Both plants and animals are living things made up of similar cells as well as organelles, and their essence of life is the same. However, plants face more environmental stress than animals and ...generate excessive reactive oxygen species (ROS), a group of small molecules that can harm proteins, necessitating distinctive metabolic processes. Secondary metabolites in plants are a group of chemical components that can eliminate ROS and can also exhibit medicinal properties; therefore, herbal medicines are often closely linked to the ecological significance of secondary metabolites. Why plants contain so many, not few, active medicinal ingredients is unknown. The root of Scutellaria baicalensis, a popular herbal medicine, is rich in various flavonoids with diverse structural features. Sodium hydrosulfite (Na.sub.2 S.sub.2 O.sub.4) can produce O.sup.- .sub.2 radicals and induce physical conditions under environmental stress. Using UHPLC-ESI-Q-TOF-MS/MS analysis, a total of 25 different compounds were identified in the roots of S. baicalensis between the Na.sub.2 S.sub.2 O.sub.4 groups and suitable conditions. Based on the results of the t-test (P0.05) performed for the groups and ions with values of VIP greater than or equal to 2, the most significantly different chemical markers with Na.sub.2 S.sub.2 O.sub.4 treatment were shikimic acid, citric acid, baicalin, wogonoside, baicalein, wogonin, 3,5,7,2,6-pentahydroxyflavanone, 5,2,6-trihydroxy-7,8-dimethoxy flavone, chrysin, eriodictyol, 5,8-dihydroxy-6,7 -dimethoxy flavone, skullcapflavone II, and 5,7-dihydroxy-6,8,2,3-tetrame thoxyflavone, and most of them were free flavonoids with many phenolic hydroxyl or methoxyl groups and characteristically high antioxidant activities. S. baicalensis roots modified their ability to eliminate ROS and maintained the equilibrium of ROS through the multitudinous biosynthesis and conversion of flavonoids, which is similar to the equilibrium established by an intricate buffer solution and perfectly explains the diversity and complexity of medicinal plant ingredients.
The present study was carried out to investigate the hypoglycemic effect of soy isoflavones from hypocotyl in GK diabetic rats. A single administration and long-term administration tests were ...conducted in GK diabetic rats to test the hypoglycemic effect of soy isoflavones. At the end of long-term administration trial, blood protein, cholesterol, triglyceride, glycosylated serum protein, C-reactive protein, insulin, aminotransferase, lipid peroxide, interleukin-6, tumor necrosis factor-α were estimated. Inhibition of soy isoflavones against α-amylase and α-glucosidase, as well as on glucose uptake into brush border membrane vesicles or Caco-2 cells were determined in vitro. In single administration experiment, soy isoflavones reduced postprandial blood glucose levels in GK rats. In long-term administration, hypoglycemic effect of soy isoflavones was first observed at week 12 and maintained till week 16. A significant reduction in fasting blood glucose, C-reactive protein, and lipid peroxide was noted at week 16. However, there was no significant treatment effect on blood insulin. Furthermore, soy isoflavone administration resulted in significant decreases in glycosylated serum protein, tumor necrosis factor-α, and interleukin-6. Other biochemical parameters, such as protein, cholesterol, triglyceride and aminotransferases were not modified, however. The results in vitro showed that soy isoflavones showed a potent inhibitory effect on intestinal α-glucosidase, but not on pancreatic α-amylase. Soy isoflavones also decreased glucose transport potency into brush border membrane vesicles or Caco-2 cells. It is concluded that soy isoflavones from hypocotyl, performs hypoglycemic function in GK rats with type 2 diabetes, maybe via suppression of carbohydrate digestion and glucose uptake in small intestine.
Problem
This study aimed to identify subsets of regulatory T cells (Tregs) associated with ovarian aging and determine whether they can be used as markers of reproductive aging.
Method
This ...prospective cohort study was conducted among women of reproductive age. Basic physiological characteristics, reproductive hormones, Treg cell subsets, and correlations between these parameters were assessed. The POSEIDON criteria was used to identify women with low reproductive potential.
