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Background: Severe community-acquired pneumonia was associated with high morbidity and mortality in children. However, species-level microbiome of lower airway was sparse, and we used shotgun metagenomic next-generation sequencing to explore microbial signatures. Methods: We conducted a prospective cohort study to recruit children under 18 who required admission to an intensive care unit for community-acquired pneumonia between December 2019 and February 2022. Lower respiratory specimens were collected on admission for shotgun metagenomic sequencing. The children were divided into two groups. Critical cases were patients with respiratory failure requiring endotracheal ventilator support, and severe cases did not require intubation. Signatures of lower respiratory tract microbiome were compared between groups using an exact k-mer matching metagenomic analysis pipeline (Kraken 2) and a metagenome-assembled genomes pipeline (MetaWRAP). Results: Totally 66 children were enrolled, and 27 children were critical cases, and the rest were severe cases. There were significant differences in microbial community structure between different severity groups, and microbial abundance was negatively correlated with disease severity. The results showed that Haemophilus influenzae was more prominent in children who were critical, accompanied with increased expression of intracellular transport, secretion, and vesicle transport genes. Rothia mucilaginosa, Dolosigranulum pigrum, and Prevotella melaninogenica tended to be present in less severe community-acquired pneumonia group. Conclusion: This study demonstrated that significantly different microbial community was associated with severity of community-acquired pneumonia requiring intensive care admission. Species-level shotgun metagenomic sequencing facilitates the exploration of potentially pathogenic or protective microbes and shed the light of probiotic development in lower respiratory tract.

Background: During the COVID-19 pandemic, parental involvement in NICU and post-discharge follow-up for preterm infants in Taiwan were limited. This study aimed to investigate the impact of the pandemic on the neurodevelopmental outcomes of preterm infants in Taiwan. Method: This was a retrospective study enrolling very-low-birth weight (VLBW) preterm infants born between January 2018 and December 2021 from two hospitals. The pre-COVID-19 group (PCG) consisted of VLBW infants born between January 2018 and April 2019, before the pandemic. VLBW infants born after May 2019 and followed-up for at least 24 months during the pandemic were assigned to the COVID-19 group (CG). The antenatal, perinatal, and postnatal data, and neurodevelopmental outcomes at 12 and/or 24 months corrected age (CA) of the participants were collected and compared. Results: A total of 547 VLBW infants were born during the study period. CG had significantly longer hospital stay and delayed follow-up time compared to PCG. No significant differences were observed in the composite cognitive, language, and motor scores between two groups. The percentages of moderate neurodevelopmental impairment (NDI) were higher at 12 months CA, but not at 24 months. The severe NDI also presented no significant difference between the groups. Conclusion: VLBW preterm infants during the pandemic had extended hospital stays and delayed follow-ups, with higher moderate NDI at 12 months CA. Long-term monitoring and care are essential for this at-risk group.

Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral disorder beginning in childhood and often extending into adulthood. ADHD may negatively impact emotional regulation and cause addictive behaviors such as social media addiction. The present study investigated the association of ADHD symptoms (i.e., attention deficit [AD] and hyperactivity/impulsivity [HI]) with social media addiction among young adults. The mediating effect of internalizing and externalizing emotional regulation (i.e., self-blame [SB] and blaming others [BO]) were examined. Participants (n = 96; mean age = 19.9 years [SD = 2.07]) comprising 35 individuals with probable ADHD and 61 individuals who did not have ADHD completed measures assessing social media addiction, ADHD symptoms, and emotional regulation strategies. Results of Hayes' Process Micro showed that both ADHD symptoms were significantly positively associated with social media addiction (standardized coefficient [β] = 0.30 and 0.38 for AD and HI) and emotional regulation strategies (β = 0.38 and 0.27 for AD to SB and BO, β = 0.23 and 0.28 for HI to SB and BO). In addition, BO was a significant mediator in the association between AD and social media addiction (β = 0.07, 95 % confidence interval = 0.003, 0.11). The results suggest that externalizing emotional regulation may mediate the association between symptoms of AD and social media addiction. It is recommended that individuals with probable ADHD should focus on improving self-awareness (such as mindfulness), developing resilience skills, and/or incorporating positive coping strategies (such as physical activity) to reduce the negative impacts derived from symptoms of ADHD.

