAMT in the developmental period of A. gossypii. This study contributes to further clarify the molecular mechanisms of delaying the growth and development of cotton aphids by the transgenic cotton lines expressing dsAgCYP6CY3.
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We have developed a new method for measuring mass dependent Si isotope fractionation via critical mixture double-spiking. Samples need to be spiked before column chemistry to guarantee full equilibrium between the sample and double-spike (29Si-30Si spike). An iterative addition of the double-spike to the sample, usually 2-4 times, is needed to generate a solution very close to the critically spiked mixture. We use a double-pass cyclonic quartz spray chamber, as it gives the highest signal-to-noise ratio. In conjunction with 6 µg ml-1 Si solution to yield intense Si isotope beams, this setup results in an â¼25 V (with 1011 Ω resistor) signal on 28Si+, while on-peak noise is less than 0.06 V. A typical sample analysis comprises 8 repeats (n = 8) of an individual sample measurement (for each repeat n = 1, 168 second analysis time) normalised to bracketing measurements of critically double-spiked NIST SRM 8546 (commonly known as NBS28). Each of these n = 8 analyses consumes about 13 µg of sample Si and yields a mean δ 30/28Si with a precision of approximately ±0.03 (2 s.e., 2 × standard error of the mean). Over a 16 month period, the reproducibility of the 11 mean δ 30/28Si values of such n = 8 analyses of the silicate reference material BHVO-2 is ±0.03 (2 s.d., 2 × standard deviation), which is 2 to 8 times better than the long-term reproducibility of traditional Si isotope measurement methods (â¼±0.1, 2 s.d., δ 30/28Si). This agreement between the long-term and short-term variability illustrates that the data sample the same population over the long and short terms, i.e., there is no scatter on the timescale of 16 months additional to what we observe over twenty hours (the typical timescale in one analytical session). Thus, for any set of n repeats, including n >8, their 2 s.e. should prove a useful metric of the reproducibility of their mean. Three international geological reference materials and a Si isotope reference material, diatomite, were characterised via the critical mixture double-spiking technique. Our results, expressed as δ 30/28SiNBS28, for BHVO-2 (-0.276 ± 0.011, 2 s.e., n = 94), BIR-1 (-0.321 ± 0.025, 2 s.e., n = 27), JP-1 (-0.273 ± 0.030, 2 s.e., n = 19) and diatomite (1.244 ± 0.025, 2 s.e., n = 20), are consistent with literature data, i.e., within the error range, but much more precise.
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Increasing cohort studies have examined the link between mitochondrial DNA copy number (mtDNA-CN) and cardiovascular disease (CVD), with inconsistent findings. We searched PubMed, EMBASE, and Web of Science up to July 11, 2023 and used a random-effects model to calculate summary hazard ratios (HRs) and 95% confidence intervals (CIs). This systematic review and meta-analysis included 8 articles encompassing 29 studies with 646,398 participants. Individuals with the lowest mtDNA-CN had a summary HR of 1.27 (95% CI 1.02-1.59) for CVD, 1.18 (95% CI 0.92-1.50) for coronary heart disease (CHD), 1.10 (95% CI 0.89-1.37) for stroke, and 1.30 (95% CI 1.07-1.56) for heart failure (HF). Decreased mtDNA-CN is linked to an increased risk of CVD and HF but not CHD and stroke. These findings suggest mtDNA-CN from leukocytes may be a potential early biomarker for CVD. However, more prospective studies with long follow-up are needed.
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Mild alkali treatment can potentially be developed as a greener alternative to the traditional alkali treatment of starch, but the effect of mild alkali on starch is still understudied. Normal and waxy rice starches were subjected to mild alkali combined with hydrothermal treatment to investigate their changes in physicochemical properties. After mild alkali treatment, the protein content of normal and waxy rice starches decreased from 0.76% to 0.23% and from 0.89% to 0.23%, respectively. Mild alkali treatment decreased gelatinization temperature but increased the swelling power and solubility of both starches. Mild alkali treatment also increased the gelatinization enthalpy of waxy rice starch from 20.01 J/g to 25.04 J/g. Mild alkali treatment at room temperature increased the pasting viscosities of both normal and waxy rice starches, whereas at high temperature, it decreased pasting viscosities during hydrothermal treatment. Alkali treatment significantly changed the properties of normal and waxy rice starch by the ionization of hydroxyl groups and the removal of starch granule-associated proteins. Hydrothermal conditions promoted the effect of alkali. The combination of hydrothermal and alkali treatment led to greater changes in starch properties.
