Transient neonatal hyperglycemia induces metabolic shifts in the rat hippocampus: a 1H NMR-based metabolomics analysis.

Diabetes has been reported to induce brain metabolic disturbance, but the effect of transient neonatal hyperglycemia (TNH) on brain metabolism remains unclear. Herein the rats were treated with a single intraperitoneal injection of 100 µg/g body weight of streptozotocin within 12 h after birth and displayed a typical clinical characteristic of TNH. Then we used NMR-based metabolomics to examine the metabolic changes in the hippocampus between TNH and normal control (Ctrl) rats at postnatal 7 days (P7) and 21 days (P21). The results show that TNH rats had significantly increased levels of N-acetyl aspartate, glutamine, aspartate and choline in the hippocampus relative to Ctrl rats at P7. Moreover, we found that the levels of alanine, myo-inositol and choline were significantly lower in TNH rats, although their blood glucose levels have been recovered to the normal level at P21. Therefore, our results suggest that TNH may have a long-term effect on hippocampal metabolic changes mainly involving neurotransmitter metabolism and choline metabolism.

Amelioration of Obesity-Related Disorders in High-Fat Diet-Fed Mice following Fecal Microbiota Transplantation from Inulin-Dosed Mice.

The role of inulin in alleviating obesity-related disorders has been documented; yet, its underlying mechanisms still need to be further investigated. This study attempted to elucidate the causative link between the gut microbiota and the beneficial effect of inulin on obesity-related disorders via transferring the fecal microbiota from inulin-dosed mice to high-fat diet (HFD)-induced obese recipient mice. The results show that inulin supplementation can decrease body weight, fat accumulation, and systemic inflammation and can also enhance glucose metabolism in HFD-induced obese mice. Treatment with inulin reshaped the structure and composition of the gut microbiota in HFD-induced obese mice, as characterized by increases in the relative abundances of Bifidobacterium and Muribaculum and decreases in unidentified_Lachnospiraceae and Lachnoclostridium. In addition, we found that these favorable effects of inulin could be partially transferable by fecal microbiota transplantation, and Bifidobacterium and Muribaculum might be the key bacterial genera. Therefore, our results suggest that inulin ameliorates obesity-related disorders by targeting the gut microbiota.

Magnetic Resonance Imaging Findings of Foetal Congenital Toxoplasma Encephalitis: A Case Report.

BACKGROUND: Toxoplasma gondii infection is not uncommon in daily life; primary infection with Toxoplasma gondii (T. gondii) acquired during gestation may lead to a series of fetal complications. Prenatal ultrasound and postpartum neonatal T. gondii encephalitis have been reported previously, but fetal MRI findings of T. gondii encephalitis are quite rare. It is important to identify the severity of cerebral damage and assess fetal prognosis. OBJECTIVE: The purpose of this report is to emphasize that MRI can provide more excellent anatomic information on abnormalities in cerebral parenchyma than ultrasound, which is helpful for the diagnosis of prenatal infectious encephalitis. CASE PRESENTATION: A 38-year-old woman presented to our hospital at a gestation age of 29 weeks due to an ultrasound that showed fetal ventriculomegaly. The fetus demonstrated ventriculomegaly, intrauterine growth restriction, and multiple cystic lesions close to the corticomedullary junction of the frontal, temporal and parietal lobes on both sides. The woman chose to terminate the pregnancy, and pathological examination confirmed the diagnosis of congenital toxoplasma encephalitis. CONCLUSION: This is a rare report of MRI manifestations of fetal congenital toxoplasma encephalitis. Detailed knowledge of MRI findings in fetal congenital toxoplasma encephalitis is helpful for prenatal consultation and pregnancy management.

Adhesive, injectable, and ROS-responsive hybrid polyvinyl alcohol (PVA) hydrogel co-delivers metformin and fibroblast growth factor 21 (FGF21) for enhanced diabetic wound repair.

