Evaluation of the impact of overlapping upper gastrointestinal symptoms on the clinical characteristics of patients with functional constipation, along with risk factor analysis.

OBJECTIVES: Functional constipation (FC), a common functional gastrointestinal disorder, is usually overlapping with upper gastrointestinal symptoms (UGS). We aimed to explore the clinical characteristics of patients with FC overlapping UGS along with the related risk factors. METHODS: The differences in the severity of constipation symptoms, psychological state, quality of life (QoL), anorectal motility and perception function, autonomic function, and the effect of biofeedback therapy (BFT) among patients with FC in different groups were analyzed, along with the risk factors of overlapping UGS. RESULTS: Compared with patients with FC alone, those with FC overlapping UGS had higher scores in the Patient Assessment of Constipation Symptoms and Self-Rating Anxiety Scale and lower scores in the Short Form-36 health survey (P < 0.05). Patients with FC overlapping UGS also had lower rectal propulsion, more negative autonomic nervous function, and worse BFT efficacy (P < 0.05). Overlapping UGS, especially overlapping functional dyspepsia, considerably affected the severity of FC. Logistic regression model showed that age, body mass index (BMI), anxiety, exercise, and sleep quality were independent factors influencing overlapping UGS in patients with FC. CONCLUSIONS: Overlapping UGS reduces the physical and mental health and the QoL of patients with FC. It also increases the difficulty in the treatment of FC. Patient's age, BMI, anxiety, physical exercise, and sleep quality might be predictors for FC overlapping UGS.

A Phase 3, Randomized, Controlled Trial Evaluating the Efficacy and Safety of Ropeginterferon Alfa-2b in Patients with Moderate COVID-19.

INTRODUCTION: Ropeginterferon alfa-2b is a novel mono-pegylated proline-interferon. This clinical study aimed to evaluate its antiviral efficacy of ropeginterferon alfa-2b against SARS-CoV-2 infection. METHODS: This is a multicenter, randomized, open-label study. Adult patients with confirmed SARS-CoV-2 infection with initial cycle threshold (Ct) value < 30 and symptom onset within 4 days were enrolled. Eligible patients were randomized in a 2:1 ratio to receive a single 250-µg dose of ropeginterferon alfa-2b subcutaneously plus standard of care (SOC) or to receive SOC alone. The primary endpoint was the proportion of patients with a negative RT-PCR result for SARS-CoV-2 or discharged from the hospital before Day 8. Change in clinical status based on the World Health Organization (WHO) clinical progression scale and pulmonary infiltrations through chest radiograph were also evaluated. RESULTS: A total of 132 patients were enrolled and treated with study medication. Higher percentages of patients who achieved Ct ≥ 30 or were discharged from the hospital were observed on Day 8 and every other time point of assessment, i.e., Days 5, 11, 15, and 22, in the ropeginterferon alfa-2b group compared to the SOC alone group. However, the difference was statistically significant on Day 11 but not on Day 8. The primary endpoint was not met. The ropeginterferon alfa-2b group showed a higher improvement rate in lung infiltration on Day 5 (27.6% vs. 0.0%, p = 0.0087) and a higher improvement rate in WHO clinical progression scores on Day 8 (69.4% vs. 35.3%, p = 0.03) than those in the SOC group. No ropeginterferon alfa-2b-related serious adverse event was observed. CONCLUSION: Our data show that ropeginterferon alfa-2b with SOC shortened the duration of SARS-CoV-2 shedding compared with SOC alone. In addition, ropeginterferon alfa-2b as an additional therapy could be beneficial by improving lung infiltration.

Stimulus-Induced Dynamic Behavior Regulation of Flexible Crystals through the Tuning of Module Rigidity.

