Birth Outcomes of Pregnant Women Infected with COVID-19 in Highland Areas of China from 2020 to 2022: A Retrospective Analysis.

Purpose: To explore the effect of coronavirus disease 2019 (COVID-19) infection on neonates in plateau regions. Methods: Cases of newborns born to pregnant women infected with COVID-19 who received prenatal care or treatment at the Women and Children's Hospital of the Tibet Autonomous Region and the Lhasa People's Hospital between January 2020 and December 2022 (infected group) and newborns born to healthy pregnant women (non-infected group) who were included by age, underlying disease and length of hospital stay were retrospectively collected. According to the inclusion and exclusion criteria, 381 patients in the infected group and 314 patients in the non-infected group were included in the study. Results: The results of multivariate analysis showed that admission to the neonatal intensive care unit (OR = 3.342, 95% CI = 1.564-6.764), shortness of breath (OR = 2.853, 95% CI = 1.789-3.154), irregular breathing (OR = 2.465, 95% CI = 1.879-4.112) and neonatal jaundice (OR = 2.324, 95% CI = 1.989-2.445) were the factors influencing the low Apgar scores of neonates in the infected group (all P < 0.05). Conclusion: Neonates born to pregnant women infected with COVID-19 had lower Apgar scores and higher incidences of complications, such as shortness of breath, groaning, irregular breathing and neonatal jaundice, than newborns born to pregnant women not infected with COVID-19.

Polypeptide from Moschus Suppresses Lipopolysaccharide-Induced Inflammation by Inhibiting NF-κ B-ROS/NLRP3 Pathway.

OBJECTIVE: To examine the anti-inflammatory effects and potential mechanisms of polypeptide from Moschus (PPM) in lipopolysaccharide (LPS)-induced THP-1 macrophages and BALB/c mice. METHODS: The polypeptide was extracted from Moschus and analyzed by high-performance liquid chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Subsequently, LPS was used to induce inflammation in THP-1 macrophages and BALB/c mice. In LPS-treated or untreated THP-1 macrophages, cell viability was observed by cell counting kit 8 and lactate dehydrogenase release assays; the proinflammatory cytokines and reactive oxygen species (ROS) were measured by enzyme-linked immunosorbent assay and flow cytometry, respectively; and protein and mRNA levels were measured by Western blot and real-time quantitative polymerase chain reaction (qRT-PCR), respectively. In LPS-induced BALB/c mice, the proinflammatory cytokines were measured, and lung histology and cytokines were observed by hematoxylin and eosin (HE) and immunohistochemical (IHC) staining, respectively. RESULTS: The SDS-PAGE results suggested that the molecular weight of purified PPM was in the range of 10-26 kD. In vitro, PPM reduced the production of interleukin 1ß (IL-1ß), IL-18, tumor necrosis factor α (TNF-α), IL-6 and ROS in LPS-induced THP-1 macrophages (P<0.01). Western blot analysis demonstrated that PPM inhibited LPS-induced nuclear factor κB (NF-κB) pathway and thioredoxin interacting protein (TXNIP)/nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3 (NLRP3) inflammasome pathway by reducing protein expression of phospho-NF-κB p65, phospho-inhibitors of NF-κB (Iκ Bs) kinase α/ß (IKKα/ß), TXNIP, NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and pro-caspase-1 (P<0.05 or P<0.01). In addition, qRT-PCR revealed the inhibitory effects of PPM on the mRNA levels of TXNIP, NLRP3, ASC, and caspase-1 (P<0.05 or P<0.01). Furthermore, in LPS-induced BALB/c mice, PPM reduced TNF-α and IL-6 levels in serum (P<0.05 or P<0.01), decreased IL-1ß and IL-18 levels in the lungs (P<0.01) and alleviated pathological injury to the lungs. CONCLUSION: PPM could attenuate LPS-induced inflammation by inhibiting the NF-κB-ROS/NLRP3 pathway, and may be a novel potential candidate drug for treating inflammation and inflammation-related diseases.

Untethered Small-Scale Machines for Microrobotic Manipulation: From Individual and Multiple to Collective Machines.

