Pleionea litopenaei sp. nov., isolated from the gastric tract of juvenile Pacific white shrimp Litopenaeus vannamei.

A Gram-stain-negative, aerobic, rod-shaped and motile strain HL-JVS1T, was isolated from the gastric tract of a juvenile Pacific white shrimp. Molecular phylogenetic analysis based on 16S rRNA gene sequences of strain HL-JVS1T revealed its affiliation with the genus Pleionea, with close relatives including Pleionea mediterranea MOLA115T (97.5%) and Pleionea sediminis S1-5-21T (96.2%). The complete genome of strain HL-JVS1T consisted of a circular 4.4 Mb chromosome and two circular plasmids (6.6 and 35.0 kb) with a G + C content of 43.1%. The average nucleotide identity and digital DNA-DNA hybridization values between strain HL-JVS1T and the type strains of described Pleionea species were 69.7-70.4% and 18.3-18.6%, respectively. Strain HL-JVS1T grew at 10-40 °C (optimum, 30 °C) in the presence of 0.5 - 9.0% (w/v) sea salts (optimum, 2.0 - 2.5%), and at pH range of 5.5 - 10.0 (optimum, pH 6.5). The major fatty acids (> 10%) were summed feature 9 (iso-C17:1 ω9c and/or C16:0 10-methyl) (23.3%), iso-C16:0 (14.5%), iso-C11:0 3-OH (13.8%) and iso-C15:0 (11.0%). The polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, an unidentified aminophospholipid, two unidentified aminolipids, and two unidentified lipids. The respiratory quinone was ubiquinone-8. The comprehensive phylogenetic, phylogenomic, phenotypic and chemotaxonomic results showed that strain HL-JVS1T is distinct from other Pleionea species. Hence, we propose strain HL-JVS1T as a novel species belonging to the genus Pleionea, for which the name Pleionea litopenaei sp. nov. is proposed with HL-JVS1T (= KCCM 90514T = JCM 36490T) as the type strain.

Analysis of SARS-CoV-2 Mutations after Nirmatrelvir Treatment in a Lung Cancer Xenograft Mouse Model.

Paxlovid is the first approved oral treatment for coronavirus disease 2019 and includes nirmatrelvir, a protease inhibitor targeting the main protease (Mpro) of SARS-CoV-2, as one of the key components. While some specific mutations emerged in Mpro were revealed to significantly reduce viral susceptibility to nirmatrelvir in vitro, there is no report regarding resistance to nirmatrelvir in patients and animal models for SARS-CoV-2 infection yet. We recently developed xenograft tumors derived from Calu-3 cells in immunodeficient mice and demonstrated extended replication of SARS-CoV-2 in the tumors. In this study, we investigated the effect of nirmatrelvir administration on SARS-CoV-2 replication. Treatment with nirmatrelvir after virus infection significantly reduced the replication of the parental SARS-CoV-2 and SARS-CoV-2 Omicron at 5 days post-infection (dpi). However, the virus titers were completely recovered at the time points of 15 and 30 dpi. The virus genomes in the tumors at 30 dpi were analyzed to investigate whether nirmatrelvir-resistant mutant viruses had emerged during the extended replication of SARS-CoV-2. Various mutations in several genes including ORF1ab, ORF3a, ORF7a, ORF7b, ORF8, and N occurred in the SARS-CoV-2 genome; however, no mutations were induced in the Mpro sequence by a single round of nirmatrelvir treatment, and none were observed even after two rounds of treatment. The parental SARS-CoV-2 and its sublineage isolates showed similar IC50 values of nirmatrelvir in Vero E6 cells. Therefore, it is probable that inducing viral resistance to nirmatrelvir in vivo is challenging differently from in vitro passage.

Sports promote brain evolution: a resting-state fMRI study of volleyball athlete.

