Background and purpose: Increasing evidence suggests that ferroptosis plays a key role in the pathophysiology of acute kidney injury induced by cisplatin. The Nrf2 signaling pathway regulates oxidative stress and lipid peroxidation and positively regulates cisplatin-induced AKI (CI-AKI). However, Nrf2 and its activator leonurine on ferroptosis after CI-AKI remain unclear. Experimental Approach: The anti-ferroptotic effects of Nrf2 and its activator leonurine were assessed using a mouse model of cisplatin-induced AKI. In vitro, the potential effects of leonurine on erastin- and RSL3-induced HK-2 human PTEC ferroptosis were examined. Key Results: As expected, Nrf2 deletion induced ferroptosis-related protein expression and iron accumulation in vivo, further aggravating CI-AKI. The Nrf2 activator leonurine prevented iron accumulation and lipid peroxidation and inhibited ferroptosis in vitro, while these effects were abolished in siNrf2-treated cells. Moreover, leonurine potently ameliorated cisplatin-induced renal damage, as indicated by the assessment of SCr, BUN, KIM-1, and NGAL. Importantly, leonurine activated the Nrf2 antioxidative signaling pathway and prohibited changes in ferroptosis-related morphological and biochemical indicators, such as the MDA level, SOD and GSH depletion and GPX4 and xCT downregulation, in CI-AKI. Moreover, Nrf2 KO mice were more susceptible to ferroptosis after CI-AKI than control mice, and the protective effects of leonurine on AKI and ferroptosis were largely abolished in Nrf2 KO mice. Conclusion and Implications: These data suggest that the renal protective effects of Nrf2 and its activator leonurine on CI-AKI are achieved at least partially by inhibiting lipid peroxide-mediated ferroptosis and highlight the potential of leonurine as a CI-AKI treatment.

Treatment of recurrent ruptured aneurysms incorporating a branch vessel arising from the dome is challenging. Here, we attempted horizontal stent-assisted coil embolisation via a retrograde route from the contralateral internal carotid artery to treat a small ruptured posterior communicating artery aneurysm incorporating a foetal variant posterior cerebral artery after clipping.

Bioconversion process with a single target product often lacks economic competitiveness owing to incomplete use of raw material and high costs of downstream processing (DSP). Here, we show with the microbial conversion of crude glycerol that an integrated strain engineering and catalytic conversion of the so-called byproducts can greatly improve DSP and the process economy. Specifically, Clostridium pasteurianum was first adapted to increased concentration of crude glycerol in a novel automatic laboratory evolution system. At m3 scale bioreactor the strain achieved a simultaneous production of 1,3-propanediol (PDO), acetic and butyric acids at 81.21, 18.72 and 11.09 g/L within only 19 h, respectively, representing the most efficient fermentation of crude glycerol to targeted products. A heterogeneous catalytic step was developed and integrated into the DSP process to obtain high-value methyl esters from acetic and butyric acids at high yields. The co-production of the esters also greatly simplified the recovery of PDO. For example, a cosmetic grade PDO (96% PDO) was easily obtained by a simple single-stage distillation process (with an overall yield more than 77%). This integrated approach provides an industrially attractive route for a complete use of the raw material with the simultaneous production of three appealing products which greatly improve the process economy and ecology.

Soil–rock mixtures are widely encountered in geotechnical engineering projects. The instability and failure mechanism of grap-graded soil–rock mixtures under rainfall conditions has always been the focus of geological disaster research. To deeply explore the mechanism of seepage deformation of soil–rock mixtures, an indoor physical permeability test that considers soil–rock mixtures with different fine contents was conducted, and a particle-scale numerical simulation test of the permeability evolution was carried out using the coupling model of PFC3D and ABAQUS. The test results showed that the spatial distribution of fine particle loss along the height direction could be divided into three areas: top loss, middle uniform, and bottom loss area. The “island” effect of coarse particles, which is caused by excessive fine content and makes the fine particles bear more load, was eliminated with the loss of fine particles. In this preset working condition of coarse and fine particle diameters, setting FC to 35% may be the best way to fill the voids between the coarse particles. Particle migration leads to a change in the load-bearing skeleton structure, thereby causing seepage deformation. Therefore, the particle-scale numerical test method can better reproduce the seepage deformation process of grap-graded soil–rock mixtures.

