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Abstract Online food delivery has become a popular mode of urban food consumption in China as its underlying business mechanism, Online To Offline (O2O), gaining popularity. However, the environmental impacts of a rapidly expanding online food delivery industry and its potential to mitigate environmental burdens remained unexplored in China. Our research found that Chinese cities generated 1.67 MtCO2-equivalent (CO2e) from 13.07 billion times of deliveries in 2019, including transport and packaging. The transportation-related GHG emissions were 745 KtCO2e in 2019, with an average of 0.057 kg CO2e per order and an average of 0.011 kg CO2e per capita. These emissions have surged from 0.31 MtCO2e in 2014 to 2.74 MtCO2e in 2021. We predict that this figure will increase further to 5.94 MtCO2e by 2035. However, with a range of policies such as replacing motorcycles with electric bikes and optimizing traffic routes, it is possible to mitigate such GHG emissions by 4.39–10.97 MtCO2e between 2023 and 2035. These findings highlight the need for further research into the environmental impact of online food delivery and the potential for mitigating it.

Abstract Cancer is rarely the straightforward consequence of an abnormality in a single gene, but rather reflects a complex interplay of many genes, represented as gene modules. Here, we leverage the recent advances of model-agnostic interpretation approach and develop CGMega, an explainable and graph attention-based deep learning framework to perform cancer gene module dissection. CGMega outperforms current approaches in cancer gene prediction, and it provides a promising approach to integrate multi-omics information. We apply CGMega to breast cancer cell line and acute myeloid leukemia (AML) patients, and we uncover the high-order gene module formed by ErbB family and tumor factors NRG1, PPM1A and DLG2. We identify 396 candidate AML genes, and observe the enrichment of either known AML genes or candidate AML genes in a single gene module. We also identify patient-specific AML genes and associated gene modules. Together, these results indicate that CGMega can be used to dissect cancer gene modules, and provide high-order mechanistic insights into cancer development and heterogeneity.

Abstract Understanding the impacts of COVID-19 on citizens from different cities is crucial for urban resilience-building and reducing inequal resilience distribution. However, little research focuses on urban life at the individual level, particularly in second- and third-tier cities. An online survey was therefore conducted to collect data on how COVID-19 affected the cities and urban residents in mainland China. The results indicate that COVID-19 limited citizens’ access to healthcare facilities and socioeconomic activities apart from the immediate health crisis. Most citizens suffered reduced income, unemployment, and social anxiety. However, COVID-19 also raised social awareness and actions for disaster adaptation. The Chinese pandemic management has strengthened governmental leadership and credibility among most citizens in the early stage. Importantly, the results suggested that citizens in first-tier cities appeared more resilient to pandemics than those in second-tier cities. A networked resilience framework was therefore discussed for resilience-building policy implications.

Abstract Topologically associating domains (TADs), megabase-scale features of chromatin spatial architecture, are organized in a domain-within-domain TAD hierarchy. Within TADs, the inner and smaller subTADs not only manifest cell-to-cell variability, but also precisely regulate transcription and differentiation. Although over 20 TAD callers are able to detect TAD, their usability in biomedicine is confined by a disagreement of outputs and a limit in understanding TAD hierarchy. We compare 13 computational tools across various conditions and develop a metric to evaluate the similarity of TAD hierarchy. Although outputs of TAD hierarchy at each level vary among callers, data resolutions, sequencing depths, and matrices normalization, they are more consistent when they have a higher similarity of larger TADs. We present comprehensive benchmarking of TAD hierarchy callers and operational guidance to researchers of life science researchers. Moreover, by simulating the mixing of different types of cells, we confirm that TAD hierarchy is generated not simply from stacking Hi-C heatmaps of heterogeneous cells. Finally, we propose an air conditioner model to decipher the role of TAD hierarchy in transcription.

ABSTRACT: Objectives: Recently, blaCTX-Ms have become the dominant ESBLs for E. coli strains worldwide. We aim to provide a systematic study on the relationships between sequence types (STs), clinical origins, and the blaCTX-Ms genotypes of E. coli strains. Methods: Totally, 1005 complete sequences of clinical E. coli were collected from NCBI. Multilocus sequence typing (MLST) and antibiotic resistance genes screening were performed. Results: Faeces (26.27%), urine (16.02%), and blood (8.26%) were shown to be the main sources of clinical E. coli isolates. The isolates belong to 153 STs and 26 clonal complexes (CCs). The most prevalent STs were ST2 (11.3%), ST43 (8.6%), and ST8 (5.7%). The positive rate for blaCTX-Ms was 34.7%. Different samples showed significantly different blaCTX-Ms positive rates (P

With the improvement of urbanization and living standards, waste disposal has become an urgent environmental problem. In recent years, object detection networks based on deep learning have greatly improved classification accuracy and speed by learning feature expression and object detection through deep neural networks. However, with the increase of model depth and number of parameters, object detection models based on deep neural networks require a lot of computing and storage resources, and are difficult to deploy on edge devices. To solve this problem, this paper proposes a lightweight garbage classification object detection algorithm based on improved YOLOv7. Firstly, the DW-SPPFCSPC module is constructed according to the depth-separable volume product, replacing the original SPPCSPC module. Second, the ECA channel attention mechanism was added to the backbone of YOLOv7. By paying more attention to important feature channels, the model can better capture important information in images and thus improve the performance of target detection. Finally, the network channel is pruned by analyzing the network dependency graph. Experimental results show that the model size is greatly reduced by this method. Compared with the original YOLOv7 model, the number of parameters is reduced to 6.05% and floating-point operations (FLOPs) are reduced to 1/16 with a loss of only 0.56% in average accuracy. The method is tested on VOC and H2O data sets, and good compression results are obtained.

In existing methods, the data distribution between different domains may have large differences, which can lead to performance degradation in the target domain, and the modelling of feature variability between different domains is not sufficient. Aiming at the problem of severe performance degradation during cross-domain migration, this paper proposes a cross-domain person re-identification method based on normalized IBN-Net. The normalized IBN-Net network introduces instance normalization and batch normalization to handle the feature maps at different scales. First, this study employed the normalized IBN-Net network as the backbone of the ResNet50 network. Second, the SimAM attention mechanism is integrated into the backbone network, which is an attention mechanism for inter-modal fusion,that is mainly used in multimodal data processing tasks,and it learns the spatial attention weights in the person images to obtain person information with more discriminative features. Finally, supervised learning was performed using the cross-entropy loss function during source domain training. Meanwhile, it can obtain the details of the source domain samples using the triplet loss function, thereby improving the classification performance. During target domain training, adaptation to the challenges of viewpoint, illumination, background, and feature distribution differences between samples is achieved by learning variations between the source and target domains. In the test stage, comparative experiments were conducted on two large-scale public data sets, Market-1501 and DukeMTMC-reID, achieving Rank-1 accuracies of 86.6% and 79.3%, respectively, with mean average precision mAPs of 68.7% and 62.6%, respectively. The experimental results show that the proposed method performs better in terms of improving the generalization ability of the model.

