The non-cell-autonomous function of ID1 promotes AML progression via ANGPTL7 from the microenvironment.

The bone marrow microenvironment (BMM) can regulate leukemia stem cells (LSCs) via secreted factors. Increasing evidence suggests that dissecting the mechanisms by which the BMM maintains LSCs may lead to the development of effective therapies for the eradication of leukemia. Inhibitor of DNA binding 1 (ID1), a key transcriptional regulator in LSCs, previously identified by us, controls cytokine production in the BMM, but the role of ID1 in acute myeloid leukemia (AML) BMM remains obscure. Here, we report that ID1 is highly expressed in the BMM of patients with AML, especially in BM mesenchymal stem cells, and that the high expression of ID1 in the AML BMM is induced by BMP6, secreted from AML cells. Knocking out ID1 in mesenchymal cells significantly suppresses the proliferation of cocultured AML cells. Loss of Id1 in the BMM results in impaired AML progression in AML mouse models. Mechanistically, we found that Id1 deficiency significantly reduces SP1 protein levels in mesenchymal cells cocultured with AML cells. Using ID1-interactome analysis, we found that ID1 interacts with RNF4, an E3 ubiquitin ligase, and causes a decrease in SP1 ubiquitination. Disrupting the ID1-RNF4 interaction via truncation in mesenchymal cells significantly reduces SP1 protein levels and delays AML cell proliferation. We identify that the target of Sp1, Angptl7, is the primary differentially expression protein factor in Id1-deficient BM supernatant fluid to regulate AML progression in mice. Our study highlights the critical role of ID1 in the AML BMM and aids the development of therapeutic strategies for AML.

Development of neonatal connectome dynamics and its prediction for cognitive and language outcomes at age 2.

The functional brain connectome is highly dynamic over time. However, how brain connectome dynamics evolves during the third trimester of pregnancy and is associated with later cognitive growth remains unknown. Here, we use resting-state functional Magnetic Resonance Imaging (MRI) data from 39 newborns aged 32 to 42 postmenstrual weeks to investigate the maturation process of connectome dynamics and its role in predicting neurocognitive outcomes at 2 years of age. Neonatal brain dynamics is assessed using a multilayer network model. Network dynamics decreases globally but increases in both modularity and diversity with development. Regionally, module switching decreases with development primarily in the lateral precentral gyrus, medial temporal lobe, and subcortical areas, with a higher growth rate in primary regions than in association regions. Support vector regression reveals that neonatal connectome dynamics is predictive of individual cognitive and language abilities at 2  years of age. Our findings highlight network-level neural substrates underlying early cognitive development.

Causal association of blood lipids with all-cause and cause-specific mortality risk: a Mendelian randomization study.

Dyslipidemia has long been implicated in elevating mortality risk; yet, the precise associations between lipid traits and mortality remained undisclosed. Our study aimed to explore the causal effects of lipid traits on both all-cause and cause-specific mortality. One-sample Mendelian randomization (MR) with linear and nonlinear assumptions was conducted in a cohort of 407,951 European participants from the UK Biobank. Six lipid traits, consisting of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), and lipoprotein(a), were included to investigate the causal associations with mortality. Two-sample MR was performed to replicate the association between each lipid trait and all-cause mortality. Univariable MR results showed that genetically predicted higher ApoA1 was significantly associated with a decreased all-cause mortality risk (HR[95% CI]:0.93 [0.89-0.97], P value = 0.001), which was validated by the two-sample MR analysis. Higher lipoprotein(a) was associated with an increased risk of all-cause mortality (1.03 [1.01-1.04], P value = 0.002). Multivariable MR confirmed the direct causal effects of ApoA1 and lipoprotein(a) on all-cause mortality. Meanwhile, nonlinear MR found no evidence for nonlinearity between lipids and all-cause mortality. Our examination into cause-specific mortality revealed a suggestive inverse association between ApoA1 and cancer mortality, a significant positive association between lipoprotein(a) and cardiovascular disease mortality, and a suggestive positive association between lipoprotein(a) and digestive disease mortality. High LDL-C was associated with an increased risk of cardiovascular disease mortality but a decreased risk of neurodegenerative disease mortality. The findings suggest that implementing interventions to raise ApoA1 and decrease lipoprotein(a) levels may improve overall health outcomes and mitigate cancer and digestive disease mortality.