Untethered small-scale machines (USSMs) that can actively adjust their motion, deformation, and collective states in response to external stimuli have gained enormous interest in various manipulation, sensing, and biomedical applications. Because they can be efficiently operated in confined and tortuous environments, USSMs are capable of conducting wireless microrobotic manipulation tasks that tethered machines find hard to achieve. Over the past decade of development, significant research progress has been achieved in designing USSM-based manipulation strategies, which are enabled by investigating machine-object, machine-environment, and machine-machine interactions. This review summarizes the latest developments in USSMs for microrobotic manipulation by utilizing individual machines, coordinating multiple machines, and inducing collective behaviors. Providing recent studies and relevant applications in microrobotic and biomedical areas, we also discuss the challenges and future perspectives facing USSMs-based intelligent manipulation systems to achieve manipulation in complex environments with imaging-guided processes and increasing autonomy levels.

Regulating mechanical performance of poly (l-lactide acid) stent by the combined effects of heat and aqueous media.

Annealing process has been applied to the development of thermoforming polymer braided stent and treating its basic constitute monofilaments, especially for Poly (l-lactide acid) (PLLA) condensed by lactic acid monomer made from the plant starch. In this work, high performance monofilaments were produced by melting spun and solid-state drawing methods. Inspired by the effects of water plasticization on semi-crystal polymer, PLLA monofilaments were annealed with and without constraint in vacuum and aqueous media. Then, the co-effects of water infestation and heat on the micro-structure and mechanical properties of these filaments were characterized. Furtherly, mechanical performance of PLLA braided stents shaped by different annealing methods was also compared. Results showed that annealing in aqueous media generated more obvious structure change of PLLA filaments. Interestingly, the combined effects of aqueous phase and thermal effectively increased the crystallinity, and decreased the molecular weight and orientation of PLLA filaments. Therefore, higher modulus, smaller strength, and elongation at the break for filaments could be obtained, which could furtherly realize better radial compression resistance of the braided stent. This annealing strategy could provide new perspectives between anneal and material properties of PLLA monofilaments, and provide more suitable manufacturing technics for polymer braided stent.

Differences of gut microbiota and behavioral symptoms between two subgroups of autistic children based on γδT cells-derived IFN-γ Levels: A preliminary study.

Background: Autism Spectrum Disorders (ASD) are defined as a group of pervasive neurodevelopmental disorders, and the heterogeneity in the symptomology and etiology of ASD has long been recognized. Altered immune function and gut microbiota have been found in ASD populations. Immune dysfunction has been hypothesized to involve in the pathophysiology of a subtype of ASD. Methods: A cohort of 105 ASD children were recruited and grouped based on IFN-γ levels derived from ex vivo stimulated γδT cells. Fecal samples were collected and analyzed with a metagenomic approach. Comparison of autistic symptoms and gut microbiota composition was made between subgroups. Enriched KEGG orthologues markers and pathogen-host interactions based on metagenome were also analyzed to reveal the differences in functional features. Results: The autistic behavioral symptoms were more severe for children in the IFN-γ-high group, especially in the body and object use, social and self-help, and expressive language performance domains. LEfSe analysis of gut microbiota revealed an overrepresentation of Selenomonadales, Negatiyicutes, Veillonellaceae and Verrucomicrobiaceae and underrepresentation of Bacteroides xylanisolvens and Bifidobacterium longum in children with higher IFN-γ level. Decreased metabolism function of carbohydrate, amino acid and lipid in gut microbiota were found in the IFN-γ-high group. Additional functional profiles analyses revealed significant differences in the abundances of genes encoding carbohydrate-active enzymes between the two groups. And enriched phenotypes related to infection and gastroenteritis and underrepresentation of one gut-brain module associated with histamine degradation were also found in the IFN-γ-High group. Results of multivariate analyses revealed relatively good separation between the two groups. Conclusions: Levels of IFN-γ derived from γδT cell could serve as one of the potential candidate biomarkers to subtype ASD individuals to reduce the heterogeneity associated with ASD and produce subgroups which are more likely to share a more similar phenotype and etiology. A better understanding of the associations among immune function, gut microbiota composition and metabolism abnormalities in ASD would facilitate the development of individualized biomedical treatment for this complex neurodevelopmental disorder.