BackgroundPancreatic ductal adenocarcinoma (PDAC) is frequently diagnosed in advanced stages, necessitating pancreaticoduodenectomy (PD) as a primary therapeutic approach. However, PD surgery can engender intricate complications. Thus, understanding the factors influencing postoperative complications documented in electronic medical records and their impact on survival rates is crucial for improving overall patient outcomes.MethodsA total of 749 patients were divided into two groups: 598 (79.84%) chose the RPD (Robotic pancreaticoduodenectomy) procedure and 151 (20.16%) chose the LPD (Laparoscopic pancreaticoduodenectomy) procedure. We used correlation analysis, survival analysis, and decision tree models to find the similarities and differences about postoperative complications and prognostic survival.ResultsPancreatic cancer, known for its aggressiveness, often requires pancreaticoduodenectomy as an effective treatment. In predictive models, both BMI and surgery duration weigh heavily. Lower BMI correlates with longer survival, while patients with heart disease and diabetes have lower survival rates. Complications like delayed gastric emptying, pancreatic fistula, and infection are closely linked post-surgery, prompting conjectures about their causal mechanisms. Interestingly, we found no significant correlation between nasogastric tube removal timing and delayed gastric emptying, suggesting its prompt removal post-decompression.ConclusionThis study aimed to explore predictive factors for postoperative complications and survival in PD patients. Effective predictive models enable early identification of high-risk individuals, allowing timely interventions. Higher BMI, heart disease, or diabetes significantly reduce survival rates in pancreatic cancer patients post-PD. Additionally, there’s no significant correlation between DGE incidence and postoperative extubation time, necessitating further investigation into its interaction with pancreatic fistula and infection.

IntroductionStenotrophomonas maltophilia complex (Smc) comprises opportunistic Gram-negative bacilli responsible for various nosocomial infections. Limited data exists concerning its evolutionary lineage, global prevalence and pathogenicity.MethodsWe conducted an extensive genomic analysis on 734 Smc genomes, of which 90 were newly sequenced and isolated from different patients. The species composition and evolutionary relationships of Smc were examined using core protein sequence analysis. Pathogenicity evaluation was used by assays for swimming motility, biofilm formation and identification of virulence factors. The broth microdilution method was used to evaluate the drug resistance spectrum of clinical isolates.ResultsPhylogenetic analyses delineated 24 species-level clades, dominated by S. maltophilia (42.8%), S. sepilia (13.6%) and S. geniculata (9.9%). Geographically, strains were primarily distributed in Europe (34.2%), Asia (33.7%) and North America (24.0%), with intricate global distribution patterns. Meanwhile, 154 virulence-associated genes and 46 antimicrobial resistance genes within Smc were identified. These genes encoded span various functions, including motility, adherence, toxin, RND antibiotic efflux pumps, beta-lactamases and aminoglycoside-modifying enzymes. Moreover, significant variations were indicated in swimming motility and biofilm-forming capability across the different species, with S. sepilia exhibiting superior levels of both traits. Additionally, no statistically significant discrepancy was detected among Smc species to other antibiotics, despite the fact that all S. geniculata isolates were resistant to Ceftazidime and much higher than other species.ConclusionOur findings indicate the need to pay increased attention to other mainstream species of Smc besides S. maltophilia in order to better manage Smc-related infections and tailor effective treatment strategies.

Vibrio metschnikovii is an emergent pathogen that causes human infections which may be fatal. However, the phylogenetic characteristics and pathogenicity determinants of V. metschnikovii are poorly understood. Here, the whole-genome features of 103 V. metschnikovii strains isolated from different sources are described. On phylogenetic analysis V. metschnikovii populations could be divided into two major lineages, defined as lineage 1 (L1) and 2 (L2), of which L1 was more likely to be associated with human activity. Meanwhile, we defined 29 V. metschnikovii O-genotypes (VMOg, named VMOg1–VMOg29) by analysis of the O-antigen biosynthesis gene clusters (O-AGCs). Most VMOgs (VMOg1 to VMOg28) were assembled by the Wzx/Wzy pathway, while only VMOg29 used the ABC transporter pathway. Based on the sequence variation of the wzx and wzt genes, an in silico O-genotyping system for V. metschnikovii was developed. Furthermore, nineteen virulence-associated factors involving 161 genes were identified within the V. metschnikovii genomes, including genes encoding motility, adherence, toxins, and secretion systems. In particular, V. metschnikovii was found to promote a high level of cytotoxicity through the synergistic action of the lateral flagella and T6SS. The lateral flagellar-associated flhA gene played an important role in the adhesion and colonization of V. metschnikovii during the early stages of infection. Overall, this study provides an enhanced understanding of the genomic evolution, O-AGCs diversity, and potential pathogenic features of V. metschnikovii.

Abstract There is a growing recognition that responding to climate change necessitates urban adaptation. We sketch a transdisciplinary research effort, arguing that actionable research on urban adaptation needs to recognize the nature of cities as social networks embedded in physical space. Given the pace, scale and socioeconomic outcomes of urbanization in the Global South, the specificities and history of its cities must be central to the study of how well-known agglomeration effects can facilitate adaptation. The proposed effort calls for the co-creation of knowledge involving scientists and stakeholders, especially those historically excluded from the design and implementation of urban development policies.

Abstract Background DNA double-strand breaks (DSBs) are among the most deleterious DNA lesions, and they can cause cancer if improperly repaired. Recent chromosome conformation capture techniques, such as Hi-C, have enabled the identification of relationships between the 3D chromatin structure and DSBs, but little is known about how to explain these relationships, especially from global contact maps, or their contributions to DSB formation. Results Here, we propose a framework that integrates graph neural network (GNN) to unravel the relationship between 3D chromatin structure and DSBs using an advanced interpretable technique GNNExplainer. We identify a new chromatin structural unit named the DNA fragility–associated chromatin interaction network (FaCIN). FaCIN is a bottleneck-like structure, and it helps to reveal a universal form of how the fragility of a piece of DNA might be affected by the whole genome through chromatin interactions. Moreover, we demonstrate that neck interactions in FaCIN can serve as chromatin structural determinants of DSB formation. Conclusions Our study provides a more systematic and refined view enabling a better understanding of the mechanisms of DSB formation under the context of the 3D genome.