Abstract The transition from natal downs for heat conservation to juvenile feathers for simple flight is a remarkable environmental adaptation process in avian evolution. However, the underlying epigenetic mechanism for this primary feather transition is mostly unknown. Here we conducted time-ordered gene co-expression network construction, epigenetic analysis, and functional perturbations in developing feather follicles to elucidate four downy-juvenile feather transition events. We report that extracellular matrix reorganization leads to peripheral pulp formation, which mediates epithelial-mesenchymal interactions for branching morphogenesis. α-SMA (ACTA2) compartmentalizes dermal papilla stem cells for feather renewal cycling. LEF1 works as a key hub of Wnt signaling to build rachis and converts radial downy to bilateral symmetry. Novel usage of scale keratins strengthens feather sheath with SOX14 as the epigenetic regulator. We show that this primary feather transition is largely conserved in chicken (precocial) and zebra finch (altricial) and discuss the possibility that this evolutionary adaptation process started in feathered dinosaurs.

Abstract The incidence of melanoma, the most lethal form of skin cancer, has increased due to ultraviolet exposure. The treatment of advanced melanoma, particularly metastatic cases, remains challenging with poor outcomes. Targeted therapies involving BRAF/MEK inhibitors and immunotherapy based on anti-PD1/anti-CTLA4 antibodies have achieved long-term survival rates of approximately 50% for patients with advanced melanoma. However, therapy resistance and inadequate treatment response continue to hinder further breakthroughs in treatments that increase survival rates. This review provides an introduction to the molecular-level pathogenesis of melanoma and offers an overview of current treatment options and their limitations. Cells can die by either accidental or regulated cell death (RCD). RCD is an orderly cell death controlled by a variety of macromolecules to maintain the stability of the internal environment. Since the uncontrolled proliferation of tumor cells requires evasion of RCD programs, inducing the RCD of melanoma cells may be a treatment strategy. This review summarizes studies on various types of nonapoptotic RCDs, such as autophagy-dependent cell death, necroptosis, ferroptosis, pyroptosis, and the recently discovered cuproptosis, in the context of melanoma. The relationships between these RCDs and melanoma are examined, and the interplay between these RCDs and immunotherapy or targeted therapy in patients with melanoma is discussed. Given the findings demonstrating melanoma cell death in response to different stimuli associated with these RCDs, the induction of RCD shows promise as an integral component of treatment strategies for melanoma.

In this study, a three-dimensional (3D) interconnected porous Ni/SiC skeleton (3D Ni/SiC) was synthesized by binder-free hydrogen bubble template-assisted electrodeposition in an electrolyte containing Ni2+ ions and SiC nanopowders. This 3D Ni/SiC skeleton served as a substrate for directly synthesizing nickel–cobalt layered double hydroxide (LDH) nanosheets via electrodeposition, allowing the formation of a nickel–cobalt LDH nanosheet-decorated 3D Ni/SiC skeleton (NiCo@3D Ni/SiC). The multiscale hierarchical structure of NiCo@3D Ni/SiC was attributed to the synergistic interaction between the pseudocapacitor (3D Ni skeleton and Ni–Co LDH) and electrochemical double-layer capacitor (SiC nanopowders). It provided a large specific surface area to expose numerous active Ni and Co sites for Faradaic redox reactions, resulting in an enhanced pseudocapacitance. The as-fabricated NiCo@3D Ni/SiC structure demonstrated excellent rate capability with a high areal capacitance of 1565 mF cm−2 at a current density of 1 mA cm−2. Additionally, symmetrical supercapacitor devices based on this structure successfully powered commercial light-emitting diodes, indicating the potential of as-fabricated NiCo@3D Ni/SiC in practical energy storage applications.

