Astragalus polysaccharide promotes the regeneration of intestinal stem cells through HIF-1 signalling pathway.

Ionizing radiation (IR)-induced intestinal injury is usually accompanied by high lethality. Intestinal stem cells (ISCs) are critical and responsible for the regeneration of the damaged intestine. Astragalus polysaccharide (APS), one of the main active ingredients of Astragalus membranaceus (AM), has a variety of biological functions. This study was aimed to investigate the potential effects of APS on IR-induced intestine injury via promoting the regeneration of ISCs. We have established models of IR-induced intestinal injury and our results showed that APS played great radioprotective effects on the intestine. APS improved the survival rate of irradiated mice, reversed the radiation damage of intestinal tissue, increased the survival rate of intestinal crypts, the number of ISCs and the expression of intestinal tight junction-related proteins after IR. Moreover, APS promoted the cell viability while inhibited the apoptosis of MODE-K. Through organoid experiments, we found that APS promoted the regeneration of ISCs. Remarkably, the results of network pharmacology, RNA sequencing and RT-PCR assays showed that APS significantly upregulated the HIF-1 signalling pathway, and HIF-1 inhibitor destroyed the radioprotection of APS. Our findings suggested that APS promotes the regeneration of ISCs through HIF-1 signalling pathway, and it may be an effective radioprotective agent for IR-induced intestinal injury.

FG-4592 protected haematopoietic system from ionising radiation in mice.

Ionising radiation exposure can lead to acute haematopoietic radiation syndrome. Despite significant advancements in the field of radioprotection, no drugs with high efficacy and low toxicity have yet been approved by the Food and Drug Administration. FG-4592, as a proline hydroxylase inhibitor, may play an important role in radioprotection of the haematopoietic system. Mice were peritoneal injected with FG-4592 or normal saline. After irradiation, the survival time, body weight, peripheral blood cell and bone marrow cell (BMC) count, cell apoptosis, pathology were analysed and RNA-sequence technique (RNA-Seq) was conducted to explore the mechanism of FG-4592 in the haematopoietic system. Our results indicated that FG-4592 improved the survival rate and weight of irradiated mice and protected the spleen, thymus and bone marrow from IR-induced injury. The number of BMCs was increased and protected against IR-induced apoptosis. FG-4592 also promoted the recovery of the blood system and erythroid differentiation. The results of RNA-Seq and Western blot showed that the NF-κB signalling pathway and hypoxia-inducible factor-1 (HIF-1) signalling pathway were upregulated by FG-4592. Meanwhile, RT-PCR results showed that FG-4592 could promote inflammatory response significantly. FG-4592 exhibited radioprotective effects in the haematopoietic system by promoting inflammatory response and targeting the NF-κB, HIF signalling pathway.

Autophagy inhibition improves the targeted radionuclide therapy efficacy of 131I-FAP-2286 in pancreatic cancer xenografts.

PURPOSES: Radiotherapy can induce tumor cell autophagy, which might impair the antitumoral effect. This study aims to investigate the effect of autophagy inhibition on the targeted radionuclide therapy (TRT) efficacy of 131I-FAP-2286 in pancreatic cancer. METHODS: Human pancreatic cancer PANC-1 cells were exposed to 131I-FAP-2286 radiotherapy alone or with the autophagy inhibitor 3-MA. The autophagy level and proliferative activity of PANC-1 cells were analyzed. The pancreatic cancer xenograft-bearing nude mice were established by the co-injection of PANC-1 cells and pancreatic cancer-associated fibroblasts (CAFs), and then were randomly divided into four groups and treated with saline (control group), 3-MA, 131I-FAP-2286 and 131I-FAP-2286 + 3-MA, respectively. SPECT/CT imaging was performed to evaluate the bio-distribution of 131I-FAP-2286 in pancreatic cancer-bearing mice. The therapeutic effect of tumor was evaluated by 18F-FDG PET/CT imaging, tumor volume measurements, and the hematoxylin and eosin (H&E) staining, and immunohistochemical staining assay of tumor tissues. RESULTS: 131I-FAP-2286 inhibited proliferation and increased the autophagy level of PANC-1 cells in a dose-dependent manner. 3-MA promoted 131I-FAP-2286-induced apoptosis of PANC-1 cells via suppressing autophagy. SPECT/CT imaging of pancreatic cancer xenograft-bearing nude mice showed that 131I-FAP-2286 can target the tumor effectively. According to 18F-FDG PET/CT imaging, the tumor growth curves and immunohistochemical analysis, 131I-FAP-2286 TRT was capable of suppressing the growth of pancreatic tumor accompanying with autophagy induction, but the addition of 3-MA enabled 131I-FAP-2286 to achieve a better therapeutic effect along with the autophagy inhibition. In addition, 3-MA alone did not inhibit tumor growth. CONCLUSIONS: 131I-FAP-2286 exposure induces the protective autophagy of pancreatic cancer cells, and the application of autophagy inhibitor is capable of enhancing the TRT therapeutic effect.

