The shortage of physicians in rural and underserved areas is an obstacle to the implementation of Universal Health Coverage (UHC). We carried out a systematic review to analyze the effectiveness of initiatives in medical education aimed to increase the supply of physicians in rural or underserved areas. We searched for studies published between 1999 and 2019 in six databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Interventional or observational controlled studies were defined as inclusion criteria. A total of 955 relevant unique records were selected for inclusion, which resulted in the identification of 17 articles for analysis. The admission of students from rural areas associated with a rural curriculum represented 52.95% of the interventions. Medical practice after graduation in rural or underserved areas was the most evaluated outcome, representing 12 publications (70.59%). Participants of these educational initiatives were more likely to work in rural or underserved areas or to choose family medicine, with significant differences between the groups in 82.35% of the studies. Educational strategies in undergraduate and medical residencies are effective. However, it is necessary to expand these interventions to ensure the supply of physicians in rural or urban underserved areas. Full article

As technological advancements increase exponentially, mobile phones become smarter with machine learning and artificial intelligence algorithms. These advancements have allowed mobile phone users to perform most of their daily routine tasks on mobile phones; tasks performed in daily routines are called repetitive tasks and are performed manually by the users themselves. However, machine learning and artificial intelligence have enabled those tasks to be performed automatically, known as task automation. The users can perform task automation, e.g., through creating automation rules or an intelligent agent, e.g., conversational agents, virtual personal assistants, etc. Several techniques to achieve task automation have been proposed, but this review shows that task automation by programming by demonstration has had massive developmental growth because of its user-centered approach. Apple Siri, Google Assistant, MS Cortana, and Amazon Alexa are the most known task automation agents. However, these agents are not widely adopted because of their usability issues. In this study, two research questions are evaluated through the available literature to expand the research on intelligent task automation agents: (1) What is the state-of-the-art in task automation agents? (2) What are the existing methods and techniques for developing usability heuristics, specifically for intelligent agents? Research shows groundbreaking developments have been made in mobile phone task automation recently. However, it must still be conducted per usability principles to achieve maximum usability and user satisfaction. The second research question further justifies developing a set of domain-specific usability heuristics for mobile task automation intelligent agents. Full article

Neuropsychological testing has intrinsic challenges, including the recruitment of patients and their participation in research projects. To create a method capable of collecting multiple datapoints (across domains and participants) while imposing low demands on the patients, we have developed PONT (Protocol for Online Neuropsychological Testing). Using this platform, we recruited neurotypical controls, individuals with Parkinson’s disease, and individuals with cerebellar ataxia and tested their cognitive status, motor symptoms, emotional well-being, social support, and personality traits. For each domain, we compared each group to previously published values from studies using more traditional methods. The results show that online testing using PONT is feasible, efficient, and produces results that are in line with results obtained from in-person testing. As such, we envision PONT as a promising bridge to more comprehensive, generalizable, and valid neuropsychological testing. Full article

Honey bees, like other livestock, may be affected by infectious, parasitic, and abiotic diseases that need proper sanitary monitoring and control. Currently, there are limited opportunities for undergraduate students to receive education in Honey Bee Veterinary Medicine (HBVM) as part of their regular degree program, despite the professional requirements for veterinarians to carry out the increasing tasks related to honey bee health and production. Additionally, postgraduate training and specialization in HBVM is also underdeveloped. This study was an observational survey that evaluated the educational opportunities available in HBVM for current and future veterinarians in Italy. The survey analyzed both undergraduate and postgraduate programs, including Undergraduate Degree Programs in Veterinary Medicine (UDPVM), “Scuole di Specializzazione”, Masters, and other postgraduate courses. The results indicate that the current training available for veterinarians in the field of apiculture, both before and after graduation, is also insufficient in Italy, as already reported in other EU- and extra-EU countries. Finally, a roadmap for veterinary training in HBVM is developed here describing objectives and teachings aimed at fulfilling the needs of the profession in the field of beekeeping, considering the existing rules and regulations governing public health and possible evolution of this legal framework in the future. Full article

