There has been an explosion in the number of papillomaviruses that have been identified and fully sequenced. Yet only a minute fraction of these has been studied in any detail. Most of our research efforts have focused on the E6 and E7 proteins of “high-risk”, cancer-associated human papillomaviruses (HPVs). Interactions of the high-risk HPV E6 and E7 proteins with cellular targets, the p53 and the retinoblastoma tumor suppressors have been investigated in minute detail. Some have thus questioned if research on papillomaviruses remains an exciting and worthwhile area of investigation. However, fundamentally new insights on the biological activities and cellular targets of the high-risk HPV E6 and E7 proteins have been discovered and previously unstudied HPVs have been associated with human diseases. HPV infections continue to be an important cause of human morbidity and mortality and since there are no antivirals to combat HPV infections, research on HPVs should remain attractive to new investigators and biomedical funding agencies, alike.

9α-Hydroxyandroster-4-ene-3,17-dione (9-OH-AD) is a representative steroid drug intermediate that can be prepared by phytosterols (PS) biotransformation with mycobacteria in a resting cell-cyclodextrin system. In this study, over-expression of 17β-hydroxysteroid dehydrogenase (Hsd4A) was testified to enhance the side-chain degradation of PS and to reduce the incomplete degradation by-products. Meanwhile, the complete degradation product 4-androstene-3,17-dione (AD) was increased due to lack of 3-Ketosteroid 9α-Hydroxylase (KshA1) activities. To increase the production and purity of 9-OH-AD, the metabolic pathway of the side-chain degradation of PS and 9-position hydroxylation was modulated by balancing the over-expression of Hsd4A and KshA1 in mycobacteria and reducing the bioconversion rate via lowering the ratio of PS and cyclodextrin. The production and purity of 9-OH-AD in broth were improved from 22.18 g/L and 77.13% to 28.27 g/L and 87.84%, with a molar yield of 78.32%.

Background: To obtain high yields of recombinant insulin and advancing therapeutic avenues for diabetes patients, the development of innovative designer insulin analogs have critical importance. The modified insulin analog presents a cost-effective remedy by being produced as inclusion bodies (IBs) within Escherichia coli BL21 (DE3) Rosetta-2 strain. This approach to production not only offers reduced production time but also yields high recovery rates. The prime aim of this investigation was to optimize the composition of the cultivation media, thereby accomplishing higher cell density fermentation of the proinsulin. Result: Various factors, including carbon and nitrogen sources, salts, metal ions, and pH, were systematically investigated through experimental screening using the BioLector multiwell bright plate. Additionally, computational analysis employing the Plackett-Burman Design within the Design Expert software was utilized to assess their effectiveness in terms of insulin concentration as a surrogate measure of insulin yield. Among the tested variables, glucose, glycerol, MgSO4, and lower Luria-Bertani mix concentration have a significant influence on insulin production, as determined by the screening experiment. Subsequently, the Central Composite Design approach was operated to further evaluate and optimize the precise levels of these influential variables. This systematic methodology achieved an optimized cultivation media formulation, resulting in a remarkable enhancement of insulin production, with levels reaching up to 13 mg/ml when applied in BioLector fermentation. Conclusion: The formulated cultivation media exhibited suitability for promoting high cell density fermentation of the modified insulin, thereby facilitating the attainment of optimal yields for the proinsulin expression.

IntroductionGastrointestinal lipomas, scarce benign tumors of the gut, are rarely located in the duodenum. There is a narrow number of the patient which are symptomatic and may have upper gastrointestinal obstruction or bleeding(1-3). We report a case of a 63-year-old woman who presented to us with intermittent gastric outlet obstruction along with duodenal lipoma which underwent surgical resection.

Introduction:Obstructive uropathy resulting from mature cystic teratomas is a rare complication that has received limited attention in the literature. We describe a case of unilateral ovarian teratoma presenting with acute flank pain and renal involvement.

One of the greatest alternatives to Li-ion batteries is an Al-air battery. The aluminium (Al) is more effective as a battery because of its viability and nontoxicity. The design of cell and electrode stacking affect the performance of Al-air battery. The present study focuses on designing an efficient air cathode host to lengthen the battery’s lifespan using highly porous carbon aerogel. Initially, the carbon aerogel (CA) material is synthesized using sol-gel polymerization process and characterized using XRD, SEM, and BET. The synthesized CA is used to fabricate the electrode stacking using the in-house-built Al-air cell. The performance of carbon aerogel coated on carbon cloth as air cathode has been evaluated using a galvanostatic discharge of the assembly at different current rates, and the specific capacity is recorded. The highest specific capacity observed is ~ 683 mAh g-1 at 2.551 mA cm -2 current density. The acquired results demonstrate the superiority of the present electrodes material compared to currently used air electrode. The improved electrochemical stability and the robust pore network in CA allow oxygen to pass through the cathode end for chemical reaction. Overall, this enhances kinetics and makes the interactions between oxygen and aluminum to generate higher current because of relatively faster chemical reaction.