SALL4 in gastrointestinal tract cancers: upstream and downstream regulatory mechanisms.

Effective therapeutic targets and early diagnosis are major challenges in the treatment of gastrointestinal tract (GIT) cancers. SALL4 is a well-known transcription factor that is involved in organogenesis during embryonic development. Previous studies have revealed that SALL4 regulates cell proliferation, survival, and migration and maintains stem cell function in mature cells. Additionally, SALL4 overexpression is associated with tumorigenesis. Despite its characterization as a biomarker in various cancers, the role of SALL4 in GIT cancers and the underlying mechanisms are unclear. We describe the functions of SALL4 in GIT cancers and discuss its upstream/downstream genes and pathways associated with each cancer. We also consider the possibility of targeting these genes or pathways as potential therapeutic options for GIT cancers.

Cell-Based Micro/Nano-Robots for Biomedical Applications: A Review.

Micro/nano-robots are powerful tools for biomedical applications and are applied in disease diagnosis, tumor imaging, drug delivery, and targeted therapy. Among the various types of micro-robots, cell-based micro-robots exhibit unique properties because of their different cell sources. In combination with various actuation methods, particularly externally propelled methods, cell-based microrobots have enormous potential for biomedical applications. This review introduces recent progress and applications of cell-based micro/nano-robots. Different actuation methods for micro/nano-robots are summarized, and cell-based micro-robots with different cell templates are introduced. Furthermore, the review focuses on the combination of cell-based micro/nano-robots with precise control using different external fields. Potential challenges, further prospects, and clinical translations are also discussed.

Optoelectronic Tweezers Micro-Well System for Highly Efficient Single-Cell Trapping, Dynamic Sorting, and Retrieval.

Single-cell arrays have emerged as a versatile method for executing single-cell manipulations across an array of biological applications. In this paper, an innovative microfluidic platform is unveiled that utilizes optoelectronic tweezers (OETs) to array and sort individual cells at a flow rate of 20 µL min-1. This platform is also adept at executing dielectrophoresis (DEP)-based, light-guided single-cell retrievals from designated micro-wells. This presents a compelling non-contact method for the rapid and straightforward sorting of cells that are hard to distinguish. Within this system, cells are individually confined to micro-wells, achieving an impressive high single-cell capture rate exceeding 91.9%. The roles of illuminating patterns, flow velocities, and applied electrical voltages are delved into in enhancing the single-cell capture rate. By integrating the OET system with the micro-well arrays, the device showcases adaptability and a plethora of functions. It can concurrently trap and segregate specific cells, guided by their dielectric signatures. Experimental results, derived from a mixed sample of HepG2 and L-O2 cells, reveal a sorting accuracy for L-O2 cells surpassing 91%. Fluorescence markers allow for the identification of sequestered, fluorescence-tagged HepG2 cells, which can subsequently be selectively released within the chip. This platform's rapidity in capturing and releasing individual cells augments its potential for future biological research and applications.

Immune features revealed by single-cell RNA and single-cell TCR/BCR sequencing in patients with rheumatoid arthritis receiving COVID-19 booster vaccination.

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, have profoundly affected human health. Booster COVID-19 vaccines have demonstrated significant efficacy in reducing infection and severe cases. However, the effects of booster COVID-19 vaccines on key immune cell subsets and their responses in rheumatoid arthritis (RA) are not well understood. By using single-cell RNA sequencing (scRNA-seq) combined with scTCR/BCR-seq analysis, a total of 8 major and 27 minor cell clusters were identified from paired peripheral blood mononuclear cells (PBMCs) which were collected 1 week before and 4 weeks after booster vaccination in stable RA patients. Booster vaccination only had limited impact on the composition and proportions of PBMCs cell clusters. CD8+ cytotoxic T cells (CD8+T_CTL) showed a trend toward an increase after vaccination, while naive B cells and conventional dendritic cells (cDCs) showed a trend toward a decrease. Transcriptomic changes were observed after booster vaccination, primarily involving T/B cell receptor signaling pathways, phagosome, antigen processing and presenting, and viral myocarditis pathways. Interferon (IFN) and pro-inflammatory response gene sets were slightly upregulated across most major cell subpopulations in COVID-19 booster-vaccinated RA individuals. Plasma neutralizing antibody titers significantly increased after booster COVID-19 vaccination (p = 0.037). Single-cell TCR/BCR analysis revealed increased B cell clone expansion and repertoire diversity postvaccination, with no consistent alterations in T cells. Several clonotypes of BCRs and TCRs were identified to be significantly over-represented after vaccination, such as IGHV3-15 and TRBV28. Our study provided a comprehensive single-cell atlas of the peripheral immune response and TCR/BCR immune repertoire profiles to inactivated SARS-CoV-2 booster vaccination in RA patients, which helps us to understand vaccine-induced immune responses better.