Introducing dynamic behavior into periodic frameworks has borne fruit in the form of flexible porous crystals. The detailed molecular design of frameworks in order to control their collective dynamics is of particular interest, for example, to achieve stimulus-induced behavior. Herein, by varying the degree of rigidity of ditopic pillar linkers, two isostructural flexible metal-organic frameworks (MOFs) with common rigid supermolecular building bilayers were constructed. The subtle substitution of single (in bibenzyl-4,4'-dicarboxylic acid; H2BBDC) with double (in 4,4'-stilbenedicarboxylic acid; H2SDC) C-C bonds in pillared linkers led to markedly different flexible behavior of these two MOFs. Upon the removal of guest molecules, both frameworks clearly show reversible single-crystal-to-single-crystal transformations involving the cis-trans conformation change and a resulting swing of the corresponding pillar linkers, which gives rise to Flex-Cd-MOF-1a and Flex-Cd-MOF-2a, respectively. Strikingly, a more favorable gas-induced dynamic behavior in Flex-Cd-MOF-2a was verified in detail by stepwise C3H6/C3H8 sorption isotherms and the corresponding in situ powder X-ray diffraction experiments. These insights are strongly supported by molecular modeling studies on the sorption mechanism that explores the sorption landscape. Furthermore, a consistency between the macroscopic elasticity and microscopic flexibility of Flex-Cd-MOF-2 was observed. This work fuels a growing interest in developing MOFs with desired chemomechanical functions and presents detailed insights into the origins of flexible MOFs.

Addressing the safety of new food sources and production systems.

New food sources and production systems (NFPS) are garnering much attention, driven by international trade, changing consumer preferences, potential sustainability benefits, and innovations in climate-resilient food production systems. However, NFPS can introduce new challenges for food safety agencies and food manufacturers. Most food safety hazards linked to new foods have been identified in traditional foods. However, there can be some food safety challenges that are unique to new foods. New food ingredients, inputs, and processes can introduce unexpected contaminants. To realize the full potential of NFPS, there is a need for stakeholders from governments, the food industry, and the research community to collectively work to address and communicate the safety of NFPS products. This review outlines known food safety hazards associated with select NFPS products on the market, namely, plant-derived proteins, seaweeds, jellyfish, insects, microbial proteins, as well as foods derived from cell-based food production, precision fermentation, vertical farming, and 3D food printing. We identify common elements in emerging NFPS regulatory frameworks in various countries/regions. Furthermore, we highlight current efforts in harmonization of terminologies, use of recent scientific tools to fill in food safety knowledge gaps, and international multi-stakeholder collaborations to tackle safety challenges. Although there cannot be a one-size-fits-all approach when it comes to the regulatory oversight for ensuring the safety of NFPS, there is a need to develop consensus-based structured protocols or workflows among stakeholders to facilitate comprehensive, robust, and internationally harmonized approaches. These efforts increase consumers' confidence in the safety of new foods and contribute toward fair practices in the international trade of such foods.

Acupuncture at "Die E acupoint" alleviates inflammatory reaction via inhibiting TLR4/MyD88/NF-κB signaling in rats with allergic rhinitis. / 基于Tollæ ·å—ä½“4/é«“æ ·åˆ†åŒ–å› å­88/æ ¸è½¬å½•å› å­κB信号通路探讨针刺"è¶è ­ç©´"æ”¹å–„å˜åº”æ€§é¼»ç‚Žå¤§é¼ å ç–«ç‚Žæ€§ååº”çš„æœºåˆ¶.

