Miracle-dz/UniFAR-FTUs huggingface dataset:
Engineering the β-Carotene Metabolic Pathway of Microalgae Dunaliella To Confirm Its Carotenoid Synthesis Pattern in Comparison To Bacteria and Plants

The synthesis mode of all trans-lycopene in bacteria and plants is clear, but there are still doubts in microalgae. Dunaliella is the organism with the highest β-carotene content, and plant-type and bacterial-type enzyme genes have been found in its carotenoid metabolism pathway. In this study, the entire plant-type enzyme gene was completely cloned into Escherichia coli, and high-efficiency expression was obtained, which proved that carotenoid synthesis of algae is similar to that of plants. ABSTRACT Dunaliella salina is the most salt-tolerant eukaryote and has the highest β-carotene content, but its carotenoid synthesis pathway is still unclear, especially the synthesis of lycopene, the upstream product of β-carotene. In this study, DsGGPS, DsPSY, DsPDS, DsZISO, DsZDS, DsCRTISO, and DsLYCB genes were cloned from D. salina and expressed in Escherichia coli. A series of carotenoid engineering E. coli strains from phytoene to β-carotene were obtained. ZISO was first identified from Chlorophyta, while CRTISO was first isolated from algae. It was found that DsZISO and DsCRTISO were essential for isomerization of carotenoids in photosynthetic organisms and could not be replaced by photoisomerization, unlike some plants. DsZDS was found to have weak beta cyclization abilities, and DsLYCB was able to catalyze 7,7′,9,9′-tetra-cis-lycopene to generate 7,7′,9,9′-tetra-cis-β-carotene, which had not been reported before. A new carotenoid 7,7′,9,9′-tetra-cis-β-carotene, the beta cyclization product of prolycopene, was discovered. Compared with the bacterial-derived carotenoid synthesis pathway, there is higher specificity and greater efficiency of the carotenoid synthesis pathway in algae. This research experimentally confirmed that the conversion of phytoene to lycopene in D. salina was similar to that of plants and different from bacteria and provided a new possibility for the metabolic engineering of β-carotene. IMPORTANCE The synthesis mode of all trans-lycopene in bacteria and plants is clear, but there are still doubts in microalgae. Dunaliella is the organism with the highest β-carotene content, and plant-type and bacterial-type enzyme genes have been found in its carotenoid metabolism pathway. In this study, the entire plant-type enzyme gene was completely cloned into Escherichia coli, and high-efficiency expression was obtained, which proved that carotenoid synthesis of algae is similar to that of plants. In bacteria, CRT can directly catalyze 4-step continuous dehydrogenation to produce all trans-lycopene. In plants, four enzymes (PDS, ZISO, ZDS, and CRTISO) are involved in this process. Although a carotenoid synthetase similar to that of bacteria has been found in algae, it does not play a major role. This research reveals the evolutionary relationship of carotenoid metabolism in bacteria, algae, and plants and is of methodologically innovative significance for molecular evolution research.
Are hyperuricemia and gout different diseases? Comment on the guidelines for the diagnosis and management of hyperuricemia and gout with the healthcare professional perspectives in China

