Bile acid-sensitive human norovirus strains are susceptible to sphingosine-1-phosphate receptor 2 inhibition.

Human noroviruses (HuNoVs) are a diverse group of RNA viruses that cause endemic and pandemic acute viral gastroenteritis. Previously, we reported that many HuNoV strains require bile or bile acid (BA) to infect human jejunal intestinal enteroid cultures. BA was not essential for the replication of a pandemic-causing GII.4 HuNoV strain. We found the hydrophobic BA glycochenodeoxycholic acid (GCDCA) promotes the replication of the BA-dependent strain GII.3 in jejunal enteroids. Furthermore, we found that inhibition of the G-protein-coupled BA receptor, sphingosine-1-phosphate receptor 2 (S1PR2), by JTE-013, reduced GII.3 infection dose-dependently and inhibited GII.3 cellular uptake in enteroids. Herein, we sought to determine whether S1PR2 is required for other BA-dependent HuNoV strains, the BA-independent GII.4, and whether S1PR2 is required for BA-dependent HuNoV infection in HIEs from other small intestinal segments. We found a second S1PR2 inhibitor, GLPG2938, reduces GII.3 infection dose-dependently, and an S1PR2 agonist (CYM-5520) enhances GII.3 replication in the absence of GCDCA. GII.3 replication also is abrogated in the presence of JTE-013 and CYM-5520. JTE-013 inhibition of S1PR2 in jejunal HIEs reduces GI.1, GII.3, and GII.17 (BA-dependent) but not GII.4 Sydney (BA-independent) infection, providing additional evidence of strain-specific differences in HuNoV infection. Finally, GII.3 infection of duodenal, jejunal, and ileal lines derived from the same individual is reduced with S1PR2 inhibition, indicating a common mechanism of BA-dependent infection among multiple segments of the small intestine. Our results support a model where BA-dependent HuNoVs exploit BA effects on S1PR2 to infect the entire small intestine.IMPORTANCEHuman noroviruses (HuNoVs) are important viral human pathogens that cause both outbreaks and sporadic gastroenteritis. These viruses are diverse, and many strains are capable of infecting humans. Our previous studies have identified strain-specific requirements for hydrophobic bile acids (BAs) to infect intestinal epithelial cells. Moreover, we identified a BA receptor, sphingosine-1-phosphate receptor 2 (S1PR2), required for infection by a BA-dependent strain. To better understand how various HuNoV strains enter and infect the small intestine and the role of S1PR2 in HuNoV infection, we evaluated infection by additional HuNoV strains using an expanded repertoire of intestinal enteroid cell lines. We found that multiple BA-dependent strains, but not a BA-independent strain, all require S1PR2 for infection. In addition, BA-dependent infection requires S1PR2 in multiple segments of the small intestine. Together, these results indicate that S1PR2 has value as a potential therapeutic target for BA-dependent HuNoV infection.

MEMO: dataset and methods for robust multimodal retinal image registration with large or small vessel density differences.

The measurement of retinal blood flow (RBF) in capillaries can provide a powerful biomarker for the early diagnosis and treatment of ocular diseases. However, no single modality can determine capillary flowrates with high precision. Combining erythrocyte-mediated angiography (EMA) with optical coherence tomography angiography (OCTA) has the potential to achieve this goal, as EMA can measure the absolute RBF of retinal microvasculature and OCTA can provide the structural images of capillaries. However, multimodal retinal image registration between these two modalities remains largely unexplored. To fill this gap, we establish MEMO, the first public multimodal EMA and OCTA retinal image dataset. A unique challenge in multimodal retinal image registration between these modalities is the relatively large difference in vessel density (VD). To address this challenge, we propose a segmentation-based deep-learning framework (VDD-Reg), which provides robust results despite differences in vessel density. VDD-Reg consists of a vessel segmentation module and a registration module. To train the vessel segmentation module, we further designed a two-stage semi-supervised learning framework (LVD-Seg) combining supervised and unsupervised losses. We demonstrate that VDD-Reg outperforms existing methods quantitatively and qualitatively for cases of both small VD differences (using the CF-FA dataset) and large VD differences (using our MEMO dataset). Moreover, VDD-Reg requires as few as three annotated vessel segmentation masks to maintain its accuracy, demonstrating its feasibility.