Key Clinical Message Staphylococcal scalded skin syndrome (SSSS) is a rare condition in premature infants. We report a case of SSSS in a preterm neonate who displayed all clinical manifestations at birth, leading to a fatal outcome from Candida parapsilosis fungemia. The clinical presentation was challenging to differential diagnosis. SSSS diagnosis was confirmed by skin biopsy. This case emphasizes the significance of early recognition and diagnosis of SSSS promptly for clinicians. Congenital SSSS in premature infants can be fatal, but with early recognition and appropriate supportive and antimicrobial therapy, outcomes can be improved and lives can be saved.

The well-interconnected ternary Ni–Co–O nanosheets were grown on silicon carbide microspheres/graphite composite (gra@SiC/Ni–Co–O) by optimizing the electrodeposition method. Silicon carbide microspheres/graphite composite (gra@SiC) serves as a conductive template for the growth of Ni–Co–O nanosheets to form a binder-free 3D well-designed hierarchical interconnected network between the Ni–Co–O nanosheets and SiC microspheres. The obtained gra@SiC/Ni–Co–O is proposed as a great capacitance performance for supercapacitors. Field emission scanning electron microscopy (FESEM), Raman spectroscopy, high-resolution transmission electron microscopy (HRTEM) with selected area electron diffraction (SAED) and energy dispersive X-ray spectroscopy (EDS), X-ray photoelectron spectroscopy, and electrochemical analysis were employed to investigate the morphology and structural and electrochemical characteristics. The synergistic effects of EDLC (SiC microspheres) and pseudo-capacitance (Ni–Co–O nanosheets) can effectively improve the supercapacitive performance. It is also worth mentioning that after electrochemical testing, the redox reaction of Ni–Co–O nanosheets greatly promoted the faradic pseudo-capacitance contribution, and silicon carbide microspheres/graphite composite contributed to the formation of a 3D interconnected network, improving the cycling stability during the charging/discharging processes.

Among amniotic skin appendages, avian feathers and mammalian hairs protect their stem cells in specialized niches, located in the collar bulge and hair bulge, respectively. In chickens and alligators, label retaining cells (LRCs), which are putative stem cells, are distributed in the hinge regions of both avian scutate scales and reptilian overlapping scales. These LRCs take part in scale regeneration. However, it is unknown whether other types of scales, for example, symmetrically shaped reticulate scales, have a similar way of preserving their stem cells. In particular, the foot sole represents a special interface between animal feet and external environments, with heavy mechanical loading. This is different from scutate-scale-covered metatarsal feet that function as protection. Avian reticulate scales on foot soles display specialized characteristics in development. They do not have a placode stage and lack β-keratin expression. Here, we explore the molecular and cellular characteristics of avian reticulate scales. RNAscope analysis reveals different molecular profiles during surface and hinge determination compared with scutate scales. Furthermore, reticulate scales express Keratin 15 (K15) sporadically in both surface- and hinge-region basal layer cells, and LRCs are not localized. Upon wounding, the reticulate scale region undergoes repair but does not regenerate. Our results suggest that successful skin appendage regeneration requires localized stem cell niches to guide regeneration.

Abstract Objective Palladin is a ubiquitous phosphoprotein expressed in vertebrate cells that works as a scaffolding protein. Several isoforms deriving from alternative splicing are originated from the palladin gene and involved in mesenchymal and muscle cells formation, maturation, migration, and contraction. Recent studies have linked palladin to the invasive spread of cancer and myogenesis. However, since its discovery, the promoter region of the palladin gene has never been studied. The objective of this study was to predict, identify, and measure the activity of the promoter regions of palladin gene. Results By using promoter prediction programs, we successfully identified the transcription start sites for the Palld isoforms and revealed the presence of a variety of transcriptional regulatory elements including TATA box, GATA, MyoD, myogenin, MEF, Nkx2-5, and Tcf3 upstream promoter regions. The transcriptome profiling approach confirmed the active role of predicted transcription factors in the mouse genome. This study complements the missing piece in the characterization of palladin gene and certainly contributes to understanding the complexity and enrollment of palladin regulatory factors in gene transcription.