Identification, source tracking, and surveillance of food pathogens is a crucial factor for the food-producing industry. Over the last decade, the techniques used for this have moved from conventional enrichment methods, through species-specific detection by PCR to sequencing-based methods, whole-genome sequencing (WGS) being the ultimate method. However, using WGS requires the right infrastructure, high computational power, and bioinformatics expertise. Therefore, there is a need for faster, more cost-effective, and more user-friendly methods. A newly developed method, ON-rep-seq, combines the classical rep-PCR method with nanopore sequencing, resulting in a highly discriminating set of sequences that can be used for species identification and also strain discrimination. This study is essentially a real industry case from a salmon processing plant. Twenty Listeria monocytogenes isolates were analyzed both by ON-rep-seq and WGS to identify and differentiate putative L. monocytogenes from a routine sampling of processing equipment and products, and finally, compare the strain-level discriminatory power of ON-rep-seq to different analyzing levels delivered from the WGS data. The analyses revealed that among the isolates tested there were three different strains. The isolates of the most frequently detected strain (n=15) were all detected in the problematic area in the processing plant. The strain level discrimination done by ON-rep-seq was in full accordance with the interpretation of WGS data. Our findings also demonstrate that ON-rep-seq may serve as a primary screening method alternative to WGS for identification and strain-level differentiation for surveillance of potential pathogens in a food-producing environment.

Silk is a fibrous protein, has been a part of human lives for centuries and was used as suture and textile material. Silk is mainly produced by members of certain arthropods such as spiders, butterflies, mites, and moths. However, recent biotechnological advances have revolutionized silk as a biomaterial for various applications ranging from diverse sensors to robust fibers. The biocompatibility, mechanical resilience, and biodegradability of the material make it a suitable candidate for biomaterials. Silk can also be easily converted into several morphological forms, including fibers, films, sponges, and hydrogels. Provided these abilities, silk has received excellent traction from scientists worldwide for various developments, one of them being its use as a bio-sensor. The diversity of silk materials offers various options, giving scientists the freedom to choose from and personalize them as per their needs. In this review, we foremost look upon the composition, production, properties, and various morphologies of silk. The numerous applications of silk and its derivatives for fabricating biosensors to detect small molecules, macromolecules, and cells have been explored comprehensively. Also, the data from various globally developed sensors using silk have been described into organized tables for each category of molecules, along with their important analytical details.

High-throughput sequencing for analysis of environmental microbial diversity has evolved vastly over the last decade. Currently the go-to method for microbial eukaryotes is short-read metabarcoding of variable regions of the 18S rRNA gene with <500 bp amplicons. However, there is a growing interest in long-read sequencing of amplicons covering the rRNA operon for improving taxonomic resolution. For both methods, the choice of primers is crucial. It determines if community members are covered, if they can be identified at a satisfactory taxonomic level, and if the obtained community profile is representative. Here, we designed new primers targeting 18S and 28S rRNA based on 177,934 and 21,072 database sequences, respectively. The primers were evaluated in silico along with published primers on reference sequence databases and marine metagenomics datasets. We further evaluated a subset of the primers for short- and long-read sequencing on environmental samples in vitro and compared the obtained community profile with primer-unbiased metagenomic sequencing. Of the short-read pairs, a new V6-V8 pair and the V4_Balzano pair used with a simplified PCR protocol provided good results in silico and in vitro. Fewer differences were observed between the long-read primer pairs. The long-read amplicons and ITS1 alone provided higher taxonomic resolution than V4. Together, our results represent a reference and guide for selection of robust primers for research on and environmental monitoring of microbial eukaryotes.

