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Abstract Background Sepsis remains a major challenge in intensive care units, causing unacceptably high mortality rates due to the lack of rapid diagnostic tools with sufficient sensitivity. Therefore, there is an urgent need to replace time-consuming blood cultures with a new method. Ideally, such a method also provides comprehensive profiling of pathogenic bacteria to facilitate the treatment decision. Methods We developed a Random Forest with balanced subsampling to screen for pathogenic bacteria and diagnose sepsis based on cell-free DNA (cfDNA) sequencing data in a small blood sample. In addition, we constructed a bacterial co-occurrence network, based on a set of normal and sepsis samples, to infer unobserved bacteria. Results Based solely on cfDNA sequencing information from three independent datasets of sepsis, we distinguish sepsis from healthy samples with a satisfactory performance. This strategy also provides comprehensive bacteria profiling, permitting doctors to choose the best treatment strategy for a sepsis case. Conclusions The combination of sepsis identification and bacteria-inferring strategies is a success for noninvasive cfDNA-based diagnosis, which has the potential to greatly enhance efficiency in disease detection and provide a comprehensive understanding of pathogens. For comparison, where a culture-based analysis of pathogens takes up to 5 days and is effective for only a third to a half of patients, cfDNA sequencing can be completed in just 1 day and our method can identify the majority of pathogens in all patients.

Abstract Background Developing effective strategies for signaling the pre-disease state of complex diseases, a state with high susceptibility before the disease onset or deterioration, is urgently needed because such state usually followed by a catastrophic transition into a worse stage of disease. However, it is a challenging task to identify such pre-disease state or tipping point in clinics, where only one single sample is available and thus results in the failure of most statistic approaches. Methods In this study, we presented a single-sample-based computational method to detect the early-warning signal of critical transition during the progression of complex diseases. Specifically, given a set of reference samples which were regarded as background, a novel index called single-sample Kullback–Leibler divergence (sKLD), was proposed to explore and quantify the disturbance on the background caused by a case sample. The pre-disease state is then signaled by the significant change of sKLD. Results The novel algorithm was developed and applied to both numerical simulation and real datasets, including lung squamous cell carcinoma, lung adenocarcinoma, stomach adenocarcinoma, thyroid carcinoma, colon adenocarcinoma, and acute lung injury. The successful identification of pre-disease states and the corresponding dynamical network biomarkers for all six datasets validated the effectiveness and accuracy of our method. Conclusions The proposed method effectively explores and quantifies the disturbance on the background caused by a case sample, and thus characterizes the criticality of a biological system. Our method not only identifies the critical state or tipping point at a single sample level, but also provides the sKLD-signaling markers for further practical application. It is therefore of great potential in personalized pre-disease diagnosis.

Nowadays, emerging evidence has shown adverse pregnancy outcomes, including preterm birth, preeclampsia, cesarean, and perinatal death, occurring in pregnant women after getting infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the underlying mechanisms remain elusive. Thyroid hormone disturbance has been unveiled consistently in various studies. As commonly known, thyroid hormone is vital for promoting pregnancy and optimal fetal growth and development. Even mild thyroid dysfunction can cause adverse pregnancy outcomes. We explored and summarized possible mechanisms of thyroid hormone abnormality in pregnant women after coronavirus disease 2019 (COVID-19) infection and made a scientific thypothesis that adverse pregnancy outcomes can be the result of thyroid hormone disorder during COVID-19. In which case, we accentuate the importance of thyroid hormone surveillance for COVID-19-infected pregnant women.

Inspired by the human brain, the spike-based neuromorphic system has attracted strong research enthusiasm because of the high energy efficiency and powerful computational capability, in which the spiking neurons and plastic synapses are two fundamental building blocks. Recently, two-terminal threshold switching (TS) devices have been regarded as promising candidates for building spiking neurons in hardware. However, how circuit parameters affect the spiking behavior of TS-based neurons is still an open question. Here, based on a leaky integrate-and-fire (LIF) neuron circuit, we systematically study the effect of both the extrinsic and intrinsic factors of NbOx -based TS neurons on their spiking behaviors. The extrinsic influence factors contain input intensities, connected synaptic weights, and parallel capacitances. To illustrate the effect of intrinsic factors, including the threshold voltage, holding voltage, and high/low resistance states of NbOx devices, we propose an empirical model of the fabricated NbOx devices, fitting well with the experimental results. The results indicate that with enhancing the input intensity, the spiking frequency increases first then decreases after reaching a peak value. Except for the connected synaptic weights, all other parameters can modulate the spiking peak frequency under high enough input intensity. Also, the relationship between energy consumption per spike and frequency of the neuron cell is further studied, leading guidance to design neuron circuits in a system to obtain the lowest energy consumption. At last, to demonstrate the practical applications of TS-based neurons, we construct a spiking neural network (SNN) to control the cart-pole using reinforcement learning, obtaining a reward score up to 450. This work provides valuable guidance on building compact LIF neurons based on TS devices and further bolsters the construction of high-efficiency neuromorphic systems.

Purpose. This study aims to assess the corneal epithelial remodeling within a 9 mm diameter zone induced by small incision lenticule extraction (SMILE) and evaluate its relationship with the refractive outcomes. Methods. A total of 64 eyes of 64 patients were included. Wide-field optical coherence tomography (OCT) was used to measure the epithelial thickness (ET) across a 9 mm diameter area, preoperatively, and after one day, one week, one month, three months, and six months postoperatively. The ET changes were compared among the different time points and analyzed zones. Results. The ET increases from one week to three months and stabilized from three months to six months. Compared to the preoperative values, the mean ET changes at six months in central (2 mm), paracentral (2–5 mm), mid-peripheral (5–7 mm), and peripheral (7–9 mm) zones were 4.37, 4.36, 1.61, and −1.59 μm, respectively. The correlation between the epithelial thickening and the amount of myopia correction was positive in central (P = 0.001) and paracentral zones (P

One of the main failure modes of an insulated-gate bipolar transistor (IGBT) module is the reconstruction of an aluminum (Al) metallization layer on the surface of the IGBT chip. In this study, experimental observations and numerical simulations were used to investigate the evolution of the surface morphology of this Al metallization layer during power cycling, and both internal and external factors affecting the surface roughness of the layer were analyzed. The results indicate that the microstructure of the Al metallization layer evolves during power cycling, where the initially flat surface gradually becomes uneven, such that the roughness varies significantly across the IGBT chip surface. The surface roughness depends on several factors, including the grain size, grain orientation, temperature, and stress. With regard to the internal factors, reducing the grain size or orientation differences between neighboring grains can effectively decrease the surface roughness. With regard to the external factors, the reasonable design of the process parameters, a reduction in the stress concentration and temperature hotspots, and preventing large local deformation can also reduce the surface roughness.

Accompanying the process of growth and development, plants are exposed to ever-changing environments, which consequently trigger abiotic or biotic stress responses. The large protein family known as receptor-like protein kinases (RLKs) is involved in the regulation of plant growth and development, as well as in the response to various stresses. Understanding the biological function and molecular mechanism of RLKs is helpful for crop breeding. Research on the role and mechanism of RLKs has recently received considerable attention regarding the balance between plant growth and environmental adaptability. In this paper, we systematically review the classification of RLKs, the regulatory roles of RLKs in plant development (meristem activity, leaf morphology and reproduction) and in stress responses (disease resistance and environmental adaptation). This review focuses on recent findings revealing that RLKs simultaneously regulate plant growth and stress adaptation, which may pave the way for the better understanding of their function in crop improvement. Although the exact crosstalk between growth constraint and plant adaptation remains elusive, a profound study on the adaptive mechanisms for decoupling the developmental processes would be a promising direction for the future research.