In 2020, the Chinese Society of Endocrinology, Chinese Medical Association, published guidelines for the diagnosis and management of hyperuricemia (HUA) and gout in China (2019). The guideline was completed by following the international general GRADE classification method. The diagnosis, treatment and management of HUA and gout are covered through the description of 3 recommended general rules and 10 clinical questions.1 We are heartened that the guideline has made improvements for HUA and gout, which is largely consistent with global understanding. The guideline standardizes the original serum uric acid (UA, 420 μmol/L) used to assess HUA in men and women, although blood UA varies between genders. Significantly, this guideline recognizes subgout (asymptomatic) for the first time. In previous studies, the concept of “subclinical gout” has been derived from the timing of gout onset.2 The understanding of the turning point from HUA to gout has been ambiguous, especially with imaging techniques. Usually, diseasefree, asymptomatic, disease episodes and secondary episodes are the manifesting processes. Asymptomatic contains the stage of HUA and urate deposition.3 All the studies in the guidelines are focused on urate as a spotlight. A large body of evidence suggests that HUA is associated with gout; but we found that the genetic and mechanistic basis for the progression from HUA to inflammatory and clinical gout remains uncertain. However, the specific determinants of gout, independent of HUA, are the focus of much needed further research. Inflammation accompanies the full stage of HUA to gout. Inflammation is ubiquitous in metabolic diseases and even becomes a controller of disease progression.4 HUA already has chronic inflammation that progresses to acute with the deposition of urate crystals.5 We note that there is little focus in the guidelines on chronic inflammation in the HUA phase. This may be related to the inconsistency of existing understanding. Although HUA and gout can be distinguished as 2 diseases, the inflammatory status throughout correlates with them, and the possible treatment strategies are different. In addition, traditional Chinese medical (TCM) theory has a unique understanding of the “Bi Pattern” of gout. It considers that the basic cause of gout attacks from HUA to gout lies in damp pathogen. Western medicine focuses on localization while Chinese medicine focuses on a holistic view. Western medicine directly considers lesions of the target organ, including UA and inflammatory factors. This is fundamentally different from the TCM philosophy. In China, TCM is also an option for patients.
The POLARBEAR CMB polarization experiment

POLARBEAR is a Cosmic Microwave Background (CMB) polarization experiment that will search for evidence of inflationary gravitational waves and gravitational lensing in the polarization of the CMB. This proceeding presents an overview of the design of the instrument and the architecture of the focal plane, and shows some of the recent tests of detector performance and early data from the ongoing engineering run.
Effect of colour–shape associations on visual feature discrimination

Non-synesthetes exhibit a tendency to associate specific shapes with particular colours (i.e., circle-red, triangle-yellow, and square-blue). Here, we used two Go/No-go tasks to examine the congruency priming effect of colour–shape associations on recognition efficiency of colour and shape features. At the beginning of each trial, a target colour or shape word was introduced, followed by a coloured-shape visual stimulus. Participants were required to press a key to a target stimulus (“go” cues), while withholding their responses to a non-target stimulus (“no-go” cues). The targets were presented either visually (visual word, Experiment 1) or auditorily (spoken word, Experiment 2). Results showed a congruency effect of colour–shape associations on recognition efficiency for colour and shape features in both experiments. Response times were shorter in congruent than in incongruent conditions, that a target could be recognised faster when it was presented with the congruent visual features than with incongruent ones, irrespective of the presentation form (visual or auditory). These results suggest that colour–shape associations can be strong to influence visual recognition of colour and shape features.
An Overview of Polymeric Nanoparticles-Based Drug Delivery System in Cancer Treatment

Cancer is recognized as one of the world's deadliest diseases, with more than 10 million new cases each year. Over the past 2 decades, several studies have been performed on cancer to pursue solutions for effective treatment. One of the vital benefits of utilizing nanoparticles (NPs) in cancer treatment is their high adaptability for modification and amalgamation of different physicochemical properties to boost their anti-cancer activity. Various nanomaterials have been designed as nanocarriers attributing nontoxic and biocompatible drug delivery systems with improved bioactivity. The present review article briefly explained various types of nanocarriers, such as organic–inorganic-hybrid NPs, and their targeting mechanisms. Here a special focus is given to the synthesis, benefits, and applications of polymeric NPs (PNPs) involved in various anti-cancer therapeutics. It has also been discussed about the drug delivery approach by the functionalized/encapsulated PNPs (without/with targeting ability) that are being applied in the therapy and diagnostic (theranostics). Overall, this review can give a glimpse into every aspect of PNPs, from their synthesis to drug delivery application for cancer cells.
Molecular Effects of Silicon on Arabidopsis thaliana Seedlings under UV‐B Stress

