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Abstract Objective In this study, we aimed to identify differentially expressed heat shock protein (HSP) profiles in the villi and decidua from patients with early missed abortion (EMA). Methods By using high-throughput and high-precision parallel reaction monitoring (PRM)-based targeted proteomics techniques, this study examined the abundance of HSPs in the villi and decidua of 10 patients with EMA and 10 controls. Moreover, the abundance of 3 HSPs in the villi of another 22 patients with EMA and 22 controls was verified with Western blotting and immunohistochemistry (IHC). Results There were potential differences in the abundance of 16 HSPs and 42 polypeptides in human villi and decidua compared with those of the control group. Among them, HSP90AB1, HSPD1 and HSPA13 were downregulated in abundance in villi of patients with EMA, with a statistically significant difference, which was consistent with the verification results of Western blots and IHC. Conclusion Using a PRM-based targeted proteomics technique, this study is the first to screen and quantitatively analyze the expression profile of HSPs in the villi and decidua of patients with EMA. The significant downregulation of HSP90AB1, HSPD1 and HSPA13 was found to have a potentially intimate association with the occurrence of EMA. The findings in our study may provide novel potential research targets related to HSPs for the pathogenesis, prevention and treatment of EMA.

Abstract As one kind of novel noncoding RNA, circular RNAs (circRNAs) are involved in different biological processes. Although growing evidences have supported the important role of circRNAs in renal diseases, the mechanism remains unclear in neonatal acute kidney injury (AKI). High‐throughput sequencing analysis was used to investigate the expression of circRNAs between hypoxia‐induced AKI neonates and controls. Bioinformatics analysis was conducted to predict the function of differentially expressed circRNAs. Finally, the differentially expressed circRNAs were screened and determined by quantitative real‐time PCR (qPCR). (1) A total of 296 differentially expressed circRNAs were identified (Fold change >2 and p

Abstract Background Elucidation of the post‐transcriptional modification has led to novel strategies to treat intractable tumors, especially glioblastoma (GBM). The ubiquitin‐proteasome system (UPS) mediates a reversible, stringent and stepwise post‐translational modification which is closely associated with malignant processes of GBM. To this end, developing novel therapeutic approaches to target the UPS may contribute to the treatment of this disease. This study aimed to screen the vital and aberrantly regulated component of the UPS in GBM. Based on the molecular identification, functional characterization, and mechanism investigation, we sought to elaborate a novel therapeutic strategy to target this vital factor to combat GBM. Methods We combined glioma datasets and human patient samples to screen and identify aberrantly regulated E3 ubiquitin ligase. Multidimensional database analysis and molecular and functional experiments in vivo and in vitro were used to evaluate the roles of HECT, UBA and WWE domain‐containing E3 ubiquitin ligase 1 (HUWE1) in GBM. dCas9 synergistic activation mediator system and recombinant adeno‐associated virus (rAAV) were used to endogenously overexpress full‐length HUWE1 in vitro and in glioma orthotopic xenografts. Results Low expression of HUWE1 was closely associated with worse prognosis of GBM patients. The ubiquitination and subsequent degradation of N‐Myc mediated by HUWE1, leading to the inactivation of downstream Delta‐like 1 (DLL1)‐NOTCH1 signaling pathways, inhibited the proliferation, invasion, and migration of GBM cells in vitro and in vivo. A rAAV dual‐vector system for packaging and delivery of dCas9‐VP64 was used to augment endogenous HUWE1 expression in vivo and showed an antitumor activity in glioma orthotopic xenografts. Conclusions The E3 ubiquitin ligase HUWE1 acts through the N‐Myc‐DLL1‐NOTCH1 signaling axis to suppress GBM progression. Antitumor activity of rAAV dual‐vector delivering dCas9‐HUWE1 system uncovers a promising therapeutic strategy for GBM.

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused many significant changes to all aspects of day to day life. The disease has spread and reached pandemic proportions. The principle route of transmission is the respiratory route. Infants, pregnant women and breastfeeding mothers have all been affected. Many interventions and guidelines from important societies have been instituted in order to curb the transmission of the disease. These have involved both pharmacological and non-pharmacological methods. COVID-19 vaccines have also emerged as important methods of primary prevention of the disease. But several questions have been raised concerning the safety and efficacy of their use in pregnant and breastfeeding mothers. It has also not been clear if the vaccines are effective in generating a robust immune response in the pregnant women and breastfeeding mothers to confer passive immunity to the fetuses and infants, respectively. And they have not been tested in infants. The aspect of infant feeding has equally been affected. Although breast milk has not been known to serve as the vehicle of transmission of the virus, there is still some lack of uniformity of practice regarding breastfeeding when a mother has SARS-CoV-2 infection. This has led to infant feeding being done by the use of commercial formula feeds, pasteurized human donor breast milk, feeding on the mother's own expressed breast milk by a care giver and directly breastfeeding with skin to skin contact. This is despite breast milk being the most physiologically appropriate type of feed for infants. Therefore the pertinent question remains; should breastfeeding continue during the pandemic continue? This review also seeks to analyse the vast amount of scientific information regarding the subject and to synthesize science-based information

