Miracle-dz/UniFAR-FTUs huggingface dataset:
The Inhibitory Properties of a Novel, Selective LMTK3 Kinase Inhibitor

Recently, the oncogenic role of lemur tyrosine kinase 3 (LMTK3) has been well established in different tumor types, highlighting it as a viable therapeutic target. In the present study, using in vitro and cell-based assays coupled with biophysical analyses, we identify a highly selective small molecule LMTK3 inhibitor, namely C36. Biochemical/biophysical and cellular studies revealed that C36 displays a high in vitro selectivity profile and provides notable therapeutic effect when tested in the National Cancer Institute (NCI)-60 cancer cell line panel. We also report the binding affinity between LMTK3 and C36 as demonstrated via microscale thermophoresis (MST). In addition, C36 exhibits a mixed-type inhibition against LMTK3, consistent with the inhibitor overlapping with both the adenosine 5′-triphosphate (ATP)- and substrate-binding sites. Treatment of different breast cancer cell lines with C36 led to decreased proliferation and increased apoptosis, further reinforcing the prospective value of LMTK3 inhibitors for cancer therapy.
Rosmarinic and Glycyrrhetinic Acid-Modified Layered Double Hydroxides as Functional Additives for Poly(Lactic Acid)/Poly(Butylene Succinate) Blends

Immobilizing natural antioxidant and biologically active molecules in layered double hydroxides (LDHs) is an excellent method to retain and release these substances in a controlled manner, as well as protect them from thermal and photochemical degradation. Herein, we describe the preparation of host–guest systems based on LDHs and rosmarinic and glycyrrhetinic acids, two molecules obtained from the extraction of herbs and licorice root, respectively, with antioxidant, antimicrobial, and anti-inflammatory properties. Intercalation between the lamellae of the mono-deprotonated anions of rosmarinic and glycyrrhetinic acid (RA and GA), alone or in the presence of an alkyl surfactant, allows for readily dispersible systems in biobased polymer matrices such as poly(lactic acid) (PLA), poly(butylene succinate) (PBS), and a 60/40 wt. /wt. PLA/PBS blend. The composites based on the PLA/PBS blend showed better interphase compatibility than the neat blend, correlated with increased adhesion at the interface and a decreased dispersed phase size. In addition, we proved that the active species migrate slowly from thin films of the composite materials in a hydroalcoholic solvent, confirming the optimization of the release process. Finally, both host–guest systems and polymeric composites showed antioxidant capacity and, in the case of the PLA composite containing LDH-RA, excellent inhibitory capacity against E. coli and S. aureus.
Electrochemical Biosensor for the Determination of Specific Antibodies against SARS-CoV-2 Spike Protein

In this article, we report the development of an electrochemical biosensor for the determination of the SARS-CoV-2 spike protein (rS). A gold disc electrode was electrochemically modified to form the nanocrystalline gold structure on the surface. Then, it was further altered by a self-assembling monolayer based on a mixture of two alkane thiols: 11-mercaptoundecanoic acid (11-MUA) and 6-mercapto-1-hexanol (6-MCOH) (SAMmix). After activating carboxyl groups using a N-(3-dimethylaminopropyl)-N’-ethyl-carbodiimide hydrochloride and N-hydroxysuccinimide mixture, the rS protein was covalently immobilized on the top of the SAMmix. This electrode was used to design an electrochemical sensor suitable for determining antibodies against the SARS-CoV-2 rS protein (anti-rS). We assessed the association between the immobilized rS protein and the anti-rS antibody present in the blood serum of a SARS-CoV-2 infected person using three electrochemical methods: cyclic voltammetry, differential pulse voltammetry, and potential pulsed amperometry. The results demonstrated that differential pulse voltammetry and potential pulsed amperometry measurements displayed similar sensitivity. In contrast, the measurements performed by cyclic voltammetry suggest that this method is the most sensitive out of the three methods applied in this research.
Correlation between the Serum Concentration of Vitamin A and Disease Severity in Patients Carrying p.G90D in RHO, the Most Frequent Gene Associated with Dominant Retinitis Pigmentosa: Implications for Therapy with Vitamin A

