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Background: There is a corresponding increase in the prevalence of osteoporosis and related fractures with the aging population on the rise. Furthermore, osteoporotic vertebral compression fractures (OVCF) may contribute to higher patient mortality rates. It is essential to conduct research on risk factors for OVCF and provide a theoretical basis for preventing such fractures., Methods: We retrospectively recruited patients who had spine CT for OVCF or back pain. Demographic and CT data were collected. Quantitative computed tomography (QCT) software analyzed the CT data, using subcutaneous fat and paraspinal muscles as reference standards for BMD processing. BMD of cortical and cancellous bones in each patient's vertebral body was determined., Results: In this study, 144 patients were divided into non-OVCF (96) and OVCF (48) groups. Non-OVCF patients had higher cortical BMD of 382.5 ± 52.4 to 444.6 ± 70.1 mg/cm 3 , with T12 having the lowest BMD (p < 0.001, T12 vs. L2). Cancellous BMD ranged from 128.5 ± 58.4 to 140.9 ± 58.9 mg/cm 3 , with L3 having the lowest BMD. OVCF patients had lower cortical BMD of 365.0 ± 78.9 to 429.3 ± 156.7 mg/cm 3 , with a further decrease in T12 BMD. Cancellous BMD ranged from 71.68 ± 52.07 to 123.9 ± 126.2 mg/cm 3 , with L3 still having the lowest BMD. Fractured vertebrae in OVCF patients (T12, L1, and L2) had lower cortical bone density compared to their corresponding vertebrae without fractures (p < 0.05)., Conclusions: T12 had the lowest cortical BMD and L3 had the lowest cancellous BMD in OVCF patients, with T12 also having the highest incidence of osteoporotic fractures. These findings suggest that reduction in cortical BMD has a greater impact on OVCF than reduction in cancellous BMD, along with biomechanical factors., (© 2024. The Author(s).)

Pulsed electromagnetic field (PEMF) therapy has been extensively investigated in clinical studies for the treatment of angiogenesis-related diseases. However, there is a lack of research on the impact of PEMFs on energy metabolism and mitochondrial dynamics during angiogenesis. The present study included tube formation and CCK-8 assays. A Seahorse assay was conducted to analyze energy metabolism, and mitochondrial membrane potential assays, mitochondrial imaging, and reactive oxygen species assays were used to measure changes in mitochondrial structure and function in human umbilical vein endothelial cells (HUVECs) exposed to PEMFs. Real-time polymerase chain reaction was used to analyze the mRNA expression levels of antioxidants, glycolytic pathway-related genes, and genes associated with mitochondrial fission and fusion. The tube formation assay demonstrated a significantly greater tube network in the PEMF group compared to the control group. The glycolysis and mitochondrial stress tests revealed that PEMFs promoted a shift in the energy metabolism pattern of HUVECs from oxidative phosphorylation to aerobic glycolysis. Mitochondrial imaging revealed a wire-like mitochondrial morphology in the control group, and treatment with PEMFs led to shorter and more granular mitochondria. Our major findings indicate that exposure to PEMFs accelerates angiogenesis in HUVECs, likely by inducing energy metabolism reprogramming and mitochondrial fission., (© 2024. The Author(s).)

Aberrant activity of NLRP3 has been shown associations with severe diseases. Palmitoylation is a kind of protein post-translational modification, which has been shown to regulate cancer development and the innate immune system. Here, we showed that NLRP3 is palmitoylated at Cys419 and that palmitoyltransferase ZDHHC17 is the predominant enzyme that mediates NLRP3 palmitoylation and promotes NLRP3 activation by interacting with NLRP3 and facilitating NIMA-related kinase 7 (NEK7)-NLRP3 interactions. Blockade of NLRP3 palmitoylation by a palmitoylation inhibitor, 2-bromopalmitate, effectively inhibited NLRP3 activation in vitro. Also, in a dextran sulfate sodium-induced colitis model in mice, 2-bromopalmitate application could attenuate weight loss, improve the survival rate, and rescue pathological changes in the colon of mice. Overall, our study reveals that palmitoylation of NLPR3 modulates inflammasome activation and inflammatory bowel disease development. We propose that drugs targeting NLRP3 palmitoylation could be promising candidates in the treatment of NLRP3-mediated inflammatory diseases., (Copyright © 2024 by The American Association of Immunologists, Inc.)

Endogenous hydrogen sulfide (H 2 S) plays an important role in bone metabolism. However, the exact role of H 2 S in intestinal calcium and phosphorus absorption and its potential in preventing and treating primary osteoporosis remains unknown. Therefore, this study aimed to investigate the potential of H 2 S in promoting intestinal calcium and phosphorus absorption and alleviating primary osteoporosis. We measured the apparent absorptivity of calcium, femoral bone density, expression and sulfhydration of the duodenal endoplasmic reticulum protein of 57 kDa (ERp57), duodenal cystathionine γ-lyase (CSE) expression, and serum H 2 S content in adult and old CSE-knockout and wild-type mice. We also assessed intracellular reactive oxygen species (ROS) and Ca 2+ content in CSE-overexpressing or knockout intestinal epithelial cell (IEC)-6 cells. In senile mice, CSE knockout decreased endogenous H 2 S, ERp57 sulfhydration, and intestinal calcium absorption and worsened osteoporosis, which were partially reversed by GYY4137, an H 2 S donor. CSE overexpression in IEC-6 cells increased ERp57 sulfhydration, protein kinase A and C activity, and intracellular Ca 2+ , whereas CSE knockout exerted the opposite effects. Furthermore, hydrogen peroxide (H 2 O 2 ) stimulation had similar effects as in CSE knockout, which were reversed by pretreatment with sodium hydrosulfide before H 2 O 2 stimulation and restored by DL-dithiothreitol. These findings suggest that H 2 S attenuates primary osteoporosis by preventing ROS-induced ERp57 damage in intestinal epithelial cells by enhancing ERp57 activity and promoting intestinal calcium absorption, thereby aiding in developing therapeutic interventions to prevent osteoporosis., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Flexible surface-enhanced Raman scattering (SERS) substrates are very promising to meet the needs for real-time and on-field detection in practical applications. However, high-performance flexible SERS substrates often suffer from complexity and high cost in fabrication, limiting their widespread applications. Herein, we developed a facile method to fabricate a flexible multicavity SERS substrate composed of a silver nanoparticle (AgNP)-decorated aluminum hydrous oxide nanoflake array (NFA) grown on a polydimethylsiloxane (PDMS) membrane. Strong plasmon couplings promoted by multiple nanocavities afford high-density hotspots within such a flexible AgNPs@NFA/PDMS film, boosting high SERS sensitivity with an enhancement factor (EF) of ∼1.54 × 10 9 , and a limit of detection (LOD) of ∼7.4 × 10 -13 M for rhodamine 6G (R6G) molecules. Furthermore, benefiting from the high sensitivity, high mechanical stability, and transparency of this substrate, in situ SERS detections of trace thiram and crystal violet (CV) molecules on the surface of cherry tomatoes and fish have been realized, with LODs much lower than the maximum allowable limit in food, demonstrating the great potential of such a flexible substrate in food safety monitoring. More importantly, the preparation processes are very simple and environmentally friendly, and the techniques involved are completely compatible with well-established silicon device technologies. Therefore, large-area fabrication with low cost can be readily realized, enabling the extensive applications of SERS sensors in daily life.

Ojective: To understand hypertensive patients' preference for catheter-based therapy to manage hypertension., Methods: Survey data regarding catheter-based therapies performed at MacKay Memorial Hospital in Taipei, Taiwan, between 2019-2020 were analyzed. The questionnaire was circulated either in the clinics or during admission. A total of 46 patients completed the questionnaire., Results: A total of 46 patients (mean age 53.4 ± 13.5 years, 78.3% male) completed the questionnaire. In subgroup analysis according to Taiwan renal denervation (RDN) consensus, patients with drug intolerance (61.8% vs. 31.3%, p = 0.02) were more likely to choose RDN. Moreover, although lacking statistical significance, it is noteworthy that numerically more of the resistant hypertension group (55.6% vs. 28.0%, p = 0.09) and non-adherence group (38.5% vs. 30.0%, p = 0.20) were willing to undergo RDN. Conversely, numerically fewer patients with hypertension-mediated organ damage accepted RDN compared to those who did not have hypertension-mediated organ damage (26.1% vs. 43.5%, p = 0.21), although this disparity did not reach statistical significance., Conclusions: Approximately one-third of the patients expressed interest in considering RDN in this study. The most influential factor in patients' preference for RDN was drug intolerance due to medication-related side effects., Competing Interests: All the authors declare no conflict of interest.