Abstract Transformative urban development is urgent to achieve future sustainable development and wellbeing. Transformation can benefit from shared and cumulative learning on strategies to guide urban development across local to national scales, while also reflecting the complex emergent nature of urban systems, and the need for context-specific and place-based solutions. The article addresses this challenge, drawing on extensive transdisciplinary engagement and National Strategy co-development processes for Australia. This includes generation of two frameworks as boundary objects to assist such transdisciplinary strategy development. An ‘enabling urban systems transformation’ framework comprises four generic overarching transformation enablers and a set of necessary underpinning urban capacities. This also built cumulatively on other sustainability and urban transformation studies. A complementary ‘knowledge for urban systems transformation’ framework comprises key knowledge themes that can support an integrated systems approach to mission-focused urban transformations, such as decarbonising cities. The article provides insights on the transdisciplinary processes, urban systems frameworks, and scoping of key strategies that may help those developing transformation strategies from local to national scales. Science highlights • Transdisciplinary national urban strategy development is used to distil generic frameworks and strategy scopes with potential international application. • The frameworks also build on other published framings to support convergent, cumulative and transdisciplinary urban science. • The ‘enabling transformations’ and ‘urban knowledge’ frameworks include the perspective of those developing sustainable urban systems strategies. • The enabling framework also informs ‘National Urban Policy’ and ‘Knowledge and Innovation Hub’ strategies, and prevailing power imbalances. • The knowledge framework can help frame urban challenges, missions and knowledge programs. Policy and practice recommendations • An urban ‘transformation imperative’ and ‘strategic response’ can be co-developed from local to national scales. • Local initiative is crucial to drive urban strategies, but sustained national leadership with coherent policy across sectors and scales is also key. • Diversity in engagement participation and processes generates whole-of-urban-systems and local-to-national perspectives. • Urban solutions are context-specific but generic frameworks can help collaborative issue framing and responses. • Collaborative issue framing informed by generic frameworks can bring broader perspectives to context-specific and contested policy and practice issues.

Abstract Hydrogen energy from renewables has the potential to address climate challenges, and technological advancements are vital for driving this energy transition. Globally, an increasing number of cities are actively adopting hydrogen strategies. The literature on the urban sustainability transition primarily focuses on policy innovations for technology adoption, while the role of cities in enabling technological innovation is underexplored. Here, we address this gap by analyzing 122 policy documents from 39 Chinese cities with hydrogen plans by using qualitative content analysis methods. The findings reveal myriad and critical roles of cities in fostering technological innovations in an emergent hydrogen economy via targeted policy support and investment in desired technologies. By moving ahead of the national government, these early movers play a critical role in creating early momentum and laying the foundation for future scale transition. Our findings also point to a clear need for these bottom-up initiatives to be better guided and channeled toward clean hydrogen development, as the lack of upper-level policy guidance can lead to diversified priorities and outcomes. Our findings call for renewed research and policy attention to the proactive role of cities in technological innovation and the sustainability transition and they stress the importance of engaging cities in hydrogen economy development nationally and internationally.

Abstract The signaling adaptor MAVS forms prion-like aggregates to activate the innate antiviral immune response after viral infection. However, spontaneous aggregation of MAVS can lead to autoimmune diseases. The molecular mechanism that prevents MAVS from spontaneous aggregation in resting cells has been enigmatic. Here we report that protein arginine methyltransferase 9 targets MAVS directly and catalyzes the arginine methylation of MAVS at the Arg41 and Arg43. In the resting state, this modification inhibits MAVS aggregation and autoactivation of MAVS. Upon virus infection, PRMT9 dissociates from the mitochondria, leading to the aggregation and activation of MAVS. Our study implicates a form of post-translational modification on MAVS, which can keep MAVS inactive in physiological conditions to maintain innate immune homeostasis.

A rising incidence of clinical infections has been caused by Kluyvera, a significant opportunistic pathogen. Meanwhile, Kluyvera acts as an important reservoir of blaCTX-Ms, which are the dominant genes of class A extended-spectrum β-lactamases (ESBLs). In this work, 60 strains of Kluyvera were subjected to phylogenetic relationship reconstruction, antimicrobial susceptibility testing, and antibiotic resistance genes prediction. All mature blaCTX-Ms were gathered to perform subgroup reclassification. The findings demonstrate that Kluyvera has a large gene pool with significant genetic flexibility. Notably, 25% of strains showed simultaneous detection of ESBLs and carbapenem resistance genes. The genotypes of fourteen novel blaCTX-Ms were identified. A new subgroup classification approach for blaCTX-Ms was defined by using 20 amino acid site variants, which could split blaCTX-Ms into 10 subgroups. The results of the subgroup division were consistent with the phylogenetic clustering. More significantly, we proposed a novel blaCTX-M subgroup, KLUS, that is chromosomally encoded in K. sichuanensis and the new species put forward in this study, showing amino acid differences from the currently known sequences. Cloning and transformation tests demonstrated that the recipient bacteria had a robust phenotype of cefotaxime resistance. Closely related Kluyvera species had blaCTX-Ms in the same subgroup. Our research lays the groundwork for a deeper comprehension of Kluyvera and emphasizes how important a blaCTX-M reservoir it is. We provide an update on blaCTX-M subgroups reclassification from the aspects of phylogenetic relationship, amino acid differences, and the new subgroup KLUS, which needs to be strengthen monitored due to its strong resistance phenotype to cefotaxime.

Streptococcus suis, an emerging zoonotic pathogen, is important reservoirs of antibiotic resistance genes that play critical roles in the horizontal transfer of corresponding resistances. In the present study, 656 antibiotic resistance (AR) genes were detected in 154 of 155 genomes of S. suis strains isolated from the nasopharynx of slaughtered pigs and the lungs of diseased pigs in China. The AR genes were clustered into 11 categories, consisting of tetracycline, macrolides, lincosamide, streptogramin, aminoglycoside, trimethoprim, amphenicols, nucleoside, quinupristin/dalfopristin, glycopeptide, and oxazolidinones resistance genes. In order to investigate the transmission patterns of the AR genes, AR genes-associated the mobile genetic elements (MGEs) were extracted and investigated. Twenty ICEs, one defective ICE, one tandem ICE, and ten prophages were found, which mainly carried tetracycline, macrolides/lincosamides/streptogramin (MLS), and aminoglycosides resistance genes. Three types of DNA cargo with AR genes were integrated into specific sites of ICEs: integrative mobilizable elements (IMEs), cis-IMEs (CIMEs), and transposon Tn916. Obvious differences in AR gene categories were found among the three cargo types. IMEs mainly harbored tetracycline and MLS resistance genes. CIMEs mainly carried aminoglycoside resistance genes, while transposon Tn916 carried only the tet (M) gene. Nearly all AR genes in ICEs were carried by IMEs and CIMEs. IMEs were prevalent and were also detected in additional 29 S. suis genomes. The horizontal transfer of IMEs and CIMEs may play critical role in ICE evolution and AR gene transmission in the S. suis population. Our findings provide novel insights into the transmission patterns of AR genes and the evolutionary mechanisms of ICEs in S. suis.