Silicon‐plant interaction studies have shown that silicon reduces the harmful effects of stress in plants. Ultraviolet‐B (UV‐B) radiation, one of the abiotic stress affecting plants, poses a severe problem due to global warming. In this context, it is crucial to examine silicon's effects on UV‐B radiation stress at the molecular level. The experiments were carried out on 17 days old Arabidopsis seedlings that were treated with 800 μWatt cm−2 doses of UV‐B for 60 min and harvested on the 28th day. 1 mM orthosilicic acid was applied to the in vitro plant tissue culture for experimental groups. According to the results of the osmolyte accumulation analyses, silicon has been shown to play a role in the osmotic stress response. Gene expression levels of DGK2, CHS, FLC, RAD51, and UVR8 were measured via qPCR, and it has been shown that silicon interacts with these genes under UV‐B radiation stress. The result of genomic DNA methylation analysis demonstrated that silicon might affect DNA methylation levels by increasing the 5‐mC percentage compared with the control group. This study focused on the molecular effects of silicon application. It supports silicon–plant interaction research by demonstrating that silicon might affect UV‐B response at the molecular level.
Interaction of human HelQ with DNA polymerase delta halts DNA synthesis and stimulates DNA single-strand annealing

Abstract DNA strand breaks are repaired by DNA synthesis from an exposed DNA end paired with a homologous DNA template. DNA polymerase delta (Pol δ) catalyses DNA synthesis in multiple eukaryotic DNA break repair pathways but triggers genome instability unless its activity is restrained. We show that human HelQ halts DNA synthesis by isolated Pol δ and Pol δ-PCNA-RPA holoenzyme. Using novel HelQ mutant proteins we identify that inhibition of Pol δ is independent of DNA binding, and maps to a 70 amino acid intrinsically disordered region of HelQ. Pol δ and its POLD3 subunit robustly stimulated DNA single-strand annealing by HelQ, and POLD3 and HelQ interact physically via the intrinsically disordered HelQ region. This data, and inability of HelQ to inhibit DNA synthesis by the POLD1 catalytic subunit of Pol δ, reveal a mechanism for limiting DNA synthesis and promoting DNA strand annealing during human DNA break repair, which centres on POLD3.
In Vitro Effect of Photobiomodulation Therapy with 980 nm Diode Laser on Gene Expression of Key Regulators of Bone Remodeling by Human Periodontal Ligament Cells under Mild Orthodontic Forces

This study investigated the effect of photobiomodulation (PBM) with 980 nm diode laser as monotherapy and in combination with compressive and tensile orthodontic forces on expression of osteoprotegerin (OPG), receptor activator of nuclear factor‐κB ligand (RANKL), sclerostin (SOST) and periostin (POSTN), by human periodontal ligament cells. Isolated cells were cultured and subjected to either tensile (10% elongation) or compressive forces (25 g cm−2) for 24 and 48 h. Subsequently, the cells received PBM (100 mW power, 3 or 6 J cm−2 energy density) immediately after load cycle. RT‐PCR was applied to assess the genes expression. Data were analyzed by one‐way ANOVA, followed by post hoc Tukey test (P ≤ 0.05). We found that PBM in combination with orthodontic forces led to upregulation of bone resorption genes (RANKL and SOST) at the pressure side and their downregulation at the tension side. The expression of osteogenic genes (OPG and POSTN) increased at the tension side and decreased at the pressure side. PBM alone did not affect gene expression. In conclusion, these findings suggest that this PBM protocol may be effective in enhancement of the gene expression in favor of bone remodeling acceleration that should be confirmed in future animal and human studies.
SPRTN-dependent DPC degradation precedes repair of damaged DNA: a proof of concept revealed by the STAR assay