Objective: The COVID-19 pandemic is an important cause of morbidity and mortality, which has had a negative impact worldwide. Our aim was to describe clinical findings and outcomes of SARS-CoV-2 viral infection and Covid-19 disease cared for at a large pediatric tertiary care hospital during the first year of the pandemic. Methods: Patients aged 1 month to 18 years who were diagnosed as having COVID-19 between March 2020 and April 2021 were included. The files of patients diagnosed with covid-19 were reviewed retrospectively. Results: 467 children were included in the study. There were 34 (7.3%) patients under one year of age, 111 (23.8%) between 1-5 years, 98 (30.4%) between 5-10 years, 142 (30.4%) between 11-15 years, and 82 (17.6%) age over 15 years. Fever (88.2%), vomiting (32.4%), and diarrhea (29.4%) in patients aged under 1 year, sore throat (36.6%) in patients aged 11-15 years, and dysgeusia (11%), anosmia (14.6%), headache (18.3%), malaise (40.8%), myalgia (28%), and dyspnea (17.1%) in those aged over 15 years of age were found significantly more common compared with the other age groups (p<0.05). Thirty-five (7.5%) patients were asymptomatic, 365 (78.1%) had mild disease, 35 (7.5%) were moderate, 27 (5.8%) were severe, and five (1.07%) were critical. Leukocyte count, erythrocyte sedimentation rate, ferritin, and C-reactive protein values were significantly higher in hospitalized patients. Four patients died during the study period (0.8%, 4/467). Conclusion: While SARS-CoV-2 infection may be asymptomatic and Covid-19 disease usually has a mild clinical course, some children have severe disease or mortality.

The circadian rhythm is an adaptive biological process, allows organisms to anticipate daily environmental changes and implement appropriate strategies. Circadian rhythms play a crucial role in the health and survival of organisms. However, little is known concerning how intrinsic and extrinsic factors affect animal daily rhythms in the field, especially in nocturnal animals. Here, we investigated the emergence and return times of Vesperilio sinensis, and also integrated environmental conditions (temperature, humidity and light intensity) and biotic factors (reproductive status and predation risk) to determine causes of variation in the activity rhythms of the bats. We found that variation in the first emergence time, the mid-emergence time, and the final return time were distinct. The results demonstrated that the emergence and return times of bats were affected by light intensity, reproductive status, and predation risk in a relatively complex pattern. Light intensity had the greatest contribution to activity rhythms. Moreover, we first investigated the effects of actual predators on the activity rhythms of bats; the results showed that the mid-emergence time of bats was earlier as predators were hunting, but the final return time was later when predators were present. This challenges the traditional view that high predation risk leads to later emergence and earlier return. Finally, our results also highlighted the importance of higher energy demands during the lactation period in bats to variation in activity rhythms. These results improve our understanding of the patterns and causes of variation in activity rhythms in bats and other nocturnal animals.

Primary ciliary dyskinesis (PCD) is an autosomal recessive disorder associated with impaired mucociliary clearance caused by defects in ciliary structure and function. The major clinical feature of PCD is recurring or persistent respiratory tract infection. Respiratory tract colonization with drug-resistant organisms impact the frequency of infections and lung function decline. Protective gear has been employed by caregivers in an attempt to control respiratory tract bacterial spread between patients with cystic fibrosis but use in PCD is not known. We conducted a web-based survey to investigate infection control and prevention practices of PCD centers in North America. The response rate was 87.0%. Prior to the COVID-19 pandemic, glove, gown and mask use was variable, and only 3.7% of centers used masks during encounters with PCD outpatients. After COVID-19 mandates are lifted, 48.1% of centers plan to continue to use masks during outpatient care, while the practice regarding use of gloves and gowns was not influenced by the current pandemic. There is no uniform practice for infection control in PCD care indicating the need for practice guidelines. Mitigation of respiratory virus transmission learned during the COVID-19 pandemic may impact future infection control approaches used for patients with PCD and other lung diseases.

Background: Parapneumonic effusions and empyema are the most frequent complication of paediatric pneumonia. Treatment options include chest drain and fibrinolytics (CDF) or thoracoscopic surgery. CDF is considered less invasive, more cost effective though with higher rates of reintervention. Pleural fluid characteristics on ultrasound may identify cases at increased risk of treatment failure with primary CDF. Methods: A retrospective cohort 2011-2018 of complicated pneumonia managed with primary CDF. Cases were reviewed using ultrasound criteria to describe pleural fluid. We compared ultrasound findings and treatment failure. Results: We report 137 cases with a median age 3.8 years and 43% female. Treatment failure occurred for 32/137 (23%) cases. The interobserver reliability was substantial for the number of septations (Kappa 0.72, 95% CI 0.6 to 0.8), moderate for the size of the largest locule (Kappa 0.55, 95% CI 0.4 to 0.7) and fair for the level of echogenicity (Kappa 0.22, 95%CI 0.1 to 0.3), pleural thickening (Kappa 0.28, 95% CI 0.2 to 0.4), maximum effusion depth (Kappa 0.37, 95%CI 0.2 to 0.5) and radiologist’s risk for reintervention (Kappa 0.32, 95% CI 0.2 to 0.5). Hyperechoic pleural fluid was associated with treatment failure, with cases nearly five times more likely than anechoic fluid to have a reintervention (OR 4.9 95%CI 1.7 to 14.2, p=0.04). Treatment failure was not associated with other variables. Conclusion: We did not find an association between ultrasound characteristics and treatment failure for complicated pneumonia managed with primary CDF. Inter-observer agreement of ultrasound findings was difficult despite more objective criteria.