Rapid determination of 111 anti-infective drugs possibly added in cosmetics using high-performance liquid chromatography-tandem mass spectrometry with scheduled multiple reaction monitoring.

RATIONALE: Illegal addition of anti-infective drugs to cosmetics at low concentrations has been found. The illicit addition of anti-infective drugs encompasses a wide variety of medications. The current sample purification methods are inadequate to detect all these compounds. A sensitive, wide-coverage, and weak-matrix-effect measurement method needs to be established to address this issue. METHODS: Samples were extracted using acetonitrile, diluted 25 times, and then analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to detect 111 anti-infective drugs. The method was validated and assessed for matrix effect before being applied to cosmetic products. RESULTS: The calibration curves for the analytes exhibited a strong correlation coefficient (r > 0.995). The limit of detection ranged from 0.006 to 0.6 mg/kg. Matrix effects were significantly improved after a 25-fold dilution. The method was successfully applied to various cosmetics. Two of 82 samples tested contained lincomycin and miconazole, respectively. CONCLUSIONS: The developed method is quick and reliable to analyze anti-infective drugs in cosmetics, with potential for both qualitative and quantitative analyses. It is a valuable tool for cosmetic research and development, contributing to safer and more effective cosmetic products.

Efficacy and safety of ultrasound-assisted wound debridement in the treatment of diabetic foot ulcers: a systematic review and meta-analysis of 11 randomized controlled trials.

Objective: Research data suggests that ultrasound-assisted wound debridement (UAWD) can effectively promote the healing of diabetic foot ulcers (DFU). However, existing research is not consistent with this viewpoint. Therefore, we conducted this study to investigate the effect of UAWD on the healing of diabetic foot ulcers. Methods: From the establishment of the database to January 2024, we searched 8 databases to study the effectiveness and safety of UAWD in the treatment of DFU. Two authors independently screened the qualifications of the articles, while two authors extracted relevant data. Statistical analysis was conducted using Review Manager 5.4 and STATA 18.0 software. Results: A total of 11 randomized controlled studies were included, with 6 countries and 696 participants participating. Our findings showed that UAWD was associated with a significant benefit in healing rate (OR = 2.60, 95% CI: [1.67, 4.03], P < 0.0001, I2 = 25%), wound healing time (MD = -11.94, 95% CI: [-23.65, -0.23], P = 0.05, I2 = 99%), percentage reduction in wound size (MD = 14.2, 95% CI: [10.8, 17.6], P = 0.47, I2 = 32%), effectiveness of treatment (OR = 10.3, 95% CI: [4.68, 22.66], P < 0.00001, I2 = 0%). Moreover, UAWD did not cause any significant adverse reactions. However, there was no obvious difference in wound blood perfusion (MD = 0.25, 95% CI: [-0.01, 0.52], P = 0.06, I2 = 90%), transcutaneous oxygen partial pressure (MD = 14.34, 95% CI: [-10.03, 38.71], P = 0.25, I2 = 98%). Conclusion: UAWD can significantly improve wound healing rate, shorten wound healing time, accelerate wound area reduction, and improve clinical treatment effectiveness without significant adverse reactions. Although there is no significant difference in transcutaneous oxygen pressure and wound blood flow perfusion between UAWD and SWC. So we look forward to more scientifically blinded, placebo-controlled, high-quality studies in the future, to enable researchers to obtain more complete and accurate analytical data, in order to improve the scientific and credibility of the evidence. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024501198.

Bile acid-sensitive human norovirus strains are susceptible to sphingosine-1-phosphate receptor 2 inhibition.