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Background: Limited and conflicting evidence exists for the associations between tea, coffee, and caffeine intake and risk of dementia and Alzheimer's disease (AD). This meta-analysis aimed to elucidate these associations and quantify potential dose-response relationships. Methods: PubMed, EMBASE, and Web of Science were searched up to 11 June 2024 for cohort studies. Random effects models were used to calculate pooled relative risks (RRs) and 95% confidence intervals (CIs), with the dose-response relationship assessed using restricted cubic splines. The Grading of Recommendations Assessment Development and Evaluation (GRADE) tool was used to assess the risk of bias. Results: Our analysis encompassed 38 cohorts, totalling 751 824 participants and 13 017 dementia and 17 341 AD cases. For dementia, compared with the lowest category, the pooled RRs (95% CI) in the highest category of tea, coffee, and caffeine were 0.84 (0.74-0.96, n = 6), 0.95 (0.87-1.02, n = 9), and 0.94 (0.70-1.25, n = 5), with all rated as low certainty in GRADE. For AD, the pooled RRs (95% CI) in the highest category of tea, coffee, and caffeine compared to the lowest category were 0.93 (0.87-1.00, n = 6), 1.01 (0.90-1.12, n = 10), and 1.34 (1.04-1.74, n = 2), with certainty ratings of low, low, and very low, respectively. Dose-response analysis indicated a non-linear relationship between coffee intake (Poverall = 0.04 and Pnonlinear = 0.01) and dementia risk, showing the protective association of risk of dementia with 1 to 3 cups per day of coffee intake. There is a linear association between tea intake and risk of dementia, with a significantly decreased risk of dementia for each 1 cup per day increase in tea consumption (0.96, 95% CI 0.94-0.99, Poverall = 0.01 and Pnonlinear = 0.68). Conclusion: Increased tea consumption was associated with a decreased risk of dementia and AD, and a non-linear relationship was found between coffee and dementia, supporting public health recommendations for dementia prevention.
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Doença de Alzheimer , Cafeína , Café , Demência , Chá , Chá/química , Café/química , Humanos , Doença de Alzheimer/prevenção & controle , Cafeína/administração & dosagem , Demência/epidemiologia , Demência/prevenção & controle , Estudos de Coortes , Feminino , Idoso , Masculino , Fatores de RiscoRESUMO
Phosphorus (P) release from sediment poses a severe challenge for eutrophication management in the aquatic environment. The dissolved organic carbon (DOC) concentrations in riverine ecosystems have shown an increasing trend due to intensified climate change and anthropogenic activities, while their impact on sediment P cycling remains unclear. To investigate the effects of different DOC loads on sediment P release and the underlying mechanisms, we conducted a two-month experiment in 15 plexiglass tanks, with five gradient-increasing target DOC concentrations set according to reality: control (S0), 5 mg/L (S5), 10 mg/L (S10), 15 mg/L (S15), and 20 mg/L (S20). The results demonstrated that: i) DOC enrichment promoted the sediment P mobilization and release, with the underlying mechanisms exhibited periodic characteristics. ii) reduced dissolved oxygen (DO) concentration and stimulated alkaline phosphatase activity (APA) were likely the primary and sustained facilitating mechanisms. While after the termination of DOC load, elevated pH level was also considered a contributing factor when chlorophyll a (Chl a) ranged between 5.9 µg/L and 7.7 µg/L iii) ultimate concentration of total P (TP) in the overlying water depended on DOC load. After DOC addition was terminated, decreased TP concentrations were observed when DOC concentration was in the range of 5-15 mg/L, which may be attributed to the direct uptake of P by phytoplankton counteracting the minor promotion of P release induced by anoxic conditions. However, when DOC concentrations exceeded 15-20 mg/L, there were notable increments in TP concentrations. Our findings provide further insight into the response mechanisms of sediment P release to the increasing organic C load in natural ecosystems. The impact of broader C forms or C loads on sediment P cycling needs to be fully elucidated and even quantified in future studies, especially through large-scale field investigations to further clarify the coupled roles between C and P.