The evaluation of pathobiome strains should be conducted at the strain level, involving the identification of the functional genes, while considering the impact of ecological niche and drug interactions. The safety, efficacy, and quality management of live biotherapeutic products (LBPs), especially pathobiome strains, have certain peculiarities. Promising development methods include the recombinant LBP and active metabolites., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors. iMeta published by John Wiley & Sons Australia, Ltd on behalf of iMeta Science.)

Background: In recent years, simultaneous or sequential occurrence of MOG antibody disease and anti-NMDAR encephalitis in the same patient has been reported with increasing frequency. Scholars refer to the overlapping occurrence of these two disorders as MOG antibody disease and anti-NMDAR encephalitis overlap syndrome (MNOS). Cortical T2-weighted fluid-attenuated inversion recovery (FLAIR) -hyperintense lesions in anti-MOG-associated encephalitis with seizures (FLAMES) is a rare clinical phenotype of MOGAD in which cortical FLAIR high-signal lesions are unilateral, with little spread to the cortex and meninges bilaterally. Although cases of FLAMES have been consistently reported. However, to our knowledge, such cases of FLAMES combined with NMDARE are rare., Case Presentation: Here, we describe a case of FLAMES combined with anti-NMDARE. The patient was a young male, 29 years old, admitted to our hospital with isolated seizures, whose MRI showed unilateral thalamic and bilateral frontal and parietal leptomeningeal involvement. Since we were unaware of the possibility of bilateral meningo-cortical MOGAD manifestations, the case was initially diagnosed as viral encephalitis and was given antiviral therapy. The diagnosis was not clarified until anti-NMDAR-IgG and MOG-IgG positivity was detected in the cerebrospinal fluid and serum. The patient was then treated with high-dose corticosteroids and his symptoms responded well to the steroids. Therefore, this case expands the clinical spectrum of MNOS overlap syndrome. In addition, we describe the clinical features of MNOS by summarizing the existing literature and exploring the possible mechanisms of its immune response., Conclusions: Our case serves as a reminder to clinicians that when patients present with atypical clinical manifestations such as seizures, consideration should be given to MNOS and conduct testing for various relevant autoantibodies (including MOG abs) and viruses in both serum and cerebrospinal fluid, as it is easy to misdiagnose the disease as other CNS diseases, such as viral meningoencephalitis. This syndrome exhibits a high responsiveness to steroids, highlighting the critical importance of recognizing the clinical and neuroimaging features of this overlap syndrome for prompt diagnosis and treatment. Furthermore, it enriches the disease spectrum of MNOS., (© 2024. The Author(s).)

Covalent Organic Frameworks (COFs) demonstrate promising potential in the photocatalytic synthesis of H 2 O 2 owing to favorable light absorption, superior charge separation, and considerable surface area. However, the efficiency of H 2 O 2 photosynthesis is impeded by insufficient O 2 adsorption sites and a high reaction barrier. In this work, various metal single atoms (Fe, Co, Ni) are introduced onto covalent triazine frameworks (CTFs) with N-N coordination sites to significantly enhance O 2 adsorption and optimize H 2 O 2 synthesis. Computational findings suggest that the presence of Fe, Co, and Ni not only enhances O 2 adsorption but also exerts an influence on the reaction pathway of H 2 O 2 . Significantly, Fe exhibits a distinct advantage in modulating O 2 adsorption through its unique electron spin state when compared to Co and Ni, as confirmed by crystal orbital Hamilton population (COHP) analysis. Additionally, this integration of metal atoms also improves light absorption and charge separation in CTFs. The study provides strategic insight into elevating H 2 O 2 production by incorporating tailored metal single atoms into COFs.

Background: Shotgun metagenomic and 16S rDNA sequencing are commonly used methods to identify the taxonomic composition of microbial communities. Previously, we analysed the gut microbiota and intestinal pathogenic bacteria configuration of migratory seagulls by using 16S rDNA sequencing and culture methods., Methods: To continue in-depth research on the gut microbiome and reveal the applicability of the two methods, we compared the metagenome and 16S rDNA amplicon results to further demonstrate the features of this animal., Results: The number of bacterial species detected by metagenomics gradually increased from the phylum to species level, consistent with 16S rDNA sequencing. Several taxa were commonly shared by both sequencing methods. However, Escherichia , Shigella , Erwinia , Klebsiella , Salmonella , Escherichia albertii , Shigella sonnei , Salmonella enterica , and Shigella flexneri were unique taxa for the metagenome compared with Escherichia-Shigella , Hafnia-Obesumbacterium , Catellicoccus marimammalium , Lactococcus garvieae , and Streptococcus gallolyticus for 16S rDNA sequencing. The largest differences in relative abundance between the two methods were identified at the species level, which identified many pathogenic bacteria to humans using metagenomic sequencing. Pearson correlation analysis indicated that the correlation coefficient for the two methods gradually decreased with the refinement of the taxonomic levels. The high consistency of the correlation coefficient was identified at the genus level for the beta diversity of the two methods., Conclusions: In general, relatively consistent patterns and reliability could be identified by both sequencing methods, but the results varied following the refinement of taxonomic levels. Metagenomic sequencing was more suitable for the discovery and detection of pathogenic bacteria of gut microbiota in seagulls. Although there were large differences in the numbers and abundance of bacterial species of the two methods in terms of taxonomic levels, the patterns and reliability results of the samples were consistent., Competing Interests: The authors declare that they have no competing interests., (© 2023 Liao et al.)

Background: The current ISO guidelines for minimal erythema dose (MED) determination require assessment of erythema area of UV-irradiated skin sites. However, this parameter has not been adequately quantified in daily practice. The aims of this study were to investigate the dose response on the unprotected skin sites by quantifying the erythema area and intensity and to show the potential for improving the precision and consistency of MEDu determination by developing predictive models., Methods: Standard radiation tests were conducted on the back of 31 healthy Chinese volunteers and the MEDu site of each subject was clinically determined by dermatologists. Images of test sites were captured 24 h after radiation, and the erythema area (%EA) and intensity (∆a*) were measured by image analysis. The data were fitted to a logistic 3P function to obtain dose-response curves, and a set of logit (inverse-logistic) models were then derived. An erythema area threshold of %EA = 52% was established to predict MEDu based on the clinical endpoints defined by ISO 24444:2019., Results: Analysis of the clinically determined MEDu sites revealed wide ranges of %EA (62.3 ± 15% SD) and ∆a* (2.96 ± 0.92 SD). The dose response fitted well to a logistic 3P model (mean R 2  = 0.965 and 0.975 for %EA and ∆a*, respectively). Applying the area threshold, values of MEDu were determined by the logit model for the test population, which significantly improved the consistency of MEDu determination (52 ± 0% SD and 2.73 ± 0.61 SD for %EA and ∆a*, respectively)., Conclusion: This study demonstrated that the dose response of UV-induced erythema can be quantified and modeled once the erythema area and intensity are measured. The results of this study show the potential to improve the precision and consistency of MEDu determination in an SPF test. The similar potential in photodermatological, therapeutic, and diagnostic applications was also implied., (© 2023 John Wiley & Sons Ltd.)