[68Ga]Pentixafor PET/CT for staging and prognostic assessment of newly diagnosed multiple myeloma: comparison to [18F]FDG PET/CT.

PURPOSE: To evaluate the prognostic performance of [68Ga]Pentixafor PET/CT at baseline for staging of patients with newly diagnosed multiple myeloma (MM) and to compare it with [18F]FDG PET/CT and the Revised-International Staging System (R-ISS). METHODS: Patients who underwent [68Ga]Pentixafor and [18F]FDG PET/CT imaging were retrospectively included. Patient staging was performed according to the Durie-Salmon PLUS staging system based on [68Ga]Pentixafor PET/CT and [18F]FDG PET/CT images, and the R-ISS. Progression-free survival (PFS) at patient follow-up was estimated using the Kaplan-Meier estimator and compared using the log-rank test. Area under the receiver operating characteristic curve (AUC) was calculated to assess predictive performance. RESULTS: Fifty-five MM patients were evaluated. Compared with [18F]FDG PET, [68Ga]Pentixafor PET detected 25 patients as the same stage, while 26 patients were upstaged and 4 patients were downstaged (P = 0.001). After considering the low-dose CT data, there was no statistically significant difference in the number of patients classified in each stage using [68Ga]Pentixafor PET/CT and [18F]FDG PET/CT (P = 0.091). [68Ga]Pentixafor PET/CT-based staging discriminated PFS outcomes in patients with different disease stages (stage I vs. stage II, stage I vs. stage III, and stage II vs. stage III; all P < 0.05), whereas for [18F]FDG PET/CT, there was only a difference in median PFS between stage I and III (P = 0.021). When staged by R-ISS, the median PFS for stage III was significantly lower than that for stage I and II (P = 0.008 and 0.035, respectively). When predicting 2-year PFS based on staging, the AUC of [68Ga]Pentixafor PET/CT was significantly higher than that of [68Ga]Pentixafor PET (0.923 vs. 0.821, P = 0.002), [18F]FDG PET (0.923 vs. 0.752 P = 0.002), and R-ISS (0.923 vs. 0.776, P = 0.005). CONCLUSIONS: [68Ga]Pentixafor PET/CT-based staging possesses substantial potential to predict disease progression in newly diagnosed MM patients.

[68Ga]Ga­LNC1007 PET/CT in the evaluation of renal cell carcinoma: comparison with 2-[18F]FDG/[68Ga]Ga-PSMA PET/CT.