Background: Long-term skill learning can lead to structure and function changes in the brain. Different sports can trigger neuroplasticity in distinct brain regions. Volleyball, as one of the most popular team sports, heavily relies on individual abilities such as perception and prediction for high-level athletes to excel. However, the specific brain mechanisms that contribute to the superior performance of volleyball athletes compared to non-athletes remain unclear. Method: We conducted a study involving the recruitment of ten female volleyball athletes and ten regular female college students, forming the athlete and novice groups, respectively. Comprehensive behavioral assessments, including Functional Movement Screen and audio-visual reaction time tests, were administered to both groups. Additionally, resting-state magnetic resonance imaging (MRI) data were acquired for both groups. Subsequently, we conducted in-depth analyses, focusing on the amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo), and functional connectivity (FC) in the brain for both the athlete and novice groups. Results: No significant differences were observed in the behavioral data between the two groups. However, the athlete group exhibited noteworthy enhancements in both the ALFF and ReHo within the visual cortex compared to the novice group. Moreover, the functional connectivity between the visual cortex and key brain regions, including the left primary sensory cortex, left supplementary motor cortex, right insula, left superior temporal gyrus, and left inferior parietal lobule, was notably stronger in the athlete group than in the novice group. Conclusion: This study has unveiled the remarkable impact of volleyball athletes on various brain functions related to vision, movement, and cognition. It indicates that volleyball, as a team-based competitive activity, fosters the advancement of visual, cognitive, and motor skills. These findings lend additional support to the early cultivation of sports talents and the comprehensive development of adolescents. Furthermore, they offer fresh perspectives on preventing and treating movement-related disorders. Trial registration: Registration number: ChiCTR2400079602. Date of Registration: January 8, 2024.

Analysis of SARS-CoV-2 omicron mutations that emerged during long-term replication in a lung cancer xenograft mouse model.

SARS-CoV-2 Omicron has the largest number of mutations among all the known SARS-CoV-2 variants. The presence of these mutations might explain why Omicron is more infectious and vaccines have lower efficacy to Omicron than other variants, despite lower virulence of Omicron. We recently established a long-term in vivo replication model by infecting Calu-3 xenograft tumors in immunodeficient mice with parental SARS-CoV-2 and found that various mutations occurred majorly in the spike protein during extended replication. To investigate whether there are differences in the spectrum and frequency of mutations between parental SARS-CoV-2 and Omicron, we here applied this model to Omicron. At 30 days after infection, we found that the virus was present at high titers in the tumor tissues and had developed several rare sporadic mutations, mainly in ORF1ab with additional minor spike protein mutations. Many of the mutant isolates had higher replicative activity in Calu-3 cells compared with the original SARS-CoV-2 Omicron virus, suggesting that the novel mutations contributed to increased viral replication. Serial propagation of SARS-CoV-2 Omicron in cultured Calu-3 cells resulted in several rare sporadic mutations in various viral proteins with no mutations in the spike protein. Therefore, the genome of SARS-CoV-2 Omicron seems largely stable compared with that of the parental SARS-CoV-2 during extended replication in Calu-3 cells and xenograft model. The sporadic mutations and modified growth properties observed in Omicron might explain the emergence of Omicron sublineages. However, we cannot exclude the possibility of some differences in natural infection.

DNA methylation-based organ tissue identification: Marker identification, SNaPshot multiplex assay development, and interlaboratory comparison.

