Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine

The FLAIR study demonstrated noninferiority of monthly long-acting cabotegravir + rilpivirine versus daily oral dolutegravir/abacavir/lamivudine for maintaining virologic suppression. Three participants who received long-acting therapy had confirmed virologic failure (CVF) at Week 48, and all had HIV-1 that was originally classified as subtype A1 and contained the baseline integrase polymorphism L74I; updated classification algorithms reclassified all 3 as HIV-1 subtype A6. ABSTRACT The FLAIR study demonstrated noninferiority of monthly long-acting cabotegravir + rilpivirine versus daily oral dolutegravir/abacavir/lamivudine for maintaining virologic suppression. Three participants who received long-acting therapy had confirmed virologic failure (CVF) at Week 48, and all had HIV-1 that was originally classified as subtype A1 and contained the baseline integrase polymorphism L74I; updated classification algorithms reclassified all 3 as HIV-1 subtype A6. Retrospectively, the impact of L74I on in vitro sensitivity and durability of response to cabotegravir in HIV-1 subtype B and A6 backgrounds was studied. Site-directed L74I and mutations observed in participants with CVF were generated in HIV-1 subtype B and a consensus integrase derived from 3 subtype A6 CVF baseline sequences. Rilpivirine susceptibility was assessed in HIV-1 subtype B and A1 containing reverse transcriptase mutations observed in participants with CVF. HIV-1 subtype B L74I and L74I/G140R mutants and HIV-1 subtype A6 I74L and I74/G140R mutants remained susceptible to cabotegravir; L74I/Q148R double mutants exhibited reduced susceptibility in HIV-1 subtypes B and A6 (half maximal effective capacity fold change, 4.4 and 4.1, respectively). Reduced rilpivirine susceptibility was observed across HIV-1 subtypes B and A1 with resistance-associated mutations K101E or E138K (half maximal effective capacity fold change, 2.21 to 3.09). In cabotegravir breakthrough experiments, time to breakthrough was similar between L74 and I74 viruses across HIV-1 subtypes B and A6; Q148R was selected at low cabotegravir concentrations. Therefore, the L74I integrase polymorphism did not differentially impact in vitro sensitivity to cabotegravir across HIV-1 subtype B and A6 integrase genes (ClinicalTrials.gov identifier: NCT02938520).
Silencing of RIPK4 inhibits epithelial-mesenchymal transition by inactivating the Wnt/β-catenin signaling pathway in osteosarcoma

Subsequently to the publication of the above article, the authors have realized that the same western blotting data shown for the vimentin bands for the U2OS cell line in Fig. 3B on p. 1159 had inadvertently been re‑used for the β‑catenin bands for the U2OS cell line in Fig. 5A on p. 1161. The authors have re‑examined their original data, and have realized that Fig. 5 was assembled incorrectly. The corrected version of Fig. 5, showing the correct β‑catenin bands for the U2OS cell line, is shown opposite. Note that this error did not quantitatively affect either the results or the overall conclusions reported in this paper. The authors are grateful to the Editor of Molecular Medicine Reports for allowing them this opportunity to publish a Corrigendum, and they apologize to the readership for any inconvenience caused. [the original article was published in Molecular Medicine Reports 21: 1154‑1162, 2020; DOI: 10.3892/mmr.2020. 10939].
Influence of Micro and Nano Particles on Mechanical Behaviour of Slag Reinforced AA7075 Composites

Present studies are based on adding ferrochrome slag as reinforcement in AA 7075 alloy manufactured via the stir casting process. Two different slag particles are chosen; they are 36μm (Micro) and 68 nm (Nano). This was added to evaluate the size effects in the given alloy matrix. The composites were tested for unique microstructural properties and mechanical properties. The results Revealed uniform particle distribution within the matrix and good bonding between the matrix and the reinforcement. Better mechanical properties are obtained for both micro and nanocomposites than base alloy. This is further enhanced by ageing treatments. nanocomposites show superior mechanical properties than either alloy or micro composite. Interestingly, nanocomposite exhibits an increase in strength with good ductility; same is confirmed with fracture studies.
Progress in Foldcore Sandwich Manufacturing and Application

