Clinical Analysis of Inhaled Nitric Oxide Therapy in Preterm Infants at Different Gestational Ages: A National Retrospective Multicenter Study.

OBJECTIVE: This study aimed to investigate clinical features of inhaled nitric oxide (iNO) in preterm infants with a gestational age (GA) < 34 weeks in China. STUDY DESIGN: The clinical data of 434 preterm infants with GA < 34 weeks, treated with iNO in the neonatology departments of eight Class A tertiary hospitals in China over a 10-year period from January 2013 to December 2022, were included in this retrospective multicenter investigation. The infants were divided into three groups based on GA: 24 to 27 weeks (extremely preterm infants), 28 to 31 weeks (very preterm infants), and 32 to 33 weeks (moderate preterm infants). The use of iNO, perinatal data, incidence and mortality of indication for iNO treatment, therapeutic effects of iNO, incidence of short-term complications for iNO treatment, and mortality were compared among these three groups. RESULTS: Over the past 10 years, the proportion of iNO use was highest in extremely preterm infants each year. The lower the GA, the higher the iNO use rate: 4.20% for GA 24 to 27 weeks, 1.54% for GA 28 to 31 weeks, and 0.85% for GA 32 to 33 weeks. There was no significant difference in the therapeutic effect of iNO among the three groups. The incidence of neonatal pulmonary hemorrhage, neonatal shock, late-onset diseases, retinopathy of prematurity requiring intervention, intracranial hemorrhage (grade 3 or 4), periventricular leukomalacia, neonatal necrotizing enterocolitis (≥stage II), and moderate to severe bronchopulmonary dysplasia was highest in extremely preterm infants and increased with decreasing GA. Mortality was negatively correlated with GA and birth weight. The highest rate of iNO treatment in 24 to 27 weeks' preterm infants was due to hypoxic respiratory failure (HRF), whereas the highest rate of iNO treatment in 32 to 33 weeks' preterm infants was due to documented persistent pulmonary hypertension of the newborn (PPHN). The rates of iNO treatment due to HRF and documented PPHN were 54.3 and 60.6%, respectively, in extremely preterm infants, significantly higher than in very preterm and moderate preterm infants (all p < 0.05). Within the same GA group, the proportion of preterm infants treated with iNO for HRF was lower than that for documented PPHN (all p < 0.05), but there was no statistically significant difference in mortality between HRF and documented PPHN treated with iNO (all p > 0.05). CONCLUSION: Among preterm infants with GA < 34 weeks, the rate of iNO usage was highest in extremely preterm infants. However, iNO failed to improve the clinical outcome of extremely preterm infants with refractory hypoxemia, and there was no significant difference in the therapeutic effect of iNO among preterm infants with different GAs.

Resistance and virulence genes characteristic of a South Asia Clade (I) Candida auris strain isolated from blood in Beijing.

INTRODUCTION: Candida auris is a globally disseminated invasive ascomycetous yeast, that imposes a substantial burden on healthcare systems. It has been documented to have spread to over 40 countries across six continents, necessitating in-depth comprehension through advanced techniques like Whole-Genome Sequencing. METHOD: This study entailed the isolation and Whole-Genome Sequencing of a fluconazole-resistant C. auris strain (CA01) obtained from a patient's blood in Beijing. Genome analysis was conducted to classify the strain, and molecular docking was performed to understand the impact of mutations on drug resistance. RESULTS: Genome analysis revealed that CA01 belongs to the South Asia Clade (I) and shares the closest genetic relationship with previously reported strains BJCA001 and BJCA002. Notably, unlike BJCA001, CA01 exhibits significant resistance to fluconazole primarily due to the A395T mutation in the ERG11 gene. Molecular docking studies demonstrated that this mutation leads to geometric changes in the active site where fluconazole binds, resulting in decreased binding affinity. Additionally, the present findings have identified several core virulence genes in C. auris, such as RBF1. DISCUSSION: The findings from this study expand the understanding of the genetic diversity and adaptive mechanisms of C. auris within the South Asia Clade (I). The observed fluconazole resistance driven by the ERG11 mutation A395T highlights the need for heightened awareness and adaptation in clinical treatment strategies in China. This study provides critical insights into drug resistance and virulence profiles at a genetic level, which could guide future therapeutic and management strategies for C. auris infections.

Orbital angular momentum and rotational properties of off-axis vortex beams in two-dimensional media with anisotropic nonlocal nonlinearity.