Focus on the crucial deformation region to adjust the comprehensive performance of poly (L-lactic acid) stent.

The fully biodegradable polymer stent is considered as the fourth-generation vascular implant with good biocompatibility and long-term therapeutic potential. It has attracted much attention because it overcomes the disadvantage of the permanently implanted metal stent. However, compared with the metal stent, its mechanical properties are slightly inferior, which is an urgent problem. Based on previous studies, fully biodegradable polymer stents are prone to experience cracks and damage in large deformation region during the crimping and expansion process. The large deformation region is mainly located at the ring bend of the stent. We supposed that these damages are the leading causes of weakening the mechanical performance of polymer stents and are mainly affected by the crucial deformation region. For this purpose, this work studies the relationship between different crucial deformation regions and the mechanical performance of the polymer stent. Firstly, the volume of the crucial deformation region is improved by increasing the ring width. Although the radial strength of the stent is enhanced with the increase in ring width, the radial stiffness also increases, and correspondingly, the flexibility of the stent decreases. To obtain acceptable comprehensive mechanical performance, two types of slotting design in critical deformation region were proposed. The proposed slotted stent with a bulge has sufficient radial strength and low radial stiffness, having a good radial support capacity and flexibility. In other words, the proposed stent has improved the radial support without sacrificing flexibility. Overall, different crucial deformation regions cause different degrees of damage to the stent during crimping and expansion, which affects the mechanical properties of the stent. Reasonable structural design of the crucial deformation region is the key to adjust the comprehensive performance of the stent.

Accuracy and capability of tri-ponderal mass index in assessing cardio-metabolic risk factors in Chinese children and adolescents aged 3 to 17 years, compared with body mass index / 中华医学杂志(英文版)

BACKGROUND@#Tri-ponderal mass index (TMI) has been reported to be a more accurate estimate of body fat than body mass index (BMI). This study aims to compare the effectiveness of TMI and BMI in identifying hypertension, dyslipidemia, impaired fasting glucose (IFG), abdominal obesity, and clustered cardio-metabolic risk factors (CMRFs) in 3- to 17-year-old children.@*METHODS@#A total of 1587 children aged 3 to 17 years were included. Logistic regression was used to evaluate correlations between BMI and TMI. Area under the curves (AUCs) were used to compare discriminative capability among indicators. BMI was converted to BMI- z scores, and accuracy was compared by false-positive rate, false-negative rate, and total misclassification rate.@*RESULTS@#Among children aged 3 to 17 years, the mean TMI was 13.57 ± 2.50 kg/m 3 for boys and 13.3 ± 2.33 kg/m 3 for girls. Odds ratios (ORs) of TMI for hypertension, dyslipidemia, abdominal obesity, and clustered CMRFs ranged from 1.13 to 3.15, higher than BMI, whose ORs ranged from 1.08 to 2.98. AUCs showed similar ability of TMI (AUC: 0.83) and BMI (AUC: 0.85) in identifying clustered CMRFs. For abdominal obesity and hypertension, the AUC of TMI was 0.92 and 0.64, respectively, which was significantly better than that of BMI, 0.85 and 0.61. AUCs of TMI for dyslipidemia and IFG were 0.58 and 0.49. When 85th and 95th of TMI were set as thresholds, total misclassification rates of TMI for clustered CMRFs ranged from 6.5% to 16.4%, which was not significantly different from that of BMI- z scores standardized according to World Health Organization criteria.@*CONCLUSIONS@#TMI was found to have equal or even better effectiveness in comparison with BMI in identifying hypertension, abdominal obesity, and clustered CMRFs TMI was more stable than BMI in 3- to 17-year-old children, while it failed to identify dyslipidemia and IFG. It is worth considering the use of TMI for screening CMRFs in children and adolescents.

The Difference of Gut Microbiota and Their Correlations With Urinary Organic Acids Between Autistic Children With and Without Atopic Dermatitis.