During in-situ mining and leaching of ionic rare earth ore, a chemical replacement reaction occurs between the leaching agent and rare earth ore. The thickness of the shear layer on the surface of colloidal particles is an important physical parameter. Based on the Gouy–Chapman double-layer theory and Poisson–Boltzmann equation, the relational expression for the thickness of the shear layer in the electric double layer on the particle surface under the condition of 2:2 + 3:2 mixture electrolytes (MgSO₄ + RE₂(SO₄)₃) is derived. On this basis, an indoor column leaching experiment of MgSO₄ solution is conducted, and the surface Zeta potential of rare earth ore particles is measured using a Zetaprobe potential analyzer. The surface potential and the thickness of the shear layer in the leaching process with different concentrations solutions (2.5%, 3.0%, and 3.5%) are calculated. The effects of a MgSO₄ solution concentration and particle surface potential on the thickness of the shear layer in the electric double layer are analyzed. It provides a theoretical basis for the study of the internal seepage of the ore body under the condition of the coexistence of multiple ions in the leaching process. Full article

The potential to improve the effectiveness and efficiency of potential oestrogen-based oral contraceptives (fertility control) for possums was investigated by comparing the inhibitory potential of hepatic CYP3A and UGT2B catalytic activity using a selected compound library (CYP450 inhibitor-based compounds) in possums to that of three other species (mouse, avian, and human). The results showed higher CYP3A protein levels in possum liver microsomes compared to other test species (up to a 4-fold difference). Moreover, possum liver microsomes had significantly higher basal p-nitrophenol glucuronidation activity than other test species (up to an 8-fold difference). However, no CYP450 inhibitor-based compounds significantly decreased the catalytic activity of possum CYP3A and UGT2B below the estimated IC₅₀ and 2-fold IC₅₀ values and were therefore not considered to be potent inhibitors of these enzymes. However, compounds such as isosilybin (65%), ketoconazole (72%), and fluconazole (74%) showed reduced UGT2B glucuronidation activity in possums, mainly at 2-fold IC₅₀ values compared to the control (p < 0.05). Given the structural features of these compounds, these results could provide opportunities for future compound screening. More importantly, however, this study provided preliminary evidence that the basal activity and protein content of two major drug-metabolising enzymes differ in possums compared to other test species, suggesting that this could be further exploited to reach the ultimate goal: a potential target-specific fertility control for possums in New Zealand. Full article

Cromoglycate (SCG) is widely used for allergy processes, and inflammatory states acting as a mast cell membrane stabilizer that inhibits the histamine and mediator release. Currently, SCG topical extemporaneous compounding formulations are prepared in hospitals and community pharmacies, as no industrial fabricated medicines are available in Spain. The stability of these formulations is unknown. Additionally, there are no clear guidelines on which concentration and vehicle are more suitable to enhance permeation across the skin. In this work, the stability of commonly prescribed topical SCG formulations in clinical practice was evaluated. Different vehicles commonly employed by pharmacists daily for formulating topical SCG were investigated (Eucerinum, Acofar Creamgel, and Beeler’s base) at different concentrations, ranging from 0.2 to 2%. The stability of topical extemporaneous compounded SCG formulations can be extended for up to three months at room temperature (25 °C). Creamgel 2% formulations significantly improved the topical permeation of SCG across the skin, being 4.5-fold higher than formulations prepared with Beeler’s base. The reason attributed to this performance can be related to the lower droplet size formed upon dilution in aqueous media combined with a lower viscosity, which facilitates its application and extensibility on the skin. The higher the SCG concentration in Creamgel formulations, the higher the permeability across both synthetic membranes and pig skin (p-value < 0.05). These preliminary results can be used as a guide to prompt a rational prescription of topical SCG formulations. Full article

Components of civil buildings are frequently made of low-alloyed steel, which can suffer from corrosion damage. This damage reduces their bearing capacity and/or redistributes the load to neighboring regions with the potential risk of their collapse. For this reason, this study deals with the non-destructive monitoring of bodies made of these steels based on Barkhausen noise emission. The superimposing contribution of corrosion extent and exerted tensile load is investigated on samples of variable yield strength in the range from 235 to 1100 MPa. It is found that the presence of a corroded layer attenuates Barkhausen noise and makes the body harder from a magnetic point of view. The reduced effective thickness of the samples as a result of corrosion damage increases the true stress. Barkhausen noise grows along with the tensile stress in the direction of exerted stress at the expense of decreasing Barkhausen noise in the perpendicular direction. The evolution of Barkhausen noise versus tensile stress is mostly shifted to the lower values of Barkhausen noise, along with the increasing degree of corrosion damage. The evolution of Barkhausen noise versus tensile stress is also affected by the initial microstructure and the corresponding yield strength of the low-alloyed steel. Corrosion attack results in the growth of FWHM, which is compensated by the decreasing evolution along with the tensile stresses. The effective values drop down with the higher extent of corrosion damage. However, the response with respect to the tensile stress is asymmetric in RD and TD due to the realignment of DWs into RD. Finally, PP tends to increase with the corrosion attack as well as the tensile stress and this parameter only exhibits the systematic behavior in RD as well as TD. On the other hand, MBN-extracted parameters as well as their combination provide no exclusive values on which the pure contribution of corrosion and tensile stress can be distinguished. Full article