Identifying body fluids and organ tissues is highly significant as they can offer crucial evidence in criminal investigations and aid the court in making informed decisions, primarily through evaluating the biological source and possibly at the activity level up to death or fatal damage. In this study, organ tissue-specific CpG markers were identified from Illumina's methylation EPIC array data of nine organ tissues, including epidermis, dermis, heart, skeletal muscle, blood, kidney, brain, lung, and liver, from autopsies of 10 Koreans. Through the validation test using 43 samples, 18 hypomethylation markers, with two markers for each organ tissue type, were selected to construct a SNaPshot assay. Two multiplex assays involving forward and reverse SBE primers were designed to help investigators accurately determine the organ origin of the analyzed tissue samples through repeated analysis of the same PCR products for markers. The developed multiplex demonstrated high accuracy, achieving 100.0 % correct detection of the presence of nine organ tissue types in 88 samples from autopsies of 10 Asians. However, two lung samples showed additional positive indications of the presence of blood. An interlaboratory comparison using 80 autopsy samples (heart, skeletal muscle, blood, kidney cortex, kidney medulla, brain, lung, and liver) from 10 individuals in Germany revealed overall comparable results with correct detection of the presence of eight organ tissue types in 92.5 % samples (74 of 80 samples). In the case of six samples, it was impossible to determine the correct tissue successfully due to drop-outs of unmethylation signals at target tissue marker loci. One of these lung samples revealed only non-intended off-target signals for blood. The observed differences might be due to differences in sample collection during routine autopsy, technical differences due to the PCR cycler, and the threshold used for signal calling. Indicating the presence of additional tissue type and off-target unmethylation signals seems alleviated by applying more stringent hypomethylation thresholds. Therefore, the developed SNaPshot multiplex assays will be valuable for forensic investigators dealing with organ tissue identification, as well as for prosecutors and defense aiming to establish the circumstances that occurred at the crime scene.

Photochemically Inert Broad-Spectrum Sunscreen by Metal-Phenolic Network Coatings of Titanium Oxide Nanoparticles.

Titanium dioxide (TiO2) nanoparticles are extensively used as a sunscreen filter due to their long-active ultraviolet (UV)-blocking performance. However, their practical use is being challenged by high photochemical activities and limited absorption spectrum. Current solutions include the coating of TiO2 with synthetic polymers and formulating a sunscreen product with additional organic UV filters. Unfortunately, these approaches are no longer considered effective because of recent environmental and public health issues. Herein, TiO2-metal-phenolic network hybrid nanoparticles (TiO2-MPN NPs) are developed as the sole active ingredient for sunscreen products through photochemical suppression and absorption spectrum widening. The MPNs are generated by the complexation of tannic acid with multivalent metal ions, forming a robust coating shell. The TiO2-MPN hybridization extends the absorption region to the high-energy-visible (HEV) light range via a new ligand-to-metal charge transfer photoexcitation pathway, boosting both the sun protection factor and ultraviolet-A protection factor about 4-fold. The TiO2-MPN NPs suppressed the photoinduced reactive oxygen species by 99.9% for 6 h under simulated solar irradiation. Accordingly, they substantially alleviated UV- and HEV-induced cytotoxicity of fibroblasts. This work outlines a new tactic for the eco-friendly and biocompatible design of sunscreen agents by selectively inhibiting the photocatalytic activities of semiconductor nanoparticles while broadening their optical spectrum.

Comparison of pain relief in soft tissue tumor excision: anesthetic injection using an automatic digital injector versus conventional injection.

BACKGROUND: The pain caused by local anesthetic injection can lead to patient anxiety prior to surgery, potentially necessitating sedation or general anesthesia during the excision procedure. In this study, we aim to compare the pain relief efficacy and safety of using a digital automatic anesthetic injector for local anesthesia. METHODS: Thirty-three patients undergoing excision of a benign soft tissue tumor under local anesthesia were prospectively enrolled from September 2021 to February 2022. A single-blind, randomized controlled study was conducted. Patients were divided into two groups by randomization: the experimental group with digital automatic anesthetic injector method (I-JECT group) and the control group with conventional injection method. Before surgery, the Amsterdam preoperative anxiety information scale was used to measure the patients' anxiety. After local anesthetic was administered, the Numeric Pain Rating Scale was used to measure the pain. The amount of anesthetic used was divided by the surface area of the lesion was recorded. RESULTS: Seventeen were assigned to the conventional group and 16 to the I-JECT group. The mean Numeric Pain Rating Scale was 1.75 in the I-JECT group and 3.82 in conventional group. The injection pain was lower in the I-JECT group (p< 0.01). The mean Amsterdam preoperative anxiety information scale was 11.00 in the I-JECT group and 9.65 in conventional group. Patient's anxiety did not correlate to injection pain regardless of the method of injection (p= 0.47). The amount of local anesthetic used per 1 cm 2 of tumor surface area was 0.74 mL/cm2 in the I-JECT group and 2.31 mL/cm2 in the conventional group. The normalization amount of local anesthetic was less in the I-JECT group (p< 0.01). There was no difference in the incidence of complications. CONCLUSION: The use of a digital automatic anesthetic injector has shown to reduce pain and the amount of local anesthetics without complication.