This study employs fMRI to examine the neural substrates of response to cognitive training in healthy old adults. Twenty Japanese healthy elders participated in a 4-week program and practiced a verbal articulation task on a daily basis. Functional connectivity analysis revealed that in comparison to age- and education-matched controls, elders who received the cognitive training demonstrated increased connectivity in the frontotemporal regions related with language and memory functions and showed significant correlations between the behavioral change in a linguistic task and connectivity in regions for goal-oriented persistence and lexical processing. The increased hippocampal connectivity was consistent with previous research showing efficacious memory improvement and change in hippocampal functioning. Moreover, the increased intra-network connectivity following cognitive training suggested an improved neural differentiation, in contrast to the inter-network activation pattern typical in the aging brain. This research not only validates the relationship of functional change in the frontal and temporal lobes to age-associated cognitive decline but also shows promise in turning neural change toward the right direction by cognitive training.

Fraser’s dolphins (Lagenodelphis hosei) possess great healing abilities. Their skin composition can be restored after wounding, including collagen spacing, orientation, and bundle thickness. However, it remains unclear how collagens are involved in the wound-healing process and eventually regain normality in Fraser’s dolphins. Learned from the other two scarless healing animals, changes in type III/I collagen composition are believed to modulate the wound healing process and influence the scarring or scarless fate determination in human fetal skin and spiny mouse skin. In the current study, Herovici’s, trichrome, and immunofluorescence staining were used on normal and wounded skin samples in Fraser’s dolphins. The results suggested that type I collagens were the main type of collagens in the normal skin of Fraser’s dolphins, while type III collagens were barely seen. During the wound healing process, type III collagens showed at early wound healing stages, and type I collagen increased in the mature healed wound. In an early healed wound, collagens were organized in a parallel manner, showing a transient hypertrophic-like scar, and eventually restored to normal collagen configuration and adipocyte distribution in the mature healed wound. The remarkable ability to remove excessive collagens merits further investigation to provide new insights into clinical wound management.

Wearable cuffless photoplethysmographic blood pressure monitors have garnered widespread attention in recent years; however, the long-term performance values of these devices are questionable. Most cuffless blood pressure monitors require initial baseline calibration and regular recalibrations with a cuffed blood pressure monitor to ensure accurate blood pressure estimation, and their estimation accuracy may vary over time if left uncalibrated. Therefore, this study assessed the accuracy and long-term performance of an upper-arm, cuffless photoplethysmographic blood pressure monitor according to the ISO 81060-2 standard. This device was based on a nonlinear machine-learning model architecture with a fine-tuning optimized method. The blood pressure measurement protocol followed a validation procedure according to the standard, with an additional four weekly blood pressure measurements over a 1-month period, to assess the long-term performance values of the upper-arm, cuffless photoplethysmographic blood pressure monitor. The results showed that the photoplethysmographic signals obtained from the upper arm had better qualities when compared with those measured from the wrist. When compared with the cuffed blood pressure monitor, the means ± standard deviations of the difference in BP at week 1 (baseline) were −1.36 ± 7.24 and −2.11 ± 5.71 mmHg for systolic and diastolic blood pressure, respectively, which met the first criterion of ≤5 ± ≤8.0 mmHg and met the second criterion of a systolic blood pressure ≤ 6.89 mmHg and a diastolic blood pressure ≤ 6.84 mmHg. The differences in the uncalibrated blood pressure values between the test and reference blood pressure monitors measured from week 2 to week 5 remained stable and met both criteria 1 and 2 of the ISO 81060-2 standard. The upper-arm, cuffless photoplethysmographic blood pressure monitor in this study generated high-quality photoplethysmographic signals with satisfactory accuracy at both initial calibration and 1-month follow-ups. This device could be a convenient and practical tool to continuously measure blood pressure over long periods of time.

Language delays are often underestimated in very-low-birth-weight (VLBW) preterm infants. We aimed to identify the risk factors of language delay at two years of corrected age in this vulnerable population. VLBW infants, who were assessed at two years of corrected age using the Bayley Scale of Infant Development, third edition, were included using a population-based cohort database. Language delay was defined as mild to moderate if the composite score was between 70 and 85 and severe if the score was < 70. Multivariable logistic regression analysis was used to identify the perinatal risk factors associated with language delay. The study comprised 3797 VLBW preterm infants; 678 (18%) had a mild to moderate delay and 235 (6%) had a severe delay. After adjusting for confounding factors, low maternal education level, low maternal socioeconomic status, extremely low birth weight, male sex, and severe intraventricular hemorrhage (IVH) and/or cystic periventricular leukomalacia (PVL) were found to be significantly associated with both mild to moderate and severe delays. Resuscitation at delivery, necrotizing enterocolitis, and patent ductus arteriosus requiring ligation showed significant associations with severe delay. The strongest factors predicting both mild to moderate and severe language delays were the male sex and severe IVH and/or cystic PVL; thus, early targeted intervention is warranted in these populations.