Engineering Artificial Atomic Systems of Giant Electric Dipole Moment.

The electric dipole moment (EDM) plays a crucial role in determining the interaction strength of an atom with electric fields, making it paramount to quantum technologies based on coherent atomic control. We propose a scheme for engineering the potential in a Paul trap to realize a two-level quantum system with a giant EDM formed by the motional states of a trapped electron. We show that, under realistic experimental conditions, our system exhibits enhanced EDMs compared to those attainable with Rydberg atoms, serving as a complementary counterpart in the megahertz (MHz) resonance-frequency range. Furthermore, we show that such artificial atomic dipoles can be efficiently initialized, read out, and coherently controlled, thereby providing a potential platform for quantum technologies such as ultrahigh-sensitivity electric-field sensing.

Protecting Quantum Information via Destructive Interference of Correlated Noise.

Decoherence and imperfect control are crucial challenges for quantum technologies. Common protection strategies rely on noise temporal autocorrelation, which is not optimal if other correlations are present. We develop and demonstrate experimentally a strategy that uses the cross-correlation of two noise sources. Utilizing destructive interference of cross-correlated noise extends the coherence time tenfold, improves control fidelity, and surpasses the state-of-the-art sensitivity for high frequency quantum sensing, significantly expanding the applicability of noise protection strategies.

High-resolution MRI vessel wall enhancement in moyamoya disease: risk factors and clinical outcomes.

OBJECTIVES: Intracranial vessel wall enhancement (VWE) on high-resolution magnetic resonance imaging (HRMRI) is associated with the progression and poor prognosis of moyamoya disease (MMD). This study assessed potential risk factors for VWE in MMD. METHODS: We evaluated MMD patients using HRMRI and traditional angiography examinations. The participants were divided into VWE and non-VWE groups based on HRMRI. Logistic regression was performed to compare the risk factors for VWE in MMD. The incidence of cerebrovascular events of the different subgroups according to risk factors was compared using Kaplan-Meier survival and Cox regression. RESULTS: We included 283 MMD patients, 84 of whom had VWE on HRMRI. The VWE group had higher modified Rankin Scale scores at admission (p = 0.014) and a higher incidence of ischaemia and haemorrhage (p = 0.002) than did the non-VWE group. Risk factors for VWE included the ring finger protein 213 (RNF213) p.R4810K variant (odds ratio [OR] 2.01, 95% confidence interval [CI] 1.08-3.76, p = 0.028), hyperhomocysteinaemia (HHcy) (OR 5.08, 95% CI 2.34-11.05, p < 0.001), and smoking history (OR 3.49, 95% CI 1.08-11.31, p = 0.037). During the follow-up of 63.9 ± 13.2 months (median 65 months), 18 recurrent stroke events occurred. Cox regression showed that VWE and the RNF213 p.R4810K variant were risk factors for stroke. CONCLUSION: The RNF213 p.R4810K variant is strongly associated with VWE and poor prognosis in MMD. HHcy and smoking are independent risk factors for VWE. CLINICAL RELEVANCE STATEMENT: Vessel wall enhancement in moyamoya disease is closely associated with poor prognosis, especially related to the ring finger protein 213 p.R4810K variant, hyperhomocysteinaemia, and smoking, providing crucial risk assessment information for the clinic. KEY POINTS: • The baseline presence of vessel wall enhancement is significantly associated with poor prognosis in moyamoya disease. • The ring finger protein 213 p.R4810K variant is strongly associated with vessel wall enhancement and poor prognosis in moyamoya disease. • Hyperhomocysteinaemia and smoking are independent risk factors for vessel wall enhancement in moyamoya disease.

Effect of Sarcoplasmic Protein Solutions Dried at Different Times and Rates on Water Migration in Lamb Myofibril In Vitro.