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Carbono , Sedimentos Geológicos , Fósforo , Fósforo/análise , Sedimentos Geológicos/química , Carbono/análise , Poluentes Químicos da Água/análise , Clorofila A/análise , Eutrofização , Clorofila/análiseRESUMO
Rice was collected over the entire grain filling period (about 40 days) to explore the multi-structure evolution and gelatinization behavior changes of starch. During the early stage (DAA 6-14), the significant reduction in lamellar repeat distance (10.04 to 9.68 nm) and relative crystallinity (26.6 % to 22.7 %) was due to initial rapid accumulation of amylose (from 9.38 % to 14.05 %) and short amylopectin chains. Meanwhile, the decreased proportion of aggregation structure resulted in a decrease in the gelatinization temperature and a narrowed range of gelatinization temperature also indicated an increase in homogeneity as starch matured. Gelatinization enthalpy was mainly controlled by aggregation structure, which was negatively and positively related to the amylose content and the degree of order respectively. Peak viscosity of starch pasting increased and reached a maximum (924 cP) at DAA-21 due to larger granule size. Amylose and short amylopectin chains with degree of polymerization 6-12 showed positive and negative correlation with short-term retrogradation ability (setback value) respectively. The dynamics of different scale structure during grain filling had varying degrees of impact on gelatinization properties.
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Amilopectina , Amilose , Oryza , Amido , Oryza/química , Amilose/química , Amido/química , Amilopectina/química , Viscosidade , Temperatura , Gelatina/química , Grão Comestível/químicaRESUMO
Discoidin, CUB, LCCL domain-containing 2 (DCBLD2) is a type I transmembrane protein with a similar structure to neuropilin, which acts as a co-receptor for certain receptor tyrosine kinases (RTKs). The insulin receptor is an RTK and plays a critical role in endothelial cell function and glycolysis. However, how and whether DCBLD2 regulates insulin receptor activity in endothelial cells is poorly understood. Diabetes was induced through treatment of Dcbld2 global-genome knockout mice and endothelium-specific knockout mice with streptozotocin. Vascular ultrasound, vascular tension test, and hematoxylin and eosin staining were performed to assess endothelial function and aortic remodeling. Glycolytic rate assays, real-time PCR and western blotting were used to investigate the effects of DCBLD2 on glycolytic activity and insulin receptor (InsR)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway in endothelial cells. Co-immunoprecipitation was used to assess the effects of DCBLD2 on insulin receptor endocytosis and recycling. Membrane and cytoplasmic proteins were isolated to determine whether DCBLD2 could affect the localization of the insulin receptor. We found that Dcbld2 deletion exacerbated endothelial dysfunction and vascular remodeling in diabetic mice. Both Dcbld2 knockdown and Dcbld2 deletion inhibited glycolysis and the InsR/PI3K/Akt signaling pathway in endothelial cells. Furthermore, Dcbld2 deletion inhibited insulin receptor recycling. Taken together, Dcbld2 deficiency exacerbated diabetic endothelial dysfunction and vascular remodeling by inhibiting the InsR/PI3K/Akt pathway in endothelial cells through the inhibition of Rab11-dependent insulin receptor recycling. Our data suggest that DCBLD2 is a potential therapeutic target for diabetes and cardiovascular diseases.
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Diabetes Mellitus Experimental , Hiperglicemia , Camundongos Knockout , Receptor de Insulina , Remodelação Vascular , Animais , Receptor de Insulina/metabolismo , Receptor de Insulina/genética , Camundongos , Hiperglicemia/metabolismo , Hiperglicemia/genética , Hiperglicemia/patologia , Remodelação Vascular/genética , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patologia , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Humanos , Transdução de Sinais , Masculino , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Glicólise/genética , Endocitose/genética , Deleção de Genes , Camundongos Endogâmicos C57BLRESUMO
The admixture of heavy metals on struvite during the P recovery process from wastewater will affect its value for safe agricultural application, but it is not clear how to effectively separate heavy metals from struvite. Herein, a two-stage separation reactor (static and dynamic) has been developed to achieve efficient separation of heavy metals and struvite. The generation of struvite from real swine wastewater would naturally precipitate to the lowest layer under static conditions, leading to an enrichment of heavy metals (75 % Cu and 84 % Zn) in suspension. Meanwhile, phosphorus recovery from real swine wastewater results in the generation of a large amount of fines flowing out of the reactor due to the effects of suspended solids (SS), etc., making it necessary to recover phosphorus by static separation. For the dynamic separation step, we also analyzed the characteristics of struvite formation at different rotational speeds in a continuous reaction system. The results demonstrated that the shear rate of the fluid affects the particle size of struvite, which in turn determines the rate and the distribution of struvite in either primary or secondary recovery tanks. The implementation of zonal regulation in the flow field can produce a higher phosphorus efficiency (from 85.8 to 95.5 % at pH=8.1-8.2, from 93.8 to 98.5 % at pH=9.0-9.1) and a lower alkali consumption (55.56 % of alkali cost), which is favorable for the separation of struvite crystals and heavy metals (the amount of Cu and Zn metals separated increased by more than 50 %), and ultimately yield high quality of struvite. The findings in this study will provide insights for the separation and reduction of heavy metals through a combined method with dynamic and static in a continuous system, providing a reference for the safe application of struvite in agriculture.