The m 6 A is one of the most abundant and widespread modifications in eukaryotic mRNAs, which regulates gene expression at the post-transcriptional level and plays key roles in many physiological processes. The YT521-B homologous (YTH) domain-containing proteins act as m 6 A readers to regulate m 6 A-RNA metabolism processes and mediate the various functions of m 6 A modification. Previously, we reported tomato contains 9 YTH genes, among which SlYTH2 is relatively highly expressed. This study reports the physiological functions of SlYTH2 in tomato. SlYTH2 protein is distributed in the nucleus and cytoplasm, and its three-dimensional structure is highly similar to human HsYTHDF1. SlYTH2 knockout through Crispr/Cas9 gene editing technology leaded to pleiotropic phenotypes, including dwarfing plant, delayed fruit internal ripening process, and increased seed abortion rate. The deletion of SlYTH2 gene increased the accumulation of endogenous ABA, decreased the content of endogenous GA 3 , and enhanced the sensitivity of seed germination to exogenous ABA and seedling growth to exogenous GA 3 . RNA-Seq data showed that the expression levels of multiple hormone-related genes were altered in SlYTH2 knockout line. These facts suggested SlYTH2 plays its physiological roles related to ABA, gibberellin and other hormones in tomato., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Edible bird's nest (EBN) mainly made of saliva that secreted by a variety of swiftlets is a kind of precious traditional Chinese medicine. EBNs from different biological and geographical origins exhibit varieties in morphology, material composition, nutritive value and commercial value. Here, we collected four different EBN samples from Huaiji, China (Grass EBN), Nha Trang, Vietnam (Imperial EBN) and East Kalimantan, Indonesia (White EBN and Feather EBN) respectively, and applied label-free quantitative MS-based proteomics technique to identify its protein composition. First, phylogenetic analysis was performed based on cytb gene to identify its biological origin. Second, a total of 37 proteins of EBNs were identified, among which there were six common proteins that detected in all samples and exhibited relatively higher content. Gene ontology analysis revealed the possible function of EBN proteins, and principal component analysis and hierarchical clustering analysis based on 37 proteins were performed to compare the difference of various EBNs. In summary, our study deciphered the common and characteristic protein components of EBNs of different origins and described their possible functions by GO enrichment analysis, which helps to establish an objective and reliable quality evaluation system., (© 2023. Springer Nature Limited.)

Objective: To investigate the relationship between upper airway morphology and the severity of obstructive sleep apnea (OSA) in patients with anatomically small retruded mandibles., Methods: Fifty-two patients with small retruded mandibles underwent polysomnography and airway computed tomography. The airway morphology parameters and sleep assessment were compared between the patients with or without OSA., Results: Twenty-eight patients diagnosed with OSA, according to polysomnography, had a higher distance between the hyoid bone and mandibular plane (HMP), lateral dimension (LAT)/anteroposterior dimension (AP), but lower minimum cross-sectional area (mCSA), AP, surface area, volume, avgCSA, and airway uniformity (U). The apnea-hypopnea index had negative correlations with mCSA, AP, surface area, volume, avgCSA, and U, and had a positive correlation with HMP and LAT/AP., Conclusion: OSA is common among patients with small retruded mandibles and is associated with a more compressed upper airway shape and longer HMP.

Zika virus (ZIKV) infection poses a significant threat to global public health and is associated with microcephaly. There are no approved ZIKV-specific vaccines or drugs for the clinical treatment of the infection. Currently, there are no approved ZIKV-specific vaccines or drugs for the clinical treatment of the infection. In this study, we investigated the antiviral potential of aloperine, a quinolizidine alkaloid, against ZIKV infection in vivo and in vitro. Our results demonstrate that aloperine effectively inhibits ZIKV infection in vitro, with a low nanomolar half maximal effective concentration (EC 50 ). Specifically, aloperine strongly protected cells from ZIKV multiplication, as indicated by decreased expression of viral proteins and virus titer. Our further investigations using the time-of-drug-addition assay, binding, entry, and replication assays, detection of ZIKV strand-specific RNA, the cellular thermal shift assay, and molecular docking revealed that aloperine significantly inhibits the replication stage of the ZIKV life cycle by targeting the domain RNA-dependent RNA polymerase (RDRP) of ZIKV NS5 protein. Additionally, aloperine reduced viremia in mice and effectively lowered the mortality rate in infected mice. These findings highlight the potency of aloperine and its ability to target ZIKV infection, suggesting its potential as a promising antiviral drug against ZIKV., (© 2023 Wiley Periodicals LLC.)

To determine the optimal position of three cannulated screws in an inverted triangle pattern for internal fixation of femoral neck fractures, including the apex-subchondral bone distance, computed tomography (CT) images of the hip were processed using the MIMICS (Materialize Interactive Medical Image Control System) Research software. Points adjacent to the inferior, anterosuperior, and posterior cortex of the femoral neck were selected on the axial view. Subsequently, the positions of these points were adjusted to maximize the area between them, and splines were drawn in the coronal and sagittal planes to represent the cannulated screws. Finally, the virtual anteroposterior and lateral fluoroscopy images of the proximal femur and splines were created and the parameters calculated. Finite element analysis showed this fixation scheme provides stronger fracture support and stability. Twenty patients with femoral neck fractures (Modified group), with the area and perimeter of the triangle formed on axial postoperative CT images, including the shortest distance from the tip of the screw to the subchondral bone was compared with 23 matched patients for whom the conventional inverted isosceles triangle configuration of screws for internal fixation was used (Conventional group). The area and perimeter of the stabilization screws were larger, with a shorter apex-subchondral bone distance for the Modified group. There was no incidence of screw penetration in the femoral neck or head in either group, and all fractures healed within a follow-up period of 10 months. The modified screw placement method is simple and safe and provides greater fracture stability than the conventional empirical method of fixation., (© 2022 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Background: Neonatal nurses' working environments are highly stressful, and burnout is common. This study examines the effect of socioeconomic factors, perceived stress, and social support on neonatal nurse burnout., Methods: A total of 311 neonatal nurses participated in this study. They were administered a validated Maslach Burnout Inventory. The study employed a 14-item perceived stress scale (PSS-14) and a social support rate scale (SSRS) to examine stress, socioeconomic factors, and lifestyles., Results: Of the neonatal nurses, 40.19% had burnout, 89.60% had mild burnout, and 10.40% had moderate burnout; no neonatal nurse experienced severe burnout. Young nurses and those with low technical skills, poor interpersonal relationships, irregular diet, and insufficient rest were exposed to burnout (all p < 0.05).Most burnout nurses experienced moderate-severe perceived stress, and their PSS-14 scores were higher (all p < 0.05).The scores for objective social support, subjective social support, utilization of social support, total SSRS scores, and the level of social support were all lower in burnout nurses (all p < 0.05). Perceived stress was correlated positively and significantly with emotional exhaustion and personal accomplishment (all p < 0.05). Social support correlated significantly with and reduced personal accomplishments (p < 0.05). Age, poor interpersonal relationships, perceived stress, and social support were all independent factors associated with neonatal nurse burnout (all p < 0.05)., Conclusion: The prevalence of burnout in neonatal nurses was higher than average. Socioeconomic factors, higher perceived stress, and lower social support contribute to neonatal nurse burnout. Nursing managers should pay attention to socioeconomic factors, perceived stress, and social support among neonatal nurses and employ strategies to reduce neonatal nurse burnout., (© 2023. The Author(s).)

Purpose: To compare the merits and demerits of percutaneous robot-assisted screw fixation for nondisplaced pelvic fractures with other treatments via long-term follow-up., Methods: This was a retrospective analysis of nondisplaced pelvic fractures treated between January 2015 and December 2021. The number of fluoroscopy exposures, operative duration, intraoperative blood loss, surgical complications, screw placement accuracy and Majeed score were compared among the nonoperative group (24 cases), open reduction and internal fixation (ORIF) group (45 cases), free-hand empirical screw fixation (FH) group (10 cases) and robot-assisted screw fixation (RA) group (40 cases)., Results: There was less intraoperative blood loss in the RA and FH groups than in the ORIF group. The number of fluoroscopy exposures in the RA group was lower than that in the FH group but much higher than that in the ORIF group. There were five cases of wound infection in the ORIF group and no surgical complications in the FH or RA group. The medical expenses were higher in the RA group than in the FH group, with no significant difference from the ORIF group. The Majeed score was lowest in the nonoperative group three months after injury (64.5±12.0) but lowest in the ORIF group one year after injury (88.6±4.1)., Conclusion: Percutaneous RA for nondisplaced pelvic fractures is effective and minimally invasive and does not increase medical expenses compared with ORIF. Therefore, it is the best choice for patients with nondisplaced pelvic fractures., (© 2023. The Author(s).)