Carbon nanotubes (CNTs) were considered a promising activator for persulfates due to their high electrical conductivity, large specific surface area and low toxicity. The functional groups and surface defects of CNTs could significantly affect their activation performance. In this study, CNTs with high C=O ratio and defect density (CNT-O-H) were prepared through a facile treatment of raw CNTs with HNO3 oxidation followed by calcination at 800 °C under an argon atmosphere. X-ray photoelectron spectroscopy (XPS) and Raman results showed that the C=O proportion and defect degree (ID/IG) rose to 75% and 1.53, respectively. The obtained CNT-O-H possessed a superior performance towards peroxydisulfate (PDS) activation, and the degradation efficiency of tetracycline (TC) in the CNT-O-H/PDS system was increased to 75.2% from 56.2% of the raw CNTs/PDS system within 40 min. Moreover, the activity of CNT-O-H after use could be easily recovered with re-calcination. In addition, the CNT-O-H/PDS system exhibited high adaptabilities towards wide solution pH (2–10), common coexisting substances and diverse organic pollutants. Singlet oxygen (1O2) was confirmed to be the dominant reactive oxygen species (ROS) generated in the CNT-O-H/PDS system. It was inferred that surface C=O groups and defects of CNTs were the key site to activate PDS for TC degradation.

American ginseng (Panax quinquefolius L.) has been recognized as a valuable herb medicine, and ginsenosides are the most important components responsible for the health-beneficial effects. This study investigated the secondary metabolites responsible for the differentiation of wild and cultivated American ginsengs with ultrahigh-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS)-based metabolomic approach. An in-house ginsenoside library was developed to facilitate data processing and metabolite identification. Data visualization methods, such as heatmaps and volcano plots, were utilized to extract discriminated ion features. The results suggested that the ginsenoside profiles of wild and cultivated ginsengs were significantly different. The octillol (OT)-type ginsenosides were present in greater abundance and diversity in wild American ginsengs; however, a wider distribution of the protopanaxadiol (PPD)-and oleanolic acid (OA)-type ginsenosides were found in cultivated American ginseng. Based on the tentative identification and semi-quantification, the amounts of five ginsenosides (i.e., notoginsenoside H, glucoginsenoside Rf, notoginsenoside R1, pseudoginsenoside RT2, and ginsenoside Rc) were 2.3–54.5 fold greater in wild ginseng in comparison to those in their cultivated counterparts, and the content of six ginsenosides (chicusetsusaponin IVa, malonylginsenoside Rd, pseudoginsenoside Rc1, malonylfloralginsenoside Rd6, Ginsenoside Rd, and malonylginsenoside Rb1) was 2.6–14.4 fold greater in cultivated ginseng compared to wild ginseng. The results suggested that the in-house metabolite library can significantly reduce the complexity of the data processing for ginseng samples, and UHPLC-HRMS is effective and robust for identifying characteristic components (marker compounds) for distinguishing wild and cultivated American ginseng.

Dandelion (Taraxacum mongolicum Hand.-Mazz.) is a medicinal and edible plant. Dandelion has great development value for its health promoting benefits; additionally, Dandelion grows almost anywhere in the world. In this study, we report the structural characteristics and anti-cancer activity of novel dandelion leaf polysaccharides extracted by pressurized hot water extraction at 120 °C (DLP120) with Mw relative to dextran of 1.64 × 106 Da. Structural analysis indicated that DLP120 is a complex polysaccharide composed of pectin and arabinogalactan. It was mainly composed of arabinose (32.35 mol%) and galactose (44.91 mol%). The main glycosidic linkages of DLP120 were 4-β-D-Galp, 4-α-D-GalpA, T-β-D-Galp, 5-α-L-Araf, 3,5-α-L-Araf, and T-α-L-Araf. In vitro, DLP120 inhibited HepG2 cell proliferation in a dose-dependent manner by inducing cell apoptosis. Cell cycle detection results revealed that DLP120 mainly arrests the cell cycle in S phase. Cells treated with DLP120 displayed obvious apoptotic morphology, including cell volume shrinks and cytoskeleton breaks down. In short, DLP120 has potential as an anti-cancer agent.

Nowadays, the bone osseointegration in different environments is comparable, but the mechanism is unclear. This study aimed to investigate the osseointegration of different bioactive titanium surfaces under normoxic or high-altitude hypoxic environments. Titanium implants were subjected to one of two surface treatments: (1) sanding, blasting, and acid etching to obtain a rough surface, or (2) extensive polishing to obtain a smooth surface. Changes in the morphology, proliferation, and protein expression of osteoblasts on the rough and smooth surfaces were examined, and bone formation was studied through western blotting and animal-based experiments. Our findings found that a hypoxic environment and rough titanium implant surface promoted the osteogenic differentiation of osteoblasts and activated the JAK1/STAT1/HIF-1α pathway in vitro. The animal study revealed that following implant insertion in tibia of rabbit, bone repair at high altitudes was slower than that at low altitudes (i.e., in plains) after 2weeks; however, bone formation did not differ significantly after 4weeks. The results of our study showed that: (1) The altitude hypoxia environment would affect the early osseointegration of titanium implants while titanium implants with rough surfaces can mitigate the effects of this hypoxic environment on osseointegration, (2) the mechanism may be related to the activation of JAK1/STAT1/HIF-1α pathway, and (3) our results suggest the osteogenesis of titanium implants, such as oral implants, is closely related to the oxygen environment. Clinical doctors, especially dentists, should pay attention to the influence of hypoxia on early osseointegration in patients with high altitude. For example, it is better to choose an implant system with rough implant surface in the oral cavity of patients with tooth loss at high altitude.

BackgroundAlternative splicing (AS) plays a key role in the diversity of proteins and is closely associated with tumorigenicity. The aim of this study was to systemically analyze RNA alternative splicing (AS) and identify its prognostic value for papillary thyroid cancer (PTC).MethodsAS percent-splice-in (PSI) data of 430 patients with PTC were downloaded from the TCGA SpliceSeq database. We successfully identified recurrence-free survival (RFS)-associated AS events through univariate Cox regression, LASSO regression and multivariate regression and then constructed different types of prognostic prediction models. Gene function enrichment analysis revealed the relevant signaling pathways involved in RFS-related AS events. Simultaneously, a regulatory network diagram of AS and splicing factors (SFs) was established.ResultsWe identified 1397 RFS-related AS events which could be used as the potential prognostic biomarkers for PTC. Based on these RFS-related AS events, we constructed a ten-AS event prognostic prediction signature that could distinguish high-and low-risk patients and was highly capable of predicting PTC patient prognosis. ROC curve analysis revealed the excellent predictive ability of the ten-AS events model, with an area under the curve (AUC) value of 0.889; the highest prediction intensity for one-year RFS was 0.923, indicating that the model could be used as a prognostic biomarker for PTC. In addition, the nomogram constructed by the risk score of the ten-AS model also showed high predictive efficiency for the prognosis of PTC patients. Finally, the constructed SF-AS network diagram revealed the regulatory role of SFs in PTC.ConclusionThrough the limited analysis, AS events could be regarded as reliable prognostic biomarkers for PTC. The splicing correlation network also provided new insight into the potential molecular mechanisms of PTC.