Prostate specific membrane antigen (PSMA) is an excellent target for imaging and treatment of prostate carcinoma (PCa). Unfortunately, not all PCa cells express PSMA. Therefore, alternative theranostic targets are required. The membrane protein prostate stem cell antigen (PSCA) is highly overexpressed in most primary prostate carcinoma (PCa) cells and in metastatic and hormone refractory tumor cells. Moreover, PSCA expression positively correlates with tumor progression. Therefore, it represents a potential alternative theranostic target suitable for imaging and/or radioimmunotherapy. In order to support this working hypothesis, we conjugated our previously described anti-PSCA monoclonal antibody (mAb) 7F5 with the bifunctional chelator CHX-A″-DTPA and subsequently radiolabeled it with the theranostic radionuclide ¹⁷⁷Lu. The resulting radiolabeled mAb ([¹⁷⁷Lu]Lu-CHX-A″-DTPA-7F5) was characterized both in vitro and in vivo. It showed a high radiochemical purity (>95%) and stability. The labelling did not affect its binding capability. Biodistribution studies showed a high specific tumor uptake compared to most non-targeted tissues in mice bearing PSCA-positive tumors. Accordingly, SPECT/CT images revealed a high tumor-to-background ratios from 16 h to 7 days after administration of [¹⁷⁷Lu]Lu-CHX-A″-DTPA-7F5. Consequently, [¹⁷⁷Lu]Lu-CHX-A″-DTPA-7F5 represents a promising candidate for imaging and in the future also for radioimmunotherapy. Full article

Given the increase in stroke-related social costs, studies on survival and functional prognosis after stroke are urgently needed. Therefore, we investigated the relationship between the frequency of rehabilitation treatments in the acute and subacute phases of stroke and the long-term mortality of stroke survivors with mild-to-moderate disabilities. We performed a retrospective cohort study using data from the Korean National Health Insurance Service database. Our final cohort included 733 patients with national disability registration grades 4–6. The number of special rehabilitation treatment claim codes was used as a proxy for the frequency of rehabilitation treatments. Furthermore, we categorized the rehabilitation frequencies within 24 months of stroke onset as 1–50, 51–200, 201–400, and >400. The dependent variable was all-cause mortality, and it was evaluated from 24 to 84 months after stroke onset. Severe disability was associated with a lower long-term mortality rate in the chronic phase (p < 0.001). In the Cox regression analysis, severe disability, older age, male sex, and chronic kidney disease were independent risk factors for long-term mortality in patients with stroke and mild-to-moderate disabilities. However, the frequency of acute/subacute rehabilitation treatments did not significantly improve long-term mortality. Our results suggest that the association between rehabilitation frequency and lower long-term mortality for patients with mild-to-moderate stroke was inconclusive. Therefore, further study is needed to determine a better-customized rehabilitation treatment system for these patients. Full article