The sandwich structure with foldcore is a new type of structural material with light weight, high specific strength, high specific rigidity and multi-functional potential, which is connected with each other in core space, this kind of three dimensional structures can be formed by folding based on two dimensional materials. The main research achievements and characteristics of sandwich structure with foldcore in recent years are summarized and analyzed according to the lightweight and multi-functional requirements of aircraft structure in this paper. The configuration optimization scheme and fabrication process of the sandwich structure with foldcore are described. Moreover, the research status of multi-function of the sandwich structure with foldcore are summarized, including sound insulation, thermal protection, stealth performance of the structure, etc.
Third-Order Nonlinear Optical Properties of Ge-Ga-S Chalcogenide Glasses

We have prepared GexGa4S96-x glasses for x=22.5, 27, 30 and 33.3 and GexGa8S92-x for x=32, 36 and measured their linear and nonlinear optical properties. The glasses exhibit broad transmission at a wavelength range from 1 to 12 μm. The evolution of linear, nonlinear index and two-photon absorption as a function of the content of Ge, and the relationship of n2 and β with linear refractive index and optical bandgap are analyzed. While the evolution of n2 and β is closer to the prediction by Sheik-Bahae et.al for optical nonlinearity of semiconductors. Eg of Ge-Ga-S is found to vary from 2.33 to 2.99eV, and the largest nonlinear index is 1.16×10-14cm2/W at composition of Ge32Ga8S60 .
Recent developments in the synthesis and anti-cancer activity of acridine and xanthine-based molecules

Abstract Cancer is the uncontrolled growth and development of abnormal cells which is a major cause of death in both advanced and emerging countries. Although currently chemotherapy is most broadly used among an extensive range of anti-cancer therapies, it includes many demerits, such as highly toxic, side-effects, expensive and partial lack of targeting specificity. So the design and synthesis of new molecules that perform specifically on target proteins in tumor cells is a focus of contemporary research. So many researchers aim for new drugs that will be more efficient, more selective, and less toxic. Because of the interesting structures and significant biological profile, naturally occurring acridines and xanthines as well as their analogues have attracted considerable interest in researchers and technologists. Natural and synthetic acridine derivatives form a significant category of heterocycles having nitrogen that is of considerable interest for organic chemists and biological communities due to their attractive anti-cancer activity. Another important class of therapeutic agents with diverse biological properties including cytotoxic effects is xanthine derivatives which are collectively called xanthines (a group of alkaloids). Among many significant molecules based on the structure of the purine, there is a group of natural xanthines, involving theobromine, caffeine, and theophylline and analogues of xanthine display anti-cancer activity. Hence the present chapter wishes to concentrate the attention on the synthesis and anti-cancer activity of acridine and xanthine-based compounds brilliantly.
Prenatal murine skeletogenesis partially recovers from absent skeletal muscle as development progresses

Skeletal muscle contractions are critical for normal growth and morphogenesis of the skeleton, but it is unclear how the detrimental effects of absent muscle on the bones and joints change over time. Joint size, shape and cavitation, and rudiment length and mineralisation were assessed in multiple rudiments at two developmental stages (Theiler Stage (TS)24 and TS27) in the splotch-delayed “muscleless limb” mouse model and littermate controls. As development progressed, the effects of absent muscle on all parameters except for cavitation become less severe. All major joints in muscleless limbs were qualitatively and quantitatively abnormal in shape at TS24, while, by TS27, most muscleless joint shapes were normal, or nearly normal. In contrast, any joints which were fused at TS24 did not cavitate by TS27. Therefore, recovery in joint shape over development occurred despite absent cavitation. Mineralisation showed the most pronounced changes between TS24 and TS27 in the muscleless limbs. At TS24, all muscleless rudiments studied had less mineralisation than the controls, while at TS27, muscleless limb rudiments had either the same or significantly more mineralisation than controls of the same age. We conclude that the effects of absent muscle on prenatal murine skeletogenesis are most pronounced in early skeletal development and reduce in severity prior to birth. Understanding how mammalian bones and joints continue to develop in an environment without muscle contractions, but with mechanical stimulation due to the movement of the mother, provides important insights into conditions affecting human babies such as developmental dysplasia of the hip and arthrogryposis.
A wMel Wolbachia variant in Aedes aegypti from field‐collected Drosophila melanogaster with increased phenotypic stability under heat stress