Fungi perform crucial roles in nutrient cycles, but there is limited information on how soil fungal communities vary with stand age and tree species. Eucalyptus has been extensively planted in China, which has caused severe soil erosion and water deficiency due to short rotation management. In this study, the fungal community structure and potential function in Eucalyptus plantations with different ages (1–5+ years) and species (Eucalyptus urophylla × Eucalyptus grandis, Eucalyptus camaldulens, and Eucalyptus pellita) under a tropical monsoon climate in China were characterized by Illumina Miseq coupled with FUNGuild analysis. The results showed that the fungal alpha diversity decreased with an increase in the age of the plantation. Plantations of different ages and species formed distinct fungal communities and potential functional structures, respectively (p < 0.05), in which the age of the plantation contributed more to the variations. At high taxonomic levels, the soil fungal community changed from the dominance of orders belonging to Ascomycota (Pleosporales, Chaetothyriales, and Eurotiales) to orders belonging to Basidiomycota (Agaricales, Sebacinales, Cantharellales, and Russulales) with increasing plantation age. The community potential function shifted from the dominance of plant pathogens to a higher abundance of saprotrophs and symbiotrophs. The organic carbon of the soil was the key environmental driver to both the fungal community and potential functional structure. The results provide useful information on the importance of fungi for the management of Eucalyptus plantations.

Previous studies have indicated that Brca1 (Breast cancer suppressor gene 1) plays an important role in neural development and degenerative diseases. However, the bioactivity and regulatory mechanism of Brca1 expression in retinal neurocytes remain unclear. In the present study, our data indicated that Brca1 maintains the state of neuronal precursor cells. Brca1 silencing induces differentiation in 661W cells. Nestin, a marker of precursor cells, was significantly decreased in parallel with Brca1 silencing in 661W cells, whereas Map2 (Microtubule associated protein 2), a marker of differentiated neurons, was significantly increased. Neurite outgrowth was increased by ~4.0-fold in Brca1-silenced cells. Moreover, DNA affinity purification assays and ChIP assays demonstrated that Gata3 (GATA binding protein 3) regulates Brca1 transcription in 661W cells. Silencing or overexpressing Gata3 could significantly regulate the expression of Brca1 and affect its promoter inducibility. Furthermore, the expression of Gata3 generally occurred in parallel with that of Brca1 in developing mouse retinas. Both Gata3 and Brca1 are expressed in the neonatal mouse retina but are developmentally silenced with age. Exogenous Gata3 significantly inhibited neural activity by decreasing synaptophysin and neurite outgrowth. Thus, this study demonstrated that Brca1 is transcriptionally regulated by Gata3. Brca1/Gata3 silencing is involved in neuronal differentiation and maturation.

Dandelion is an edible plant with a variety of bioactive components. This paper mainly reports the antitumor activity of dandelion polysaccharide DLP120 on H22 tumor-bearing mice. DLP120 is an acidic polysaccharide composed of pectin and arabinogalactan. The results indicate that DLP120 markedly inhibited tumor growth in a dose-dependent manner and attenuated and regulated negative effects on organs. In addition, DLP120 not only increased the viability of spleen lymphocytes and natural killer (NK) cells, but also increased the proportion of lymphocyte subsets in peripheral blood. Furthermore, Hematoxylin-Eosin (HE) staining showed that tumor tissues and cells exhibited typical pathology features. Annexin V FITC/PI staining and cell cycle distribution results further confirmed apoptosis and cell cycle arrest in S and G2 phases. Notably, there was a significant accumulation of reactive oxygen species. Western blotting results demonstrated that the expression of p53 was up-regulated in the DLP120 group. Moreover, the pro-apoptotic protein Bax was up-regulated while the inhibitory-apoptotic protein Bcl-2 was down-regulated. In addition, the expression of Fas and FasL, associated with the death receptor pathway, were also up-regulated. Overall, administration of DLP120 in H22 tumor-bearing mice can not only enhance immunity but also directly induce tumor cell apoptosis.

Immunotherapy has achieved positive clinical responses in various cancers. However, in advanced colorectal cancer (CRC), immunotherapy is challenging because of the deterioration of T-cell exhaustion, the mechanism of which is still unclear. In this study, we depicted CD8+ T-cell developmental trajectories and characterized the pre-exhausted T cells isolated from CRC patients in the scRNA-seq data set using a dynamic network biomarker (DNB). Moreover, CCT6A identified by DNB was a biomarker for pre-exhausted T-cell subpopulation in CRC. Besides, TUBA1B expression was triggered by CCT6A as DNB core genes contributing to CD8+ T cell exhaustion, indicating that core genes serve as biomarkers in pre-exhausted T cells. Remarkably, both TUBA1B and CCT6A expressions were significantly associated with the overall survival of COAD patients in the TCGA database (p = 0.0082 and p = 0.026, respectively). We also observed that cellular communication between terminally differentiated exhausted T cells and pre-exhausted T cells contributes to exhaustion. These findings provide new insights into the mechanism of T-cell exhaustion and provide clue for targeted immunotherapy in CRC.

Summary: Inorganic halide perovskites have emerged as a promising platform in a wide range of applications from solar energy harvesting to computing and light emission. The recent advent of epitaxial thin film growth of halide perovskites has made it possible to investigate low-dimensional quantum electronic devices based on this class of materials. This study leverages advances in vapor-phase epitaxy of halide perovskites to perform low-temperature magnetotransport measurements on single-domain cesium tin iodide (CsSnI3) epitaxial thin films. The low-field magnetoresistance carries signatures of coherent quantum interference effects and spin-orbit coupling. These weak anti-localization measurements reveal a micron-scale low-temperature phase coherence length for charge carriers in this system. The results indicate that epitaxial halide perovskite heterostructures are a promising platform for investigating long coherent quantum electronic effects and potential applications in spintronics and spin-orbitronics.

ABSTRACT HIV-1 remains incurable due to viral reservoirs, which lead to durably latent HIV infection. Identifying novel host factors and deciphering the molecular mechanisms involved in the establishment and maintenance of latency are critical to discover new targets for the development of novel anti-HIV agents. Here, we show that ubiquitin-like with PHD and RING finger domain 1 (UHRF1) modulates HIV-1 5′-long terminal repeat (LTR)-driven transcription of the viral genome as a novel HIV-1 restriction factor. Correspondingly, UHRF1 depletion reversed the latency of HIV-1 proviruses. Mechanistically, UHRF1 competed with positive transcription factor b (p-TEFb) for the binding to the cysteine-rich motifs of HIV-1 Tat via its TTD, PHD, and RING finger domains. Furthermore, UHRF1 mediated K48-linked ubiquitination and proteasomal degradation of Tat in RING-dependent ways, leading to the disruption of Tat/cyclin T1/CDK9 complex and consequential impediment of transcription elongation. In summary, our findings revealed that UHRF1 is an important mediator of HIV-1 latency by controlling Tat-mediated transcriptional activation, providing novel insights on host-pathogen interaction for modulating HIV-1 latency, beneficial for the development of anti-AIDS therapies. IMPORTANCE HIV-1 latency is systematically modulated by host factors and viral proteins. In our work, we identified a critical role of host factor ubiquitin-like with PHD and RING finger domain 1 (UHRF1) in HIV-1 latency via the modulation of the viral protein Tat stability. By disrupting the Tat/cyclin T1/CDK9 complex, UHRF1 promotes the suppression of HIV-1 transcription and maintenance of HIV-1 latency. Our findings provide novel insights in controlling Tat expression via host-pathogen interaction for modulating HIV-1 latency. Based on our results, modulating UHRF1 expression or activity by specific inhibitors is a potential therapeutic strategy for latency reversal in HIV-1 patients.

