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At the center of the SARS-CoV2 infection, the spike protein and its interaction with the human receptor ACE2 play a central role in the molecular machinery of SARS-CoV2 infection of human cells. Vaccine therapies are a valuable barrier to the worst effects of the virus and to its diffusion, but the need of purposed drugs is emerging as a core target of the fight against COVID19. In this respect, the repurposing of drugs has already led to discovery of drugs thought to reduce the effects of the cytokine storm, but still a drug targeting the spike protein, in the infection stage, is missing. In this work, we present a multifaceted computational approach strongly grounded on a biophysical modeling of biological systems, so to disclose the interaction of the SARS-CoV2 spike protein with ACE2 with a special focus to an allosteric regulation of the spike-ACE2 interaction. Our approach includes the following methodologies: Protein Contact Networks and Network Clustering, Targeted Molecular Dynamics, Elastic Network Modeling, Perturbation Response Scanning, and a computational analysis of energy flow and SEPAS as a protein-softness and monomer-based affinity predictor. We applied this approach to free (closed and open) states of spike protein and spike-ACE2 complexes. Eventually, we analyzed the interactions of free and bound forms of spike with hepcidin (HPC), the major hormone in iron regulation, recently addressed as a central player in the COVID19 pathogenesis, with a special emphasis to the most severe outcomes. Our results demonstrate that, compared with closed and open states, the spike protein in the ACE2-bound state shows higher allosteric potential. The correspondence between hinge sites and the Allosteric Modulation Region (AMR) in the S-ACE complex suggests a molecular basis for hepcidin involvement in COVID19 pathogenesis. We verify the importance of AMR in different states of spike and then study its interactions with HPC and the consequence of the HPC-AMR interaction on spike dynamics and its affinity for ACE2. We propose two complementary mechanisms for HPC effects on spike of SARS-CoV-2; (a) HPC acts as a competitive inhibitor when spike is in a preinfection state (open and with no ACE2), (b) the HPC-AMR interaction pushes the spike structure into the safer closed state. These findings need clear molecular in vivo verification beside clinical observations.

The electrode is the crucial component of a brain–computer interface (BCI), and is the key for the development of the BCI technology. Compared with non-intrusive electrodes and intrusive electrodes, semi-invasive BCI electrodes could make a balance between the quality of the electroencephalogram (EEG) signal and security. However, the application of the compressed mesh electrodes, typical semi-invasive electrodes, has been restricted due to the folds and tangles of the electrode material during injection and the insufficient deployment after injection. To solve the problem, we develop a novel semi-invasive BCI flexible electrode material based on the Fe3O4@GO/P(NIPAM–MAA) hydrogel with magnetic field controlled rheology. The rheology test results indicate that the hydrogel is injectable and its expansion during the transition from sol to gel at ∼37 °C can be actively controlled by applying a magnetic field. Its resistivity is less than 120 Ω m, which makes it sensitive enough to transmit electrical signals between brains and computers. The signal waveform and amplitude recorded by the Fe3O4@GO/P(NIPAM–MAA) hydrogel electrode and wet electrode are basically the same, which proves that the prepared hydrogel electrode material can acquire and record effective EEG signals. Compared with the wet electrode, hydrogel electrodes show higher average peak-to-peak values and higher noise levels. Although the signal-to-noise ratio is similar between the Fe3O4@GO/P(NIPAM–MAA) hydrogel electrode and the wet electrode, the hydrogel electrode is more stable, which proves that the Fe3O4@GO/P(NIPAM–MAA) hydrogel electrode can accurately collect and record EEG signals with a stable signal-to-noise ratio.