SETD2 belongs to the family of histone methyltransferase proteins and has been associated with three nosologically distinct entities with different clinical and molecular features: Luscan–Lumish syndrome (LLS), intellectual developmental disorder, autosomal dominant 70 (MRD70), and Rabin–Pappas syndrome (RAPAS). LLS [MIM #616831] is an overgrowth disorder with multisystem involvement including intellectual disability, speech delay, autism spectrum disorder (ASD), macrocephaly, tall stature, and motor delay. RAPAS [MIM #6201551] is a recently reported multisystemic disorder characterized by severely impaired global and intellectual development, hypotonia, feeding difficulties with failure to thrive, microcephaly, and dysmorphic facial features. Other neurologic findings may include seizures, hearing loss, ophthalmologic defects, and brain imaging abnormalities. There is variable involvement of other organ systems, including skeletal, genitourinary, cardiac, and potentially endocrine. Three patients who carried the missense variant p.Arg1740Gln in SETD2 were reported with a moderately impaired intellectual disability, speech difficulties, and behavioral abnormalities. More variable findings included hypotonia and dysmorphic features. Due to the differences with the two previous phenotypes, this association was then named intellectual developmental disorder, autosomal dominant 70 [MIM 620157]. These three disorders seem to be allelic and are caused either by loss-of-function, gain-of-function, or missense variants in the SETD2 gene. Here we describe 18 new patients with variants in SETD2, most of them with the LLS phenotype, and reviewed 33 additional patients with variants in SETD2 that have been previously reported in the scientific literature. This article offers an expansion of the number of reported individuals with LLS and highlights the clinical features and the similarities and differences among the three phenotypes associated with SETD2. Full article

An axial compressor has high efficiency under design conditions, but its stable working range is narrow. Adjusting the rotational speed can effectively expand the stable working range. In this paper, a five-stage axial compressor for a specific compressed air energy storage (CAES) system is taken as the research object, and different rotational speed (DRS) characteristics are studied with NUMECA software. Firstly, the influence of DRS on overall aerodynamic performance is explored, and the working flow range of the compressor is increased from 11.5% to 54.0%. Secondly, the effect of DRS on inlet parameters of the first stage rotor is analyzed, and the reasonable distribution of inlet parameters is obtained. Thirdly, the changing law of the internal flow is investigated at DRS. The corner separation is gradually enhanced when the rotational speed increases, and the leakage flow velocity at the rotor tip gradually improves. Finally, the loss distribution of tip clearance is researched. The result shows that the loss distribution increases significantly in both circumferential and spanwise directions when the speed increases. This work aims to provide a reference for the stable and efficient operation of axial compressors in CAES systems under the wide working range. Full article

As a natural biomass material, bamboo is subject to variations in culm size as well as in physical and mechanical properties that substantially influence processing and product quality. The diameter, thickness, and hardness of bamboo culms are critical factors for the output and quality of flattened bamboo board (FBB). In this study, the effects of different hardness modulus (HM) grades on the physical and mechanical properties of FBB were examined. The results showed that the HM of Moso bamboo (Phyllostachys pubescens) followed a normal distribution. Nine grades of HM could be divided by an interval of 5 KN/mm². The physical and mechanical properties of FBB were positively correlated with the HM of bamboo culms. Compressive strength, tensile strength, and shear strength, as well as the bending properties of FBB, each increased with increasing HM. Furthermore, under the same conditions, the mechanical properties of FBB were superior to those of both bamboo strips and bamboo culms. The softening, flattening, and planing processes were beneficial in improving the performance of bamboo. The strong correlation between HM and the properties of FBB indicates that the HM grading of bamboo culms can be used in bamboo processing to produce high-quality FBB products with uniform performance. Full article

The enzymatic degradation of different chitin polymers into chitin oligosaccharides (COSs) is of great significance given their better solubility and various biological applications. Chitinase plays a pivotal role in the enzymatic preparation of COSs. Herein, a cold-adapted and efficient chitinase (ChiTg) from the marine Trichoderma gamsii R1 was purified and characterized. The optimal temperature of ChiTg was 40 °C, and the relative activity at 5 °C was above 40.1%. Meanwhile, ChiTg was active and stable from pH 4.0 to 7.0. As an endo-type chitinase, ChiTg exhibited the highest activity with colloidal chitin, then with ball-milled and powdery chitin. In addition, ChiTg showed high efficiency when hydrolyzing colloidal chitin at different temperatures, and the end products were mainly composed of COSs with one to three degrees of polymerization. Furthermore, the results of bioinformatics analysis revealed that ChiTg belongs to the GH18 family, and its acidic surface and the flexible structure of its catalytic site may contribute to its high activity in cold conditions. The results of this study provide a cold-active and efficient chitinase and ideas for its application regarding the preparation of COSs from colloidal chitin. Full article