As conventional treatments for diabetic wounds often fail to achieve rapid satisfactory healing, the development of effective strategies to accelerate diabetic wound repair is highly demanded. Herein, fibroblast growth factor 21 (FGF21) and metformin co-loaded multifunctional polyvinyl alcohol (PVA) hydrogel were fabricated for improved diabetic wound healing. The in vitro results proved that the hydrogel was adhesive and injectable, and that it could particularly scavenge reactive oxygen species (ROSs), while the in vivo data demonstrated that the hydrogel could promote angiogenesis by recruiting endothelial progenitor cells (EPCs) through upregulation of Ang-1. Both ROSs' removal and EPCs' recruitment finally resulted in enhanced diabetic wound healing. This work opens a strategy approach to diabetic wound management by combining biological macromolecules and small chemical molecules together using one promising environmental modulating drug delivery system.

Potential Therapeutic Mechanism of Traditional Chinese Medicine on Diabetes in Rodents: A Review from an NMR-Based Metabolomics Perspective.

Traditional Chinese medicine (TCM) has been used to treat diabetes for a long time, but its application has not been widely accepted due to unstandardized product quality and complex pharmacological mechanisms. The modernization of TCM is crucial for its further development, and in recent years the metabolomics technique has largely driven its modernization. This review focuses on the application of NMR-based metabolomics in diabetic therapy using TCM. We identified a series of metabolic pathways that altered significantly after TCM treatment, providing a better understanding of the metabolic mechanisms of TCM for diabetes care.

The maximum length of T2-dark intraplacental bands may help predict intraoperative haemorrhage in pregnant women with placenta accreta spectrum (PAS).

PURPOSE: To investigate the relationship between the maximum length of T2-dark intraplacental bands (MLTIB) and intraoperative haemorrhage in pregnant women with placenta accreta spectrum (PAS). METHODS: Between February 2018 and February 2021, 86 pregnant women with PAS who delivered in Taizhou Hospital of Zhejiang Province and underwent preoperative magnetic resonance imaging (MRI) examination were retrospectively recruited. The presence of T2-dark intraplacental bands, placental/uterine bulge, loss of retroplacental T2-hypointense line, myometrial thinning, bladder wall interruption, focal exophytic mass, and abnormal vascularization of placental bed were recorded, and the MLTIB was measured. The relative risk ratios of the MRI findings and intraoperative bleeding were measured. Receiver operating characteristic (ROC) analysis was used to evaluate the ability of the MLTIB to help predict intraoperative haemorrhage in pregnant women with PAS. RESULTS: Of the 86 pregnant women, 32 had intraoperative blood loss ≥ 1000 ml; of these, 18 had intraoperative blood loss ≥ 2000 ml. Abnormal vascularization of placental bed was associated with the highest relative risk ratio for the detection of intraoperative haemorrhage (RR = 10.66), followed by the presence of T2-dark intraplacental bands (RR = 8.02). The optimal cut-off of the MLTIB for predicting intraoperative haemorrhage (≥ 1000 ml) in pregnant women with PAS was 28.95 mm, and the AUC was 0.91 (sensitivity: 84%; specificity: 91%). The optimal cut-off of the MLTIB for predicting massive intraoperative haemorrhage (≥ 2000 ml) was 35.65 mm, and the AUC was 0.94 (sensitivity: 89%; specificity: 85%). CONCLUSION: MLTIB was related to intraoperative haemorrhage in pregnant women with PAS. An MLTIB greater than 28.95 mm is an effective predictor of intraoperative haemorrhage. An MLTIB of 35.65 mm or greater strongly suggests the possibility of massive intraoperative haemorrhage.

Survival Analysis and Prediction Model of ASCP Based on SEER Database.

Background: This study aims to compare the incidence and clinical and survival characteristics of adenosquamous carcinoma of the pancreas (ASCP) and adenomatous carcinoma of the pancreas (ACP), analyze the survival factors of ASCP and construct a prognostic model. Method: Patients diagnosed with pancreatic cancer from 2000 to 2018 are selected from the SEER database. ASCP and ACP are compared in terms of epidemiology, clinical characteristics and prognosis. Cases are matched in a 1:2 ratio, and survival analysis is performed. The Cox proportional hazard model is used to determine covariates related to overall survival (OS), and an ASCP prognosis nomogram is constructed and verified by consistency index (C-index), calibration chart and decision curve analysis (DCA). The accuracy of the model is compared with that of AJCC.Stage and SEER.Stage to obtain the area under the receiver operating characteristic (ROC) curve. Results: the age-adjusted incidence of ACP increased significantly over time from 2000 to 2008 and from 2008 to 2018 (P < 0.05). APC was 2.01% (95% CI: 1.95-2.21) and 1.08% (95% CI: 0.93-1.25) respectively. The age-adjusted incidence of ASCP increased with time from 2000 to 2018 (P < 0.05) and APC was 3.64% (95% CI: 3.25-4.01).After propensity score matching (PSM), the OS and cancer-specific survival (CSS) of ACP are better than those of ASCP. The survival time of ASCP is significantly improved by the combined treatment of surgery + chemotherapy + radiotherapy, with a median OS of 31 months. Cox proportional hazard regression analysis shows that age, race, surgery, radiotherapy, chemotherapy and tumor size are independent factors affecting the prognosis. DCA and area under the curve (AUC) value shows that the model has good discrimination ability. Conclusion: The OS prognosis of ASCP is worse than that of ACP, and the nomogram has high accuracy for the prognosis prediction of ASCP.