Mosquito-borne diseases such as dengue, Zika and chikungunya remain a major cause of morbidity and mortality across tropical regions. Population replacement strategies involving the wMel strain of Wolbachia are being used widely to control mosquito-borne diseases transmitted by Aedes aegypti. However, these strategies may be influenced by environmental temperature because wMel is vulnerable to heat stress. wMel infections in their native host Drosophila melanogaster are genetically diverse, but few transinfections of wMel variants have been generated in Ae. aegypti mosquitoes. Here we successfully transferred a wMel variant (termed wMelM) originating from a field-collected D. melanogaster population from Victoria, Australia into Ae. aegypti. The new wMelM variant (clade I) is genetically distinct from the original wMel transinfection (clade III) generated over ten years ago, and there are no genomic differences between wMelM in its original and transinfected host. We compared wMelM with wMel in its effects on host fitness, temperature tolerance, Wolbachia density, vector competence, cytoplasmic incompatibility and maternal transmission under heat stress in a controlled background. wMelM showed a higher heat tolerance than wMel, with stronger cytoplasmic incompatibility and maternal transmission when eggs were exposed to heat stress, likely due to higher overall densities within the mosquito. Both wMel variants had minimal host fitness costs, complete cytoplasmic incompatibility and maternal transmission, and dengue virus blocking under standard laboratory conditions. Our results highlight phenotypic differences between closely related Wolbachia variants. wMelM shows potential as an alternative strain to wMel in dengue control programs in areas with strong seasonal temperature fluctuations.
The non-specific Lipid Transfer Protein (nsLTP) is involved at early and late stages of symbiosis between Alnus glutinosa and Frankia alni

Alnus glutinosa response to Frankia alni is driven by several sequential physiological modifications that include calcium spiking, root hair deformation, penetration, induction of primordium, formation and growth of nodule. Here, we have conducted a transcriptomic study to analyse plant responses to Frankia alni at early stages of symbiosis establishment. Forty-two genes were significantly activated by either with a Frankia culture supernatant or with living cells separated from the roots by a dialysis membrane permitted to identify plant genes which expression changes upon early contact with Frankia. Most of these genes encode biological processes, including oxidative stress and response to stimuli. The most upregulated gene is the non-specific lipid transfer protein (nsLTP) encoding gene with a fold change of 141. Physiological experiments showed that nsLTP increases Frankia nitrogen fixation at sub-lethal concentration. Immunohistochemistry experiments conducted at an early infection stage indicated that nsLTP protein is localized at the deformed root hair region after Frankia inoculation and later in nodules, precisely around bacterial vesicles. Taken together, these results suggest that nsLTP acts at early and late stages of symbiosis, probably by increasing nitrogen uptake by Frankia.
Genome-Wide Identification and Co-Expression Analysis of ARF and IAA Family Genes in Euscaphis konishii: Potential Regulators of Triterpenoids and Anthocyanin Biosynthesis