Background: Seagull as a migratory wild bird has become most popular species in southwest China since 1980s. Previously, we analyzed the gut microbiota and intestinal pathogenic bacteria configuration for this species by using 16S rRNA sequencing and culture methods. To continue in-depth research on the gut microbiome of migratory seagulls, the metagenomics, DNA virome and RNA virome were both investigated for their gut microbial communities of abundance and diversity in this study., Results: The metagenomics results showed 99.72% of total species was bacteria, followed by viruses, fungi, archaea and eukaryota. In particular, Shigella sonnei, Escherichia albertii, Klebsiella pneumonia, Salmonella enterica and Shigella flexneri were the top distributed taxa at species level. PCoA, NMDS, and statistics indicated some drug resistant genes, such as adeL, evgS, tetA, PmrF, and evgA accumulated as time went by from November to January of the next year, and most of these genes were antibiotic efflux. DNA virome composition demonstrated that Caudovirales was the most abundance virus, followed by Cirlivirales, Geplafuvirales, Petitvirales and Piccovirales. Most of these phages corresponded to Enterobacteriaceae and Campylobacteriaceae bacterial hosts respectively. Caliciviridae, Coronaviridae and Picornaviridae were the top distributed RNA virome at family level of this migratory animal. Phylogenetic analysis indicated the sequences of contigs of Gammacoronavirus and Deltacoronavirus had highly similarity with some coronavirus references., Conclusions: In general, the characteristics of gut microbiome of migratory seagulls were closely related to human activities, and multiomics still revealed the potential public risk to human health., (© 2023. The Author(s).)

Introduction: Dairy products have long been regarded as a controversial nutrient for the skin. However, a clear demonstration of donkey milk (DM) on skincare is required., Methods: In this study, spectrum and chemical component analyses were applied to DM. Then, the effects of DM on UVB-induced skin barrier damage and melanin pigmentation were first evaluated in vitro and in vivo . Cell survival, animal models, and expression of filaggrin (FLG) were determined to confirm the effect of DM on UVB-induced skin barrier damage. Melanogenesis and tyrosinase (TYR) activity were assessed after UVB irradiation to clarify the effect of DM on whitening activities. Further, a network pharmacology method was applied to study the interaction between DM ingredients and UVB-induced skin injury. Meanwhile, an analysis of the melanogenesis molecular target network was developed and validated to predict the melanogenesis regulators in DM., Results: DM was rich in cholesterols, fatty acids, vitamins and amino acids. The results of evaluation of whitening activities in vitro and in vivo indicated that DM had a potent inhibitory effect on melanin synthesis. The results of effects of DM on UVB‑induced skin barrier damage indicated that DM inhibited UVB-induced injury and restored skin barrier function via up-regulation expression of FLG (filaggrin). The pharmacological network of DM showed that DM regulated steroid biosynthesis and fatty acid metabolism in keratinocytes and 64 melanin targets which the main contributing role of DM might target melanogenesis, cell adhesion molecules (CAMs), and Tumor necrosis factor (TNF) pathway., Discussion: These results highlight the potential use of DM as a promising agent for whitening and anti-photoaging applications., Competing Interests: FL and YF were employed by Dong-E-E-Jiao Co. Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer RD declared a shared affiliation with the authors LX, AL, HH, YC, JT, and LL to the handling editor at the time of review., (Copyright © 2023 Li, He, Chen, Liao, Tang, Li, Fan, Li, and Xiong.)

Zika virus (ZIKV) is an RNA-enveloped virus that belongs to the Flavivirus genus , and ZIKV infections potentially induce severe neurodegenerative diseases and impair male fertility. Palmitoylation is an important post-translational modification of proteins that is mediated by a series of DHHC-palmitoyl transferases, which are implicated in various biological processes and viral infections. However, it remains to be investigated whether palmitoylation regulates ZIKV infections. In this study, we initially observed that the inhibition of palmitoylation by 2-bromopalmitate (2-BP) enhanced ZIKV infections, and determined that the envelope protein of ZIKV is palmitoylated at Cys308. ZDHHC11 was identified as the predominant enzyme that interacts with the ZIKV envelope protein and catalyzes its palmitoylation. Notably, ZDHHC11 suppressed ZIKV infections in an enzymatic activity-dependent manner and ZDHHC11 knockdown promoted ZIKV infection. In conclusion, we proposed that the envelope protein of ZIKV undergoes a novel post-translational modification and identified a distinct mechanism in which ZDHHC11 suppresses ZIKV infections via palmitoylation of the ZIKV envelope protein.

Background: Current guidelines recommend that all infected cardiac implantable electronic devices (CIEDs) should be removed. However, financial or anatomical concerns can lead to management of infection with simple debridement, as opposed to complete removal. In this observational study, we report the outcomes of our modified procedure for this real-world dilemma., Methods and Results: The Quarantine (RESQ) method is characterized as follows: the removal (R) of all non-essential foreign materials, including old sutures and leads; the excision (E) of all non-viable, chronically inflamed, granulation, or scar tissue; the sterilization (S) of the remaining generator; and the quarantine (Q) of a new pocket in the sub-muscular layer for reimplantation. From a review of electronic medical records, 30 patients were selected and divided into three groups according to the intervention used: RESQ (n = 9) in group A, simple debridement (n = 16) in group B, and guideline-recommended replacement (n = 5) in group C. Patient baseline characteristics were similar between the groups. After analyzing the proportion of patients that were free from infection one year following their respective interventions, we found that group A performed better than group B (100% and 31.2% infection-free, respectively, p = 0.001), and was comparable to group C (both 100% infection-free, p = not applicable)., Conclusions: The RESQ method is a feasible and beneficial alternative for selected patients with CIED infections who are unable to receive a generator replacement according to the recommended guideline.

Background: Synchronous multiple primary malignant neoplasms occurring at the same time (SMPMNS) are not currently uncommon in clinical oncological practice; however, the diagnostic performance of 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) for SMPMNS needs further elucidation., Purpose: This study aimed to evaluate the application of 18 F-FDG PET/CT in patients with SMPMNS., Materials and Methods: The clinical and imaging data of 37 patients with SMPMNS who had undergone 18 F-FDG PET/CT from October 2010 to December 2020 were retrospectively analyzed. The kappa consistency test was applied to evaluate the consistency of the diagnostic performance between PET/CT and conventional imaging (CI). The sensitivity, specificity, and accuracy of PET/CT and CI in the detection of metastatic lesions were compared., Results: This retrospective diagnostic study included 74 lesions identified in 37 patients with SMPMNS, with 94.6% of patients having double primary tumors. Of the incidences of SMPMNS, 18.9% occurred in the same organ system, with respiratory tumors being the most common type of neoplasm (43.2%) and the lung being the most common primary site (40.5%). The overall survival of SMPMNS patients without metastases was longer than that of those with metastases ( χ 2  = 12.627, p  = 0.000). The maximum standardized uptake value (SUV max ), the SUV max ratio (larger SUV max /smaller SUV max ), and the difference index of SUV max (DISUV max ) [(larger SUV max  - smaller SUV max )/larger SUV max ] of the primary lesions ranged from 0.9 to 41.7 (average = 12.3 ± 7.9), from 0.3 to 26.7 (average = 4.4 ± 6.9), and from 0.0% to 96.3% (average = 50.3% ± 29.3%), respectively. With regard to diagnostic accuracy, PET/CT and CI showed poor consistency ( κ  = 0.096, p  = 0.173). For the diagnosis of primary lesions (diagnosed and misdiagnosed), PET/CT and CI also showed poor consistency ( κ  = 0.277, p  = 0.000), but the diagnostic performance of PET/CT was better than that of CI. In the diagnosis of metastases, the patient-based sensitivity, specificity, and accuracy of PET/CT were 100.0%, 81.8%, and 89.2%, respectively, while those of CI were 73.3%, 100.0%, 89.2%, respectively. The sensitivity and specificity values were significantly different, with PET/CT having higher sensitivity ( p  = 0.02) and CI showing higher specificity ( p  = 0.02)., Conclusions: 18 F-FDG PET/CT improves the diagnostic performance for SMPMNS and is a good imaging modality for patients with SMPMNS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Luo, Qi, Jin, Liao, Liu and Zeng.)