The failure of highly active antiretroviral therapy (HAART) has been largely responsible for the existence of latent human immunodeficiency virus type 1 (HIV-1) reservoirs. The “shock and kill” strategy was confirmed to reactivate HIV-1 latent reservoirs by latency-reversing agents (LRAs) for accelerated HIV-1 clearance. However, a single LRA might be insufficient to induce HIV-1 reactivation from latency due to the complexity of the multiple signaling regulatory pathways that establish the HIV-1 latent reservoir. Therefore, combinations of LRAs or dual-mechanism LRAs are urgently needed to purge the latent reservoirs. We demonstrate here for the first time that a dual-target inhibitor with a specific suppressive effect on both BRD4 and TIP60, CPI-637, could reactivate latent HIV-1 in vitro by permitting Tat to bind positive transcription elongation factor b (P-TEFb) and assembling Tat-super-elongation complex (SEC) formation. In addition, CPI-637-mediated TIP60 downregulation further stimulated BRD4 dissociation from the HIV-1 long terminal repeat (LTR) promoter, allowing Tat to more effectively bind P-TEFb compared to BRD4 inhibition alone. Much more importantly, CPI-637 exerted a potent synergistic effect but alleviated global T cell activation and blocked viral spread to uninfected bystander CD4+ T cells with minimal cytotoxicity. Our results indicate that CPI-637 opens up the prospect of novel dual-target inhibitors for antagonizing HIV-1 latency and deserves further investigation for development as a promising LRA with a “shock and kill” strategy.

Cerebral ischemia/reperfusion (I/R) injury is a serious condition that leads to increased apoptosis of microglial and neurons in the brain. In this study, we identified that Cx43 expression level is significantly increased in the microglial cells during I/R injury. Using an in vitro model (hypoxia/reoxygenation-H/R injury), we observed that H/R injury leads to an increase in activation of microglial cells and increase in levels of pro-inflammatory markers such as IL-1β, IL-6, and TNF-α. Additionally, we could also observe significant increase in phosphorylation of Cx43 and Cav3.2 levels. To assess the role of H/R injured microglial cells on neuronal population, we cultured the neurons with conditioned media (MCS) from H/R injured microglial cells. Interestingly, we observed that microglial H/R injury significantly decreased Map2 expression and affected neuronal morphology. Further, we aimed to assess the effects of propofol on cerebral H/R injury, and observed that 40 μM propofol significantly decreased Cx43, Cx43 phosphorylation, and CaV3.2 levels. Additionally, propofol decreased apoptosis and increased Map2 expression levels in H/R injured neurons. Using silencing experiments, we confirmed that siCx43 could significantly improve the propofol’s rescue after H/R injury in both microglia and neurons. We further developed an in vivo MCAO (middle cerebral artery occlusion) rat model to understand the effect of propofol in I/R injury. Interestingly, propofol treatment and downregulation of Cx43 significantly decreased the infract volume and apoptosis in these MCAO rats. Thus, this study clearly establishes that propofol protects the brain against I/R injury through the downregulation of Cx43 in microglial cells.

Background Italy surpassed 1.5 million confirmed Coronavirus Disease 2019 (COVID-19) infections on November 26, as its death toll rose rapidly in the second wave of COVID-19 outbreak which is a heavy burden on hospitals. Therefore, it is necessary to forecast and early warn the potential outbreak of COVID-19 in the future, which facilitates the timely implementation of appropriate control measures. However, real-time prediction of COVID-19 transmission and outbreaks is usually challenging because of its complexity intertwining both biological systems and social systems. Methods By mining the dynamical information from region networks and the short-term time series data, we developed a data-driven model, the minimum-spanning-tree-based dynamical network marker (MST-DNM), to quantitatively analyze and monitor the dynamical process of COVID-19 spreading. Specifically, we collected the historical information of daily cases caused by COVID-19 infection in Italy from February 24, 2020 to November 28, 2020. When applied to the region network of Italy, the MST-DNM model has the ability to monitor the whole process of COVID-19 transmission and successfully identify the early-warning signals. The interpretability and practical significance of our model are explained in detail in this study. Results The study on the dynamical changes of Italian region networks reveals the dynamic of COVID-19 transmission at the network level. It is noteworthy that the driving force of MST-DNM only relies on small samples rather than years of time series data. Therefore, it is of great potential in public surveillance for emerging infectious diseases.

Abstract Background Hydroxychloroquine (HCQ), a well-known immunomodulator, has recently been found to be a promising and safe anti-proteinuric agent for treating IgA nephropathy (IgAN). We aimed to compare the efficacy and safety of HCQ and corticosteroid treatment in patients with IgAN. Methods This is a case-control study. Ninety-two patients with IgAN who received HCQ in addition to routine renin-angiotensin-aldosterone system inhibitors (RAASi) therapy were included. Ninety-two matched historical controls who received corticosteroids were selected by propensity score matching. The clinical data over 6 months were compared. Results Baseline proteinuria levels were comparable between the HCQ and corticosteroid groups (1.7 [1.2, 2.3] vs. 1.8 [1.3, 2.5] g/d, p = 0.96). The percentage reduction in proteinuria at 6 months was smaller in the HCQ group than in the corticosteroid group (− 48.5% [− 62.6, − 31.4] vs. -62.9% [− 81.1, − 34.9], p = 0.006). The time averaged proteinuria within the 6 months of observation was comparable for the HCQ and corticosteroid groups (1.1 [0.8, 1.5] vs. 1.1 [0.5, 1.8] g/d, p = 0.48). The cumulative frequency of patients with a 50% reduction in proteinuria during the study was also comparable between the two groups (52.2% vs. 62.0%, p = 0.25). However, six of the 92 (6.5%) patients suffered from severe adverse events (SAEs) in the corticosteroid group, while no SAEs were observed in the HCQ group (6.5% vs. 0%, p = 0.03). Conclusions The antiproteinuric effect of HCQ might be slightly inferior to that of corticosteroids over 6 months in patients with IgAN who were deemed to be candidates for HCQ and not corticosteroids treatment. However, HCQ treatment was safer than corticosteroid treatment.