Autism is a kind of biologically based neurodevelopmental condition, and the coexistence of atopic dermatitis (AD) is not uncommon. Given that the gut microbiota plays an important role in the development of both diseases, we aimed to explore the differences of gut microbiota and their correlations with urinary organic acids between autistic children with and without AD. We enrolled 61 autistic children including 36 with AD and 25 without AD. The gut microbiota was sequenced by metagenomic shotgun sequencing, and the diversity, compositions, and functional pathways were analyzed further. Urinary organic acids were assayed by gas chromatography-mass spectrometry, and univariate/multivariate analyses were applied. Spearman correlation analysis was conducted to explore their relationships. In our study, AD individuals had more prominent gastrointestinal disorders. The alpha diversity of the gut microbiota was lower in the AD group. LEfSe analysis showed a higher abundance of Anaerostipes caccae, Eubacterium hallii, and Bifidobacterium bifidum in AD individuals, with Akkermansia muciniphila, Roseburia intestinalis, Haemophilus parainfluenzae, and Rothia mucilaginosa in controls. Meanwhile, functional profiles showed that the pathway of lipid metabolism had a higher proportion in the AD group, and the pathway of xenobiotics biodegradation was abundant in controls. Among urinary organic acids, adipic acid, 3-hydroxyglutaric acid, tartaric acid, homovanillic acid, 2-hydroxyphenylacetic acid, aconitic acid, and 2-hydroxyhippuric acid were richer in the AD group. However, only adipic acid remained significant in the multivariate analysis (OR = 1.513, 95% CI [1.042, 2.198], P = 0.030). In the correlation analysis, Roseburia intestinalis had a negative correlation with aconitic acid (r = -0.14, P = 0.02), and the latter was positively correlated with adipic acid (r = 0.41, P = 0.006). Besides, the pathway of xenobiotics biodegradation seems to inversely correlate with adipic acid (r = -0.42, P = 0.18). The gut microbiota plays an important role in the development of AD in autistic children, and more well-designed studies are warranted to explore the underlying mechanism.

Evaluation of resistance to radial cyclic loads of poly(L-lactic acid) braided stents with different braiding angles.

Poly(L-lactic acid) (PLLA) braided stents have superior biocompatibility and flexibility, substituting metal stents in peripheral blood vessels. However, the radial supporting capacity of PLLA braided stent should be improved to bear the dynamic load from the peripheral artery. This paper evaluated the radial support performance of PLLA braided stents with different braiding angles after the radial cyclic loads test. The results indicate that braiding angle of stents is an important parameter affecting its ability to resist radial cyclic loads. The stent with a smaller braiding angle has better initial radial support but insufficient durability, while the stent with a larger braiding angle could maintain adequate radial support and suitable ability to resist radial cyclic loads. The theoretical analysis, verified by observing the surface morphology of filament crossover points, found that filaments of the stents with smaller braiding angles have more significant axial displacement and axial rotation angle during radial compression, which made the friction phenomenon more intense and led to insufficient ability to resist radial cyclic loads. This study could provide a meaningful idea for preparing biodegradable braided stents with suitable ability to resist radial cyclic loads.

Hybrid diffusion imaging reveals altered white matter tract integrity and associations with symptoms and cognitive dysfunction in chronic traumatic brain injury.

The detection and association of in vivo biomarkers in white matter (WM) pathology after acute and chronic mild traumatic brain injury (mTBI) are needed to improve care and develop therapies. In this study, we used the diffusion MRI method of hybrid diffusion imaging (HYDI)to detect white matter alterations in patients with chronic TBI (cTBI). 40 patients with cTBI presenting symptoms at least three months post injury, and 17 healthy controls underwent magnetic resonance HYDI. cTBI patients were assessed with a battery of neuropsychological tests. A voxel-wise statistical analysis within the white matter skeleton was performed to study between group differences in the diffusion models. In addition, a partial correlation analysis controlling for age, sex, and time after injury was performed within the cTBI cohort, to test for associations between diffusion metrics and clinical outcomes. The advanced diffusion modeling technique of neurite orientation dispersion and density imaging (NODDI) showed large clusters of between-group differences resulting in lower values in the cTBI across the brain, where the single compartment diffusion tensor model failed to show any significant results. However, the diffusion tensor model appeared to be just as sensitive in detecting self-reported symptoms in the cTBI population using a within-group correlation. To the best of our knowledge this study provides the first application of HYDI in evaluation of cTBI using combined DTI and NODDI, significantly enhancing our understanding of the effects of concussion on white matter microstructure and emphasizing the utility of full characterization of complex diffusion to diagnose, monitor, and treat brain injury.