Objectives The primary aim is to provide a summary of evidence for the diagnostic accuracies of multiplex PCR gastrointestinal (GI) panels—BioFire FilmArray and Luminex xTAG on the detection of gastroenteritis pathogens. The secondary aim is to compare the performance of these GI panels head to head.Methods A comprehensive search up to 1 December 2019 was conducted on PubMed, Embase, Ovid Medline and Web of Science for studies that used FilmArray or Luminex xTAG Gastrointestinal Pathogen Panel (GPP) for diagnosis of acute gastroenteritis. A summary of diagnostic accuracies for the 16 pathogens were calculated by comparing the GI panels to the current gold standards (conventional standard microbiology techniques such as culture or PCR for bacteria, PCR or enzyme immunoassay (EIA) for viruses, microscopy or EIA for parasite). Hierarchical summary receiver operating characteristic (HSROC) curve analysis, pretest and post-test probabilities were used for estimating the pathogen detection performance.Results A total of 11 studies with 7085 stool samples were eligible for analysis. Multiplex PCRs demonstrated high diagnostic accuracy, with specificity ≧0.98 and area under the ROC curve (AUROC) ≧0.97 for all the pathogens except for Yersinia enterocolitica (AUROC 0.91). The FilmArray panel demonstrated a higher sensitivity than xTAG GPP for most of the pathogens with the exception of Rotavirus A (xTAG GPP and FilmArray were both 0.93).Conclusions This is the first meta-analysis that is a head-to-head comparison examining the performance of the novel multiplex PCR-based tests Luminex xTAG GPP and FilmArray GI panel in detecting each pathogen. Point estimates calculated from eligible studies showed that both GI panels are highly accurate and may provide important diagnostic information for early identification of gastroenteritis. In addition, although FilmArray has higher sensitivity and post-test probability than xTAG GPP for most of the pathogens, how this will translate to a clinical setting remains unclear.

Abstract Background Blood-based methods using cell-free DNA (cfDNA) are under development as an alternative to existing screening tests. However, early-stage detection of cancer using tumor-derived cfDNA has proven challenging because of the small proportion of cfDNA derived from tumor tissue in early-stage disease. A machine learning approach to discover signatures in cfDNA, potentially reflective of both tumor and non-tumor contributions, may represent a promising direction for the early detection of cancer. Methods Whole-genome sequencing was performed on cfDNA extracted from plasma samples (N = 546 colorectal cancer and 271 non-cancer controls). Reads aligning to protein-coding gene bodies were extracted, and read counts were normalized. cfDNA tumor fraction was estimated using IchorCNA. Machine learning models were trained using k-fold cross-validation and confounder-based cross-validations to assess generalization performance. Results In a colorectal cancer cohort heavily weighted towards early-stage cancer (80% stage I/II), we achieved a mean AUC of 0.92 (95% CI 0.91–0.93) with a mean sensitivity of 85% (95% CI 83–86%) at 85% specificity. Sensitivity generally increased with tumor stage and increasing tumor fraction. Stratification by age, sequencing batch, and institution demonstrated the impact of these confounders and provided a more accurate assessment of generalization performance. Conclusions A machine learning approach using cfDNA achieved high sensitivity and specificity in a large, predominantly early-stage, colorectal cancer cohort. The possibility of systematic technical and institution-specific biases warrants similar confounder analyses in other studies. Prospective validation of this machine learning method and evaluation of a multi-analyte approach are underway.