In this article, we want to present a patient with Burtonian or lead line at the gum tooth line, a rare presentation of lead poisoning.

Objectives: First, to examine the predictive performance for placental dysfunction related stillbirths of the competing risks model for small for gestational age (SGA) fetuses based on a combination of maternal risk factors, estimated fetal weight (EFW) and uterine artery pulsatility index (UtA-PI); and second, to compare the performance of this model to that of stillbirth-specific model utilizing the same biomarkers and to the Royal College of Obstetricians and Gynecologists (RCOG) guideline for the investigation and management of the SGA fetus. Design: Prospective observational study. Setting: Two UK maternity hospitals. Population: 131,514 women with singleton pregnancies attending for routine ultrasound examination at 19-24 weeks’ gestation. Methods: The predictive performance for stillbirth achieved by three models was compared. Main outcome measures: Placental dysfunction related stillbirth. Results: At 10% false positive rate, the competing risks model predicted 59%, 66% and 71% of placental dysfunction related stillbirths, at any gestation, at <37 weeks and at <32 weeks, respectively, which were similar to the respective figures of 62%, 70% and 73% for the stillbirth-specific model. At a screen positive rate of 21.8 %, as defined by the RCOG guideline, the new model predicted 71%, 76% and 79% of placental dysfunction related stillbirths at any gestation, at <37 weeks and at <32 weeks, respectively, and the respective figures for the RCOG guideline were 42%, 44% and 40%. Conclusion: The predictive performance for placental dysfunction related stillbirths by the competing risks model for SGA was similar to the stillbirth-specific model and superior to the RCOG guideline.

The gut microbiomes of the host are large and complex communities, which helps to maintain homeostasis, improves digestive efficiency, and promotes the development of the immune system. The small mammals distributed in Sichuan Province are the most popular species for biodiversity research in Southwest China. However, the effects of different diets on the structure and function of the gut microbial community of these small mammals are poorly understood. In this study, whole-metagenome shotgun sequencing has been used to analyze the composition and functional structures of the gut microbiota of seven small mammals in Laojunshan National Nature Reserve, Sichuan Province, China. Taxonomic classification revealed that the most abundant phyla in the gut of seven small mammals were Bacteroides, Proteobacteria and Firmicutes. Moreover, Hafnia, Raoultella and Aeromonas were most abundant genus in the gut microbiomes of these seven species. At the functional level, we annotated a series of KEGG functional pathways, six Cazy categories and 46,163 AROs in the gut microbiomes of the seven species. Comparative analysis found that the difference in the gut microbiomes between the Soricidea and Muridae concentrated on the increase in the F/B (Firmicutes/Bacteroides) ratio in the Soricidea group, probably driven by the high fat and calorie digestive requirements due to their insectivorous diet. The comparative functional profiling revealed that functions related to metabolism and carbohydrates were significantly more abundant in Muridae group, which may be attributed to their high carbohydrate digestion requirements caused by their herbivorous diet. These data suggested that different diets in the host may play an important role in shaping the gut microbiota, and lay the foundation for teasing apart the influences of heritable and environmental factors on the evolution of gut microbial communities.

Objective To quantify parents’ experiences of respectful care around stillbirth globally. Design Multi-country, online, cross-sectional survey. Setting and Population Self-identified bereaved parents (n=3769) of stillborn babies from 44 high- and middle-income countries. Methods Parents’ perspectives of 7 aspects of care quality, factors associated with respectful care, and 7 bereavement care practices were compared across geographical regions using descriptive statistics. Respectful care was compared between country income groups using multivariable logistic regression. Main Outcome Measures Self-reported experience of care around the time of stillbirth Results A quarter (25.4%) of 3769 respondents reported disrespectful care after stillbirth and 23.5% reported disrespectful care of their baby. Gestation <30 weeks, and primiparity were associated with disrespect. Reported respectful care was lower in middle-income countries (MICs) than in high-income countries (HICs) (aOR=0.35, 95%CI (0.29-0.42), p <0.01). In many countries, aspects of care quality need improvement, such as ensuring families have enough time with providers. Participating respondents from Latin America and Southern Europe reported lower satisfaction across all aspects of care quality compared to Northern Europe. Unmet need for memory-making activities in MICs is high. Conclusions Despite improvements, many parents still experience disrespectful care around stillbirth. The gap between parents’ access to memory-making activities in MICs and HICs needs urgent attention. Tweetable abstract A quarter of parents of stillborn babies experience disrespectful care. There is global unmet need for memory-making activities