The pathogenic variant p.G90D in RHO is believed to be responsible for a spectrum of phenotypes, including congenital stationary blindness (for the purpose of this study termed night blindness without degeneration; NBWD), Sector RP, Pericentral RP, and Classic RP. We present a correlation between the serum concentration of vitamin A and disease severity in patients with this variant. This prospective study involved 30 patients from 7 families (17 male; median age 46 years, range 8–73). Full ophthalmological examination including visual acuity, Goldmann perimetry, slit-lamp exam, optical coherence tomography, fundus autofluorescence, and electrophysiology was performed to determine the presenting phenotype. The serum concentration of vitamin A was determined from a fasting blood sample taken on the day of the exam, where it was found that 23.3% (7/30) of patients had NBWD, 13.3% (4/30) had Sector RP, 3.3% (1/30) had Pericentral RP, and 60% (18/30) had Classic RP. Multiple logistic regression revealed a significantly higher probability of having a milder phenotype (NBWD or Sector RP) in association with younger age (p < 0.05) and a higher concentration of vitamin A (p < 0.05). We hypothesize that vitamin A in its 11-cis-retinal form plays a role in stabilizing the constitutively active p.G90D rhodopsin and its supplementation could be a potential treatment strategy for p.G90D RHO patients.
Gold Nanoparticles as a Biosensor for Cancer Biomarker Determination

Molecular biology applications based on gold nanotechnology have revolutionary impacts, especially in diagnosing and treating molecular and cellular levels. The combination of plasmonic resonance, biochemistry, and optoelectronic engineering has increased the detection of molecules and the possibility of atoms. These advantages have brought medical research to the cellular level for application potential. Many research groups are working towards this. The superior analytical properties of gold nanoparticles can not only be used as an effective drug screening instrument for gene sequencing in new drug development but also as an essential tool for detecting physiological functions, such as blood glucose, antigen-antibody analysis, etc. The review introduces the principles of biomedical sensing systems, the principles of nanomaterial analysis applied to biomedicine at home and abroad, and the chemical surface modification of various gold nanoparticles.
Low Intraoperative Cerebral Oxygen Saturation Is Associated with Acute Kidney Injury after Off-Pump Coronary Artery Bypass

By monitoring the brain as the index organ of global oxygen supply–demand balance including major organs, regional cerebral oxygen saturation (rScO2) may indicate adequacy of renal perfusion. The aim of this study was to investigate the relationship between perioperative rScO2 and acute kidney injury (AKI) after off-pump coronary artery bypass (OPCAB). AKI was diagnosed according to the Kidney Disease: Improving Global Outcomes criteria. Collected rScO2 variables were baseline, mean, and lowest value during surgery, maximal percentage decrease from baseline, and areas under the threshold below an absolute value of 50% (AUT50) and of 80% of baseline (AUT80%base). Among 580 patients, AKI developed in 143 (24.7%) patients. Patients with AKI had lower baseline, mean, and lowest rScO2 and higher AUT50 and AUT80%base than those without AKI despite routine efforts to restore the rScO2 values within 20% of the baseline. Among the rScO2 variables, the area under the receiver operating characteristic curve of mean rScO2 was the highest (0.636), which was used for the multivariable logistic regression. Multivariable logistic regression revealed mean rScO2 as an independent predictor of AKI (odds ratio, 0.964; 95% confidence interval, 0.937–0.990; p = 0.008), along with chronic kidney disease and emergency surgery. Low intraoperative mean rScO2 was independently associated with AKI after OPCAB, which may serve as an early marker of renal injury.
Stable plasma configurations in a cylindrical magnetron discharge

Transition between different plasma configurations is studied in a system with negative biased cylindrical target in crossed E×B fields. It was found that the diffuse plasma torus formed around the cylindrical target in relatively small magnetic field (0.02T on target surface) changes the shape with magnetic field to form a thin disk with a width lower than 1cm when target voltage is less than −400V. The target current decreases sharply when the magnetic field reaches some critical value. When the target voltage exceeds 400V, the target current increases with the magnetic field and the plasma has always toroidal shape. The plasma behavior can be understood taking in account the interaction of the drift currents and the magnetic field.
Pandemic impacts on cinema industry and over-the-top platforms in China