By introducing anisotropy into nonlinear propagations, off-axis vortex beams exhibit significantly different characteristics compared to the isotropic case. The orbital angular momentum (OAM) is non-conservative and can periodically change between positive and negative values. Accordingly, the rotation of phase singularity can transit between clockwise and counterclockwise directions. Furthermore, the phase singularity can move to infinity when the OAM approaches zero. By using the Ehrenfest theorem, the motion of the beam center is obtained. Its trajectory can be circular and parabolic or follow other complex shapes, depending closely on the anisotropy of the nonlinearity. The rotational velocity of the beam center can be modulated by the nonlinearity anisotropy and can far exceed the initial value during its propagation. These results may find potential applications in beam shaping and optical manipulation.

A multicenter epidemiological survey of iNO use in preterm infants in China.

OBJECTIVE: To investigate the use of inhaled nitric oxide (iNO) in hospitalized preterm infants in China over 10 years and its clinical outcomes. METHODS: A total of 616 premature infants who were administered iNO in the Neonatology Departments of 5 Class A tertiary hospitals in China for ten years from January 2013 to December 2022 were included retrospectively. Based on their enrollment periods, the patients were divided into two groups: Group 1 from January 2013 to December 2017 and Group 2 from January 2018 to December 2022, respectively. The perinatal characteristics, short-term clinical outcomes, and mortality rates were compared between these two groups. RESULTS: The utilization of iNO in preterm infants grew annually over the past10 years; the utilization of iNO in Group 2 infants increased approximately one-fold when compared with Group 1 (1.52% vs. 0.80%, p < .001), and the increase was greater in gestational age (GA) < 34 weeks compared with 34-36 weeks preterm infants. Moreover, the iNO usage in Group 1 infants with GA < 34 weeks increased from 1.14% to 2.46% and 0.60% to 0.99% in 34-36 weeks preterm infants (p < .001) in Group 2, respectively. Apart from a smaller GA (32.9 w vs. 33.5 w, p < .001) and birth weight (BW, 1900 g vs. 2141 g, p < .001), the initial [14 parts per million (ppm) versus 10 ppm, p < .001] and maximum (15 ppm vs. 10 ppm, p < .001) doses of Group 2 were larger; however, their recent clinical outcomes did not improve with increasing iNO utilization (p > .05)as compared to Group 1, respectively. Although the overall iNO preterm mortality rates over the past 10 years were 25.8%, the mortality rates for preterm infants at 34-36 weeks were significantly lower than for preterm infants at GA < 34 weeks (15.4% vs. 33.8%, p < .001). Nonetheless, no improvement in mortality was observed in Group 2 preterm infants with GA < 34 weeks for the past 5 years when compared with Group 1 (32.9% vs. 35.8%, p > .05) infants, and significantly lower mortality rates were noticed in preterm infants with 34-36 weeks (11.2% vs. 22.7%, p < .001). Patients with hypoxic respiratory failure (HRF) or persistent pulmonary hypertension of the newborn (PPHN) iNO preterm infants did not show lower mortality rates with the increase of iNO use rate (p > .05). The overall mortality rates of preterm PPHN infants with iNO were lower than that of HRF (20.2% vs. 36.5%, p < .001), while the mortality rates of Group 2 preterm PPHN infants with iNO significantly lower than that of HRF (17.7% vs 36.0%, p < .001). CONCLUSION: The iNO has been extensively used in Chinese preterm infants over the past 10 years, this increase was more significant in preterm infants with GA < 34 weeks. Moreover, preterm infants using iNO have lower GA and BW, larger initial and maximum doses, and more aggressive strategies in the last past 5 years. Although iNO use in preterm infants with GA of 34-36 weeks has significantly reduced mortality, mortality rates and short-term clinical outcomes of iNO in preterm infants <34 weeks of GA has no obvious improvement. Further studies are required to investigate the efficacy and safety of iNO in preterm infants <34 weeks of GA.

Serological Investigation into the Infected Genotypes of Patients with Japanese Encephalitis in the Coastal Provinces of China.