Human noroviruses (HuNoVs) are a diverse group of RNA viruses that cause both endemic and pandemic acute viral gastroenteritis. Previously we reported that many strains of HuNoV require bile or bile acid (BA) to infect human jejunal intestinal enteroid cultures. Of note, BA was not essential for replication of a pandemic-causing GII.4 HuNoV strain. Using the BA-requiring strain GII.3, we found that the hydrophobic BA GCDCA induces multiple cellular responses that promote replication in jejunal enteroids. Further, we found that chemical inhibition of the G-protein coupled receptor, sphingosine-1- phosphate receptor 2 (S1PR2), by JTE-013 reduced both GII.3 infection in a dose- dependent manner and cellular uptake in enteroids. Herein, we sought to determine if S1PR2 is required by other BA-dependent HuNoV strains and BA-independent GII.4, and if S1PR2 is required for BA-dependent HuNoV infection in other segments of the small intestine. We found JTE-013 inhibition of S1PR2 in jejunal HIEs reduces GI.1, GII.3, and GII.17 (BA-dependent) but not the GII.4 Sydney variant (BA-independent) infection, providing additional evidence of strain-specific differences in HuNoV infection. GII.3 infection of duodenal, jejunal and ileal lines derived from the same individual was also reduced with S1PR2 inhibition, indicating a common mechanism of BA-dependent infection among multiple segments of the small intestine. Our results support a model where BA-dependent HuNoV exploit the activation of S1PR2 by BA to infect the entire small intestine. Importance: Human noroviruses (HuNoVs) are important viral human pathogens that cause both outbreaks and sporadic gastroenteritis. These viruses are diverse, and many strains are capable of infecting humans. Our previous studies have identified strain-specific requirements for hydrophobic bile acids (BAs) to infect intestinal epithelial cells. Moreover, we identified a BA receptor, sphingosine-1-phosphate receptor 2 (S1PR2), required for infection by a BA-dependent strain. To better understand how various HuNoV strains enter and infect the small intestine and the role of S1PR2 in HuNoV infection, we evaluated infection by additional HuNoV strains using an expanded repertoire of intestinal enteroid cell lines. We found that multiple BA-dependent strains, but not a BA- independent strain, all required S1PR2 for infection. Additionally, BA-dependent infection required S1PR2 in multiple segments of the small intestine. Together these results indicate S1PR2 has value as a potential therapeutic target for BA-dependent HuNoV infection.

Controllable mitochondrial aggregation and fusion by a programmable DNA binder.

DNA nanodevices have been feasibly applied for various chemo-biological applications, but their functions as precise regulators of intracellular organelles are still limited. Here, we report a synthetic DNA binder that can artificially induce mitochondrial aggregation and fusion in living cells. The rationally designed DNA binder consists of a long DNA chain, which is grafted with multiple mitochondria-targeting modules. Our results indicated that the DNA binder-induced in situ self-assembly of mitochondria can be used to successfully repair ROS-stressed neuron cells. Meanwhile, this DNA binder design is highly programmable. Customized molecular switches can be easily implanted to further achieve stimuli-triggered mitochondrial aggregation and fusion inside living cells. We believe this new type of DNA regulator system will become a powerful chemo-biological tool for subcellular manipulation and precision therapy.

Plasmonic Cavity-Catalysis by Standing Hot Carrier Waves.

Manipulating active sites of catalysts is crucial but challenging in catalysis science and engineering. Beyond the design of the composition and structure of catalysts, the confined electromagnetic field in optical cavities has recently become a promising method for catalyzing chemical reactions via strong light-matter interactions. Another form of confined electromagnetic field, the charge density wave in plasmonic cavities, however, still needs to be explored for catalysis. Here, we present an unprecedented catalytic mode based on plasmonic cavities, called plasmonic cavity-catalysis. We achieve direct control of catalytic sites in plasmonic cavities through standing hot carrier waves. Periodic catalytic hotspots are formed because of localized energy and carrier distribution and can be well tuned by cavity geometry, charge density, and excitation angle. We also found that the catalytic activity of the cavity mode increases several orders of magnitude compared with conventional plasmonic catalysis. We ultimately demonstrate that the locally concentrated long-lived hot carriers in the standing wave mode underlie the formation of the catalytic hotspots. Plasmonic cavity-catalysis provides a new approach to manipulate the catalytic sites and rates and may expand the frontier of heterogeneous catalysis.