PURPOSE: To compare the potential efficiency of [68Ga]Ga-LNC1007 with 2-[18F]FDG/[68Ga]Ga-PSMA PET/CT for detecting renal cell carcinoma (RCC) and to explore parameters derived from [68Ga]Ga-LNC1007 PET/CT for discriminating pathological characteristics in RCC. METHODS: Twenty-five RCC patients confirmed by pathology were enrolled in this prospective study. The maximum standardized uptake value (SUVmax), mean SUV (SUVmean), gross tumor volume (GTV) and total lesion-tracer (TL-tracer) of lesions were calculated from the corresponding PET/CT images. Pathological characteristics included World Health Organization/International Society of Urological Pathology (WHO/ISUP) grade and adverse pathological features (tumor necrosis or sarcomatoid or rhabdoid feature). RESULTS: [68Ga]Ga-LNC1007 PET/CT showed a higher detection rate for primary lesions than 2-[18F]FDG and [68Ga]Ga-PSMA (LNC1007 vs. FDG: 13/17 vs. 4/17, P = 0.005; LNC1007 vs. PSMA: 9/11 vs. 6/11, P = 0.361). [68Ga]Ga-LNC1007 PET/CT showed higher SUVmax (6.6 vs. 3.7, P = 0.005), SUVmean (4.1 vs. 2.3, P = 0.001) and TBR (2.6 vs. 1.7, P = 0.011) compared with 2-[18F]FDG PET/CT, and it also showed higher TBR (2.9 vs. 0.5, P = 0.003), TBR-delay (2.8 vs. 0.3, P = 0.003), GTV (84.1 vs. 42.9, P = 0.003) and TL-tracer (442.7 vs. 235.8, P = 0.008) compared with [68Ga]Ga-PSMA PET/CT. SUVmax and TBR derived from [68Ga]Ga-LNC1007 PET/CT could effectively differentiate WHO/ISUP grade (3-4 vs. 1-2) and adverse pathological features (positive vs. negative) (SUVmax: AUC 0.81, P = 0.04; AUC 0.80, P = 0.033; TBR: AUC 0.84, P = 0.026; AUC 0.85, P = 0.014). The SUVmax was positively correlated with the FAP expression, integrin αvß3 expression and the total expression of FAP and integrin αvß3 (r = 0.577, P = 0.006, r = 0.701, P < 0.001, and r = 0.702, P < 0.001, respectively). CONCLUSION: [68Ga]Ga-LNC1007 is a promising tracer for RCC imaging and can effectively identify aggressive pathological characteristics of RCC.

A 12-Vertex Metallacarborane of Silver(I).

The discovery of ferrocene in 1951 was a significant landmark in the field of organometallic chemistry, and since then, numerous sandwich- or half-sandwich metallic complexes have been reported. However, silver stands as an intriguing exception in this regard, and knowledge of its bonding situation has remained undisclosed. Herein, unprecedented 12-vertex metallacarboranes of Ag(I) (2a and 2b) were synthesized through the reaction of sodium hexamethyldisilazide (NaHMDS) with the mixture of nido-C2B9 carborane anion-supported N-heterocyclic carbene precursors (1a and 1b) and [Ag(PPh3)Cl]4. The X-ray structural analysis of the resulting metallacarboranes revealed a unique "slipped" half-sandwich structure, which is a rarity among cyclopentadienyl analogues. DFT calculations provided insights into the asymmetric π-interactions between the pentagonal C2B3 face and the silver ion.

Protective effect of small extracellular vesicles (EVs) derived from ACE2-modified human umbilical cord mesenchymal stem cells against renal ischemia-reperfusion injury.

AIM: Acute kidney injury is a severe disease that is closely associated with substantial morbidity and mortality. The most common cause of AKI is renal ischemia-reperfusion injury. Mesenchymal stem cells (MSCs) have previously been shown to have renoprotective effects. However, extracellular vesicles secreted by MSCs are thought to be the key for the therapeutic effects of MSCs. This study investigated whether small EVs derived from ACE2-modified human umbilical cord MSCs could alleviate RIRI and explored their underlying molecular mechanisms METHODS: A lentivirus carrying an ACE2 overexpression vector was constructed and used to infect MSCs. The small EVs were isolated from MSC-conditioned medium by ultracentrifugation. HK-2 cells were cocultured with MSC-ACE2-EVs and subjected to hypoxia/reoxygenation injury. MSCs-ACE2-EVs were injected into RIRI mice. Biochemical and morphological characteristics were assessed, and the levels of inflammatory-related factors, oxidative stress products, and apoptosis in HK-2 cells and kidney tissues were assessed RESULTS: In vitro, MSC-ACE2-EVs had stronger anti-inflammatory, antioxidative stress, and antiapoptotic effects in HK-2 cells subjected to H/R than MSC-NC-EVs. In vivo, MSC-ACE2-EVs could target the injured kidney, reduce blood creatinine and urea nitrogen levels, and protect the kidney from I/R, and this effect may have been related to the activation of the Nrf2/HO-1 signalling pathway CONCLUSION: Taken together, our results demonstrated the anti-inflammatory, antioxidative stress, and antiapoptotic effects of MSC-ACE2-EVs, which protected against I/R injury in vitro and vivo. MSC-ACE2-EVs may be therapeutic agents for RIRI.

Community-dwelling older adults' perspectives on health risks: a qualitative study exploring anxieties, priorities, and expectations in ageing.

