Miracle-dz/UniFAR-FTUs huggingface dataset:
An Insight to Brain Targeting Utilizing Polymeric Nanoparticles: Effective Treatment Modalities for Neurological Disorders and Brain Tumor

The delivery of therapeutic molecules to the brain remains an unsolved problem to the researchers due to the existence of the blood–brain barrier (BBB), which halts the entry of unwanted substances to the brain. Central nervous system (CNS) disorders, mainly Parkinson’s disease, Alzheimer’s disease, schizophrenia, brain tumors, and stroke, are highly prevalent globally and are a growing concern for researchers due to restricting the delivery of pharmaceutical drugs to the brain. So effective treatment modalities are essential to combat the growing epidemic of CNS diseases. Recently, the growing attention in the field of nanotechnology has gained the faith of researchers for the delivery of therapeutics to the brain by targeting them to the specific target site. Polymeric nanoparticles (PNPs) emerge out to be an instrumental approach in drug targeting to the brain by overcoming the physiological barrier, biomedical barrier, and BBB. Preclinical discovery has shown the tremendous potential and versatility of PNPs in encapsulating several drugs and their targeting to the deepest regions of the brain, thus improving therapeutic intervention of CNS disorders. The current review will summarize advances in the development of PNPs for targeting therapeutics to the brain and the functional and molecular effects obtained in the preclinical model of most common CNS diseases. The advancement of PNPs in clinical practice and their prospect in brain targeting will also be discussed briefly.
Dynamics of Gastrointestinal Activity and Ruminal Absorption of the Methane-Inhibitor, Nitroethane, in Cattle

Nitroethane is a potent methane-inhibitor for ruminants but little is known regarding simultaneous effects of repeated administration on pre- and post-gastric methane-producing activity and potential absorption and systemic accumulation of nitroethane in ruminants. Intraruminal administration of 120 mg nitroethane/kg body weight per day to Holstein cows (n = 2) over a 4-day period transiently reduced (P < 0.05) methane-producing activity of rumen fluid as much as 3.6-fold while concomitantly increasing (P < 0.05) methane-producing activity of feces by as much as 8.8-fold when compared to pre-treatment measurements. These observations suggest a bacteriostatic effect of nitroethane on ruminal methanogen populations resulting in increased passage of viable methanogens to the lower bovine gut. Ruminal VFA concentrations were also transiently affected by nitroethane administration (P < 0.05) reflecting adaptive changes in the rumen microbial populations. Mean (± SD) nitroethane concentrations in plasma of feedlot steers (n = 6/treatment) administered 80 or 160 mg nitroethane/kg body weight per day over a 7-day period were 0.12 ± 0.1 and 0.41 ± 0.1 μmol/mL 8 h after the initial administration indicating rapid absorption of nitroethane, with concentrations peaking 1 day after initiation of the 80 or 160 mg nitroethane/kg body weight per day treatments (0.38 ± 0.1 and 1.14 ± 0.1 μmol/mL, respectively). Plasma nitroethane concentrations declined thereafter to 0.25 ± 0.1 and 0.78 ± 0.3 and to 0.18 ± 0.1 and 0.44 ± 0.3 μmol/mL on days 2 and 7 for the 80 or 160 mg nitroethane/kg body weight per day treatment groups, respectively, indicating decreased absorption due to increased ruminal nitroethane degradation or to more rapid excretion of the compound.
Targeting SARS-CoV-2 Proteases for COVID-19 Antiviral Development

The emergence of severe acute respiratory syndrome (SARS-CoV-2) in 2019 marked the third occurrence of a highly pathogenic coronavirus in the human population since 2003. As the death toll surpasses 5 million globally and economic losses continue, designing drugs that could curtail infection and disease progression is critical. In the US, three highly effective Food and Drug Administration (FDA)–authorized vaccines are currently available, and Remdesivir is approved for the treatment of hospitalized patients. However, moderate vaccination rates and the sustained evolution of new viral variants necessitate the ongoing search for new antivirals. Several viral proteins have been prioritized as SARS-CoV-2 antiviral drug targets, among them the papain-like protease (PLpro) and the main protease (Mpro). Inhibition of these proteases would target viral replication, viral maturation, and suppression of host innate immune responses. Knowledge of inhibitors and assays for viruses were quickly adopted for SARS-CoV-2 protease research. Potential candidates have been identified to show inhibitory effects against PLpro and Mpro, both in biochemical assays and viral replication in cells. These results encourage further optimizations to improve prophylactic and therapeutic efficacy. In this review, we examine the latest developments of potential small-molecule inhibitors and peptide inhibitors for PLpro and Mpro, and how structural biology greatly facilitates this process.
Current Concepts of Neural Stem/Progenitor Cell Therapy for Chronic Spinal Cord Injury