Transcriptome Dynamics during Spike Differentiation of Wheat Reveal Amazing Changes in Cell Wall Metabolic Regulators.

Coordinated cell proliferation and differentiation result in the complex structure of the inflorescence in wheat. It exhibits unique differentiation patterns and structural changes at different stages, which have attracted the attention of botanists studying the dynamic regulation of its genes. Our research aims to understand the molecular mechanisms underlying the regulation of spike development genes at different growth stages. We conducted RNA-Seq and qRT-PCR evaluations on spikes at three stages. Our findings revealed that genes associated with the cell wall and carbohydrate metabolism showed high expression levels between any two stages throughout the entire process, suggesting their regulatory role in early spike development. Furthermore, through transgenic experiments, we elucidated the role of the cell wall regulator gene in spike development regulation. These research results contribute to identifying essential genes associated with the morphology and development of wheat spike tissue.

A Surprising Diversity of Xyloglucan Endotransglucosylase/Hydrolase in Wheat: New in Sight to the Roles in Drought Tolerance.

Drought has become a major limiting factor for wheat productivity, and its negative impact on crop growth is anticipated to increase with climate deterioration in arid areas. Xyloglucan endoglycosylases/hydrolases (XTHs) are involved in constructing and remodeling cell wall structures and play an essential role in regulating cell wall extensibility and stress responses. However, there are no systematic studies on the wheat XTH gene family. In this study, 71 wheat XTH genes (TaXTHs) were characterized and classified into three subgroups through phylogenetic analysis. Genomic replication promoted the expansion of TaXTHs. We found a catalytically active motif and a potential N-linked glycosylation domain in all TaXTHs. Further expression analysis revealed that many TaXTHs in the roots and shoots were significantly associated with drought stress. The wheat TaXTH12.5a gene was transferred into Arabidopsis to verify a possible role of TaXTHs in stress response. The transgenic plants possessed higher seed germination rates and longer roots and exhibited improved tolerance to drought. In conclusion, bioinformatics and gene expression pattern analysis indicated that the TaXTH genes played a role in regulating drought response in wheat. The expression of TaXTH12.5a enhanced drought tolerance in Arabidopsis and supported the XTH genes' role in regulating drought stress response in plants.

Correlation between Hashimoto's thyroiditis and polycystic ovary syndrome: A systematic review and meta-analysis.

Objective: A growing body of research suggests that patients with polycystic ovary syndrome (PCOS) may be at increased risk of developing Hashimoto's thyroiditis (HT), and having both conditions can make the condition worse. However, current research views are not uniform. Therefore, to explore the link between PCOS and HT, we conducted this study. Methods: From the establishment of the database to August 2022, we searched 2 databases to study the correlation between Hashimoto's and polycystic ovary syndrome. Two authors independently screened the articles for eligibility, and three authors extracted relevant data. Statistical analysis was performed using STATA16.0 software. Results: A total of 20 studies were included, including 7 case-control studies and 13 cross-sectional studies. A total of 13 countries and 7857 participants were embraced. Studies have demonstrated that both PCOS patients have an increased risk of HT, and meanwhile, HT patients also have an increased risk of PCOS compared with controls. The study also incorporated that the prevalence of HT in PCOS patients in India and Turkey was higher than in other countries, and the prevalence of HT in PCOS patients in South America was higher than in Asia and Europe. Conclusions: In conclusion, our study illustrates that there is a correlation between PCOS and HT, and it is necessary to further study the underlying mechanism between PCOS and HT. At the same time, it is of great significance to regularly screen PCOS patients for HT risk and HT patients for PCOS risk. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD 42022351168.