Short-term post-weaning nutrition can result in long-lasting effects in later life. Partial replacement of glucose by galactose in the post-weaning diet showed direct effects on liver inflammation. Here, we examined this program on body weight, body composition, and insulin sensitivity at the adult age. Three-week-old female C57BL/6JRccHsd mice were fed a diet with glucose plus galactose (GAL; 16 energy% (en%) each) or a control diet with glucose (GLU; 32 en%) for three weeks, and afterward, both groups were given the same high-fat diet (HFD). After five weeks on a HFD, an oral glucose tolerance test was performed. After nine weeks on a HFD, energy metabolism was assessed by indirect calorimetry, and fasted mice were sacrificed fifteen minutes after a glucose bolus, followed by serum and tissue analyses. Body weight and body composition were not different between the post-weaning dietary groups, during the post-weaning period, or the HFD period. Glucose tolerance and energy metabolism in adulthood were not affected by the post-weaning diet. Serum adiponectin concentrations were significantly higher (p = 0.02) in GAL mice while insulin, leptin, and insulin-like growth factor 1 concentrations were not affected. Expression of Adipoq mRNA was significantly higher in gonadal white adipose tissue (gWAT; p = 0.03), while its receptors in the liver and skeletal muscles remained unaffected. Irs2 expression was significantly lower in skeletal muscles (p = 0.01), but not in gWAT or Irs1 expression (in both tissues). Gene expressions of inflammatory markers in gWAT and the liver were also not affected. Conclusively, galactose in the post-weaning diet significantly improved circulating adiponectin concentrations and reduced skeletal muscle Irs2 expression in adulthood without alterations in fat mass, glucose tolerance, and inflammation.

Glioma is the most common malignant tumor of the central nervous system, and it is characterized by high relapse and fatality rates and poor prognosis. Bufalin is one of the main ingredients of Chan-su, a traditional Chinese medicine (TCM) extracted from toad venom. Previous studies revealed that bufalin exerted inhibitory effects on a variety of tumor cells. To demonstrate the inhibitory effect of bufalin on glioma cells and glioma stem-like cells (GSCs) and discuss the underlying mechanism, the proliferation of glioma cells was detected by MTT and colony formation assays following treatment with bufalin. In addition, we investigated whether bufalin inhibits or kills GSCs using flow cytometry, Western blotting, and reverse transcription polymerase chain reaction analysis (RT-PCR). Finally, we investigated whether bufalin could improve the therapeutic effect of temozolomide (TMZ) and discussed the underlying mechanism. Taken together, our data demonstrated that bufalin inhibits glioma cell growth and proliferation, inhibits GSC proliferation, and kills GSCs. Bufalin was found to induce the apoptosis of GSCs by upregulating the expression of the apoptotic proteins cleaved caspase 3 and poly(ADP-ribose) polymerase (PARP) and by downregulating the expression of human telomerase reverse transcriptase, which is a marker of telomerase activity. Bufalin also improved the inhibitory effect of TMZ on GSCs by activating the mitochondrial apoptotic pathway. These results suggest that bufalin damages GSCs, induces apoptosis, and enhances the sensitivity of GSCs to TMZ.

Gliomas are the most invasive and fatal primary malignancy of the central nervous system that have poor prognosis, with maximal safe resection representing the gold standard for surgical treatment. To achieve gross total resection (GTR), neurosurgery relies heavily on generating continuous, real-time, intraoperative glioma descriptions based on image guidance. Given the limitations of currently available equipment, developing a real-time image-guided resection technique that provides reliable functional and anatomical information during intraoperative settings is imperative. Nowadays, the application of intraoperative ultrasound (IOUS) has been shown to improve resection rates and maximize brain function preservation. IOUS, which presents an attractive option due to its low cost, minimal operational flow interruptions, and lack of radiation exposure, is able to provide real-time localization and accurate tumor size and shape descriptions while helping distinguish residual tumors and addressing brain shift. Moreover, the application of new advancements in ultrasound technology, such as contrast-enhanced ultrasound, three-dimensional ultrasound, navigable ultrasound, ultrasound elastography, and functional ultrasound, could help to achieve GTR during glioma surgery. The current review describes current advancements in ultrasound technology and evaluates the role and limitation of IOUS in glioma surgery.