ABSTRACT Many RNA modifications have been detected in rRNA, tRNA and small noncoding RNA (sncRNA) as well as in low-abundance RNA species such mRNA. Although RNA modifications play roles in many cellular and biological processes in various domains of life, knowledge about the diversity and role of RNA modifications in Toxoplasma gondii is limited. In this study, RNA modifications in three T. gondii strains (RH type I, PRU type II, and VEG type III) with distinct virulence abilities were determined by liquid chromatography-tandem mass spectrometry. We compared the levels of modifications of four nucleotides in tRNA and sncRNA, characterized RNA modification patterns of different T. gondii strains, and determined the diversity of RNA modifications. We detected and quantified 22 modified nucleosides in both tRNA and sncRNA. Significant differences in the diversity of the modified nucleosides were found between the three T. gondii strains. RNA modifications were correlated with the expression of many T. gondii virulence proteins. Some of the identified modifications (e.g., 2’-O-methylinosine, pseudouridine) play a role in mediating the host-parasite interaction. These results provide novel insight into the global modifications in tRNA and sncRNA, and the diversity of RNA modifications between T. gondii strains with different virulence backgrounds. IMPORTANCE Although RNA modifications play roles in many cellular and developmental processes in various domains of life, knowledge about the patterns and functions of RNA modifications in T. gondii is limited. Here, a quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach was used to study global RNA modifications in T. gondii strains of distinct virulence backgrounds. We quantified 22 modified nucleosides in both tRNA and sncRNA. Significant T. gondii strain-specific differences in RNA modifications were detected. More tRNA modifications correlated with T. gondii virulence proteins than sncRNA modifications. RNA modifications were significantly correlated with virulence proteins. Our data provide the first comprehensive profiling of the modifications tRNA and sncRNA in T. gondii, expanding the diversity of RNA modifications in this parasite and suggesting new regulators for modulating its virulence.

Abstract Background Glioblastoma (GB) is the most common and highly malignant brain tumor characterized by aggressive growth and resistance to alkylating chemotherapy. Autophagy induction is one of the hallmark effects of anti-GB therapies with temozolomide (TMZ). However, the non-classical form of autophagy, autophagy-based unconventional secretion, also called secretory autophagy and its role in regulating the sensitivity of GB to TMZ remains unclear. There is an urgent need to illuminate the mechanism and to develop novel therapeutic targets for GB. Methods Cancer genome databases and paired-GB patient samples with or without TMZ treatment were used to assess the relationship between HMGB1 mRNA levels and overall patient survival. The relationship between HMGB1 protein level and TMZ sensitivity was measured by immunohistochemistry, ELISA, Western blot and qRT-PCR. GB cells were engineered to express a chimeric autophagic flux reporter protein consisting of mCherry, GFP and LC3B. The role of secretory autophagy in tumor microenvironment (TME) was analyzed by intracranial implantation of GL261 cells. Coimmunoprecipitation (Co-IP) and Western blotting were performed to test the RAGE-NFκB-NLRP3 inflammasome pathway. Results The exocytosis of HMGB1 induced by TMZ in GB is dependent on the secretory autophagy. HMGB1 contributed to M1-like polarization of tumor associated macrophages (TAMs) and enhanced the sensitivity of GB cells to TMZ. Mechanistically, RAGE acted as a receptor for HMGB1 in TAMs and through RAGE-NFκB-NLRP3 inflammasome pathway, HMGB1 enhanced M1-like polarization of TAMs. Clinically, the elevated level of HMGB1 in sera may serve as a beneficial therapeutic-predictor for GB patients under TMZ treatment. Conclusions We demonstrated that enhanced secretory autophagy in GB facilitates M1-like polarization of TAMs to enhance TMZ sensitivity of GB cells. HMGB1 acts as a key regulator in the crosstalk between GB cells and tumor-suppressive M1-like TAMs in GB microenvironment and may be considered as an adjuvant for the chemotherapeutic agent TMZ.