OBJECTIVES: To observe effects of acupuncture at "Die E acupoint" on the protein expression levels of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear transcription factor κB (NF-κB), transcription factor T-bet (T-bet), and GATA-binding protein-3 (GATA-3) in the nasal mucosa and the serum contents of related inflammatory cytokines in rats with allergic rhinitis, so as to explore the mechanism of acupuncture in treating allergic rhinitis. METHODS: Twenty-four healthy SD rats were randomly divided into blank, model, acupuncture, and sham acupuncture groups, with 6 rats in each group. The rat model of allergic rhinitis was established by using ovalbumin induction. The rats in the acupuncture group received bilateral acupuncture at the "Die E acupoint" with a depth of 15-20 mm, while the rats in the sham acupuncture group received only sham acupuncture (light and shallow acupunture of the skin at the "Die E acupoint" ). Both interventions were performed once daily for a total of 6 days. Behavioral scores of rats in each group were recorded. Pathological changes of nasal mucosa were observed by H.E. staining. Serum contents of IgE, ovalbumin-specific IgE (OVA-sIgE), interferon(IFN)-γ, interleukin(IL)-4, IL-10 and IL-17 were measured by ELISA and the protein expression levels of T-bet, GATA-3, TLR4, MyD88 and NF-κB p65 in the nasal mucosa were detected by Western blot. RESULTS: After modeling, compared with the blank group, rats in the model group showed increased behavioral scores, serum IgE, OVA-sIgE, IL-4, and IL-17 contents, and nasal mucosal GATA-3, TLR4, MyD88, and NF-κB p65 protein expression levels (P<0.05), whereas the contents of serum IFN-γ, IL-10 and the protein expression level of T-bet in the nasal mucosa were decreased (P<0.05). Comparison between the EA and model groups showed that acupuncture intervention can decrease the behavioral scores of rats with allergic rhinitis, the contents of serum IgE, OVA-sIgE, IL-4, IL-17, and the protein expression levels of GATA-3, TLR4, MyD88, and NF-κB p65 in the nasal mucosa (P<0.05), and up-regulate the contents of serum IFN-γ, IL-10, and the nasal mucosal T-bet protein expression level. Sham acupuncture did not have a significant modulating effect on the above indicators. Inflammatory infiltration of nasal mucosa was seen in the model group and sham acupuncture, and the inflammatory reaction was milder in the acupuncture group. CONCLUSIONS: Acupuncture at "Die E acupoint" can alleviate the symptoms of allergic rhinitis and suppress the inflammation of nasal mucosa in rats, which may be related to inhibiting the TLR4/MyD88/NF-κB signaling and balancing the levels of cytokines of Th1/Th2 and Treg/Th17, and T-bet/GATA-3.

Substance P in the medial amygdala regulates aggressive behaviors in male mice.

Behavioral and clinical studies have revealed a critical role of substance P (SP) in aggression; however, the neural circuit mechanisms underlying SP and aggression remain elusive. Here, we show that tachykinin-expressing neurons in the medial amygdala (MeATac1 neurons) are activated during aggressive behaviors in male mice. We identified MeATac1 neurons as a key mediator of aggression and found that MeATac1→ventrolateral part of the ventromedial hypothalamic nucleus (VMHvl) projections are critical to the regulation of aggression. Moreover, SP/neurokinin-1 receptor (NK-1R) signaling in the VMHvl modulates aggressive behaviors in male mice. SP/NK-1R signaling regulates aggression by influencing glutamate transmission in neurons in the VMHvl. In summary, these findings place SP as a key node in aggression circuits.

Broadband Emission Induced by Band-Edge Carrier Reconfiguration in 2D Hybrid Lead Halide Perovskites.

Broadband emission in hybrid lead halide perovskites (LHPs) has gained significant attention due to its potential applications in optoelectronic devices. The origin of this broadband emission is primarily attributed to the interactions between electrons and phonons. Most investigations have focused on the impact of structural characteristics of LHPs on broadband emission, while neglecting the role of electronic mobility. In this work, the study investigates the electronic origins of broadband emission in a family of 2D LHPs. Through spectroscopic experiments and density functional theory calculations, the study unveils that the electronic states of the organic ligands with conjugate effect in LHPs can extend to the band edges. These band-edge carriers are no longer localized only within the inorganic layers, leading to electronic coupling with molecular states in the barrier and giving rise to additional interactions with phonon modes, thereby resulting in broadband emission. The high-pressure photoluminescence measurements and theoretical calculations reveal that hydrostatic pressure can induce the reconfiguration of band-edge states of charge carriers, leading to different types of band alignment and achieving macroscopic control of carrier dynamics. The findings can provide valuable guidance for targeted synthesis of LHPs with broadband emission and corresponding design of state-of-the-art optoelectronic devices.

Translation and adaptation of Shared Care Instrument-Revised for the older adults and their caregivers in Taiwan.

