Fecal microbiota transplantation alleviates mild-moderate COVID-19 associated diarrhoea and depression symptoms: A prospective study of a randomized, double-blind clinical trial.

Currently, the emergence of the endemic Coronavirus disease (COVID-19) situation still poses a serious threat to public health. However, it remains elusive about the role of fecal microbiota transplantation in treating COVID-19. We performed a randomized, double-blind, placebo-controlled clinical trial enrolling a cohort of 40 COVID-19 patients with mild-moderate symptoms. Our results showed that fecal microbiota transplantation provided an amelioration in diarrhoea (p = 0.026) of digestive system and depression (p = 0.006) of neuropsychiatric-related symptom in COVID-19 patients, respectively. Meanwhile, we found that the number of patients with diarrhoea decreased from 19 to 0 on day 7 after fecal microbiota transplantation treatment, and it was statistically changed compared to the placebo group (p = 0.047). Of note, the serum concentration of aspartate aminotransferase-to-alanine aminotransferase ratio (AST/ALT, fecal microbiota transplantation, pre vs. post: 0.966 vs. 0.817), a biomarker for predicting long COVID-19, was significantly reduced by fecal microbiota transplantation. In all, our study supports that fecal microbiota transplantation could be a novel therapeutic strategy for COVID-19 patients with diarrhoea and depressive symptoms, which is potentially valuable in ameliorating long COVID-19 symptoms.

Structural diversity, biosynthesis, and biological functions of lipopeptides from Streptomyces.

Covering: up to 2022Streptomyces are ubiquitous in terrestrial and marine environments, where they display a fascinating metabolic diversity. As a result, these bacteria are a prolific source of active natural products. One important class of these natural products is the nonribosomal lipopeptides, which have diverse biological activities and play important roles in the lifestyle of Streptomyces. The importance of this class is highlighted by the use of related antibiotics in the clinic, such as daptomycin (tradename Cubicin). By virtue of recent advances spanning chemistry and biology, significant progress has been made in biosynthetic studies on the lipopeptide antibiotics produced by Streptomyces. This review will serve as a comprehensive guide for researchers working in this multidisciplinary field, providing a summary of recent progress regarding the investigation of lipopeptides from Streptomyces. In particular, we highlight the structures, properties, biosynthetic mechanisms, chemical and chemoenzymatic synthesis, and biological functions of lipopeptides. In addition, the application of genome mining techniques to Streptomyces that have led to the discovery of many novel lipopeptides is discussed, further demonstrating the potential of lipopeptides from Streptomyces for future development in modern medicine.

Intestinal dysbiosis mediates cognitive impairment via the intestine and brain NLRP3 inflammasome activation in chronic sleep deprivation.

Growing evidence suggests the involvement of the microbiota-gut-brain axis in cognitive impairment induced by sleep deprivation (SD), however how the microbiota-gut-brain axis work remains elusive. Here, we discovered that chronic SD induced intestinal dysbiosis, activated NLRP3 inflammasome in the colon and brain, destructed intestinal/blood-brain barrier, and impaired cognitive function in mice. Transplantation of "SD microbiota" could almost mimic the pathological and behavioral changes caused by chronic SD. Furthermore, all the behavioral and pathological abnormalities were practically reversed in chronic sleep-deprived NLRP3-/- mice. Regional knockdown NLRP3 expression in the gut and hippocampus, respectively. We observed that down-regulation of NLRP3 in the hippocampus inhibited neuroinflammation, and ameliorated synaptic dysfunction and cognitive impairment induced by chronic SD. More intriguingly, the down-regulation of NLRP3 in the gut protected the intestinal barrier, attenuated the levels of peripheral inflammatory factors, down-regulated the expression of NLRP3 in the brain, and improved cognitive function in chronic SD mice. Our results identified gut microbiota as a driver in chronic SD and highlighted the NLRP3 inflammasome as a key regulator within the microbiota-gut-brain axis.

Aurantimonas marianensis sp. nov., isolated from deep-sea sediment of the Mariana Trench.