BackgroundThe widespread occurrence of syphilis remains a global public health problem. Although penicillin has been recommended as the first-line therapy for syphilis for more than 70 years, treatment failure occurs in 10–20% of patients with early syphilis. Recent studies have reported varied single-nucleotide polymorphisms (SNPs) of Treponema pallidum related to penicillin resistance. The clinical relevance of these SNPs to treatment failure in patients with early syphilis is unresolved. In this work, a protocol is developed to evaluate the association between treatment failure in patients with early syphilis and penicillin resistance-related gene mutations of T. pallidum.MethodsA multicentre nested case–control study is designed, and patients who are diagnosed with early syphilis and treated with penicillin will be recruited for the study cohort. Before the first treatment, baseline information and biological specimens will be collected from the subjects, and serological tests for syphilis will be performed. Each participant will be followed up at 1, 3, 6, 9, and 12 months after the first treatment, and the clinical manifestations and serum non-treponemal test titres will be evaluated at each follow-up. Patients who will fail treatment are defined as cases, and those who will respond to treatment are defined as controls. Tests for SNPs related to penicillin-binding proteins and Tp47 will be performed in these cases and controls. Survival analysis is used performed to identify gene mutations of T. pallidum related to penicillin resistance and their combinations associated with treatment failure.DiscussionThis protocol provides a practical clinical study design that illustrates the role of gene mutations of T. pallidum related to penicillin resistance in the treatment outcome of patients with early syphilis.

ObjectiveErythropoietin (EPO) seems to have a good application prospect both in experimental models and patients with hypoxic ischaemic encephalopathy (HIE). Data regarding the effect of EPO on death or neurodevelopmental impairment are conflicting.MethodsA search was conducted by two investigators involved in this research in PubMed, Embase, and Cochrane databases for studies in English, in Wanfang, VIP, and Cnki databases for Chinese studies (all last launched on 2022/08/31). Ultimately, we identified 11 original studies, including the EPO group (n = 636) and the control group (n = 626). Odds ratio (OR) and weighted mean difference were calculated using a random effects or fixed effects model, depending on the data type and heterogeneity of the included studies.Results1. The comparison of effectiveness of EPO treatment on HIE: (1) With respect to death, data showed no significant difference between EPO and control groups (OR = 0.97, 95% CI, 0.66–1.43; P = 0.88); Considering the additional effect of mild hypothermia treatment (MHT), no significant difference was found between EPO + MHT/control + MHT groups either (OR = 1.09, 95% CI, 0.69–1.73; P = 0.72); With respect to the interference of different routes of medication administration, Meta-analysis further showed no difference between intravenous EPO/control groups (OR = 1.13, 95% CI, 0.70–1.82; P = 0.62). (2) With respect to cerebral palsy, the analysis showed no significant difference (OR = 0.76, 95% CI, 0.50–1.15; P = 0.20); Considering the effect of MHT and routes of medication administration, data further showed no difference between EPO group and control group (OR = 1.26, 95% CI, 0.73–2.19; P = 0.41). (3) Regarding epilepsy, no significant difference was found (OR = 0.49, 95% CI, 0.20–1.19; P = 0.12). MR abnormality was less common in EPO group (OR = 0.39, 95% CI, 0.19–0.79; P = 0.008). 2. The comparison of possible adverse events of EPO: EPO treatment would not increase the risk of thrombocytopenia, hypotension, and hepatic and kidney injury.ConclusionsThis meta-analysis showed that EPO treatment is not beneficial for reducing death and improving neurological impairment, though it would not increase the risk of adverse events.

ObjectiveIntraventricular hemorrhage (IVH) is a serious neurological complication in premature infants. This study aimed to investigate the white matter impairments and neurodevelopmental outcomes of severe IVH in extremely preterm infants with gestation age less than 28 weeks.MethodsWe retrospectively evaluated the extremely preterm infants between 2017 and 2020. Neurodevelopmental outcomes were evaluated with the Bayley Scales of Infant and Toddler Development-III at 2 years of corrected age. Diffusional kurtosis imaging (DKI) was employed to evaluate the microstructural changes in white matter tracts. Mean kurtosis (MK) and fractional anisotropy (FA) values of DKI were measured in the brain regions including posterior limbs of the internal capsule (PLIC) and the corpus callosum at term equivalent age.ResultsOf 32 extremely preterm infants with severe IVH during the follow-up period, 18 cases were identified as neurodevelopmental impairments. The delay rates of motor and language were 58.4% and 52.7%. The cases with neurodevelopmental impairments had lower MK and FA values in both bilateral PLIC and the corpus callosum. The analysis of multivariable regression models predicting motor and language outcomes at 2 years of corrected age, showed that the decreases of MK values in both PLIC and the corpus callosum at the term equivalent age contributed to a significantly increased risk of neurodevelopmental impairments (all p