To determine whether sarcoplasmic proteins affected water migration in myofibrils during air-drying, with protein denaturation as an indicator of sarcoplasmic protein changes, the extent of sarcoplasmic protein changes in lamb during air-drying was first studied. The results showed that sarcoplasmic protein's thermal stability decreased and secondary structure changed, indicating sarcoplasmic protein denatured in lamb during air-drying (35 °C, 60% RH, 3 m/s wind speed). Subsequently, the effect of sarcoplasmic protein solutions, dried at different times and rates, on myofibril protein-water interaction was studied in vitro. Two sets of sarcoplasmic protein solutions were dried for 0, 3, 6, and 9 h in a drying oven, resulting in different degrees of change. These two sets with higher or lower drying rates were achieved by controlling the contact area between sarcoplasmic protein solution and air. These dried sarcoplasmic protein solutions were then mixed with extracted myofibril and incubated for 2 h. The results showed a significant increase in T21 relaxation time of the incubation system when sarcoplasmic protein solution was dried at 35 °C for 3 h. This indicated that myofibrillar protein-water interaction was weakened, facilitating water migration from the inside to the outside of myofibrils. The denaturation degree of sarcoplasmic proteins was slowed by a higher drying rate, thereby alleviating the increase in the amount of immobile water within myofibrils when dried for 6 h. In conclusion, the properties of sarcoplasmic proteins were influenced by both drying rate and time, thereby influencing the water migration within myofibrils during air-drying.

Differentiating HCC from ICC and prediction of ICC grade based on MRI deep-radiomics: Using lesions and their extended regions.

PURPOSE: This study aimed to evaluate the ability of MRI-based intratumoral and peritumoral radiomics features of liver tumors to differentiate between hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) and to predict ICC differentiation. METHODS: This study retrospectively collected 87 HCC patients and 75 ICC patients who were confirmed pathologically. The standard region of interest (ROI) of the lesion drawn by the radiologist manually shrank inward and expanded outward to form multiple ROI extended regions. A three-step feature selection method was used to select important radiomics features and convolution features from extended regions. The predictive performance of several machine learning classifiers on dominant feature sets was compared. The extended region performance was assessed by area under the curve (AUC), specificity, sensitivity, F1-score and accuracy. RESULTS: The performance of the model is further improved by incorporating convolution features. Compared with the standard ROI, the extended region obtained better prediction performance, among which 6 mm extended region had the best prediction ability (Classification: AUC = 0.96, F1-score = 0.94, Accuracy: 0.94; Grading: AUC = 0.94, F1-score = 0.93, Accuracy = 0.89). CONCLUSION: Larger extended region and fusion features can improve tumor predictive performance and have potential value in tumor radiology.

Zinc and Chronic Kidney Disease: A Review.

Chronic kidney disease (CKD) poses a major global public health challenge. The World Health Organization's data shows that CKD affects about 10% of the world's population, particularly in low- and middle-income countries. Due to limited access to diagnosis and treatment, CKD has become the 12th leading cause of death worldwide. The advanced stage of CKD can lead to kidney failure, which is clinically referred to as end-stage renal disease (ESRD). In such cases, patients can only sustain life through dialysis or kidney transplantation. However, the long-term affordability of these treatments remains low. Moreover, the effectiveness of kidney transplantation is modest, posing a significant treatment barrier in resource-limited settings, and significantly impacting patient survival. To address this issue, we suggest using dietary supplementation of the trace element zinc to impede CKD development and prolong patient survival.

4D Flow MRI of Portal Vein Hemodynamics in Healthy Volunteers and Patients with Chronic Liver Disease.

AIM: To identify age-matched healthy volunteers, non-cirrhotic chronic liver disease (CLD) and cirrhotic patients based on portal hemodynamic parameters using 4D flow MRI. METHODS: A total of 10 age-matched healthy volunteers and 69 CLD patients were enrolled and underwent 4D flow MRI prospectively. 4D flow MR images were processed by an MD in biomedical engineering working on the GTFlow platform. Portal hemodynamic parameters include net flow (mL/cycle), flow volume per second through the lumen (mL/sec), average flow velocity (cm/sec), and maximum flow velocity (cm/sec). The difference in portal hemodynamic parameters of 4D flow MRI was compared among healthy volunteers, non-cirrhotic CLD patients and patients with cirrhosis by one-way ANOVA or Kruskal-Wallis nonparametric test and post hoc tests. RESULTS: 10 CLD patients without cirrhosis and 56 patients with cirrhosis were eventually included, along with 10 healthy volunteers who were divided into three groups. 3 patients with cirrhosis whose image quality did not meet the requirements were excluded. There were no significant differences in portal hemodynamic parameters among the three groups except portal average velocity (P > 0.05). There was no statistical difference in all portal hemodynamic parameters of 4D flow MRI between healthy volunteers and patients with cirrhosis (P > 0.05). There were significant differences in portal average velocity between non-cirrhotic CLD patients, healthy volunteers and patients with cirrhosis, respectively (11.44±3.93 vs 8.10±2.66, P=0.013; 11.44±3.93 vs 8.60±2.22, P=0.007). CONCLUSION: Portal average velocity obtained by 4D flow MRI can be an auxiliary means to identify cirrhosis in patients with CLD.

