Search

Background: Previous research has raised concerns regarding inconsistencies between reported and pre-specified outcomes in randomized controlled trials (RCTs) across various biomedical disciplines. However, studies examining whether similar discrepancies exist in RCTs focusing on gastrointestinal and liver diseases are limited. This study aimed to assess the extent of discrepancies between registered and published primary outcomes in RCTs featured in journals specializing in gastroenterology and hepatology., Methods: We retrospectively retrieved RCTs published between January 1, 2017 and December 31, 2021 in the top three journals from each quartile ranking of the 2020 Journal Citation Reports within the "Gastroenterology and Hepatology" subcategory. We extracted data on trial characteristics, registration details, and pre-specified versus published primary outcomes. Pre-specified primary outcomes were retrieved from the World Health Organization's International Clinical Trials Registry Platform. Only trials reporting specific primary outcomes were included in analyzing primary outcome discrepancies. We also assessed whether there was a potential reporting bias that deemed to favor statistically significant outcomes. Statistical analyses included chi-square tests, Fisher's exact tests, univariate analyses, and logistic regression., Results: Of 362 articles identified, 312 (86.2%) were registered, and 79.8% of the registrations (249 out of 312) were prospective. Among the 285 trials reporting primary outcomes, 76 (26.7%) exhibited at least one discrepancy between registered and published primary outcomes. The most common discrepancies included different assessment times for the primary outcome (n = 32, 42.1%), omitting the registered primary outcome in publications (n = 21, 27.6%), and reporting the registered secondary outcomes as primary outcomes (n = 13, 17.1%). Univariate analyses revealed that primary outcome discrepancies were lower in the publication year 2020 compared to year 2021 (OR = 0.267, 95% CI: 0.101, 0.706, p = 0.008). Among the 76 studies with primary outcome discrepancies, 20 (26.3%) studies were retrospectively registered, and 32 (57.1%) of the prospectively registered trials with primary outcome discrepancies showed statistically significant results. However, no significant differences were found between journal quartiles regarding primary outcome consistency and potential reporting bias (p = 0.14 and p = 0.28, respectively)., Conclusions: This study highlights the disparities between registered and published primary outcomes in RCTs within gastroenterology and hepatology journals. Attention to factors such as the timing of primary outcome assessments in published trials and the consistency between registered and published primary outcomes is crucial. Enhanced scrutiny from journal editors and peer reviewers during the review process is necessary to ensure the reliability of gastrointestinal and hepatic trials., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Adriano R. Tonelli plays as an advisory board for Janssen and Merck and received grant from Janssen; Szymon Bialka is the secretary of the Silesian Branch of the Polish Society of Anesthesiology and Intensive Care from 2021 till now, the president of the Section of Regional Anesthesia and Pain Therapy and Polish Society of Anesthesiology and Intensive Care from 2021 til now, continued Treasurer of the Polish Society of Regional Anesthesia and Pain Therapy from 2023 till now, a co-creator patent device for isolating a patient with suspected infectious disease (exclusive right number: Pat.243051)., (Copyright: © 2024 Shang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Insulinoma-associated protein 1 (INSM1), a recently identified neuroendocrine marker, is a transcriptional regulator with highly conserved INSM1 homologues in various species. This study investigated the immunohistochemical reactivity of the INSM1 antibody in 20 normal canine neuroendocrine tissues from various anatomical locations, 87 hyperplastic or neoplastic tissues of neuroendocrine origin, and 62 non-neuroendocrine neoplasms and compared the results with those of chromogranin A and synaptophysin in neuroendocrine neoplasms. Western blot was performed on fresh canine pituitary glands and canine parathyroid glands to confirm the specificity of the anti-INSM1 antibody. The results showed that the anti-INSM1 antibody could detect nuclear expression in normal canine neuroendocrine tissues, except for the parathyroid glands. INSM1 was detectable in 79/87 (91%) of the hyperplastic and neoplastic neuroendocrine lesions, but all parathyroid carcinomas and parathyroid adenomas (three samples each) were negative for INSM1. In contrast, INSM1 was detected in only one of 62 (2%) non-neuroendocrine neoplasms. The overall percentage of neuroendocrine neoplasms that immunolabeled positively for all three markers was 89%. In addition, the nuclear expression of INSM1 was easier to interpret than that of chromogranin A or synaptophysin. These findings confirm that INSM1 is a useful immunohistochemical marker for diagnosing canine neuroendocrine neoplasms, except for parathyroid neoplasms, and should be considered as part of immunohistochemistry panels to improve diagnostic capability., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Reproductive travel for gamete donation is becoming increasingly common. South Africa is renowned for its availability and relative affordability of high-quality assisted reproductive technology (ART) services. In South Africa (SA) gamete donation is anonymous by law and donors are compensated. Due to its significant availability of donors, SA is a popular destination for people who need donor gametes. The aim of this study was to assess the quality and comprehensiveness of information for oocyte donors available on donor agency websites in SA. A Google search was performed to compile a list of oocyte donor agency websites and content analysis was used to assess the comprehensiveness of the information for donors. Information on 12 websites was analysed. Overall, wording suggested that oocyte donation is a safe and easy procedure which is a process worth experiencing. Possible physical risks and psychological implications of donating oocytes were either not mentioned or downplayed. No website mentioned if or how donors would be followed up after oocyte retrieval or how they would be cared for in case of complications. No website informed donors about the possibility of genetic testing revealing their identity to a child born from their donation. The lack of transparency about the psychological implications and potential risks of donating oocytes suggests that women who contemplate donating oocytes in SA may not have the information they need to make informed decisions about whether to proceed. Since donor agency websites are potential donors' primary source of information, they should provide comprehensive information about all aspects of oocyte donation. This should include transparent and comprehensive information about the known physical and psychological risks. Donors also need to know that oocyte donation may have unknown long-term health risks and that direct-to-consumer genetic testing may reveal their identity to children conceived through their donation in the future.

Background: Pancreatic cancer-associated fibroblasts (CAFs) play a crucial role in tumor progression and immune evasion. Asperuloside (ASP) is an iridoid glycoside with potential anti-tumor properties. This study aimed to explore the molecular mechanisms of ASP on CAFs, particularly focusing on its effects on activating transcription factor 6 (ATF6), a key regulator of endoplasmic reticulum stress., Method: CAFs were treated with different concentrations of ASP (0, 1, 3, and 5 mM), and the role of ATF6 was investigated by over-expressing it in CAFs. Subsequently, western blot was used to detect ATF6, α-smooth muscle actin (α-SMA), fibroblast activating protein (FAP), and vimentin protein levels in CAFs. The collagen gel contraction assay and Transwell assay were applied to evaluate the contraction and migration ability of CAFs. In addition, the interleukin (IL)-6, C-C motif chemokine ligand (CCL)-2, and C-X-C motif chemokine ligand (CXCL)-10 levels were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR)., Results: CAFs had significantly higher expression levels of α-SMA, FAP, and vimentin compared to normal fibroblasts (NFs). ASP significantly inhibited the activation, contraction, and migration of CAFs in a concentration-dependent manner. ASP treatment also reduced the expression of cytokines (IL-6, CCL2, and CXCL10) and down-regulated ATF6 levels. Over-expression of ATF6 mitigated the inhibitory effects of ASP., Conclusion: ASP exerts its anti-tumor effects by down-regulating ATF6, thereby inhibiting the activation and function of pancreatic CAFs. These findings suggest that ASP could be a promising therapeutic agent for pancreatic cancer by modulating the tumor microenvironment., (© 2024. The Author(s).)