A mouse xenograft long-term replication yields a SARS-CoV-2 Delta mutant with increased lethality.

We recently established a long-term SARS-CoV-2 infection model using lung-cancer xenograft mice and identified mutations that arose in the SARS-CoV-2 genome during long-term propagation. Here, we applied our model to the SARS-CoV-2 Delta variant, which has increased transmissibility and immune escape compared with ancestral SARS-CoV-2. We observed limited mutations in SARS-CoV-2 Delta during long-term propagation, including two predominant mutations: R682W in the spike protein and L330W in the nucleocapsid protein. We analyzed two representative isolates, Delta-10 and Delta-12, with both predominant mutations and some additional mutations. Delta-10 and Delta-12 showed lower replication capacity compared with SARS-CoV-2 Delta in cultured cells; however, Delta-12 was more lethal in K18-hACE2 mice compared with SARS-CoV-2 Delta and Delta-10. Mice infected with Delta-12 had higher viral titers, more severe histopathology in the lungs, higher chemokine expression, increased astrocyte and microglia activation, and extensive neutrophil infiltration in the brain. Brain tissue hemorrhage and mild vacuolation were also observed, suggesting that the high lethality of Delta-12 was associated with lung and brain pathology. Our long-term infection model can provide mutant viruses derived from SARS-CoV-2 Delta and knowledge about the possible contributions of emergent mutations to the properties of new variants.

Associations between Serum Mineral Nutrients, Gut Microbiota, and Risk of Neurological, Psychiatric, and Metabolic Diseases: A Comprehensive Mendelian Randomization Study.

Recent observational studies have reported associations between serum mineral nutrient levels, gut microbiota composition, and neurological, psychiatric, and metabolic diseases. However, the causal effects of mineral nutrients on gut microbiota and their causal associations with diseases remain unclear and require further investigation. This study aimed to identify the associations between serum mineral nutrients, gut microbiota, and risk of neurological, psychiatric, and metabolic diseases using Mendelian randomization (MR). We conducted an MR study using the large-scale genome-wide association study (GWAS) summary statistics of 5 serum mineral nutrients, 196 gut microbes at the phylum, order, family, and genus levels, and a variety of common neurological, psychiatric, and metabolic diseases. Initially, the independent causal associations of mineral nutrients and gut microbiota with diseases were examined by MR. Subsequently, the causal effect of mineral nutrients on gut microbiota was estimated to investigate whether specific gut microbes mediated the association between mineral nutrients and diseases. Finally, we performed sensitivity analyses to assess the robustness of the study results. After correcting for multiple testing, we identified a total of 33 causal relationships among mineral nutrients, gut microbiota, and diseases. Specifically, we found 4 causal relationships between 3 mineral nutrition traits and 3 disease traits, 15 causal associations between 14 gut microbiota traits and 6 disease traits, and 14 causal associations involving 4 mineral nutrition traits and 15 gut microbiota traits. Meanwhile, 118 suggestive associations were identified. The current study reveals multiple causal associations between serum mineral nutrients, gut microbiota, risk of neurological, psychiatric, and metabolic diseases, and potentially provides valuable insights for subsequent nutritional therapies.

Analysis of spike protein variants evolved in a novel in vivo long-term replication model for SARS-CoV-2.

