ZFHX3 variants cause childhood partial epilepsy and infantile spasms with favourable outcomes.

BACKGROUND: The ZFHX3 gene plays vital roles in embryonic development, cell proliferation, neuronal differentiation and neuronal death. This study aims to explore the relationship between ZFHX3 variants and epilepsy. METHODS: Whole-exome sequencing was performed in a cohort of 378 patients with partial (focal) epilepsy. A Drosophila Zfh2 knockdown model was used to validate the association between ZFHX3 and epilepsy. RESULTS: Compound heterozygous ZFHX3 variants were identified in eight unrelated cases. The burden of ZFHX3 variants was significantly higher in the case cohort, shown by multiple/specific statistical analyses. In Zfh2 knockdown flies, the incidence and duration of seizure-like behaviour were significantly greater than those in the controls. The Zfh2 knockdown flies exhibited more firing in excitatory neurons. All patients presented partial seizures. The five patients with variants in the C-terminus/N-terminus presented mild partial epilepsy. The other three patients included one who experienced frequent non-convulsive status epilepticus and two who had early spasms. These three patients had also neurodevelopmental abnormalities and were diagnosed as developmental epileptic encephalopathy (DEE), but achieved seizure-free after antiepileptic-drug treatment without adrenocorticotropic-hormone/steroids. The analyses of temporal expression (genetic dependent stages) indicated that ZFHX3 orthologous were highly expressed in the embryonic stage and decreased dramatically after birth. CONCLUSION: ZFHX3 is a novel causative gene of childhood partial epilepsy and DEE. The patients of infantile spasms achieved seizure-free after treatment without adrenocorticotropic-hormone/steroids implies a significance of genetic diagnosis in precise treatment. The genetic dependent stage provided an insight into the underlying mechanism of the evolutional course of illness.

Sodium Houttuyfonate Alleviates MCT-induced Pulmonary Hypertension by Regulating Orai1 and Orai2.

Elevated intracellular Ca2+ concentration ([Ca2+]i) is a key trigger for pulmonary arterial smooth muscle cell (PASMC) proliferation and contributes greatly to pulmonary hypertension (PH). Extracellular Ca2+ influx via a store-operated Ca2+ channel (SOCC), termed store-operated Ca2+ entry (SOCE), is a crucial mechanism for [Ca2+]i elevation in PASMCs. Calcium release-activated calcium modulator (Orai) proteins, consisting of three members (Orai1-3), are the main components of SOCC. Sodium houttuyfonate (SH) is a product of the addition reaction of sodium bisulfite and houttuynin and has antibacterial, anti-inflammatory, and other properties. In this study, we assessed the contributions of Orai proteins to MCT-enhanced SOCE, [Ca2+]i, and cell proliferation in PASMCs and determined the effect of SH on MCT-PH and the underlying mechanism, focusing on Orai proteins, SOCE, and [Ca2+]i in PASMCs. Our results showed that 1) Orai1 and Orai2 were selectively upregulated in the distal pulmonary arteries (PAs) and the PASMCs of MCT-PH rats. 2) Knockdown of Orai1 or Orai2 reduced SOCE, [Ca2+]i, and cell proliferation without affecting their expression in PASMCs in MCT-PH rats. 3) SH significantly normalized the characteristic parameters in a dose-dependent manner in the MCT-PH rat model. 4) SH decreased MCT-enhanced SOCE, [Ca2+]i and PASMC proliferation via Orai1 or Orai2. These results indicate that SH likely exerts its protective role in MCT-PH by inhibiting the Orai1,2-SOCE-[Ca2+]i signaling pathway.

CCDC88C variants are associated with focal epilepsy and genotype-phenotype correlation.

CCDC88C gene, which encodes coiled-coil domain containing 88C, is essential for cell communication during neural development. Variants in the CCDC88C caused congenital hydrocephalus, some accompanied by seizures. In patients with epilepsy without acquired etiologies, we performed whole-exome sequencing (trio-based). Two de novo and two biallelic CCDC88C variants were identified in four cases with focal (partial) epilepsy. These variants did not present or had low frequencies in the gnomAD populations and were predicted to be damaging by multiple computational algorithms. Patients with de novo variants presented with adult-onset epilepsy, whereas patients with biallelic variants displayed infant-onset epilepsy. They all responded well to anti-seizure medications and were seizure-free. Further analysis showed that de novo variants were located at crucial domains, whereas one paired biallelic variants were located outside the crucial domains, and the other paired variant had a non-classical splicing and a variant located at crucial domain, suggesting a sub-molecular effect. CCDC88C variants associated with congenital hydrocephalus were all truncated, whereas epilepsy-associated variants were mainly missense, the proportion of which was significantly higher than that of congenital hydrocephalus-associated variants. CCDC88C is potentially associated with focal epilepsy with favorable outcome. The underlying mechanisms of phenotypic variation may correlation between genotype and phenotype.