Background: While the protective effects of n-3 polyunsaturated fatty acids (PUFAs) on cardiac ischemia-reperfusion (IR) injury have been previously reported, limited data are available regarding how these fatty acids affect membrane receptors and their downstream signaling following IR injury. We aimed to identify potential receptors activated by n-3 PUFAs in IR hearts to understand the regulatory mechanisms of these receptors. Methods: We used fat-1 mice, which naturally have elevated levels of n-3 PUFAs, and C57BL/6J mice as a control group to create a myocardial IR injury model through Langendorff perfusion. We assessed the impact of endogenous n-3 PUFAs on left ventricular function, myocardial infarct size, myocardial apoptosis, and ATP production. RNA sequencing (RNA-seq) and bioinformatics analysis were conducted to identify molecular targets affected by n-3 PUFAs. Based on these analyses we then treated IR hearts of WT and fat-1 mice with an antagonist (ML221) or an agonist (apelin-13) for the predicted receptor to assess cardiac contractile function and intracellular signaling pathways. An in vitro hypoxia-reoxygenation (HR) model was also used to confirm the effects of n-3 PUFAs on the examined intracellular signaling pathways. Results: Endogenous n-3 PUFAs protected cardiac structure and function in post-IR hearts, and modulated phosphorylation patterns in the PI3K-AKT-mTOR signaling pathways. RNA-seq analysis revealed that n-3 PUFAs affected multiple biological processes as well as levels of the apelin receptor (APLNR). Consistent with a role for the PLNNR, ML221 synchronized the activation of the PI3K-AKT-mTOR signaling axis, suppressed the expression of PKCδ and phosphorylated p38α, upregulated PKCε expression, upregulated or restored the phosphorylation of myofilaments, and prevented myocardial injury and contractile dysfunction in WT IR hearts. By contrast, apelin-13 disrupted the PI3K-AKT-mTOR signaling axis in post-IR fat-1 hearts. The phosphorylation signaling targeted by APLNR inhibition in post-IR fat-1 hearts was also observed after treating HR cells with eicosatetraenoic acid (EPA). Conclusion: Endogenous n-3 PUFAs protect against post-IR injury and preserve cardiac contractile function possibly through APLNR inhibition. This inhibition synchronizes the PI3K-AKT-mTOR axis, suppresses detrimental phosphorylation signaling, and restores or increases myofilament phosphorylation in post-IR hearts. The beneficial effects observed in fat-1 transgenic mouse hearts can be attributed, at least in part, to elevated EPA levels. This study is the first to demonstrate that n-3 PUFAs protect hearts against IR injury through APLNR inhibition., 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. The reviewer KZ declared a past co-authorship with the author JW to the handling editor., (Copyright © 2023 Zheng, Tan, Li, Wang, Zhu, Pyle, Chen, Wu, Ren, Chen, Zou, Backx and Yang.)

The immune synapse, a highly organized structure formed at the interface between T lymphocytes and antigen-presenting cells (APCs), is essential for T cell activation and the adaptive immune response. It has been shown that this interface shares similarities with the primary cilium, a sensory organelle in eukaryotic cells, although the roles of ciliary proteins on the immune synapse remain elusive. Here, we find that inositol polyphosphate-5-phosphatase E (INPP5E), a cilium-enriched protein responsible for regulating phosphoinositide localization, is enriched at the immune synapse in Jurkat T-cells during superantigen-mediated conjugation or antibody-mediated crosslinking of TCR complexes, and forms a complex with CD3ζ, ZAP-70, and Lck. Silencing INPP5E in Jurkat T-cells impairs the polarized distribution of CD3ζ at the immune synapse and correlates with a failure of PI(4,5)P 2 clearance at the center of the synapse. Moreover, INPP5E silencing decreases proximal TCR signaling, including phosphorylation of CD3ζ and ZAP-70, and ultimately attenuates IL-2 secretion. Our results suggest that INPP5E is a new player in phosphoinositide manipulation at the synapse, controlling the TCR signaling cascade., (© 2023. Springer Nature Limited.)

The design of earth-abundant and highly efficient bifunctional electrocatalysts for hydrogen evolution and oxygen evolution reactions (HER/OER) is crucial for hydrogen production through overall water splitting. Herein, we report a novel nanostructure consisting of vertically oriented CoP hierarchical nanosheet arrays with in situ-assembled carbon skeletons on a Ti foil electrode. The novel Zeolitic Imidazolate Framework-67 (ZIF-67) template-derived hierarchical nanosheet architecture effectively improved electrical conductivity, facilitated electrolyte transport, and increased the exposure of the active sites. The obtained bifunctional hybrid exhibited a low overpotential of 72 mV at 10 mA cm -2 and a small Tafel slope of 65 mV dec -1 for HER, and an improved overpotential of 329 mV and a Tafel slope of 107 mV dec -1 for OER. Furthermore, the assembled C@CoP||C@CoP electrolyzer showed excellent overall water splitting performance (1.63 V) at a current density of 10 mA cm -2 and superior durability. This work provides a structure engineering strategy for metal-organic framework (MOF) template-derived hybrids with outstanding electrocatalytic performance.

A comprehensive view of the role of NLRP3/caspase-1/GSDMD-mediated pyroptosis in pressure overload cardiac hypertrophy is presented in this study. Furthermore, mitigation of NLRP3 deficiency-induced pyroptosis confers cardioprotection against pressure overload through activation of TAK1, whereas this salutary effect is abolished by inhibition of TAK1 activity, highlighting a previously unrecognized reciprocally regulatory role of NLRP3-TAK1 governing inflammation-induced cell death and hypertrophic growth. Translationally, this study advocates strategies based on inflammation-induced cell death might be exploited therapeutically in other inflammatory and mechanical overload disorders, such as myocardial infarction and mitral regurgitation., Competing Interests: This work was supported by the National Natural Science Foundation of China grants 81941002 (Dr Zou), 82170389 (Dr Wu), 82170255 (Dr S. Wang), 81730009 (Dr Zou), 81770274 (Dr S. Wang), 81670228 (Dr Wu), and 81500191 (Dr You), Laboratory Animal Science Foundation of Science and Technology Commission of Shanghai Municipality grants 201409004300 (Dr Zou) and 21140904400 (Dr Wu), Health Science and Technology Project of Shanghai Pudong New Area Health Commission grant PW2019A-13 (Dr You), and "Rising Sun" Excellent Young Medical Talents Program of Shanghai East Hospital grant 2019xrrcjh03 (Dr You). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

Previous studies have shown that peptides isolated from C-phycocyanin (C-PC) possess various functions including antioxidant and anticancer activities. However, there is little research on C-PC peptides applied for the neuroprotective effect against a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) model. In this study, twelve novel peptides from C-PC were isolated, purified and identified, and the anti-PD effect of the synthesized peptides was evaluated in a zebrafish PD model. As a result, three of these peptides (MAAAHR, MPQPPAK, and MTAAAR) significantly reversed the loss of dopamine neurons and cerebral vessels, and reduced the locomotor impairment in PD zebrafish. In addition, three novel peptides could inhibit the MPTP-induced decrease of antioxidant enzymes (SOD, CAT, and GSH-Px) and increase the ROS and protein carbonylation content. In addition, they can also alleviate apoptosis of brain regions and acetylcholinesterase (AChE) activity in zebrafish. Further studies elucidated the potential molecular mechanism of peptides' anti-PD effects in the larvae. The results showed that C-PC peptides could modulate multiple genes associated with oxidative stress, autophagy and apoptosis signaling pathways, and thereby alleviate the occurrence of PD symptoms. Overall, our results highlight the neuroprotective effects of three novel peptides and provide valuable mechanistic insights and a promising drug target for the treatment of PD.