Objective: Syndrome differentiation is a unique part of traditional Chinese medicine (TCM). Syndrome factors play an important role in the diagnosis and treatment of TCM syndromes. Thromboelastography (TEG) intuitively reflects the blood status of patients with acute ischemic stroke (AIS) and is important in the treatment and prognosis of AIS. To identify the relationship between TCM syndrome factors and TEG in AIS patients and standardize TCM syndrome differentiation and treatment objectives, we designed a prospective cohort study of 103 AIS patients. Methods: We used the diagnostic criteria for AIS in the Chinese Guideline for Diagnosis and Management of Acute Ischemic Stroke 2010. Diagnosis of phlegm-heat and fu-organ excess syndrome was based on the TCM Scale for the Syndrome of Phlegm-heat and fu-organ Excess. The ischemic Stroke TCM Syndrome Factor Diagnostic Scale was used to identify and diagnose syndrome factors. General information, scores of syndrome factors and values of TEG parameters of all enrolled patients were recorded. Results: There were significant differences in internal fire and phlegm-dampness scores between patients with and without phlegm-heat and fu-organ excess syndrome (P .05) or between both syndrome factors and TEG parameters in patients without phlegm-heat and fu-organ excess syndrome. Conclusion: The syndrome factor internal fire is a potential predictor of increased platelet function and fibrinogen activity in AIS patients with phlegm-heat and fu-organ excess, and a potentially important predictor of blood hypercoagulability in TCM. Keywords: Clinical relevance, Phlegm-heat and fu-organ excess syndrome, Syndrome factors, Thromboelastography

Hot-water and ethanol extracts of Chrysanthemum morifolium cv. Fubaiju were investigated for their chemical compositions, effects on gut microbiota, anti-inflammatory, and free radical scavenging capacities. UPLC-IMS-QTOF-MS analysis detected tuberonic acid glucoside and tasumatrol B in the Fubaiju for the first time. The hot-water extract had greater anti-inflammation and free radical scavenging activities than its counterpart ethanol extract under the experimental conditions. The total phenolic content, relative ABTS·+, DPPH· and oxygen radical scavenging capacities of the hot-water extract were 33.48 mg gallic acid equivalents/g, and 121.57, 110.11 and 1638.99 µmol Trolox equivalents/g, respectively. In addition, the hot-water extract enhanced the abundance of Bacteroidetes, Firmicutes, Bifidobacteria and Precotella, suggesting that drinking chrysanthemum tea may modulate gut microbiota. The results from this research could be used to improve the production and consumption of C. morifolium cv. Fubaiju as a functional food ingredient and promote local agricultural economics.

Vehicle inspection systems (VIS) have been extensively used by automobile manufacturers, maintenance companies, and the traffic administrative departments for the inspection of safety, reliability, and other indicators of both newly produced and in-used vehicles. How to increase their productivity by effectively operating such systems is an interesting and crucial problem. Because of the space limitation of testing field in such a system, a vehicle must complete pre-set inspection items at multiple stations in sequence. Hence, it is very challenging to sequence the vehicles to be tested to shorten the unnecessary waiting time for vehicle testing. This paper investigates the vehicle scheduling problem of such systems, where the time for vehicle movement in the system can be ignored. The system is modeled by resource-oriented Petri net, a graphical and mathematical modeling tool. Based on the model, this work analyzes the testing cycle time and develops a heuristic algorithm to efficiently solve the vehicle scheduling problem in such a system. For the first time, a heuristic algorithm for generating an optimal vehicle queue for testing is proposed. Industrial examples are used to illustrate the proposed algorithm and results show that a significant reduction in total test turnaround time can be obtained in comparison with the existing methods.

In this paper, a direct computational method is presented which combines optical flow and structure from motion (SfM) by putting the SfM problem in the framework of optical flow estimation. In other word, the optical flow is reparametrized in term of the camera's motion and scene's depth, resulting in a similar variation optimization as in optical flow estimation. Meanwhile, three techniques are proposed to improve the accuracy and robustness of the direct approach, including the fast guided interpolation (FGI), the left-right consistency constraint and the soft segment constraint. Experimental results on the Middlebury dataset and KITTI2012 dataset show that the proposed approach can achieve highly-accurate 3D reconstruction with the dense and smooth surface which results in a state-of-the-art performance in optical flow.

Abstract Acquired sensorineural hearing loss (SNHL), including age-related hearing loss (ARHL), noise-induced hearing loss (NIHL), drug-induced hearing loss (DIHL) and sudden sensorineural hearing loss (SSHL), is one of the most common sensory deficits in humans. Several studies have reported that antioxidant gene glutathione s-transferase M1 and T1 (GST M1 and T1) polymorphisms have a close relationship with the susceptibility to acquired SNHL, but other articles have reported opposite results. This meta-analysis aims to identify whether an association exists between GST M1 and T1 polymorphisms and the susceptibility to acquired SNHL. Seventeen independent studies containing 1749 cases and 2018 controls were included. According to the I2 value of the heterogeneity test, random-effects model was selected to calculate the pooled odds ratios (ORs) with their 95% confidence intervals (95% CIs) and p values. The pooled ORs (95% CI, p-value) of GST M1 and T1 were 1.186(0.955–1.473, p = 0.122) and 1.107(0.841–1.458, p = 1.467), respectively. In addition, subgroup analyses according to the type of SNHL and ethnicity showed no relationship between GST M1 and T1 polymorphisms and the susceptibility to acquired SNHL. Our results suggest that no significant relationship was found between GST M1 and T1 polymorphisms and the susceptibility to acquired SNHL.

BackgroundChildhood cancers are associated with high mortality and morbidity, and some maternal prescription drug use during pregnancy has been implicated in cancer risk. There are few studies on the effects of hypertension, preeclampsia, and the use of antihypertensives in pregnancy on children's cancer risks.ObjectiveThis population-based cohort study analyzed the relationship between hypertension, preeclampsia, and antihypertensives taken during pregnancy and the risks of childhood cancers in the offspring.MethodsData on all children born in Taiwan between 2004 and 2015 (N = 2,294,292) were obtained from the Maternal and Child Health Database. This registry was linked with the National Health Insurance Database and Cancer Registry to get the records of maternal use of diuretics or other antihypertensives in pregnancy and records of children with cancer diagnosed before 13 years. We used Cox proportional hazard modeling to estimate the influence of maternal health conditions and antihypertensive drug exposure on the risks of developing childhood cancers.ResultsOffspring of mothers with hypertension (chronic or gestational) had a higher risk of acute lymphocytic lymphoma [hazard ratio (HR) = 1.87, 95% Confidence Interval (CI) 1.32 - 2.65] and non-Hodgkin's lymphoma (HR = 1.96, 95% CI 1.34 - 2.86). We estimated only a weak increased cancer risk in children whose mothers used diuretics (HR = 1.16, 95% CI 0.77 - 1.74) or used antihypertensives other than diuretics (HR = 1.15, 95% CI 0.86 - 1.54) before birth.ConclusionsIn this cohort study, children whose mothers had chronic and gestational hypertension had an increased risk of developing childhood cancer.

The current global coronavirus disease 2019 (COVID-19) outbreak is still exerting severe global implications, and its development in various regions is complex and variable. The high risk of cross-infection poses a great challenge to the dental practice environment; it is therefore urgent to develop a set of pandemic prevention measures to ensure dental practice safety during the COVID-19 outbreak. Therefore, we combined the epidemiological characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), public emergency measures for COVID-19, characteristics of dental practice, and relevant literature reports to develop a set of dynamic practice measures for dental practices in high-, medium-, and low-risk areas affected by COVID-19. This will help dental practices to achieve standard prevention and ensure their safe and smooth operation during the pandemic. It is hoped that these measures will provide a reference basis for dental hospitals and dental clinics in their care and pandemic prevention work.