BACKGROUND: The aging population in Taiwan has resulted in an increase in the dependent population and the care load on caregivers. Shared care is an interpersonal process in which support is "traded" to "handle" chronic illnesses by home-care patients and family caregivers. The scale of shared care has received little attention in the Taiwanese cultural context. Thus, this study examined the reliability and validity of the Taiwanese versions of Shared Care Instrument-Revised (SCI-R). METHODS: The content validity, construct validity, and discriminant validity were used to test the validity of the translated questionnaires. The Cronbach's α was used to examine reliability. A total of 500 older adults and their caregivers were recruited from three counties in Taiwan. RESULTS: The reliability and validity of the Chinese version of the scale were within the acceptable range. The Cronbach's α was between 0.838 and 0.95. However, the scale's reliability was higher than that of the original version. This might be because of the inclusion of participants with less severe diseases than the participants in the original study, high social expectations in the Chinese traditional culture, and a large number of similar items. Future research should simplify the items and consider adopting diverse participant selection criteria. CONCLUSIONS: The results of this study can be used to understand shared care in Taiwan.

Staphylococcus aureus foldase PrsA contributes to the folding and secretion of protein A.

BACKGROUND: Staphylococcus aureus secretes a variety of proteins including virulence factors that cause diseases. PrsA, encoded by many Gram-positive bacteria, is a membrane-anchored lipoprotein that functions as a foldase to assist in post-translocational folding and helps maintain the stability of secreted proteins. Our earlier proteomic studies found that PrsA is required for the secretion of protein A, an immunoglobulin-binding protein that contributes to host immune evasion. This study aims to investigate how PrsA influences protein A secretion. RESULTS: We found that in comparison with the parental strain HG001, the prsA-deletion mutant HG001ΔprsA secreted less protein A. Deleting prsA also decreased the stability of exported protein A. Pulldown assays indicated that PrsA interacts with protein A in vivo. The domains in PrsA that interact with protein A are mapped to both the N- and C-terminal regions (NC domains). Additionally, the NC domains are essential for promoting PrsA dimerization. Furthermore, an immunoglobulin-binding assay revealed that, compared to the parental strain HG001, fewer immunoglobulins bound to the surface of the mutant strain HG001ΔprsA. CONCLUSIONS: This study demonstrates that PrsA is critical for the folding and secretion of protein A. The information derived from this study provides a better understanding of virulent protein export pathways that are crucial to the pathogenicity of S. aureus.

A Pyrophosphate Bifunctional Cathode with Inductive Effect for High-Voltage and Self-Charging Zinc Ion Battery.

With the growing demand for new energy storage devices, rechargeable aqueous zinc ion batteries (ZIBs) have attracted widespread attention due to their low cost and high safety. Among the cathode materials for ZIBs, polyanionic-based cathode materials with high voltage, high stability, and low cost have great potential. In this paper, tetragonal Na2VOP2O7 was prepared using a simple sol-gel method. The discharge platform voltage amounted to 1.8 V and had good rate and cycle performance due to the inductive effect of pyrophosphate. Then, a protective layer of Zn-hydroxyapatite (ZnHAP) modification was applied to the cathode surface, which can inhibit the hydrolysis of vanadium ions. The capacity was enhanced by 19 % after modification and the capacity retention after 100 cycles was also higher. Interestingly, the Na2VOP2O7 cathode also possesses a self-charging effect, recovering to 48 % of its initial capacity with an open-circuit voltage (OCV) of 1.1 V within a certain period, and light exposure can reduce the self-charging time by 83 %. These beneficial results indicate that the pyrophosphate bifunctional cathode with inductive effect has a great potential to construct high-voltage and multifunctional zinc ion battery.

MiRNA-296-5p promotes the sensitivity of nasopharyngeal carcinoma cells to cisplatin via targeted inhibition of STAT3/KLF4 signaling axis.