Background: Dengue virus (DENV) infection induces various clinical manifestations and even causes organ injuries, leading to severe dengue haemorrhagic fever and dengue shock syndrome. Hepatic dysfunction was identified as a risk predictor of progression to severe disease during the febrile phase of dengue. However, the underlying mechanisms of hepatic injury remain unclear., Methods: A model of dengue disease was established in IFNAR -/- C57BL/6 mice by challenge with DENV-2. Body weight, symptoms, haematological parameters and liver pathological observations in mice were used to determine the effects of DENV infection. Liver transcriptome sequencing was performed to evaluate the features of the host response in IFNAR -/- mice challenged with DENV. Functional enrichment analysis and analysis of significantly differentially expressed genes (DEGs) were used to determine the critical molecular mechanism of hepatic injury., Results: We observed haemoconcentration, leukopenia and liver pathologies in mice, consistent with findings in clinical dengue patients. Some differences in gene expression and biological processes were identified in this study. Transcriptional patterns in the liver indicated that antiviral responses to DENV and tissue damage via abnormal expression of proinflammatory cytokines were induced. Further analysis showed that the upregulated DEGs were significantly enriched in the leukocyte transendothelial migration, complement and coagulation cascades, and cytokine-cytokine receptor interactions signalling pathways, which are considered to be closely associated with the pathogenic mechanism of dengue. IL6, IL 10, ICAM-1, VCAM-1, MMP9 and NLRP3 were identified as biomarkers of progression to severe disease., Conclusions: The interactions of these cytokines, which activate inflammatory signalling, may lead to organ injury and haemoconcentration and even to vascular leakage in tissues, including the mouse liver. Our study identifies candidate host targets that could be used for further functional verification., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zheng, Yan, Li, Wang, Wu, Liao, Lao, Jiang, Liu, Zhan and Li.)

Background: Sublingual immunotherapy (SLIT) has been proved to be an effective and safe treatment for allergic asthma (AS) in children. Nonetheless, several issues regarding SLIT remain to be resolved, including the information about optimal administration timing., Methods: A total of 163 AS children aged 4-13 years were enrolled and randomized into the morning dosing (MD) group and the evening dosing (ED) group. Participants received SLIT with Dermatophagoides farinae drops between 7:00 a. m. and 9:00 a.m. (for the MD group) or between 8:00 p. m. and 10:00 p.m. (for the ED group). The total asthma symptom score (TASS), total asthma medicine score (TAMS), Asthma Control Questionnaire (ACQ), forced expiratory volume in one second (FEV 1 ), FEV 1 /forced volume vital capacity (FVC), fractional exhaled nitric oxide (FeNO) and adverse events (AEs) were assessed at baseline, 0.5 and 1 year during the 1-year SLIT., Results: After 1 year, 62 patients in the MD group and 63 patients in the ED group completed the entire study. The clinical efficacy, pulmonary function and FeNO in both groups improved significantly at 0.5 and 1 year ( p < 0.001). Compared to the MD group, the ED group showed significant lower ACQ score at 0.5 year ( p < 0.001) and lower FeNO at 1 year ( p < 0.05). No significant difference between two groups was observed in AE rate ( p > 0.05). All AEs occurred in the first month, with no systemic AEs reported., Conclusion: 1-year house dust mite (HDM) SLIT is effective and well-tolerated in AS children regardless of administration time. SLIT dosing in the evening might enhance the asthma control level and reduce FeNO level compared with SLIT dosing in the morning., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liao, Chen, Wang, Quan, Chen and Lin.)

Background: Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasm that can involve multisystem organs. Positron emission tomography/computed tomography (PET/CT) has been widely used in tumor staging and efficacy evaluation. However, at present, there are few 18 F-fluorodeoxyglucose (FDG) PET/CT studies on LCH. This study aimed to explore the possible role of 18 F-FDG PET/CT in the diagnosis and management of patients with LCH., Methods: 18 F-FDG PET/CT images of 22 Chinese patients diagnosed with LCH on biopsy or surgery histopathology between January 2011 and December 2020 were retrospectively analyzed. The incidence of LCH in each system was assessed by a PET/CT scan. The imaging characteristics were analyzed semiquantitatively and qualitatively. The discrepancies between PET/CT and conventional imaging modalities were recorded. Evaluations of curative effect according to RECIST1.1 and PERCIST1.0 were compared using Fisher's exact chi-squared test, and P values <0.05 were considered significant., Results: Eight (36.4%) of the 22 patients presented with single system involvement (4 isolated site involvement, 4 multiple site involvement), and 14 (63.6%) presented with multiple system involvement. Twenty-one (95.5%) patients had hypermetabolic lesions. Musculoskeletal, lymphatic, respiratory, liver, skin-soft tissue and thyroid involvement were seen in 14 (63.6%), 13 (59.1%), 5 (22.7%), 4 (18.2%), 5 (22.7%) and 1 (4.5%) patient, respectively. Cranial and facial bones were the most common sites of musculoskeletal involvement. Ten patients underwent PET/CT follow-up, and there was no significant difference in curative effect evaluations according to RECIST1.1 and PERCIST1.0. However, among the complete remission cases assessed by RECIST1.1, three were partial metabolic responses assessed by PERCIST1.0, while among the partial response cases assessed by RECIST1.1, one was metabolic progressive disease assessed by PERCIST1.0., Conclusions: 18 F-FDG PET/CT is an imaging modality option for the diagnosis and assessment of the curative effect of LCH., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-21-823/coif). The authors have no conflicts of interest to declare., (2022 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Gut microbial lipopolysaccharides (LPS)-induced inflammatory responses in adipose tissue are associated with the dysfunction of adipocytes, insulin resistance and the development of metabolic syndrome. The aim of this study is to investigate (1) the effects of LPS on the differentiation and inflammatory responses of THP-1 monocytes and OP9 preadipocytes under serum free conditions and (2) the repressive effects of enzyme-digested Colla Corii Asini (CCAD) and fish gelatin (FGD) on LPS-induced inflammatory responses in THP-1 macrophages and OP9 adipocytes. Immunofluorescence and oil red O staining showed that a serum free medium supplied with phorbol 12-myristate 13-acetate (PMA) could induce differentiation and lipid accumulation in THP-1 cells as well as OP9 cells. ELISA showed that LPS significantly increased interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) secretions in PMA-differentiated THP-1 macrophages in a dose-dependent manner. LPS significantly suppressed lipid accumulation and adiponectin secretions, and enhanced IL-6 secretions in OP9 adipocytes. Both CCAD and FGD significantly reduced the levels of both macrophages- and adipocytes-derived inflammatory cytokines and increased the level of OP9-secreted adiponectin. In conclusion, LPS could induce inflammatory responses in both THP-1 and OP9 cells and cause dysfunction of OP9 adipocytes under the serum free conditions. CCAD and FGD can repress LPS-induced inflammatory responses in both THP-1 macrophages and OP9 adipocytes, and increase the secretion of adiponectin in OP9 adipocytes. They could be used as health care supplements for improving metabolic syndrome., (© 2022. The Author(s) under exclusive licence to Japan Human Cell Society.)

Background: Reuse of cardiac implantable electronic devices (CIEDs) can reduce the cost of using these expensive devices. However, whether resterilized CIEDs will increase the risk of reinfection in patients with previous device infection remains unknown. The aim of the present study is to compare the reinfection rates in patients who had initial CIED infection and underwent reimplantation of resterilized CIEDs or new devices., Methods: Data from patients with initial CIED infection who received debridement of the infected pocket and underwent reimplantation of new or resterilized CIEDs at MacKay Memorial Hospital, Taipei, Taiwan, between January 2014 and June 2019 were retrospectively analyzed. Patient characteristics, relapse rates of infection, and potential contributing factors to the infection risk were examined., Results: Twenty-seven patients with initial CIED infection and reimplanted new CIEDs (n = 11) or resterilized CIEDs (n = 16) were included. During the 2-year follow-up, there were 1 (9.1%) and 2 (12.5%) infection relapses in the new and resterilized CIED groups, respectively. No relapse occurred for either group if the lead was completely removed or cut short. The median duration between debridement and device reimplantation in patients with infection relapse vs patients without relapse was 97 vs 4.5 days for all included patients, and 97 vs 2 days and 50.5 vs 5.5 days for the new and resterilized CIED groups, respectively., Conclusions: Subpectoral reimplanting of resterilized CIEDs in patients with previous device infection is safe and efficacious. With delicate debridement and complete extraction of the leads, the CIED pocket infection relapse risk can be greatly decreased., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