The current state of the study of different liquid crystalline (LC) systems doped with carbon nanotubes (CNTs) is discussed. An attempt is endeavored to outline the state-of-the-art technology that has emerged after two past decades. Systematization and analysis are presented for the integration of single- and multi-walled carbon nanotubes in thermotropic (nematic, smectic, cholesteric, ferroelectric, etc.) and lyotropic LCs. Special attention is paid to the effects of alignment and supramolecular organization resulting from orientational coupling between CNTs and the LC matrix. The effects of the specific inter-molecular and inter-particle interactions and intriguing microstructural, electromagnetic, percolation, optical, and electro-optical properties are also discussed. Full article

Facial skin analysis has attracted considerable attention in the skin health domain. The results of facial skin analysis can be used to provide skin care and cosmetic recommendations in aesthetic dermatology. Because of the existence of several skin features, grouping similar features and processing them together can improve skin analysis. In this study, a deep-learning-based method of simultaneous segmentation of wrinkles and pores is proposed. Unlike color-based skin analysis, this method is based on the analysis of the morphological structures of the skin. Although multiclass segmentation is widely used in computer vision, this segmentation was first used in facial skin analysis. The architecture of the model is U-Net, which has an encoder–decoder structure. We added two types of attention schemes to the network to focus on important areas. Attention in deep learning refers to the process by which a neural network focuses on specific parts of its input to improve its performance. Second, a method to enhance the learning capability of positional information is added to the network based on the fact that the locations of wrinkles and pores are fixed. Finally, a novel ground truth generation scheme suitable for the resolution of each skin feature (wrinkle and pore) was proposed. The experimental results revealed that the proposed unified method achieved excellent localization of wrinkles and pores and outperformed both conventional image-processing-based approaches and one of the recent successful deep-learning-based approaches. The proposed method should be expanded to applications such as age estimation and the prediction of potential diseases. Full article

In order to reduce our dependence on nonrenewable plastics and solve the problem of non-biodegradable plastic waste, there has been much attention paid to the development of biodegradable plastics from natural resources. Starch-based materials have been widely studied and developed for commercial production, primarily from corn and tapioca. However, the use of these starches could generate food security problems. Therefore, the use of alternative starch sources, such as agricultural waste, would be of great interest. In this work, we investigated the properties of films prepared from pineapple stem starch, which has a high amylose content. Pineapple stem starch (PSS) films and glycerol-plasticized PSS films were prepared and characterized using X-ray diffraction and water contact angle measurements. All films exhibited some degree of crystallinity, making them water-resistant. The effect of glycerol content on mechanical properties and gas (oxygen, carbon dioxide and water vapor) transmission rates was also studied. The tensile modulus and tensile strength of the films decreased with increasing glycerol content, while gas transmission rates increased. Preliminary studies showed that coatings made from PSS films could slow down the ripening process of bananas and extend their shelf life. Full article

This paper presents results coming from a non-linear model predictive controller used to generate optimized trajectories specifically for an omnidirectional robot equipped with a spraying unit to mark on the floor the perimeter of dangerous areas or to move large palletized goods inside warehouses. Results on different trajectories and with moving obstacles are provided along with considerations on the controller performance. Full article

Heart failure (HF) and cancer have similar risk factors. HMG-CoA reductase inhibitors, also known as statins, are chemoprotective agents against carcinogenesis. We aimed to evaluate the chemoprotective effects of statins against liver cancer in patients with HF. This cohort study enrolled patients with HF aged ≥20 years between 1 January 2001 and 31 December 2012 from the National Health Insurance Research Database in Taiwan. Each patient was followed to assess liver cancer risk. A total of 25,853 patients with HF were followed for a 12-year period; 7364 patients used statins and 18,489 did not. The liver cancer risk decreased in statin users versus non-users (adjusted hazard ratio (aHR) = 0.26, 95% confidence interval (CI): 0.20–0.33) in the entire cohort in the multivariate regression analysis. In addition, both lipophilic and hydrophilic statins reduced the liver cancer risk in patients with HF (aHR 0.34, 95% CI: 0.26–0.44 and aHR 0.42, 95% CI: 0.28–0.54, respectively). In the sensitivity analysis, statin users in all dose-stratified subgroups had a reduced liver cancer risk regardless of age, sex, comorbidity, or other concomitant drug use. In conclusion, statins may decrease liver cancer risk in patients with HF. Full article