Results
The percentages of HLA‐DR+ CD45RAˉ Tregs and CD28ˉ Treg‐like cells significantly increased with age. Women between 40 and 49 years had significantly higher percentages of HLA‐DR+ CD45RAˉ Tregs and CD28ˉ Treg‐like cells than those at 20–29, 30–34, and 35–39 years old. Age positively correlated with FSH levels and the percentages of HLA‐DR+ CD45RAˉ Tregs and CD28ˉ Treg‐like cells, but inversely correlated with antral follicle count (AFC) and AMH levels. Interestingly, a positive correlation was found between the percentages of HLA‐DR+ CD45RAˉ Tregs and FSH levels, whereas an inverse correlation was found between those of HLA‐DR+ CD45RAˉ Tregs and AFC or AMH levels. Furthermore, a significant positive correlation was observed between the percentages of CD28ˉ Treg‐like cells and AFC. Based on POSEIDON criteria, women with the percentages of HLA‐DR+ CD45RAˉ Tregs and CD28ˉ Treg‐like cells above reference value ranges were assigned to the low prognosis groups.
Conclusion
These findings suggest that HLA‐DR+ CD45RAˉ Tregs and CD28ˉ Treg‐like cells can be used as immunologic markers of reproductive aging, which helps clinicians identify women with low reproductive potential and establish individualized therapeutic strategies.
Abstract
The near‐infrared (NIR) light polarization metrology is crucial in a broad area of applications, such as optical sensing, imaging, and communications. The conventional measurement of NIR ...light polarization requires bulky polarization optics by the spatial or temporal splitting of the input light beam with expensive infrared detectors. Here, an intelligent fiber‐integrated NIR polarimeter based on upconversion nanoparticles (UCNPs) is demonstrated. Er‐doped UCNPs are synthesized in core–shell structures for bright upconversion luminescence (UCL), and the tapered multimode fiber (MMF) is designed for random Rayleigh‐distributed speckles. It is demonstrated for the first time that spectra‐polarization‐dependent upconverted speckle patterns captured by a cost‐effective visible image sensor can be accurately decoded via a deep neural network (ResNet50). The experimental results show that ResNet50 has a recognition accuracy of over 99.5% for the full‐Stokes parameters of NIR light polarization, along with 100% accuracy for the light wavelength ranging from 1535 nm to 1565 nm. The developed intelligent optical sensors provide a new design paradigm for fiber‐integrated multi‐dimensional NIR light field detection and can be applied in fiber‐optic sensors and communications networks.
Purpose
The magnetic compression technique (MCT) is a new surgical method that has been used for gastrointestinal anastomosis, choledochojejunostomy, and intestinal anastomosis, but there are no ...reports on its use for esophagogastric anastomosis. This study aimed to investigate the feasibility of using MCT to fashion esophagogastric anastomoses in rabbits.
Methods
Twenty rabbits were randomized into an MCT group (study group,
n
= 10) and a hand-sewn group (control group,
n
= 10). The magnetic compression anastomosis device used in this study was made of neodymium iron boron (NdFeB) and possessed parent (PMR) and daughter (DMR) magnetic rings. To fashion the anastomosis, the PMR and DMR were inserted into the lower esophagus and gastric fundus, respectively. The coupled magnets automatically compressed the sandwiched tissues and were expelled once the anastomosis was installed. The two groups were further compared in terms of the anastomosis construction time, survival rate, and postoperative complications. One month after the anastomosis was installed, the burst pressure and gross appearance of the anastomoses were evaluated.
Results
The anastomosis construction time in the study group was significantly shorter than that in the control group (10.50 ± 1.58 min vs. 18.60 ± 2.22 min;
P
< 0.05), and the magnetic rings were defecated out in 10.70 ± 3.49 days. The incidence of anastomotic blockage in both the study and control groups did not differ significantly (0%, 0/10 vs. 20%, 2/10;
P
> 0.05). Anastomotic leakage was not found in either of the groups, and the anastomoses burst pressures were similar in the two groups. However, the magnetically compressed anastomoses in the study group had a relatively smoother gross appearance than the hand-sewn anastomoses.
Conclusion
The magnetic compression anastomosis device is a safe and feasible tool for fashioning esophagogastric anastomoses in this animal model.