The mechanical characteristics of high-pressure frozen ice are a basis for the design of deep underground frozen walls, the drilling of thick permafrost and ice sheets, and the probing of extraterrestrial ice. The continuous control of the sample stress state from freezing to testing is essential for the experimental study of in situ mechanical response of high-pressure frozen ice. In the context, we developed a preparation technique for freezing pressurized water into a standard cylindrical ice sample in a triaxial cell. Through theoretical analysis, a cylindrical water sample with precise dimensions and strong sealing was fabricated using heat shrinkable tubing, sectional end caps, and an assembly cylinder. A mounting device was designed to insert the water sample into the triaxial cell without deformation. In order to deal with the lateral surface irregular of the resulting ice sample caused by freezing expansion, we proposed a pressurization method in which the volume of the confining medium is controlled to restrict the radial deformation of the sample, and the axial pressure on the sample is kept constant; thus, the freezing expansion will develop along the height direction through releasing the expansion pressure. Based on the analysis of sample deformation and finite element numerical simulations, the control method of the temperature fields of the sample and the confining medium was obtained, and the standard cylindrical ice sample which satisfies the geometric accuracy requirements was produced. The comparison of ice samples frozen by different freezing methods showed that the control of the confining medium mean temperature and the sample unidirectional freezing is necessary to improve the dimensional precision of the ice sample.

Gliomas are the most common primary malignant brain tumors associated with a low survival rate. Even after surgery, radiotherapy, and chemotherapy, gliomas still have a poor prognosis. Extracellular vesicles are a heterogeneous group of cell-derived membranous structures. Exosomes are a type of extracellular vesicles, their size ranges from 30 nm to 100 nm. Recent studies have proved that glioma cells could release numerous exosomes; therefore, exosomes have gained increasing attention in glioma-related research. Recent studies have confirmed the importance of extracellular vesicles, particularly exosomes, in the development of brain tumors, including gliomas. Exosomes mediate intercellular communication in the tumor microenvironment by transporting biomolecules (proteins, lipids, deoxyribonucleic acid, and ribonucleic acid); thereby playing a prominent role in tumor proliferation, differentiation, metastasis, and resistance to chemotherapy or radiation. Given their nanoscale size, exosomes can traverse the blood-brain barrier and promote tumor progression by modifying the tumor microenvironment. Based on their structural and functional characteristics, exosomes are demonstrating their value not only as diagnostic and prognostic markers, but also as tools in therapies specifically targeting glioma cells. Therefore, exosomes are a promising therapeutic target for the diagnosis, prognosis, and treatment of malignant gliomas. More research will be needed before exosomes can be used in clinical applications. Here, we describe the exosomes, their morphology, and their roles in the diagnosis and progression of gliomas. In addition, we discuss the potential of exosomes as a therapeutic target/drug delivery system for patients with gliomas.

During the development of oil fields in permafrost regions, once the surface casing buckling occurs under the formation thawing and subsidence, it will cause great economic losses. In this paper, sinusoidal buckling of surface casing under negative friction is studied and preliminarily discussed. Based on the Winkler foundation theory and considering the different distribution forms of negative friction and soil resistance, the elastic stability model of casing is established. Combining dimensionless and Rayleigh-Ritz method, the critical slenderness ratio of sinusoidal buckling is obtained. The influence of boundary conditions, soil resistance and negative friction distribution on casing stability is quantitatively analysed on the basis of sufficient data calculation. It is found that the product of the critical slenderness ratio and the square root of the strain at the lower boundary is a fixed value which only depends on the boundary conditions and the value of soil resistance parameter, and the negative friction of different distribution forms can be superimposed according to the principle of ‘inverse square’ of the critical slenderness ratio. On this basis, the approximate calculation formula of the critical slenderness ratio is obtained by fitting, and the average error is less than 0.4%. The numerical example shows that the increase of soil resistance will weaken the influence of negative friction distribution on the critical slenderness ratio significantly. The ability to resist sinusoidal buckling can be improved by increasing the constraint of the lower casing section and increasing the casing thickness.