Objective: Genotypes (G) 1, 3, and 5 of the Japanese encephalitis virus (JEV) have been isolated in China, but the dominant genotype circulating in Chinese coastal areas remains unknown. We searched for G5 JEV-infected cases and attempted to elucidate which JEV genotype was most closely related to human Japanese encephalitis (JE) in the coastal provinces of China. Methods: In this study, we collected serum specimens from patients with JE in three coastal provinces of China (Guangdong, Zhejiang, and Shandong) from 2018 to 2020 and conducted JEV cross-neutralization tests against G1, G3, and G5. Results: Acute serum specimens from clinically reported JE cases were obtained for laboratory confirmation from hospitals in Shandong (92 patients), Zhejiang (192 patients), and Guangdong (77 patients), China, from 2018 to 2020. Seventy of the 361 serum specimens were laboratory-confirmed to be infected with JEV. Two cases were confirmed to be infected with G1 JEV, 32 with G3 JEV, and two with G5 JEV. Conclusion: G3 was the primary infection genotype among JE cases with a definite infection genotype, and the infection caused by G5 JEV was confirmed serologically in China.

A small molecule compound targeting hemagglutinin inhibits influenza A virus and exhibits broad-spectrum antiviral activity.

Influenza A virus (IAV) is a widespread pathogen that poses a significant threat to human health, causing pandemics with high mortality and pathogenicity. Given the emergence of increasingly drug-resistant strains of IAV, currently available antiviral drugs have been reported to be inadequate to meet clinical demands. Therefore, continuous exploration of safe, effective and broad-spectrum antiviral medications is urgently required. Here, we found that the small molecule compound J1 exhibited low toxicity both in vitro and in vivo. Moreover, J1 exhibits broad-spectrum antiviral activity against enveloped viruses, including IAV, respiratory syncytial virus (RSV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human coronavirus OC43 (HCoV-OC43), herpes simplex virus type 1 (HSV-1) and HSV-2. In this study, we explored the inhibitory effects and mechanism of action of J1 on IAV in vivo and in vitro. The results showed that J1 inhibited infection by IAV strains, including H1N1, H7N9, H5N1 and H3N2, as well as by oseltamivir-resistant strains. Mechanistic studies have shown that J1 blocks IAV infection mainly through specific interactions with the influenza virus hemagglutinin HA2 subunit, thereby blocking membrane fusion. BALB/c mice were used to establish a model of acute lung injury (ALI) induced by IAV. Treatment with J1 increased survival rates and reduced viral titers, lung index and lung inflammatory damage in virus-infected mice. In conclusion, J1 possesses significant anti-IAV effects in vitro and in vivo, providing insights into the development of broad-spectrum antivirals against future pandemics.

[Application of micro-computed tomography (µCT)in quantifying xylem vessels of broadleaved trees]. / 计算机显微断层扫描技术(µCT)åœ¨é‡åŒ–é˜”å¶æ ‘ç§å¯¼ç®¡ä¸­çš„åº”ç”¨.

Quantitative analysis of vessel characteristics at the cellular scale is of great significance for understan-ding plant adaptation strategies to environment. The direct grinding combined with stereo-microscope imaging is one of the main approaches to examine the anatomical structure of xylem (conifer tracheid and hardwood vessel) wood structure, which inevitably damages xylem cells, hindering the accurate understanding of anatomical structures. In this study, we applied X-ray micro-computed tomography (µCT) and stereo-microscope technology to quantitatively measure the diameter and area of vessels of seven Canadian broadleaved tree species (Acer saccharum, Betula papyrifera, Fraxinus americana, Ostrya virginiana, Populus grandidentata, Quercus rubra, and Carya cordiformis). We fitted the results by linear model and tested the feasibility of µCT technology in quantifying the vessel size of broadleaved species. We found that the results of the two methods for measuring vessel size were highly similar (R2=0.98). The goodness of fit of the vessel diameter results measured by the two methods for the ring-porous wood species (C. cordiformis, R2=0.98; F. americana, R2=0.96; Q. rubra, R2=0.99) was higher than that of the diffuse-porous wood species (B. papyrifera, R2=0.88; O. virginiana, R2=0.73; A. saccharum, R2=0.68; P. grandiden-tata, R2=0.88). The goodness of fit of small vessels (diameter≤200 µm, R2=0.94) measured by the two methods was higher than that of large vessels (diameter>200 µm, R2=0.92). Thus, the µCT technique provided a new non-destructive detection method for quantifying xylem vessels of broadleaved tree species.

Molecular Evolution of SNAREs in Vitis vinifera and Expression Analysis under Phytohormones and Abiotic Stress.

