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ABSTRACT: Objectives: Herein, we detected one multidrug-resistant Aeromonas hydrophila strain K522 co-carrying two blaKPC-2 genes together with a novel chromosomal integrative and mobilizable element (IME) Tn7548 from China. To reveal the genetic characteristics of the novel reservoir of blaKPC-2 and IME in Aeromonas, a detailed genomic characterization of K522 was performed, and a phylogenetic analysis of Tn7412-related IMEs was carried out. Methods: Carbapenemases were detected by using the immunocolloidal gold technique and antimicrobial susceptibility was tested by using VITEK 2. The whole-genome sequences of K522 were analysed using phylogenetics, detailed dissection, and comparison. Results: Strain K522 carried a Tn7412-related chromosomal IME Tn7548 and three resistance plasmids pK522-A-KPC, pK522-B-KPC, and pK522-MOX. A phylogenetic tree of 82 Tn7412-related IMEs was constructed, and five families of IMEs were divided. These IMEs shared four key backbone genes: int, repC, and hipAB, and carried various profiles of antimicrobial resistance genes (ARGs). pK522-A-KPC and pK522-B-KPC carried blaKPC-2 and belonged to IncG and unclassified type plasmid, respectively. The blaKPC-2 regions of these two plasmids were the truncated version derived from Tn6296, resulting in the carbapenem resistance of K522. Conclusion: We first reported A. hydrophila harbouring a novel Tn7412-related IME Tn7548 together with two blaKPC-2 carrying plasmids and a MDR plasmid. Three of these four mobile genetic elements (MGEs) discovered in A. hydrophila K522 were novel. The emergence of novel MGEs carrying ARGs indicated the rapid evolution of the resistance gene vectors in A. hydrophila under selection pressure and would contribute to the further dissemination of various ARGs in Aeromonas.

Despite China's building into a leading sporting nation and sport-tourism integration high-quality development strategy in the 20th National Congress of the Communist Party of China, existing tourism studies seldom concern sport-tourism integration, especially their spatial hot spots and evolutional trend based on geospatial big data. This study aims to probe into the spatiality and the underlying mechanism of sport tourism through internet attention data in 2015, 2018, and 2021 by social network analysis, with a specific focus on aero-sports tourism. Shaanxi Province is chosen as the study site given its advantages of rich aero-sports tourism resources and various aero-sports modes (e.g., sky diving, paragliding, etc.). The results are concluded: (1) At the provincial scale, the aero-sports tourism internet attention shows a pattern of “strong in the middle and weak in the north and south”. (2) At the regional scale, the sub-group clusters within the three specific regions (Shanbei, Guanzhong, and Shannan) of Shaanxi Province turn to be inter-regional clusters. Guanzhong region, especially with Xi'an as the core, is dominant in connecting its peripheral area. Since 2016, the radiation effects of the Guanzhong Region have shown a homogeneous trend of yearly growth and effect strengthening, yet become loosely connected with a heterogeneous trend in 2021 due to the COVID-19 epidemic. (3) At the city scale, the core area of aero-sports tourism internet attention expanded from Xi'an and Xianyang to Yulin and Baoji from 2015 to 2021, resulting from urban economic strength and aviation flight camp club development. (4) The number of general aviation manufacturers, tourist attendance, and tourism revenue significantly affect aero-sports tourism internet attention.