Introduction: The spectrum of SARS-CoV-2 mutations have increased over time, resulting in the emergence of several variants of concern. Persistent infection is assumed to be involved in the evolution of the variants. Calu-3 human lung cancer cells persistently grow without apoptosis and release low virus titers after infection. Methods: We established a novel in vivo long-term replication model using xenografts of Calu-3 human lung cancer cells in immunodeficient mice. Virus replication in the tumor was monitored for 30 days and occurrence of mutations in the viral genome was determined by whole-genome deep sequencing. Viral isolates with mutations were selected after plaque forming assays and their properties were determined in cells and in K18-hACE2 mice. Results: After infection with parental SARS-CoV-2, viruses were found in the tumor tissues for up to 30 days and acquired various mutations, predominantly in the spike (S) protein, some of which increased while others fluctuated for 30 days. Three viral isolates with different combination of mutations produced higher virus titers than the parental virus in Calu-3 cells without cytopathic effects. In K18-hACE2 mice, the variants were less lethal than the parental virus. Infection with each variant induced production of cross-reactive antibodies to the receptor binding domain of parental SARS-CoV-2 S protein and provided protective immunity against subsequent challenge with parental virus. Discussion: These results suggest that most of the SARS-CoV-2 variants acquired mutations promoting host adaptation in the Calu-3 xenograft mice. This model can be used in the future to further study SARS-CoV-2 variants upon long-term replication in vivo.

Molecular detection of Dirofilaria immitis and its Wolbachia endosymbionts in dogs from Myanmar.

Heartworm disease in dogs and cats caused by Dirofilaria immitis continues to be a major clinical issue globally. This study focused on dogs suspicious of having tick-borne diseases (TBD) brought to a clinic and a veterinary teaching hospital in Myanmar. Blood samples were collected and initially screened using SNAP® 4Dx® Plus test kit. All dog blood samples were subjected to conventional PCR to detect both Dirofilaria spp. (cox1 gene) and Wolbachia spp. (16S rDNA) infections. Infection with D. immitis was detected in 14 (28.0%) of 50 examined samples, while the detection rate of TBD causative agents, including Anaplasma phagocytophilum and Ehrlichia canis, was 26.0% (13/50) and 26.0% (13/50), respectively, as determined by ELISA rapid test. In this study, D. immitis infection was moderately but significantly correlated with TBD infections (Pearson's r = 0.397, P = 0.008). Comparative sequence and phylogenetic analyses provided molecular identification of D. immitis in Myanmar and confirmed the identity of its Wolbachia endosymbiont with Wolbachia endosymbionts isolated from D. immitis, Rhipicephalus sanguineus and Aedes aegypti. The present study contributes to our understanding of the coexistence of D. immitis and Wolbachia endosymbiosis in dogs, and the findings may benefit the future prevention and control of dirofilariasis in dogs.

Sustainable Strategies for Synthesizing Lignin-Incorporated Bio-Based Waterborne Polyurethane with Tunable Characteristics.

In this study, we introduce a novel approach for synthesizing lignin-incorporated castor-oil-based cationic waterborne polyurethane (CWPU-LX), diverging significantly from conventional waterborne polyurethane dispersion synthesis methods. Our innovative method efficiently reduces the required solvent quantity for CWPU-LX synthesis to approximately 50% of that employed in traditional WBPU experimental procedures. By incorporating lignin into the polyurethane matrix using this efficient and reduced-solvent method, CWPU-LX demonstrates enhanced properties, rendering it a promising material for diverse applications. Dynamic interactions between lignin and polyurethane molecules contribute to improved mechanical properties, enhanced thermal stability, and increased solvent resistance. Dynamic interactions between lignin and polyurethane molecules contribute to improved tensile strength, up to 250% compared to CWPU samples. Furthermore, the inclusion of lignin enhanced thermal stability, showcasing a 4.6% increase in thermal decomposition temperature compared to conventional samples and increased solvent resistance to ethanol. Moreover, CWPU-LX exhibits desirable characteristics such as protection against ultraviolet light and antibacterial properties. These unique properties can be attributed to the presence of the polyphenolic group and the three-dimensional structure of lignin, further highlighting the versatility and potential of this material in various application domains. The integration of lignin, a renewable and abundant resource, into CWPU-LX exemplifies the commitment to environmentally conscious practices and underscores the significance of greener materials in achieving a more sustainable future.

The Endoplasmic Reticulum Is a Key Battleground between Phytoplasma Aggression and Host Plant Defense.