Airborne microorganisms in the waste associated environments are more active and complex compared to other places. However, the diversity and structure of airborne bacteria in waste-associated environments are still not clearly understood. The purpose of this study was to assess airborne bacterial community in electronic waste dismantling site and a waste transfer station based on culture-dependent and culture-independent methods. A total of 229 isolates were obtained from four airborne sites collected from residential area, electronic industrial park, and office area in or near an electronic waste dismantling site and a waste transfer station in Southern China in the morning, afternoon, and evening. Most of the isolates were isolated from air for the first time and 14 potentially novel species were identified by Sanger sequencing. Bacterial communities in waste-associated bioaerosols were predominated by Proteobacteria and Bacteroidetes. Abundant genera (>1%) included Paracaedibacteraceae (uncultured EF667926), Ralstonia, Chroococcidiopsis, Chitinophagaceae (uncultured FN428761), Sphingobium, and Heliimonas. One-third of the species in these genera were uncultured approximately. Differences community structure existed in airborne bacterial diversity among different sampling sites. These results showed that waste-associated environments have unique bacterial diversity. Further studies on such environments could provide new insights into bacterial community.

PurposeThe prognostic value of caveolin-1 in prostate cancer remains uncertain. Hence, this meta-analysis was performed to evaluate the prognostic value of caveolin-1 in prostate cancer, as well as ascertain the relationship between caveolin-1 expression and clinicopathological characteristics of prostate cancer patients.MethodsThe PubMed, Embase, Chinese National Knowledge Infrastructure and Chinese Biology Medicine databases were electronically searched to retrieve published studies on caveolin-1 expression in prostate cancer. After study selection and data extraction, the meta-analysis was conducted using Review manager 5.3 software. Odds ratio (OR) with 95% confidence interval (CI) was used to estimate the pooled effect. Funnel plot was used to assess publication bias.ResultsA total of ten studies were enrolled, which included 3976 cases of prostate cancer, 72 cases of high-grade intraepithelial neoplasia (HGPIN), and 157 normal controls. Results of the meta-analysis showed that the positive rate of caveolin-1 expression in prostate cancer was 18.28 times higher than that in normal control (OR= 18.28, 95% CI: 9.02–37.04, p10 vs. ≤ 10 (OR=2.09, 95% CI: 1.35–3.22, p

The global spread of the novel coronavirus SARS-CoV-2 urgently requires discovery of effective therapeutics for the treatment of COVID-19. The spike (S) protein of SARS-CoV-2 plays a key role in receptor recognition, virus-cell membrane fusion and virus entry. Our previous studies have reported that 3-hydroxyphthalic anhydride-modified chicken ovalbumin (HP-OVA) serves as a viral entry inhibitor to prevent several kinds of virus infection. Here, our results reveal that HP-OVA can effectively inhibit SARS-CoV-2 replication and S protein-mediated cell-cell fusion in a dose-dependent manner without obvious cytopathic effects. Further analysis suggests that HP-OVA can bind to both the S protein of SARS-CoV-2 and host angiotensin-converting enzyme 2 (ACE2), the functional receptor of SARS-CoV-2, and disrupt the S protein-ACE2 interaction, thereby exhibiting inhibitory activity against SARS-CoV-2 infection. In summary, our findings suggest that HP-OVA can serve as a potential therapeutic agent for the treatment of deadly COVID-19.

Shi-Zhen-An-Shen decoction (SZASD), a Chinese herbal medicine that is a liquor extracted from plants by boiling, has been reported to be effective in treating schizophrenia. However, the mechanism is unclear. Abnormal demyelination has been implicated in schizophrenia. The aim of this study was to investigate the effect of SZASD on myelin in demyelinated mice exhibiting schizophrenia-like behaviors. Sixty male C57BL/6 mice were randomly divided into six groups (n=10 per group): (1) control group, (2) cuprizone (CPZ, a copper chelator that induced demyelination, 0.2% w/w)+saline, (3) CPZ+low-dose SZASD (8.65 g·kg-1·d-1), (4) CPZ+medium-dose SZASD (17.29 g·kg-1·d-1), (5) CPZ+high-dose SZASD (25.94 g·kg-1·d-1), and (6) CPZ+quetiapine (QTP, an atypical antipsychotic that served as a positive treatment control, 10 mg·kg-1·d-1). Mice in groups 2-6 were treated with CPZ added to rodent chow for six weeks to induce demyelination. During the last two weeks, these mice were given an oral gavage of sterile saline, SZASD, or quetiapine. Behavioral tests and brain analyses were conducted after the last treatment. The brain expression of myelin basic protein (MBP) and neuregulin-1 (NRG-1) was assessed using immunohistochemistry and Western blots. CPZ induced significant schizophrenia-like behaviors in the mice, including reduced nest-building activity and sensory gating deficits. Hyperlocomotor activity was accompanied by significant reductions in MBP expression in the corpus callosum, hippocampus, and cerebral cortex. However, both QTP and SZASD significantly reversed the schizophrenia-like behaviors and demyelination in CPZ-fed mice. The QTP and medium-dose SZASD resulted in better therapeutic effects compared to the low and high SZASD doses. Reduced NRG-1 expression was observed in CPZ-fed mice compared with controls, but neither QTP nor SZASD showed significant influence on NRG-1 expression in the hippocampus. Together, SZASD showed a therapeutic effect on demyelinated mice, and the improvement of demyelination might not be through the NRG-1 pathway.

The health problems caused by the frequent relapse of papillary thyroid carcinoma (PTC) remain a worldwide concern since the morbidity rate of PTC ranks the highest among thyroid cancers. Residues from contralateral central lymph node metastases (con-CLNM) are the key reason for persistence or recurrence of unilateral papillary thyroid carcinoma (uni-PTC); however, the ability to assess the status of con-CLNM in uni-PTC patients is limited. To clarify the risk factors of con-CLNM, a total of 250 patients with uni-PTC who underwent total thyroidectomy and bilateral central lymph node dissection were recruited in this study. We compared the clinical, sonographic, and pathological characteristics of patients with con-CLNM to those without con-CLNM and established a nomogram for con-CLNM in uni-PTC. We found that male sex, without Hashimoto’s thyroiditis, present capsular invasion, with ipsilateral lateral lymph node metastases, and the ratio of ipsilateral central lymph node metastases ≥0.16 were independent con-CLNM predictors of uni-PTC (ORs: 2.797, 0.430, 2.538, 2.202, and 26.588; 95% CIs: 1.182–6.617, 0.211–0.876, 1.223–5.267, 1.064–4.557, and 7.596–93.069, respectively). Additionally, a preoperative nomogram for the prediction of con-CLNM based on these risk factors showed good discrimination (C-index 0.881; 95% CI: 0.840–0.923; sensitivity 85.3%; specificity 76.0%) and good agreement via the calibration plot. Our study provided a way to quantitatively and accurately predict whether con-CLNM occurred in patients with uni-PTC, which may guide surgeons to evaluate the nodal status and perform tailored therapeutic central lymph node dissection.