Euscaphis konishii is an evergreen plant that is widely planted as an industrial crop in Southern China. It produces red fruits with abundant secondary metabolites, giving E. konishii high medicinal and ornamental value. Auxin signaling mediated by members of the AUXIN RESPONSE FACTOR (ARF) and auxin/indole-3-acetic acid (Aux/IAA) protein families plays important roles during plant growth and development. Aux/IAA and ARF genes have been described in many plants but have not yet been described in E. konishii. In this study, we identified 34 EkIAA and 29 EkARF proteins encoded by the E. konishii genome through database searching using HMMER. We also performed a bioinformatic characterization of EkIAA and EkARF genes, including their phylogenetic relationships, gene structures, chromosomal distribution, and cis-element analysis, as well as conserved motifs in the proteins. Our results suggest that EkIAA and EkARF genes have been relatively conserved over evolutionary history. Furthermore, we conducted expression and co-expression analyses of EkIAA and EkARF genes in leaves, branches, and fruits, which identified a subset of seven EkARF genes as potential regulators of triterpenoids and anthocyanin biosynthesis. RT-qPCR, yeast one-hybrid, and transient expression analyses showed that EkARF5.1 can directly interact with auxin response elements and regulate downstream gene expression. Our results may pave the way to elucidating the function of EkIAA and EkARF gene families in E. konishii, laying a foundation for further research on high-yielding industrial products and E. konishii breeding.
Shedding Light on Autophagy During Human Tuberculosis. A Long Way to Go

Immunity against Mycobacterium tuberculosis (Mtb) is highly complex, and the outcome of the infection depends on the role of several immune mediators with particular temporal dynamics on the host microenvironment. Autophagy is a central homeostatic mechanism that plays a role on immunity against intracellular pathogens, including Mtb. Enhanced autophagy in macrophages mediates elimination of intracellular Mtb through lytic and antimicrobial properties only found in autolysosomes. Additionally, it has been demonstrated that standard anti-tuberculosis chemotherapy depends on host autophagy to coordinate successful antimicrobial responses to mycobacteria. Notably, autophagy constitutes an anti-inflammatory mechanism that protects against endomembrane damage triggered by several endogenous components or infectious agents and precludes excessive inflammation. It has also been reported that autophagy can be modulated by cytokines and other immunological signals. Most of the studies on autophagy as a defense mechanism against Mycobacterium have been performed using murine models or human cell lines. However, very limited information exists about the autophagic response in cells from tuberculosis patients. Herein, we review studies that face the autophagy process in tuberculosis patients as a component of the immune response of the human host against an intracellular microorganism such as Mtb. Interestingly, these findings might contribute to recognize new targets for the development of novel therapeutic tools to combat Mtb. Actually, either as a potential successful vaccine or a complementary immunotherapy, efforts are needed to further elucidate the role of autophagy during the immune response of the human host, which will allow to achieve protective and therapeutic benefits in human tuberculosis.
The Work Gratitude Scale: Development and Evaluation of a Multidimensional Measure

This study explores gratitude as a multidimensional and work-specific construct. Utilizing a sample of 625 employees from a variety of positions in a medium-sized school district in the United States, we developed and evaluated a new measure, namely the Work Gratitude Scale (WGS), which encompasses recognized conative (intentional), cognitive, affective, and social aspects of gratitude. A systematic, six-phased approach through structural equation modeling (SEM) was used to explore and confirm the factorial structure, internal consistency, measurement invariance, concurrent, convergent, and discriminant validity of the WGS. The results supported a 10-item measure with three dimensions: “grateful appraisals” (three items), “gratitude toward others” (four items), and “intentional attitude of gratitude” (three items). Thereafter, first-order, second-order, and bifactor confirmatory models were estimated and compared. Work gratitude was found to be best described by a second-order construct with three underlying first-order dimensions. Measurement invariance was supported in relation to gender. Concurrent validity was supported in relation to two existing dispositional gratitude scales, namely the Gratitude Questionnaire and the Gratitude, Resentment, and Appreciation Scale (GRAT). Convergent validity was supported in relation to the Core Self-Evaluations Scale (CSES) and the Psychological Capital Questionnaire. Discriminant validity was supported in relation to various demographic factors such as age, gender, occupation, and tenure. The findings support the WGS as a multidimensional measure that can be used in practice to measure overall work-related gratitude and to track the effectiveness of gratitude-related workplace interventions.
Genetic Diversity and Selection of Plasmodium vivax Apical Membrane Antigen-1 in China–Myanmar Border of Yunnan Province, China, 2009–2016