Background/purpose: In Taiwan, dental radiology has a long history of development. However, there are very few dental radiology curricula in Taiwan's dental education system. This study explored preliminarily the dental radiology course designed for dentist continuing education in Taiwan., Materials and Methods: This study used the method of dental radiology education survey by questionnaire to evaluate participating dentists' learning outcomes by assessing their perceptions of the dental radiology course., Results: In this study, 117 participating dentists filled out the questionnaires completely after the class of dentist continuing education. The results showed that most of participating dentists agreed that dental radiology courses were rare in dental school curriculum and dentist continuing education. Moreover, most of participating dentists found this course to be helpful in raising their basic knowledge and skill about dental radiology, their attitude towards dental radiology, and their interest in further learning of dental radiology. They were satisfied with the course. The degree of agreement for each question was high, and all the mean scores for each question were between 4.53 and 4.77. The numbers (rates) of respondents who answered as agree were between 105 and 113 (between 89.74% and 96.58%)., Conclusion: The dental radiology course contributed to an increase in dentists' basic knowledge and skill about dental radiology and their awareness and understanding of the importance of dental radiology. Considering the effectiveness of the dental radiology course on dentists' basic knowledge/skill and attitude of dental radiology, this model shows promise for further use in dentist continuing education., Competing Interests: The authors have no conflicts of interest relevant to this article., (© 2023 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)

Increasing evidence indicates that an altered immune system is closely linked to the pathophysiology of anxiety disorders, and inhibition of neuroinflammation may represent an effective therapeutic strategy to treat anxiety disorders. Harmine, a beta-carboline alkaloid in various medicinal plants, has been widely reported to display anti-inflammatory and potentially anxiolytic effects. However, the exact underlying mechanisms are not fully understood. Our recent study has demonstrated that dysregulation of neuroplasticity in the basolateral amygdala (BLA) contributes to the pathological processes of inflammation-related anxiety. In this study, using a mouse model of anxiety challenged with Escherichia coli lipopolysaccharide (LPS), we found that harmine alleviated LPS-induced anxiety-like behaviors in mice. Mechanistically, harmine significantly prevented LPS-induced neuroinflammation by suppressing the expression of pro-inflammatory cytokines including IL-1β and TNF-α. Meanwhile, ex vivo whole-cell slice electrophysiology combined with optogenetics showed that LPS-induced increase of medial prefrontal cortex (mPFC)-driven excitatory but not inhibitory synaptic transmission onto BLA projection neurons, thereby alleviating LPS-induced shift of excitatory/inhibitory balance towards excitation. In addition, harmine attenuated the increased intrinsic neuronal excitability of BLA PNs by reducing the medium after-hyperpolarization. In conclusion, our findings provide new evidence that harmine may exert its anxiolytic effect by downregulating LPS-induced neuroinflammation and restoring the changes in neuronal plasticity in BLA PNs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

This study investigated the effects of workplace ostracism on emotional labor and burnout among current nursing staff during the COVID-19 pandemic, as well as the relationship between the surface acting and deep acting of emotional labor as the mediators of workplace ostracism and burnout. The sample for this study consisted of 250 nursing staff recruited from Taiwanese medical institutions, and the questionnaire was divided into two stages. The first stage included questions about ostracism and personal data, and then two months later the same respondents completed part two of the questionnaire regarding emotional labor and burnout, which solved the problem of common-method variance (CMV). The results of this study indicate that ostracism had a positive and significant effect on burnout and surface acting, but its negative effect on deep acting was not supported. While surface acting showed partial mediation between ostracism and burnout, deep acting did not have a significant mediating effect between ostracism and burnout. These results can provide a reference for practice and researchers.

Background: 2,3-Dihydro-3,5-dihydroxy-6-methyl-4(H)-pyran-4-one (DDMP) and 5-hydroxymethylfurfural (HMF) are two main enolization products in the Maillard reaction and found in some foodstuffs. For many years, whether they are functional or noxious to human health has been a matter of debate. Thus, insight into their formation pathways is important to manage Maillard reaction products. In this study, DDMP and HMF were quantified and compared with regard to their formation and degradation in the d-glucose and l-proline Maillard reaction models using different moisture contents (0, 0.1, 0.5, 1.0, and 4.0 mL) at 150 °C for various heating times., Results: DDMP was predominantly generated in dry or low water-content heating models along with n increased 1-deoxyglucosone (1-DG) generation via 2,3-enolization. However, increasing moisture content resulted in a decay of reaction intensity, 1-DG, and DDMP due to a change in the reaction mechanism from 2,3-enolization to 1,2-enolization, which facilitated 3-deoxyglucosone (3-DG) and HMF formation., Conclusion: Increased moisture content in glucose-proline models reduced reaction intensity and also inhibited DDMP and facilitated HMF formation by promoting the pathway change from 2,3-enolization to 1,2-enolization to generate more 3-DG. A water content of 1.0 mL was identified as a critical value, from which the 1,2-enolization became a primary pathway occurring in the Maillard reaction. © 2022 Society of Chemical Industry., (© 2022 Society of Chemical Industry.)

Animal bite injuries are common in free-ranging cats in Taiwan, and most fatal animal bite events are presumed to be caused by dogs. However, speculation regarding animal abuse may occur when carcasses with prominent injuries are found by members of the general public. Local animal protection offices and veterinary clinicians sometimes face difficulties in convincing these individuals by identifying specific features of dog bite injuries in cat carcasses. Therefore, the present study analyzed injury patterns and distribution in 31 necropsied cats with animal bite injuries, and applied deoxyribonucleic acid (DNA) analysis for canine DNA identification in 13 cats. The main necropsy findings included puncture wounds (26 (83.9%)), linear or small, round contusions/abrasions (20 (64.5%)), lacerations/avulsions (17 (54.8%)), abdominal wall rupture/laceration (19 (61.3%)), herniation (16 (51.6%)), fractures (21 (67.7%)), broken claws (16 (51.6%)), and hair tufts on the body surface (28 (90.3%)). The most-commonly injured regions were the ventral thorax and axilla (23 (74.2%)), hind limbs (22 (71.0%)), shoulder-to-dorsal thorax (21 (67.7%)), back and flank (20 (64.5%)), abdomen (19 (61.3%)), neck (19 (61.3%)), and hip/tail/perineum (17 (54.8%)). Canine mitochondrial DNA was identified in 3 out of 11 cases (27.3%) that were sampled using wound swabs and in 4 out of 5 cases that had hair entrapped in broken claws. In conclusion, this study determined the distribution and features of dog bite injuries in cats and developed an elemental method using trace evidence for DNA identification in animal bites.

Virtual anime endorsement has been prevalent as an advertising strategy, and many companies invest massive amounts of money into virtual endorsements. While previous studies have found that endorser-product congruence is related to consumer brand attitude and purchase intention, it is not known whether moderate incongruence between a virtual anime endorser and a product has a positive influence on brand attitude and purchase intention. This study developed a 1 × 2 experiment to investigate the influences of virtual anime endorser-product congruence and moderate the endorser-product incongruence on consumer brand attitude and purchase intention. Product involvement played a key moderating role in the relationships of virtual anime endorser-product congruence and the endorser-product incongruence with consumer attitudes. A total of 919 participants were recruited from animation-related venues and stores in Taiwan. The findings of this study validated the interaction effects of virtual anime endorser-product congruence and incongruence on these two consumer responses, i.e., brand attitude and purchase intention. This study further investigated the moderating effect of product involvement in the relationships of virtual anime endorser-product congruence and moderate the endorser-product incongruence with consumer responses. The findings of this study provide a valuable reference regarding endorsers and product patterns through which enterprises can maximize their value., 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 Liang and Yang.)

Over the last 2 decades, omalizumab is the only anti-IgE antibody that has been approved for asthma and chronic spontaneous urticaria (CSU). Ligelizumab, a higher-affinity anti-IgE mAb and the only rival viable candidate in late-stage clinical trials, showed anti-CSU efficacy superior to that of omalizumab in phase IIb but not in phase III. This report features the antigenic-functional characteristics of UB-221, an anti-IgE mAb of a newer class that is distinct from omalizumab and ligelizumab. UB-221, in free form, bound abundantly to CD23-occupied IgE and, in oligomeric mAb-IgE complex forms, freely engaged CD23, while ligelizumab reacted limitedly and omalizumab stayed inert toward CD23; these observations are consistent with UB-221 outperforming ligelizumab and omalizumab in CD23-mediated downregulation of IgE production. UB-221 bound IgE with a strong affinity to prevent FcԑRI-mediated basophil activation and degranulation, exhibiting superior IgE-neutralizing activity to that of omalizumab. UB-221 and ligelizumab bound cellular IgE and effectively neutralized IgE in sera of patients with atopic dermatitis with equal strength, while omalizumab lagged behind. A single UB-221 dose administered to cynomolgus macaques and human IgE (ε, κ)-knockin mice could induce rapid, pronounced serum-IgE reduction. A single UB-221 dose administered to patients with CSU in a first-in-human trial exhibited durable disease symptom relief in parallel with a rapid reduction in serum free-IgE level.