SNARE proteins (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) play a key role in mediating a variety of plant biological processes. Currently, the function of the SNARE gene family in phytohormonal and abiotic stress treatments in grapevine is currently unknown, making it worthwhile to characterize and analyze the function and expression of this family in grapevine. In the present study, 52 VvSNARE genes were identified and predominantly distributed on 18 chromosomes. Secondary structures showed that the VvSNARE genes family irregular random coils and α-helices. The promoter regions of the VvSNARE genes were enriched for light-, abiotic-stress-, and hormone-responsive elements. Intraspecific collinearity analysis identified 10 pairs collinear genes within the VvSNARE family and unveiled a greater number of collinear genes between grapevine and apple, as well as Arabidopsis thaliana, but less associations with Oryza sativa. Quantitative real-time PCR (qRT-PCR) analyses showed that the VvSNARE genes have response to treatments with ABA, NaCl, PEG, and 4 °C. Notably, VvSNARE2, VvSNARE14, VvSNARE15, and VvSNARE17 showed up-regulation in response to ABA treatment. VvSNARE2, VvSNARE15, VvSNARE18, VvSNARE19, VvSNARE20, VvSNARE24, VvSNARE25, and VvSNARE29 exhibited significant up-regulation when exposed to NaCl treatment. The PEG treatment led to significant down-regulation of VvSNARE1, VvSNARE8, VvSNARE23, VvSNARE25, VvSNARE26, VvSNARE31, and VvSNARE49 gene expression. The expression levels of VvSNARE37, VvSNARE44, and VvSNARE46 were significantly enhanced after exposure to 4 °C treatment. Furthermore, subcellular localization assays certified that VvSNARE37, VvSNARE44, and VvSNARE46 were specifically localized at the cell membrane. Overall, this study showed the critical role of the VvSNARE genes family in the abiotic stress response of grapevines, thereby providing novel candidate genes such as VvSNARE37, VvSNARE44, and VvSNARE46 for further exploration in grapevine stress tolerance research.

Shen-yan-yi-hao oral solution ameliorates IgA nephropathy via intestinal IL-17/NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis in the world, it is one of the most common causes of kidney disease and can lead to end-stage kidney disease, however, its pathogenesis is still complicated. The Shen-yan-yi-hao oral solution (SOLI) is an effective prescription for the clinical treatment of IgAN while its specific mechanism remains to be further elucidated. AIM OF THE STUDY: This study investigates SOLI's effects on IgAN in rats, particularly on the intestinal mucosal barrier, and identifies potential therapeutic targets through network pharmacology and molecular docking, validated experimentally. MATERIALS AND METHODS: Target genes for SOLI in IgAN were identified and analysed through molecular docking and KEGG pathway enrichment. An IgAN rat model examined SOLI's effect on renal biomarkers and cytokines involved in specific pathways, ileum mucosal lesions, and the intestinal immune system. The IL-17 pathway's role was studied in IEC-6 cells with SOLI in vitro. RESULT: Rats developed increased proteinuria and kidney damage marked by IgA deposition and inflammation. SOLI treatment significantly ameliorated these symptoms, reduced galactose-deficient Ig A1 (Gd-IgA1), and decreased cytokines like IL-17, TNF-α, IL-6 and IL-1ß etc. SOLI also normalized intestinal tight junction protein expression, ameliorated intestinal damage, and regulated intestinal immune response (focused on IL-17/NF-κB signal pathway). SOLI moderated the abnormally activated IL-17 pathway, which damages intestinal epithelial cells, suggesting IgAN treatment potential. CONCLUSION: SOLI reduces proteinuria and enhances intestinal mucosal function in IgAN rats, kidney protection in the IgAN rat model may initiate from modulating the intestinal IL-17/NF-κB pathway and subsequent Gd-IgA1 accumulation.

Baicalein improves renal interstitial fibrosis by inhibiting the ferroptosis in vivo and in vitro.