Endometrial cancer (EC) is one of the three fatal tumors of the female reproductive system. Epigenetic alterations have been reported to be important in tumorigenesis, especially the chromatin accessibility changes and transcription factor binding differences. However, the regulatory mechanism underlying epigenetic alterations in EC development remains unclear. Here, we identified and characterized transcription factor binding site clustered regions (TFCRs) by integrating chromatin accessibility and transcription factor binding information. We totally identified 78,820 TFCRs and explored the relationship between TFCRs and regulatory elements, gene expression and mutation. Finally, we constructed a bioinformatic framework to identify candidate oncogenes and screened 13 candidate key genes, which may serve as potential diagnostic markers or therapeutic targets of EC.

Abstract Urbanization can be a challenge and an opportunity for earthquake risk mitigation. However, little is known about the changes in exposure (for example, population and urban land) to earthquakes in the context of global urbanization, and their impacts on fatalities in earthquake-prone areas. We present a global analysis of the changes in population size and urban land area in earthquake-prone areas from 1990 to 2015, and their impacts on earthquake-related fatalities. We found that more than two thirds of population growth (or 70% of total population in 2015) and nearly three quarters of earthquake-related deaths (or 307,918 deaths) in global earthquake-prone areas occurred in developing countries with an urbanization ratio (percentage of urban population to total population) between 20 and 60%. Holding other factors constant, population size was significantly and positively associated with earthquake fatalities, while the area of urban land was negatively related. The results suggest that fatalities increase for areas where the urbanization ratio is low, but after a ratio between 40 and 50% occurs, earthquake fatalities decline. This finding suggests that the resistance of building and infrastructure is greater in countries with higher urbanization ratios and highlights the need for further investigation. Our quantitative analysis is extended into the future using Shared Socioeconomic Pathways to reveal that by 2050, more than 50% of the population increase in global earthquake-prone areas will take place in a few developing countries (Pakistan, India, Afghanistan, and Bangladesh) that are particularly vulnerable to earthquakes. To reduce earthquake-induced fatalities, enhanced resilience of buildings and urban infrastructure generally in these few countries should be a priority.

An increase in the carbapenem-hydrolyzing capacity of class D β-lactamase has been observed in strains of multiple species, posing a significant challenge to the control of antibiotic resistance. In this study, we aimed to investigate the genetic diversity and phylogenetic characteristics of new blaOXA-48-like variants derived from Shewanella xiamenensis. Three ertapenem-non-susceptible S. xiamenensis strains were identified, one isolated from the blood sample of an inpatient, the other two isolated from the aquatic environment. Phenotypic characterization confirmed that the strains were carbapenemase producers and exhibited antimicrobial resistance patterns to ertapenem, with some showing lower susceptibility to imipenem, chloramphenicol, ciprofloxacin, and tetracycline. No significant resistance to cephalosporins was observed. Sequence analysis revealed that one strain harbored blaOXA-181 and the other two strains harbored blaOXA-48-like genes, with open reading frame (ORF) similarities with blaOXA-48 ranging from 98.49% to 99.62%. The two novel blaOXA-48-like genes, named blaOXA-1038 and blaOXA-1039, respectively, were cloned and expressed in E. coli. The three OXA-48-like enzymes demonstrated significant hydrolysis activity against meropenem, and the classical β-lactamase inhibitor had no significant inhibitory effect. In conclusion, this study demonstrated the diversity of the blaOXA gene and highlighted the emergence of novel OXA carbapenemases in S. xiamenensis. Further attention to S. xiamenensis and OXA carbapenemases is recommended for the effective prevention and control of antibiotic-resistant bacteria.

In this work, a series of chitosan (CS)-grafted carbon oxynitride (OCN) nanoparticles (denoted as CS-OCN) were successfully synthesized for the first time by thermal polycondensation and subsequent esterification. The structure and photocatalytic performance of CS-OCN nanoparticles were investigated. The XPS spectra of CS-OCN-3 showed the presence of amino bonds. The optimal photocatalytic degradation efficiency of the synthesized CS-OCN-3 could reach 94.3% within 390 min, while the photocurrent response intensity was about 150% more than that of pure OCN. The improved photocatalytic performance may be mainly attributed to the enhanced photogenerated carrier’s separation and transportation and stronger visible light response after CS grafting. In addition, the inhibition diameter of CS-OCN-3 reached 23 mm against E. coli within 24 h under visible light irradiation, exhibiting excellent photocatalytic bactericidal ability. The results of bacterial inhibition were supported by absorbance measurements (OD600) studies of E. coli. In a word, this work provided a rational design of an efficient novel metal-free photocatalyst to remove bacterial contamination and accelerate the degradation of organic dyes.

Recent studies have shown that the three-dimensional (3D) structure of chromatin is associated with cancer progression. However, the roles of the 3D genome structure and its dynamics in cancer remains largely unknown. In this study, we investigated hierarchical topologically associating domain (TAD) structures in cancers and defined a “TAD hierarchical score (TH score)” for genes, which allowed us to assess the TAD nesting level of all genes in a simplified way. We demonstrated that the TAD nesting levels of genes in a tumor differ from those in normal tissue. Furthermore, the hierarchical TAD level dynamics were related to transcriptional changes in cancer, and some of the genes in which the hierarchical level was altered were significantly related to the prognosis of cancer patients. Overall, the results of this study suggest that the folding dynamics of TADs are closely related to transcriptional abnormalities in cancers, emphasizing that the function of hierarchical chromatin organization goes beyond simple chromatin packaging efficiency.