The current treatment paradigm for atrial fibrillation (AF) prioritizes rate control over rhythm control; however, rhythm control has shown benefits over other AF strategies. This study compares the outcomes of rivaroxaban with and without concomitant antiarrhythmic drugs (AADs), using propensity score matching to correct for statistical effects of baseline discrepancies. This multi-center retrospective study included 1,477 patients with non-permanent AF who took rivaroxaban for at least one month between 2011 and 2016 and had not received catheter ablation. Concomitant AAD use was compared against clinical outcome endpoints for effectiveness, safety, and major adverse cardiac events (MACE). Associations with concomitant AAD use were evaluated using multivariate Cox proportional hazard analyses. Patients were divided into two matched groups: rivaroxaban alone (n = 739) and with concomitant AADs (n = 738). The cumulative incidences of safety (p = 0.308), effectiveness (p = 0.583), and MACE (p = 0.754) were similar between the two groups, and multivariate analysis showed no significant differences. The new thromboembolism and all-cause death rates were higher in rivaroxaban alone (2.7% vs 0.8%, p = 0.005; and 10% vs. 6.9%, p = 0.032, respectively). The heart failure readmission rate was higher in the concomitant-AAD group (8.4% vs. 13.3%, p = 0.003). The concomitant use of rivaroxaban with AADs appears to be well-tolerated, with lower rates of thromboembolism and all-cause death, but is associated with more occurrences of congestive heart failure., (© 2022. The Author(s).)

Objectives: This systematic review and meta-analysis investigated the accuracy of prenatal fetal ultrasound (US) to detect cleft palate during the second and third trimester (12-36 weeks) of pregnancy in high-risk fetuses., Methods: Pubmed and Embase databases were searched for studies that performed prenatal fetal US (comparator) and postnatal examination (reference standard) in fetuses at high risk for orofacial clefts. Risk of bias among included studies was assessed using the QUADAS-2. Area under the summary receiver operating characteristic (SROC) curve and pooled sensitivity and specificity were calculated., Results: This meta-analysis included 7 studies involving 663 high-risk fetuses. The individual studies showed that prenatal fetal US accurately predicted the possibility of cleft palate in these fetuses. Pooled sensitivity was 87% (95% CI 71%-95%), pooled specificity was 98% (95%CI 90%-100%), and the area under the SROC curve was 0.98 (95% CI 0.97-0.99)., Conclusion: Second and third trimester fetal US has excellent sensitivity and specificity for the detection of cleft palate in high-risk pregnancies., (© 2021 American Institute of Ultrasound in Medicine.)

In the context of extreme climate due to global climate transition, rainwater adaptation in resilient cities is a key issue for countries. The purpose of this study is to identify the rainfall hotspots in urban areas and investigate whether these hotspots have environmental conditions for rainfall adaptation. The study site is located in the Taichung area. This study collects rainfall data from rainfall stations at elevations below 500 m, employs QGIS (quantum GIS) to create an inverse distance weighted graphical distribution of rainfall to determine the hotspots where the maximum and minimum rainfalls occur, identifies the topography, green spaces, water areas, and buildings in the catchment, integrates the coverage area in the project, and estimates the amount of rainwater that could be directly absorbed by the land within the catchment. The results of this study show that, among the rainfall stations at an elevation below 100 m where most urban areas are located, the Taichung rainfall station is the area with the highest number of rainfall events from May to August. Without reliance on gully or river drainage, the natural infiltration of the land in the catchment could only adjust to 80 mm of heavy precipitation within 24 h of the rainfall warning level of the Central Weather Bureau., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Androgenic alopecia (AGA) has a high incidence. Excess dihydrotestosterone in blood capillaries, which is converted from testosterone by 5α-reductase, is an AGA causative factor. We identified the inhibitory activity of four Polygonum multiflorum compounds against 5α-reductase via high-performance liquid chromatography, and the results showed that Physcion was a potent 5α-reductase inhibitor. Additionally, we found that through inhibiting 5α-reductase expression, Physcion could shorten the time of dorsal skin darkening and hair growth, improve hair follicle morphology, and significantly increase hair follicle count. Eventually, through molecular docking study, we found the binding energy and molecular interactions between Physcion and 5α-reductase type II. These results suggested that Physcion is a potent 5α-reductase inhibitor, as well as a new natural medicine for treating AGA., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Methicillin-resistant Staphylococcus aureus (MRSA) has become the most important pathogen of hospital-acquired (HA) or community-acquired (CA) infections. However, it is unclear of the cytokines responsible for pathological hyper-inflammation in sepsis related cytokine storm for MRSA infection. In this study, we selected typical HA-MRSA strain (YNSA163: ST239-t030-SCCmecⅢ) and two CA-MRSA isolates (YNSA7: ST59-t439-SCCmecⅣa and YNSA53: ST59-t437-SCCmecⅤb) from our previous research, infected on BALB/c mice, and analyzed the cytokine storm patterns during infection process. The animal experiments revealed the most serious lethal effect on BALB/c mice caused by YNSA7 strain infection, followed by YNSA53, and no BALB/c mice died for YNSA163 infection. Histopathological analyses revealed that lung was the most seriously damaged organs, followed by spleen and kidney, especially for CA-MRSA infection. The severe inflammatory reactions, tissue destruction, and massive exudation of inflammatory mediators and cells could be identified in CA-MRSA strains infected mice. Interleukin-6 (IL-6) and IL-10 were both highly expressed in spleen and lung of YNSA7 and YNSA53 dead cases compared with YNSA53 survived and YNSA163 cases, which demonstrated cytokine storm pattern for CA-MRSA strains infection. The results of IL-6 intervention experiment verified that the enhanced IL-6 secretion was responsible for the host lethality of YNSA7 infection. RNA-sequencing results among three MRSA isolates indicated most of the differentially expressed genes referred to cellular process, metabolism and genetic information processing of bacteria. Specifically, clpP, chp chemotaxis inhibit, fnbB, pathogencity island protein and virulence associated protein E were highly expressed in YNSA7 strain. In general, CA-MRSA strains provoked cytokine storm on BALB/c mice led to severe infection and lethality, the up-regulated of some virulence genes might play important role in pathogenesis., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen for human infection. Hospital-acquired (HA) and community-acquired (CA) MRSA infections are serious clinical problems worldwide. In this study, we selected typical HA-MRSA strain and CA-MRSA isolates from our previous research and compared their phenotypic and pathogenic abilities both in vitro and in vivo., Results: ST59-t437-SCCmecIVa (YNSA7) and ST59-t437-SCCmecVb (YNSA53) belonged to two prevalent subclones of CA-MRSA, while ST239-t030-SCCmecIII (YNSA163) was an HA-MRSA epidemic clone in Southwest China. ST59-t437 strains demonstrated faster growth ability, higher survival rate resistance to human blood, and more toxin secretion levels and cytotoxicity than ST239-t030. The virulence and regulatory genes of hld, psm-α, RNAIII, agrA, and crtN were highly expressed on CA-MRSA isolates, especially the ST59-t437-SCCmecIVa subclone. However, the ST239-t030 strain had the strongest adhesion and biofilm ability among these MRSA bacteria. Animal experiments revealed the most serious lethal effect on BALB/c mice caused by the YNSA7 strain infection. The survival rates of BALB/c mice infected with the three MRSA strains were 16.7, 50.0 and 100.0% for YNSA7, YNSA53 and YNSA163, respectively. Histopathological analyses of infected animals indicated that the lungs were the most seriously damaged organs, especially for ST59-t437 MRSA. Severe inflammatory reactions, tissue destruction, and massive exudation of inflammatory mediators and cells could be identified in ST59-t437 strain-infected animals., Conclusions: In general, ST59-t437 strains showed higher pathogenic ability than the ST239-t030 isolate, while ST239-t030 MRSA revealed the features prevalent in hospital settings, specifically for adhesion and biofilm ability., (© 2021. The Author(s).)