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Phosphorus recovery from wastewater is receiving more attention due to its non-renewable property. As copper (Cu) and zinc (Zn) usually occur in livestock wastewater, this study focused on metal sorption in struvite from swine wastewater and the release properties of granular struvite in solution with varying pH conditions (2, 4, 7). The results demonstrated pH values presented a slightly decreasing trend with increasing Cu/Zn ratio, and Zn exhibited higher sorption performance on struvite crystals than that of Cu. Under the high content of metals in the wastewater, Cu/Zn ratios in the wastewater contributed to varying metal binding forms and mechanisms, resulting in the difference in the leaching properties of nutrients and metal. For the granular struvite manufactured with the adhesion of alginate, the P release percentage achieved 30.3-40.5% after 96 h in the wastewater of pH 2, whereas they were only 5.63-8.92% and 1.05-1.50% in the wastewater of pH 4 and 7, respectively. Acid wastewater contributed to the release of two metals, and the release amount of Zn was higher than that of Cu, which is associated with their sorption capacity in crystals. During the latter soil leaching test of adding granular struvite, the NH4+-N and PO43--P concentration in the effluent ranged from 0.34 to 1.26 and 0.62 to 2.56 mg/L after 96 h, respectively. However, the Cu and Zn could not be measured due to lower than the detection limit under varying treatments. Struvite might be accompanied by quicker metal leaching and slower nutrient leaching when surface sorption dominates in wastewater with lower metal concentrations.
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Gado , Metais Pesados , Estruvita , Águas Residuárias , Águas Residuárias/química , Estruvita/química , Animais , Metais Pesados/química , Adsorção , Poluentes Químicos da Água/química , Eliminação de Resíduos Líquidos , Concentração de Íons de HidrogênioRESUMO
Normal and waxy maize starches were treated with mild alkali treatment (pH 8.5, 9.9, 11.3) in two temperature-time combinations (25 °C for 1 h and 50 °C for 18 h) to investigate the effect on starch structure and properties. Mild alkali treatment partly removed the starch granule-associated proteins and lipids of normal (from 0.31 % to 0.24 % and from 0.77 % to 0.55 %, respectively) and waxy maize starches (from 0.22 % to 0.18 % and from 0.24 % to 0.15 %, respectively). Gelatinization enthalpy of waxy maize starch increased with alkali treatment from 16.20 J·g-1 to 21.95 J·g-1, indicating that amylopectin (AP) rearrangement and AP-AP double helices formation might occur. But amylose could inhibit these effects by restricting mobility of amylopectin, and no such changes occurred for normal maize starch. Alkali treatment decreased gelatinization temperature and increased peak and final viscosity. Alkali treatment decreased trough viscosity and increased setback of normal maize starch. The hydrothermal treatment promoted the effect of alkali, attributed to the more rapid molecular motion at higher temperature. Normal and waxy starches showed different changes after alkali treatment, indicating that amylose played an important role in controlling the effect of alkali and hydrothermal treatment, primarily as an obstructer of amylopectin rearrangement in mild alkali treatment.