Global prevalence and epidemiological trends of Hashimoto's thyroiditis in adults: A systematic review and meta-analysis.

Objective: Although Hashimoto's thyroiditis is associated with cardiovascular disease and malignancy, the global status of Hashimoto's thyroiditis is not well characterized across regions. Our objective was to evaluate the prevalence and trends of Hashimoto's thyroiditis in adults in regions with different economic income levels around the world. Methods: For this systematic review and meta-analysis, we searched PubMed, Embase, MEDLINE, Scopus, and Web of Science databases, and 48 random-effects representative studies from the inception to June 2022 were included without language restrictions to obtain the overall prevalence of Hashimoto's thyroiditis in adults worldwide. In addition, we stratified by time of publication, geographic region, economic level of the region of residence, gender, diagnostic method, etc. Results: A total of 11,399 studies were retrieved, of which 48 met the research criteria: 20 from Europe, 16 from Asia, five from South America, three from North America, and three from Africa. Furthermore, there are two projects involving 19 countries and 22,680,155 participants. The prevalence of Hashimoto's thyroiditis was 7.5 (95%CI 5.7-9.6%), while in the low-middle-income group the prevalence was 11.4 (95%CI 2.5-25.2%). Similarly, the prevalence was 5.6 (95%Cl 3.9-7.4%) in the upper-middle-income group, and in the high-income group, the prevalence was 8.4 (95%Cl 5.6-11.8). The prevalence of Hashimoto's varied by geographic region: Africa (14.2 [95% CI 2.5-32.9%]), Oceania (11.0% [95% CI 7.8-14.7%]), South America and Europe 8.0, 7.8% (95% Cl 0.0-29.5%) in North America, and 5.8 (95% Cl 2.8-9.9%) in Asia. Although our investigator heterogeneity was high (I2), our results using a sensitivity analysis showed robustness and reliability of the findings. People living in low-middle-income areas are more likely to develop Hashimoto's thyroiditis, while the group in high-income areas are more likely to develop Hashimoto's thyroiditis than people in upper-middle-income areas, and women's risk is about four times higher than men's. Conclusions: Global Hashimoto's thyroiditis patients are about four times as many as males, and there are discrepancies in the regions with different economic levels. In low-middle-income areas with a higher prevalence of Hashimoto's thyroiditis, especially countries in Africa, therefore local health departments should take strategic measures to prevent, detect, and treat Hashimoto's thyroiditis. At the same time, the hidden medical burden other diseases caused by Hashimoto's thyroiditis should also be done well. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD 42022339839.

Electrochemical selective annulative amino-ketalization and amino-oxygenation of 1,6-enynes.

A new electrochemical selective annulative amino-ketalization and amino-oxygenation of 1,6-enynes with disulfonimides and alcohols is reported, producing a series of functionalized benzofurans under catalyst- and oxidant-free conditions. The annulative aminoketalization proceeds with simple short-chain alcohols such as methanol, ethanol and n-propanol as O-nucleophilic reagents, while the reaction occurs in the annulative aminooxygenation direction in the presence of water and large steric sec-butyl alcohol (SBA).

Multifunctional Human Serum Albumin Fusion Protein as a Docetaxel Nanocarrier for Chemo-photothermal Synergetic Therapy of Ovarian Cancer.