Background: To investigate the preventive effect of elastic stockings on deep vein thrombosis (DVT) after orthopedic surgery by literature search and meta-analysis., Methods: PubMed, Embase and Cochrane were selected as the search database platforms to search the literature of randomized controlled trials related to elastic stockings and DVT published from 2008 to date. Revman 5.3.5 software was used for statistical analysis of the data to obtain forest and funnel plots., Results: In this study, 90 studies were initially screened and 7 were finally included, covering a total of 3,116 patients. Meta-analysis showed that the 7 studies had statistical heterogeneity (I2=32%, P=0.18), so a random effect model was used. The obtained statistic was [odds ratio (OR) =0.59, 95% confidence interval (CI): (0.34, 1.03)], the statistical effect size was Z=1.84, P=0.07, and the difference was not statistically significant, so a stepwise sensitivity analysis was performed by the exclusion method. One study was excluded, and the remaining 6 showed homogeneity (I2=0%, P=0.46). They were analyzed by subgroup according to the type of operation: ankle surgery or hip and knee arthroplasty. The internal literatures of each subgroup were homogeneous: ankle surgery subgroup (I2=0%, P=0.43), hip and knee arthroplasty subgroup (I2=0%, P=0.88). Therefore, fixed effect mode analysis was used, and the effect size of elastic stockings after ankle surgery was Z=3.65, P=0.0003, while the effect size of elastic stockings in the hip and knee arthroplasty subgroup was Z=1.23, P=0.22., Discussion: Elastic stockings had an obvious preventive effect on DVT in patients undergoing ankle surgery, but not in patients undergoing lumbar, knee or spinal surgery. It is necessary to combine anticoagulant drugs and other physical therapies to prevent DVT.

Long-term and excessive alcohol consumption are risk factors for osteoporosis. Excessive drinking can reduce bone density and also cause imbalance of gut microbiota. And gut microbiota can affect bone metabolism through various mechanisms, and the regulation of gut microbiota is closely related to age. However, the effects of gut microbiota on alcohol-induced osteoporosis at different ages are unclear. In this study, young and old rats were used to induce osteoporosis by long-term alcohol consumption, and alcohol metabolism, bone morphology, bone absorption and immune activity of rats were analyzed to determine the effects of alcohol on rats of different ages. In addition, changes of gut microbiota in rats were analyzed to explore the role of gut microbiota in alcohol-induced osteoporosis in rats of different ages. The results showed the ability of alcohol metabolism was only associated with age, but not with alcohol consumption. Long-term alcohol consumption resulted in the changes of bone metabolism regulating hormones, bone loss, activation of receptor activator of NF- κ B ligand (RANKL) signaling and inflammatory response. And osteoporosis was more severe in old rats than young rats, suggesting that alcohol-induced osteoporosis is age-related. In addition, long-term drinking also affected the composition of gut microbiota in rats, with a significant increase in the proportion of pro-inflammatory microorganisms. Overall, this study found that long-term alcohol consumption induced osteoporosis and affected the composition of gut microbiota. And alcohol can activate T lymphocytes directly or indirectly by regulating the changes of gut microbiota to produce cytokines, and further activate osteoclasts. In addition, the osteoporosis was more severe in the old rats than young rats, which may be due to the higher diversity and stronger regulation ability of gut microbiota in young rats compared with old rats., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Cheng, Tan, Wu, Liao, Wang and Huang.)

Goal-directed spatial learning is crucial for the survival of animals, in which the formation of the route from the current location to the goal is one of the central problems. A distributed brain network comprising the hippocampus and prefrontal cortex has been shown to support such capacity, yet it is not fully understood how the most similar brain regions in birds, the hippocampus (Hp) and nidopallium caudolaterale (NCL), cooperate during route formation in goal-directed spatial learning. Hence, we examined neural activity in the Hp-NCL network of pigeons and explored the connectivity dynamics during route formation in a goal-directed spatial task. We found that behavioral changes in spatial learning during route formation are accompanied by modifications in neural patterns in the Hp-NCL network. Specifically, as pigeons learned to solve the task, the spectral power in both regions gradually decreased. Meanwhile, elevated hippocampal theta (5 to 12 Hz) connectivity and depressed connectivity in NCL were also observed. Lastly, the interregional functional connectivity was found to increase with learning, specifically in the theta frequency band during route formation. These results provide insight into the dynamics of the Hp-NCL network during spatial learning, serving to reveal the potential mechanism of avian spatial navigation.

Introduction: Rivaroxaban reduces the risk of thromboembolism in atrial fibrillation (AF) patients, who often also receive antiarrhythmic drugs (AADs) to maintain sinus rhythm. Current guidelines contraindicate concomitant use of rivaroxaban with the popular AAD dronedarone, despite little data demonstrating interactions with AADs. This study investigates the outcomes of concomitant rivaroxaban and AAD drug use in a real-world cohort., Methods: This retrospective study included 1777 non-permanent AF patients taking rivaroxaban for ≥ 1 month between 2011 and 2016 from a multicenter cohort in Taiwan, and compared concomitant AAD use against clinical outcome endpoints for safety, effectiveness, and major adverse cardiac events (MACE). Multivariate Cox proportional hazard analyses were used to evaluate the association between concomitant AAD use and outcomes., Results: Patients were divided into rivaroxaban alone (n = 1205) and with concomitant amiodarone (n = 177), dronedarone (n = 231), or propafenone (n = 164) groups. The proportion of patients using rivaroxaban 10 mg was highest in the concomitant dronedarone group: rivaroxaban alone, 53.6%; with amiodarone, 57.6%; with dronedarone, 77.1%; and with propafenone, 46.3% (p < 0.001). The cumulative incidences of safety (p = 0.892), effectiveness (p = 0.336), and MACE (p = 0.674) were similar between the four groups; however, there were significantly fewer new systemic thromboembolisms in the dronedarone group: rivaroxaban alone, 2.5%; with amiodarone, 0.6%; with dronedarone, 0%; and with propafenone, 1.2% (p = 0.029). The all-cause death rate was also lowest in the dronedarone group: rivaroxaban alone, 9.0%; with amiodarone, 9.6%; with dronedarone, 3.0%; and with propafenone: 6.1% (p = 0.013). After covariate adjustment, there were no differences in the safety, effectiveness, and MACE endpoints between patients receiving or not receiving AADs., Conclusion: Concomitant use of rivaroxaban with AADs appears to be well tolerated, warranting further investigation into the apparent benefits of a reduced dose of rivaroxaban combined with dronedarone.