Plasmodium vivax apical membrane antigen-1 (PvAMA-1) is an important vaccine candidate for vivax malaria. However, antigenic variation within PvAMA-1 is a major obstacle to the design of a global protective malaria vaccine. In this study, we analyzed the genetic polymorphism and selection of the PvAMA-1 gene from 152 P. vivax isolates from imported cases to China, collected in the China–Myanmar border (CMB) area in Yunnan Province (YP) during 2009–2011 (n = 71) and 2014–2016 (n = 81), in comparison with PvAMA-1 gene information from Myanmar (n = 73), collected from public data. The overall nucleotide diversity of the PvAMA-1 gene from the 152 YP isolates was 0.007 with 76 haplotypes identified (Hd = 0.958). Results from the population structure suggested three groups among the YP and Myanmar isolates with optimized clusters value of K = 7. In addition, YP (2014–2016) isolates generally lacked some K components that were commonly found in YP (2009–2011) and Myanmar. Meanwhile, PvAMA-1 domain I is found to be the dominant target of positive diversifying selection and most mutation loci were found in this domain. The mutation frequencies of D107N/A, R112K/T, K120R, E145A, E277K, and R438H in PvAMA-1 were more than 70% in the YP isolates. In conclusion, high genetic diversity and positive selection were found in the PvAMA-1 gene from YP isolates, which are significant findings for the design and development of PvAMA-1-based malaria vaccine.
Recent Development of Optoelectronic Application Based on Metal Halide Perovskite Nanocrystals

In the past years, metal halide perovskite (MHP) single crystals have become promising candidates for optoelectronic devices since they possess better optical and charge transport properties than their polycrystalline counterparts. Despite these advantages, traditional bulk growth methods do not lend MHP single crystals to device integration as readily as their polycrystalline analogues. Perovskite nanocrystals (NCs), nanometer-scale perovskite single crystals capped with surfactant molecules and dispersed in non-polar solution, are widely investigated in solar cells and light-emitting diodes (LEDs), because of the direct bandgap, tunable bandgaps, long charge diffusion length, and high carrier mobility, as well as solution-processed film fabrication and convenient substrate integration. In this review, we summarize recent developments in the optoelectronic application of perovskite nanocrystal, including solar cells, LEDs, and lasers. We highlight strategies for optimizing the device performance. This review aims to guide the future design of perovskite nanocrystals for various optoelectronic applications.
The Impact of Cardiac Rehabilitation on Activities of Daily Life in Elderly Patients With Heart Failure

Background: In elderly chronic heart failure (HF) patients, activities of daily living (ADLs) require the use of a high proportion of patients’ peak aerobic capacity, heart rate, and ventilation. Objectives: To assess the effects of short-term comprehensive cardiac rehabilitation (CR) on the metabolic requirement of ADLs in elderly patients with chronic HF. Methods: The study population comprised 99 elderly chronic HF patients (mean age 72 ± 5 years, 80% male, 61% ejection fraction <40%, mean NT-proBNP 2,559 ± 4,511 pg/ml) participating in a short-term (mean days 19 ± 7) residential CR program. Before and after CR, participants, while wearing a portable ergospirometer, performed a standardized ADL battery: ADL1 (getting dressed), ADL2 (folding 8 towels), ADL3 (putting away 6 bottles), ADL4 (making a bed), ADL5 (sweeping the floor for 4 min), ADL6 (climbing 1 flight of stairs carrying a 1.5 Kg load), and ADL7 (a standard 6-min walking test). Results: After CR, task-related oxygen uptake did not change in any of the domestic ADLs. Notably, there was a significant decrease in the cumulative time required to perform ADLs (ADL 1–4 and ADL6; from 412 ± 147 to 388 ± 141 s, p = 0.001) and a reduction in maximal heart rate in ADL1 and 3 (p = 0.005 and p = 0.027, respectively). Changes occurred in the 6MWT with an increase in oxygen uptake (p = 0.005) and in the distance covered (p < 0.001) and a significant decrease in the Borg scale of dyspnea (p = 0.004). Conclusion: Elderly patients with chronic heart failure who are engaged in a short-term residential CR program improve the performance of routine ADLs.