Purpose: To assess the predictive validity of the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) cognitive scores at 6 months of corrected age (CA) for cognitive outcomes at 24 months of CA in very-low-birth-weight (VLBW) infants and investigate the predictors of change in cognitive outcomes.Methods: We retrospectively evaluated VLBW children enrolled in the Taiwan Premature Infant Follow-up Network between 2010 and 2015 and completed the Bayley-III at CA of 6 and 24 months. The predictive validity of the cognitive performance at 6-month CA for the cognitive outcomes at 24-month CA was analyzed. The positive and negative predictive factors were also evaluated using logistic regression. Cut-off scores of

Fraser’s dolphins (Lagenodelphis hosei) exhibit the capability to restore nearly normal pigmentation after full-thickness wounding. However, the association among melanocytes, melanin and skin pigmentation during wound healing in cetaceans has yet to be addressed. Here, the number of melanocytes and the distribution of melanocytes and melanin in different-colored skin and different wound-healing stages in Fraser’s dolphins were analyzed by using Fontana–Masson staining, immunofluorescence staining and immunohistochemical staining. It was noticed that there was the highest number of melanocytes in dark skin and the lowest number of melanocytes in white skin. The appearance of functional melanocytes and full-melanized neoepidermis was observed in the early stage of wound healing in Fraser’s dolphins. Furthermore, the melanocyte number and skin pigmentation and pattern in healed wounds recovered to a similar condition of unwounded skin. This study provides fundamental knowledge of skin repigmentation in cetaceans for further research, and it will be warranted to elucidate the mechanisms of the replenishment of melanocytes and the regulation of melanocyte activity that contribute to the successful repigmentation in cetacean skin wounds.

We designed an English as a foreign language (EFL) learning activity supported by smart watches to combine EFL learning with physical exercise such as walking around the school community. We tested the feasibility of our approach to facilitate EFL learning and make it healthy and enjoyable through single subject experimental design. In addition, we researched the affordances of smart watches for EFL learning and healthy and enjoyable living. We collected the following data: (1) student learning outcomes evaluations, (2) a questionnaire survey, and (3) interviews with the students. According to our results, the students performed the best on learning tasks when they used smart watches. The students perceived that smart watches were easy to use and useful for EFL learning. They also perceived that the learning activity supported by smart watches was useful for their health and positive emotions. The students mentioned several features of smart watches that were useful for EFL learning, physical activity, and positive emotions. For example, the dictionary in smart watches helped the students translate unfamiliar vocabulary, and the fitness tracking tool helped track and record the number of steps taken. The students were happy to learn EFL and to monitor their physical activity progress using smart watches. Furthermore, a significant correlation between learning performance and physical activity was revealed, suggesting that the students who did more physical exercise are those who demonstrate better learning performance. On the other hand, no correlation between learning performance and student perceptions and between physical activity and student perceptions was found, suggesting that most students, no matter how well they performed and exercised, had positive perceptions. Based on our results, we suggest designing learning activities combined with physical exercise supported by smart watches to facilitate EFL learning, physical activity, and positive emotions.

Cetaceans are tight-skinned mammals that exhibit an extraordinary capacity to heal deep soft tissue injuries. However, essential information of large full-thickness wound healing in cetaceans is still lacking. Here, the stages of full-thickness wound healing were characterized in Fraser’s dolphins (Lagenodelphis hosei). The skin samples were collected from normal skin and full-thickness cookiecutter shark (Isistius brasiliensis)-bite wounds of stranded carcasses. We defined five stages of wound healing according to macroscopic and histopathological examinations. Wounds in Stage 1 and 2 were characterized by intercellular and intracellular edema in the epidermal cells near the wound edge, mixed inflammatory cell infiltration, and degradation of collagen fibers. In Stage 3 wounds, melanocytes, melanin granules, rete and dermal ridges were noticed in the neo-epidermis, and the adipose tissue in adjacent blubber was replaced by cells and fibers. Wounds in Stage 4 and 5 were characterized by gradual restoration of the normal skin architecture including rete and dermal ridges, collagen bundles, and adipose tissue. These phenomena were quite different from previous studies in terrestrial tight-skinned mammals, and therefore, further in-depth research into the mechanisms of dolphin wound healing would be needed to gain new insights into veterinary and human regenerative medicine.