Improving drug sensitivity is an important strategy in chemotherapy of cancer and accumulating evidence indicates that miRNAs are involved in the regulation of drug sensitivity, but the specific mechanism is still unclear. Our previous study has found that miR-296-5p was significantly downregulated in nasopharyngeal carcinoma (NPC). Here, we aim to explore whether miR-296-5p is involved in regulating cisplatin sensitivity in NPC by regulating STAT3/KLF4 signaling axis. The cell proliferation and clonogenic capacity of NPC cells were evaluated by CCK8 Assay and plate colony assay, respectively. The Annexin V-FITC staining kit was used to determine and quantify the apoptotic cells using flow cytometry. The drug efflux ability of NPC cells were determined by Rhodamine 123 efflux experiment. The expression of miR-296-5p, apoptosis-related genes and protein in NPC cell lines were detected by qPCR and Western blot, respectively. Animal study was used to evaluate the sensitivity of NPC cells to DDP treatment in vivo. Our results showed that elevated miR-296-5p expression obviously promoted the sensitivity of NPC cells to DDP by inhibiting cell proliferation and clonogenic capacity, and inducing apoptosis. In addition, we found that miR-296-5p inhibited the expression of STAT3 and KLF4 in NPC cells, while overexpression of exogenous STAT3 reversed miR-296-5p-mediated enhancement in cell death of DDP-treated NPC cells. In vivo studies further confirmed that miR-296-5p promotes the sensitivity of NPC cells to DDP treatment. miRNA-296-5p enhances the drug sensitivity of nasopharyngeal carcinoma cells to cisplatin via STAT3/KLF4 signaling pathway.

A linker selective retention strategy to construct hierarchical porous metal-organic frameworks with high catalytic activity for oxidative desulfurization.

In order to improve the oxidative desulfurization (ODS) performance of MOF materials, an effective way is to convert a microporous MOF into a hierarchical porous MOF (HP-MOF) by utilizing the linker selective retention strategy. Herein, UiO-66 with the introduction of an unstable linker ligand (dihydro-1,2,4,5-tetrazine-3,6-dicarboxylate, dhtz) can selectively remove dhtz ligands to form HP-MOF (HP-UiO-66-dhtz) through heat treatment at high temperature. While maintaining the original structure of UiO-66, HP-UiO-66-dhtz features mesopores and abundant Lewis acid sites, showing excellent ODS performance for diphenylthiophene (DBT).

RNA Control via Redox-Responsive Acylation.

Incorporating stimuli-responsive components into RNA constructs provides precise spatiotemporal control over RNA structures and functions. Despite considerable advancements, the utilization of redox-responsive stimuli for the activation of caged RNAs remains scarce. In this context, we present a novel strategy that leverages post-synthetic acylation coupled with redox-responsive chemistry to exert control over RNA. To achieve this, we design and synthesize a series of acylating reagents specifically tailored for introducing disulfide-containing acyl adducts into the 2'-OH groups of RNA ("cloaking"). Our data reveal that these acyl moieties can be readily appended, effectively blocking RNA catalytic activity and folding. We also demonstrate the traceless release and reactivation of caged RNAs ("uncloaking") through reducing stimuli. By employing this strategy, RNA exhibits rapid cellular uptake, effective distribution and activation in the cytosol without lysosomal entrapment. We anticipate that our methodology will be accessible to laboratories engaged in RNA biology and holds promise as a versatile platform for RNA-based applications.

Dietary Interventions in Atopic Dermatitis: A Comprehensive Scoping Review and Analysis.

BACKGROUND: This scoping review aims to critically assess gaps in the current literature on atopic dermatitis (AD) by evaluating the overall effectiveness of dietary interventions. Through a comprehensive analysis that follows the Preferred Reporting Item for Systematic Review and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines, we conducted a thorough search on the Web of Science database in May 2023 using specific search strategies to identify all relevant studies on the research topic. SUMMARY: A total of 104 full-text articles were included for review. Our synthesis identified seven notable categories of dietary interventions for AD, showcasing the diversity of interventions utilized. This includes vitamin supplementation, probiotic and prebiotic supplementation, dietary fat, biological compounds, foods from natural sources, major nutrients, and diet-related approaches. Further analyses stratified by targeted populations revealed a predominant focus on pediatrics, particularly in probiotic supplementation, and on adults, with an emphasis on vitamin D and E supplementation. KEY MESSAGES: Despite most dietary interventions demonstrating overall effectiveness in improving AD severity and its subjective symptoms, several significant gaps were identified. There was a scarcity of studies on adults and whole-diet interventions, a prevalence of short-term interventions, heterogeneity in study outcomes, designs, and population, occasional disparity between statistical significance and clinical relevance, and a lack of a comprehensive multidisciplinary approach. Nonetheless, these findings offer valuable insights for future AD research, guiding additional evidence-driven dietary interventions and informing healthcare professionals, researchers, and individuals, advancing both understanding and management of AD.