Evidence indicates that Baicalein can ameliorate renal interstitial fibrosis by inducing myofibroblast apoptosis and inhibit the RLS3-induced ferroptosis in melanocytes. However, the relationship between renal interstitial fibrosis and anti-ferroptosis affected by Baicalein remains unclear. In our study, the anti-fibrosis and anti-ferroptosis effects of Baicalein were assessed in a rat model induced by the UUO method in vivo, and the effects of Baicalein on Erastin-induced ferroptosis of renal MPC-5 cells were examined by Western blot of fibrosis-related and ferroptosis-related proteins in vitro. In the UUO-induced rat model, Baicalein decreased kidney weight loss, improved renal function assessed the biomarks of urinary albumin excretion, serum creatine, and BUN levels, and reduced renal tubular injury. Furthermore, Baicalein inhibited renal ferroptosis by reducing ROS and MDA levels and increasing SOD and GSH levels in the UUO rat model. In addition, Baicalein potently reduced the expression of fibrosis-related proteins such as TGF-ß1, a-SMA, and Smad-2 to prevent renal interstitial fibrosis, and increased the expression of ferroptosis-related proteins such as SLC7A11, GPX4, and FTH to inhibit ferroptosis both in vitro and in vivo. Taken together, Baicalein exerts anti-fibrosis activity by reducing the ferroptosis response on the UUO-induced rat model and renal MPC5 cells. Therefore, Baicalein, as a novel therapeutic method on kidney diseases with strong activity in suppressing ferroptosis, could be a potential alternative treatment for renal interstitial fibrosis.

Development of a High-throughput Sequencing Platform for Detection of Viral Encephalitis Pathogens Based on Amplicon Sequencing.

Objective: Viral encephalitis is an infectious disease severely affecting human health. It is caused by a wide variety of viral pathogens, including herpes viruses, flaviviruses, enteroviruses, and other viruses. The laboratory diagnosis of viral encephalitis is a worldwide challenge. Recently, high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections. Thus, In this study, we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods: We designed nine pairs of specific polymerase chain reaction (PCR) primers for the 12 viruses by reviewing the relevant literature. The detection ability of the primers was verified by software simulation and the detection of known positive samples. Amplicon sequencing was used to validate the samples, and consistency was compared with Sanger sequencing. Results: The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×, and the sequence lengths were consistent with the sizes of the predicted amplicons. The sequences were verified using the National Center for Biotechnology Information BLAST, and all results were consistent with the results of Sanger sequencing. Conclusion: Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis. It is also a useful tool for the high-volume screening of clinical samples.

Emodin suppresses alkali burn-induced corneal inflammation and neovascularization by the vascular endothelial growth factor receptor 2 signaling pathway.

OBJECTIVE: To investigate the effects of emodin on alkali burn-induced corneal inflammation and neovascularization. METHODS: The ability of emodin to target vascular endothelial growth factor receptor 2 (VEGFR2) was predicted by molecular docking. The effects of emodin on the invasion, migration, and proliferation of human umbilical vein endothelial cells (HUVEC) were determined by cell counting kit-8, Transwell, and tube formation assays. Analysis of apoptosis was performed by flow cytometry. CD31 levels were examined by immunofluorescence. The abundance and phosphorylation state of VEGFR2, protein kinase B (Akt), signal transducer and activator of transcription 3 (STAT3), and P38 were examined by immunoblot analysis. Corneal alkali burn was performed on 40 mice. Animals were divided randomly into two groups, and the alkali-burned eyes were then treated with drops of either 10 µM emodin or phosphate buffered saline (PBS) four times a day. Slit-lamp microscopy was used to evaluate inflammation and corneal neovascularization (CNV) in all eyes on Days 0, 7, 10, and 14. The mice were killed humanely 14 d after the alkali burn, and their corneas were removed and preserved at －80 ℃ until histological study or protein extraction. RESULTS: Molecular docking confirmed that emodin was able to target VEGFR2. The findings revealed that emodin decreased the invasion, migration, angiogenesis, and proliferation of HUVEC in a dose-dependent manner. In mice, emodin suppressed corneal inflammatory cell infiltration and inhibited the development of corneal neovascularization induced by alkali burn. Compared to those of the PBS-treated group, lower VEGFR2 expression and CD31 levels were found in the emodin-treated group. Emodin dramatically decreased the expression of VEGFR2, p-VEGFR2, p-Akt, p-STAT3, and p-P38 in VEGF-treated HUVEC. CONCLUSION: This study provides a new avenue for evaluating the molecular mechanisms underlying corneal inflammation and neovascularization. Emodin might be a promising new therapeutic option for corneal alkali burns.

Porous α-Fe2O3 Hollow Rods/Reduced Graphene Oxide Composites Templated by MoO3 Nanobelts for High-Performance Supercapacitor Applications.