A novel strain, designated as LRZ36T, was isolated from deep-sea sediment (from a depth of 5400 m) from the Mariana Trench. Cells of this strain are rod-shaped, Gram-stain-negative, strictly aerobic and non-motile. Phylogenetic analysis of LRZ36T based on 16S rRNA gene sequences revealed a lineage in the family Aurantimonadaceae but distinct from the most closely related species Aurantimonas marina CGMCC 1.17725T, 'Aurantimonas litoralis' KCTC 12094 and Aurantimonas coralicida DSM 14790T with sequence identities of 99.4 %, 98.0 and 97.9 %, respectively. The genome of LRZ36T was 3.8 Mbp in size with a DNA G+C content of 64.8 %, containing 3623 predicted coding genes. LRZ36T showed average nucleotide identity values of 89.8 %, 78.7 and 78.5 % and digital DNA-DNA hybridization values of 38.9 %, 21.7 and 21.6 % with A. marina CGMCC 1.17725T, 'A. litoralis' KCTC 12094 and A. coralicida DSM 14790T, respectively. The major respiratory quinone was ubiquinone-10 (Q-10), and the predominant fatty acids were C18 : 1ω7c (74.4 %) and C16 : 0 (12.1 %). The polar lipids in LRZ36T are diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylmethylethanolamine, phosphatidylcholine, phosphatidylinositol mannoside, an unidentified aminophospholipid, three unidentified lipids, three unidentified phospholipids and two unidentified aminolipids. On the basis of genotypic and phenotypic evidence, LRZ36T represents a novel species of the genus Aurantimonas, for which the name Aurantimonas marianensis sp. nov. is proposed. The type strain is LRZ36T (= KCTC 92065T = GDMCC 1.2985T=MCCC 1K07227T).

Modulating the affinity and signaling bias of cannabinoid receptor 1 antagonists.

Cannabinoid receptor 1 (CB1) is a G protein-coupled receptor and a therapeutic target for metabolic disorders. Numerous CB1 antagonists have been developed, but their functional selectivities and bias towards G protein or ß-arrestin signaling have not been systemically characterized. In this study, we analyzed the binding affinities and downstream signaling of two series of pyrazole derivatives bearing 1-aminopiperidine (Series I) or 4-aminothiomorpholine 1,1-dioxide (Series II) moieties, as well as the well-known CB1 antagonists rimonabant and taranabant. Analyses of the results for the Series I and II derivatives showed that minor structure modifications to their functional groups and especially the incorporation of 1-aminopiperidine or 4-aminothiomorpholine 1,1-dioxide motifs can profoundly affect their bias toward G protein or ß-arrestin signaling, and that their binding affinity and functional activity can be disassociated. Docking and molecular dynamics simulations revealed that the binding modes of Series I and II antagonists differed primarily in that Series I antagonists formed an additional hydrogen bond with the receptor, whereas those in Series II formed a water bridge.

Contrasting frontal cortical responses to food versus money rewards across BMI groups.

Previous research has linked obesity with an altered perception of rewards. This study aimed to contrast frontal cortical activities across body mass index (BMI) groups, in responding to differential rewards (monetary versus food). A total of 60 male participants (27.43 ± 6.07 years of age; 21 normal weight [BMI: 18.5-24.9 kg·m-2]; 20 overweight [BMI: 25.0-29.9 kg·m-2]; and 19 individuals with obesity [BMI ≥ 30 kg·m-2]) were tested for their response bias towards food and money rewards using the Probabilistic Reward Task (PRT), while their frontal cortical responses were recorded using electroencephalography (EEG). The feedback-related negativity (FRN), a reliable measure of reward valuation and learning, was calculated for food (FRN(Food)) and money (FRN(Money)). Results indicate a left-lateralised frontal cortical activity associated with the food reward condition, in the group of overweight and obesity. In contrast, a right-lateralisation was observed in the money reward condition only in the group with obesity. More specifically, FRN(Food) was shown to significantly differ between left and right frontal cortical areas among individuals with obesity (p = 0.035) and overweight (p = 0.012), but not in normal-weight individuals (p = 0.153). Additionally, results revealed that FRN(Food) and FRN(Money) were significantly different for individuals with obesity (p = 0.019), but such a significant difference was not evident in the overweight and normal-weight individuals (p ≥ 0.05). These findings offer intriguing new insights into neuropsychological differentiation across BMI groups, adding to the understanding of obesity-related behaviour.

Peak early diastolic strain rate improves prediction of adverse cardiovascular outcomes in patients with ST-elevation myocardial infarction.