A wide variety of leguminous plant-released (iso)flavonoids, such as genistein, are potential inducers of the nodulation (nod) genes of endosymbiotic rhizobia for the production of Nod factors, which are vital signaling molecules for triggering the symbiotic process. However, these (iso)flavonoids are generally thought to be toxic to the bacterial partner to varying degrees. Here, a novel TetR-like regulator gene of the soybean symbiont Bradyrhizobium diazoefficiens USDA110, bdtR (systematic designation blr7023), was characterized. It was found to be rapidly and preferentially induced by genistein, and its mutation resulted in significantly increased expression of the neighboring bll7019-bll7021 genes, encoding a multidrug resistance efflux pump system, in the absence of this isoflavonoid. Then, the transcriptional start site of BdtR was determined, and it was revealed that BdtR acted as a transcriptional repressor of the above efflux system through the binding of an AT-rich operator, which could be completely prevented by genistein. In addition, the ΔbdtR deletion mutant strain showed higher accumulation of extracellular genistein and became less susceptible to the isoflavonoid. In contrast, the inactivation of BdtR led to the significantly decreased induction of a nodulation gene (nodY) independent of the expression of nodD1 and nodW and to much weaker nodulation competitiveness. Taken together, the results show that BdtR plays an early sensing role in maintaining the intracellular homeostasis of genistein, helping to alleviate its toxic effect on this bacterium by negatively regulating neighboring genes encoding an efflux pump system while being essentially required for nodule occupancy competitiveness.[Graphic: see text] Copyright © 2020 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Abstract With an increasingly urban population, cities have an important role to play in global environmental sustainability. Cities engaged in pioneering and ongoing sustainability experimentation—the frontrunners—can lead the way towards sustainability transition, and often become the beacon for others to follow. However, the nature and the internal dynamics that make a city a frontrunner, or the role of frontrunner cities in sustainability transition beyond their boundary, remain unclear. In addition, most studies on the influence of these frontrunners are limited to passive influencing, i.e. how the practice has been duplicated by others, or how the practice is adopted and mainstreamed into system level. Based on in-depth case studies on a frontrunner city and two other cities influenced by it, this paper examines how momentum for positive changes has been initiated, built, and sustained towards changing the status quo of practice through a succession of actors and a series of reinforcing feedback loops. We argue that creating a positive inertia through sustained momentum and embedding the frontrunner identity in a city is essential for it to continue the process of sustainability transition. Frontrunners can create flow-on benefits for other cities through a proactive influencing. Supported by multiple two-way benefits, such proactive influencing is a new mechanism of mainstreaming and up-scaling urban sustainability experiments in system innovation and transition.

To understand the characteristics of Vibrio isolates in aquatic environments in China and their public health significance, this study investigated water samples in six cities in China in 2020. A total of 88 sampling locations were included and Vibrio isolates were identified in 81 of them. A total of 143 Vibrio isolates belonging to 16 species were selected for characterization. The population structure of Vibrio species showed great differences among the six cities, indicating regional specificity. The presence of virulence genes was examined for the isolates (n = 78) of five pathogenic Vibrio species. All isolates except one (n = 77) contained at least one virulence gene and isolates belonging to the same species showed very similar virulence gene profiles. Then, 26 isolates from 12 species were examined by multilocus sequence typing and were assigned to 25 STs, of which 24 STs were new. Also, the presence of antibiotic-resistant genes was investigated for all 143 isolates and only three isolates were found to contain genes from aminoglycosides, phenicols, beta-lactams or the tetracycline family. Our results provide valuable insights into the Vibrio community in Chinese aquatic environments and can be applied as guidance for the environmental surveillance of the risk of Vibrio isolates.

Summary: Record climate extremes are reducing urban liveability, compounding inequality, and threatening infrastructure. Adaptation measures that integrate technological, nature-based, and social solutions can provide multiple co-benefits to address complex socioecological issues in cities while increasing resilience to potential impacts. However, there remain many challenges to developing and implementing integrated solutions. In this Viewpoint, we consider the value of integrating across the three solution sets, the challenges and potential enablers for integrating solution sets, and present examples of challenges and adopted solutions in three cities with different urban contexts and climates (Freiburg, Germany; Durban, South Africa; and Singapore). We conclude with a discussion of research directions and provide a road map to identify the actions that enable successful implementation of integrated climate solutions. We highlight the need for more systematic research that targets enabling environments for integration; achieving integrated solutions in different contexts to avoid maladaptation; simultaneously improving liveability, sustainability, and equality; and replicating via transfer and scale-up of local solutions. Cities in systematically disadvantaged countries (sometimes referred to as the Global South) are central to future urban development and must be prioritised. Helping decision makers and communities understand the potential opportunities associated with integrated solutions for climate change will encourage urgent and deliberate strides towards adapting cities to the dynamic climate reality.

Staphylococcus spp., especially Staphylococcus aureus (S. aureus), is an important pathogen in hospital-acquired infection and food poisoning. Here, we developed a multienzyme isothermal rapid amplification combined with duplex quantitative PCR (duplex MIRA-qPCR) method, which can simultaneously detect the S. aureus species-specific conserved gene FMN-bgsfp and the Staphylococcus genus-specific conserved gene tuf. This assay enabled the amplification of DNA within 20 min at a constant temperature of 39 °C. Specificity analysis indicated that all nine common Staphylococcus species were positive and non-Staphylococcus spp. were negative for tuf gene, whereas S. aureus was positive, non-aureus Staphylococci species and non-Staphylococcus spp. were negative for FMN-bgsfp gene, suggesting that duplex MIRA-qPCR exhibited high specificity. Meanwhile, the sensitivity was tested and the limit of detection (LoD) was 3 × 102 CFU/mL. The coefficient variation values ranged from 0.13% to 2.09%, indicating that the assay had good repeatability. Furthermore, all the nine common Staphylococcus species (including S. aureus) could be detected from four kinds of simulated samples and the LoD of S. aureus was 8.56 × 103 CFU/mL. In conclusion, the duplex MIRA-qPCR has advantages of stronger specificity, lower detection threshold, shorter detection time, and simpler operation, which is an effective tool to detect S. aureus and non-aureus Staphylococci spp. infections rapidly.

Abstract Keeping the Earth system in a stable and resilient state, to safeguard Earth's life support systems while ensuring that Earth's benefits, risks, and related responsibilities are equitably shared, constitutes the grand challenge for human development in the Anthropocene. Here, we describe a framework that the recently formed Earth Commission will use to define and quantify target ranges for a “safe and just corridor” that meets these goals. Although “safe” and “just” Earth system targets are interrelated, we see safe as primarily referring to a stable Earth system and just targets as being associated with meeting human needs and reducing exposure to risks. To align safe and just dimensions, we propose to address the equity dimensions of each safe target for Earth system regulating systems and processes. The more stringent of the safe or just target ranges then defines the corridor. Identifying levers of social transformation aimed at meeting the safe and just targets and challenges associated with translating the corridor to actors at multiple scales present scope for future work.