Two-Phase Electrosynthesis of Dihydroxycoumestans: Discovery of a New Scaffold for Topoisomerase I Poison.

Coumestan represents a biologically relevant structural motif distributed in a number of natural products, and the rapid construction of related derivatives as well as the characterization of targets would accelerate lead compound discovery in medicinal chemistry. In this work, a general and scalable approach to 8,9-dihydroxycoumestans via two-electrode constant current electrolysis was developed. The application of a two-phase (aqueous/organic) system plays a crucial role for success, protecting the sensitive o-benzoquinone intermediates from over-oxidation. Based on the structurally diverse products, a primary SAR study on coumestan scaffold was completed, and compound 3 r exhibited potent antiproliferative activities and a robust topoisomerase I (Top1) inhibitory activity. Further mechanism studies demonstrates that compound 3 r was a novel Top1 poison, which might open an avenue for the development of Top1-targeted antitumor agent.

Different levels of prepulse inhibition among patients with first-episode schizophrenia, bipolar disorder and major depressive disorder.

BACKGROUND: Deficits in prepulse inhibition may be a common feature in first-episode schizophrenia, bipolar disorder (BD) and major depressive disorder (MDD). We sought to explore the levels and viability of prepulse inhibition to differentiate first-episode schizophrenia, BD and MDD in patient populations. METHODS: We tested patients with first-episode schizophrenia, BD or MDD and healthy controls using prepulse inhibition paradigms, namely perceived spatial co-location (PSC-PPI) and perceived spatial separation (PSS-PPI). RESULTS: We included 53 patients with first-episode schizophrenia, 30 with BD and 25 with MDD, as well as 82 healthy controls. The PSS-PPI indicated that the levels of prepulse inhibition were smallest to largest, respectively, in the first-episode schizophrenia, BD, MDD and control groups. Relative to the healthy controls, the prepulse inhibition deficits in the first-episode schizophrenia group were significant (p < 0.001), but the prepulse inhibitions were similar between patients with BD and healthy controls, and between patients with MDD and healthy controls. The receiver operating characteristic curve analysis showed that PSS-PPI (area under the curve [AUC] 0.73, p < 0.001) and latency (AUC 0.72, p < 0.001) were significant for differentiating patients with first-episode schizophrenia or BD from healthy controls. LIMITATIONS: The demographics of the 4 groups were not ideally matched. We did not perform cognitive assessments. The possible confounding effect of medications on prepulse inhibition could not be eliminated. CONCLUSION: The level of prepulse inhibition among patients with first-episode schizophrenia was the lowest, with levels among patients with BD, patients with MDD and healthy controls increasingly higher. The PSS-PPI paradigm was more effective than PSC-PPI to recognize deficits in prepulse inhibition. These results provide a basis for further research on biological indicators that can assist differential diagnoses in psychosis.

The relationship between the systemic immune inflammation index and the nonalcoholic fatty liver disease in American adolescents.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a growing health crisis in the general population of the United States (U.S.), but the relationship between systemic immune-inflammation (SII) index and NAFLD is not known. METHODS: We collected data from the National Health and Nutrition Examination Survey 2017-2018. Next, propensity score matching (PSM), collinearity analysis, restricted cubic spline (RCS) plot, logistic regression, quantile regression analysis, subgroup analysis, mediation analysis, and population attributable fraction were used to explore the association of the SII with risk of NAFLD. RESULTS: A total of 665 participants including the 532 Non-NAFLD and 133 NAFLD were enrolled for further analysis after PSM analysis. The RCS results indicated that there was a linear relationship between the SII and controlled attenuation parameter (p for nonlinear = 0.468), the relationship also existed after adjustment for covariates (p for nonlinear = 0.769). The logistic regression results indicated that a high SII level was an independent risk factor for NAFLD (OR = 3.505, 95% CI: 1.092-11.249, P < 0.05). The quantile regression indicated that at higher quantiles (0.90, and 0.95) the SII was significantly associated with NAFLD (p < 0.05). Mediation analysis indicated that alanine aminotransferase (ALT), triglycerides, and blood urea nitrogen (BUN) were partially contribute to the relationship between SII and NAFLD. The population attributable fractions indicated that 23.19% (95% CI: 8.22%, 38.17%) of NAFLD cases could be attributed to SII corresponding to 133 NAFLD cases. CONCLUSION: There was a positive linear relationship between the SII and the risk of NAFLD. The ALT, triglycerides, and BUN had a partial mediating effect on the relationship between the SII and NAFLD.