Chronic spinal cord injury (SCI) is a devastating condition that results in major neurological deficits and social burden. It continues to be managed symptomatically, and no real therapeutic strategies have been devised for its treatment. Neural stem/neural progenitor cells (NSCs/NPCs) being used for the treatment of chronic SCI in experimental SCI models can not only replace the lost cells and remyelinate axons in the injury site but also support their growth and provide neuroprotective factors. Currently, several clinical studies using NSCs/NPCs are underway worldwide. NSCs/NPCs also have the potential to differentiate into all three neuroglial lineages to regenerate neural circuits, demyelinate denuded axons, and provide trophic support to endogenous cells. This article explains the challenging pathophysiology of chronic SCI and discusses key NSC/NPC-based techniques having the greatest potential for translation over the next decade.
Associations of Visceral Adipose Tissue, Circulating Protein Biomarkers, and Risk of Cardiovascular Diseases: A Mendelian Randomization Analysis

Aim: To evaluate the genetic associations of visceral adipose tissue (VAT) mass with metabolic risk factors and cardiovascular disease (CVD) endpoints and to construct a network analysis about the underlying mechanism using Mendelian randomization (MR) analysis. Methods and Results: Using summary statistics from genome-wide association studies (GWAS), we conducted the two-sample MR to assess the effects of VAT mass on 10 metabolic risk factors and 53 CVD endpoints. Genetically predicted VAT mass was associated with metabolic risk factors, including triglyceride (odds ratio, OR, 1.263 [95% confidence interval, CI, 1.203–1.326]), high-density lipoprotein cholesterol (OR, 0.719 [95% CI, 0.678–0.763]), type 2 diabetes (OR, 2.397 [95% CI, 1.965–2.923]), fasting glucose (OR, 1.079 [95% CI, 1.046–1.113]), fasting insulin (OR, 1.194 [95% CI, 1.16–1.229]), and insulin resistance (OR, 1.204 [95% CI, 1.16–1.25]). Genetically predicted VAT mass was associated with CVD endpoints, including atrial fibrillation (OR, 1.414 [95% CI, 1.332 = 1.5]), coronary artery disease (OR, 1.573 [95% CI, 1.439 = 1.72]), myocardial infarction (OR, 1.633 [95% CI, 1.484 =1.796]), heart failure (OR, 1.711 [95% CI, 1.599–1.832]), any stroke (OR, 1.29 [1.193–1.394]), ischemic stroke (OR, 1.292 [1.189–1.404]), large artery stroke (OR, 1.483 [1.206–1.823]), cardioembolic stroke (OR, 1.261 [1.096–1.452]), and intracranial aneurysm (OR, 1.475 [1.235–1.762]). In the FinnGen study, the relevance of VAT mass to coronary heart disease, stroke, cardiac arrhythmia, vascular diseases, hypertensive heart disease, and cardiac death was found. In network analysis to identify the underlying mechanism between VAT and CVDs, VAT mass was positively associated with 23 cardiovascular-related proteins (e.g., Leptin, Hepatocyte growth factor, interleukin-16), and inversely with 6 proteins (e.g., Galanin peptides, Endothelial cell-specific molecule 1). These proteins were further associated with 32 CVD outcomes. Conclusion: Mendelian randomization analysis has shown that VAT mass was associated with a wide range of CVD outcomes including coronary heart disease, cardiac arrhythmia, vascular diseases, and stroke. A few circulating proteins may be the mediators between VAT and CVDs.
Metagenomics Versus Metatranscriptomics of the Murine Gut Microbiome for Assessing Microbial Metabolism During Inflammation