Sciatica caused by spinal epidural abscess as the initial clinical presentation of colon cancer: a rare case report and review of literature.

BACKGROUND: Colorectal cancer is one of the most frequently diagnosed forms of cancer, and it is associated with several common symptoms and signs such as rectal bleeding, altered bowel habits, abdominal pain, anemia, and unintentional weight loss. Sciatica, a debilitating condition in which the patient experiences paresthesia and pain in the dermatome of associated lumbosacral nerve roots or sciatic nerve distribution, is not considered one of these. Here we present a case of colorectal cancer manifesting symptoms of sciatica alone. CASE PRESENTATION: A 68-year-old male presented with progressive lower back pain radiating to his left thigh and calf over L5/S1 dermatome. Sciatica was suspected and initially underwent conservative treatment with analgesics. However, the symptoms progressed and MRI revealed an epidural abscess surprisingly. Surgical debridement was performed and pus culture isolated Streptococcus gallolyticus. Based on the strong association of S. gallolyticus with colorectal cancer, the presence of this pathogen prompted further tumor evaluation, even in the absence of the typical symptoms and signs. This investigation ultimately leads to the diagnosis of sigmoid adenocarcinoma. CONCLUSIONS: Although rare, sciatica caused by S. gallolyticus infection of the spinal epidural space may serve as the initial presentation of colorectal cancer. Physicians should be aware of the strong association between S. gallolyticus and colorectal cancer. Based on what we currently know about the condition; a thorough systematic assessment of occult neoplasia for patients with S. gallolyticus infection is recommended.

Impact of pretreatment quality of life on tolerance and survival outcome in head and neck cancer patients undergoing definitive CCRT.

BACKGROUND: Health-related quality of life (HRQoL) is a predictor of treatment outcomes in cancer patients. This study aimed to evaluate the effect of pretreatment HRQoL on treatment tolerance and survival outcomes in patients with HNC planned for concurrent chemoradiotherapy (CCRT) in Taiwan. METHODS: This study included 461 patients with HNC planned for definitive CCRT at three medical centers in Taiwan between August 2017 and December 2018. HRQoL was assessed using the QLQ-HN35 one week before the initiation of CCRT. Patients were grouped based on the sum scores of QLQ-HN35 (

BCL6 attenuates hyperoxia-induced lung injury by inhibiting NLRP3-mediated inflammation in fetal mouse.

BACKGROUND: The transcriptional repressor B-cell lymphoma 6 (BCL6) has been reported to inhibit inflammation. So far, experimental evidence for the role of BCL6 in bronchopulmonary dysplasia (BPD) is lacking. Our study investigated the roles of BCL6 in the progression of BPD and its downstream mechanisms. METHODS: Hyperoxia or lipopolysaccharide (LPS) was used to mimic the BPD mouse model. To investigate the effects of BCL6 on BPD, recombination adeno-associated virus serotype 9 expressing BCL6 (rAAV9-BCL6) and BCL6 inhibitor FX1 were administered in mice. The pulmonary pathological changes, inflammatory chemokines and NLRP3-related protein were observed. Meanwhile, BCL6 overexpression plasmid was used in human pulmonary microvascular endothelial cells (HPMECs). Cell proliferation, apoptosis, and NLRP3-related protein were detected. RESULTS: Either hyperoxia or LPS suppressed pulmonary BCL6 mRNA expression. rAAV9-BCL6 administration significantly inhibited hyperoxia-induced NLRP3 upregulation and inflammation, attenuated alveolar simplification and dysregulated angiogenesis in BPD mice, which were characterized by decreased mean linear intercept, increased radical alveolar count and alveoli numbers, and the upregulated CD31 expression. Meanwhile, BCL6 overexpression promoted proliferation and angiogenesis, inhibited apoptosis and inflammation in hyperoxia-stimulated HPMECs. Moreover, administration of BCL6 inhibitor FX1 arrested growth and development. FX1-treated BPD mice exhibited exacerbation of alveolar pathological changes and pulmonary vessel permeability, with upregulated mRNA levels of pro-inflammatory cytokines and pro-fibrogenic factors. Furthermore, both rAAV9-BCL6 and FX1 administration exerted a long-lasting effect on hyperoxia-induced lung injury (≥4 wk). CONCLUSIONS: BCL6 inhibits NLRP3-mediated inflammation, attenuates alveolar simplification and dysregulated pulmonary vessel development in hyperoxia-induced BPD mice. Hence, BCL6 may be a target in treating BPD and neonatal diseases.