Scleroglucan protects the intestine from irradiation-induced injury by targeting the IL-17 signaling pathway.

BACKGROUND: Intestinal tissue is extremely sensitive to ionizing radiation (IR), which is easy to cause intestinal radiation sickness, and the mortality rate is very high after exposure. Recent studies have found that intestinal immune cells and intestinal stem cells (ISCs) may play a key role in IR-induced intestinal injury. METHODS: C57BL6 mice matched for age, sex and weight were randomly grouped and intraperitoneal injected with PBS, Scleroglucan (125.0 mg/kg) or Anti-mouse IL-17A -InVivo (10 mg/kg), the number of mice in each group was n ≥ 3.Survival time, body weight, pathology, organoids and immune cell markers of the mice after IR (10.0 Gy) were compared, and the mechanism of action in intestinal tissues was verified by transcriptome sequencing. RESULTS: Scleroglucan has significant radiation protective effects on the intestine, including improving the survival rate of irradiated mice, inhibiting the radiation damage of intestinal tissue, and promoting the proliferation and differentiation of intestinal stem cells (ISCs). The results of RNA sequencing suggested that Scleroglucan could significantly activate the immune system and up-regulate the IL-17 and NF-κB signaling pathways. Flow cytometry showed that Scleroglucan could significantly up-regulate the number of Th17 cells and the level of IL-17A in the gut. IL-17A provides radiation protection. After intraperitoneal injection of Scleroglucan and Anti-mouse IL-17A -InVivo, mice can significantly reverse the radiation protection effect of Scleroglucan, down-regulate the molecular markers of intestinal stem cells and the associated markers of DC, Th1 and Th17 cells, and up-regulate the associated markers of Treg and Macrophage cells. CONCLUSION: Scleroglucan may promote the proliferation and regeneration of ISCs by regulating the activation of intestinal immune function mediated by IL-17 signaling pathway and play a protective role in IR-induced injury.

The hypothesis of an effective safe and novel radioprotective agent hydrogen-rich solution / La hipótesis de una solución rica en hidrógeno como agente radioprotector novedoso, seguro y efectivo

Most ionizing radiation-induced damage is caused by radical oxygen species (ROS). Some radioprotectors, such as amifostine, exert radioprotective effects by scavenging radical oxygen species. Recent studies show that hydrogen (H2) has antioxidant activities that protect the brain and intestine against ischaemia-reperfusion injury and stroke by selectively reducing hydroxyl and peroxynitrite radicals. However, it is seldom regarded as a radioprotective agent. In like manner, we hypothesize that hydrogen may be an effective, specific and novel radioprotective agent. But H2 is explosive, while hydrogen-rich solution (solution such as physiological saline saturated with molecular hydrogen) is safer.

La mayor parte de los efectos dañinos inducidos por la radiación ionizante, son causados por especies radicales de oxígeno (ROS). Algunos radioprotectores, tales como la amifostina, ejercen efectos radioprotectores mediante el rescate de especies radicales de oxígeno. Estudios recientes muestran que el hidrógeno (H2) posee una actividad antioxidante que protege el cerebro y el intestino contra las lesiones por repercusión isquémica y accidente cerebrovascular, mediante la reducción selectiva de radicales de hidroxilo y peroxinitrito. Sin embargo, raramente se le considera como un agente radioprotector. De manera similar, planteamos la hipótesis de que el hidrógeno puede ser un agente radioprotector efectivo, específico y novedoso. Pero el H2 es explosivo, mientras que la solución rica en hidrógeno (como es el caso del suero fisiológico saturado con hidrógeno molecular) es más segura.