ObjectiveThis study aims to identify the risk factors associated with short stature in children born small for gestational age (SGA) at full-term.MethodsThis was a retrospective study. The subjects were full-term SGA infants who were followed up until the age of 2 years. The risk factors for short stature were identified with univariate and multivariate analyses.ResultsOf 456 full-term SGA children enrolled in this study, 28 cases had short stature at 2 years of age. A significant decrease in placental perfusion was found in the short children group with intravoxel incoherent motion (IVIM) technology, which was an advanced bi-exponential diffusion-weighted imaging (DWI) model of magnetic resonance imaging (MRI) (p = 0.012). Compared to non-short children born SGA at full-term, the short children group underwent an incomplete catch-up growth. Mothers who suffered from systemic lupus erythematosus were more likely to have a short child born SGA (p = 0.023). The morbidity of giant placental chorioangioma was higher in the short children group. The pulsatility index (PI), resistivity index (RI), and systolic-diastolic (S/D) ratio of umbilical artery were higher in the short children group than in the non-short control group (p = 0.042, 0.041, and 0.043). Multivariate analysis demonstrated that decrease of perfusion fraction (fp) in IVIM of placental MRI, chromosomal abnormalities, short parental height, and absence of catch-up growth were associated with a higher risk of short stature in children born SGA at full-term.ConclusionRisk factors for short stature in full-term SGA children at 2 years of age included a decrease of perfusion fraction fp in IVIM of placental MRI, chromosomal abnormalities, and short parental height.

Bile acid (BA) metabolism is an attractive therapeutic target in nonalcoholic fatty liver disease (NAFLD). We aimed to investigate the effect of ilexsaponin A1 (IsA), a major bioactive ingredient of Ilex, on high-fat diet (HFD)-induced NAFLD in mice with a focus on BA homeostasis. Male C57BL/6J mice were fed an HFD to induce NAFLD and were treated with IsA (120 mg/kg) for 8 weeks. The results showed that administration of IsA significantly decreased serum total cholesterol (TC), attenuated liver steatosis, and decreased total hepatic BA levels in HFD-induced NAFLD mice. IsA-treated mice showed increased BA synthesis in the alternative pathway by upregulating the gene expression levels of sterol 27-hydroxylase (CYP27A1) and cholesterol 7b-hydroxylase (CYP7B1). IsA treatment accelerated efflux and decreased uptake of BA in liver by increasing hepatic farnesoid X receptor (FXR) and bile salt export pump (BSEP) expression, and reducing Na+-taurocholic acid cotransporting polypeptide (NTCP) expression. Alterations in the gut microbiota and increased bile salt hydrolase (BSH) activity might be related to enhanced fecal BA excretion in IsA-treated mice. This study demonstrates that consumption of IsA may prevent HFD-induced NAFLD and exert cholesterol-lowering effects, possibly by regulating the gut microbiota and BA metabolism.

Previous studies pointed out that a variety of microRNAs (miRNAs) are involved in the pathogenesis of neonatal acute respiratory distress syndrome (NARDS) and play different roles in the pathological process. However, there have been few studies reporting the connection between circular RNA (circRNA) and NARDS, so the expression profile of circRNAs in newborns with acute respiratory distress syndrome remains largely unknown. In the present study, 10 samples obtained from remaining clinical blood samples of newborns hospitalized in a neonatal ward of the First Affiliated Hospital of Nanjing Medical University from January 2020 to October 2020 were divided into the “NARDS” group and “non-NARDS” group according to the Montelux standard and then were analyzed in microarray, and 10 other samples collected from the same place and from January 1, 2021 to August 31, 2021, were used to do RT-qPCR experiment. circRNA expression profiles, in which 741 circRNAs were downregulated and 588 were upregulated, were screened with circRNA high-throughput sequencing. Subsequently, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis of parent genes of the differentially expressed circRNAs revealed that these circRNAs may be related to the process of protein synthesis and metabolism in NARDS. Moreover, five circRNAs—hsa_circ_0058495, hsa_circ_0000367, hsa_circ_0005389, hsa_circ_0059571, and hsa_circ_0006608—were selected randomly among the top 10 circRNAs of the downregulated or upregulated expression profiles. Then, bioinformatics tools were used to predict correlative miRNA and its target genes, which were also subjected to the same bioinformatics analysis for further study. The top 30 enriched KEGG pathway analyses of the 125 target genes suggested that these target genes are widely involved in the synthesis and secretion of endocrine hormones, and the top 30 enriched GO terms based on the 125 target genes are also focused on the protein and DNA processing. Thus, the present results show that circRNAs could promote the inflammation of NARDS which may provide a new therapeutic direction and it can be used as molecular markers for early diagnosis of NARDS, but further molecular biology verification is needed to define the specific role of differentially expressed circRNAs in NARDS.