Over-the-top platforms are increasingly being accepted by the younger generation. This study examines the different modes of watching films that have emerged due to the proliferation of over-the-top platforms, smartphones, and 5G technologies during the pandemic period in China. Using survey data, we examine the perception and behavior of 592 respondents. The top five factors in increasing over-the-top platforms to watch movies include easy access, various genres, no time to visit a cinema, pandemic, and new films. Findings also show that users tend to use smartphones to access over-the-top platforms. Bilibili, Tencent Video, and iQIYI are China's most popular over-the-top platforms among viewers. Increasing cinema ticket prices, pandemics, lack of quality content, and film stories are significant challenges for the cinema industry in the near future. These results suggest that the film industry should maintain the quality of the movies, especially those released on the cinema screen. These findings also designate significant substitution between the over-the-top platform and cinema and recommend that competition authorities widen market definitions. The cinema environment and IMAX/3D appear to have little incentive to degrade over-the-top platforms, despite over-the-top's films contributing to declining box office revenue.
Optimization of the Alizarin Red S Assay by Enhancing Mineralization of Osteoblasts

The alizarin red S assay is considered the gold standard for quantification of osteoblast mineralization and is thus widely used among scientists. However, there are several restrictions to this method, e.g., moderate sensitivity makes it difficult to uncover slight but significant effects of potentially clinically relevant substances. Therefore, an adaptation of the staining method is appropriate and might be obtained by increasing the mineralization ability of osteoblasts. In this study, cell culture experiments with human (SaOs-2) and murine (MC3T3-E1) osteoblasts were performed under the addition of increasing concentrations of calcium chloride (1, 2.5, 5, and 10 mM) or calcitonin (1, 2.5, 5, and 10 nM). After three or four weeks, the mineralization matrix was stained with alizarin red S and the concentration was quantified photometrically. Only calcium chloride was able to significantly increase mineralization, and therefore enhanced the sensitivity of the alizarin red S staining in a dose-dependent manner in both osteoblastic cell lines as well as independent of the cell culture well surface area. This cost- and time-efficient optimization enables a more sensitive analysis of potentially clinically relevant substances in future bone research.
Glucose Homeostasis and Pancreatic Islet Size Are Regulated by the Transcription Factors Elk-1 and Egr-1 and the Protein Phosphatase Calcineurin

Pancreatic β-cells synthesize and secrete insulin. A key feature of diabetes mellitus is the loss of these cells. A decrease in the number of β-cells results in decreased biosynthesis of insulin. Increasing the number of β-cells should restore adequate insulin biosynthesis leading to adequate insulin secretion. Therefore, identifying proteins that regulate the number of β-cells is a high priority in diabetes research. In this review article, we summerize the results of three sophisticated transgenic mouse models showing that the transcription factors Elk-1 and Egr-1 and the Ca2+/calmodulin-regulated protein phosphatase calcineurin control the formation of sufficiently large pancreatic islets. Impairment of the biological activity of Egr-1 and Elk-1 in pancreatic β-cells leads to glucose intolerance and dysregulation of glucose homeostasis, the process that maintains glucose concentration in the blood within a narrow range. Transgenic mice expressing an activated calcineurin mutant also had smaller islets and showed hyperglycemia. Calcineurin induces dephosphorylation of Elk-1 which subsequently impairs Egr-1 biosynthesis and the biological functions of Elk-1 and Egr-1 to regulate islet size and glucose homeostasis.
Immunopathogenesis of Atopic Dermatitis: Focus on Interleukins as Disease Drivers and Therapeutic Targets for Novel Treatments

Atopic dermatitis is a chronic, recurrent inflammatory skin disorder manifesting by eczematous lesions and intense pruritus. Atopic dermatitis develops primarily as a result of an epidermal barrier defect and immunological imbalance. Advances in understanding these pathogenetic hallmarks, and particularly the complex role of interleukins as atopic dermatitis drivers, resulted in achieving significant therapeutic breakthroughs. Novel medications involve monoclonal antibodies specifically blocking the function of selected interleukins and small molecules such as Janus kinase inhibitors limiting downstream signaling to reduce the expression of a wider array of proinflammatory factors. Nevertheless, a subset of patients remains refractory to those treatments, highlighting the complexity of atopic dermatitis immunopathogenesis in different populations. In this review, we address the immunological heterogeneity of atopic dermatitis endotypes and phenotypes and present novel interleukin-oriented therapies for this disease.
Silencing DTX3L Inhibits the Progression of Cervical Carcinoma by Regulating PI3K/AKT/mTOR Signaling Pathway