Abstract DNA-protein crosslinks (DPCs), formed by the covalent conjugation of proteins to DNA, are toxic lesions that interfere with DNA metabolic processing and transcription. The development of an accurate biochemical assay for DPC isolation is a priority for the mechanistic understanding of their repair. Here, we propose the STAR assay for the direct quantification of DPCs, sensitive to physiologically relevant treatment conditions. Implementing the STAR assay revealed the formation of small cross-linked peptides on DNA, created by the proteolytic degradation of DPCs by SPRTN. The initial proteolytic degradation of DPCs is required for the downstream activation of DNA repair, which is mediated through the phosphorylation of H2Ax. This leads to the accumulation of DNA repair factors on chromatin and the subsequent complete removal of the cross-linked peptides. These results confirmed that the repair of DPCs is a two-step process, starting with proteolytic resection by SPRTN, followed by the repair of the underlying damage to the DNA.
Ultrasound characterization of mammary gland development in heifer calves fed at two different levels until weaning

Ultrasound technologies allow for a non‐invasive assessment of mammary gland (MG) development, the differentiation between the tissue types of the MG, and the evaluation of changes in its composition. This study aimed to work out a detailed description of the different stages of MG development that are visually discernible by ultrasonography for providing a template to classify the different structures. With this basis, the qualitative categorization of the developmental stage, as well as further quantitative assessments via pixel densities in the structures of interest, should be facilitated. Ultrasonic images were acquired from all four quarters of 37 German Holstein heifer calves fed either at a high feeding level of milk replacer (MR; 14% solids) at 10 L/day (1.4 kg MR/day; HI, n = 18) or at a restrictive low level of 5.7 L/day (0.8 kg MR/day; RES, n = 19) until linear weaning from week 13 to 14 of life. Ultrasound MG scans were performed first in week 3 of life, fortnightly from week 8–16, and in week 20 of life, in standing position, of each quarter, using a B‐mode ultrasound device equipped with a linear probe (18 MHz). The developmental stages of the mammary gland parenchyma (PAR), visible in ultrasound images, obtained over 20 weeks of life, were categorized, described, and drawn by hand. On this basis, a template for classifying the visible categories of mammary PAR development and its surrounding tissue (SURR), and for measuring their pixel brightness was created thus providing an ultrasonographic atlas of the developing bovine MG, describing 11 categories. The ultrasound images were further classified by PAR structure, and pixel brightness was measured in PAR and SURR by using ImageJ Fiji. The difference in pixel brightness between PAR and SURR, the delta (Δ) pixel value was calculated. With increasing age, higher atlas categories of PAR developmental stages were shown. Pixel values, i.e. the brightness of PAR, its SURR, and Δ pixel value changed with age but were neither affected by the feeding group nor by a group × time interaction. With progressing PAR development, its pixel brightness increased from week 10 to 20 of life, i.e., the PAR became more hyperechoic since it spread and grew into its SURR. The atlas can serve as a template for the categorization and qualitative assessment of MG structures and for the quantitative assessment of PAR's development by measuring pixel brightness. With our study, we could show the structural development in PAR as well as in SURR in MG simultaneously in early life and confirm the spreading of PAR into its SURR by ultrasound scanning.
Comprehensive refractive manipulation of water waves using electrostriction

Significance Although water waves are the most common example of waves, controlling their propagation is often limited. The extensive capabilities of refraction-based devices such as lenses or waveguides which are ubiquitous in optics, are only partially fulfilled by a change in the liquid depth. Here, we propose a method to achieve such control based on electrostriction using electrodes placed above the liquid surface. This enables the creation of all the classical refraction-based devices used in optics with an electrical tunability and no contact with the liquid. It offers an unprecedented comprehensive control of water waves both in time and space.
Distal Femur Allograft Selection Using a Spectral Shape Descriptor

The automatic selection of bone allografts in a virtual bone databank is an active line of research. This work presents a new approach to solve this problem, based on a recently published image descriptor, called Volumetric Heat Kernel Signature. This descriptor is used to compare the size and shape of three dimensional thresholded computed tomography volumes. This approach is compared to a published method that uses the Iterative Closest Points algorithm to register a segmented search template to different candidates present in the databank. Statistical testing of the agreement between the two methods show that both approaches render similar results in the relevant clinical context. The proposed method avoids incorrect registrations due to local minima and does not require lengthly manual image segmentation and positioning before its use. The new method is conceptually simple and its mathematical basis is sound.
Voice Assistants’ Responses to Questions About the COVID-19 Vaccine: National Cross-sectional Study