Convenient, nondestructive monitoring and sustained-release of ethephon/chitosan film for on-demand of fruit ripening.

The microstructure changes (such as micro defects and free volume, etc.) is a deep factor that determines the sustained release behavior of polymer film. However, there are few reports exploring the micro defects of sustained-release materials. Herein, we develop a facile method to non-destructive monitoring and sustained-release ethylene within chitosan. The comprehensive means of positron annihilation lifetime spectroscopy, atomic force microscopy and Raman spectrums are performed together to study the microstructures change of ethylene sustained-release and its mechanism. When ethylene is in chitosan film, it shows good ripening performance and mechanical properties. The sustained-release ethylene improves its bioavailability and can control the fruit-ripening on-demand. More importantly, the microstructural changes of cavities have a significant impact on the sustained release of ethylene, due to the creation of cavities, the free volume of positrons undergoes a process of increasing from less to more and then gradually decreasing, reaching a maximum at 120 h. Furthermore, the ethephon/chitosan film could on-demand control the ripening time of mangoes and bananas. Therefore, this research presents a comprehensive means to study of microstructure change monitoring and controllable sustained release, and provides the possibility to solve the problem of on-demand ripening of fruit and reducing pesticide residue.

Experimental Study on Shear Wave Transmission in Fractured Media.

Unconventional oil and gas reservoirs have broad exploration and development prospects. Fracture parameters and effectiveness evaluation are two of the key tasks for the evaluation of these types of reservoirs. Array acoustic logging can be used for fracture evaluation to compensate for the deficiencies of the image logging fracture evaluation method. Therefore, to develop acoustic logging evaluation methods as well as nondestructive testing methods for fractures, experiments were conducted to study the shear wave transmission in fractured media. Experiment data demonstrate a good correlation between the shear wave attenuation coefficient and fracture width, and the shear wave attenuation coefficients rise logarithmically with the increase in the fracture width for all models with different porosities and distinct dip angles of fractures. The shear wave attenuation coefficient changes relatively faster with the fracture width when the fracture width is within 250 µm. In addition, the shear wave attenuation is affected by the core porosity and fracture dip angle. When the fracture width is constant, the shear wave attenuation caused by the 0° fracture is relatively larger and is obviously greater than that of the fractures at other angles, which is consistent with the existing experimental results. The results of this study can be used to guide further research on amplitude compensation methods for sonic signal transmission in fractured media and fracture evaluation methods.

Fabrication of silk fibroin film enhanced by acid hydrolyzed silk fibroin nanowhiskers to improve bacterial inhibition and biocompatibility efficacy.

In this study, silk fibroin nanowhiskers (SNWs) were extracted from natural silk fiber by sulfuric acid hydrolysis with the assistance of ultrasonic wave treatment. The obtained SNWs were mixed with regenerated silk fibroin (RSF) solution to fabricate the SNWs/RSF films. The fabricating SNWs were systematically characterized by using SEM, FTIR, and the SNWs/RSF films were observed by digital camera, PM, etc. The results show that the monodisperse SNWs are evenly distributed in the RSF film. The presence of SNWs in RSF film significantly improves the performances of the film, including the swelling ability, mechanical properties, hydrophilicity, antibacterial efficacy, cytocompatibility. Meanwhile, the SNWs/RSF film can endorse the wound healing efficiency in vivo mice wound site. The proposed techniques for extracting SNWs and fabricating silk fibroin composite film may provide a valuable method for creating an ideal silk-based material for biomedical applications.