This study investigated cecal bacterial community profile, cecal and serum metabolites, and its biosynthesis pathway in late-phase laying hens during 6 weeks feeding restriction (FR), using 16S rDNA as gene sequencing and non-targeted LC-MS/MS as metabolomics approach. We used three groups (ad libitum, FR20, and FR40). FR can reduce excessive fat in late-phase laying hens, while egg production rate is not affected, except for the FR40 group. In phylum level, FR20 had more population of Bacteriodetes and Firmicutes amongst groups. The same result is at genus level, FR20 were higher of the predominant genus (Bacteroides and Rikenellaceae_RC9_gut_group). Both of FR20 and FR40 reduced Proteobacteria as potential pathogenic bacteria. Non-targeted metabolomic analysis revealed that FR20 modified 20 metabolites in cecal and 10 metabolites in serum of laying hens, whereas 48 cecal metabolites and 31 serum metabolites has revealed in FR40. KEGG assay showed FR20 and FR40 upregulated lipid, carbohydrate, amino acid, nucleic acid pathway, and FR40 modified steroid metabolism in cecal analysis. In serum, only FR40 modified lipid, amino acid pathway, and carbohydrate biosynthesis were shown. This study showed that FR during late-phase laying hens altered the microbiome composition, modified metabolites profile and biosynthesis of the cecal as well as serum.

BACKGROUND:The present study aimed to develop a new scale to evaluate the level of difficulty in treating major depressive disorder with antidepressants based on the lifetime treatment profile. METHODS:In addition to evaluating the difficulty of treatment with antidepressants (A subscale), the Treatment Resistance to Antidepressants Evaluation Scale (TRADES) is comprised of a subscale to account for the attributes that compromise the efficacy of treatment (B subscale). One hundred and six participants aged 18 to 65 years with remitted major depressive disorder were enrolled. Eligible cases were those with at least 2 years from disease onset until the scoring date of the TRADES (the index date), with a complete treatment record. Various psychosocial and clinical features, such as neuroticism, harm avoidance, and utilization of psychiatric services, were used to validate the TRADES. RESULTS:The mean duration of the course before and after the index date were 5.5 ± 3.5 and 3.1 ± 1.7 years, respectively. In a multiple regression analysis, the final total scores of the TRADES independently correlated with higher levels of neuroticism and harm avoidance. Total scores were also associated with a higher utilization of psychiatric outpatient and admission services before the index date. Furthermore, it is thought that total scores could predict a higher number of visits to psychiatric outpatient, emergency, and admission services following the index date. CONCLUSIONS:The TRADES has acceptable validity and could help to quantify the level of treatment difficulty with antidepressants in major depressive disorder.

Alternative growth promoters are able to not only effectively replace the traditional use of antibiotics but also provide additional health benefits for livestock and reduce food safety concerns. This study investigated the effects of dry Hydrastis canadensis on the laying performance and fecal microbial community of laying hens. Twenty-four Lohmann (LSL, white layer strain) hens were reared from 40 to 48 weeks of age and randomly allotted to four dietary treatments (six birds/treatment). The dietary treatments comprised a basal diet with no treatment as control, a basal diet plus 0.6% powder of dry Hydrastis canadensis roots (R) or leaves (L), and a basal diet plus 0.6% powder of a mixture of dry Hydrastis canadensis roots and leaves (1:1, LR). No mortality was observed in the whole experimental period. The results indicated that albumen height in the LR group was significantly greater than that in the control group. The diet supplemented with Hydrastis canadensis had no significant effects on egg production rate, egg weight, eggshell strength, eggshell thickness, Haugh unit, or yolk height during the whole experimental phase. However, principal coordinate analysis, comparative heat map analysis, and cluster dendrogram analysis of cecal microbiota showed distinct clusters among the groups treated with Hydrastis canadensis and the control group. Regarding blood biochemical parameters, serum cholesterol levels were significantly lower in all Hydrastis canadensis-treated groups compared with those in the control group. Moreover, serum low-density lipoprotein levels were lower in hens supplemented with the leaf of Hydrastis canadensis. The abundances of the phyla Fusobacteria and Kiritimatiellaeota were increased (p < 0.05) in laying hens fed with 0.6% Hydrastis canadensis leaves, whereas the abundance of the phylum Firmicutes in cecum digesta decreased in response to treatment with Hydrastis canadensis roots and leaves. The relative abundance of the Fusobacterium genus was higher in the LR group compared with that in the control. On the contrary, we found a different trend in the Synergistes genus. The potential influences of these microbiota on the performance of laying hens were discussed. The results demonstrate that Hydrastis canadensis can improve the egg albumen height and modulate the cecum digesta microbiota composition of laying hens.