Compared with debris flows in other areas, debris flows in scenic areas not only seriously threaten residents, tourists, roads, walkways, and other infrastructure, but also cause considerable damage to the landscapes and ecosystems of these areas. Extreme rainfall events in the future will increase the complexities and challenges involved in debris flow control in scenic areas. Currently, the systematic planning of the entire scenic area is not considered in the treatment of debris flows. It is not possible to realize the rapid planning of any debris flow gully control project in a scenic area and to quantify the volume of debris flow material retained by each engineering structure. Based on field investigations and data collected from debris flow control projects in gullies in Jiuzhaigou Valley, China, an engineering planning method for debris flow control projects in scenic areas is herein proposed, and the challenges confronting existing control projects in scenic areas are discussed. Moreover, based on the example of Jiuzhaigou Valley, corresponding control engineering schemes for debris flow gullies in Xiajijie Lake Gully, Zhuozhui Gully, Xuan Gully, Pingshitou Gully, and West-Zhuozhui Gully are formulated. Four control modes for debris flow disasters in scenic areas are proposed, namely, “blocking + deposit stopping,” “deposit stopping,” “blocking,” and “drainage + deposit stopping,” which provide a systematic control strategy for post-earthquake debris flow disaster management in Jiuzhaigou Valley and other similar scenic areas.

Abstract Deleterious consequences of the management of respiratory distress syndrome (RDS) with invasive ventilation have led to more in-depth investigation of non-invasive ventilation (NIV) modalities. NIV has significantly and positively altered the treatment outcomes and improved mortality rates of preterm infants with RDS. Among the different NIV modes, nasal intermittent positive pressure ventilation (NIPPV) has shown considerable benefits compared to nasal continuous positive airway pressure (NCPAP). Despite reports of heated humidified high-flow nasal cannula’s (HHHFNC) non-inferiority compared to NCPAP, some trials have been terminated due to high treatment failure rates with HHHFNC use. Moreover, RDS management with the combination of INSURE (INtubation SURfactant Extubation) technique and NIV ensures higher success rates. This review elaborates on the currently used various modes of NIV and novel techniques are also briefly discussed.

Objectives The primary purpose was to measure the birth weight of infants of mothers with gestational diabetes (IMGDs) at different gestational ages to develop new reference charts and curves for them. A further purpose was to compare them with those of 159 334 infants in China to provide more accurate reference charts for the diagnosis of suspected abnormal birth weight of IMGDs. The final purpose was to evaluate the key periods for such mothers to control their weight in line with the difference of fetal weight of each two neighbouring gestational ages.Setting A specialised hospital in South ChinaParticipants IMGDs born here from January 2014 to December 2018.Primary and secondary outcome variables Birth weight, gestational ages of IMGDs, gender and year of birth.Results Data of 14 311 singleton live births at the gestational weeks 25–42 here were collected. The proportions of low birth weight, normal birth weight and macrosomia were 7.26%, 87.04%, and 5.70%, respectively. The proportions of small for gestational age, appropriate for gestational age and large for gestational age were 5.69%, 84.42% and 9.89%, respectively. In the macrosomia group, the mean of all birth weight in 2017 decreased for the first time since 2014. Both the means of birth weight of male infants at gestational weeks 36–41 and of female at weeks 38–40 were greater than that of the 159 334 infants. The increase of each weekly mean of IMGDs at gestational weeks 27–31 and 33–35 was >10% compared with the former. Based on this, new reference charts of birth weight for IMGDs in terms of different gestational age and gender were formulated.Conclusion These charts may be applied as reference for more accurate diagnosis and quick treatment of abnormal birth weight. This study showed that the identification of key periods for fetal weight gain was helpful for the management of the weight of women with gestational diabetes.

Entamoeba spp. is a common zoonotic intestinal protozoan that can parasitize most vertebrates, including humans and pigs, causing severe intestinal diseases and posing a serious threat to public health. However, the available data on Entamoeba spp. infection in pigs are relatively limited in China. To characterize the infection of Entamoeba spp. within pigs in southern China, 1254 fecal samples of diarrheic pigs were collected from 37 intensive pig farms in Hunan, Jiangxi and Fujian provinces and the infection of Entamoeba spp. was investigated based on the small subunit rRNA (SSU rRNA) gene. The overall infection rate of Entamoeba spp. was 58.4% (732/1254), including 38.4% (118/307) in suckling piglets, 51.2% (153/299) in weaned piglets, 57.9% (55/95) in fattening pigs and 73.4% (406/553) in sows, respectively. Moreover, age and the sampling cities in Jiangxi and Fujian provinces were found to be the key factors influencing the infection of Entamoeba spp. (p < 0.05). Two subtypes (ST1 and ST3) with a zoonotic potential of Entamoeba polecki and Entamoeba suis were detected in all age groups of pigs and all sampling areas, with the predominant species and predominant subtype being E. polecki (91.3%, 668/732) and E. polecki ST1 (573/668), respectively, and E. polecki ST1 + E. polecki ST3 (78.6%, 239/304) being the most frequently detected form of mixed infection. Severe Entamoeba spp. infection and zoonotic subtypes were found in this study, exposing a large public health problem in the study area, and strategies need to be implemented to eliminate the risk in the future.