Methacrylated gelatin shape-memorable cryogel subcutaneously delivers EPCs and aFGF for improved pressure ulcer repair in diabetic rat model.

Pressure ulcer (PU) in patients with diabetes mellitus (DM) is still a clinical intractable issue due to the complicated physiological characteristics by the prolonged high glucose level and impaired angiogenesis. The PU treatment includes surgical debridement, stem cell therapy and growth factors, leading to high cost and repeated professional involvement. Developing effective wound dressing combining the therapeutic cells and growth factors has become highly demanded. Herein, we reported the direct subcutaneous administration of endothelial progenitor cells (EPCs) and acid fibroblast growth factor (aFGF) with a shape-memorable methacrylated gelatin cryogel (EPCs/aFGF@GelMA) for the therapy of PU in rats with DM. This EPCs/aFGF@GelMA cryogel system presented microporous structure, elastic mechanical strength and enhanced cell migration property with controlled release of aFGF. Moreover, compared with EPCs/aFGF and GelMA alone, in vivo results showed that this EPCs/aFGF@GelMA system exhibited accelerated wound closure rate, enhanced granulation formation, collagen deposition as well as re-epithelization. Importantly, we found that the excellent positive performance of EPCs/aFGF@GelMA is due to its up-regulation of HIF-ɑ upon the wound site, modulating the microenvironment of wound site to initiate the impaired local angiogenesis. Collectively, this hybrid gelatin cryogels show great promise for biomedical applications, especially in tissue engineering and regenerative medicine.

A Biomimetic Approach for Spatially Controlled Cell Membrane Engineering Using Fusogenic Spherical Nucleic Acid.

Engineering of the cell plasma membrane using functional DNA is important for studying and controlling cellular behaviors. However, most efforts to apply artificial DNA interactions on cells are limited to external membrane surface due to the lack of suitable synthetic tools to engineer the intracellular side, which impedes many applications in cell biology. Inspired by the natural extracellular vesicle-cell fusion process, we have developed a fusogenic spherical nucleic acid construct to realize robust DNA functionalization on both external and internal cell surfaces via liposome fusion-based transport (LiFT) strategy, which enables applications including the construction of heterotypic cell assembly for programmed signaling pathway and detection of intracellular metabolites. This approach can engineer cell membranes in a highly efficient and spatially controlled manner, allowing one to build anisotropic membrane structures with two orthogonal DNA functionalities.

Potential Use of Serum Proteomics for Monitoring COVID-19 Progression to Complement RT-PCR Detection.

RT-PCR is the primary method to diagnose COVID-19 and is also used to monitor the disease course. This approach, however, suffers from false negatives due to RNA instability and poses a high risk to medical practitioners. Here, we investigated the potential of using serum proteomics to predict viral nucleic acid positivity during COVID-19. We analyzed the proteome of 275 inactivated serum samples from 54 out of 144 COVID-19 patients and shortlisted 42 regulated proteins in the severe group and 12 in the non-severe group. Using these regulated proteins and several key clinical indexes, including days after symptoms onset, platelet counts, and magnesium, we developed two machine learning models to predict nucleic acid positivity, with an AUC of 0.94 in severe cases and 0.89 in non-severe cases, respectively. Our data suggest the potential of using a serum protein-based machine learning model to monitor COVID-19 progression, thus complementing swab RT-PCR tests. More efforts are required to promote this approach into clinical practice since mass spectrometry-based protein measurement is not currently widely accessible in clinic.

Fraxetin Inhibits the Proliferation and Metastasis of Glioma Cells by Inactivating JAK2/STAT3 Signaling.

Glioma is the most common brain tumor and is characterized by high mortality rates, high recurrence rates, and short survival time. Migration and invasion are the basic features of gliomas. Thus, inhibition of migration and invasion may be beneficial for the treatment of patients with glioma. Due to its antitumor activity and chemical reactivity, fraxetin has attracted extensive interest and has been proven to be an effective antitumor agent in various cancer types. However, currently, the potential effects of fraxetin on glioma have not been investigated. Here, we demonstrate that fraxetin can inhibit the proliferation, invasion, and migration of glioma and induce apoptosis of glioma cells in vitro and in vivo. Therefore, these findings establish fraxetin as a drug candidate for glioma treatment. Furthermore, fraxetin was able to effectively inhibit the JAK2/STAT3 signaling in glioma. In summary, our results show that fraxetin inhibits proliferation, invasion, and migration of glioma by inhibiting JAK2/STAT3 signaling and inducing apoptosis of glioma cells. The present study provides a solid basis for the development of new glioma therapies.