Fallback foods (FBF), classified into staple and filler types, are low-quality food resources chosen by animals due to a shortage of preferred food during a specific period. The selection of lichens as FBF for Yunnan snub-nosed monkeys (Rhinopithecus bieti) represents a unique ecological adaptation and evolutionary development in the animal kingdom. This study investigates the yearly dietary selection of five R. bieti groups to address the issues and elucidate the nutritional value and ecological selection of lichens for this monkey species, which resides at the highest altitude among nonhuman primates. The results indicate that the consumed lichens serve as the staple FBF. Two main lichen species taken by the monkeys are Bryoria spp. and Usnea longissimi, with Bryoria spp. being the primary choice (67.25 ± 12.20% compared to 15.79 ± 11.66% from U. longissimi). Bryoria spp. provides a higher level of digestible fiber (NDF) and a lower level of tannin, fat, ADF, and energy compared to U. longissimi, which offers higher availability. Lichens are the dominant food and nutritional resource for the monkey species during the dry season, while they serve as a primary food source rather than a nutritional resource during the wet season. Therefore, they compensate for nutrients from other food types, such as fruits, seeds, and leaves. Compared to other Asian colobine counterparts, this species consumes the highest amount of lichens but the lowest proportions of leaves, flowers, and seeds. This dietary pattern demonstrates a specific type of ecological selection and evolutionary development during the Quaternary. The biomass of lichens in the monkeys’ habitat has significantly decreased due to environmental degradation. This study also provides evidence and information to develop or amend conservation strategies and guidelines for the dietary management of captive Yunnan snub-nosed monkeys.

Modern mobile robots require precise and robust localization and navigation systems to achieve mission tasks correctly. In particular, in the underwater environment, where Global Navigation Satellite Systems (GNSSs) cannot be exploited, the development of localization and navigation strategies becomes more challenging. Maximum A Posteriori (MAP) strategies have been analyzed and tested to increase navigation accuracy and take into account the entire history of the system state. In particular, a sensor fusion algorithm relying on a MAP technique for Simultaneous Localization and Mapping (SLAM) has been developed to fuse information coming from a monocular camera and a Doppler Velocity Log (DVL) and to consider the landmark points in the navigation framework. The proposed approach can guarantee to simultaneously locate the vehicle, thanks to the onboard sensors, and map the surrounding environment with the information extracted from the images acquired by a bottom-looking optical camera. Optical sensors can provide constraints between the vehicle poses and the landmarks belonging to the observed scene. The DVL measurements have been employed to solve the unknown scale factor and to guarantee the correct vehicle localization even in absence of visual features. After validating the solution through realistic simulations, an experimental campaign at sea was conducted in Stromboli Island (Messina), Italy. In conclusion, an algorithm, which works with the Poisson surface reconstruction method to obtain a smooth seabed surface, for mesh creation has been developed.

To establish a relationship between the glymphatic system of brain and circadian rhythm, we analyzed the effect of anomalies in water thermodynamics on dependence of dynamic, electrical, and optical characteristics of physiological fluids on temperature. The dynamics of hydrogen bonds in bulk and hydrated water affected the activation energies of ion currents of voltage-dependent channels that regulate signaling and trophic bonds in neuropil of the cortical parenchyma. The physics of minimizing of isobaric heat capacity of water made it possible to explain stabilization and functional optimization of thermodynamics of eyeball fluids at 34.5 °C and human brain during sleep at 36.5 °C. At these temperatures, thermoreceptors of cornea and cells of ganglionic layer of the retina, through connections with suprachiasmatic nucleus and pineal gland, switch circadian rhythm from daytime to nighttime. The phylogenesis of circadian rhythm was reflected in dependence of duration of nighttime sleep of mammals on diameter of eyeball, mass of pineal gland, and density of neurons in parenchyma of cortex. The activity of all nerves of eyeball led to division of night sleep into slow and fast phases. In the first phase, there are relaxation processes of synaptic plasticity and in the second - increase water exchange in parenchyma and flush out toxins into the venous system. Electrophysics of clearance and conductivity of ionic and water channels of membranes of blood vessels and astrocytes modulate oscillations of polarization potentials of water dipole domains in parietal plasma layers of arterioles and capillaries.