Shotgun metagenomics studies have improved our understanding of microbial population dynamics and have revealed significant contributions of microbes to gut homeostasis. They also allow in silico inference of the metagenome. While they link the microbiome with metabolic abnormalities associated with disease phenotypes, they do not capture microbial gene expression patterns that occur in response to the multitude of stimuli that constantly ambush the gut environment. Metatranscriptomics closes that gap, but its implementation is more expensive and tedious. We assessed the metabolic perturbations associated with gut inflammation using shotgun metagenomics and metatranscriptomics. Shotgun metagenomics detected changes in abundance of bacterial taxa known to be SCFA producers, which favors gut homeostasis. Bacteria in the phylum Firmicutes were found at decreased abundance, while those in phyla Bacteroidetes and Proteobacteria were found at increased abundance. Surprisingly, inferring the coding capacity of the microbiome from shotgun metagenomics data did not result in any statistically significant difference, suggesting functional redundancy in the microbiome or poor resolution of shotgun metagenomics data to profile bacterial pathways, especially when sequencing is not very deep. Obviously, the ability of metatranscriptomics libraries to detect transcripts expressed at basal (or simply low) levels is also dependent on sequencing depth. Nevertheless, metatranscriptomics informed about contrasting roles of bacteria during inflammation. Functions involved in nutrient transport, immune suppression and regulation of tissue damage were dramatically upregulated, perhaps contributed by homeostasis-promoting bacteria. Functions ostensibly increasing bacteria pathogenesis were also found upregulated, perhaps as a consequence of increased abundance of Proteobacteria. Bacterial protein synthesis appeared downregulated. In summary, shotgun metagenomics was useful to profile bacterial population composition and taxa relative abundance, but did not inform about differential gene content associated with inflammation. Metatranscriptomics was more robust for capturing bacterial metabolism in real time. Although both approaches are complementary, it is often not possible to apply them in parallel. We hope our data will help researchers to decide which approach is more appropriate for the study of different aspects of the microbiome.
Land Degradation Changes the Role of Above- and Belowground Competition in Regulating Plant Biomass Allocation in an Alpine Meadow

The allocation pattern of plant biomass presents the strategy of the plant community to adopt environmental changes, while the driver of biomass allocation is still unclear in degraded alpine grassland ecosystems. To explore the issue, this study investigated the shoot-to-root (R/S) ratio, plant aboveground traits, and root competition of three functional groups (i.e., grasses, sedges, and forbs) at three degradation levels (i.e., no obvious degradation, ND; moderate degradation, MD; and severe degradation, SD) in an alpine meadow in the eastern Qinghai-Tibetan Plateau. The relationships among plant aboveground traits, root competition, and R/S ratio were tested using the structural equation model (SEM). The results showed that the shoot and root biomass tended to decrease, but the R/S ratio of the plant community did not change along the degradation gradient. Plant height, lateral spread, and leaf length of most plant functional groups reduced, while leaf width and leaf area of most plant functional groups did not change along the degradation gradients. The root competition ability (presented as the fraction of root biomass in total biomass) of sedges in MD was the lowest, while that of grasses was the highest. The effects of aboveground competition on the R/S ratio were non-linear because of the different roles of plant height, lateral spread, and leaf area in regulating the R/S ratio along the degradation gradient. In contrast, the effects of belowground competition on the R/S ratio were linear because belowground competition promoted the R/S ratio, and the strength of this effect reduced along the degradation gradient. These results indicate that plant competition might be a critical factor to maintain the high R/S ratio in degraded alpine meadows.
Expanding the TDP-43 Proteinopathy Pathway From Neurons to Muscle: Physiological and Pathophysiological Functions