Since 1953, sinus tachycardia has been defined as a heart rate (HR) in sinus rhythm of >100 beats per minute (bpm). However, this number has never been formally evaluated, and no established threshold values for special groups, such as those with heart failure (HF) accompanied by a reduced ejection fraction (HFrEF). Herein, we provided evidence that lowering the HR of patients with HFrEF to <70 bpm with medications such as ivabradine improves outcomes. Numerous large-scale trials and smaller clinical studies have shown that reducing the HR in patients with HFrEF improves cardiovascular and overall outcomes. Evidence suggests that a HR of <70 bpm is appropriate for patients with HFrEF. Examination of HF registries indicates that in a large proportion of these patients the HR exceeds 80 bpm, and no consideration is given to lowering the HR, due in large part to lack of physician awareness of the benefits of a lower HR. Evidence indicates that the first-line medication for lowering HR in patients with HFrEF is ivabradine. In conclusion, the improved prognosis following appropriate HR management in patients with HFrEF suggest that the cut-off value for sinus tachycardia in these patients should be redefined as 75 bpm. Maintaining a HR of <70 bpm in patients with HFrEF is associated with improved cardiovascular and overall outcomes., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aims: Post-fracture calcium and phosphorus excretion is greater than influx, which might be caused by stress. Glucocorticoid is known to enhance calcium and phosphorous excretion, and hydrogen sulfide (H 2 S) has been shown to exert inhibitory effects on glucocorticoid. Therefore, this study explored whether H 2 S could inhibit calcium and phosphorus loss after fracture by regulating glucocorticoid and/or its receptor., Main Methods: The following properties were analyzed in rats with femur fractures: serum and urinary calcium and phosphorus (by colorimetry); bone turnover markers alkaline phosphatase, serum type 1 collagen amino terminal peptide, type 1 procollagen carboxy terminal peptide, and anti-tartaric acid phosphatase (by ELISA); factors related to calcium-phosphorus metabolism including glucocorticoid, parathyroid hormone, calcitonin, fibroblast growth factor 23, and 1,25(OH) 2 D 3 (by ELISA); and sulfhydration of glucocorticoid receptor α in the kidney (by immunoprecipitation linked biotin-switch assay), after supplementing with mifepristone, the H 2 S donor GYY4137 or H 2 S generating enzyme inhibitors aminooxyacetic acid and propargylglycine., Key Findings: Serum H 2 S decreased and glucocorticoid secretion increased in rats post-fracture. The glucocorticoid receptor inhibitor mifepristone partly blunted calcium and phosphorus loss. Furthermore, supplementation with GYY4137 reduced glucocorticoid secretion; inhibited glucocorticoid receptor α activity by sulfhydration; downregulated vitamin D 1α-hydroxylase expression; and upregulated 24-hydroxylase, calbindin-D28k, and sodium phosphate cotransporter 2a expression in the kidney; thereby inhibiting calcium and phosphorus loss induced by fracture. Moreover, inhibiting endogenous H 2 S generation showed opposite effects., Significance: Our findings suggest that H 2 S antagonized calcium and phosphorus loss after fracture by reducing glucocorticoid secretion and inhibiting glucocorticoid receptor α activity by sulfhydration., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) with a complex aetiology that commonly recurs. Most drugs for UC treatment interfere with metabolism and immune responses, often causing some serious adverse reactions. Therefore, the development of alternative treatments, including nutritional supplements and probiotics, have been one of the main areas of current research due to fewer side effect. As both a Chinese medicine and a food, edible bird's nest (EBN) has high nutritional value. Modern pharmacological studies have shown that it has anti-inflammatory, immunoregulatory, antiviral and neuroprotective effects. In this study, UC was induced with dextran sulfate sodium (DSS) to investigate the protective effect of EBN on colitis mice and the related mechanism. The body weight, faecal morphology and faecal occult blood results of mice were recorded every day from the beginning of the modelling period. After the end of the experiment, the length of the colon was measured, and the colon was collected for histopathological detection, inflammatory factor detection and immunohistochemical detection. Mouse spleens were dissected for flow cytometry. The results showed that in mice with colitis, EBN improved symptoms of colitis, reduced colonic injury, and inhibited the increases in the levels of the pro-inflammatory cytokines IL-1β and TNF-α. The T helper 17 (Th17)/regulatory T (Treg) cell balance was restored by decreasing the expression of IL-17A and IL-6 in intestinal tissues, increasing the expression of TGF-β, and decreasing the number of Th17 cells in each EBN dose group. These findings suggest that EBN has a protective effect on DSS-mediated colitis in mice, mainly by restoring the Th17/Treg cell balance., Competing Interests: Authors YF (2nd author), XZ and YW were employed by the company Xiamen Yan Palace Seelong Food Co., Ltd. Author YL was employed by the company Guangzhou Tongkang pharmaceutical Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Fan, Fan, Liu, Lonan, Liao, Huo, Zhong, Liang, Wang, Hou, Lai, Li and Kuang.)

Objectives: We aimed to determine predictors of mortality within 90 days and develop a simple score for patients with mechanical thrombectomy (MT)., Design: Analysis of a multicentre prospective registry., Setting: In six participating centres, patients who had an acute ischaemic stroke (AIS) treated by MT between March 2017 and May 2018 were documented prospectively., Participants: 224 patients with AIS were treated by MT., Results: Of 224 patients, 49 (21.9%) patients died, and 87 (38.8%) were independent. Variables associated with 90-day mortality were age, previous stroke, admission National Institutes of Health Stroke Scale (NIHSS), fasting blood glucose and occlusion site. Logistic regression identified four variables independently associated with 90-day mortality: age ≥80 years (OR 3.26, 95% CI 1.45 to 7.33), previous stroke (OR 2.33, 95% CI 1.04 to 5.21), admission NIHSS ≥18 (OR 2.37, 95% CI 1.13 to 4.99) and internal carotid artery or basilar artery occlusion (OR 2.92, 95% CI 1.34 to 6.40). Using these data, we developed predicting 90-day mortality of AIS with MT (PRACTICE) score ranging from 0 to 6 points. The receiver operator curve analysis found that PRACTICE score (area under the curve (AUC)=0.744, 95% CI 0.669 to 0.820) was numerically better than iScore (AUC=0.661, 95% CI 0.577 to 0.745) and Predicting Early Mortality of Ischemic Stroke score (AUC=0.638, 95% CI 0.551 to 0.725) for predicting 90-day mortality., Conclusions: We developed a simple score to estimate the 90-day mortality of patients who had an AIS treated with MT. But the score needs to be prospectively validated., Trial Registration Number: Chinese Clinical Trial Registry (ChiCTR-OOC-17013052)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Hepatitis B virus (HBV) infection represents the major etiology of hepatocellular carcinoma (HCC) and results in poor outcomes. Accumulating evidence suggests that composite immune cell-based biomarkers such as neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) have prognostic value in postoperative HCC patients. However, due to the complexity, differential etiology, and the presence of variable confounding factors in different studies, the relationship between these markers with clinical outcomes in HBV-related posthepatectomy HCC is unclear from an immune perspective. Thus, this meta-analysis was conducted to determine NLR and PLR and assess their relation to overall survival (OS) and recurrence-free survival (RFS) in patients with post-hepatectomy HCC with HBV infection., Methods: The databases PubMed, Embase, Scopus, and Cochrane Library were searched using relevant keywords. We included studies which compared the outcomes of RFS and OS between different levels of NLR and PLR in HBV-related HCC patients who had undergone hepatectomy. Hazard ratios (HRs) and their 95% confidence intervals (CIs) were considered as effective measures and were calculated by a pooled analysis. Evidence supporting the association of neutrophils, platelets, and lymphocytes with HBV infection, liver injury, and tumor progression in HCC was evaluated., Results: A total of 11 cohort studies with 5083 patients were included. Elevated NLR was significantly associated with poor RFS (HR: 1.28, 95% CI: 1.09-1.50, P=0.000) and poor OS (HR: 1.64, 95% CI: 1.32-2.03, P=0.000). Decreased PLR was significantly associated with a low risk of posthepatectomy relapse (HR: 1.40, 95% CI: 1.28-1.53, P=0.000) and better survival (HR: 1.63, 95% CI: 1.42-1.87, P=0.000). The subgroup and sensitivity analysis showed consistent and stable results., Conclusions: Both NLR and PLR can be used as biomarkers for the prediction of RFS and OS in patients with HBV-associated HCC after hepatectomy., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tcr-20-3125). The authors have no conflicts of interest to declare., (2021 Translational Cancer Research. All rights reserved.)

The emerging data supports rhythm control to prevent major adverse cardiac events (MACE) in high-risk patients with atrial fibrillation (AF). Limited data demonstrated rivaroxaban 10 mg combining dronedarone seemed feasible. This study aimed at investigating clinical events in a dronedarone-treated cohort. This exploratory, retrospective chart review was conducted in nonpermanent AF patients receiving dronedarone for ≥ 3 months between 2009/1 and 2016/2. In Taiwan, dronedarone's labeled indication was strict to age ≥ 70 or 65 to 70 years with either hypertension, diabetes, prior stroke, or left atrium >50 mm. We divided all into 4 groups using antithrombotic strategies to evaluate the safety, effectiveness, and MACE endpoints. A total of 689 patients (mean CHA 2 DS 2 -VASc score 3.8 ± 1.4) were analyzed: rivaroxaban 10 mg (n = 93, 13.5%), warfarin (n = 89, 12.9%), antiplatelet (n = 331, 48.0%), and none (n = 176, 25.5%). During the follow-up period (mean 946 ± 493.8 days), the rivaroxaban group did not report any stroke or thromboembolism (ishcmeic stroke rate: antiplatelet [0.6%], none [1.1%]; hemorrahgic stroke rate: warfarin [2.2%]; thromboembolism rate: warfarin [2.2%]). There was no significant difference in safety, effectiveness, and MACE endpoints between groups. Also, >104 weeks of dronedarone use was the independent predictor for MACE after adjusting the strategy and other covariates (hazard ratio 0.14 [95% confidence interval 0.04-0.44], P  = .001). Our findings warrant concomitant rivaroxaban 10 mg and dronedarone for further investigation. Regardless of antithrombotic strategies, a more extended persistence of dronedarone was associated with fewer MACE.