Porous α-Fe2O3 hollow rods/reduced graphene oxide (α-Fe2O3 HR/RGO) composites with unique morphological characteristics and a high surface area are prepared through a template strategy, which was systematically studied and found to have outstanding supercapacitive properties. When served as active material in a three-electrode setup, the optimized α-Fe2O3 HR/RGO-30, comprised 76.5 wt% α-Fe2O3 and 23.2 wt% RGO, was able to offer the largest specific capacitance of 426.3 F g-1, an excellent rate capability as well as satisfactory cycle life with capacitance retention of 87.7% and Coulombic efficiency of 98.9% after continuously charging/discharging at 10 A g-1 for beyond 10,000 cycles. Such electrochemical behaviors of the α-Fe2O3 HR/RGO-30 electrode can rival or even surpass those of many Fe2O3-based electrodes documented in the previous literature. Later, a symmetric supercapacitor cell of α-Fe2O3 HR/RGO-30//α-Fe2O3 HR/RGO-30 was fabricated. The assembled device offers the maximum energy density of 18.7 Wh kg-1, and also exhibits commendable rate capability, and features stable cycling durability (with capacitance retention of 83.2% together with a Coulombic efficiency of 99.3% after 10,000-cycle charge/discharge at 5 A g-1). These notable electrochemical performances enable the α-Fe2O3 HR/RGO-30 composite to be a high-potential material for advanced energy storage systems.

Accelerometer-measured sedentary volume and bouts during the segmented school day among Chinese school students.

Background: This study examined sedentary volume and bouts of Chinese primary and middle school students during different segments of a school day and determined whether gender and school level are associated with their sedentary volume and bouts. Methods: A total of 472 students participated in this study. Accelerometers were used to measure the sedentary volume and sedentary bouts of different durations (i.e., 1-4 min, 5-9 min and ≥10 min) during all segments. Results: The participants spent the majority of their time in sitting (61.7%) and sitting bouts of ≥10 min (37.3%). They spent higher percentages of time in sitting during regular classes (76.7%) and out-of-school time (54.5%), and lower during physical education (PE) classes (32.2%), lunch break (35.4%) and recess (38.0%). The highest proportions of time were in sedentary bouts of ≥10 min during regular classes (50.2%), out-of-school time (28.0%) and lunch break (18.8%), while the greatest percentages occurred in sitting bouts of 1-4 min during PE class (16.4%) and recess (18.6%). Girls and middle school students had higher percentages of sedentary volume than boys and primary school students during most segments. They spent greater proportions of time in sitting bouts of ≥10 min during regular classes, lunch break, and out-of-school time, and higher proportions in sedentary bouts of 1-4 min than boys and primary students during PE classes. Conclusion: Regular class and out-of-school time were identified as key segments for reducing sedentary volume and breaking up prolonged sitting. Interventions on interrupting prolonged sitting during lunch break should also be explored. Girls and middle school students should receive more attention in future interventions.

Pleural empyema with endobronchial mass due to Rhodococcus equi infection after renal transplantation: A case report and review of literature.

BACKGROUND: Kidney transplantation is the best option for patients with end-stage renal disease. However, the need for lifelong immunosuppression results in renal transplant recipients being susceptible to various infections. Rhodococcus equi (R. equi) is a rare opportunistic pathogen in humans, and there are limited reports of infection with R. equi in post-renal transplant recipients and no uniform standard of treatment. This article reports on the diagnosis and treatment of a renal transplant recipient infected with R. equi 21 mo postoperatively and summarizes the characteristics of infection with R. equi after renal transplantation, along with a detailed review of the literature. CASE SUMMARY: Here, we present the case of a 25-year-old man who was infected with R. equi 21 mo after renal transplantation. Although the clinical features at the time of presentation were not specific, chest computed tomography (CT) showed a large volume of pus in the right thoracic cavity and right middle lung atelectasis, and fiberoptic bronchoscopy showed an endobronchial mass in the right middle and lower lobe orifices. Bacterial culture and metagenomic next-generation sequencing sequencing of the pus were suggestive of R. equi infection. The immunosuppressive drugs were immediately suspended and intravenous vancomycin and azithromycin were administered, along with adequate drainage of the abscess. The endobronchial mass was then resected. After the patient's clinical symptoms and chest CT presentation resolved, he was switched to intravenous ciprofloxacin and azithromycin, followed by oral ciprofloxacin and azithromycin. The patient was re-hospitalized 2 wk after discharge for recurrence of R. equi infection. He recovered after another round of adequate abscess drainage and intravenous ciprofloxacin and azithromycin. CONCLUSION: Infection with R. equi in renal transplant recipients is rare and complex, and the clinical presentation lacks specificity. Elaborate antibiotic therapy is required, and adequate abscess drainage and surgical excision are necessary. Given the recurrent nature of R. equi, patients need to be followed-up closely.