Circular RNA (circRNA) has been increasingly proven as a new type of promising therapeutic RNA molecule in a variety of human diseases. However, the role of circRNA in bronchopulmonary dysplasia (BPD) has not yet been elucidated. Here, a new circRNA circABCC4 was identified from the Agilent circRNA chip as a differentially expressed circRNA in BPD. The relationship between circABCC4 level and BPD clinicopathological characteristics was analyzed. The function of circABCC4 was evaluated by performing CCK-8 and apoptosis analysis in vitro and BPD model analysis in vivo. RNA immunoprecipitation (RIP), luciferase reporter and rescue experiments were used to elucidate the interaction between circABCC4 and miR-663a. Luciferase reporter assay and rescue experiments were used to elucidate the interaction between PLA2G6 and miR-663a. CircABCC4 and PLA2G6 levels were increased, while miR-663a levels were decreased in the BPD group, compared to the control group. MiR-663a inhibited apoptosis by repressing PLA2G6 expression, while circABCC4 enhanced the apoptosis and inhibited the proliferation of A549 cells by sponging miR-663a and increasing PLA2G6 expression. In conclusion, circABCC4 promotes the evolving of BPD by spongening miR-663a and up-regulating PLA2G6 expression, which makes circABCC4 an ideal molecular target for early diagnosis and intervention of BPD.

Objective To investigate the application value of eye tracking in lie detection. Methods The 40 subjects were randomly divided into two groups. The pupil diameter, fixation duration, points of fixation and blink frequency of the subjects in the experimental group in observing target stimulation and non-target stimulation were recorded with eye tracker after they accomplished the mock crime. The eye movement parameters of subjects in the control group were directly collected. The differences in eye movement parameters of the experimental group and the control group in observing target stimulation and non-target stimulation were analyzed by t-test. Pearson coefficient analysis of correlation between eye movement parameters that had differences was conducted. The effectiveness of eye movement parameters to distinguish between the experimental group and the control group was calculated by the receiver operator characteristic （ROC） curve. Results Participants from the experimental group had shorter average pupil diameter, longer average fixation duration and fewer fixation points （P

Current digital coding metasurfaces are only space-encoded. Here, the authors propose space-time modulated digital coding metasurfaces to obtain simultaneous manipulations of electromagnetic waves and present harmonic beam steering, beam shaping, and scattering-signature control as application examples.

Space-time and time-varying metastructures have attracted a lot of research interest in recent years. On the other hand, digital programmable metasurfaces have also gained great attention owing to their powerful capabilities in controlling electromagnetic (EM) fields and waves in real time, which is very suitable for implementing spatiotemporal modulations in a digital manner. Accordingly, space-time-coding (STC) digital metasurfaces have recently been proposed to realize advanced manipulations of EM wavefronts and digital information, allowing simultaneous control of propagation directions in the space domain and harmonic distributions in the frequency domain. However, their instantaneous responses and the connection between the time- and frequency-domain characteristics have not yet been fully revealed. Here, we present a joint time-frequency analysis method to revisit STC digital metasurfaces, in which the time-domain instantaneous scattering patterns and frequency-domain equivalent excitations are investigated to analyze the spatial-spectral distributions of the modulated waves. This joint time-frequency analysis method helps to better explain the basic working principle of STC digital metasurfaces and is expected to facilitate more applications in wireless communications, radar, imaging, and beamforming.

Giardia duodenalis is a flagellated zoonotic parasite that can infect various animals and humans, causing economic losses in husbandry and detriments to public health. Although it has been reported in pigs worldwide, there are few reports on the prevalence and assemblages of G. duodenalis infection in pigs in China. In this study, the 396 pig fecal samples were randomly collected from seven farms in Zhejiang, Guangdong and Yunnan provinces in southern China, and were examined by means of the nested PCR amplification of β-giardin (bg), glutamate dehydrogenase (gdh), and triose phosphate isomerase (tpi) for the detection of G. duodenalis. Overall, 21 fecal samples were positive for G. duodenalis, with a prevalence of 5.3%. Three risk factors are associated with G. duodenalis infection, namely, region, age and gender. Moreover, 13, six and two samples were successfully amplified at the bg, gdh and tpi gene loci, respectively. Three assemblages of G. duodenalis were identified, including assemblage E (n = 17), assemblage A (n = 3) and assemblage B (n = 1). Assemblage E was the dominating genotype and was distributed in three provinces. These assemblages of G. duodenalis have also been found in human beings, non-human primates, sheep, goats and cattle, which further reveals that farmed pigs pose a potential threat to public health.