N-3 PUFA supplementation alleviates anxiety symptoms by manipulating erythrocyte fatty acid levels in depression.

PURPOSE: Major depressive disorder (MDD) is frequently accompanied by the symptoms of clinical anxiety. Since our previous research has found that n-3 PUFA supplementation alleviates anxiety in MDD, this study was aimed to further explore whether n-3 PUFA supplementation improves anxiety symptoms in depression by directly manipulating fatty acid levels. METHODS: A secondary analysis of biomarker data (erythrocyte fatty acid composition) collected as part of the randomized clinical trial which investigated the adjunctive effect of n-3 PUFAs was conducted on 72 venlafaxine-treated outpatients with first-diagnosed, drug-naïve depression. All participants with longitudinal biomarker data were included in the association analysis to determine how n-3 PUFA supplementation influences fatty acid composition and alleviates anxiety symptoms in depression. RESULTS: Decreases of the C20:3n6 were found in all participants at both follow-up time points (χ2 = 96.36, p = 0.000). The n-3 index (χ2 = 10.59, p = 0.001), EPA (χ2 = 24.31, p = 0.000), and C22:5n3/C20:5n3 ratio (χ2 = 10.71, p = 0.001) were increased, while C22:4n6 (χ2 = 7.703, p = 0.006) was decreased in n-3 PUFA group compared to the placebo group. The improvement in anxiety symptoms positively correlates with the extent of reduction of C16:0, C18:0, and total fatty acid levels as well as D5 desaturase activity (p < 0.05). CONCLUSION: These data suggest that the anxiolytic effect exerted by n-3 PUFAs in first-diagnosed, drug-naïve depression is manipulated by erythrocyte fatty acid levels. Saturated fatty acid levels have an important role in predicting the severity of anxiety symptoms.

Association between obstructive sleep apnea severity and depression risk: a systematic review and dose-response meta-analysis.

Obstructive sleep apnea (OSA) has received considerable attention as a potential risk factor for depressive symptoms. The systematic review was conducted to confirm the dose‒response connection between OSA severity and depression risk. A systematic literature search of English and Chinese articles published in PubMed, EMBASE, Scopus, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), and SinoMed databases from their inception to 28 August 2023 was conducted. An evaluation using the Newcastle‒Ottawa Scale was performed. A meta-analysis was used to evaluate the impact of OSA severity. A random-effects dose‒response model was conducted to evaluate the linear and nonlinear dose‒response connections. We evaluated publication bias by funnel plots, and symmetry by Egger's test. We identified 18 cross-sectional researches. 3143 participants which were involved in the dose‒response meta-analysis. Contrasted with mild OSA, individuals with severe OSA had a higher adjusted risk of depression (rate ratio: 1.34, 95% confidence interval = 1.05-1.70), with substantial heterogeneity (I2 = 70.9%, Pheterogeneity<0.001). There is a significant linear connection between OSA severity and depression risk. The depression risk increased by 0.4% for every 1 event per hour increase in the apnea-hypopnea index (AHI). The protocol for this unfunded research was drafted and registered at PROSPERO (ID CRD42023474097).

Evaluation of Clinical Efficacy of Acupuncture and Moxibustion for Asthma: Systematic Review and Meta-Analysis.