Background: Hemodialysis (HD) leads to cognitive impairment; however, the pathophysiology of maintenance HD remains unclear. This study aimed to investigate the longitudinal alterations in gray matter volume (GMV) and cerebral blood flow (CBF) in patients on follow-up HD compared with baseline HD, examine the alterations in functional connectivity (FC) by defining co-changed brain regions as seed points, and investigate the correlation between the co-changed brain regions and neuropsychological test scores. Methods: Twenty-seven patients with HD and 30 healthy controls were enrolled in this study. All participants underwent high-resolution T1-weighted imaging, arterial spin labeling, and functional MR imaging to measure GMV, CBF, and FC. The patients on HD were assessed at baseline and 3 years subsequently. Results: The right and left medial superior frontal gyrus (SFGmed.L) exhibited significantly lower GMV and CBF in patients on follow-up HD compared with patients on baseline HD and lower FC between the SFGmed.L and left middle temporal gyrus (MTG.L). Decreased FC between the SFGmed.L and MTG.L was positively correlated with neuropsychological test scores in the follow-up HD group. Conclusions: Reduced GMV and CBF may result in decreased FC between the SFGmed.L and MTG.L, which may be associated with cognitive impairment in patients on maintenance HD. Our findings provide unique insights into the pathological mechanisms of patients on maintenance HD with cognitive impairment.

Background: Stroke causes numerous symptoms, including impaired motor skills, sensation languages, and cognitive functions. Previous studies revealed non-invasive brain stimulation techniques could enhance sensory, cognitive, and motor function. Objective: This study aimed to evaluate the effectiveness of transcranial direct current stimulation on functional communication, motor learning, and cognitive function in patients with ischemic stroke. Methods and Materials: The research method of this study was quasi-experimental with pre-test and post-test designs with three groups. Twenty-four patients were enrolled at the beginning. After written consent before the intervention, the Fugl-Meyer Assessment, Montreal Cognitive Assessment Test, and Mini-Mental State Exam were performed at three different time points. Furthermore, functional and structural neuroimaging (DTI, fMRI) were exploited before and after the intervention. Regarding the intervention process, transcranial direct current stimulation (tDCS) was used for twelve 30-minute daily sessions for the patients. Data were analyzed via in-house MATLAB-SPM12, FSL, and scikit-learn. Results: The figures for the FMA test of the active group increased after the intervention (P<0.05). Additionally, the figure for both screening tests increased after the treatment in the active group (P<0.05). Regarding the results of DTI, a significant difference was found in some regions, such as the right inferior occipital. Moreover, the best results were achieved by Random Forest, CatBoost, and XGBoost models in classifying groups by DTI data. Conclusion: Transcranial direct-current stimulation has been proven to be an effective rehabilitation for post-stroke impairments. We assessed the different structural and functional neuroimaging methods to determine which could display the effect of tDCS.

Brunsting-Perry pemphigoid (BPP) is a variant of cicatricial pemphigoid characterised by tense, pruritic subepidermal bullae which eventually heals with atophic scarring. BPP has a predilection for head and neck area with little or no mucosal involvement. Average age of onset is 58 with a 2:1 male/female ratio. Here, we report a

Wireless power transfer (WPT) system in seawater exhibits distinct transmission characteristics from those in air due to the unique properties of seawater medium and the complexity of the seawater environment. In this paper, a 2-transmitter (2TX) and 1-receiver (1RX) WPT system in the frequency band of 350~550 kHz in seawater is observed. When the transfer distance is at midrange, the maximum load voltage point of the system is shifted from 460 kHz to 430 kHz compared to that in air, and the maximum transfer efficiency is 7 times of that in air. The system maintains a stable output voltage when the receiving coil is at different offsets. To grasp the influence mechanism of seawater on wireless power transfer, two new parameters, complex self-inductance and complex mutual inductance, are introduced into the circuit model to summarize the propagation of electromagnetic waves in attenuating medium, and the model is verified through experiments.

IntroductionThrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy that manifests as microangiopathic hemolytic anemia, severe thrombocytopenia, and ischemia damage to important organs caused by platelet-rich thrombi produced in the microvasculature. TTP is caused by a congenital or acquired lack of the von Willebrand factor-cleaving protease, ADAMTS13 (A Disintegrin and Metalloproteinase with a Thrombospondin type 1 motif, member 13). Anti-ADAMTS13 autoantibodies are the primary cause of ADAMTS13 deficiency, which can be idiopathic or associated with various pathological processes such as neoplasias, infections, and autoimmune disorders like systemic lupus erythematous (SLE) 1. If left untreated, TTP is a dangerous illness with a high death rate. The prognosis has significantly improved with therapeutic plasma exchange (TPE), and mortality has dropped from 85%-100% to 10%-30% 2, 3. TPE is a technique that involves separating blood cells from plasma. When elements in the plasma are responsible for the pathophysiology of the disease, this approach is employed. This method is used as a treatment method for various diseases, but the reason for using TPE in a patient suffering from acquired TTP is to remove Anti-ADAMTS13 autoantibodies. Relapse happens in 40% of patients, and there are cases that are resistant to treatment. Various immunosuppressive medications, including rituximab (RTX), have been used in these cases 4. TTP is relatively uncommon in SLE patients. It is unknown how often TTP occurs overall in SLE patients; however, it has been estimated to be as low as 0.5% 5. Instances of simultaneous TTP and SLE are often discussed in the medical literature in patients who have substantial renal dysfunction and lupus activity 6. Here we present a clinical case of a woman who developed myocardial infarction (MI) in the context of TTP. After further investigation, undiagnosed SLE disease was suggested as the cause of TTP.

The ability of trophectodermal cells (outer layer of the embryo) to attach to the endometrial cells and subsequently invade the underlying matrix are critical stages of embryo implantation during successful pregnancy establishment. Extracellular vesicles (EVs) have been implicated in embryo-maternal crosstalk, capable of reprogramming endometrial cells towards a pro-implantation signature and phenotype. However, challenges associated with EV yield and direct loading of biomolecules limit their therapeutic potential. We have previously established generation of cell-derived nanovesicles (NVs) from human trophectodermal cells (hTSCs) and their capacity to reprogram endometrial cells to enhance adhesion and blastocyst outgrowth. Here, we employed a rapid NV loading strategy to encapsulate potent implantation molecules such as HB-EGF (NVHBEGF). We show these loaded NVs elicit EGFR-mediated effects in recipient endometrial cells, activating kinase phosphorylation sites that modulate their activity (AKT S124/129, MAPK1 T185/Y187), and downstream signalling pathways and processes (AKT signal transduction, GTPase activity). Importantly, they enhanced target cell attachment and invasion. The phosphoproteomics and proteomics approach highlight NVHBEGF-mediated short-term signalling patterns and long-term reprogramming capabilities on endometrial cells which functionally enhance trophectodermal-endometrial interactions. This proof-of-concept study demonstrate feasibility in enhancing the potency of NVs in the context of embryo attachment and establishment.

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Dynamic flux balance analysis (FBA) allows estimation of intracellular reaction rates using organism-specific genome scale metabolic models (GSMM) and by assuming instantaneous pseudo steady states for processes that are inherently dynamic. This technique is well-suited for industrial bioprocesses employing complex media characterized by a hierarchy of substrate uptake and product secretion. However, knowledge of exchange rates of many components of the media would be required to obtain meaningful results. Here, we performed spent media analysis using mass spectrometry (MS) coupled with liquid (LCMS) and gas chromatography (GCMS) for a fed-batch, high cell density cultivation of E. coli BL21(DE3) expressing a recombinant protein. Time course measurements thus obtained for 246 metabolites were converted to instantaneous exchange rates. These were then used as constraints for dynamic FBA using a previously reported GSMM, thus providing insights into how the flux map evolves through the process. Changes in TCA cycle fluxes correlated with the increased demand for energy during recombinant protein production. The results show how amino acids act as hubs for the synthesis of other cellular metabolites. Our results provide a deeper understanding of an industrial bioprocess and will have implications in further optimizing the process.

In this paper, Long Short-Term Memory (LSTM) networks and multilayered feedforward neural networks (FFNNs) were combined with first principles equations in a hybrid workflow to describe human embryonic kidney 293 (HEK293) culture dynamics. Experimental data of 27 extracellular state variables in 20 fed-batch HEK293 cultures were collected in a parallel high throughput 250 mL cultivation system. The adaptive moment estimation method (ADAM) with stochastic regularization and cross-validation were employed for deep learning. A total of 784 hybrid models with varying deep neural network (DNN) architectures, depths, layers sizes and node activation functions were compared. In most scenarios, hybrid LSTM models outperformed hybrid FFNN models in terms of training and testing error. Hybrid LSTM models revealed to be less sensitive to data resampling than FFNN hybrid models. As disadvantages, Hybrid LSTM models are in general more complex (higher number of parameters) and have a higher computation cost than FFNN hybrid models. The hybrid model with the highest prediction accuracy consisted in a LSTM network with 7 internal states connected in series with dynamic material balance equations. This hybrid model correctly predicted the dynamics of the 27 state variables (R 2=0.93 in the test data set), including biomass, key substrates, amino acids and metabolic by-products for around 10 cultivation days.