Fluid-Guided CVD Growth for Large-Scale Monolayer Two-Dimensional Materials.

Atmospheric pressure chemical vapor deposition (APCVD) has been used extensively for synthesizing two-dimensional (2D) materials because of its low cost and promise for high-quality monolayer crystal synthesis. However, the understanding of the reaction mechanism and the key parameters affecting the APCVD processes is still in its embryonic stage. Hence, the scalability of the APCVD method in achieving large-scale continuous film remains very poor. Here, we use MoSe2 as a model system and present a fluid guided growth strategy for understanding and controlling the growth of 2D materials. Through the integration of experiment and computational fluid dynamics (CFD) analysis in the full-reactor scale, we identified three key parameters, precursor mixing, fluid velocity, and shear stress, which play a critical role in the APCVD process. By modifying the geometry of the growth setup to enhance precursor mixing and decrease nearby velocity shear rate and adjusting flow direction, we have successfully obtained inch-scale monolayer MoSe2. This unprecedented success of achieving scalable 2D materials through fluidic design lays the foundation for designing new CVD systems to achieve the scalable synthesis of nanomaterials.

Fluid-Assisted Sorted Assembly of Graphene on Polymer.

The significant size distribution of as-synthesized nanomaterials presents a challenge for reproducable and reliable applications. In this paper, we report a fluidic-assisted sorted assembly method in which nanomaterial sorting and enhanced assembly can be achieved simultaneously. As a proof of concept, a two-dimensional (2D) graphene flake, with a large size variation, was chosen as the target nanomaterial system. This study synergizes a novel fluidic assembly design, suspending a rotating disk over a polydimethylsiloxane (PDMS) substrate, and a computational fluid dynamics (CFD) model using Ansys CFX to disclose the mechanism of sorted assembly. By controlling the rotating speed and the gap between the disk and the substrate, the flow field is altered. In contrast to centrifugal sorting, where larger particles move outward, in this study, the size of assembled graphene flake (average lateral size, Xc) reduces significantly from the center (Xc = 3 µm) to the edge of the disk (Xc = 2 µm). The particle sorting process is dictated by the fluid shear-stress, with higher shear-stress leading to smaller particles, while the assembly process is mainly dominated by the pressure field with higher pressure magnitude leading to better assembly. Near the edge of the disk, enhanced particle sorting is coupled with an enhanced assembly where a continuous graphene film with smaller Xc can be formed. To prove the potential application of this method, an ultrasensitive strain sensor with one of the lowest detection limits, 0.02%, is demonstrated. This research presents a novel route toward large-scale and cost-effective manufacturing of nanomaterial-based flexible electronics.

DL-CNV: A deep learning method for identifying copy number variations based on next generation target sequencing.

Copy number variations (CNVs) play an important role in many types of cancer. With the rapid development of next generation sequencing (NGS) techniques, many methods for detecting CNVs of a single sample have emerged: (i) require genome-wide data of both case and control samples, (ii) depend on sequencing depth and GC content correction algorithm, (iii) rely on statistical models built on CNV positive and negative sample datasets. These make them costly in the data analysis and ineffective in the targeted sequencing data. In this study, we developed a novel alignment-free method called DL-CNV to call CNV from the target sequencing data of a single sample. Specifically, we collected two sets of samples. The first set consists of 1301 samples, in which 272 have CNVs in ERBB2 and the second set is composed of 1148 samples with 63 samples containing CNVs in MET. Finally, we found that a testing AUC of 0.9454 for ERBB2 and 0.9220 for MET. Furthermore, we hope to make the CNV detection could be more accurate with clinical "gold standard" (e.g. FISH) information and provide a new research direction, which can be used as the supplement to the existing NGS methods.