Ruthenium-dihydroartemisinin complex: a promising new compound for colon cancer prevention via G1 cell cycle arrest, apoptotic induction, and adaptive immune regulation.

BACKGROUND: Artemisinin (ART) and its derivatives are important antimalaria agents and have received increased attention due to their broad biomedical effects, such as anticancer and anti-inflammation activities. Recently, ruthenium-derived complexes have attracted considerable attention as their anticancer potentials were observed in preclinical and clinical studies. METHODS: To explore an innovative approach in colorectal cancer (CRC) management, we synthesized ruthenium-dihydroartemisinin complex (D-Ru), a novel metal-based artemisinin derivative molecule, and investigated its anticancer, anti-inflammation, and adaptive immune regulatory properties. RESULTS: Compared with its parent compound, ART, D-Ru showed stronger antiproliferative effects on the human CRC cell lines HCT-116 and HT-29. The cancer cell inhibition of D-Ru comprised G1 cell cycle arrest via the downregulation of cyclin A and the induction of apoptosis. ART and D-Ru downregulated the expressions of pro-inflammatory cytokines IL-1ß, IL-6, and IL-8. Although ART and D-Ru did not suppress Treg cell differentiation, they significantly inhibited Th1 and Th17 cell differentiation. CONCLUSIONS: Our results demonstrated that D-Ru, a novel ruthenium complexation of ART, remarkably enhanced its parent compound's anticancer action, while the anti-inflammatory potential was not compromised. The molecular mechanisms of action of D-Ru include inhibition of cancer cell growth via cell cycle arrest, induction of apoptosis, and anti-inflammation via regulation of adaptive immunity.

Microplastics affect mosquito from aquatic to terrestrial lifestyles and are transferred to mammals through mosquito bites.

Microplastics (MPs) transfer from the environment to living organisms is a nonignorable global problem. As a complete metamorphosis insect, the larvae and adult Culex quinquefasciatus mosquito live in aquatic and terrestrial environments, respectively, where they easily access MPs. However, little is known about mosquitoes' potential role in MPs accumulation throughout ecosystems. Therefore, we conducted a study with different MPs particle sizes (0.1/1/10 µm) and concentrations (0.5/5/50 µg/mL) on Cx. quinquefasciatus to address this issue. Once exposed at the young larval stage, MPs could accompany the mosquitoes their entire life. The fluorescence signals of MPs in the larvae were mainly located in the intestines. Its intensity increased (from 3.72 × 106 AU to 5.45 × 107 AU) as the concentrations of MPs increases. The fluorescence signals of MPs were also detected in the blood and skin tissues of mice bitten by adult mosquitoes with MPs containing in their bodies. Mosquitos exposed to MPs showed longer larval pupation and eclosion time as well as lower adult body weight. In addition, MPs significantly reduced the lethal effect of pyrethroid insecticides (97.77 % vs. 48.88 %, p < 0.05) with 15.1 % removal of the deltamethrin concentration. After MPs exposure, the relative abundance of the Cx. quinquefasciatus gut microbiome, such as Wolbachia spp., Elizabethkingia spp., and Asaia spp., changed as the MPs size and concentration changes. Mosquitoes provide a new pathway for MPs accumulation and transfer to higher-level living organisms. Moreover, MPs significantly reduce the control effect of deltamethrin, providing new guidelines for mosquito insecticide application in MPs contamination circumstances.

Clinical and Pathological Correlation in Concomitant Celiac Disease and Eosinophilic Esophagitis Suggests Separate Etiologies.