Debris flows in tributaries rush into and block the main branches of rivers and often result in serious hazards. Dam failures cause large floods in the downstream area and can lead to fatalities and property damage. This study proposes an assessment method to evaluate the formation of a debris flow dam, which includes two conditions: (1) the sediment transported by the debris flow must reach across the river; and (2) the thickness of the deposit by the debris flow must be higher than the in situ water depth. This methodology was used to study the case of a debris flow dam caused by debris flow across the Er River in Taiwan, which blocked the Chishan River and led to the formation of the Namasha debris flow dam. This methodology can also be applied to identify the formation of debris flow dams.

Blastocystis sp. is a common pathogen that infects the intestines of humans and animals, causing a threat to public health. However, little information on the prevalence and subtypes of Blastocystis sp. in diarrheic pigs in China is available. Herein, 1254 fecal samples were collected from diarrheic pigs in 37 intensive pig farms in Hunan, Jiangxi, and Fujian provinces in southern China, and the prevalence and subtypes of Blastocystis sp. were investigated. Blastocystis sp. was detected by PCR assay, which amplified the small subunit rRNA (SSU rRNA) gene. Overall prevalence of Blastocystis sp. was 31.4% (394/1254), including 21.5% (66/307), 33.1% (99/299), 58.9% (56/95), and 31.3% (173/553) in suckling piglets, weaned piglets, fattening pigs, and sows, respectively. Moreover, age and region factors were significantly related to prevalence of Blastocystis sp. (p < 0.05). Four Blastocystis sp. subtypes were identified, including ST1, ST3, ST5, and ST14. The preponderant subtype was ST5 (76.9%, 303/394). To our knowledge, ST14 was firstly found in pigs in China. The human-pathogenic subtypes (ST1, ST3, ST5, and ST14) that were observed in this study indicate a potential threat to public health. These findings provided a new sight for studying the genetic structure of Blastocystis sp.

Abstract Background Toxoplasma gondii, a common opportunistic protozoan, is a leading cause of illness and mortality among immunosuppressed individuals and during congenital infections. Current therapeutic strategies for toxoplasmosis are not fully effective at curtailing disease progression in these cases. Given the parasite ability to influence host immunity and metabolism, understanding of the metabolic alterations in the host’s immune organs during T. gondii infection may enhance the understanding of the molecular mechanisms that define the pathophysiology of T. gondii infection. Methods We investigated the global metabolic changes in the spleen of BALB/c mice at early and late stage of infection with T. gondii using LC-MS/MS-based metabolomics. Multivariate data analysis methods, principal components analysis (PCA) and partial least squares discriminant analysis (PLS-DA), were used to identify metabolites that are influenced by T. gondii infection. Results Multivariate analyses clearly separated the metabolites of spleen of infected and control mice. A total of 132 differential metabolites were identified, 23 metabolites from acutely infected versus control mice and 109 metabolites from chronically infected versus control mice. Lipids, hormones, lactones, acids, peptides, antibiotics, alkaloids and natural toxins were the most influenced chemical groups. There were 12 shared differential metabolites between acutely infected versus control mice and chronically infected versus control mice, of which 4,4-Dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol was significantly upregulated and ubiquinone-8 was significantly downregulated. Major perturbed metabolic pathways included primary bile acid biosynthesis, steroid hormone biosynthesis, biotin metabolism, and steroid biosynthesis, with arachidonic acid metabolism being the most significantly impacted pathway. These metabolic changes suggest a multifactorial nature of the immunometabolic responses of mouse spleen to T. gondii infection. Conclusions This study demonstrated that T. gondii infection can cause significant metabolomic alterations in the spleen of infected mice. These findings provide new insights into the molecular mechanisms that underpin the pathogenesis of T. gondii infection.

The increase of blood pressure accelerates endothelial progenitor cells (EPCs) senescence, hence a significant reduction in the number of EPCs is common in patients with hypertension. Autophagy is a defense and stress regulation mechanism to assist cell homeostasis and organelle renewal. A growing number of studies have found that autophagy has a positive role in repairing vascular injury, but the potential mechanism between autophagy and senescence of EPCs induced by hypertension has rarely been studied. Therefore, in this study, we aim to explore the relationship between senescence and autophagy, and investigate the protective effect of rhynchophylline (Rhy) on EPCs. In angiotensin II (Ang II)-treated EPCs, enhancing autophagy through rapamycin mitigated Ang II-induced cell senescence, on the contrary, 3-methyladenine aggravated the senescence by weakening autophagy. Similarly, Rhy attenuated senescence and improved cellular function by rescuing the impaired autophagy in Ang II-treated EPCs. Furthermore, we found that Rhy promoted autophagy by activating AMP-activated protein kinase (AMPK) signaling pathway. Our results show that enhanced autophagy attenuates EPCs senescence and Rhy rescues autophagy impairment to protect EPCs against Ang II injury.