Controllable performance of a dopamine-modified silk fibroin-based bio-adhesive by doping metal ions.

Bio-adhesives are essential for wound healing because of their convenience and safety. Although widely used as biomaterials, silk fibroin's (SF's) further application as bio-adhesive is hindered due to its weak stickiness with tissue and slow gelation speed. Here, a dopamine-modified SF-based bio-adhesive is fabricated by using genipin as the chemical cross-linking agent. Furthermore, metal ions have been used to adjust the adhesion property of the bio-adhesive. The experimental results shows that the dopamine-modified SF-based composite holds a better stickiness except slow gelation speed. The doping of Cu2+and Fe3+can accelerate the gelation of the bio-adhesive. Compared with Cu2+, Fe3+has a stronger effect on the gelation speed of the bio-adhesive, which is positive correlative to the concentration of Fe3+. The adhesive has injectability and degradability. In addition, the SF-based adhesive has good biocompatibility and good improvement for cell migrationin vitro. The SF-based bio-adhesive holds potential application in the field of rapid fixation of wounds.

Acute fibrinous and organizing pneumonia with myelodysplastic syndrome and pneumocystis jiroveci pneumonia: a case report.

Acute fibrinous and organizing pneumonia (AFOP) is an unusual pathological pattern which is characterized by intra-alveolar deposition of fibrin (fibrin ball) and organizing pneumonia in a scattered distribution, and the pathological diagnosis plays an irreplaceable role in the diagnosis. Most Patients cannot confirm etiology, till now, known etiology included connective tissue disease, infection, environmental and occupational exposure, drugs, organ transplant, and tumor. It can be divided into acute and subacute subtype according to the extent of progress. The most common symptoms of AFOP were fever, cough, and dyspnea. Bilateral consolidations and ground-glass opacities (GGO) usually can be seen on chest CT images. At present, the treatment protocol for AFOP has not reached a consensus Glucocorticoid, immunosuppressants, stem cell transplantation or lung transplantation may contribute to improved clinical outcome. Here, we report a case of AFOP with myelodysplastic syndrome and pneumocystis jiroveci pneumonia (PJP). After treatments of glucocorticoid, immunosuppressant, chemotherapy, antibiotics and blood transfusion, the patient's clinical symptoms, peripheral blood test, and imaging findings were obviously improved. In this case, we consider the AFOP was caused by MDS and the immunodeficiency after chemotherapy lead to secondary PJP. This typical case highlights the importance of appropriate therapy for coexisted diseases of those patients with refractory AFOP.

Quantitative Secretome Analysis Reveals Clinical Values of Carbonic Anhydrase II in Hepatocellular Carcinoma.

Early detection and intervention are key strategies to reduce mortality, increase long-term survival, and improve the therapeutic effects of hepatocellular carcinoma (HCC) patients. Herein, the isobaric tag for relative and absolute quantitation (iTRAQ)-based quantitative proteomic strategy was used to study the secretomes in conditioned media from HCC cancerous tissues, surrounding noncancerous tissues, and distal noncancerous tissues to identify diagnostic and prognostic biomarkers for HCC. In total, 22 and 49 dysregulated secretory proteins were identified in the cancerous and surrounding noncancerous tissues, respectively, compared with the distal noncancerous tissues. Among these proteins, carbonic anhydrase II (CA2) was identified to be significantly upregulated in the secretome of cancerous tissues; correspondingly, the serum concentrations of CA2 were remarkably increased in HCC patients compared with that in normal populations. Interestingly, a significant increase of serum CA2 in recurrent HCC patients after radical resection was also confirmed compared with HCC patients without recurrence, and the serum level of CA2 could act as an independent prognostic factor for time to recurrence and overall survival. Regarding the mechanism, the secreted CA2 enhances the migration and invasion of HCC cells by activating the epithelial mesenchymal transition pathway. Taken together, this study identified a novel biomarker for HCC diagnosis and prognosis, and provided a valuable resource of HCC secretome for investigating serological biomarkers.