BACKGROUND: The prognostic role of diastolic dysfunction measured by the circumferential peak early diastolic strain rate (PEDSR) on ST-elevation myocardial infarction (STEMI) is not completely established. OBJECTIVES: We aimed to investigate the prognostic value of diastolic function by measuring PEDSR within 1 week after STEMI. METHODS: The cardiac magnetic resonance (CMR) pictures of 420 subjects from a clinical registry study (NCT03768453) were analyzed and the composite major adverse cardiac events (MACEs) were followed up. RESULTS: The PEDSR of patients was significantly lower compared with that of control subjects (P < 0.001). Within the median follow-up period of 52 months, PEDSR of patients who experienced MACEs deceased more significantly than that of patients without MACEs (P < 0.001). After adjusting with clinical or CMR indexes, per 0.1/s reduction of PEDSR increased the risks of MACEs to 1.402 or 1.376 fold and the risk of left ventricular (LV) remodeling to 1.503 or 1.369 fold. When PEDSR divided by best cutoff point, significantly higher risk of MACEs (P < 0.001) and more remarkable LV remodeling (P < 0.001) occurred in patients with PEDSR ≤ 0.485/s. Moreover, when adding the PEDSR to the conventional prognostic factors such as LV ejection fraction and infarction size, better prognostic risk classification models were created. Finally, aging, tobacco use, remarkable LV remodeling, and a low LV ejection fraction were factors related with the reduction of PEDSR. CONCLUSIONS: Diastolic dysfunction has an important prognostic effect on patients with STEMI. Measurement of the PEDSR in the acute phase could serve as an effective index to predict the long-term risk of MACEs and cardiac remodeling.

Intubation using video laryngeal mask airway SaCoVLM and laryngeal mask airway Ambu® Aura-i in anesthetized children with microtia: a randomized controlled study.

The Ambu Aura-i laryngeal mask is considered to be a device for blind intubation as well as for fiberoptic guided intubation. The novel video laryngeal airway mask SaCoVLM is a supraglottic airway device that allows intubation under direct vision. We hypothesized that success rates for device placement and tracheal intubation with the SaCoVLM would be comparable with the Ambu Aura-i mask. A prospective, randomized clinical trial was conducted from March 2021 to December 2021. One hundred and twenty patients were enrolled and randomized in the study. Direct intubation was performed with the SaCoVLM, and fiberoptic guided intubation was performed with the Ambu Aura-i mask. The primary outcome measure was the first success rate of LMA placement. Secondary outcome measures were the time from device placement and time from endotracheal intubation (as well as the time for LMA removal after successful intubation), differences in airway leak pressure, fiberoptic grade of the laryngeal view, and incidence of blood staining. The first success rate of LMA placement was similar for the two devices. There was no difference in the time for successful endotracheal intubation between the Ambu Aura-i and SaCoVLM groups (24.1 s ± 6.3 versus 25.7 s ± 2.1; p > 0.05). The time for removal was slower in the SaCoVLM group than in the Ambu Aura-i group (20.8 s ± 0.8 versus 14.7 s ± 6.1; p < 0.01). The airway leak pressure was higher in the SaCoVLM group than in the Ambu Aura-i group (27.0 s ± 1.0 versus 22.3 s ± 3.6; p < 0.01), and the incidence of blood staining was higher in the SaCoVLM group (16.7%). The SaCoVLM has an overall comparable performance to the Ambu Aura-i mask. However, the SaCoVLM is better relative to direct intubation without the assistance of a flexible intubation scope, which reduces the device's demand.

[Advances in Research on the Mechanism of Association Between Periodontitis and Diabetes Mellitus].

Periodontitis and diabetes mellitus are both chronic diseases with a rather high prevalence and they are closely associated with each other. On one hand, diabetes mellitus poses as a risk factor for periodontitis. On the other hand, periodontitis has a negative impact on glucose control in diabetic patients. The two-way relationship has aroused a lot of research interest in recent years. Herein, approaching the issue by looking at the effect of periodontitis on diabetes, we summarized the mechanism of the traditional periodontal pocket-blood circulation pathway and reviewed the role of the oral-gut axis in the mechanism, which has been proposed in recent years. In addition, regarding the impact of diabetes on periodontitis, we summarized new findings concerning changes in oral microbiota, abnormal levels of cytokines and adipokines, oxidative stress, unbalanced osteogenic and osteoclastic activities, and the accumulation of advanced glycation end-products. We hope this paper will be helpful for further studies on the mechanism of association between periodontitis and diabetes.