1. Resource polymorphism is common across taxa and can result in alternate ecotypes with specific morphologies, feeding modes, and behaviours that increase performance in a specific habitat. This can result in high intraspecific variation in the expression of specific traits and the extent to which these traits are correlated within a single population. Although metabolic rate influences resource aquisition and the overall pace of life of individuals it is not clear how metabolic rate interact with the larger suite of traits to ultimately determine individual fitness. 2. We examined the relationship between metabolic rates and the major differences (habitat use, morphology, and resource use) between littoral and pelagic ecotypes of European perch (Perca fluviatilis) from a single lake in Central Sweden. 3. Standard metabolic rate (SMR) was significantly higher in pelagic perch but did not correlate with resource use or morphology. Maximum metabolic rate (MMR) was not correlated with any of our explanatory variables or with SMR. Aerobic scope (AS) showed the same pattern as SMR, differing across habitats, but contrary to expectations, was lower in pelagic perch. 4. This study helps to establish a framework for future experiments further exploring the drivers of intraspecific differences in metabolism. In addition, since metabolic rates scale with temperature and determine predator energy requirements, our observed differences in SMR across habitats will help determine ecotype-specific vulnerabilities to climate change and differences in top-down predation pressure across habitats.

Sexual selection frequently promotes the evolution of aggressive behaviours that help males compete against their rivals, but which may harm females and hamper their fitness. Kin selection theory predicts that optimal male-male competition levels can be reduced when competitors are more genetically related to each other than to the population average, contributing to resolve this sexual conflict. Work in Drosophila melanogaster has spearheaded empirical tests of this idea, but studies so far have been conducted in lab-adapted populations in homogeneous rearing environments that may hamper kin recognition, and used highly skewed sex ratios that may fail to reflect average natural conditions. Here, we performed a fully factorial design with the aim of exploring how rearing environment (i.e. familiarity) and relatedness affect male-male aggression, male harassment, and overall male harm levels in a natural population of Drosophila melanogaster, under more natural conditions. Namely, we: a) manipulated relatedness and familiarity so that larvae reared apart were raised in different environments, as is common in the wild, and b) studied the effects of relatedness and familiarity under average levels of male-male competition in the field. We show that, contrary to previous findings, groups of unrelated-unfamiliar males were as likely to fight with each other and harass females than related-familiar males, and that overall levels of male harm to females were similar across treatments. Our results suggest that the role of kin selection in modulating sexual conflict is yet unclear in Drosophila melanogaster, and call for further studies that focus on natural populations and realistic socio-sexual and ecological environments.

Over the course of time, new developments associated with embryogenesis of the murine heart have served to clarify the developmental processes observed in the human heart. This evidence allows for creation of a developmental framework for many congenital cardiac defects. Here, we aim to solidify the framework related to the categorization of both solitary and multiple ventricular septal defects. Mice having genetic perturbation of the Furin enzyme have demonstrated perimembranous and juxta-arterial ventricular septal defects, permitting the inference to be made that these defects can co-exist with defects occurring within the apical muscular septum. Based on developmental evidence, furthermore, all interventricular communications can be placed into one of three groups, namely, those which are perimembranous, juxta-arterial, and muscular. All of the defects are described based on their borders as seen from the morphologically right ventricle. Our focus here will be on those defects within the muscular ventricular septum, recognizing that such defects can co-exist with those that are perimembranous. We discuss the differentiation of multiple discrete defects from those referred to as the ‘Swiss cheese’ variant. As we show, appropriate surgical management requires understanding of the specific terminology, as the surgical approach may differ depending on the combination of the individual defects. Data from the Society for Thoracic Surgeons revealed that both mortality and morbidity were increased in the setting of multiple as opposed to solitary ventricular septal defects.