Phytoplasmas are intracellular plant pathogens that heavily rely on host cell nutrients for survival and propagation due to their limited ability to synthesize essential substrates. The endoplasmic reticulum (ER), which plays a vital role in various cellular processes, including lipid and protein biosynthesis, is an attractive target for numerous intracellular pathogens to exploit. This study investigated the impact of potato purple top (PPT) phytoplasma infection on the ER in tomato plants. Abnormal accumulation of ER-resident proteins, disrupted ER network structures, and formation of protein aggregates in the phloem were observed using confocal microscopy and transmission electron microscopy, indicating a phytoplasma-infection-induced disturbance in ER homeostasis. The colocalization of phytoplasmas with the accumulated ER-resident proteins suggests an association between ER stress, unfolded protein response (UPR) induction, and phytoplasma infection and colonization, with the ER stress response likely contributing to the host plant's defense mechanisms. Quantitative real-time PCR revealed a negative correlation between ER stress/UPR activation and PPT phytoplasma titer, implying the involvement of UPR in curbing phytoplasma proliferation. Inducing ER stress and activating the UPR pathway effectively decreased phytoplasma titer, while suppressing the ER-resident protein, binding immunoglobulin protein (BiP) increased phytoplasma titer. These results highlight the ER as an intracellular battleground where phytoplasmas exploit host components for survival and multiplication, while host plants deploy defense mechanisms to counteract the invasion. Understanding the intricate interactions between phytoplasmas and plant hosts at the subcellular level, particularly within the ER, provides valuable insights for developing new strategies to control phytoplasma diseases.

Effectiveness of sleep interventions for rotating night shift workers: a systematic review and meta-analysis.

Background: Sleep disturbance is a common issue among rotating night shift workers and is closely related to health risks. The present study aimed to determine the effectiveness of pharmacological and non-pharmacological sleep interventions for the management of sleep disturbance among rotating night shift workers. Methods: For this systematic review and meta-analysis, we searched six electronic databases-EMBASE, CINAHL, Cochrane Library, PubMed, Scopus, and Web of Science-for randomized controlled trials and clinical trials published from January 1990 to June 2022. The quality of eligible studies was independently assessed by three authors using the Joanna Briggs Institute Critical Appraisal Checklist for randomized controlled trials and quasi-experimental studies. The meta-analysis was performed based on the random effects model using the Comprehensive Meta-Analysis software. The study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: Of the 1019 studies retrieved, 30 met the inclusion criteria for the systematic review; 25 were selected for the meta-analysis. Sleep interventions were categorized as follows: pharmacological approach (n = 7), light therapy (n = 9), cognitive behavioral approach (n = 7), aroma or alternative therapy (n = 4), and shift schedule modification (n = 3). The overall mean effect size of the interventions was moderate (Hedges' g = 0.59; 95% confidence interval = 0.33-0.84, z = 4.50, p < 0.001). Conclusion: Sleep interventions were effective in promoting sleep or reducing sleep disturbance among rotating night shift workers. These findings provide evidence of the effectiveness of various pharmacological and non-pharmacological sleep interventions for managing sleep health in the work environment of rotating night shift workers.

In vitro and in vivo suppression of SARS-CoV-2 replication by a modified, short, cell-penetrating peptide targeting the C-terminal domain of the viral spike protein.

Peptides are promising therapeutic agents for COVID-19 because of their specificity, easy synthesis, and ability to be fine-tuned. We previously demonstrated that a cell-permeable peptide corresponding to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike C-terminal domain (CD) inhibits the interaction between viral spike and nucleocapsid proteins that results in SARS-CoV-2 replication in vitro. Here, we used docking studies to design R-t-Spike CD(D), a more potent short cell-penetrating peptide composed of all D-form amino acids and evaluated its inhibitory effect against the replication of SARS-CoV-2 S clade and other variants. R-t-Spike CD(D) was internalized into Vero cells and Calu-3 cells and suppressed the replication of SARS-CoV-2 S clade, delta variant, and omicron variant with higher potency than the original peptide. In hemizygous K18-hACE2 mice, intratracheal administration of R-t-Spike CD(D) effectively delivered the peptide to the trachea and lungs, whereas intranasal administration delivered the peptide mostly to the upper respiratory system and stomach, and a small amount to the lungs. Administration by either route reduced viral loads in mouse lungs and turbinates. Furthermore, intranasally administered R-t-Spike CD(D) mitigated pathological change in the lungs and increased the survival of mice after infection with the SARS-CoV-2 S clade or delta variant. Our data suggest that R-t-Spike CD(D) has potential as a therapeutic agent against SARS-CoV-2 infection.