CrisprVi: a software for visualizing and analyzing CRISPR sequences of prokaryotes.

BACKGROUND: Clustered regularly interspaced short palindromic repeats (CRISPR) and their spacers are important components of prokaryotic CRISPR-Cas systems. In order to analyze the CRISPR loci of multiple genomes more intuitively and comparatively, here we propose a visualization analysis tool named CrisprVi. RESULTS: CrisprVi is a Python package consisting of a graphic user interface (GUI) for visualization, a module for commands parsing and data transmission, local SQLite and BLAST databases for data storage and a functions layer for data processing. CrisprVi can not only visually present information of CRISPR direct repeats (DRs) and spacers, such as their orders on the genome, IDs, start and end coordinates, but also provide interactive operation for users to display, label and align the CRISPR sequences, which help researchers investigate the locations, orders and components of the CRISPR sequences in a global view. In comparison to other CRISPR visualization tools such as CRISPRviz and CRISPRStudio, CrisprVi not only improves the interactivity and effects of the visualization, but also provides basic statistics of the CRISPR sequences, and the consensus sequences of DRs/spacers across the input strains can be inspected from a clustering heatmap based on the BLAST results of the CRISPR sequences hitting against the genomes. CONCLUSIONS: CrisprVi is a convenient tool for visualizing and analyzing the CRISPR sequences and it would be helpful for users to inspect novel CRISPR-Cas systems of prokaryotes.

The adaptor protein GIPC1 stabilizes the scavenger receptor SR-B1 and increases its cholesterol uptake.

The scavenger receptor class B type 1 (SR-B1), a high-density lipoprotein (HDL) receptor, is a membrane glycoprotein that mediates selective uptake of HDL-cholesterol and cholesterol ester (CE) into cells. SR-B1 is subject to posttranslational regulation; however, the underlying mechanisms still remain obscure. Here, we identified a novel SR-B1-interacting protein, GIPC1 (GAIP-interacting protein, C terminus 1) that interacts with SR-B1 and stabilizes SR-B1 by negative regulation of its proteasomal and lysosomal degradation pathways. The physiological interaction between SR-B1 and GIPC1 was supported by co-immunoprecipitation of wild-type and mutant GIPC1 constructs in SR-B1 ± GIPC1 overexpressing cells, in native liver cells, and in mouse liver tissues. Overexpression of GIPC1 increased endogenous SR-B1 protein levels, subsequently increasing selective HDL-cholesterol/CE uptake and cellular triglyceride (TG) and total cholesterol (TC) levels, whereas silencing of GIPC1 in the mouse liver was associated with blunted hepatic SR-B1 levels, elevated plasma TG and TC, and attenuated hepatic TG and TC content. A positive correlation was identified between GIPC1 and SR-B1 expression, and both expressions of GIPC1 and SR-B1 from human liver samples were inversely correlated with body mass index (BMI) from human subjects. We therefore conclude that GIPC1 plays a key role in the stability and function of SR-B1 and can also effectively regulate hepatic lipid and cholesterol metabolism. These findings expand our knowledge of the regulatory roles of GIPC1 and suggest that GIPC1 exerts a major effect on cell surface receptors such as SR-B1 and its associated hepatic lipid and cholesterol metabolic processes.

Speech silence character as a diagnostic biomarker of early cognitive decline and its functional mechanism: a multicenter cross-sectional cohort study.