Based on conventional observation data, satellite images, automatic observational data of precipitation and NCEP/NCAR reanalysis data (0.25°×0.25°), the mesoscale characteristics of a rainstorm caused by warm front frontogenesis were analyzed, and the cause of the rainstorm was preliminarily discussed. The major conclusions were as follow. The rainstorm occurred under the condition of the strengthening and westward-stretching subtropical high and the influence of typhoon activity. Water vapor transport on the periphery of the subtropical high pressure provided abundant water vapor conditions for rainstorms. The increase of the lower southwest wind led to the warm front, strengthened the convergence and uplift of the warm front, and caused a large area of rainstorm weather. There existed the conditional symmetric instability (CSI) in the frontogenetical area. The frontogenetical effect and the release of CSI strengthened the oblique upward flow along the frontal surface and the frontal secondary circulation. The developments of slantwise convection by CSI further triggered the convective instability. The convective instability led to a large area of vertical ascending motion, and the precipitation was significantly enhanced. The sounding analysis showed that the atmosphere of warm front cloud belt was in an unstable state, which was advantageous to the convection development with short time heavy rainfall. The rainstorm was produced by the β mesoscale finger cloud. The mesoscale cloud had the characteristics of backward propagation, which was caused by the rebirth and merging of convective clouds. Heavy precipitation was mainly composed of warm cloud precipitation, high precipitation efficiency and heavy rain. The warm front was stable and less active, and the convective cell caused by warm front was repeated in the same region, and traveled along the warm front from west to east to form the train effect. The strong echo activity of the rainstorm center had a high precipitation efficiency exceeding 4 hours (maximum reflectivity of the radar echo exceeding 45 dBz), resulting in long duration of heavy rainfall and large precipitation accumulation.

We examined the effect of the Qi-invigorating Traditional Chinese Medicines (TCM) herb Panax ginseng ( P.G. ) on mitochondrial functions and cellular antioxidant capacity in different organs of mice. We found that the P.G. extracts had a significant effect on tissues of mice, with the generation of total adenylate pool (TAP) enhanced in all visceral tissues, but not for the brain. The mitochondrial membrane potential (MMP) and antioxidant capacity reflected by superoxide dismutase (SOD) and glutathione (GSH) increased only for the meridian tissues that P.G. belongs to including Heart, Spleen and Lung. Reactive oxygen species (ROS), as a combined result of the increased energy metabolism and antioxidant capacity, varied in different organs. We concluded that: 1) the Qi-invigorating TCM herb P.G. had a significant effect on mice by enhancing TAP production in all of the visceral tissues examined, except for the brain; 2) for the meridional tissues of P.G. (Heart, Spleen and Lung), the P.G. extracts not only promoted the TAP production, but also boosted the antioxidant capacity demonstrated by the simultaneous increase in TAP, and SOD and GSH.

Escherichia coli sequence type 131 (ST131) is well known for its multidrug resistance profile. Carbapenems have been considered the treatment of choice for E. coli ST131 infections, and resistance to carbapenems is emerging due to the acquisition of carbapenemase-encoding genes. In this study, 45 carbapenem-resistant E. coli strains were collected in a hospital. The resistance mechanisms, plasmid profiles, and genetic relatedness of these strains were determined. Phylogenetic relationships between these strains were assessed by molecular profiling and aligned with patient clinical details. The genetic context of blaKPC–2 was analyzed to trace the potential dissemination of blaKPC–2. The 45 carbapenem-resistant E. coli ST131 strains were closely related. Initially prevalent only in a single ward, ST131 subsequently spread to other ward, resulting in a respiratory infection outbreak of carbapenem-resistant E. coli ST131. Eight of the 30 patients died within 28 days of the first isolation of E. coli ST131. The blaKPC–2-positive plasmid profiles suggest that the carbapenem resistance was due to the acquisition by E. coli ST131 of transmissible plasmids pE0272_KPC and pE0171_KPC carrying blaKPC–2. Additionally, diverse multidrug resistance elements were transferred and rearranged between these plasmids mediated by IS26. Our research indicates that clinical attention should be paid to the importance of E. coli ST131 in respiratory infections and the spread of blaKPC-carrying E. coli ST131.

Purmorphamine (PUR), an agonist of the Smoothened (Smo) receptor, has been shown to function as a neuroprotectant in acute experimental ischemic stroke. Its role in hypoxic-ischemic (HI) brain injury in neonatal mice remains unknown. Here we show that PUR attenuated acute brain injury, with a decrease in Bax/Bcl-2 ratio as well as inhibition of caspase-3 activation. These beneficial effects of PUR were associated with suppressing neuro-inflammation and oxidative stress. PUR exerted long-term protective effects upon tissue loss and improved neurobehavioral outcomes as determined at 14 and 28 days post-HI insult. Moreover, PUR increased synaptophysin (Syn) and postsynaptic density (PSD) protein 95 expression in HI-treated mice and attenuated synaptic loss. PUR upregulated the expression of Shh pathway mediators, while suppression of the Shh signaling pathway with cyclopamine (Cyc) reversed these beneficial effects of PUR on HI insult. Our study suggests a therapeutic potential for short-term PUR administration in HI-induced injury as a result of its capacity to exert multiple protective actions upon acute brain injury, long-term memory deficits, and impaired synapses. Moreover, we provide evidence indicating that one of the mechanisms underlying these beneficial effects of PUR involves activation of the Shh signaling pathway.

Cerebral ischemia is a common cerebrovascular condition which often induces neuronal apoptosis, leading to brain damage. The sonic hedgehog (Shh) signaling pathway has been reported to be involved in ischemic stroke, but the underlying mechanisms have not been fully elucidated. In the present study, we demonstrated that expressions of Shh, Ptch, and Gli-1 were significantly downregulated at 24 h following oxygen-glucose deprivation (OGD) injury in neurons in vitro, effects which were associated with increasing numbers of apoptotic cells and reactive oxygen species generation. In addition, expressions of synaptic proteins (neuroligin and neurexin) were significantly downregulated at 8 h following OGD, also associated with concomitant neuronal apoptosis. Treatment with purmorphamine, a Shh agonist, increased Gli-1 in the nucleus of neurons and protected against OGD injury, whereas the Shh inhibitor, cyclopamine, produced the opposite effects. Activation of Shh signals promoted CREB and Akt phosphorylation; upregulated the expressions of BDNF, neuroligin, and neurexin; and decreased NF-κB phosphorylation following OGD. Notably, this activation of Shh signals was accompanied by improved neurobehavioral responses along with attenuations in edema and apoptosis at 48 h postischemic insult in rats. Taken together, these results demonstrate that activation of the Shh signaling pathway played a neuroprotective role in response to ischemic exposure via promotion of synaptic and neuronal health.