Background: Employees are considered as one of the most important assets in many organizations, and their health well-being is critical to help achieve a sustainable and motivated workforce that is committed to delivering quality hospitality services through enhanced performance and productivity. Given the extent of the challenges and impact presented by the COVID-19 pandemic to the hospitality industry, it is timely to gain further insights on employees' health well-being. The key purpose of this study is to examine the relationships between health-related quality of life, achievement motivation and job performance in the Taiwan hospitality industry, to acquire a better understanding of their relationships through the job performance pathway models., Methods: This study has used a purposeful sampling technique to select the 10 highest-earning hospitality companies in Taiwan. A total of 292 questionnaires were collected from the employees of these hospitality companies. Based on the multi-dimensional concept of health-related quality of life (HRQoL), the relationships between the five key dimensions (i.e. psychological health, physical health, social health, achievement motivation, and job performance) were examined. To measure these dimensions, the survey questions were adapted from previous research such as the World Health Organization's WHOQOL-BREF scale, Minnesota Satisfaction Questionnaire. Partial least squares - Structural Equation Modeling method was used to explore these dimensions, and two job performance pathway models (for manager and staff) were subsequently developed., Results and Conclusions: Findings showed that psychological health directly affected the manager's job performance and physical health had a similar effect through social health. While psychological health had not affected the staff's job performance, but it could affect achievement motivation through both direct and indirect effects of social health. The pathway models that were developed indicated that the manager's job performance was mainly affected by psychological health and social health, whereas the key dimension that had affected the staff's job performance was achievement motivation., (© 2022. The Author(s).)

Dendritic spines are small, ratchet-like protrusions on neuronal dendrites that form synapses for receiving neuronal messages. Dendritic spine morphology is associated with synapse function. If neurons degrade or are damaged, the spine morphology of neurons changes. Given that most commercially available spine analysis software is expensive and complex, this study investigated a semi-automated spine analysis software, CTSpine, and used previously published data to verify the accuracy of the analysis results of this software. We also applied CTSpine to understand whether aging causes alterations in the hippocampal spine morphology and whether physical exercise can impede dendritic spine changes in 20 male Sprague Dawley rats. The spines of pyramidal cells in the hippocampal Cornu Ammonis 1 (CA1) region in the aging group were more enriched in filopodium type pattern than those in the control group, whereas the spines of the exercised aging group showed a similar pattern to that of the control. No significant changes were observed in neuronal dendritic spines in other hippocampal regions. However, long-term hippocampal memory was considerably decreased in the aging group, which was reversed to some extent in the exercised aging group. CTSpine, a self-developed semi-automatic spine analysis software, showed results similar to those noted in published data and can be effectively applied to the study of dendritic patterns, including neurodevelopment and disease., (Copyright © 2022 Elsevier Inc. All rights reserved.)

C-phycocyanin from Spirulina platensis has pharmacological effects such as anti-oxidation, anti-cancer, anti-inflammatory and anti-atherosclerosis activities as well as liver and kidney protection. However, there is little research on C-phycocyanin applied in the field of reproductive medicine, and it is therefore the focus of the current study. In this study, a GC-1 spg cell model and male mouse reproductive injury model were constructed by TNF α + Smac mimetic + zVAD-fmk (TSZ) and cyclophosphamide (Cy), respectively. It has been proved that C-phycocyanin can increase cell viability and reduce cell death in GC-1 spg cells induced by TSZ. C-phycocyanin could protect the reproductive system of male mice from cyclophosphamide, improve spermatogenesis, sperm quality and fertility, increase the release of testosterone, stabilize the feedback regulation mechanism, and ensure the spermatogenic ability of mice. It could also improve the ability of anti-oxidation. In addition, C-phycocyanin could play a protective role by down-regulating RIPK1, RIPK3, and p-MLKL to inhibit the necroptotic signaling pathway. These results suggest that C-phycocyanin could protect GC-1 spg cells and the reproductive system of male mice from TSZ and cyclophosphamide, and the protective mechanism may be achieved by inhibiting the signal pathway of necroptosis. Therefore, C-phycocyanin could serve as a promising reproductive system protective agent. C-phycocyanin may enter public life as a health product in the future.

Background: The murine transverse aortic constriction (TAC) model is frequently used to investigate molecular mechanisms underlying heart failure. However, limited data is available regarding the expression of mRNAs and circRNAs in murine heart failure progression induced by pressure overload., Methods: Transverse aortic constriction was used to induce pressure overload for 2, 4, and 8 weeks in mice. Echocardiographic measurements in B-mode and M-mode, as well as blood flow Doppler data were collected in mice without (sham) and with (2W-, 4W-, and 8W-post-TAC) pressure load. Hearts were excised and morphology, cardiomyocyte size, and fibrosis were determined. RNA sequencing, circRNA microarray, functional mRNA enrichment analysis, hub gene identification, target miRNA interaction, and competitive endogenous RNA (ceRNA) network construction were conducted., Results: Heart weight, cardiomyocyte hypertrophy, and fibrosis gradually increased over time in the hearts with pressure overload. The 2W-post-TAC hearts displayed concentric hypertrophy, thickened left ventricular walls, and increased EF and FS. The 4W-post-TAC hearts were characterized by preserved EF and FS, dilated atria, and increased left ventricle (LV) systolic volume. The 8W-post-TAC hearts presented with ventricular and atrial dilation, increased LV systolic and diastolic volume, reduced EF and FS, and increased ejection time (MV ET). mRNA expression analysis suggested that cardiac remodeling, immune response dysregulation, and metabolic disorder were the key cellular events in heart failure progression. Depression in chemotaxis and mitochondrial function were predicted in 4W- and 8W-post-TAC myocardia, respectively. A ceRNA network analysis demonstrated that the circRNAs targeted the expression of genes enriched in metabolism dysregulation in the 2W-post-TAC hypertrophic hearts, while they targeted genes enriched in cardiac remodeling in the 4W-post-TAC EF-preserved hearts and in the suppression of oxidative phosphorylation and cardiac contraction in the 8W-post-TAC EF-reduced hearts., Conclusion: Our work empirically demonstrates that distinctive features of heart failure, including ventricular hypertrophy, heart failure with preserved EF (HFpEF), and heart failure with reduced EF (HFrEF) are present in the murine pressure overload models. The three stages of heart failure vary in terms of mRNA and circRNA expression, as well as ceRNA regulation in a manner consistent with their structural, functional, and pathological differences., 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 Li, Tan, Zheng, Pyle, Zhu, Chen, Kang, Wu, Zou, Backx and Yang.)

More than half of heart failure (HF) cases are classified as heart failure with preserved ejection fraction (HFpEF) worldwide. Large animal models are limited for investigating the fundamental mechanisms of HFpEF and identifying potential therapeutic targets. This work provides a detailed description of the surgical procedure of descending aortic constriction (DAC) in Tibetan minipigs to establish a large animal model of HFpEF. This model used a precisely controlled constriction of the descending aorta to induce chronic pressure overload in the left ventricle. Echocardiography was used to evaluate the morphological and functional changes in the heart. After 12 weeks of DAC stress, the ventricular septum was hypertrophic, but the thickness of the posterior wall was significantly reduced, accompanied by dilation of the left ventricle. However, the LV ejection fraction of the model hearts was maintained at >50% during the 12-week period. Furthermore, the DAC model displayed cardiac damage, including fibrosis, inflammation, and cardiomyocyte hypertrophy. Heart failure marker levels were significantly elevated in the DAC group. This DAC-induced HFpEF in minipigs is a powerful tool for investigating molecular mechanisms of this disease and for preclinical testing.