BACKGROUND: Language deficits frequently occur during the prodromal stages of Alzheimer's disease (AD). However, the characteristics of linguistic impairment and its underlying mechanism(s) remain to be explored for the early diagnosis of AD. METHODS: The percentage of silence duration (PSD) of 324 subjects was analyzed, including patients with AD, amnestic mild cognitive impairment (aMCI), and normal controls (NC) recruited from the China multi-center cohort, and the diagnostic efficiency was replicated from the Pitt center cohort. Furthermore, the specific language network involved in the fragmented speech was analyzed using task-based functional magnetic resonance. RESULTS: In the China cohort, PSD increased significantly in aMCI and AD patients. The area under the curve of the receiver operating characteristic curves is 0.74, 0.84, and 0.80 in the classification of NC/aMCI, NC/AD, and NC/aMCI+AD. In the Pitt center cohort, PSD was verified as a reliable diagnosis biomarker to differentiate mild AD patients from NC. Next, in response to fluency tasks, clusters in the bilateral inferior frontal gyrus, precentral gyrus, left inferior temporal gyrus, and inferior parietal lobule deactivated markedly in the aMCI/AD group (cluster-level P < 0.05, family-wise error (FWE) corrected). In the patient group (AD+aMCI), higher activation level of the right pars triangularis was associated with higher PSD in in both semantic and phonemic tasks. CONCLUSIONS: PSD is a reliable diagnostic biomarker for the early stage of AD and aMCI. At as early as aMCI phase, the brain response to fluency tasks was inhibited markedly, partly explaining why PSD was elevated simultaneously.

Geological and climatic influences on population differentiation of the Phrynocephalus vlangalii species complex (Sauria: Agamidae) in the northern Qinghai-Tibet Plateau.

Extremely heterogeneous topography and complex paleoclimatic history of the Qinghai-Tibet Plateau (QTP) have a key role in promoting genetic divergence among populations and lineage/species formation. Here, we sequenced one nuclear and three mitochondrial markers of 532 individuals from the entire range of the Phrynocephalus vlangalii species complex including two species, P. putjatai and P. vlangalii, endemic to the northern QTP. We integrated multilocus phylogeny, demographic analysis and geographic barrier detection to evaluate the population structure and dynamics. We found a new mitochondrial clade (PV-I) in the Gonghe County population of P. vlangalii, partial mitochondrial DNA replacement within P. vlangalii and complete mitochondrial DNA replacement between P. putjatai and P. vlangalii. Neutrality test, mismatch distribution analysis and Extended Bayesian Skyline Plot (EBSP) analysis all supported a significant expansion of the Qaidam Basin population of P. vlangalii (PV-II-2) from 0.091 to 0.026 Ma after Penultimate Glaciation. The uplift of the Arjin and Anyemanqen Mountains during the Kunhuang Movement (∼1.2 Ma) split populations of P. vlangalii in Akesai, Qaidam Basin and source of the Yellow River. The uplift of the Elashan Mountains during the second phase of the Qingzang Movement (∼2.5 Ma) contributed to the divergence of the Gonghe County population of P. vlangalii from other conspecific populations. The third phase of the Qingzang Movement (∼1.7 Ma) contributed to the divergence of the Xinghai population of P. vlangalii from P. putjatai and to the divergence of the northern populations of P. putjatai from the southern conspecific populations. Our data support the idea that the geological and climatic changes following the orogeny of the QTP may have promoted population differentiation and shaped the current population patterns of the P. vlangalii species complex in the northeastern QTP.

High magnesium mitigates the vasoconstriction mediated by different types of calcium influx from monocrotaline-induced pulmonary hypertensive rats.

NEW FINDINGS: What is the central question of this study? What is the involvement of Mg2+ in mitigating the vasoconstriction in pulmonary arteries and smaller pulmonary arteries in the monocrotaline-induced pulmonary arterial hypertension (MCT-PAH) rat model? What are the main finding and its importance? Both store-operated Ca2+ entry- and receptor-operated Ca2+ entry-mediated vasoconstriction were enhanced in the MCT-PAH model. High magnesium inhibited vasoconstriction by directly antagonizing Ca2+ and increasing NO release, and this was more notable in smaller pulmonary arteries. ABSTRACT: Increased extracellular magnesium concentration has been shown to attenuate the endothelin-1-induced contractile response via the release of nitric oxide (NO) from the endothelium in proximal pulmonary arteries (PAs) of chronic hypoxic mice. Here, we further examined the involvement of Mg2+ in the inhibition of vasoconstriction in PAs and distal smaller pulmonary arteries (sPAs) in a monocrotaline-induced pulmonary arterial hypertension (MCT-PAH) rat model. The data showed that in control rats vasoconstriction in sPAs is more intense than that in PAs. In MCT-PAH rats, store-operated Ca2+ entry (SOCE)- and receptor-operated Ca2+ entry (ROCE)-mediated contraction were significantly strengthened. However, there was no upregulation of the vasoconstriction mediated by voltage-dependent calcium entry (VDCE). Furthermore, high magnesium greatly inhibited VDCE-mediated contraction in PAs rather than sPAs, which was the opposite of the ROCE-mediated contraction. Moreover, monocrotaline pretreatment partly eliminated the endothelium-dependent vasodilatation in PAs, which in sPAs, however, was still promoted by magnesium due to the increased NO release in pulmonary microvascular endothelial cells (PMVECs). In conclusion, the findings suggest that both SOCE- and ROCE-mediated vasoconstriction in the MCT-PAH model are enhanced, especially in sPAs. The inhibitory effect of high magnesium on vasoconstriction can be achieved partly by its direct role as a Ca2+ antagonist and partly by increasing NO release in PMVECs.