Abstract Streptococcus suis is one of the most important bacterial pathogens in the porcine industry and also a zoonotic agent. Serotype 9 is becoming one of the most prevalent serotypes within the S. suis population in certain European countries. In the present study, serotype 9 strains isolated from a country where infection due to this serotype is endemic (Spain), were compared to those recovered from Canada, where this serotype is rarely isolated from diseased pigs. For comparison purposes, strains from Brazil and the only strain isolated from a human case, in Thailand, were also incorporated. Firstly, sequence types (STs) were obtained followed by detection of putative virulence factors. Phylogenetic trees were constructed using the non-recombinant single nucleotide polymorphisms from core genomes of tested strains. Most Spanish strains were either ST123 or ST125, whereas Canadian strains were highly heterogeneous. However, the distribution of putative virulence factors was similar in both groups of strains. The fact that ST16 strains harbored more putative virulence genes and shared greater similarity with the genome of human serotype 2 strains suggests that they present a higher zoonotic and virulence potential than those from Canada and Spain. More than 80% of the strains included in this study carried genes associated with resistance to tetracycline, lincosamides and macrolides. Serotype 9 strains may be nearly 400 years old and have evolved in parallel into 2 lineages. The rapid population expansion of dominant lineage 1 occurred within the last 40 years probably due to the rapid development of the porcine industry.

Neonatal hypoxic-ischemic (HI) injury is a major cause of neonatal death and neurological dysfunction. H2S has been shown to protect against hypoxia-induced injury and apoptosis of neurons. L-Cysteine is catalyzed by cystathionine-β-synthase (CBS) in the brain and sequentially produces endogenous H2S. The present study was designed to investigate whether L-Cysteine could attenuate the acute brain injury and improve neurobehavioral outcomes following HI brain injury in neonatal mice by releasing endogenous H2S. L-Cysteine treatment significantly attenuated brain edema and decreased infarct volume and neuronal cell death, as shown by a decrease in the Bax/Bcl-2 ratio, suppression of caspase-3 activation, and reduced phosphorylation of Akt and ERK at 72 h after HI. Additionally, L-Cysteine substantially up-regulated NF-E2-related factor 2 and heme oxygenase-1 expression. L-Cysteine also decreased endoplasmic reticulum (ER) stress-associated pro-apoptotic protein expression. Furthermore, L-Cysteine had long-term effects by protecting against the loss of ipsilateral brain tissue and improving neurobehavioral outcomes. Importantly, pre-treatment with a CBS inhibitor significantly attenuated the neuroprotection of L-Cysteine on HI insult. Thus, L-Cysteine exerts neuroprotection against HI-induced injury in neonates via the CBS/H2S pathway, mediated in part by anti-apoptotic effects and reduced oxidative stress and ER stress. Thus, L-Cysteine may be a promising treatment for HI.

A growing number of studies are focusing on the effect of teachers' knowledge on their behavioral intention to use technology in teaching. This study aims to explore the influence of teachers' technological pedagogical content knowledge (TPACK) on their behavioral intention to use technology by including their technology self-efficacy and attitude toward use in a chain mediation model. Based on a thorough literature review, this study establishes a theoretical model. Then, data are collected from 314 in-service teachers in primary and secondary schools in two provinces in China and analyzed using structural equation modeling and effect analysis. Results show that (1) the teachers' technology self-efficacy and attitude toward technology play a crucial independent mediating role in the influence of TPACK on their behavioral intention to use technology, and (2) the teachers' technology self-efficacy and attitude toward use have a chain mediating effect on the influence of their TPACK on their behavioral intention to use technology. On the basis of the results, this study presents some implications to effectively understand how teachers' behavioral intention to use technology in teaching can be improved.

Cellular network operators are predicting an increase in space of more than 200 percent to carry the move and tremendous increase of total users in data traffic. The growing of investments in infrastructure such as a large number of small cells, particularly the technologies such as LTE-Advanced and 6G Technology, can assist in mitigating this challenge moderately. In this paper, we suggest a projection study in spectrum sharing of radar multi-input and multi-output, and mobile LTE multi-input multi-output communication systems near m base stations (BS). The radar multi-input multi-output and mobile LTE communication systems split different interference channels. The new approach based on radar projection signal detection has been proposed for free interference disturbance channel with radar multi-input multi-output and mobile LTE multi-input multi-output by using a new proposed interference cancellation algorithm. We chose the channel of interference with the best free channel, and the detected signal of radar was projected to null space. The goal is to remove all interferences from the radar multi-input multi-output and to cancel any disturbance sources from a chosen mobile Communication Base Station. The experimental results showed that the new approach performs very well and can optimize Spectrum Access.

Streptococcus suis sequence type 7 emerged and caused 2 of the largest human infection outbreaks in China in 1998 and 2005. To determine the major risk factors and source of the infections, we analyzed whole genomes of 95 outbreak-associated isolates, identified 160 single nucleotide polymorphisms, and classified them into 6 clades. Molecular clock analysis revealed that clade 1 (responsible for the 1998 outbreak) emerged in October 1997. Clades 2–6 (responsible for the 2005 outbreak) emerged separately during February 2002–August 2004. A total of 41 lineages of S. suis emerged by the end of 2004 and rapidly expanded to 68 genome types through single base mutations when the outbreak occurred in June 2005. We identified 32 identical isolates and classified them into 8 groups, which were distributed in a large geographic area with no transmission link. These findings suggest that persons were infected in parallel in respective geographic sites.

We have reported previously that L-cysteine-derived hydrogen sulfide (H2S) demonstrates a remarkable neuroprotective effect against hypoxia-ischemic (HI) insult in neonatal animals. Here, we assessed some of the mechanisms of this protection as exerted by L-cysteine. Specifically, we examined the capacity for L-cysteine to stimulate microglial polarization of the M2 phenotype and its modulation of complement expression in response to HI in neonatal mice. L-cysteine treatment suppressed the production of inflammatory cytokines, while dramatically up-regulating levels of anti-inflammatory cytokines in the damaged cortex. This L-cysteine administration promoted the conversion of microglia from an inflammatory M1 to an anti-inflammatory M2 phenotype, an effect which was associated with inhibiting the p38 and/or JNK pro-inflammatory pathways, nuclear factor-κB activation and a decrease in HI-derived levels of the C1q, C3a and C3a complement receptor proteins. Notably, blockade of H2S-production clearly prevented L-cysteine-mediated M2 polarization and complement expression. L-cysteine also inhibited neuronal apoptosis as induced by conditioned media from activated M1 microglia in vitro. We also show that L-cysteine promoted AMP-activated protein kinase (AMPK) activation and the AMPK inhibitor abolished these anti-apoptotic and anti-inflammatory effects of L-cysteine. Taken together, our findings demonstrate that L-cysteine-derived H2S attenuated neuronal apoptosis after HI and suggest that these effects, in part, result from enhancing microglia M2 polarization and modulating complement expression via AMPK activation.