Abstract Background Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) recommended for the patients with subsolid nodule in early lung cancer stage is not routinely. The clinical value and impact in patients with EGFR mutation on survival outcomes is further needed to be elucidated to decide whether the application of EGFR-TKIs was appropriate in early lung adenocarcinoma (LUAD) stage appearing as subsolid nodules. Materials and methods The inclusion of patients exhibiting clinical staging of IA-IIB subsolid nodules. Clinical information, computed tomography (CT) features before surgical resection and pathological characteristics including tertiary lymphoid structures of the tumors were recorded for further exploration of correlation with EGFR mutation and prognosis. Results Finally, 325 patients were enrolled into this study, with an average age of 56.8 ± 9.8 years. There are 173 patients (53.2%) harboring EGFR mutation. Logistic regression model analysis showed that female (OR = 1.944, p = 0.015), mix ground glass nodule (OR = 2.071, p = 0.003, bubble-like lucency (OR = 1.991, p = 0.003) were significant risk factors of EGFR mutations. Additionally, EGFR mutations were negatively correlated with TLS presence and density. Prognosis analysis showed that the presence of TLS was associated with better recurrence-free survival (RFS)(p = 0.03) while EGFR mutations were associated with worse RFS(p = 0.01). The RFS in patients with TLS was considerably excel those without TLS within EGFR wild type group(p = 0.018). Multivariate analyses confirmed that EGFR mutation was an independent prognostic predictor for RFS (HR = 3.205, p = 0.037). Conclusions In early-phase LUADs, subsolid nodules with EGFR mutation had specific clinical and radiological signatures. EGFR mutation was associated with worse survival outcomes and negatively correlated with TLS, which might weaken the positive impact of TLS on prognosis. Highly attention should be paid to the use of EGFR-TKI for further treatment as agents in early LUAD patients who carrying EGFR mutation.

ABSTRACT: Objectives: This study firstly identified an IncHI5 plasmid pK254-KPC_NDM co-carrying two different class carbapenemase genes blaKPC-2 and blaNDM-1 in Klebsiella michiganensis K254. Methods: The strain K254 was sequenced by high-throughput genome sequencing. A detailed genomic and phenotypic characterization of pK254-KPC_NDM was performed. Results: pK254-KPC_NDM displayed the conserve IncHI5 backbone and carried a resistant accessory region: Tn1696-related transposon Tn7414 containing blaKPC-2 and blaNDM-1. A sequence comparison was applied to a collection of four Tn1696-related transposons (Tn7414–Tn7417) harbouring carbapenemase genes. For all these four transposons, the blaNDM-1 was carried by Tn125 derivatives within three different mobile genetic elements. Tn7414 further acquired another carbapenemase gene, blaKPC-2, because of the integration of the local blaKPC-2 genetic environment from Tn6296, resulting in the high-level carbapenem resistance of K. michiganensis K254. The conjugal transfer and plasmid stability experiments confirmed that pK254-KPC_NDM could be transferred intercellularly and keep the stable vertical inheritance in different bacteria, which would contribute to the further dissemination of multiple carbapenemase genes and enhance the adaption and survival of K. michiganensis under complex and diverse antimicrobial selection pressures. Conclusion: This study was the first to report the K. michiganensis isolate coharbouring blaKPC-2 and blaNDM-1 in the Tn1696-related transposon in IncHI5 plasmid. The emergence of novel transposons simultaneously carrying multiple carbapenemase genes might contribute to the further dissemination of high-level carbapenem resistance in the isolates of the hospital settings and pose new challenges for the treatment of nosocomial infection.

The underlying complexity of urban space can be manifested by its fractal forms and scaling statistics. This paper examines these characteristics at the intra-urban scale through the lens of clustered street junctions (including road ends) in two Chinese metropolitan areas: Beijing and Shenzhen. We derived the cluster sets with Euclidean distance thresholds starting at 100 meters (m) and ending at 1000 m, and outlined each cluster using a concave-hull method to maintain their original irregular shapes. Within each delimited cluster, we examined four urban attributes: gross domestic product, number of street nodes, polygon area, and population. Our analysis revealed that power law distribution applied to almost every cluster set in terms of the four attributes, but varied from one attribute to another or from city to city, represented primarily by fluctuated power law exponents and ht-index values whose profiles along with the cluster growth can effectively characterize the urban structure. Additionally, we computed the spectrum of intra-urban scaling exponents with cluster size increments, contributing new insights into the allometric relationships between urban configuration and function.