BACKGROUND: With the conflict between the promise of ageing in health and longevity and the limited availability of health resources and social support, older adults in China inevitably experience anxieties surrounding health risks. This study aims to investigate how older adults perceive the health risks that come with getting older, explore the degree to which health risks affect older adults, and advocate for active engagement in practices for managing health risks. METHODS: Using purposive sampling, three districts of Beijing (Xicheng District, Fengtai District, and Daxing District, respectively) were selected for the research. Qualitative semi-structured and in-depth interviews were conducted with 70 community-dwelling older adults who participated in the study. Data were extracted and analyzed based on a thematic framework approach. RESULTS: Three main themes were identified: (i) the anxieties of older adults concerning health risks in ageing; (ii) the priorities of older adults for health risk management in ageing; (iii) the expectations of older adults for health risk management in ageing. The primary health concerns among older adults included disease incidence and function decline. It was found that basic health management emerged as a critical need for older adults to mitigate health risks. Moreover, it was observed that healthcare support for older adults from familial, institutional, and governmental levels exhibited varying degrees of inadequacy. CONCLUSIONS: The primary source of anxieties among older adults regarding health risks predominantly stems from a perceived sense of health deprivation. It is often compounded by persistent barriers to primary care of priorities in managing health risks among older adults. In addition, the expectations of older adults for health risk management emphasize the necessity for integrated care approaches. Therefore, further research should give priority to the prevention and management of health risks, aim to reduce anxieties, provide integrated care to meet the primary needs and expectations of older adults, and ultimately strive toward the overarching goal of promoting health and longevity.

Comprehensive identification of pathogenic microbes and antimicrobial resistance genes in food products using nanopore sequencing-based metagenomics.

Foodborne pathogens, particularly antimicrobial-resistant (AMR) bacteria, remain a significant threat to global health. Given the limitations of conventional culture-based approaches, which are limited in scope and time-consuming, metagenomic sequencing of food products emerges as a promising solution. This method provides a fast and comprehensive way to detect the presence of pathogenic microbes and antimicrobial resistance genes (ARGs). Notably, nanopore long-read sequencing provides more accurate bacterial taxonomic classification in comparison to short-read sequencing. Here, we revealed the impact of food types and attributes (origin, retail place, and food processing methods) on microbial communities and the AMR profile using nanopore metagenomic sequencing. We analyzed a total of 260 food products, including raw meat, sashimi, and ready-to-eat (RTE) vegetables. Clostridium botulinum, Acinetobacter baumannii, and Vibrio parahaemolyticus were identified as the top three foodborne pathogens in raw meat and sashimi. Importantly, even with low pathogen abundance, higher percentages of samples containing carbapenem and cephalosporin resistance genes were identified in chicken and RTE vegetables, respectively. In parallel, our results demonstrated that fresh, peeled, and minced foods exhibited higher levels of pathogenic bacteria. In conclusion, this comprehensive study offers invaluable data that can contribute to food safety assessments and serve as a basis for quality indicators.

Transcriptome-Based Identification of Candidate Flowering-Associated Genes of Blueberry in a Plant Factory with Artificial Lighting (PFAL) under Short-Day-Length Conditions.

In blueberry (Vaccinium corymbosum L.), a perennial shrub, flower bud initiation is mediated by a short-day (SD) photoperiod and buds bloom once the chilling requirement is satisfied. A plant factory with artificial lighting (PFAL) is a planting system that can provide a stable and highly efficient growing environment for blueberry production. However, the characteristics of bud differentiation of blueberry plants inside PFAL systems are poorly understood. To better understand flower bud initiation and the flowering mechanism of blueberry in PFAL systems, the anatomical structure of apical buds under SD conditions in a PFAL system was observed using the southern highbush cultivar 'Misty' and a transcriptomic analysis was performed to identify the candidate flowering genes. The results indicated that the apical bud of 'Misty' differentiated gradually along with SD time course and swelled obviously when chilling was introduced. A total of 39.28 Gb clean data were generated, and about 20.31-24.11 Mb high-quality clean reads were assembled, yielding a total of 17370 differentially expressed genes (DEGs), of which 9637 were up-regulated and 7733 were down-regulated. Based on the functional annotation, 26 DEGs were identified including 20 flowering-related and 6 low-temperature DEGs, out of which the expressive level of four flowering-related DEGs (VcFT2, VcFPA, VcFMADS1, and VcCOP1) and two low-temperature-induced DEGs (VcTIL-1 and VcLTI 65-like) were confirmed by qRT-PCR with a good consistency with the pattern of transcriptome. Functional analysis indicated that VcFT2 was highly conserved with nuclear and cytoplasmic subcellular localization and was expressed mainly in blueberry leaf tissue. In Arabidopsis, ectopic overexpression of VcFT2 results in an early flowering phenotype, indicating that VcFT2 is a vital regulator of the SD-mediated flowering pathway in blueberry. These results contribute to the investigation of photoperiod-mediated flowering mechanisms of blueberry in PFAL systems.