Abstract
Aims
Rapid over-activation of β-adrenergic receptor (β-AR) upon stress leads to cardiac inflammation, a prevailing factor that underlies heart injury. However, mechanisms by which acute β-AR ...stimulation induce cardiac inflammation still remain unknown. Here, we set out to identify the crucial role of inflammasome/interleukin (IL)-18 in initiating and maintaining cardiac inflammatory cascades upon β-AR insult.
Methods and results
Male C57BL/6 mice were injected with a single dose of β-AR agonist, isoproterenol (ISO, 5 mg/kg body weight) or saline subcutaneously. Cytokine array profiling demonstrated that chemokines dominated the initial cytokines upregulation specifically within the heart upon β-AR insult, which promoted early macrophage infiltration. Further investigation revealed that the rapid inflammasome-dependent activation of IL-18, but not IL-1β, was the critical up-stream regulator for elevated chemokine expression in the myocardium upon ISO induced β1-AR-ROS signalling. Indeed, a positive correlation was observed between the serum levels of norepinephrine and IL-18 in patients with chest pain. Genetic deletion of IL-18 or the up-stream inflammasome component NLRP3 significantly attenuated ISO-induced chemokine expression and macrophage infiltration. In addition, IL-18 neutralizing antibodies selectively abated ISO-induced chemokines, proinflammatory cytokines and adhesion molecules but not growth factors. Moreover, blocking IL-18 early after ISO treatment effectively attenuated cardiac inflammation and fibrosis.
Conclusion
Inflammasome-dependent activation of IL-18 within the myocardium upon acute β-AR over-activation triggers cytokine cascades, macrophage infiltration and pathological cardiac remodelling. Blocking IL-18 at the early stage of β-AR insult can successfully prevent inflammatory responses and cardiac injuries.
The role of locoregional radiotherapy in patients with de novo metastatic nasopharyngeal carcinoma (mNPC) is unclear.
To investigate the efficacy and safety of locoregional radiotherapy in de novo ...mNPC.
Patients with biopsy-proven mNPC, who demonstrated complete or partial response (RECIST v1.1) following 3 cycles of cisplatin and fluorouracil chemotherapy, were enrolled. Eligible patients were randomly assigned (1:1) to receive either chemotherapy plus radiotherapy or chemotherapy alone. Overall, 126 of 173 patients screened were eligible to the study, and randomized to chemotherapy plus radiotherapy (n = 63) or chemotherapy alone (n = 63). Median (IQR) follow-up duration was 26.7 (17.2-33.5) months.
The chemotherapy regimens were fluorouracil continuous intravenous infusion at 5 g/m2 over 120 hours and 100 mg/m2 intravenous cisplatin on day 1, administered every 3 weeks for 6 cycles. Patients assigned to the chemotherapy plus radiotherapy group received intensity-modulated radiotherapy (IMRT) after chemotherapy.
The primary end point of the study was overall survival (OS). The secondary end point was progression-free survival (PFS) and safety.
Overall, 126 patients were enrolled (105 men 83.3% and 21 women 16.7%; median IQR age, 46 39-52 years). The 24-month OS was 76.4% (95% CI, 64.4%-88.4%) in the chemotherapy plus radiotherapy group, compared with 54.5% (95% CI, 41.0%-68.0%) in the chemotherapy-alone group. The study met its primary end point of improved OS (stratified hazard ratio HR, 0.42; 95% CI, 0.23-0.77; P = .004) in favor of chemotherapy plus radiotherapy. Progression-free survival was also improved in the chemotherapy plus radiotherapy group compared with the chemotherapy-alone group (stratified HR, 0.36; 95% CI, 0.23-0.57). No significant differences in acute hematological or gastrointestinal toxic effects were observed between the treatment arms. The frequency of acute grade 3 or higher dermatitis, mucositis, and xerostomia was 8.1%, 33.9%, and 6.5%, respectively, in the chemotherapy plus radiotherapy group. The frequency of late severe grade 3 or higher hearing loss and trismus was 5.2% and 3.4%, respectively, in the chemotherapy plus radiotherapy group.
In this randomized clinical trial, radiotherapy added to chemotherapy significantly improved OS in chemotherapy-sensitive patients with mNPC.
ClinicalTrials.gov Identifier: NCT02111460.