Modification of inorganic nanoparticles with human serum albumin (HSA) that load with chemotherapeutic agents has been reported to conduct chemo-photothermal synergistic therapy of tumors. However, loading some highly insoluble drugs would cause the conformation disorder of HSA, which is unable to give full play to tumor targeting and biological compatibility. Besides, inorganic nanoparticles with too large of a size would appear with unsatisfactory metabolism and lead to biological toxicity. Herein, the recombinant protein integrating histidine (His), HSA, enzyme responsive site, and arginine-glycine-aspartic acid (RGD) by genetic engineering technology was developed to co-load docetaxel (DTX) and gold nanoparticles (Au NPs) to construct RHMH18@AuD NPs. In which, DTX was encapsulated in the micelle part that self-assembled by histidine, while ultrasmall Au NPs were clustered in the HSA part through biomimetic mineralization. RHMH18@AuD NPs could maintain a consistent conformation with HSA and a uniform dispersion in saline. In vitro experiments verified that RHMH18@AuD NPs could target cancer cells followed by being structurally separated into RGD-HSA@Au and His@DTX under the restriction of MMP-2 enzymes. In vivo results verified the favorable biocompatibility and positive chemo-photothermal synergetic therapy efficiency of RHMH18@AuD NPs on a human ovarian tumor.

Decreased accuracy of erythrocyte sedimentation rate in diagnosing osteomyelitis in diabetic foot infection patients with severe renal impairment: A retrospective cross-sectional study.

BACKGROUND: Rapid diagnosis and treatment of diabetic foot osteomyelitis (DFO) could reduce the risk of amputation and death in patients with diabetic foot infection (DFI). Erythrocyte sedimentation rate (ESR) is considered the most useful serum inflammatory marker for the diagnosis of DFO. However, whether severe renal impairment (SRI) affects its diagnostic accuracy has not been reported previously. OBJECTIVE: To investigate the accuracy of ESR in diagnosing DFO in DFI patients with and without SRI. METHODS: This was a retrospective cross-sectional study. From the inpatient electronic medical record system, the investigators extracted demographic information, diagnostic information, and laboratory test results of patients with DFI who had been hospitalized in Longhua Hospital from January 1, 2016 to September 30, 2021. Logistic regression was performed to analyze the interaction between ESR and SRI with adjustment for potential confounders. The area under the curve (AUC), cutoff point, sensitivity, specificity, prevalence, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+), and negative likelihood ratio (LR-) were analyzed by receiver operating characteristic (ROC) curve analysis and VassarStats. RESULTS: A total of 364 DFI patients were included in the analysis. The logistic regression analysis results showed that elevated ESR increased the probability of diagnosing DFO (adjusted odds ratio [OR], 2.40; 95% confidence interval [CI], 1.75-3.28; adjusted P < 0.001); SRI was not associated with the diagnosis of DFO (adjusted OR, 3.20; 95% CI, 0.40-25.32; adjusted P = 0.271), but it had an obstructive effect on the diagnosis of DFO by ESR (adjusted OR, 0.48; 95% CI, 0.23-0.99; adjusted P = 0.048). ROC analysis in DFI patients without SRI revealed that the AUC of ESR to diagnose DFO was 0.76 (95% CI, 0.71-0.81), with the cutoff value of 45 mm/h (sensitivity, 67.8%; specificity, 78.0%; prevalence, 44.7%; PPV, 71.3%; NPV, 75.0%; LR+, 3.08; LR-, 0.41). In contrast, in patients with SRI, the AUC of ESR to diagnose DFO was 0.57 (95% CI, 0.40-0.75), with the cutoff value of 42 mm/h (sensitivity, 95.0%; specificity, 29.2%; prevalence, 45.5%; PPV, 52.8%; NPV, 87.5%; LR+, 1.34; LR-, 0.17). CONCLUSIONS: The accuracy of ESR in diagnosing DFO in DFI patients with SRI is reduced, and it may not have clinical diagnostic value in these patients.

Repetitive Transcranial Magnetic Stimulation and Transcranial Direct Current Stimulation as Treatment of Poststroke Depression: A Systematic Review and Meta-Analysis.