Suppression of miR-34a Expression in the Myocardium Protects Against Ischemia-Reperfusion Injury Through SIRT1 Protective Pathway.

MicroRNA-34a (miR-34a) is expressed in the myocardium and expression is altered after myocardial injury. We investigated the effects of miR-34a on heart function after ischemia-reperfusion (IR) injury. Cardiomyocytes were isolated from neonatal rat hearts and simulated IR injury was induced in vitro. Following IR injury in rats, infarct size was measured and left ventricular (LV) function was evaluated using echocardiography. Protein expression of silent information regulator 1 (SIRT1), acetylated p53 (ac-p53), Bcl-2 and Bax, and miR-34a and SIRT1 gene levels were analyzed. miR-34a overexpression exacerbated myocardial injury by increasing apoptosis and infarct size and decreasing LV function. Suppression of miR-34a attenuated myocardial IR injury. SIRT1 was negatively regulated by miR-34a and the expression of downstream genes, such as ac-p53, Bcl-2, and Bax were altered correspondingly. Increased expression of miR-34a aggravates injury after IR; miR-34a suppression therapy may represent a new line of treatment for myocardial IR injury.

Insights into mutualism mechanism and versatile metabolism of Ketogulonicigenium vulgare Hbe602 based on comparative genomics and metabolomics studies.

Ketogulonicigenium vulgare has been widely used in vitamin C two steps fermentation and requires companion strain for optimal growth. However, the understanding of K. vulgare as well as its companion strain is still preliminary. Here, the complete genome of K. vulgare Hbe602 was deciphered to provide insight into the symbiosis mechanism and the versatile metabolism. K. vulgare contains the LuxR family proteins, chemokine proteins, flagellar structure proteins, peptides and transporters for symbiosis consortium. Besides, the growth state and metabolite variation of K. vulgare were observed when five carbohydrates (D-sorbitol, L-sorbose, D-glucose, D-fructose and D-mannitol) were used as carbon source. The growth increased by 40.72% and 62.97% respectively when K. vulgare was cultured on D-mannitol/D-sorbitol than on L-sorbose. The insufficient metabolism of carbohydrates, amino acids and vitamins is the main reason for the slow growth of K. vulgare. The combined analysis of genomics and metabolomics indicated that TCA cycle, amino acid and nucleotide metabolism were significantly up-regulated when K. vulgare was cultured on the D-mannitol/D-sorbitol, which facilitated the better growth. The present study would be helpful to further understand its metabolic structure and guide the engineering transformation.

[Characterizing Beijing's Airborne Bacterial Communities in PM2.5 and PM1 Samples During Haze Pollution Episodes Using 16S rRNA Gene Analysis Method].

During 8th-14th Jan., 2013, severe particulate matter (PM) pollution episodes happened in Beijing. These air pollution events lead to high risks for public health. In addition to various PM chemical compositions, biological components in the air may also impose threaten. Little is known about airborne microbial community in such severe air pollution conditions. PM2.5 and PM10 samples were collected during that 7-day pollution period. The 16S rRNA gene V3 amplification and the MiSeq sequencing were performed for analyzing these samples. It is found that there is no significant difference at phylum level for PM2.5 bacterial communities during that 7-day pollution period both at phylum and at genus level. At genus level, Arthrobacter and Frankia are the major airborne microbes presented in Beijing winter.samples. At genus level, there are 39 common genera (combined by first 50 genera bacterial of the two analysis) between the 16S rRNA gene analysis and those are found by Metagenomic analysis on the same PM samples. Frankia and Paracoccus are relatively more abundant in 16S rRNA gene data, while Kocuria and Geodermatophilus are relatively more abundant in Meta-data. PM10 bacterial communities are similar to those of PM2.5 with some noticeable differences, i.e., at phylum level, more Firmicutes and less Actinobacteria present in PM10 samples than in PM2.5 samples, while at genus level, more Clostridium presents in PM10 samples. The findings in Beijing were compared with three 16S rRNA gene studies in other countries. Although the sampling locations and times are different from each other, compositions of bacterial community are similar for those sampled at the ground atmosphere. Airborne microbial communities near the ground surface are different from those sampled in the upper troposphere.