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Álcalis , Amilopectina , Amilose , Amido , Zea mays , Zea mays/química , Amido/química , Álcalis/química , Viscosidade , Amilopectina/química , Amilose/química , Temperatura , Concentração de Íons de HidrogênioRESUMO
Background: Numerous studies reported inconsistent association between breakfast skipping and all-cause, cardiovascular disease (CVD) and cancer mortality. Therefore, we conducted a systematic review and meta-analysis to elucidate these associations. Methods: PubMed, Embase, and Web of Science databases were searched up to July 2023 for prospective cohort studies that assessed the association between breakfast skipping and all-cause, CVD and cancer mortality in general adults. A random effect model was used to estimate the pooled hazard ratio (HR) and 95% confidence intervals (CIs), with subgroup analysis and sensitivity analysis performed. The Newcastle-Ottawa Scale (NOS) was used to assess the study and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool was used to assess the risk of bias. Results: The final analysis included 9 cohort studies including 242 095 participants, with 6 studies for all-cause mortality, 4 studies for CVD mortality, and 2 studies for cancer mortality. Compared to regular breakfast consumption, skipping breakfast was associated with a higher risk of all-cause (HR: 1.27, 95% CI, 1.07-1.51, I2 = 77%), CVD (HR 1.28, 95% CI 1.10-1.50, I2 = 0), and cancer (HR: 1.34, 95% CI: 1.11-1.61, I2 = 0%) mortality. Sensitivity analysis revealed inconsistent results in all-cause and CVD mortality. Subgroup analysis showed significant association in studies with larger participants, longer follow-up, adjustments for energy intake, and high-quality articles. GRADE showed very low evidence for all-cause mortality and low evidence for CVD and cancer mortality. Conclusion: The findings underscore the importance of regular breakfast habits for health and longevity. However, these results require careful interpretation due to geographic limitations, potential heterogeneity, and instability.
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Desjejum , Doenças Cardiovasculares , Neoplasias , Humanos , Neoplasias/mortalidade , Doenças Cardiovasculares/mortalidade , Estudos Prospectivos , Adulto , Comportamento Alimentar , Masculino , Fatores de Risco , Feminino , Pessoa de Meia-Idade , Jejum IntermitenteRESUMO
The fruit of Alpinia oxyphylla Miq is an important food spice in southern China and has been used in the treatment of kidney disorders for centuries. In order to discover the natural products with potent renoprotective activities in A. oxyphylla and provide some references for its usage, systematic phytochemical studies were carried out and 24 new diverse sesquiterpenoids, including seven guaiane sesquiterpenoids (1-7), 10 eudesmane sesquiterpenoids (9-13, 18, 19, and 21-23), six cadinane sesquiterpenoids (31-35 and 38), and an eremophilane sesquiterpenoid (40), along with 24 known analogues were isolated and elucidated by analysis of spectroscopic data and quantum-chemical calculations. Biological evaluation showed that 6 sesquiterpenoids could significantly inhibit the expression of extracellular matrix components, α-SMA in TGF-ß1 induced kidney proximal tubular cells (NRK-52e) at low concentrations, and 9 sesquiterpenoids could also downregulate fibronectin and collagen I in a concentration-dependent manner, showing their potential in renal fibrosis. Further action mechanism study displayed that TGF-ß1/Smads pathway might be involved in the antifibrotic effects of active sesquiterpenoids 15 and 43. These studies suggest that A. oxyphylla may have a potential to serve as a functional food in preventing renal fibrosis-associated diseases.
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Alpinia , Frutas , Extratos Vegetais , Sesquiterpenos , Proteínas Smad , Fator de Crescimento Transformador beta1 , Alpinia/química , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Frutas/química , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta1/genética , Animais , Fosforilação/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Proteínas Smad/metabolismo , Proteínas Smad/genética , Humanos , Ratos , Linhagem Celular , Substâncias Protetoras/farmacologia , Substâncias Protetoras/química , Estrutura MolecularRESUMO
Tibial tubercle avulsion fractures (TTAFs) are rare but typical in children and adolescents and Osgood-Schlatter disease (OSD) may be involved in their pathogenesis. However, few publications have reported the relationship between OSD and TTAF. A 16-year-old healthy male adolescent presented with pain, swelling and limited range of motion of the right knee following sudden acceleration while running. Based on the radiographic evidence, the patient was diagnosed with an avulsion fracture of the right tibial tubercle and OSD. Open reduction and internal fixation were performed using two cannulated screws and two Kirschner wires. The patient returned to preinjury activity levels at the 12-month follow-up postoperatively. This case report aimed to highlight this unique injury pattern. For patients with TTAFs, not only should the fracture be treated, but the cause of the fracture, such as OSD, should also be given appropriate treatment.