Introduction. Recently, an increased risk of celiac disease or eosinophilic esophagitis has been postulated among patients with either of these disorders, prompting some to suggest a common underlying mechanism, whereas others maintain that their co-existence is coincidental. Methods. We compared clinical and pathological features of 29 patients meeting criteria for both celiac disease and eosinophilic esophagitis to 26 celiac disease and 26 eosinophilic esophagitis controls to determine whether any distinguished study patients from controls. Results. Eight (28%) study patients presented with symptoms of both celiac disease and eosinophilic esophagitis, whereas 14 (48%) had celiac disease symptoms only and 5 had (17%) esophageal symptoms only. Study patients had similar autoimmune and atopic conditions seen in both control groups. Histological severity of disease, including Marsh II-III duodenal histology (study specimens: 87%; controls: 89%), mean peak esophageal eosinophil counts (study specimens: 55/400x field; controls: 80/400X field, P = .1), and presence of eosinophil microabscesses, scale crust, and subepithelial fibrosis were also similar to controls. Gluten-free diet resolved celiac disease-related symptoms (19 of 20, 95%) and histology (10 of 12, 83%), but not esophageal symptoms or eosinophilia in most study patients. Conclusion. Patients with concomitant celiac disease and eosinophilic esophagitis lack distinguishing features compared to controls with celiac disease or eosinophilic esophagitis alone. The occurrence of both disorders is likely coincidental in most cases.

A MnO2 nanosheet-mediated CRISPR/Cas12a system for the detection of organophosphorus pesticides in environmental water.

Nowadays, easy, convenient, and sensitive sensing strategies are still critical for organophosphorus pesticides in environmental water samples. Herein, a novel organophosphorus pesticide (OP) assay based on acetylcholinesterase (AChE) and a MnO2 nanosheet-mediated CRISPR/Cas12a reaction is reported. The single-strand DNA (ssDNA) activator of CRISPR/Cas12a was simply adsorbed on the MnO2 nanosheets as the nanoswitches of the assay. In the absence of target OPs, AChE hydrolyzed acetylcholine (ATCh) to thiocholine (TCh), which reduced the MnO2 nanosheets to Mn2+, resulting in the release of the activator followed by activation of the CRISPR/Cas12a system. The activated Cas12a thereafter nonspecifically cleaved the FAM/BHQ1-labeled ssDNA (FQ-reporter), producing a fluorescence signal. Upon the addition of target OPs, the hydrolysis of ATCh by AChE was inhibited owing to OPs combining with AChE, and thus effective quantification of OPs could be achieved by measuring the fluorescence changes of the system. As a proof of concept, dichlorvos (DDVP) was chosen as a model OP analyte to address the feasibility of the proposed method. Attributed to the excellent trans-cleavage activity of Cas12a, the fluorescent biosensor exhibits a satisfactory limit of detection (LOD) for DDVP at 0.135 ng mL-1. In addition, the excellent recoveries for the detection of DDVP in environmental water samples demonstrate the applicability of the proposed assay in real sample research.

Molecular characterization and biofilm formation ability of Enterococcus faecium and Enterococcus faecalis bloodstream isolates from a Chinese tertiary hospital in Beijing.

To investigate the molecular characteristics and biofilm-forming ability of 116 Enterococcus faecium (Efm) and 72 Enterococcus faecalis (Efs) isolates obtained from patients with bloodstream infections (BSI) at a Chinese hospital between July 2011 and March 2018. The presence of glycopeptide resistance genes and five virulence genes (esp, gelE, asa1, hyl, and cylA) was screened using two multiplex PCR. MLST was used to assess the clonality. Crystal violet staining was used to detect biofilms. Vancomycin resistance was detected in 30.1% of Efm and 2.8% of Efs isolates, respectively. All VRE strains carried the vanA gene. The esp, gelE, asa1, and cylA genes in 72 Efs strains were detected at 62.5%, 84.7%, 84.7%, and 69.4%, respectively. Among the 116 Efm isolates, 74.1% and 25.8% carried esp and hyl, respectively. The esp gene was significantly associated with vancomycin-resistant Efm (VREfm) compared to vancomycin-susceptible Efm (VSEfm). In total, 91.7% of Efs and 20.0% of Efm produced biofilms. Twenty-six STs were identified among the 72 Efs isolates, with ST4 (29.2%) being the predominant. In total, 116 Efm strains were grouped into 26 STs, with ST78 (46.6%) being the predominant. Both VREfm (41.7%) and VSEfm (48.8%) were dominant in ST78. There is no clear evidence suggesting that some STs are associated with vancomycin resistance or biofilm formation. Both Efm and Efs BSI isolates showed a polyclonal pattern with a dominant clone and many unique types, implying the coexistence of clonal dissemination and an influx of new clones. The horizontal transmission of resistance genes may play a more important role in VREfm prevalence than clonal expansion.