A biomimetic gradient porous cage with a micro-structure for enhancing mechanical properties and accelerating osseointegration in spinal fusion.

Objectives: Spinal fusion is a widely employed treatment of patients with degenerative disc disease, in which a cage is used to replace the disc for spinal fusion. But it often fails for insufficient mechanical strength and poor osseointegration. Here, we designed a polyether-ether-ketone (PEEK)/tantalum (Ta) composite cage with a biomimetic gradient porous micro-structure, simultaneously enhancing mechanical properties and accelerating osseointegration in spinal fusion. Materials and methods: In the study, based on the mechanical performances of PEEK and osteogenic potential of Ta, and the three-dimensional (3D) structures of cuttlebone and vertebra, the cages were respectively 3D printed by pure PEEK, PEEK with 5 wt% Ta (PEEK/Ta-5), PEEK with 10 wt% Ta (PEEK/Ta-10) and PEEK with 15 wt% Ta (PEEK/Ta-15), then verified in vitro and in sheep cervical fusion model systematically. Results: Vertebral Gyroid structure PEEK/Ta-15 cage exhibited superior mechanical properties than Cuttlebone-like structure PEEK/Ta-15 cage, closer to the cervical vertebra. Furthermore, PEEK/Ta-15 cage with higher Ta microparticles in PEEK provided a biomimetic gradient porous micro-structure with higher surface energy, guiding cell biological behavior, promoting new bone penetration, and accelerating osseointegration in vivo. Conclusion: In conclusion, the study designed a biomimetic gradient porous cage with a micro-structure for enhancing mechanical properties, accelerating osseointegration and forming an anatomical lock in the fusion segment through composites, mechanical efficiency, surface extension, and pores.

Functional characterization of ABCA4 genetic variants related to Stargardt disease.

The ATP-binding cassette subfamily 4 (ABCA4), a transporter, is localized within the photoreceptors of the retina, and its genetic variants cause retinal dystrophy. Despite the clinical importance of the ABCA4 transporter, a few studies have investigated the function of each variant. In this study, we functionally characterized ABCA4 variants found in Korean patients with Stargardt disease or variants of the ABCA4 promoter region. We observed that four missense variants-p.Arg290Gln, p.Thr1117Ala, p.Cys1140Trp, and p.Asn1588Tyr-significantly decreased ABCA4 expression on the plasma membrane, which could be due to intracellular degradation. There are four major haplotypes in the ABCA4 proximal promoter. We observed that the H1 haplotype (c.-761C>A) indicated significantly increased luciferase activity compared to that of the wild-type, whereas the H3 haplotype (c.-1086A>C) indicated significantly decreased luciferase activity (P < 0.01 and 0.001, respectively). In addition, c.-900A>T in the H2 haplotype exhibited significantly increased luciferase activity compared with that of the wild-type. Two transcription factors, GATA-2 and HLF, were found to function as enhancers of ABCA4 transcription. Our findings suggest that ABCA4 variants in patients with Stargardt disease affect ABCA4 expression. Furthermore, common variants of the ABCA4 proximal promoter alter the ABCA4 transcriptional activity, which is regulated by GATA-2 and HLF transcription factors.

Associations of extended work, higher workloads and emotional work demands with sleep disturbance among night-shift workers.