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Fixação Interna de Fraturas , Fratura Avulsão , Osteocondrose , Fraturas da Tíbia , Humanos , Adolescente , Masculino , Fraturas da Tíbia/cirurgia , Fraturas da Tíbia/diagnóstico por imagem , Fratura Avulsão/cirurgia , Fratura Avulsão/diagnóstico por imagem , Osteocondrose/cirurgia , Osteocondrose/diagnóstico por imagem , Fixação Interna de Fraturas/métodos , Tíbia/diagnóstico por imagem , Tíbia/cirurgia , Tíbia/lesões , Tíbia/patologia , Parafusos ÓsseosRESUMO
Popliteal cysts, also termed Baker's cysts, are clinically common cystic lesions in the popliteal fossa. Typically, the contents of a ruptured cyst tend to spread into the myofascial interfaces in any direction, most commonly inferomedially or into a palpable superficial position. However, to our knowledge, reports of Baker's cysts dissecting into the deep intermuscular septum of the lower calf are extremely rare. We present here the details of the successful treatment through arthroscopy combined with lower calf incision of a patient who sustained hematoma of the knee and lower calf secondary to Baker's cyst rupture. Given the rarity of this disease in China, we present this case report to improve our understanding of the disease and avoid misdiagnosis and provide evidence for its clinical treatment, management, and prognosis.
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Research into kappa opioid receptor (KOR) agonists with attenuated central-nervous-system side effects is a critical focus for developing productive and safe analgesics. Herein, a series of ortho-substituted N-cyclopropylmethyl-7α-phenyl-6,14-endoethano-tetrahydronorthebaines were designed, synthesized, and subjected to bioassays. Compound 7a exhibited high subtype selectivity and potent agonistic activity toward KOR (KOR, Ki = 3.9 nM, MOR/KOR = 270, DOR/KOR = 1075; [35S]GTPγS binding, EC50 = 3.4 nM). Additionally, this compound exhibited robust and persistent antinociceptive effects in rodent models with different animal strains (hot plate test, ED50 = 0.20-0.30 mg/kg, i.p.; abdominal constriction test, ED50 = 0.20-0.60 mg/kg, i.p.), with its KOR-mediated mechanism for antinociception firmly established. Notably, compound 7a, unlike conventional KOR agonists, displayed minimal sedation and aversion at the antinociceptive ED50 dose. This feature addresses a crucial limitation in existing KOR agonists, positioning compound 7a as a promising novel therapeutic agent.
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Receptores Opioides kappa , Receptores Opioides kappa/agonistas , Receptores Opioides kappa/metabolismo , Animais , Camundongos , Relação Estrutura-Atividade , Masculino , Humanos , Hipnóticos e Sedativos/farmacologia , Hipnóticos e Sedativos/síntese química , Hipnóticos e Sedativos/química , Ratos , Analgésicos/farmacologia , Analgésicos/síntese química , Analgésicos/química , Descoberta de Drogas , Ratos Sprague-Dawley , CricetulusRESUMO
Extensive industrial activities and anthropogenic agricultural practices have led to substantial ammonia release to the environment. Although croplands can act as ammonia sinks, reduced crop production under high concentrations of ammonium has been documented. Alpha-ketoglutarate (AKG) is a critical carbon source, displaying pleiotropic physiological functions. The objective of the present study is to disclose the potential of AKG to enhance ammonium assimilation in poplars. It showed that AKG application substantially boosted the height, biomass, and photosynthesis activity of poplars exposed to excessive ammonium. AKG also enhanced the activities of key enzymes involved in nitrogen assimilation: glutamine synthetase (GS) and glutamate synthase (GOGAT), elevating the content of amino acids, sucrose, and the tricarboxylic acid cycle (TCA) metabolites. Furthermore, AKG positively modulated key genes tied to glucose metabolism and ATP synthesis, while suppressing ATP-depleting genes. Correspondingly, both H+-ATPase activity and ATP content increased. These findings demonstrate that exogenously applying AKG improves poplar growth under a high level of ammonium treatment. AKG might function through sufficient carbon investment, which enhances the carbon-nitrogen balance and energy stability in poplars, promoting ammonium assimilation at high doses of ammonium. Our study provides novel insight into AKG's role in improving poplar growth in response to excess ammonia exposure.