Single-cell transcriptomes from turtle livers reveal sensitivity of hepatic immune cells to bacteria-infection.

The liver is important in the synthesis, metabolism and storage of nutrients, detoxification and immune response of the body, and the liver immune response against exogenous pathogens from the intestinal tract plays a key role in the immune activities. However, the cellular composition of the liver immune atlas remains sparsely studied in reptiles. We used single-cell RNA sequencing to identify the cellular profile of the liver of the Chinese soft-shelled turtle (Pelodiscus sinensis). We obtained the transcriptional landscape based on 9938 cells from the fractionation of fresh hepatic tissues from two individuals, uninfected and infected with bacteria (Aeromonas hydrophila). We identified seven hepatic immune cell subsets, including plasma, erythroid, T/NK, B, endothelial, dendritic and Kupffer cells. Bacteria-infection altered the number of liver immune cells, as revealed by the fact that the infected turtle had more plasma, endothelial and Kupffer cells and fewer T/NK, dendritic and erythroid cells than did the uninfected turtle. Our study is the first to provide a comprehensive view of the hepatic immune landscape of P. sinensis at the single-cell resolution that outlines the characteristics of immune cells in the turtle liver and provides a liver transcriptome baseline for turtle immunology.

Plasma metabolomics in the perioperative period of defect repair in patients with pulmonary arterial hypertension associated with congenital heart disease.

The quality of life and survival rates of patients with pulmonary arterial hypertension associated with congenital heart disease (CHD-PAH) have been greatly improved by defect-repair surgery and personalized treatments. However, those who survive surgery may remain at risk of persistent PAH, the prognosis may be considerably worse than those unoperated. Dynamic monitoring of clinical measures during the perioperative period of shunt correction is therefore indispensable and of great value. In this study, we explored the plasma-metabolite profiling in 13 patients with CHD-PAH during the perioperative period of defect repair. Plasma was harvested at four time points: prior to cardiopulmonary bypass (CPB) after anesthesia (Pre), immediately after CPB (T0), 24 h (T24), and 48 h (T48) after defect repair. Untargeted metabolomics strategy based on UPLC Q-TOF MS was used to detect the metabolites. A total of 193 distinguishing metabolites were determined at different time points, enriched in pathways such as oxidation of branched-chain fatty acids. We found that 17 metabolite alterations were significantly correlated with the reduction in mean pulmonary arterial pressure (MPAP) at T48 versus Pre. Gradients in diastolic pulmonary arterial pressure (DPAP), bicarbonate in radial artery (aHCO3), bicarbonate in superior vena cava (svcHCO3), and the partial pressure of dissolved CO2 gas in radial artery (aPCO2) were positively correlated with MPAP gradient. Notably, these clinical-measure gradients were correlated with alterations in shunt-correction-associated metabolites. In total, 12 out of 17 identified metabolites in response to defect repair were increased at both T24 and T48 (all P < 0.05, except propionylcarnitine with P < 0.05 at T24). In contrast, galactinol dihydrate, guanosine monophosphate, and hydroxyphenylacetylglycine tended to decline at T24 and T48 (only galactinol dihydrate with P < 0.05 at T48). In conclusion, 17 metabolites that respond to shunt correction could be used as suitable noninvasive markers, and clinical measures, including DPAP, aHCO3, svcHCO3, and aPCO2, would be of great value in disease monitoring and evaluating future therapeutic interventions.