TAR DNA-binding protein 43, mostly referred to as TDP-43 (encoded by the TARDBP gene) is strongly linked to the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). From the identification of TDP-43 positive aggregates in the brains and spinal cords of ALS/FTD patients, to a genetic link between TARBDP mutations and the development of TDP-43 pathology in ALS, there is strong evidence indicating that TDP-43 plays a pivotal role in the process of neuronal degeneration. What this role is, however, remains to be determined with evidence ranging from gain of toxic properties through the formation of cytotoxic aggregates, to an inability to perform its normal functions due to nuclear depletion. To add to an already complex subject, recent studies highlight a role for TDP-43 in muscle physiology and disease. We here review the biophysical, biochemical, cellular and tissue-specific properties of TDP-43 in the context of neurodegeneration and have a look at the nascent stream of evidence that positions TDP-43 in a myogenic context. By integrating the neurogenic and myogenic pathological roles of TDP-43 we provide a more comprehensive and encompassing view of the role and mechanisms associated with TDP-43 across the various cell types of the motor system, all the way from brain to limbs.
Interdecadal Modulation of the Pacific Decadal Oscillation on the Relationship Between Spring Arctic Oscillation and the Following Winter ENSO

Previous studies indicated that Arctic Oscillation (AO) in boreal spring is an important extratropical trigger for the outbreak of El Niño and Southern Oscillation (ENSO) events in the succedent winter. This study reveals that the Pacific Decadal Oscillation (PDO) has a strong modulation on the linkage between the spring AO and the following winter ENSO. Particularly, impact of the spring AO on the succedent winter ENSO is strong during positive PDO phase (+PDO). By contrast, the spring AO-winter ENSO connection is weak during negative PDO phase (−PDO). During +PDO, positive spring AO induces a marked anomalous cyclone over the subtropical North Pacific via wave-mean flow interaction. The subtropical cyclonic anomaly leads to sea surface temperature (SST) warming and enhanced atmospheric heating there, which could further propagate southward to the tropical central Pacific via wind-evaporation-SST feedback mechanism and, thus, impact the following winter El Niño via the tropical process. During −PDO, the spring AO-generated SST, the atmospheric circulation, and the heating anomalies over the North Pacific are much weaker. As such, spring AO has weak impacts on the winter ENSO. The spring climatological storm track is stronger during +PDO than −PDO years due to an increase in the mean meridional temperature gradient over the North Pacific. Stronger storm track intensity during +PDO leads to stronger synoptic-scale eddy feedback to the mean flow, which results in stronger AO-related SST and atmospheric anomalies over the North Pacific and, thus, the stronger impact of the spring AO on the following winter ENSO.
Advances in MALDI Mass Spectrometry Imaging Single Cell and Tissues

Compared with conventional optical microscopy techniques, mass spectrometry imaging (MSI) or imaging mass spectrometry (IMS) is a powerful, label-free analytical technique, which can sensitively and simultaneously detect, quantify, and map hundreds of biomolecules, such as peptides, proteins, lipid, and other organic compounds in cells and tissues. So far, although several soft ionization techniques, such as desorption electrospray ionization (DESI) and secondary ion mass spectrometry (SIMS) have been used for imaging biomolecules, matrix-assisted laser desorption/ionization (MALDI) is still the most widespread MSI scanning method. Here, we aim to provide a comprehensive review of MALDI-MSI with an emphasis on its advances of the instrumentation, methods, application, and future directions in single cell and biological tissues.
Insights Into the Coinfections of Human Immunodeficiency Virus-Hepatitis B Virus, Human Immunodeficiency Virus-Hepatitis C Virus, and Hepatitis B Virus-Hepatitis C Virus: Prevalence, Risk Factors, Pathogenesis, Diagnosis, and Treatment

Human immunodeficiency virus, hepatitis B virus, and hepatitis C virus are three blood-borne viruses that can cause major global health issues by increasing severe morbidity. There is a high risk of coinfection with these viruses in individuals because of their same transmission routes through blood using shared needles, syringes, other injection equipment, sexual transmission, or even vertical transmission. Coinfection can cause various liver-related illnesses, non-hepatic organ dysfunction, followed by death compared to any of these single infections. The treatment of coinfected patients is complicated due to the side effects of antiviral medication, resulting in drug resistance, hepatotoxicity, and a lack of required responses. On the other hand, coinfected individuals must be treated with multiple drugs simultaneously, such as for HIV either along with HBV or HCV and HBV and HCV. Therefore, diagnosing, treating, and controlling dual infections with HIV, HBV, or HCV is complicated and needs further investigation. This review focuses on the current prevalence, risk factors, and pathogenesis of dual infections with HIV, HBV, and HCV. We also briefly overviewed the diagnosis and treatment of coinfections of these three blood-borne viruses.
Numerical Simulation on Cement Hydration and Microstructure Development in Repair-Substrate Interface