Background: Pressure overload can result in dilated cardiomyopathy. The beneficial effects of n-3 polyunsaturated fatty acids (n-3 PUFAs) on heart disorders have been widely recognized. However, the molecular mechanisms underlying their protective effects against cardiomyopathy remain unclear. Methods: Pressure overload in mice induced by 8 weeks of transverse aortic constriction was used to induce dilated cardiomyopathy. A transgenic fat-1 mouse model carrying the n-3 fatty acid desaturase gene fat-1 gene from Caenorhabditis elegans was used to evaluate the mechanism of n-3 PUFAs in this disease. Echocardiography, transmission electron microscopy, and histopathological analyses were used to evaluate the structural integrity and function in pressure overloaded fat-1 hearts. mRNA sequencing, label-free phosphoprotein quantification, lipidomics, Western blotting, RT-qPCR, and ATP detection were performed to examine the effects of n-3 PUFAs in the heart. Results: Compared with wild-type hearts, left ventricular ejection fraction was significantly improved (C57BL/6J [32%] vs. fat-1 [53%]), while the internal diameters of the left ventricle at systole and diastole were reduced in the fat-1 pressure overload hearts. mRNA expression, protein phosphorylation and lipid metabolism were remodeled by pressure overload in wild-type and fat-1 hearts. Specifically, elevation of endogenous n-3 PUFAs maintained the phosphorylation states of proteins in the subcellular compartments of sarcomeres, cytoplasm, membranes, sarcoplasmic reticulum, and mitochondria. Moreover, transcriptomic analysis predicted that endogenous n-3 PUFAs restored mitochondrial respiratory chain function that was lost in the dilated hearts, and this was supported by reductions in detrimental oxylipins and protection of mitochondrial structure, oxidative phosphorylation, and ATP production. Conclusions: Endogenous n-3 PUFAs prevents dilated cardiomyopathy via orchestrating gene expression, protein phosphorylation, and lipid metabolism. This is the first study provides mechanistic insights into the cardioprotective effects of n-3 PUFAs in dilated cardiomyopathy through integrated multi-omics data analysis., 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 Li, Tan, Zheng, Zhang, Zhu, Cai, Chen, Yang, Kang, Pan, Pyle, Backx, Zou and Yang.)

Alleviating odontoblast inflammation is crucial to control the progression of pulpitis. Mitochondrial DNA (mtDNA) is a vital driver of inflammation when it leaks from mitochondria of inflamed odontoblasts into the cytosol. Bacteria-induced inflammation leads to a novel type of cell death named pyroptosis. The canonical pyroptosis is a gasdermin (GSDM)-dependent cytolytic programmed cell death characterized by cell swelling and pore formation in the plasma membrane. To date, whether odontoblast cytosolic mtDNA regulates dental pulp inflammation through the canonical pyroptosis pathway remains to be elucidated. In this study, high gasdermin D (GSDMD) expression was detected in human pulpitis. We found that LPS stimulation of mDPC6T cells promoted BAX translocation from the cytosol to the mitochondrial membrane, leading to mtDNA release. Moreover, overexpression of isolated mtDNA induced death in a large number of mDPC6T cells, which had the typical appearance of pyroptotic cells. Secretion of the inflammatory cytokines CXCL10 and IFN-β was also induced by mtDNA. These results suggest that cytosolic mtDNA participates in the regulation of odontoblast inflammation through GSDMD-mediated pyroptosis in vitro. Interestingly, after overexpression of mtDNA, the expression of inflammatory cytokines CXCL10 and IFN-β was increased and not decreased in GSDMD knockdown mDPC6T cells. We further proposed a novel model in which STING-dependent inflammation in odontoblast-like cell is a compensatory mechanism to control GSDMD-mediated pyroptosis, jointly promoting the immune inflammatory response of odontoblasts. Collectively, these findings provide the first demonstration of the role of the mtDNA-GSDMD-STING in controlling odontoblast inflammation and a detailed description of the underlying interconnected relationship., (© 2021. The Author(s).)

Isatis indigotica Fort . , as a common Chinese medicinal raw material, will lose its medicinal value if it blooms early, so it is highly valuable to clarify the induction mechanism of the vernalization of I. indigotica at low temperature. In this study, the concentrations of soluble sugar, proline, glutathione and zeatin in two germplasms of I. indigotica with different degrees of low temperature tolerance (Y1 and Y2) were determined at 10 days, 20 days and 30 days of low-temperature treatment, and the full-length transcriptome of 24 samples was sequenced by Nanopore sequencing with Oxford Nanopore Technologies (ONT). After that, the data of transcripts involved in the vernalization of I. indigotica at low temperature were obtained, and these transcripts were identified using weighted gene co-expression network analysis (WGCNA). The results revealed the massive accumulation of soluble sugar and proline in Y1 and Y2 after low temperature induction. A total of 18,385 new transcripts, 6168 transcription factors and 470 lncRNAs were obtained. Differential expression analysis showed that gibberellin, flavonoids, fatty acids and some processes related to low temperature response were significantly enriched. Eight key transcripts were identified by WGCNA, among which ONT.14640.1, ONT.9119.1, ONT.13080.2 and ONT.16007.1 encodes a flavonoid transporter, 9-cis-epoxycarotenoid dioxygenase 3 (NCED3), growth factor gene and L-aspartate oxidase in plants, respectively . It indicated that secondary metabolites such as hormones and flavonoids play an important role in the vernalization of I. indigotica . qRT-PCR proved the reliability of transcriptome results. These results provide important insights on the low-temperature vernalization of I. indigotica , and provide a research basis for analyzing the vernalization mechanism of I. indigotica ., Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-021-01110-2., Competing Interests: Conflict of interestThere are no conflicts of interest., (© The Author(s) 2021.)

Aged nonhuman primate (NHP) models are of great value for studying the pathology of metabolic heart diseases and developing therapeutic strategies. In this study, aged male cynomolgus monkeys were fed a regular diet or a high-fat/high-sugar diet (HFSD) for 8 months. Metabolic disorders were diagnosed by 1 H-NMR and serum biochemistry, and cardiac function was evaluated by echocardiography. Our results showed that serum metabolic profiles were altered in aged monkeys fed a HFSD, in line with aortic tissue damage, cardiac remodeling, and contractile dysfunction. This aged monkey model significantly increased expression of proinflammatory cytokines and altered expression and phosphorylation of intracellular signaling proteins in the heart, as compared to aged monkeys on a regular diet. Furthermore, the animals demonstrated increased phosphorylation of cardiac myofilament proteins which are causatively associated with decreased myofilament contractility. We conclude that the aged monkey model fed a HFSD exhibits metabolic disorders and cardiac contractile dysfunction., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Background: Small blood stem cells (SB cells), isolated from human peripheral blood, demonstrated the ability to benefit bone regeneration and osseointegration. The primary goal of our study is to examine the safety and tolerability of SB cells in dental implantation for human patients with severe bone defects., Methods: Nine patients were enrolled and divided into three groups with SB cell treatment doses of 1 × 10 5 , 1 × 10 6 , and 1 × 10 7 SB cells, and then evaluated by computed tomography (CT) scans to assess bone mineral density (BMD) by Hounsfield units (HU) scoring. Testing was conducted before treatment and on weeks 4, 6, 8, and 12 post dental implantation. Blood and comprehensive chemistry panel testing were also performed., Results: No severe adverse effects were observed for up to 6-month trial. Grade 1 leukocytosis, anemia, and elevated liver function were observed, but related with the patient's condition or the implant treatment itself and not the transplantation of SB cells. The levels of cytokines and chemokines were detected by a multiplex immunological assay. Elevated levels of eotaxin, FGF2, MCP-1, MDC, and IL17a were found among patients who received SB cell treatment. This observation suggested SB cells triggered cytokines and chemokines for local tissue repair. To ensure the efficacy of SB cells in dental implantation, the BMD and maximum stresses via stress analysis model were measured through CT scanning. All patients who suffered from severe bone defect showed improvement from D3 level to D1 or D2 level. The HU score acceleration can be observed by week 2 after guided bone regeneration (GBR) and prior to dental implantation., Conclusions: This phase I study shows that treatment of SB cells for dental implantation is well tolerated with no major adverse effects. The use of SB cells for accelerating the osseointegration in high-risk dental implant patients warrants further phase II studies., Trial Registration: Taiwan Clinical Trial Registry ( SB-GBR001 ) and clinical trial registry of the United States ( NCT04451486 ).