Since the mid-2000s, livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) has been identified among pigs worldwide, CC398 being the most relevant LA-MRSA clone. In the present work, nasal swabs were taken from healthy pigs of different age categories (25 to 154 days) from 2019 to 2021 in four intensive farms located in three provinces of Argentina. The aim of the present study was to characterize the first LA-MRSA isolates that colonized healthy fattening pigs in Argentina in terms of their resistance phenotype and genotype and to know the circulating clones in the country. Antimicrobial susceptibility, presence of the mecA gene and PCR screening of CC398 were evaluated in all the isolates. They were resistant to cefoxitin, penicillin, tetracycline, chloramphenicol and ciprofloxacin but susceptible to nitrofurantoin, rifampicin, vancomycin and linezolid. Furthermore, 79% were resistant to clindamycin and lincomycin, 68% to erythromycin, 58% to gentamicin and 37% to trimethoprim/sulfamethoxazole. All the isolates were multidrug resistant. The clonal relation was assessed by SmaI-PFGE (pulsed-field gel electrophoresis) and a representative isolate of each PFGE type was whole genome sequenced by Illumina. MLST (multilocus sequence typing), resistance and virulence genes and SCCmec typing were performed on sequenced isolates. The isolates were differentiated in three clonal types by PFGE, and they belonged to sequence-type ST398 (58%) and ST9, CC1 (42%) by MLST. SCCmec typeV and several resistance genes detected showed complete correlation with resistance phenotypes. The present study revealed that LA-MRSA colonizing healthy pigs in Argentina belongs to CC398 and CC1, two MRSA lineages frequently associated to pigs in other countries. Full article

High-throughput sequencing (HTS), more specifically RNA sequencing of plant tissues, has become an indispensable tool for plant virologists to detect and identify plant viruses. During the data analysis step, plant virologists typically compare the obtained sequences to reference virus databases. In this way, they are neglecting sequences without homologies to viruses, which usually represent the majority of sequencing reads. We hypothesized that traces of other pathogens might be detected in this unused sequence data. In the present study, our goal was to investigate whether total RNA-seq data, as generated for plant virus detection, is also suitable for the detection of other plant pathogens and pests. As proof of concept, we first analyzed RNA-seq datasets of plant materials with confirmed infections by cellular pathogens in order to check whether these non-viral pathogens could be easily detected in the data. Next, we set up a community effort to re-analyze existing Illumina RNA-seq datasets used for virus detection to check for the potential presence of non-viral pathogens or pests. In total, 101 datasets from 15 participants derived from 51 different plant species were re-analyzed, of which 37 were selected for subsequent in-depth analyses. In 29 of the 37 selected samples (78%), we found convincing traces of non-viral plant pathogens or pests. The organisms most frequently detected in this way were fungi (15/37 datasets), followed by insects (13/37) and mites (9/37). The presence of some of the detected pathogens was confirmed by independent (q)PCRs analyses. After communicating the results, 6 out of the 15 participants indicated that they were unaware of the possible presence of these pathogens in their sample(s). All participants indicated that they would broaden the scope of their bioinformatic analyses in future studies and thus check for the presence of non-viral pathogens. In conclusion, we show that it is possible to detect non-viral pathogens or pests from total RNA-seq datasets, in this case primarily fungi, insects, and mites. With this study, we hope to raise awareness among plant virologists that their data might be useful for fellow plant pathologists in other disciplines (mycology, entomology, bacteriology) as well. Full article

RNA-binding proteins (RBPs) can regulate multiple pathways by binding to RNAs, playing a variety of functions, such as localization, stability, and immunity. In recent years, with the development of technology, researchers have discovered that RBPs play a key role in the N6-methyladenosine (m6A) modification process. M6A methylation is the most abundant form of RNA modification in eukaryotes, which is defined as methylation on the sixth N atom of adenine in RNA. Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) is one of the components of m6A binding proteins, which plays an important role in decoding m6A marks and performing various biological functions. IGF2BP3 is abnormally expressed in many human cancers, often associated with poor prognosis. Here, we summarize the physiological role of IGF2BP3 in organisms and describe its role and mechanism in tumors. These data suggest that IGF2BP3 may be a valuable therapeutic target and prognostic marker in the future. Full article