In this paper, the enhanced photonic spin hall effect (PSHE) of reflected light at terahertz (THz) frequencies is achieved by using a multilayer structure consisting of Bi2Se3, spacer layer, and distributed Bragg reflector structure. This enhanced spin hall effect (SHE) phenomenon originates from the excitation of optical Tamm states (OTSs) at the interface between the Bi2Se3 and distributed Bragg reflector structure. It is found that the PSHE of the reflected light can be flexibly controlled by properly varying the Fermi energy of the topological insulators. Moreover, the spin behavior of the composite structure is also proved sensitive to incidence angle and the dispersion characteristics of the spacer layer, thus making this configuration an effective candidate for developing photonic devices based on photonic PSHE at the terahertz range.

The intrusive rock buried-hill reservoir is one of the main targets for oil and gas exploration in the offshore sedimentary basins of China. In order to discover the reservoir as early as possible for decision-making to save costs, reservoir interpretation with mud-logging data needs to be studied. Previous studies have showed that the homogeneity rocks reservoir can be well interpreted with mud-logging data u the Kb (mechanical specific energy ratio) method and the WL (tangential power)-WH (vertical power) intersection method. However, reservoir interpretation with mud-logging data for intrusive rock buried-hill has not been reported. The key steps or parameters of these two kinds of methods used for reservoir interpretation need to be modified for the vertical variation of intrusive rock buried-hill. Furthermore, confirming the interpretation of these two kinds of methods has not been reported. Taking the Y area in the Qiongdongnan Basin of the South China Sea as an example, the intrusive rock buried-hill can be divided into four zones based on its characteristics and genesis in descending order: the sand–gravel weathering zone, the weathering fracture zone, the inner fracture zone, and the base rock zone. The reservoir can be well interpreted when taking the MSE (mechanical specific energy) geometrical mean of the base rock zone as a basic value to calculate Kb. The reservoir will also be well interpreted when WH ranges from 0 to 4.5 MPa and WL ranges from 0 to 99 MPa in the column while intersecting. The layers of the reservoir can be interpreted as Kb < 1 in the sand–gravel weathering zone and the weathering fracture zone. The Kb < 1 and effective intersection of WL-WH layers at the same time could be interpreted as a reservoir in the inner fracture zone and the base rock zone. After combining the Kb method with the WL-WH intersection method, the reservoir of intrusive rock buried-hill can be well interpreted. The total thickness of the uninterpretable reservoir ratio is less than 20% compared to reservoir interpretation with well-logging for each well.

The effect of stylolite caused by the pressure dissolution process on the reservoir petro-physical properties is still controversial. This study aims to reveal the effect of stylolite on the porosity and permeability of packstone and wackestone in the Mishrif Formation from the Ah oilfield in the Middle East. Based on the observation of thin sections and cores, X-ray diffraction analysis and porosity and permeability measurement, the lithofacies, diagenesis and patterns of stylolites have been investigated. There are six lithofacies in the Mi4 member, including bivalve green algae packstone, green algae packstone, pelletoid green algae packstone, echinoderm packstone, rudist packstone, planktonic foraminifera wackestone and bioclastic wackestone. The mechanical compaction and pressure dissolution could be observed in these lithofacies, with the development of dissolution seams and stylolites. The density of stylolite has a relationship with the lithofacies and early cementation. The boundary between the echinoderm packstone and the green algae packstone mostly developed as stylolites. There are four types of stylolite on the cores. Type A is the wave-like stylolite developed at the boundary between the echinoderm packstones and green algae packstones. Type B is the zigzag stylolite with high amplitude in the green algae packstones. Type C is the stylolites with low amplitude in the bioclastic wackestones. Type D is the high-angle stylolite, which is oblique to the bedding plane. The permeability of reservoir rocks could be improved by dissolution along the type B stylolite, while the type A and type C stylolite have little effect on permeability. The permeability of green algae packstone and echinoderm packstone will decrease with the development of stylolites. The porosity and permeability of bivalve green algae packstone will decrease after stylolitization, resulting from the relatively high density of stylolite. The physical properties of bioclastic wackestone could be improved by the bioturbation and formation of stylolite. According to the analysis of production performance in the same lithofacies, the occurrence of stylolites could result in the development of oil baffles. This study could be extended to evaluate the effect of stylolite in carbonate reservoir rocks.

An 8-week feeding trial was conducted to investigate the effects of high-starch diets and the supplementation of an olive extract (OE) on the growth performance, liver health and lipid metabolism of largemouth bass (Micropterus salmoides). Four isonitrogenous and isolipidic diets were prepared: two basal diets containing low (9.0%) and high (14.4%) levels of starch (named as LS and HS), and 0.125% OE was supplemented to each basal diet (named LSOE and HSOE). The results show that high-starch diets had significant negative effects on growth performance, with lower FR, SGR and higher FCR, whereas OE significantly lowered FCR, determined by two-way ANOVA analysis. High-starch diets induced oxidative stress, inflammatory response and liver function injury, with significant increases in the content of plasmatic AKP, AST, ALT, hepatic SOD and MDA, and up-regulation of hepatic TNFα, IL1β, and TGFβ1 gene expression. In addition, a high-starch diet decreased the phosphorylation of AMPK and upregulated the expression of SREBP, together with higher hepatic liver lipid and HSI. The oxidative stress and lipid metabolism disorders indicate metabolic liver disease (MLD) of largemouth bass fed high-starch diets. Feeding on OE-supplemented diets increased the hepatic antioxidant capacity by decreasing the content of MDA and SOD. Fish fed the HSOE diet had an activated phosphorylation of JNK and decreased expression of pro-inflammatory IL1β compared with those fed the HS diet, which strongly indicated that the degree of inflammatory responses was reduced after OE supplementation. Interestingly, this study demonstrated that OE regulates hepatic lipid metabolism in fish by inhibiting the expression of hepatic lipogenesis genes (ACC1 and FASN) and promoting lipolysis (ATGL) and β-oxidation (CPT1α) to prevent TG accumulation. In conclusion, high-starch feed induced oxidative stress and lipid metabolic disorder of largemouth bass, while supplementation with OE improved its antioxidant capacity, anti-inflammatory responses and lipid metabolism. However, hepatic histopathological results suggested that OE supplementation could not completely repair the MLD caused by the high level of starch in largemouth bass.

Motivated by the exciting properties of metal halide perovskites in photovoltaic applications, there is an evolving need to further explore the limitations of this class of materials in broader fields and high end optoelectronics, which requires better control over the film structure, defect levels, and quality. Epitaxial growth has been ubiquitously deployed in the semiconducting industry. This affords routes to precisely align the atomic arrangement to control the structure and strain and achieve the highest levels of optoelectronic performance. In this review, the recent emergence and progress in the epitaxial growth of metal halide perovskites are introduced within the context of epitaxial and quasiepitaxial approaches, and recent advances are surveyed from growth methods to application integration. The main criteria distinguishing epitaxy and quasiepitaxy, i.e., lattice matching and ordering, can be deployed to direct the selection of proper substrates, growth methods, and precursors for various applications.

Research has demonstrated a robust positive association between cyberbullying victimization and adolescent drinking behavior; however, the mediating and moderating mechanisms underlying this relationship remain largely unexplored. Grounded in the social development model and person-environment interactions model, our study explored whether deviant peer affiliation mediated the relationship between cyberbullying victimization and adolescent drinking behavior and whether this mediating effect was moderated by personal growth initiative. A sample of 1,006 adolescents (Mage = 13.16 years; SD = 0.67) anonymously completed self-report questionnaires. Structural equation modeling indicated that the positive association between cyberbullying victimization and drinking behavior was partly mediated by deviant peer affiliation for both girls and boys. Further, this mediating process was stronger for adolescents with low personal growth initiative than for those with high personal growth initiative. There were no significant gender differences for this moderating effect. These findings underline the importance of deviant peer affiliation and personal growth initiative in understanding how and when cyberbullying victimization impacts adolescent drinking behavior.