Phase unwrapping algorithm for images with local high-density noise.

Due to undersampling and the local phase with local high-density noise, it is still difficult to develop a robust phase unwrapping algorithm. In order to resolve this issue, here, we propose what we believe to be a novel multiple path-following phase unwrapping (MPIPU) algorithm based on the shearing interference principle to recover the undersampling phase (non-noise). By calculating the unwrapping coefficient k, the phase iteration filling algorithm based on least-squares is developed for the high-density noise region in order to reconstruct the three-dimensional surface topography of interferometric synthetic aperture radar (InSAR) data. The proposed algorithm takes advantage of the MPIPU's ability to fill in the missing phase with fitting data and can successfully suppress the error transfer caused by the blocky noise phase iteration process. Several experiments are conducted using both simulated and actual InSAR image data. The experimental findings show that the proposed method can achieve robust phase unwrapping performance on a phase of local high-density noise.

Multistage Attack-Defense Graph Game Analysis for Protection Resources Allocation Optimization Against Cyber Attacks Considering Rationality Evolution.

Cyber vulnerabilities become ever more critical in modern industrial systems since the attacker can utilize the vulnerabilities to degrade their performance or even cause disasters. In 2015, a series of sequential and well-organized cyber attacks intruded into the Ukrainian power grid, compromised access to the control system, and interrupted the power supply system, finally causing a widespread power outage. To assist the defender, e.g., power grid operator, to allocate protection resources against cyber attacks, existing studies have devoted considerable efforts to risk and reliability analysis and interaction analysis using game theory. The defender's protection strategy includes preevent defense strategy and postevent repair strategy. The strategy spaces of both players were static in previous studies. However, facing Ukrainian-style cyber attacks, the strategy spaces could variate during the attacker-defender confrontation. In other words, the vulnerability compromised by the attacker in one stage could expose the subsequential vulnerabilities, leading to the change of strategy spaces. In this work, a multistage attack-defense graph game model is proposed to assist the defender in allocating protection resources optimally against sequential cyber attacks during multiple stages. In addition, we consider the existence of the rationality evolution of the attacker, which mainly results from asymmetric information, capacity limitation, and progressive learning during the confrontation. Compared to previous studies based on static strategy spaces and static rationalities, our model is more practical and effective in dealing with Ukrainian-style cyber attacks. The simulation results show the superiority of our approach, and some notable observations and practical suggestions are summarized for the defender.

[New advances in the diagnosis and treatment of biliary atresia]. / 胆道闭锁的诊断及治疗新进展.

The diagnosis of biliary atresia (BA) is mainly based on clinical manifestations, screening, and related biochemistry tests. In recent years, the development of blood biomarkers and the improvement in ultrasound examination have made it possible for BA to be diagnosed at a younger age. In particular, matrix metalloproteinase-7 shows high sensitivity and specificity and has a higher diagnostic efficiency than existing biochemical parameters, thereby holding a promise for clinical application. Sound touch elastography can increase the diagnostic efficiency for BA in terms of diagnosis and prognostic evaluation. Surgery is still the only method for the treatment of BA at present, with the preferred surgical treatment regimen of Kasai portoenterostomy combined with pharmacotherapies for alleviating infection and inflammation, and the patients who fail Kasai portoenterostomy or have liver dysfunction may require liver transplantation to save their lives. Therefore, the current research on BA should focus on the biomarkers for early diagnosis, specifically targeted drugs, and drugs for preventing progressive liver fibrosis. This article reviews the current diagnosis and treatment methods for BA and discusses the potential research directions.

Velocity mismatch effect on the dynamic MTF of a TDI image sensor.

By analyzing the process of time delay integration dynamic imaging, we establish a model of velocity mismatch. Based on this model, we analyze the influence of different factors on the dynamic imaging process, and a modulation transfer function (MTF) is used to evaluate imaging quality. According to the simulation, the velocity mismatch and scan stage are the main factors for image quality. The MTF of the image sensor decreases with the velocity mismatch, and the scan stage increases. In addition, an image with higher contrast can be obtained in a short integration time. However, a shorter integration time leads to insufficient sampling. Furthermore, we establish a dynamic MTF testing system, and evaluate the experiment at different imaging modes. Through data comparison, the experimental data are consistent with theoretical data.