Selecting suitable promoters to drive gene overexpression can provide significant insight into the development of engineered bacteria. In this study, we analyzed the transcriptome data of Burkholderia pyrrocinia JK-SH007 and identified 54 highly expressed genes. The promoter sequences were located using genome-wide data and scored using the prokaryotic promoter prediction software BPROM to further screen out 18 promoter sequences. We also developed a promoter trap system based on two reporter proteins adapted for promoter optimization in B. pyrrocinia JK-SH007: firefly luciferase encoded by the luciferase gene set (Luc) and trimethoprim (TP)-resistant dihydrofolate reductase (TP^r). Ultimately, eight constitutive promoters were successfully inserted into the probe vector and transformed into B. pyrrocinia JK-SH007. The transformants were successfully grown on Tp antibiotic plates, and firefly luciferase expression was determined by measuring the relative light unit (RLU). Five of the promoters (P4, P9, P10, P14, and P19) showed 1.01–2.51-fold higher activity than the control promoter λ phage transcriptional promoter (PRPL). The promoter activity was further validated via qPCR analysis, indicating that promoters P14 and P19 showed stable high transcription levels at all time points. Then, GFP and RFP proteins were overexpressed in JK-SH007. In addition, promoters P14 and P19 were successfully used to drive gene expression in Burkholderia multivorans WS-FJ9 and Escherichia coli S17-1. The two constitutive promoters can be used not only in B. pyrrocinia JK-SH007 itself to gene overexpression but also to expand the scope of application. Full article

In this work, we report the synthesis of novel triple hydrophilic statistical terpolymers consisting of three different methacrylate monomers with varying degrees of responsivity to solution conditions. Terpolymers of the type poly(di(ethylene glycol) methyl ether methacrylate-co-2-(dimethylamino)ethylmethacrylate-co-oligoethylene glycol methyl ether methacrylate), P(DEGMA-co-DMAEMA-co-OEGMA), and of different compositions, were prepared by using the RAFT methodology. Their molecular characterization was carried out using size exclusion chromatography (SEC) and spectroscopic techniques, including ¹H-NMR and ATR-FTIR. Studies in dilute aqueous media by dynamic and electrophoretic light scattering (DLS and ELS) show their potential responsiveness regarding changes in temperature, pH, and kosmotropic salt concentration. Finally, the change in hydrophilic/hydrophobic balance of the formed terpolymer nanoparticles during heating and cooling was studied using fluorescence spectroscopy (FS) in conjunction with pyrene giving additional information on the responsiveness and internal structure of the self-assembled nanoaggregates. Full article

The outbreak of the COVID-19 pandemic has spread throughout the world, affecting almost all nations and territories. The current double-blind, randomized, placebo-controlled, phase II clinical trial sought to evaluate the clinical efficacy and safety of mebendazole as an adjuvant therapy for outpatients with COVID-19. The patients were recruited and divided into two groups: a Mebendazole-treated group and placebo group. The mebendazole and placebo groups were matched for age, sex, and complete blood count (CBC) with differential and liver and kidney function tests at baseline. On the third day, the C-reactive protein (CRP) levels were lower (2.03 ± 1.45 vs. 5.45 ± 3.95, p < 0.001) and the cycle threshold (CT) levels were higher (27.21 ± 3.81 vs. 24.40 ± 3.09, p = 0.046) significantly in the mebendazole group than in the placebo group on the third day. Furthermore, CRP decreased and CT dramatically increased on day three compared to the baseline day in the mebendazole group (p < 0.001 and p = 0.008, respectively). There was a significant inverse correlation between lymphocytes and CT levels in the mebendazole group (r = −0.491, p = 0.039) but not in the placebo group (r = 0.051, p = 0.888). Mebendazole therapy increased innate immunity and returned inflammation to normal levels in COVID-19 outpatients faster than it did in the placebo group in this clinical trial. Our findings add to the growing body of research on the clinical and microbiological benefits of repurposing antiparasitic therapy, specifically mebendazole, for SARS-CoV-2 infection and other viral infections. Full article

[3 + 2] Cycloaddition reactions of heteroaromatic N-ylides with electron-deficient olefins have been developed. The heteroaromatic N-ylides, in situ generated from N-phenacylbenzothiazolium bromides, can smoothly react with maleimides under very mild conditions, affording fused polycyclic octahydropyrrolo[3,4-c]pyrroles in good-to-excellent isolated yields. This reaction concept could also be extended to 3-trifluoroethylidene oxindoles and benzylidenemalononitriles as electron-deficient olefins for accessing highly functionalized polyheterocyclic compounds. A gram-scale experiment was also carried out to verify the practicability of the methodology. Full article