Heart failure is induced by multiple pathological mechanisms, and current therapies are ineffective against heart failure with preserved ejection fraction (HFpEF). As there are limited animal models of HFpEF, its underlying mechanisms have not yet been elucidated. Here, we employed the descending aortic constriction (DAC) technique to induce chronic pressure overload in the left ventricles of Tibetan minipigs for 12 weeks. Cardiac function, pathological and cellular changes, fibrotic signaling activation, and gene expression profiles were explored. The left ventricles developed concentric hypertrophy from weeks 4 to 6 and transition to dilation starting in week 10. Notably, the left ventricular ejection fraction was maintained at >50% in the DAC group during the 12-week period. Pathological examination, biochemical analyses, and gene profile analysis revealed evidence of inflammation, fibrosis, cell death, and myofilament dephosphorylation in the myocardium of HFpEF model animals, together with gene expression shifts promoting cardiac remodeling and downregulating metabolic pathways. Furthermore, we noted the activation of several signaling proteins that impact cardiac fibrosis and remodeling, including transforming growth factor-β/SMAD family members 2/3, type I/III/V collagens, phosphatidylinositol 3-kinase, extracellular signal-regulated kinase, matrix metalloproteinases 2 and 9, tissue inhibitor of metalloproteinases 1 and 2, interleukins 6 and 1β, and inhibitor of κBα/nuclear factor-κB. Our findings demonstrate that this chronic pressure overload-induced porcine HFpEF model is a powerful tool to elucidate the mechanisms of this disease and translate preclinical findings., 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 Tan, Li, Zheng, Li, Zhang, Pyle, Chen, Wu, Sun, Zou, Backx and Yang.)

Background: Mitochondrial DNA (mtDNA) is a vital driver of inflammation when it leaks from damaged mitochondria into the cytosol. mtDNA stress may contribute to cyclic GMP-AMP synthase (cGAS) stimulator of interferon genes (STING) pathway activation in infectious diseases. Odontoblasts are the first cells challenged by cariogenic bacteria and involved in maintenance of the pulp immune and inflammatory responses to dentine-invading pathogens. In this study, we investigated that mtDNA as an important inflammatory driver participated in defending against bacterial invasion via cGAS-STING pathway in odontoblasts., Methods: The normal tissues, caries tissues and pulpitis tissues were measured by western blotting and immunohistochemical staining. Pulpitis model was built in vitro to evaluated the effect of the cGAS-STING pathway in odontoblast-like cell line (mDPC6T) under inflammation. Western blot and real-time PCR were performed to detect the expression of cGAS-STING pathway and pro-inflammatory cytokines. The mitochondrial function was evaluated reactive oxygen species (ROS) generated by mitochondria using MitoSOX Red dye staining. Cytosolic DNA was assessed by immunofluorescent staining and real-time PCR in mDPC6T cells after LPS stimulation. Furthermore, mDPC6T cells were treated with ethidium bromide (EtBr) to deplete mtDNA or transfected with isolated mtDNA. The expression of cGAS-STING pathway and pro-inflammatory cytokines were measured., Results: The high expression of cGAS and STING in caries and pulpitis tissues in patients, which was associated with inflammatory progression. The cGAS-STING pathway was activated in inflamed mDPC6T. STING knockdown inhibited the nuclear import of p65 and IRF3 and restricted the secretion of the inflammatory cytokines CXCL10 and IL-6 induced by LPS. LPS caused mitochondrial damage in mDPC6T, which promoted mtDNA leakage into the cytosol. Depletion of mtDNA inhibited the cGAS-STING pathway and nuclear translocation of p65 and IRF3. Moreover, repletion of mtDNA rescued the inflammatory response, which was inhibited by STING knockdown., Conclusion: Our study systematically identified a novel mechanism of LPS-induced odontoblast inflammation, which involved mtDNA leakage from damaged mitochondria into the cytosol stimulating the cGAS-STING pathway and the inflammatory cytokines IL-6 and CXCL10 secretion. The mtDNA-cGAS-STING axis could be a potent therapeutic target to prevent severe bacterial inflammation in pulpitis. Video Abstract.

Objective: To explore the effect of bone marrow mesenchymal stem cells (BM-MSCs) transplantation on the changes of oligodendrocyte lineage in brain of experimental autoimmune encephalomyelitis (EAE) rats., Methods: The animals were divided into normal control group, EAE model group (EAE group), cell culture medium injection treatment group (placebo treatment group), and MSCs treatment group (treatment group). The changes of A2B5-, O4-, and CNPase-positive cells in oligodendrocyte lineage in rat brain were observed after 1, 3, 7, 14, 21, and 28 days., Results: The number of A2B5-positive cells in rat brain of the treatment group at each time point was significantly more than that of the EAE and placebo treatment groups, and most obvious at 14 days. The O4-positive cells number at each time point in the treatment group was significantly increased compared with the EAE and placebo treatment groups, and most obvious at 14 days. The CNPase-positive cells number at each time point in the treatment group was significantly increased compared with the EAE and placebo treatment groups, and most obvious at 14 days., Conclusions: MSCs treatment can increase cells expression in oligodendrocyte lineage, which laying a solid foundation for myelin regeneration., (© 2020 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Background: Mesenchymal stem cells (MSCs) have been proved to drive castration resistant prostate cancer (CRPC). In this study, we aim to investigate the contribution of MSCs to the development of docetaxel resistance in CRPC cells and its potential mechanisms., Methods: The effect of MSCs on CRPC cells resistance to docetaxel was determined using in vivo and in vitro approaches. CCK8 and PI/Annexin V-FITC assay were used to examined the cell viability and apoptosis. The concentration of transforming growth factor-β1 was measured by enzyme-linked immunosorbent assay and small interfering RNA was used for functional analyses., Results: MSCs significantly reduced the sensitivity of CRPC cells to docetaxel-induced proliferation inhibition and apoptosis promotion in vivo and in vitro. CRPC cells cocultured with MSCs under docetaxel administration have an increased autophagy activation, while autophagy inhibitor could effectively reversed MSCs-induced resistance to docetaxel. Additionally, MSCs-induced CRPC cell autophagy increase under docetaxel administration depends on MSCs secreting TGF-β1 and inhibition of TGF-β1 secretion in MSCs could consequently increase the sensitivity of CRPC cells to docetaxel., Conclusions: These results suggest that docetaxel administrated CRPC cells may elicit MSCs secreting TGF-β1 increase, which desensitizes CRPC to docetaxel chemotherapy accelerating chemoresistance occurrence via inducing cell autophagy.

Stroke may cause severe death and disability but many clinical trials have failed in the past, partially because the lack of an effective method to regenerate new neurons after stroke. In this study, we report an in vivo neural regeneration approach through AAV NeuroD1-based gene therapy to repair damaged brains after ischemic stroke in adult non-human primates (NHPs). We demonstrate that ectopic expression of a neural transcription factor NeuroD1 in the reactive astrocytes after monkey cortical stroke can convert 90% of the infected astrocytes into neurons. Interestingly, astrocytes are not depleted in the NeuroD1-converted areas, consistent with the proliferative capability of astrocytes. Following ischemic stroke in monkey cortex, the NeuroD1-mediated astrocyte-to-neuron (AtN) conversion significantly increased local neuronal density, reduced microglia and macrophage, and surprisingly protected parvalbumin interneurons in the converted areas. Furthermore, the NeuroD1 gene therapy showed a broad time window in AtN conversion, from 10 to 30 days following ischemic stroke. The cortical astrocyte-converted neurons showed Tbr1 + cortical neuron identity, similar to our earlier findings in rodent animal models. Unexpectedly, NeuroD1 expression in converted neurons showed a significant decrease after 6 months of viral infection, indicating a downregulation of NeuroD1 after neuronal maturation in adult NHPs. These results suggest that in vivo cell conversion through NeuroD1-based gene therapy may be an effective approach to regenerate new neurons for tissue repair in adult primate brains., (Copyright © 2020 Ge, Yang, Li, Wang, Lin, Feng, Chen, Jiang, Wang, Hu and Chen.)