The porous starch is prepared using physical, chemical or enzymatical methods, possessing the characteristic of high porosity, high surface area and adsorption capacity. The porous starch possesses a functional performance and application prospect due to the porous structure, and the structural and functional characteristics of porous starch may be different due to the preparation methods, resulting in the different application potential. The preparation methods and the application status of porous starch is reviewed in this work to promote the practical application of porous starch in food industry. There are some shortcomings in the preparation methods of porous starch, the surface pores of porous starch prepared using physical method are not uniform, the chemical method cause chemical residue, and the enzymatical method has high preparation cost and poor economic benefits. These modified methods should be further optimized to widespread promotion in the food industry. The application of porous starch was widely concerned due to its structure and functional characteristics. The preparation of porous starch by enzymatic combined with physical processing or chemical modification has become a research hotpot due to the characteristics of high efficiency and easy popularization. The porous starch can used to load food nutrients, effectively preventing them from being hydrolyzed in the gastrointestinal tract and improving its bioaccessibility. Food packaging prepared with porous starch has good antioxidant and antibacterial capabilities due to its load of antibacterial and antioxidant substances, which can extend the shelf life of food. The chemically modified porous starch exhibits a sensory experience similar to fat, and it can be used to prepare fat substitutes to ameliorate health problems associated with high fat intake. This review will provide a guideline for the rational preparation and applications of porous starch in food industry in the future.

Abstract The emergence of immune checkpoint inhibitors (ICIs) has heralded a transformative era in the therapeutic landscape of non‐small cell lung cancer (NSCLC). While ICIs have demonstrated clinical efficacy in a portion of patients with NSCLC, these treatments concurrently precipitate a spectrum of immune‐related adverse events (irAEs), encompassing mild to severe manifestations, collectively posing a risk of significant organ damage. Consequently, there exists an imperative to augment our comprehension of the pathophysiological underpinnings of irAEs and to formulate more efficacious preventive and ameliorative strategies. In this comprehensive review, we delineate the clinical presentation of organ‐specific irAEs in patients with NSCLC and provide an in‐depth analysis of recent advancements in understanding the mechanisms driving ICI‐induced toxicity. Furthermore, we discuss potential strategies and targets for ameliorating these irAEs. Ultimately, this review aims to furnish valuable insights to guide further research endeavours in the context of irAEs in NSCLC patients.

In the context of ecological civilization construction in China, interregional ancient trees are important natural and cultural resources, and it is vital that they are effectively protected and utilized according to their spatial distribution and regional conditions in order to provide a balance between local economic development and the ecological environment. This article analyzes the spatial heterogeneity of 26,842 ancient trees and explores the underlying natural and human factors by using geoinformatics–based techniques (i.e., the nearest neighbor index, kernel density, spatial autocorrelation, and the geographically weighted regression model) in Henan Province, Central China. The research findings conclude that: (1) The interregional ancient trees show positive spatial autocorrelation, and the aggregation effect in Western Henan is the most significant. (2) The growing environment and elevation exert a more obvious influence on the spatial pattern of interregional ancient trees. (3) The main influencing factors per region are different, for example, historical culture in Western Henan, water source and elevation in Southern Henan, and the growing environment in Eastern Henan, while ancient trees in Northern Henan have a weak relationship with each factor. This research facilitates political strategy making for sustainable development and the protection of interregional ancient trees.

Dietary intake of natural substances to regulate physiological functions is currently regarded as a potential way of promoting health. As one of the recommended dietary ingredients, phytosterols that are natural bioactive compounds distributed in plants have received increasing attention for their health effects. Phytosterols have attracted great attention from scientists because of many physiological functions, for example, cholesterol-lowering, anticancer, anti-inflammatory, and immunomodulatory effects. In addition, the physiological functions of phytosterols, the purification, structure analysis, synthesis, and food application of phytosterols have been widely studied. Nowadays, many bioactivities of phytosterols have been assessed in vivo and in vitro. However, the mechanisms of their pharmacological activities are not yet fully understood, and in-depth investigation of the relationship between structure and function is crucial. Therefore, a contemporaneous overview of the extraction, beneficial properties, and the mechanisms, as well as the current states of phytosterol application, in the food field of phytosterols is provided in this review.