Cervical carcinoma (CC) is the second most prevalent gynecologic cancer in females across the world. To obtain a better understanding of the mechanisms underlying the development of CC, high-resolution label-free mass spectrometry was performed on CC and adjacent normal tissues from eight patients. A total of 2631 proteins were identified, and 46 significant differently expressed proteins (DEPs) were found between CC and normal tissues (p < 0.01, fold change >10 or <0.1). Ingenuity pathway analysis revealed that the majority of the proteins were involved in the regulation of eIF4 and p70S6K signaling and mTOR signaling. Among 46 DEPs, Integrinβ6 (ITGB6), PPP1CB, TMPO, PTGES3 (P23) and DTX3L were significantly upregulated, while Desmin (DES) was significantly downregulated in CC tissues compared with the adjacent normal tissues. In in vivo and in vitro experiments, DTX3L knockdown suppressed CC cell proliferation, migration, invasion and xenograft tumorigenesis, and enhanced cell apoptosis. Combination of silencing DTX3L and cisplatin treatment induced higher apoptosis percentage compared to cisplatin treatment alone. Moreover, DTX3L silencing inhibited the PI3K/AKT/mTOR signal pathway. Thus, our results suggested DTX3L could regulate CC progression through the PI3K/AKT/mTOR signal pathway and is potentially a novel biomarker and therapeutic target for CC.
Environmental Regulation, Resource Misallocation, and Total Factor Productivity: An Empirical Analysis Based on 284 Cities at the Prefecture-Level and Above in China

We investigated the impact of environmental regulation on total factor productivity (TFP) based on a panel dataset of 284 cities at the prefecture-level and above in mainland China from 2006 to 2020 and examined whether environmental regulation had a resource reallocation effect and thus affected TFP. The results showed that there was an “inverted U-shaped” pattern in the impact of environmental regulation on TFP in China and a moderate strengthening of environmental regulation helped to increase TFP, which still held after endogeneity treatment and robustness tests. The “inverted U-shaped” relationship between environmental regulation and TFP in eastern, central, and western cities still held, while environmental regulation did not produce significant effects on TFP in the northeast. The effect of environmental regulation on TFP in large, medium, and small cities tested in groups by city size was consistent with the full sample findings, but the effects decreased in a gradient with city size. The analysis of the impact mechanism showed that environmental regulation had a suppressive effect on resource misallocation and could generate a positive resource reallocation effect and enhance city TFP. The labor reallocation effect of environmental regulation for TFP was stronger than the capital reallocation effect. The findings of our study are of policy reference value for optimizing resource allocation through environmental regulation and thus promoting high-quality city development in China.
Transportation Infrastructure, Population Mobility, and Public Health

This paper constructs an overlapping generations model, including health human capital, to investigate the impact of transportation investment on public health with population mobility. The theoretical analysis shows that there is an inverted U-shaped relationship between transportation infrastructure and population flow, which also exists between transportation and health. Health is affected by transportation from three aspects: positive output effect, negative substitution effect on public health investment, and an indirect effect through population flow. In the empirical part, considered with the infectious diseases, we found that the more intensive the traffic facilities, the greater the population flow, and therefore, the traffic facilities will have a negative impact on health. When population mortality is used to measure the level of public health, transportation improvement will significantly enhance public health with an inverted U-shaped relationship, which is consistent with the theoretical portion.
Phytoplankton diversity and chemotaxonomy in contrasting North Pacific ecosystems