Objective: The effectiveness of manual acupuncture for treating bronchial asthma is still debatable and broad, and the effects of different acupuncture points, treatment durations, or illness trajectories have never been rigorously assessed. The objective of this revised systematic review and subgroup meta-analysis of randomized controlled trials (RCTs) is to ascertain the clinical efficacy of manual acupuncture on bronchial asthma and whether these effects varied depending on the acupuncture points, length of treatment, or course of the disease. Materials and methods: PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria were followed for creating a systematic review and meta-analysis. From the beginning through March 25, 2022, six electronic databases were checked. For the treatment of asthma, all RCTs contrasting acupuncture therapy along with conventional treatment against conventional treatment alone were chosen. The information was examined using Review Manager version 5.3 and Comprehensive Meta-Analysis version 3. Clinical efficacy (including the effective rate and the recurrence rate) was the primary outcome, and pulmonary function (including FEV1%, PEF) and The secondary results were T-lymphocyte immunity (containing CD3+, CD4+, and CD8+). Based on the acupuncture points, length of therapy, and nature of the condition, subgroup analyses were carried out. Results: There were a total of 21 RCTs that enrolled 2510 individuals. According to the meta-findings, analysis's manual acupuncture in addition to conventional treatment significantly increased the effective rate when compared to conventional treatment alone [OR = 5.14 95% CI 3.58-7.38, P < .00001], lung functions [FEV1% (MD = 6.18, 95% CI 2.40-9.96, P = .001) and PEF (MD = 0.45 95% CI 0.18-0.73, P = .001)], immune functions [CD3+ T lymphocytes (MD = 7.55 95% CI 6.55-8.56, P < .00001), CD4+ T-lymphocytes (MD = 5.11 95% CI 4.09-6.13, P < .00001), T-lymphocyte CD8+ (MD = -0.37.11 95% CI -3.62--2.51, P < .00001)] and noteworthy reduction in the recurrence rate (OR = 0.19 95% CI 0.10-0.38, P < .00001). Results from the subgroup analysis were consistent. Conclusion: Manual acupuncture combined with Western Medicine is more effective than conventional treatment alone for bronchial asthma. Combination therapy can significantly improve clinical efficacy, lung function, and immune function while reducing the relapse rate. But to further support the results of this investigation, high-quality RCTs with long-term outcomes are still required, taking into account the inherent limitations of the included studies. Registration number: PROSPERO (no. CRD42022357805) (https://www.crd.york.ac.uk/prospero/).

Pathological Changes and Cause of Death Associated with the Global Novel Coronavirus Disease (COVID-19).

The coronavirus disease 2019 (COVID-19) has been a global epidemic for more than three years, causing more than 6.9 million deaths. COVID-19 has the clinical characteristics of strong infectivity and long incubation period, and can cause multi-system damage, mainly lung damage, clinical symptoms of acute respiratory distress syndrome (ARDS) and systemic multiple organ damage. The SARS-CoV-2 virus is still constantly mutating. At present, there is no global consensus on the pathological changes of COVID-19 associated deaths and even no consensus on the criteria for determining the cause of death. The investigation of the basic pathological changes and progression of the disease is helpful to guide the clinical treatment and the development of therapeutic drugs. This paper reviews the autopsy reports and related literature published worldwide from February 2020 to June 2023, with a clear number of autopsy cases and corresponding pathological changes of vital organs as the inclusion criteria. A total of 1 111 autopsy cases from 65 papers in 18 countries are included. Pathological manifestations and causes of death are classified and statistically analyzed, common pathological changes of COVID-19 are summarized, and analytical conclusions are drawn, suggesting that COVID-19 infection can cause life-threatening pathological changes in vital organs. On the basis of different health levels of infected groups, the direct cause of death is mainly severe lung damage and secondary systemic multiple organ failure.

Rock on the Heart: A Case of Calcifying Fibrous Tumor Arising From the Pericardium and Literature Review.

Calcifying fibrous tumors are rare benign fibrous tumors that rarely occur in the heart. We report a 33-year-old woman who was found to have a benign pericardial tumor on health checkup, which was highly suspected to be a teratoma in clinical and imaging examination. After cardiac tumor resection, histopathological features showed scattered foci of psammoma bodies or calcification among collagenized fibrous connective tissues and foci of inflammatory cell infiltration in the interstitium. The pathological diagnosis was a calcifying fibrous tumor.

An integrated wearable differential microneedle array for continuous glucose monitoring in interstitial fluids.