Glioblastoma multiforme (GBM) is a highly invasive cancer with a high recurrence rate. The prognosis of GBM patients remains poor, even after standard surgical resection combined with chemoradiotherapy. Thus, there is an urgent need for new therapeutic targets in GBM. In recent years, microRNAs have received considerable attention due to their important role in tumor development and progression. In this study, we investigated the role of miR-129-5p and miR-129-5p/ZFP36L1 axis in GBM tumorigenesis. Analysis of GSE103228 microarray data from the GEO database showed that miR-129-5p was significantly downregulated in GBM vs. normal brain tissues. Quantitative reverse transcription PCR analysis of miR-129-5p expression in seven GBM cell lines (LN229, A172, U87, T98G, U251, H4, and LN118) vs. normal human astrocytes (NHA) showed miR-129-5p was significantly downregulated in GBM cells. Overexpression of miR-129-5p in LN229 and A172 cells significantly suppressed cell proliferation, migration, invasion, and colony-forming ability. Target Scan analysis identified ZFP36L1 as the target of miR-129-5p. UALCAN dataset analysis found that ZFP36L1 was significantly upregulated in GBM vs. normal brain tissues, and high ZFP36L1 expression was positively associated with the poor survival of GBM patients. Western blot analysis demonstrated that ZFP36L1 was significantly upregulated in seven GBM cell lines vs. NHA. Overexpression of miR-129-5p in LN229 and A172 cells significantly inhibited ZFP36L1 mRNA and protein expression, while overexpression of ZFP36L1 in LN229 and A172 cells reversed miR-129-5p-mediated inhibition on GBM tumorigenesis. Our results revealed an important role of miR-129-5p in the negative regulation of ZFP36L1 expression in GBM, suggesting new candidates for targeted therapy in GBM patients.

Overburden piles at the Molycorp molybdenum mine in north central New Mexico contain neutral rock types as well as mixed volcanic rocks, which are highly weathered materials with low pH and high salinity from pyrite oxidation. The mixing of rock types during overburden pile construction has resulted in heterogeneous substrates with a range of pH and soluble salt levels. An experiment to determine grass species more likely to survive and grow in these low pH overburden materials used substrate treatments consisting of an unadulterated acid rock, an acid:neutral overburden mixture ratio of 9: I, and an acid:neutral overburden mixture ratio of 3:1. Containerized grass seedlings of 54 species/ecotypes, primarily cool-season natives of the western U.S, were transplanted into these substrates. Species grown from seed collected at the Mo\ycorp site having superior performance included Muhlenbergia montana (2 ecotypes), Blepharoneuron trieholepis, Festuea species (3 ecotypes), and a Poa species. A number of commercially available grass varieties had good survival and growth in these substrates: Deschampsia caespitosa 'Peru Creek" Festuea ari:::onica 'Redondo', Festuca ovina 'Covar" Festuea ovina 'MX-86', Festllea sp. 'Shorty', Poa compressa 'Reubens', Paseopyrum smith;; 'Arriba, Barton, and Rosana" and Elymus traehycaulus 'San Luis'. Other native grass species that showed superior survival and growth in these acid rock substrates included Elymus canadensis, Danthonia interrnedia, Sporobolus wrightii, Poa nemoralis, and Hesperostipa cornata. Additional