Manhattan, Berlin and New Delhi all need to take action to adapt to climate change and to reduce greenhouse gas emissions. While case studies on these cities provide valuable insights, comparability and scalability remain sidelined. It is therefore timely to review the state-of-the-art in data infrastructures, including earth observations, social media data, and how they could be better integrated to advance climate change science in cities and urban areas. We present three routes for expanding knowledge on global urban areas: mainstreaming data collections, amplifying the use of big data and taking further advantage of computational methods to analyse qualitative data to gain new insights. These data-based approaches have the potential to upscale urban climate solutions and effect change at the global scale.

Subarachnoid hemorrhage (SAH) is a devastating form of stroke that leads to incurable outcomes. Increasing evidence has proved that early brain injury (EBI) contributes mostly to unfavorable outcomes after SAH. A previously unknown mechanism of regulated cell death known as necroptosis has recently been reported. Necrostatin-1 (nec-1), a specific and potent inhibitor of necroptosis, can attenuate brain impairments after SAH. However, the effect of nec-1 on the hippocampus and its neuroprotective impact on synapses after SAH is not well understood. Our present study was designed to investigate the potential effects of nec-1 administration on synapses and its relevant signal pathway in EBI after SAH. Nec-1 was administrated in a rat model via intracerebroventricular injection after SAH. Neurobehavior scores and brain edema were detected at 24 h after SAH occurred. The expression of the receptor-interacting proteins 1 and 3 (RIP1and3) was examined as a marker of necroptosis. We used hematoxylin and eosin staining, Nissl staining, silver staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) to observe the morphological changes in hippocampus. The protective effect of nec-1 on synapses was evaluated using western blotting and electron microscopy and Western blotting was used to detect the cAMP responsive element binding (CREB) protein and brain-derived neurotrophic factor (BDNF), and we used transmission electron microscopy and TUNEL to detect the protective effects of nec-1 when a specific inhibitor of CREB, known as 666-15, was used. Our results showed that in the SAH group, RIP1, and RIP3 significantly increased in the hippocampus. Additionally, injection of nec-1 alleviated brain edema and improved neurobehavior scores, compared with those in the SAH group. The damage to neurons was attenuated, and synaptic structure also improved in the Sham+nec-1 group. Furthermore, nec-1 treatment significantly enhanced the levels of phospho-CREB and BDNF compared with those in the SAH group. The protective effect of nec-1 could hindered by 666-15. Thus, nec-1 mitigated SAH-induced synaptic impairments in the hippocampus through the inhibition of necroptosis in connection with the CREB-BDNF pathway. This study may provide a new strategy for SAH patients in clinical practice.

The question of what cities can contribute to mitigation and adapting to climate change is gaining traction among researchers and policy makers alike. However, while the field is rich with case studies, methods that provide rich data across municipalities and potentially at global scale remain underdeveloped, and comparative insights remain scarce. Here we summarize contributions to the focus issue on ‘Systematizing and Upscaling Urban Climate Solutions’, also drawing from presentations given at an accompanying conference in 2018. We highlight four core areas for systematizing and upscaling urban climate mitigation solutions. First, with more and better (big) data and associated machine learning methods, there is increasing potential to compare types of cities and leverage collective understanding. Second, while urban climate assessments have mostly emphasized urban planning, demand-side action as related to both behavioral change and modified social practices relevant to urban space deserve more academic attention and integration across a diverse set of social sciences. Third, climate mitigation would be intangible as a single objective at the urban scale, and measures and solutions that coordinate mitigation coherently with adaptation and broader sustainable development goals require explicit conceptualization and systematization. Forth, all insights should come together to develop governance frameworks that translate scientific exercises into concrete, realistic and organized action plans on the ground, for all cities.

In the original publication of this article [1], the author name ‘Pengchen Du’ in author list should be ‘Pengcheng Du’.

It is no longer possible nor desirable to address the dual challenges of equity and sustainability separately. Instead, they require new thinking and approaches which recognize their interlinkages, as well as the multiple perspectives and dimensions involved. We illustrate how equity and sustainability are intertwined, and how a complex social–ecological systems lens brings together advances from across the social and natural sciences to show how (in)equity and (un)sustainability are produced by the interactions and dynamics of coupled social–ecological systems. This should help understand which possible pathways could lead to sustainable and fair futures.

l-Cysteine is a semi-essential amino acid and substrate for cystathionine-β-synthase (CBS) in the central nervous system. We previously reported that NaHS, an H2S donor, significantly alleviated brain damage after subarachnoid hemorrhage (SAH) in rats. However, the potential therapeutic value of l-cysteine and the molecular mechanism supporting these beneficial effects have not been determined. This study was designed to investigate whether l-cysteine could attenuate early brain injury following SAH and improve synaptic function by releasing endogenous H2S. Male Wistar rats were subjected to SAH induced by cisterna magna blood injection, and l-cysteine was intracerebroventricularly administered 30 min after SAH induction. Treatment with l-cysteine stimulated CBS activity in the prefrontal cortex (PFC) and H2S production. Moreover, l-cysteine treatment significantly ameliorated brain edema, improved neurobehavioral function, and attenuated neuronal cell death in the PFC; these effects were associated with a decrease in the Bax/Bcl-2 ratio and the suppression of caspase-3 activation 48 h after SAH. Furthermore, l-cysteine treatment activated the CREB–brain-derived neurotrophic factor (BDNF) pathway and intensified synaptic density by regulating synapse proteins 48 h after SAH. Importantly, all the beneficial effects of l-cysteine in SAH were abrogated by amino-oxyacetic acid, a CBS inhibitor. Based on these findings, l-cysteine may play a neuroprotective role in SAH by inhibiting cell apoptosis, upregulating CREB–BDNF expression, and promoting synaptic structure via the CBS/H2S pathway.

Streptococcus suis sequence type (ST) 7 has been spreading throughout China. To determine events associated with its emergence, we tested 114 isolates. In all 106 ST7 strains responsible for human outbreaks and sporadic infections, the tetracycline-resistance gene, tetM, was detected on the conjugative transposon Tn916. Horizontal transmission of tetM is suspected.