Bio-based epoxy vitrimer with inherent excellent flame retardance and recyclability via molecular design.

The development of biobased fire-safe thermosets with recyclability heralds the switch for a transition towards a circular economy. In this framework, we introduced a novel high-performance bio-epoxy vitrimer (named GVD), which was fabricated by forming a crosslinking network between bio-epoxy glycerol triglycidyl ether (Gte), varying amounts of reactive flame-retardant agent 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO) (0-7 wt%) and a vanillin-based hardener (VA) with imine bonds. For instance, the epoxy vitrimer GVD5, featuring a DOPO content of 5 wt%, achieved a V-0 rating in the vertical burning test (UL-94) and obtained a limiting oxygen index (LOI) value of 31 %, surpassing the performance of pristine epoxy. Furthermore, the peak heat release rate and total heat release of GVD5 were reduced by 38.2 % and 26.3 %, respectively, compared to pristine epoxy. The GVD vitrimers further demonstrated exceptional reprocessability and recyclability, attributed to the presence of dynamic imine bonds within the topological crosslinking network. Remarkably, the epoxy vitrimers maintained the mechanical properties of the parent epoxy. Therefore, this work provides a facile strategy for fabricating high-performance and multi-functional bio-epoxy thermosets.

Clinically significant findings in a decade-long retrospective study of prenatal chromosomal microarray testing.

BACKGROUND: Chromosomal microarray (CMA) is commonly utilized in the obstetrics setting. CMA is recommended when one or more fetal structural abnormalities is identified. CMA is also commonly used to determine genetic etiologies for miscarriages, fetal demise, and confirming positive prenatal cell-free DNA screening results. METHODS: In this study, we retrospectively examined 523 prenatal and 319 products-of-conception (POC) CMA cases tested at Nationwide Children's Hospital from 2011 to 2020. We reviewed the referral indications, the diagnostic yield, and the reported copy number variants (CNV) findings. RESULTS: In our cohort, the diagnostic yield of clinically significant CNV findings for prenatal testing was 7.8% (n = 41/523) compared to POC testing (16.3%, n = 52/319). Abnormal ultrasound findings were the most common indication present in 81% of prenatal samples. Intrauterine fetal demise was the common indication identified in POC samples. The most common pathogenic finding observed in all samples was isolated trisomy 21, detected in seven samples. CONCLUSION: Our CMA study supports the clinical utility of prenatal CMA for clinical management and identifying genetic etiology in POC arrays. In addition, it provides insight to the spectrum of prenatal and POC CMA results as detected in an academic hospital clinical laboratory setting that serves as a reference laboratory.

Clinical Cytogenetics: Current Practices and Beyond.

BACKGROUND: Throughout history, the field of cytogenetics has witnessed significant changes due to the constant evolution of technologies used to assess chromosome number and structure. Similar to the evolution of single nucleotide variant detection from Sanger sequencing to next-generation sequencing, the identification of chromosome alterations has progressed from banding to fluorescence in situ hybridization (FISH) to chromosomal microarrays. More recently, emerging technologies such as optical genome mapping and genome sequencing have made noteworthy contributions to clinical laboratory testing in the field of cytogenetics. CONTENT: In this review, we journey through some of the most pivotal discoveries that have shaped the development of clinical cytogenetics testing. We also explore the current test offerings, their uses and limitations, and future directions in technology advancements. SUMMARY: Cytogenetics methods, including banding and targeted assessments like FISH, continue to hold crucial roles in cytogenetic testing. These methods offer a rapid turnaround time, especially for conditions with a known etiology involving recognized cytogenetic aberrations. Additionally, laboratories have the flexibility to now employ higher-throughput methodologies to enhance resolution for cases with greater complexity.