Purpose: To report the surgical outcomes of primary rhegmatogenous retinal detachment (RRD) repaired by 27-gauge pars plana vitrectomy combined with Healaflow patch and air tamponade., Methods: In an initial vitro experiment, we observed and compared the dissolution and displacement of the dispersion spots of 0.05-mL Healaflow and sodium hyaluronate. We then performed a prospective, interventional cohort study on 38 eyes in 37 consecutive patients with primary rhegmatogenous retinal detachment. All eyes underwent pars plana vitrectomy combined with Healaflow patch and air tamponade; the postoperative period did not involve prone positioning. The primary and final anatomical attachment rate, best-corrected visual acuity, and intraoperative and postoperative complications were evaluated., Results: In the in vitro experiment, the viscoelastic Healaflow remained adherent with no change in the size of the area; however, the control dissolved completely in the balance solution. The patient study included 16 women (43.2%) and 21 men (56.8%) (mean age, 59.5 ± 9.5 years; mean follow-up period, 8.9 ± 3.8 months). A single break was present in 21 (55.3%) and 2 to 5 breaks in 17 cases (44.8%). The macula was involved in 25 (65.8%) and attached in 13 cases (34.2%) intraoperatively. Initial reattachment was achieved in 37 (97.4%) and final reattachment in 38 cases (100%). In one case (2.6%), the macula redetached because of failure of the chorioretinal scar to develop around the treated break. Mean preoperative and postoperative best-corrected visual acuities were 1.02 ± 0.82 logarithm of the minimum angle of resolution (median Snellen acuity: 20/125, range: 20/20,000-20/20) and 0.23 ± 0.17 logarithm of the minimum angle of resolution (median Snellen acuity: 20/32, range: 20/100-20/20), respectively (P < 0.001). Intraocular pressure was elevated transiently in 28 eyes (73.7%). There were no other intraoperative complications or postoperative scleral incision leakage., Conclusion: A 27-gauge pars plana vitrectomy combined with Healaflow patch, and air tamponade results in a high reattachment rate in the treatment of rhegmatogenous retinal detachment. Thus, patients can benefit from early visual recovery and less complications.

Background: The secreted glycoprotein Slit2, previously known as an axon guidance cue, has recently been found to protect tissues in pathological conditions; however, it is unknown whether Slit2 functions in cardiac ischemia-reperfusion (IR) injury., Methods: Langendorff-perfused isolated hearts from Slit2-overexpressing (Slit2-Tg) mice and C57BL/6J mice (background strain) were subjected to 20 min of global ischemia followed by 40 min of reperfusion. We compared Slit2-Tg with C57BL/6J mice in terms of left ventricular function and infarct size of post-IR hearts along with tissue histological and biochemical assessments (mRNA and protein expression, phosphorylation status, and myofilament contractile properties)., Results: Slit2 played cardioprotective roles in maintaining contractile function and reducing infarct size in post-IR hearts. IR increased the expression of the Slit2 receptor Robo4 and the membrane receptor Slamf7, but these increases were suppressed by Slit2 overexpression post IR. This suppression was associated with inhibition of the nuclear translocation of NFκB p65 and reductions in IL-1β and IL-18 release into perfusates. Furthermore, Slit2 overexpression attenuated the increases in myofilament-associated PKCs and phosphorylation of cTnI at Ser43 in the post-IR myocardium. The myofilament calcium sensitivity and actomyosin MgATPase activity were preserved in the post-IR Slit2 myocardium., Conclusion: Our work demonstrates that Slit2 inhibits inflammatory responses and maintains myofilament contractile properties, thus contributing, at least in part, to the prevention of structural and functional damage during IR., (Copyright © 2020 Li, Zheng, Tan, Chen, Li, Wu, Luo, Ren, Pyle, Wang, Backx, Huang and Yang.)

Each odontoblast is tightly linked to other odontoblasts. They form a line of defense and are capable of withstanding external stimuli, particularly the inflammation caused by caries. Thus, we investigated exosomes derived from odontoblasts as an intercellular mechanism by which inflamed odontoblasts are protected from apoptosis. CD63, an exosome marker, was expressed at high levels in caries-affected regions of the dental pulp. We conducted an ex vivo experiment by applying different concentrations of lipopolysaccharide (LPS) to the odontoblast-like cells (mineralization was induced in stem cells derived from the apical papilla). Odontoblast-like cells treated with a high concentration of LPS (20 µg/mL LPS, severely affected) exhibited an accelerated release of exosomes, which attenuated the LPS-induced cell apoptosis of odontoblast-like cells treated with a low concentration of LPS (1 µg/mL LPS, mildly affected). Next, we blocked exosome uptake with chlorpromazine, and the rescue effect vanished. Based on our findings, severely inflamed odontoblasts attenuate the apoptosis of mildly inflamed neighboring cells through an exosome-mediated intercellular signaling pathway.

Background: Evidence-based studies propose that the aspirate pH test may be easily and reliably conducted to verify the proper placement of nasogastric tubes (NGTs). Nurses rarely implement this procedure because of the lack of related knowledge., Purpose: The purpose of this study was to explore the feasibility of implementing a revised standard care procedure to enhance nurses' ability to verify placement of the NGT., Methods: his study used a quasi-experimental, longitudinal research design. Nurses from two intensive care units were randomly assigned to the experimental group (n = 35) and the control group (n = 31). A revised standard-of-care procedure to confirm the proper placement of an NGT was incorporated into a slideshow presentation, a printed leaflet, and an audit checklist. The experimental group received continuous education and individual teaching on the revised standard-of-care procedure, whereas the control group did not receive additional education and continued to provide conventional care. The study gathered data using scales designed to address knowledge of and attitudes toward verification of NGT placement and the checklist for auditing the NGT care procedure. Scales were implemented before and after the practice program was conducted, in Months 1, 2, and 3, to evaluate the feasibility of the developed improvement measures., Results: This study found significant improvements in the experimental group in terms of knowledge regarding NGT placement verification and the NGT care auditing procedure. The positive improvement of the intervention on the NGT care auditing procedure remained for at least 3 months after the end of the intervention., Conclusions: The findings suggest that using an aspirate pH test is a feasible approach to verify NGT placement in critical care units, a crucial aspect of care necessary to promote patient safety and quality of care.

The Resonant Integrated Optic Gyroscope (RIOG) is a type of high accuracy gyroscope based on the Sagnac effect. A symmetrical resonance curve is very important to the performance of the RIOG. To further investigate and design a RIOG with a waveguide ring resonator, an in-depth research of the asymmetric resonance curve and its influence on the RIOG is fully developed. Four possible optical noises inducing the resonance curve asymmetry are analyzed and their mathematic models are established. These four optical noises are the normal mode effect, the backscattering noise, the backreflection noise and the polarization noise. Any asymmetry of the resonance curve will not only induce a large output bias error into the gyro output, but also seriously decrease the frequency discrimination parameter of the demodulation curve. By using a tunable fiber laser, the high aspect ratio silicon nitride WRR and the silicon dioxide WRR were tested. The experiment measured resonance curves can be well fitted with the theoretical simulation results. The experimental results show that a high aspect ratio silicon nitride waveguide can effectively suppress the polarization noise in the RIOG.

Fine particulate matter 2.5 (PM 2.5 ) induces free radicals and oxidative stress in animals, leading to a range of illnesses. In this study, Ganoderma Microsporum immunomodulatory (GMI) proteins were administered to alleviate PM 2.5 -induced inflammatory responses in mother rats, and PM 2.5 -induced inflammatory responses and neurological damage in their offspring. The results suggested that GMI administration decreased the risk of neurological disorders in mother rats and their offspring by reducing the white blood cell count, lessening inflammatory responses and PM 2.5 -induced memory impairment, and preventing dendritic branches in the hippocampi from declining and microRNAs from PM 2.5 -induced modulation.

Background: Administration of a single broadly neutralizing human immunodeficiency virus (HIV)-specific antibody to HIV-infected persons leads to the development of antibody-resistant virus in the absence of antiretroviral therapy (ART). It is possible that monotherapy with UB-421, an antibody that blocks the virus-binding site on human CD4+ T cells, could induce sustained virologic suppression without induction of resistance in HIV-infected persons after analytic treatment interruption., Methods: We conducted a nonrandomized, open-label, phase 2 clinical study evaluating the safety, pharmacokinetics, and antiviral activity of UB-421 monotherapy in HIV-infected persons undergoing analytic treatment interruption. All the participants had undetectable plasma viremia (<20 copies of HIV RNA per milliliter) at the screening visit. After discontinuation of ART, participants received eight intravenous infusions of UB-421, at a dose of either 10 mg per kilogram of body weight every week (Cohort 1) or 25 mg per kilogram every 2 weeks (Cohort 2). The primary outcome was the time to viral rebound (≥400 copies per milliliter)., Results: A total of 29 participants were enrolled, 14 in Cohort 1 and 15 in Cohort 2. Administration of UB-421 maintained virologic suppression (<20 copies per milliliter) in all the participants (94.5% of measurements at study visits 2 through 9) during analytic treatment interruption, with intermittent viral blips (range, 21 to 142 copies per milliliter) observed in 8 participants (28%). No study participants had plasma viral rebound to more than 400 copies per milliliter. CD4+ T-cell counts remained stable throughout the duration of the study. Rash, mostly of grade 1, was a common and transient adverse event; one participant discontinued the study drug owing to a rash. A decrease in the population of CD4+ regulatory T cells was observed during UB-421 monotherapy., Conclusions: UB-421 maintained virologic suppression (during the 8 to 16 weeks of study) in participants in the absence of ART. One participant discontinued therapy owing to a rash. (Funded by United Biomedical and others; ClinicalTrials.gov number, NCT02369146.)., (Copyright © 2019 Massachusetts Medical Society.)