BACKGROUND: Previous studies showed that the application of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) during stroke rehabilitation improve the depression symptoms in poststroke depression (PSD). However, some studies showed inconsistent results. The study was designed to make a meta-analysis to evaluate the effect of noninvasive brain stimulation (tDCS and rTMS) on PSD. METHODS: Articles published before July 2021 were searched in databases: PubMed, Web of Science, and Google Scholar. STATA 12.0 software was utilized to make meta-analysis. We extracted or calculated mean values and SD of reduction or increase rate of depression-related scales. Standardized mean difference (SMD) and 95% confidence intervals (CIs) were calculated as effect size. RESULTS: The study showed increased immediate and long-term improvement in depression in rTMS group compared with sham rTMS group after treatment with random-effects models (immediate: SMD=4.92, 95% CI=2.69-7.15, I2 =95.2%, P -value for Q test <0.001; long term: SMD=7.21, 95% CI=3.50-10.92, I2 =93.9%, P -value for Q test <0.001). Meta-analysis showed increased substantially immediate improvement in depression in tDCS group compared with sham tDCS group with a random effect model (SMD=5.30, 95% CI=1.30-9.30, I2 =97.3%, P- value for Q test <0.001). CONCLUSIONS: rTMS and tDCS were demonstrated to be effective and safe treatment techniques for PSD. More large-scale studies were essential to explore the effect of rTMS with different frequencies and tDCS on PSD.

Comparative Characterization of CpCDPK1 and CpCDPK9, Two Potential Drug Targets Against Cryptosporidiosis.

As the invasion, egress, and growth of Cryptosporidium spp. are regulated by the calcium ion, calcium-dependent protein kinases (CDPKs) are considered potential drug targets against these pathogens. In this study, we expressed CpCDPK1 of Cryptosporidium parvum encoded by the cgd3_920 gene and CpCDPK9 encoded by the the cgd7_1260 gene in Escherichia coli, and we conducted some comparative studies with quantitative PCR, immunofluorescence staining, and in vitro neutralization assays. By immunofluorescence microscopy, CpCDPK1 was expressed over the entirety of the sporozoites, while CpCDPK9 was mainly expressed in the apical region. The expression of the cgd3_920 gene was the highest at 12 h of the in vitro culture, whereas the expression of the cgd7_1260 gene peaked between 2 h and 6 h. Polyclonal antibodies against these two CpCDPK proteins had similar neutralization efficiency on C. parvum growth, reaching approximately 40%. Of the 50 candidate compounds from the molecular docking of CpCDPK1, 10 had significant in vitro anti-cryptosporidial effects, but only one inhibited enzyme activity. For CpCDPK9, five of the forty-five candidate compounds showed significant in vitro anti-cryptosporidial effects. Results obtained from this study suggest that CpCDPK1 and CpCDPK9 might function differently in C. parvum infection.

Cultural Adaptation and Validation of Mullen Scales of Early Learning in Taiwanese children with Autism Spectrum Disorder, Global Developmental Delay, and Typically Developing Children.

BACKGROUND: The Mullen Scales of Early Learning (MSEL) is a standardized comprehensive developmental assessment tool for children aged 0-68 months. However, few Asia-based studies have explored cultural and linguistic adaptations of the MSEL or investigated its psychometric properties in populations with autism spectrum disorder (ASD). AIMS: This study evaluated the reliability and validity of the MSEL-Taiwan version (MSEL-T) for Taiwanese children with ASD, global developmental delay (GDD), and typical development (TD). METHODS AND PROCEDURES: The MSEL items were translated and modified according to the language and culture in Taiwan. In total, 191 children (ASD, 69; GDD, 36; and TD, 86) aged 19-68 months were assessed using the MSEL-T and Peabody Developmental Motor Scales 2 (PDMS-2) at enrollment, followed by the assessments of Vineland Adaptive Behavior Scale-Chinese version (VABS-C) at the age of 36 months or later. OUTCOMES AND RESULTS: All subscales were verified to have good interrater reliability and internal consistency, and subscale scores indicated moderate to high correlations with PDMS-2 and VABS-C scores. Significant differences in MSEL-T scores were observed between same-aged pairs of children with TD and GDD and between pairs of children with TD and ASD. CONCLUSIONS AND IMPLICATIONS: The findings provide evidence of validity and reliability of the MSEL-T. And it is suggested that the culturally and linguistically adapted MSEL-T is a good tool for the clinical assessment of children with and without ASD.