Gliomatosis cerebri (GC) is a rare glial neoplasm, characterized by extensive diffuse brain infiltration and relative preservation of the underlying architecture. In the present case report, a patient with type 2 GC, which mimicked the clinicoradiological course of acute viral encephalitis, is presented. A 56-year-old male presented with fever, dizziness, headache and numbness in the right extremities three days prior to admission to hospital. The cerebrospinal fluid (CSF) showed mild pleocytosis. Brain magnetic resonance imaging (MRI) revealed hyperintensity on fluid-attenuated inversion recovery images in the left frontal, temporal, insular lobes and in the left thalamus. No signal enhancement was observed following gadolinium administration. The patient was diagnosed with acute viral encephalitis of unknown cause and received a 10-day course of acyclovir, intravenously. At the follow-up three months later, the patient had personality changes and memory deterioration. The results from the follow-up MRI revealed no remarkable changes. At the follow-up six months after presentation, the patient had expressive aphasia and severe headaches. Subsequently, the patient had two tonic-clonic seizure onsets. The results from the MRI showed an increase in lesion size, more edema around the lesion and irregular enhancement in the left frontal lobe. However, the lesions in the left temporal and insular lobes and in the left thalamus were nearly unchanged. Magnetic resonance spectroscopy (MRS) showed elevated choline (Cho)/creatine (Cr) and Cho/N-acetylaspartate (NAA) ratios, as well as decreased NAA/Cr ratios. Surgery was performed and the neuropathological diagnosis of WHO grade III astrocytoma was confirmed. Thus, it is important to pay attention to the differential diagnoses of GC and acute viral encephalitis in patients who have widespread MRI lesions. A brain biopsy is recommended for a diagnosis in this case.

Medulloblastoma (MB) is one of the most common malignant brain tumors of childhood and is associated with a poor prognosis. Gap-junctional intercellular communication (GJIC) is an important mode for cell-to-cell communication. Dysfunctional GJIC is exhibited in most cancer cells. There is significant evidence that GJIC is important in at least some prodrug/suicide gene systems by augmenting the bystander effect (BE). GJIC is made up of connexins (Cxs), among which Cx43 is present in most tissues. Bcl-2, an important apoptosis blocker, is closely associated with the sensitivity to anticancer drugs. Our study showed that dibutyryl cyclic adenosine monophosphate (db-cAMP) upregulated the Cx43 expression and GJIC function in Daoy medulloblastoma cells. It directly enhanced the BE using a herpes simplex virus thymidine kinase (HSV‑tk)/ganciclovir (GCV) system, which was blocked by a Cx43 inhibitor. In addition, db-cAMP increased the cytotoxicity of temozolomide and teniposide, possibly by downregulating the Bcl-2 expression and inducing apoptosis. Taken together, we demonstrated the beneficial effect of db-cAMP in treating medulloblastoma depending on the upregulation of BE and chemosensitivity through Cx43 and Bcl-2-mediated pathways.

The measuring accuracy of the TDR cable length measurement system relies on the recognition of the reflected wave. The reflected wave is susceptible to be affected by noise and the reflected wave detecting error is comparatively large. In order to correctly identifying and detecting the reflected wave, this dissertation studies four reflected wave recognition algorithms, which are established according to the threshold method, centroid method, polynomial fitting method and the wavelet modulus maxima method respectively. The advantages and disadvantages of these algorithms are analyzed. The repeatability and accuracies of the reflected wave arrival time for these algorithms are compared through practical applications.

This paper introduces an application customization platform by which users can package internet information resources as web services. The platform also creates a new UI layout markup language as well as an UI layout algorithm. The mobile client generates web services UI automatically based on user-defined UI layout style, and run the web services.

For the issue of increased computational complexity to improve the positioning accuracy of robots leaving in the mobile robot localization method, this paper propose a new Monte Carlo localization algorithm. This method combinated the traditional particle filter algorithm with unscented Kalman filter, markovian Monte Carlo and reduced complexities level through dynamically updating the number of particles in particle collection and ensuring the accuracy of mobile robot localization. Simulation results show that the algorithm can not only inhibit the particle degradation and improve the positioning accuracy of the robot, but also in terms of computational complexity has increased significantly.