One of the key parameters for the performance of concrete repairs is the quality of the interface between the repair material and concrete substrate, which is determined by cement hydration and microstructure development. The moisture exchange between the repair material and concrete substrate plays an important role in the cement hydration and porosity of cementitious repair materials. To better understand the influence of moisture exchange on the hydration of cementitious repair materials, this paper presents a numerical simulation of cement hydration and microstructure development of repair materials, considering moisture exchange. The simulation results reveal that the moisture exchange between the repair material and concrete substrate results in a water content change in two parts. Before the repair material setting, the water absorption of an unsaturated concrete substrate causes a reduction in the w/c ratio in the repair material, decreasing the hydration rate of the repair material. After the repair material setting, the water migrates from the concrete substrate to the repair material to provide additional water to accelerate the hydration of unhydrated cement in the repair material.
Effects of Nonpharmacological Interventions on Disruptive Vocalisation in Nursing Home Patients With Dementia—A Systematic Review

Background Vocally disruptive behaviour is a common and difficult to treat condition in older residents with dementia. The aim of this systematic review is to evaluate the efficacy of nonpharmacological interventions in its management in persons with dementia residing in a nursing home. Methodology A systematic search was conducted using Ovid MEDLINE, CINAHL, and Cochrane databases and reference lists from relevant publications on various nonpharmacological approaches to manage vocally disruptive behaviour in nursing home residents. The method of appraisal was through the National Institutes of Health scoring for the Quality Assessment of controlled intervention studies. Inclusion criteria included residents of nursing homes over the age of 65 with dementia and disruptive vocalisation. Only randomised controlled trials published in English were included. Results A total of 5,606 articles were identified, which cover 501 trials, of which 23 were selected. There were fourteen studies observed to have an impact of clinical and statistical significance with interventions including (i) a multidimensional approach with different nonpharmacological interventions, (ii) multisensory stimulation, (iii) staff education and training, (iv) personalised bathing, and (v) pain recognition and appropriate management. Seven studies demonstrated no observable effect whereas two showed worsening in vocally disruptive behaviour. Conclusions Many aspects of vocally disruptive behaviour management are poorly understood. Limited empirical evidence supports the use of several nonpharmacological interventions to reduce it. There is more robust evidence to support the use of a tailored approach to management over the universal approach.
Impacts of Soil and Antenna Characteristics on LoRa in Internet of Underground Things

Long-range (LoRa) is a suitable candidate for underground wireless communications due to its capability of communicating over a long range. However, due to the uniqueness of soil properties at a given geographical location, and the varying nature of soil moisture, it is challenging to apply a universal approach to characterize LoRa in wireless underground channels. In this paper, the performance of LoRa in underground channels is studied both theoretically and empirically. The range and bit error rate (BER) formulation of LoRa is derived as a function of soil parameters based on statistical underground channel models. To validate the model, path loss measurements are conducted under different moisture levels in two soil types (sandy and silty clay loam soil). In addition, as underground communication is also dependent on the return loss of buried antennas, the path loss measurements are performed using two different types of underground antennas. Results show that the underground channel models agree well with empirical LoRa measurements, resulting in R-squared values of 0.87-0.89. The results suggest that the performance of LoRa in underground channels can be predicted using the models developed in this paper.
Research and Application of Server Key Techniques in Informatization for Small and Medium Size Manufacturing Enterprises

This paper analyzes the issues in informatization of small and medium size manufacturing enterprise concerning enterprise's foundation information,enterprise's requirement and software model.Based on the view of software engineering,the authors also present some methods to solve the problem,such as taking union-foundation information instead of foundation information by designing a new software model with requirement driving.At last an example shows that this model is useful for small and medium size manufacturing enterprise in informatization.