Monitoring biomarkers in human interstitial fluids (ISF) using microneedle sensors has been extensively studied. However, most of the previous studies were limited to simple in vitro demonstrations and lacked system integration and analytical performance. Here we report a miniaturized, high-precision, fully integrated wearable electrochemical microneedle sensing device that works with a customized smartphone application to wirelessly and in real-time monitor glucose in human ISF. A microneedle array fabrication method is proposed which enables multiple individually addressable, regionally separated sensing electrodes on a single microneedle system. As a demonstration, a glucose sensor and a differential sensor are integrated in a single sensing patch. The differential sensing electrodes can eliminate common-mode interference signals, thus significantly improving the detection accuracy. The basic mechanism of microneedle penetration into the skin was analyzed using the finite element method (FEM). By optimizing the structure of the microneedle, the puncture efficiency was improved while the puncture force was reduced. The electrochemical properties, biocompatibility, and system stability of the microneedle sensing device were characterized before human application. The test results were closely correlated with the gold standard (blood). The platform can be used not only for glucose detection, but also for various ISF biomarkers, and it expands the potential of microneedle technology in wearable sensing.

Clickable nanozyme enhances precise colonization of probiotics for ameliorating inflammatory bowel disease.

Convincing evidence suggests that aberrant gut microbiota changes play a critical role in the progression and pathogenesis of inflammatory bowel disease (IBD). Probiotic therapeutic interventions targeting the microbiota may provide alternative avenues to treat IBD, but currently available probiotics often suffer from low intestinal colonization and limited targeting capability. Here, we developed azido (N3)-modified Prussian blue nanozyme (PB@N3) spatio-temporal guidance enhances the targeted colonization of probiotics to alleviate intestinal inflammation. First, clickable PB@N3 targets intestinal inflammation, simultaneously, it scavenges reactive oxygen species (ROS). Subsequently, utilizing "click" chemistry to spatio-temporally guide targeted colonization of dibenzocyclooctyne (DBCO)-modified Lactobacillus reuteri DSM 17938 (LR@DBCO). The "click" reaction between PB@N3 and LR@DBCO has excellent specificity and efficacy both in vivo and in vitro. Despite the complex physiological environment of IBD, "click" reaction can prolong the retention time of probiotics in the intestine. Dextran sulfate sodium (DSS)-induced colitis mice model, demonstrates that the combination of PB@N3 and LR@DBCO effectively mitigates levels of ROS, enhances the colonization of probiotics, modulates intestinal flora composition and function, regulates immune profiles, restores intestinal barrier function, and alleviates intestinal inflammation. Hence, PB@N3 spatio-temporal guidance enhances targeted colonization of LR@DBCO provides a promising medical treatment strategy for IBD.

Transcutaneous electrical acupoint stimulation attenuated neuroinflammation and oxidative stress by activating SIRT1-induced signaling pathway in MCAO/R rat models.

BACKGROUND: Silent information regulator 1 (SIRT1) plays a beneficial role in cerebral ischemic injury. Previous reports have demonstrated that transcutaneous electrical acupoint stimulation (TEAS) exerts a beneficial effect on ischemic stroke; however, whether SIRT1 participates in the underlying mechanism for the neuroprotective effects of TEAS against ischemic brain damage has not been confirmed. METHODS: The rat models of middle cerebral artery occlusion/reperfusion (MCAO/R) were utilized in the current experiment. After MCAO/R surgery, rats in TEAS, EC and EX group received TEAS intervention with or without the injection of EX527, the SIRT1 inhibitor. Neurological deficit scores, infarct volume, hematoxylin eosin (HE) staining and apoptotic cell number were measured. The results of RNA sequencing were analyzed to determine the differential expression changes of genes among sham, MCAO and TEAS groups, in order to investigate the possible pathological processes involved in cerebral ischemia and explore the protective mechanisms of TEAS. Moreover, oxidative stress markers including MDA, SOD, GSH and GSH-Px were measured with assay kits. The levels of the proinflammatory cytokines, such as IL-6, IL-1ß and TNF-α, were detected by ELISA assay, and Iba-1 (the microglia marker protein) positive cells was measured by immunofluorescence (IF). Western blot and IF were utilized to examine the levels of key molecules in SIRT1/FOXO3a and SIRT1/BRCC3/NLRP3 signaling pathways. RESULTS: TEAS significantly decreased brain infarcted size and apoptotic neuronal number, and alleviated neurological deficit scores and morphological injury by activating SIRT1. The results of RNA-seq and bioinformatic analysis revealed that oxidative stress and inflammation were the key pathological mechanisms, and TEAS alleviated oxidative injury and inflammatory reactions following ischemic stroke. Then, further investigation indicated that TEAS notably attenuated neuronal apoptosis, neuroinflammation and oxidative stress damage in the hippocampus of rats with MCAO/R surgery. Moreover, TEAS intervention in the MCAO/R model significantly elevated the expressions of SIRT1, FOXO3a, CAT, BRCC3, NLRP3 in the hippocampus. Furthermore, EX527, as the inhibitor of SIRT1, obviously abolished the anti-oxidative stress and anti-neuroinflammatory roles of TEAS, as well as reversed the TEAS-mediated elevation of SIRT1, FOXO3a, CAT and reduction of BRCC3 and NLRP3 mediated by following MCAO/R surgery. CONCLUSIONS: In summary, these findings clearly suggested that TEAS attenuated brain damage by suppressing apoptosis, oxidative stress and neuroinflammation through modulating SIRT1/FOXO3a and SIRT1/BRCC3/NLRP3 signaling pathways following ischemic stroke, which can be a promising treatment for stroke patients.