In this study, we develop a dimensionless assessment method to evaluate landslide dam formation by considering the relationship between the run-out distance of a tributary debris flow and the width of the main stream, deposition thickness of the tributary debris flow, and the water depth of the main stream. Based on the theory of debris flow run-out distance and fan formation, landslide dam formation may result from a tributary debris flow as a result of two concurrent formation processes: (1) the run-out distance of the tributary debris flow must be greater than the width of the main stream, and (2) the minimum deposition thickness of the tributary debris flow must be higher than the in situ water depth of the main stream. At the confluence, one of four types of depositional scenarios may result: (1) the tributary debris flow enters into the main stream and forms a landslide dam; (2) the tributary debris flow enters into the main stream but overflow occurs, thus preventing complete blockage of the main stream; (3) the tributary debris flow enters into the main stream, does not reach the far bank, and sediment remains partially above the water elevation of the main stream; or (4) the tributary debris flow enters into the main stream, does not reach the far bank, and sediment is fully submerged in the main stream. This method was applied to the analysis of 11 tributary debris flow events during Typhoon Morakot, and the results indicate that the dimensionless assessment method can be used to estimate potential areas of landslide dam formation caused by tributary debris flows. Based on this method, government authorities can determine potential areas of landslide dam formation caused by debris flows and mitigate possible disasters accordingly through a properly prepared response plan, especially for early identification.

Toxoplasma gondii poses a great threat to human health, with no approved vaccine available for the treatment of T. gondii infection. T. gondii infections are not limited to the brain, and may also affect other organs especially the liver. Identification of host liver molecules or pathways involved in T. gondii replication process may lead to the discovery of novel anti-T. gondii targets. Here, we analyzed the metabolic profile of the liver of mice on 11 and 30 days postinfection (dpi) with type II T. gondii Pru strain. Global metabolomics using liquid chromatography-tandem mass spectrometry (LC-MS/MS) identified 389 significant metabolites from acutely infected mice; and 368 from chronically infected mice, when compared with control mice. Multivariate statistical analysis revealed distinct metabolic signatures from acutely infected, chronically infected and control mice. Infection influenced several metabolic processes, in particular those for lipids and amino acids. Metabolic pathways, such as steroid hormone biosynthesis, primary bile acid biosynthesis, bile secretion, and biosynthesis of unsaturated fatty acids were perturbed during the whole infection process, particularly during the acute stage of infection. The present results provide insight into hepatic metabolic changes that occur in BALB/c mice during acute and chronic T. gondii infection.

Streptococcus agalactiae and Candida albicans often co-colonize the female genital tract, and under certain conditions induce mucosal inflammation. The role of the interaction between the two organisms in candidal vaginitis is not known. In this study, we found that co-infection with S. agalactiae significantly attenuated the hyphal development of C. albicans, and that EFG1-Hwp1 signal pathway of C. albicans was involved in this process. In a mouse model of vulvovaginal candidiasis (VVC), the fungal burden and the levels of pro-inflammatory cytokines, IL-1β, IL-6 and TNF-α showed a increase on co-infection with S. agalactiae, while the level of TH17 T cells and IL-17 in the cervicovaginal lavage fluid were significantly decreased. Our results indicate that S. agalactiae inhibits C. albicans hyphal development by downregulating the expression of EFG1-Hwp1. The interaction between S. agalactiae and C. albicans may attenuate host vaginal mucosal TH17 immunity and contribute to mucosal colonization by C. albicans.

Toxoplasma gondii is an obligate intracellular parasite causing severe diseases in immunocompromised individuals and congenitally infected neonates, such as encephalitis and chorioretinitis. This study aimed to determine whether serum metabolic profiling can (i) identify metabolites associated with oocyst-induced T. gondii infection and (ii) detect systemic metabolic differences between T. gondii-infected mice and controls. We performed the first global metabolomics analysis of mice serum challenged with 100 sporulated T. gondii Pru oocysts (Genotype II). Sera from acutely infected mice (11 days post-infection, dpi), chronically infected mice (33 dpi) and control mice were collected and analyzed using LC-MS/MS platform. Following False Discovery Rate filtering, we identified 3871 and 2825 ions in ESI+ or ESI− mode, respectively. Principal Component Analysis (PCA) and Partial Least Squares Discriminant Analysis (PLS-DA) identified metabolomic profiles that clearly differentiated T. gondii-infected and -uninfected serum samples. Acute infection significantly influenced the serum metabolome. Our results identified common and uniquely perturbed metabolites and pathways. Acutely infected mice showed perturbations in metabolites associated with glycerophospholipid metabolism, biosynthesis of amino acid, and tyrosine metabolism. These findings demonstrated that acute T. gondii infection induces a global perturbation of mice serum metabolome, providing new insights into the mechanisms underlying systemic metabolic changes during early stage of T. gondii infection.