In this study, the effects of a nocturnal light pulse on body weight, organ mass, gonadal function, and plasma levels of metabolites were determined in male mule ducks. In total, 32 15-week-old mule ducks were randomly allocated to either Group C (control group) or L+ (lighting group). Group C was exposed to the natural photoperiod, whereas Group L+ was provided with a 1-h lighting over 20:00–21:00 every day, in addition to the natural photoperiod. At the end of the 42-day experiment, Group L+ had significantly lower relative weights (% of live weight) of the digestive tract and abdominal fat and higher relative weights of the breast meat and testes than Group C. Moreover, Group L+ had significantly higher plasma testosterone and lower plasma glucose levels. However, no between-group differences were observed in the triacylglycerol and uric acid levels. Histological examination demonstrated that the seminiferous tubule diameter was larger in Group L+ than in Group C. Moreover, the meiosis stage in spermatogenesis had begun in Group L+ but not in Group C. In conclusion, the supplemented 1-h lighting at 20:00 stimulated gonadal development and function and reduced fat deposition.

Peptide-based vaccines have been proposed as a therapeutic strategy for many infectious diseases, including human papilloma virus (HPV)-related cervical cancer. Peptide-based vaccines are a better treatment option than traditional chemotherapeutic agents and surgery, as they rely on the use of the body’s immune system to fight cancer cells, resulting in minimal risk of side effects. However, to increase the efficacy of peptide-based vaccines, the application of potent adjuvant and a suitable delivery system is essential. In this study, we developed a self-adjuvanting delivery system based on a combination of polymer and liposomes, for a therapeutic vaccine against cervical cancer. Peptide epitope (8Qm) derived from HPV-16 E7 protein was conjugated to dendritic poly(tert-butyl acrylate) as a primary delivery system and incorporated into cationic liposomes, which served as a secondary delivery system. Our vaccine candidate was able to kill established HPV-16 E7-positive tumor (TC-1) cells in mice following a single immunization. The immunized mice had 80% survival rate after two months. In contrast, both polymer-8Qm conjugate and liposomes bearing 8Qm failed to eradicate TC-1 tumors. The survival rate of mice was only 20% when immunized with 8Qm formulated with standard incomplete Freund’s adjuvant. [READ ARTICLE](https://precisionnanomedicine.com/article/6492)

Different from the predominantly white Merlins on both big and small screens today, Merlins in medieval legends are never described as having white skin. In fact, in various texts Merlin is specifically depicted as a dark-skinned character capable of making legendary accomplishments. The few Merlins of color onscreen have informed our understanding of Merlin as a legendary character in various ways, and more diverse representations of Merlin onscreen could help to dispel the misconception that the legendary Merlin is by default white. [ABSTRACT FROM AUTHOR]

Es bien sabido que nuestra forma de hablar y el uso del lenguaje están estrechamente relacionados con el factor sociocultural. El objetivo principal de este artículo es hacer una comparación de las fórmulas de disculpa más usadas en español y en chino, desde la perspectiva cultural y pragmática. Con ello esclarecemos la influencia sociocultural en la realización del acto de habla de disculpa en español peninsular y el chino de Taiwán. Analizamos las expresiones de disculpa desde el punto de vista de su contexto y de la cortesía, ya que estas fórmulas tienen diferentes funciones en ambos ámbitos. Además comparamos las semejanzas y diferencias de su uso para ilustrar los rasgos específicos de cada sociedad. De este modo, comprobamos que para comunicarnos con interlocutores de diferente cultura, siempre hay que tomar en consideración el factor sociocultural.