Engineering Co3O4@3DOM LaCoO3 multistage-pore nanoreactor with superior SO2 resistance for toluene catalytic combustion.

Sulfur dioxide poisoning is a significant factor in catalyst deactivation during the catalytic combustion of volatile organic compounds. In this study, we prepared the LaCoO3 and Co3O4 composite catalysts using both the Ship-in-Bottle and Building-Bottle-Around-Ship approaches. Three-dimensionally ordered macropores (3DOM LaCoO3) were utilized as nanoreactors to protect the active sites during the catalytic combustion of toluene, preventing SO2 poisoning. Additionally, we grew ZIF-67 confined in the nanoreactor to create a multistage-pore structure. The Co3O4@3DOM LaCoO3 catalysts exhibited excellent activity in the complete catalytic oxidation of toluene. Various characterization studies confirmed the presence of a significant number of Co3+ species and an abundance of surface weak acid sites in the Co3O4@3DOM LaCoO3 catalysts, which synergistically enhanced the conversion of VOCs at low temperatures. Notably, the multistage pore structure provided a favorable reaction environment, accelerating the adsorption and diffusion of toluene and intermediates, resulting in excellent sulfur resistance of the catalysts. Moreover, XPS analysis confirmed a strong interaction between Co3O4 and LaCoO3, promoting rapid electron transfer and increasing the activation of O2-. In situ DRIFTS experiments verified that toluene mainly follows the MvK mechanism over Co3O4@3DOM LaCoO3 catalysts, indicating the following reaction pathway: toluene adsorption → benzyl alcohol → benzaldehyde → benzoate → anhydride → CO2 and H2O.

Targeting pyroptosis to treat ischemic stroke: From molecular pathways to treatment strategy.

Ischemic stroke is the primary reason for human disability and death, but the available treatment options are limited. Hence, it is imperative to explore novel and efficient therapies. In recent years, pyroptosis (a pro-inflammatory cell death characterized by inflammation) has emerged as an important pathological mechanism in ischemic stroke that can cause cell death through plasma membrane rupture and release of inflammatory cytokines. Pyroptosis is closely associated with inflammation, which exacerbates the inflammatory response in ischemic stroke. The level of inflammasomes, GSDMD, Caspases, and inflammatory factors is increased after ischemic stroke, exacerbating brain injury by mediating pyroptosis. Hence, inhibition of pyroptosis can be a therapeutic strategy for ischemic stroke. In this review, we have summarized the relationship between pyroptosis and ischemic stroke, as well as a series of treatments to attenuate pyroptosis, intending to provide insights for new therapeutic targets on ischemic stroke.

Transporter function characterization via continuous-exchange cell-free synthesis and solid supported membrane-based electrophysiology.

Functional characterization of transporters is impeded by the high cost and technical challenges of current transporter assays. Thus, in this work, we developed a new characterization workflow that combines cell-free protein synthesis (CFPS) and solid supported membrane-based electrophysiology (SSME). For this, membrane protein synthesis was accomplished in a continuous exchange cell-free system (CECF) in the presence of nanodiscs. The resulting transporters expressed in nanodiscs were incorporated into proteoliposomes and assayed in the presence of different substrates using the surface electrogenic event reader. As a proof of concept, we validated this workflow to express and characterize five diverse transporters: the drug/H+-coupled antiporters EmrE and SugE, the lactose permease LacY, the Na+/H+ antiporter NhaA from Escherichia coli, and the mitochondrial carrier AAC2 from Saccharomyces cerevisiae. For all transporters kinetic parameters, such as KM, IMAX, and pH dependency, were evaluated. This robust and expedite workflow (e.g., can be executed within only five workdays) offers a convenient direct functional assessment of transporter protein activity and has the ability to facilitate applications of transporters in medical and biotechnological research.