BACKGROUND: In-depth investigation of the factors that exacerbate sleep disturbance among night-shift workers is essential to develop a successful implementation strategy to improve sleep. Although some characteristics of work associated with sleep disturbances have been investigated, there are inconsistencies in the findings. This study aimed to assess the influence of working time and work characteristics on sleep disturbance among night-shift workers. METHODS: This study was a secondary data analysis of a nationally representative sample of data from the fifth Korean Working Condition Survey in 2017. A total of 1,790 wage workers aged between 19 and 64 years with night shift schedules were selected and analyzed. A multiple logistic regression analysis was conducted to analyze the influences of working time characteristics, including shift type, frequency of night shift, and extended work; as well as work characteristics, including physical work demands, workload, emotional work demands, social support, and communication, on sleep disturbance among night-shift workers. RESULTS: Of those analyzed, 8.4% of night-shift workers experienced sleep disturbances. Night-shift workers with extended work, higher workloads, and emotional work demands were more likely to experience sleep disturbances (OR = 1.53, 95% CI = 1.05 to 2.23; OR = 1.01, 95% CI = 1.01 to 1.03; OR = 1.03, 95% CI = 1.02 to 1.05; respectively). CONCLUSION: Extended work, higher workload, and emotional work demands were significant factors for sleep disturbance among night-shift workers. These findings highlight the importance of adjusting work demands and mitigating extended work to reduce sleep disturbance in night-shift workers.

A Complex Intervention Integrating Prism Adaptation and Neck Vibration for Unilateral Neglect in Patients of Chronic Stroke: A Randomised Controlled Trial.

Unilateral neglect in patients of chronic stroke reduces the quality of life and interferes with activities of daily living (ADL). This study aimed to investigate the effects of a complex rehabilitative programme that integrates prism adaptation (PA) and neck vibration (NV) for unilateral neglect in patients of chronic stroke. Thirty-six patients were randomised among the PA + NV group (Group A, n = 12), the NV-only group (Group B, n = 12), and the PA-only group (Group C, n = 12). The intervention was performed for 50 min/day, with five sessions per week, for 4 weeks. Albert's test and the Catherine Bergego Scale were used to measure the effects of each intervention on unilateral neglect, whereas the modified Barthel Index was used to assess the effect on ADL. All three groups exhibited a reduction in unilateral neglect and an improvement in activities of daily living after the intervention (p < 0.05). Notably, Group A (PA + NV) exhibited a significantly greater level of reduction in unilateral neglect than the other groups (p < 0.05); however, the improvement in ADL did not significantly vary across the three groups (p > 0.05). This novel complex intervention comprising PA + NV is recommended for the rehabilitation, in the clinical setting, of patients of chronic stroke with unilateral neglect.

Application of a custom haplotype caller to analyze sequence-based data of 56 microhaplotypes.

Microhaplotypes (microhaps) are recently introduced markers that aim to complement the limitations of conventional forensic markers such as short tandem repeats (STRs) and single nucleotide polymorphisms (SNPs). With the potential of microhaps in forensics becoming clearer through massively parallel sequencing (MPS), MPS-based studies on microhaps are being actively reported. However, simpler workflow schemes for the generation and analysis of MPS data are still required to facilitate the practical application of MPS in forensics. In this study, we developed an in-house MPS panel that simultaneously amplifies 56 microhaps and a custom haplotype caller, Visual Microhap. The developed tool works on a web browser and provides four analysis options to extract SNP-based haplotypes from sequence-based data obtained by STRait Razor 3.0. To demonstrate the utility of the MPS panel and data analysis workflow scheme, we also analyzed 56 microhaps of 286 samples from four populations (African-American, Caucasian, Hispanic, and Korean). The average effective number of alleles (Ae) for the four groups was 3.45, ranging from 1.74 to 6.98. Forensic statistical parameters showed that this microhap panel is more powerful than conventional autosomal STRs for human identification. Meanwhile, the 56-plex panel mostly comprised microhaps with high Ae; however, the four populations were grossly distinguishable from each other by cluster analysis. Consequently, the developed in-house MPS panel for 56 microhaps and the adopted workflow using open-source tools can increase the utility of microhap MPS in forensic research and practice.