Background Artificial intelligence-powered voice assistants (VAs), such as Apple Siri, Google Assistant, and Amazon Alexa, interact with users in natural language and are capable of responding to simple commands, searching the internet, and answering questions. Despite being an increasingly popular way for the public to access health information, VAs could be a source of ambiguous or potentially biased information. Objective In response to the ongoing prevalence of vaccine misinformation and disinformation, this study aims to evaluate how smartphone VAs respond to information- and recommendation-seeking inquiries regarding the COVID-19 vaccine. Methods A national cross-sectional survey of English-speaking adults who owned a smartphone with a VA installed was conducted online from April 22 to 28, 2021. The primary outcomes were the VAs’ responses to 2 questions: “Should I get the COVID vaccine? ” and “Is the COVID vaccine safe? ” Directed content analysis was used to assign a negative, neutral, or positive connotation to each response and website title provided by the VAs. Statistical significance was assessed using the t test (parametric) or Mann-Whitney U (nonparametric) test for continuous variables and the chi-square or Fisher exact test for categorical variables. Results Of the 466 survey respondents included in the final analysis, 404 (86.7%) used Apple Siri, 53 (11.4%) used Google Assistant, and 9 (1.9%) used Amazon Alexa. In response to the question “Is the COVID vaccine safe? ” 419 (89.9%) users received a direct response, of which 408 (97.3%) had a positive connotation encouraging users to get vaccinated. Of the websites presented, only 5.3% (11/207) had a positive connotation and 94.7% (196/207) had a neutral connotation. In response to the question “Should I get the COVID vaccine? ” 93.1% (434/466) of users received a list of websites, of which 91.5% (1155/1262) had a neutral connotation. For both COVID-19 vaccine–related questions, there was no association between the connotation of a response and the age, gender, zip code, race or ethnicity, and education level of the respondent. Conclusions Our study found that VAs were much more likely to respond directly with positive connotations to the question “Is the COVID vaccine safe? ” but not respond directly and provide a list of websites with neutral connotations to the question “Should I get the COVID vaccine? ” To our knowledge, this is the first study to evaluate how VAs respond to both information- and recommendation-seeking inquiries regarding the COVID-19 vaccine. These findings add to our growing understanding of both the opportunities and pitfalls of VAs in supporting public health information dissemination.
Acceptability of COVID‐19 vaccination in Chinese children aged 3–7 years with bronchopulmonary dysplasia

To describe the status of coronavirus disease 2019 (COVID‐19) vaccination with inactivated vaccines BBIBP‐CorV and CoronaVac in Chinese children aged 3–7 years with bronchopulmonary dysplasia (BPD), and explore factors influencing vaccination and reasons for nonvaccination.
Variations in leaf anatomical characteristics drive the decrease of mesophyll conductance in poplar under elevated ozone

Decline in mesophyll conductance (gm) plays a key role in limiting photosynthesis in plants exposed to elevated ozone (O3). Leaf anatomical traits are known to influence gm, but the potential effects of O3‐induced changes in leaf anatomy on gm have not yet been clarified. Here, two poplar clones were exposed to elevated O3. The effects of O3 on the photosynthetic capacity and anatomical characteristics were assessed to investigate the leaf anatomical properties that potentially affect gm. We also conducted global meta‐analysis to explore the general response patterns of gm and leaf anatomy to O3 exposure. We found that the O3‐induced reduction in gm was critical in limiting leaf photosynthesis. Changes in liquid‐phase conductance rather than gas‐phase conductance drive the decline in gm under elevated O3, and this effect was associated with thicker cell walls and smaller chloroplast sizes. The effects of O3 on palisade and spongy mesophyll cell traits and their contributions to gm were highly genotype‐dependent. Our results suggest that, while anatomical adjustments under elevated O3 may contribute to defense against O3 stress, they also cause declines in gm and photosynthesis. These results provide the first evidence of anatomical constraints on gm under elevated O3.