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The short disulfide-rich α-conotoxins derived from the venom of Conus snails comprise a conserved CICII(m)CIII(n)CIV cysteine framework (m and n, number of amino acids) and the ...majority antagonize nicotinic acetylcholine receptors (nAChRs). Depending on disulfide connectivity, α-conotoxins can exist as either globular (CI-CIII, CII-CIV), ribbon (CI-CIV, CII-CIII) or bead (CI-CII, CIII-CIV) isomers. In the present study, C. geographus α-conotoxins GI, GIB, G1.5 and G1.9 were chemically synthesized as globular and ribbon isomers and their activity investigated at human nAChRs expressed in Xenopus oocytes using the two-electrode voltage clamp recording technique. Both the globular and ribbon isomers of the 3/5 (m/n) α-conotoxins GI and GIB selectively inhibit heterologous human muscle-type α1β1δε nAChRs, whereas G1.5, a 4/7 α-conotoxin, selectively antagonizes neuronal (non-muscle) nAChR subtypes particularly human α3β2, α7 and α9α10 nAChRs. In contrast, globular and ribbon isomers of G1.9, a novel C-terminal elongated 4/8 α-conotoxin exhibited no activity at the human nAChR subtypes studied. This study reinforces earlier observations that 3/5 α-conotoxins selectively target the muscle nAChR subtypes, although interestingly, GIB is also active at α7 and α9 α10 nAChRs. The 4/7 α-conotoxins target human neuronal nAChR subtypes whereas the pharmacology of the 4/8 α-conotoxin remains unknown.
ABSTRACT
Background
Congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of kidney failure in children with phenotypic and genotypic heterogeneity. Our objective was to ...describe the genetic spectrum and identify the risk factors for kidney failure in children with CAKUT.
Methods
Clinical and genetic data were derived from a multicentre network Chinese Children Genetic Kidney Disease Database (CCGKDD) and the Chigene database. A total of 925 children with CAKUT who underwent genetic testing from 2014 to 2020 across China were studied. Data for a total of 584 children were obtained from the CCGKDD, including longitudinal data regarding kidney function. The risk factors for kidney failure were determined by the Kaplan–Meier method and Cox proportional hazards models.
Results
A genetic diagnosis was established in 96 of 925 (10.3%) children, including 72 (8%) with monogenic variants, 20 (2%) with copy number variants (CNVs) and 4 (0.4%) with major chromosomal anomalies. Patients with skeletal abnormalities were more likely to have large CNVs or abnormal karyotypes than monogenic variants. Eighty-two patients from the CCGKDD progressed to kidney failure at a median age of 13.0 years (95% confidence interval 12.4–13.6) and 24 were genetically diagnosed with variants of PAX2, TNXB, EYA1, HNF1B and GATA3 or the 48,XXYY karyotype. The multivariate analysis indicated that solitary kidney, posterior urethral valves, bilateral hypodysplasia, the presence of certain variants and premature birth were independent prognostic factors.
Conclusions
The genetic spectrum of CAKUT varies among different subphenotypes. The identified factors indicate areas that require special attention.
Graphical Abstract
Graphical Abstract
Objective Many metals, some of which have been classified as environmental endocrine disruptors, are used extensively in everyday consumer products and are ubiquitous in our living environment. In ...the present study, we aimed to explore the associations between the prevalence risk of type 2 diabetes and plasma levels of 20 trace elements as well as those of heavy metals in a Han Chinese population. Methods We conducted a case-control study to investigate the associations between plasma concentrations of 20 metals and diabetes in Jiangsu province. A total of 122 newly diagnosed cases of type 2 diabetes and 429 matched controls were recruited from community physical examinations in Suzhou City of Jiangsu Province. Plasma metal levels were measured by inductively-coupled plasma mass spectrometry. Results After adjusting for confounders, plasma vanadium, chromium, manganese, copper, zinc, arsenic, selenium, strontium, palladium, cadmium, cesium, and barium were associated with diabetes risk （P 〈 0.05）. The adjusted OR increased with increasing concentration of vanadium, manganese, copper, zinc, and cesium. Conclusion Many metals, including manganese, copper, zinc, arsenic, selenium, and cadmium in plasma, are associated with the morbidity of diabetes. Monitoring of environmental metal levels and further studies are urgently needed.
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