3D-MASNet: 3D mixed-scale asymmetric convolutional segmentation network for 6-month-old infant brain MR images.

Precise segmentation of infant brain magnetic resonance (MR) images into gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) are essential for studying neuroanatomical hallmarks of early brain development. However, for 6-month-old infants, the extremely low-intensity contrast caused by inherent myelination hinders accurate tissue segmentation. Existing convolutional neural networks (CNNs) based segmentation models for this task generally employ single-scale symmetric convolutions, which are inefficient for encoding the isointense tissue boundaries in baby brain images. Here, we propose a 3D mixed-scale asymmetric convolutional segmentation network (3D-MASNet) framework for brain MR images of 6-month-old infants. We replaced the traditional convolutional layer of an existing to-be-trained network with a 3D mixed-scale convolution block consisting of asymmetric kernels (MixACB) during the training phase and then equivalently converted it into the original network. Five canonical CNN segmentation models were evaluated using both T1- and T2-weighted images of 23 6-month-old infants from iSeg-2019 datasets, which contained manual labels as ground truth. MixACB significantly enhanced the average accuracy of all five models and obtained the most considerable improvement in the fully convolutional network model (CC-3D-FCN) and the highest performance in the Dense U-Net model. This approach further obtained Dice coefficient accuracies of 0.931, 0.912, and 0.961 in GM, WM, and CSF, respectively, ranking first among 30 teams on the validation dataset of the iSeg-2019 Grand Challenge. Thus, the proposed 3D-MASNet can improve the accuracy of existing CNNs-based segmentation models as a plug-and-play solution that offers a promising technique for future infant brain MRI studies.

HPV16 infection promotes the malignant transformation of the esophagus and progression of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) may be correlated with HPV infection, and the mechanism underlying the ESCC formation induced by HPV16 infection remains elusive. Here, we overexpressed HPV16 E6 and E7 and coordinated the overexpression of these two genes in EPC2 and ESCC cells. We found that E7 and coordinated expression of E6 and E7 promoted the proliferation of EPC2 cells, and upregulation of shh was responsible for cell proliferation since the use of vismodegib led to the failure of organoid formation. Meanwhile, overexpression of E6 and E7 in ESCC cells promoted cell proliferation, migration, and invasion in vitro. Importantly, E6 and E7 coordinately increased the capability of tumor growth in nude mice, while vismodegib slowed the growth of tumors in NCG mice. Moreover, a series of genes and proteins changed in cell lines after overexpression of the E6 and E7 genes, the potential biological processes and pathways were systematically analyzed using a bioinformatics assay. Together, these findings suggest that the activation of the hedgehog pathway induced by HPV16 infection may initially transform basal cells in the esophagus and promote following malignant processes in ESCC cells. The application of hedgehog inhibitors may represent a therapeutic avenue for ESCC treatment.

Norovirus outbreaks in China, 2000-2018: A systematic review.

To understand epidemiological characteristics of norovirus outbreaks in China from 2000 to 2018 the literature on norovirus outbreaks was identified by searching WANFANG, CNKI, PubMed, and Web of Science databases before 31 December 2018. Statistical analyses were performed using Statistical Product Service Solutions software. RStudio1.4.1717 and ArcGIS trial version were used for plotting bar graphs and maps. A total of 419 norovirus outbreaks were reported in the 394 included articles, which occurred between June 2000 and October 2018, showing an overall increasing trend. The majority of outbreaks occurred in schools (52.28%, 218/417) and kindergartens (55/417, 13.19%). Person-to-person transmission (41.64%, 137/329) was most common, followed by food-borne transmission (75/329, 22.80%) and water-borne transmission (72/329, 21.88%). GII was the most predominant norovirus genogroup, with GII.4, GII.17 and GII.2 being the dominant genotypes in 2007-2013, 2014-2015, 2016-2017, respectively. Increased outbreaks were associated with the prevalence of new variants. Most norovirus outbreaks were reported in the southeast of the country. The number of norovirus outbreaks was positively associated with the per capita gross domestic product and the year-end resident population. Norovirus outbreaks have become an important public health problem in China. It is necessary to establish surveillance in hospitals and nursing homes. Genotyping of noroviruses is important for monitoring the circulating strains and improving the vaccine design, so it should be carried out in more regions.