Vibration Analysis of Porous Cu-Si Microcantilever Beams in Fluids Based on Modified Couple Stress Theory.

The vibrations in functionally graded porous Cu-Si microcantilever beams are investigated based on physical neutral plane theory, modified coupled stress theory, and scale distribution theory (MCST&SDT). Porous microcantilever beams define four pore distributions. Considering the physical neutral plane theory, the material properties of the beams are computed through four different power-law distributions. The material properties of microcantilever beams are corrected by scale effects based on modified coupled stress theory. Considering the fluid driving force, the amplitude-frequency response spectra and resonant frequencies of the porous microcantilever beam in three different fluids are obtained based on the Euler-Bernoulli beam theory. The quality factors of porous microcantilever beams in three different fluids are derived by estimating the equation. The computational analysis shows that the presence of pores in microcantilever beams leads to a decrease in Young's modulus. Different pore distributions affect the material properties to different degrees. The gain effect of the scale effect is weakened, but the one-dimensional temperature field and amplitude-frequency response spectra show an increasing trend. The quality factor is decreased by porosity, and the degree of influence of porosity increases as the beam thickness increases. The gradient factor n has a greater effect on the resonant frequency. The effect of porosity on the resonant frequency is negatively correlated when the gradient factor is small (n<1) but positively correlated when the gradient factor is large (n>1).

Idiopathic cardiac ossification with Chiari mesh in the right atrium: a case report and literature review.

Background: Idiopathic cardiac osseous metaplasia in the right atrium of a 9-year-old boy, accompanied by right atrial Chiari network and right pulmonary artery embolism. This case is rare and can easily be misdiagnosed. Case Description: We encountered a case of a 9-year-old boy with a 3.5 cm diameter neoplasm in the right atrium. Preoperative imaging diagnosis could not determine the nature of the tumor, and the initial clinical suspicion of cardiac myxoma. After admission, a cardiotomy to remove foreign bodies and a pulmonary artery thrombectomy were performed. Conclusions: Idiopathic cardiac osseous metaplasia is relatively rare, and it is even rarer to be accompanied by a Chiari network in the right atrium. Due to the location and characteristics of the lesion in this case, it is easy to be misdiagnosed as atrial myxoma in clinical practice. Whether it is idiopathic osseous metaplasia or myxoma, it needs to be performed surgical treatment and pathological examination can easily rule out the diagnosis of myxoma. However, as idiopathic cardiac metaplasia is difficult to encounter in clinical work and there are few reports in the literature, clinicians and pathologists need to consult more relevant literature. Learn to understand and master the disease through multi-party consultation.

Development of crosslinked gelatin films through Maillard reaction and reinforced with poly(vinyl alcohol) for active food packaging.

In order to improve the functionality of natural gelatin films for active food packaging applications, a combined strategy of crosslinking via Maillard reaction and blending enhancement incorporated with poly(vinyl alcohol) (PVA) was explored. In this study, when the mass ratio of gelatin to glucose was 10:1, Maillard reaction of crosslinked gelatin films was the highest, UV absorption and browning index reached the maximum. Infrared analysis showed that PVA could form strong interfacial interactions with gelatin matrix. The presence of PVA could significantly improve the toughness, water absorption, transparency, and oxygen barrier properties of crosslinked gelatin films. When the amount of PVA reached 5 %, elongation at break and oxygen barrier properties of crosslinked gelatin films were improved by 76.7 % and 47.9 % compared with pure crosslinked gelatin film. Even when the amount of PVA reached 10 %, UV absorption (at 315 nm) of crosslinked gelatin films still exceeded 98.7 %. The addition of PVA could accelerate the dissolution and swelling of crosslinked gelatin films, promoting the migration and release of active substances (Maillard reaction products (MRPs)). The two antioxidant activities tests (DPPH and ABTS method) achieved the highest radical scavenging rates of 71.6 % and 91.2 %, respectively, with corresponding PVA addition of 5 % and 7.5 %. After continuing to add PVA, antioxidant activities began to significantly decrease, which was directly related to the decrease in the generation of MRPs. Therefore, crosslinked gelatin films reinforced with appropriate amount of PVA can be considerable potential as active films for renewable food packaging applications.