Silver fox and blue fox belong to different genera, and the hybrid males are reproductively sterile. In the present study, there was a comparison of testicular and epididymal morphology and serum hormone concentrations among silver foxes, blue foxes, and the hybrids during the pre-breeding period, using 20 male silver foxes, 20 male blue foxes, 15 male HSBs (silver fox male × blue fox female hybrids) and 15 male HBSs (blue fox male × silver fox female hybrids), respectively. Hybrids had a smaller diameter of seminiferous tubules than pure-species males, and testes of hybrid males did not differ in mean size and relative weight from pure-species males. There were many Sertoli cells and spermatogenic cells in silver foxes and blue foxes, while numbers of spermatogonia and primary spermatocytes were less with no secondary spermatocytes in the hybrids. Furthermore, mean serum testosterone and estradiol concentrations in the hybrids were less, and FSH, LH, and PRL were greater than that in silver foxes and blue foxes (P <  0.05), suggesting that lesser concentrations of testosterone and estradiol and greater concentrations of FSH, LH and prolactin can inhibit the completion of spermatogenesis during the pre-breeding period. The results indicate that fox hybrid sterility may result from failures at the early stages of spermatogenesis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Deer is valuable all over the body,which is rich in nutritional value and medicinal value. Deer breeding and processing are very advanced in North America and New Zealand where many related standards have been published. The development of Chinese deer industry lack standard and normal management,neither standards' number nor coverage area formed complete frame structure. The international standards like Panax ginseng and P. notoginseng were more lacked. This paper makes a classification statistics on standardization organizations at home and abroad,foreign standards,Chinese national standards,industry standards,local standards and enterprise standards. The classes,contents,ages,implementation and promotion and demonstration area construction of standards were compared and analyzed. We found Chinese deer industry standards were deficient in coverage,uniformity,innovation,repeatability and support. And we give advises for the construction of industry quality standard system,organizational mobility and ideology of consumers,hoping to boost the standard construction and promote international competitiveness of Chinese deer industry.

Periapical lesions are the distinct result of chronic root canal infection and could generate severe bone resorption surrounding apical regions. Despite the local cytokine and cell-mediated immune responses, periapical lesions are also characterized by its auto-restrict inflammation. However, the detailed mechanism related to its auto-restriction of immune response is still unclear. Co-inhibitory immune checkpoints are important molecules which could negatively modulate immune response especially in T cell function. In this study we detected the expressional pattern of PD-1/LAG-3 in periapical lesions. Immunohistochemical staining showed that the inflammatory response including up-regulation of TNF-α and the infiltration of T cells, was severe in granuloma and restricted in periapical cyst. PD-1 and LAG-3 both could be detected in granuloma and cyst, while scarcely observed in control group. Exhausted T cells, characterized by PD-1 or LAG-3 positive, accumulated within granuloma and reduced in cyst. Our study revealed that in periapical lesions, T cell exhaustion characterized by PD-1 or LAG-3 positive, might contribute to the auto-restriction of inflammatory response in periapical lesions., Competing Interests: None.

A series of conjugates of 10-hydroxy camptothecin (HCPT) with functionalized norcantharidin derivatives were regio-selectively synthesized in the condition of (3-dimethylaminopropyl) ethyl-carbodiimide monohydrochloride in a moderate yield. The synthesized conjugate HCPT pro-drugs can also suppress cancer cell growth in vitro . These conjugated pro-drug constructs possess therapeutic potential as novel bi-functional conjugate platforms for cancer treatment., Competing Interests: The authors declare that they have no competing interest.

Self-biting disease occurs in most farmed fur animals in the world. The mechanism and rapid detection method of this disease has not been reported. We applied bulked sergeant analysis (BSA) in combination with RAPD method to analyze a molecular genetic marker linked with self-biting trait in mink group. The molecular marker was converted into SCAR and loop-mediated isothermal amplification (LAMP) marker for rapid detection of this disease. A single RAPD marker A10 amplified a specific band of 1000bp in self-biting minks. The sequences of the bands exhibited 73% similarity to the Canis Brucella. SCAR and LAMP marker were designed for the specific fragment of RAPD marker A10 and validated in 30 self-biting minks and 30 healthy minks. c2 test showed difference (p0.05) with SCAR and significant difference (p0.01) with LAMP in the detection rate between the two groups, but LAMP method was more accurate than SCAR method. This indicated that LAMP can be used as a positive marker to detect self-biting disease in minks., (Copyright© by the Polish Academy of Sciences.)

Objective: To evaluate the clinical impact of ketogenic diet (KD) on children with pharmacoresistant epileptic encephalopathy., Methods: In all, 52 children with pharmacoresistant epileptic encephalopathy that diagnosed in our hospital from July 2012 to June 2015 were selected, including West syndrome 38 cases, Lennox-Gastaut Syndrome 7 cases, Doose Syndrome 1 case, and Dravet syndrome 6 cases, and the effect, compliance, adverse reactions, electroencephalogram (EEG), and cognitive function were analyzed. Modified Johns Hopkins protocol was used to initiate KD, and Engel scale was used to evaluate the effect, and evaluated the effect of KD on the cognition, language, and motor function., Results: At 12 weeks of KD treatment, the patients achieved I, II, III, and IV grade effect were accounted for 26.9% (14/52 cases), 17.3% (9/52 cases), 11.5% (6/52 cases), and 44.2% (23/52 cases), respectively, according to Engel scale. KD has different effect on different epileptic syndromes, best effect on Doose syndromes of 100%, and better effect on West syndrome with the effect rate of 57.9%, and the total effect number was 22 cases. The reduction of epileptiform discharges in the awake state before KD treatment was correlated with the seizure time after 3 months of KD treatment ( r  =   .330, p  = .017). The cognitive function of 23 patients was improved, 12 patients had language improvement, and the motor function was improved in 10 patients. In all, 23 patients had adverse reactions, and all patients were tolerated and improved., Conclusion: KD has certain effect on children with pharmacoresistant epileptic encephalopathy, and it can reduce interictal epileptic discharge frequency, and improve the background rhythm of EEG. The reduction of epileptiform discharges in awake state is in favor of the reduction of seizures frequency, thus increasing the efficacy, and improve the cognitive function, language, and motor function to varying degrees, combined with less adverse reaction, which is worthy of clinical application.

Objective: To study the reference ranges of six sex hormones, i.e., luteinizing hormone, follicle-stimulating hormone, progesterone, prolactin, estradiol, and testosterone, for healthy children aged 0-18 years in Shenzhen, China., Methods: Stratified cluster sampling was performed to select 2 178 healthy children aged 0-18 years in the districts of Futian, Luohu, Nanshan, Bao'an, and Longgang in Shenzhen between September 2015 and September 2016. There were 1 219 boys and 959 girls, including 81 neonates, 335 infants, 346 young children, 469 preschool children, 419 school-aged children, and 528 adolescents. The American Beckman DXI800 chemiluminescence meter was used to measure the levels of luteinizing hormone, follicle-stimulating hormone, progesterone, prolactin, estradiol, and testosterone., Results: There were significant differences in the levels of luteinizing hormone, follicle-stimulating hormone, progesterone, prolactin, estradiol, and testosterone between different age groups (P<0.05). There were also significant differences in the levels of these sex hormones between boys and girls in the same age group (P<0.05). The reference ranges of six sex hormones were established for healthy children aged 0-18 years in Shenzhen based on the levels of these hormones in different age groups., Conclusions: There are significant differences in sex hormones between different age groups or sex groups. The reference ranges of six sex hormones established for different sexes or ages have great significance in the diagnosis and treatment of endocrine diseases in children.