Progressive Stabilization of Brain Network Dynamics during Childhood and Adolescence.

Functional brain networks require dynamic reconfiguration to support flexible cognitive function. However, the developmental principles shaping brain network dynamics remain poorly understood. Here, we report the longitudinal development of large-scale brain network dynamics during childhood and adolescence, and its connection with gene expression profiles. Using a multilayer network model, we show the temporally varying modular architecture of child brain networks, with higher network switching primarily in the association cortex and lower switching in the primary regions. This topographical profile exhibits progressive maturation, which manifests as reduced modular dynamics, particularly in the transmodal (e.g., default-mode and frontoparietal) and sensorimotor regions. These developmental refinements mediate age-related enhancements of global network segregation and are linked with the expression profiles of genes associated with the enrichment of ion transport and nucleobase-containing compound transport. These results highlight a progressive stabilization of brain dynamics, which expand our understanding of the neural mechanisms that underlie cognitive development.

School bullying and its risk and protective factors in Chinese early adolescents: A latent transition analysis.

Bullying perpetration and victimization are common and problematic occurrences during adolescence. Typically, bullying incidents involve different bullying roles. However, little is known about the developmental stability and changes in these roles. In the present study, we aimed to assess the stability and changes in bullying roles and examine risk and protective factors associated with bullying involvement. A total of 1711 Chinese early adolescents (47.4% girls, Mage = 11.99) participated in the study at two time points approximately 6 months apart. Three subgroups of bullying were identified: bully-victims, victims, and the uninvolved. In terms of stability and changes, the uninvolved were the most stable over time, while victims and bully-victims tended to become the uninvolved. Bully-victims also tended to become victims. Early adolescents with higher levels of parental psychological control and depression symptoms were more likely to be victims or bully-victims. Higher levels of depression symptoms increased the risk of transitioning from being the uninvolved or bully-victims to becoming victims. Higher levels of friendship quality were associated with higher odds of being the uninvolved or transitioning from being victims or bully-victims to becoming the uninvolved. Our findings indicate that bullying roles were relatively stable, with some changes over time. The results also highlight the important function that parental psychological control, friendship quality, and depression symptoms can play in preventing and intervening in bullying.

Internet-based cognitive behavioural therapy combined with attentional bias modification training in generalized anxiety disorder: a randomized, controlled multi-session experiment.

BACKGROUND: Although attentional bias modification training (ABM) and cognitive behavioural therapy (CBT) are two effective methods to decrease the symptoms of generalized anxiety disorders (GAD), to date, no randomized controlled trials have yet evaluated the effectiveness of an intervention combining internet-based cognitive behavioural therapy (ICBT) and ABM for adults with GAD. AIMS: This study aimed to investigate the effectiveness of an intervention combining ICBT and ABM for adults with GAD. METHOD: Sixty-three participants diagnosed with GAD were randomly assigned to the treatment group (ICBT with ABM; 31 participants) or the control group (ICBT with ABM placebo; 32 participants), and received 8 weeks of treatment and three evaluations. The CBT, ABM and ABM-placebo training were conducted via the internet. The evaluations were conducted at baseline, 8 weeks later, and 1 month later, respectively. RESULTS: Both the treatment and control groups reported significantly reduced anxiety symptoms and attentional bias, with no clear superiority of either intervention. However, the treatment group showed a greater reduction in negative automatic thoughts than the control group after treatment and at 1-month follow-up (η2 = 0.123). CONCLUSION: The results suggest that although not differing in therapeutic efficacy, the intervention combining ICBT and ABM is superior to the intervention combining ICBT and ABM-placebo in the reduction of negative automatic thoughts. ABM may be a useful augmentation of ICBT on reducing anxiety symptoms.