Background Phytoplankton is the base of majority of ocean ecosystems. It is responsible for half of the global primary production, and different phytoplankton taxa have a unique role in global biogeochemical cycles. In addition, phytoplankton abundance and diversity are highly susceptible to climate induced changes, hence monitoring of phytoplankton and its diversity is important and necessary. Methods Water samples for phytoplankton and photosynthetic pigment analyses were collected in boreal winter 2017, along transect in the North Pacific Subtropical Gyre (NPSG) and the California Current System (CCS). Phytoplankton community was analyzed using light and scanning electron microscopy and photosynthetic pigments by high-performance liquid chromatography. To describe distinct ecosystems, monthly average satellite data of MODIS Aqua Sea Surface temperature and Chlorophyll a concentration, as well as Apparent Visible Wavelength were used. Results A total of 207 taxa have been determined, mostly comprised of coccolithophores (35.5%), diatoms (25.2%) and dinoflagellates (19.5%) while cryptophytes, phytoflagellates and silicoflagellates were included in the group “others” (19.8%). Phytoplankton spatial distribution was distinct, indicating variable planktonic dispersal rates and specific adaptation to ecosystems. Dinoflagellates, and nano-scale coccolithophores dominated NPSG, while micro-scale diatoms, and cryptophytes prevailed in CCS. A clear split between CCS and NPSG is evident in dendogram visualising LINKTREE constrained binary divisive clustering analysis done on phytoplankton counts and pigment concentrations. Of all pigments determined, alloxanthin, zeaxanthin, divinyl chlorophyll b and lutein have highest correlation to phytoplankton counts. Conclusion Combining chemotaxonomy and microscopy is an optimal method to determine phytoplankton diversity on a large-scale transect. Distinct communities between the two contrasting ecosystems of North Pacific reveal phytoplankton groups specific adaptations to trophic state, and support the hypothesis of shift from micro- to nano-scale taxa due to sea surface temperatures rising, favoring stratification and oligotrophic conditions.
Person-Centered Climate, Garden Greenery and Well-Being among Nursing Home Residents: A Cross-Sectional Study

Nursing home residents’ well-being is often proxy-rated in studies, and few studies have explored the association between resident-rated person-centered climate, garden greenery, and resident-rated well-being. A cross-sectional study was conducted. Questionnaire data from a convenient sample of 470 nursing home residents in a city in Southeast China in 2021 were analyzed using multiple linear regressions, with block-wise models. The instruments used were the Person-centered Climate Questionnaire-Patient version, the Nursing Home Greenery Index, and, for well-being, the EuroQol-Visual Analogue Scale, the Life Satisfaction Questionnaire, and the 9-item Patient Health Questionnaire (depression symptoms). In the unadjusted models, the person-centered climate was positively associated with general health (β 0.29, p < 0.001), person-centered climate and greenery with life satisfaction (β 0.39, and 0.18; both p < 0.001), and negatively with depression (β −0.28, and β −0.23, both p < 0.001). After adjusting for personal and nursing home characteristics, the associations between person-centered climate, greenery, and well-being remained statistically significant. The three models explained 36%, 35%, and 21% of the variance in general health, life satisfaction, and depression, respectively. This study provides knowledge on person-centered climate in long-term care and the access to greenery.
Personality and Family Risk Factors for Poor Mental Well-Being

There is evidence that differentiation of self (DoS) contributes to the regulation of emotions at a young age, resulting in reduced anxiety and improved mental well-being. However, there is little evidence of the relationships between these four dimensions (DoS, self-regulation, anxiety, and mental well-being), or of the potential mediating role of self-regulation and anxiety. Our primary goal was therefore to consider the links between DoS, self-regulation, anxiety, and mental well-being. It was hypothesized that DoS (emotional reactivity, I-position, emotional cutoff, fusion with others) will be positively associated with mental well-being through the mediation of self-regulation (promotion-focused, prevention-focused) and anxiety. The study included 460 participants with a mean age of 41.18 (SD = 14.97, range = 19–60). Of them, 224 (48.7%) were women. Participants filled out four questionnaires: the Differentiation of Self Inventory–Revised, General Regulatory Focus Measure, the anxiety scale from DASS–21, and the Warwick–Edinburgh Mental Well-being Scale. The findings showed that emotional cutoff positively predicted prevention and anxiety, but did not predict promotion. In addition, promotion positively predicted mental well-being. Finally, promotion mediated the relationship between I-position and mental well-being. The results indicate that well-differentiated individuals function optimally and enjoy good quality of life.