Ocular inflammation is a common pathological condition of a series of retinal degenerative diseases. Tetramethylpyrazine (TMP), a Chinese herbal extraction, is widely used in the treatment of several ocular diseases in Eastern countries. However, the exact mechanisms correlating the vision protective effects of TMP have not been elucidated. Thus, this study aimed to investigate TMP’s molecular targets in anti-inflammatory activity in endotoxin lipopolysaccharide (LPS)-induced retinal inflammation both in vitro and in vivo. The primary cultured retinal microglial cells were pretreated with TMP and then activated by LPS. We found pretreatment with TMP significantly inhibited LPS-induced upregulation of CD68, a marker of mononuclear microglia activation. The morphological changes induced by LPS were also inhibited by the TMP pretreatment. Moreover, Toll like receptor 4 (TLR4), phosphorylation of inhibitor of NF-κB alpha (p-IκB-α) and the translocation of nuclear factor kappa B p65 (NF-κB p65) were significantly downregulated in retinal microglial cells with TMP pretreatment, which indicated that TMP might suppress LPS-induced retinal microglial activation through TLR4/NF-κB signalling pathway. And these results were confirmed in vivo. Pretreatment with TMP inhibited microglial activation, migration and regeneration, especially in ganglion cell layer (GCL). In addition to the inhibition of TLR4, TMP significantly inhibited the translocation of NF-κB p-65 to the nucleus in vivo. The downstream genes of NF-κB, such as the pro-inflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β), were significantly downregulated by TMP pretreatment in the retina. Accordingly, the increased expression of cleaved caspase-3 and the decreased ratio of B-cell lymphoma-2 (Bcl-2) to Bcl-2 associated X Protein (Bax) were significantly attenuated by TMP. TUNEL assay also demonstrated that TMP exerted neuroprotective effects in the retina. Therefore, this study elucidated a novel mechanism that TMP inhibits retinal inflammation by inhibiting microglial activation via a TLR4/NF-κB signalling pathway.

BackgroundNumerous studies have confirmed that long-term shift work is not only associated with increased health problems and acute impact on safety but also with impaired cognitive abilities. However, very little is known about effects of shift work on cognition-related brain resting-state networks. The aim of this study was to explore the effects of shift work disorder (SWD) on granger causality connection among resting-state brain networks.MethodsThirty patients with SWD and 25 matched healthy subjects were recruited to undergo the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and resting-state fMRI scanning. We employed independent component analysis (ICA) to extract resting-state brain networks and granger causality analysis (GCA) to characterize the difference of granger causality connection among cognition-related resting-state brain networks.ResultsCompared with healthy subjects, patients with SWD showed impairments on the attention and immediate memory. Seven resting-state brain networks were identified, and patients with SWD showed more numerous granger causality connections in comparison with healthy subjects. Two-sample t test results showed that there were significantly increased inflows from the anterior default mode network (aDMN) to sensorimotor network (SMN) and left frontoparietal network (LFPN) to salience network (SN). Correlation analyses showed that the increased inflows from aDMN to SMN were negatively associated with the score of attention, while LFPN to SN were negatively associated with the score of visuospatial/constructional ability.ConclusionsThis study indicates that SWD impairs cognitive performance, and the specific intrinsic brain granger causality connectivity among resting-state networks in SWD patients is affected after long-term shift works.

The influenza pandemic causes a large number of hospitalizations and even deaths. There is an urgent need for an efficient and effective method for detecting the outbreak of influenza so that timely, appropriate interventions can be made to prevent or at least prepare for catastrophic epidemics. In this study, we proposed a computational method, the shortest-path-based dynamical network marker (SP-DNM), to detect the pre-outbreak state of influenza epidemics by monitoring the dynamical change of the shortest path in a city network. Specifically, by mapping the real-time information to a properly constructed city network, our method detects the early-warning signal prior to the influenza outbreak in both Tokyo and Hokkaido for consecutive 9 years, which demonstrate the effectiveness and robustness of the proposed method.

Ensemble local mean decomposition has been gradually introduced into mechanical vibration signal processing due to its excellent performance in electroencephalogram signal analysis. However, an unsatisfactory problem is that ensemble local mean decomposition cannot effectively process vibration signals of complex mechanical system due to the constraints of moving average. The process of moving average is time-consuming and inaccurate in complex signal analysis. Therefore, an improved ensemble local mean decomposition method called C-ELMD with modified envelope algorithm based on cubic trigonometric cardinal spline interpolation is proposed in this article. First, the shortcomings in sifting process of ensemble local mean decomposition is discussed and, furthermore, advantages and disadvantages of the common interpolation methods adopted to improve ensemble local mean decomposition are compared. Then, cubic trigonometric cardinal spline interpolation is employed to construct the local mean and envelope curves in a more precise way. In addition, the influence of shape-controlling parameter on envelope estimation accuracy in cubic trigonometric cardinal spline interpolation is also discussed in detail to select an optimal shape-controlling parameter. The effectiveness of cubic trigonometric cardinal spline interpolation for improving the accuracy of ensemble local mean decomposition is demonstrated using a synthetic signal. Finally, the proposed cubic trigonometric cardinal spline interpolation is tested to be effective in gear and bearing fault detection and diagnosis.

BACKGROUND:As the country with the largest aging population, China faces an enormous challenge with its elderly support and care. One of the proposed solutions is the development of volunteerism for elderly care. The Senior Care Volunteers Training Program (SCVTP) was initiated by the Red Cross Society of China with the purpose of training volunteers to care for community seniors. As one of the four pilot provinces, Jiangsu Province launched the program since 2017. AIMS:The present study was conducted to investigate the dropout rate of trained volunteer group leaders, the characteristics of the retained trained volunteer group leaders and the activities that their groups conducted. Additionally, the exploration of the factors influencing the SCVTP's performance was listed as another aim. METHODS:A cross-sectional study was designed. The study used purposive sampling to select participants who meet the criteria from all the trained volunteer group leaders (n = 623). Demographic questionnaire, volunteer role identity (VRI) scale, attitude toward helping others (AHO) scale, team climate and atmosphere (TCA) scale, and volunteer program performance evaluation (VPPE) questionnaire were used to collect the data online. Descriptive statistics were used to determine the dropout rate and general characteristics of the retained volunteers and the activities. A multiple linear regression equation was developed to study the factors that influence program performance. RESULTS:In total, 307 questionnaires were valid in the study. About 67.9%, 53.7%, and 30.0% of the trained volunteer group leaders dropped out of the program in the year of 2017, 2018, and 2019, respectively. The retained trained volunteer group leaders were more likely to be females (84.7%), those in excellent health (75.2%) and with a bachelor's degree or above (87.6%). Less attention has been paid to frailty care (n = 76) than other volunteer caring activities (e.g., safe care: n = 277, diet care: n = 250, drug management care: n = 226). VRI (β = 0.118, p = 0.017), AHO (β = 0.134, p = 0.021), TCA (β = 0.459, p