Hsa_circ_0024093 accelerates VSMC proliferation via miR-4677-3p/miR-889-3p/USP9X/YAP1 axis in in vitro model of lower extremity ASO.

Arteriosclerosis obliterans (ASO) of the lower extremities is identified as a kind of cardiovascular disease with aberrant proliferation and apoptosis of vascular smooth muscle cells (VSMCs). Accumulating studies have demonstrated the vital role of Yes1-associated transcriptional regulator (YAP1) in VSMCs, while its upstream regulatory mechanism in VSMCs in ASO of the lower extremities needs to be further elucidated. Herein, hsa_circ_0024093, a circular RNA (circRNA) from YAP1, was identified to positively regulate the protein level of YAP1 in VSMCs. Functionally, silencing of hsa_circ_0024093 obviously impeded cell proliferation and migration and promoted apoptosis in VSMCs in the in vitro model of ASO of the lower extremities. Mechanistically, it was found that hsa_circ_0024093 could regulate the expression of USP9X, which further induced YAP1 deubiquitination to stabilize YAP1 protein. In depth, it was revealed from mechanism experiments that hsa_circ_0024093 sequestered miR-889-3p or miR-4677-3p to enhance USP9X expression. Further, rescue assays validated that hsa_circ_0024093 regulated the miR-4677-3p/miR-889-3p/USP9X axis to accelerate the proliferation and migration of VSMCs in the in vitro model of ASO of the lower extremities. These findings may provide a novel perspective for better understanding of ASO of the lower extremities.

Cyclic Oxime Esters as Deconstructive Bifunctional Reagents for Cyanoalkyl Esterification of 1,6-Enynes.

A concise copper catalysis strategy for the addition-cyclization of cyclic oxime esters across 1,6-enynes with high stereoselectivity to generate 1-indanones bearing an all-carbon quaternary center is reported. In this process, single-electron reduction of cyclic oxime esters enables deconstructive carbon-carbon cleavage to provide a key cyanopropyl radical poised for the addition-cyclization. This reaction is redox-neutral, exhibits good functional group compatibility, and features 100% atomic utilization. This process driven by copper catalyst makes readily available cyclic oxime esters as bifunctional reagents to demonstrate convergent synthesis.

Gene Expression Analysis of Environmental Temperature and High-Fat Diet-Induced Changes in Mouse Supraclavicular Brown Adipose Tissue.

Obesity, a dysregulation of adipose tissue, is a major health risk factor associated with many diseases. Brown adipose tissue (BAT)-mediated thermogenesis can potentially regulate energy expenditure, making it an attractive therapeutic target to combat obesity. Here, we characterize the effects of cold exposure, thermoneutrality, and high-fat diet (HFD) feeding on mouse supraclavicular BAT (scBAT) morphology and BAT-associated gene expression compared to other adipose depots, including the interscapular BAT (iBAT). scBAT was as sensitive to cold induced thermogenesis as iBAT and showed reduced thermogenic effect under thermoneutrality. While both scBAT and iBAT are sensitive to cold, the expression of genes involved in nutrient processing is different. The scBAT also showed less depot weight gain and more single-lipid adipocytes, while the expression of BAT thermogenic genes, such as Ucp1, remained similar or increased more under our HFD feeding regime at ambient and thermoneutral temperatures than iBAT. Together, these findings show that, in addition to its anatomical resemblance to human scBAT, mouse scBAT possesses thermogenic features distinct from those of other adipose depots. Lastly, this study also characterizes a previously unknown mouse deep neck BAT (dnBAT) depot that exhibits similar thermogenic characteristics as scBAT under cold exposure and thermoneutrality.