Abstract Objectives Pseudomonas aeruginosa has intrinsic antibiotic resistance and the strong ability to acquire additional resistance genes. However, a limited number of investigations provide detailed modular structure dissection and evolutionary analysis of accessory genetic elements (AGEs) and associated resistance genes (ARGs) in P. aeruginosa isolates. The objective of this study is to reveal the prevalence and transmission characteristics of ARGs by epidemiological investigation and bioinformatics analysis of AGEs of P. aeruginosa isolates taken from a Chinese hospital. Methods Draft-genome sequencing was conducted for P. aeruginosa clinical isolates (n = 48) collected from a single Chinese hospital between 2019 and 2021. The clones of P. aeruginosa isolates, type 3 secretion system (T3SS)-related virulotypes, and the resistance spectrum were identified using multilocus sequence typing (MLST), polymerase chain reaction (PCR), and antimicrobial susceptibility tests. In addition, 17 of the 48 isolates were fully sequenced. An extensive modular structure dissection and genetic comparison was applied to AGEs of the 17 sequenced P. aeruginosa isolates. Results From the draft-genome sequencing, 13 STs were identified, showing high genetic diversity. BLAST search and PCR detection of T3SS genes (exoT, exoY, exoS, and exoU) revealed that the exoS+/exoU- virulotype dominated. At least 69 kinds of acquired ARGs, involved in resistance to 10 different categories of antimicrobials, were identified in the 48 P. aeruginosa isolates. Detailed genetic dissection and sequence comparisons were applied to 25 AGEs from the 17 isolates, together with five additional prototype AGEs from GenBank. These 30 AGEs were classified into five groups -- integrative and conjugative elements (ICEs), unit transposons, IncpPBL16 plasmids, Incp60512−IMP plasmids, and IncpPA7790 plasmids. Conclusion This study provides a broad-scale and deeper genomics understanding of P. aeruginosa isolates taken from a single Chinese hospital. The isolates collected are characterized by high genetic diversity, high virulence, and multiple drug resistance. The AGEs in P. aeruginosa chromosomes and plasmids, as important genetic platforms for the spread of ARGs, contribute to enhancing the adaptability of P. aeruginosa in hospital settings.

Background Lung squamous cell carcinoma (LUSC) remains a leading cause of cancer-related deaths with few therapeutic strategies. Immune checkpoint inhibitors (ICIs) have demonstrated promising efficacy in patients with LUSC. However, ICIs could also lead to a unique spectrum of immune-related adverse events (irAEs), which dampen the clinical outcome. In-depth characterization of the immune hallmarks of antitumor responses and irAEs remains an unmet need to maximize ICI-treatment benefits of patients.Methods We performed single-cell RNA sequencing (scRNA-seq) on pre-ICI and on-ICI treatment tumor biopsies. We used bulk RNA-seq data of matched pretreatment/on-treatment tumors and irAE affected organs to validate observations from scRNA-seq analysis. Two independent patient cohorts were collected to determine circulating tumor necrosis factor (TNF) protein expression levels.Results We found that increased proportions of a macrophage subcluster with highly expressed secreted phosphoprotein 1 (SPP1) and two tumor cell subclusters in irAE patients, whereas proportions of two cytotoxic CD8+ T cell subclusters were higher in patients with partial response (PR). TNF signaling pathway was conversely associated with treatment efficacy and irAE development in most macrophage and tumor cell subclusters. Cell–cell communications for TNF ligand-receptor pairs between macrophage/T cells and tumor cells were also bidirectionally remodeled in responders versus non-responders and irAE versus non-irAE patients. Bulk RNA-seq analysis on matched pretreatment/on-treatment tumors and irAE affected organs revealed remarkably enhanced macrophage abundance and TNF signaling pathway in on-treatment tumors and organs developed irAEs. Furthermore, we observed significantly increased circulating TNF protein in plasma or serum of irAE patients but not ICI responders, based on analysis of two independent LUSC patient cohorts and one published ICI patient cohort.Conclusions Our data depicts specific reprogramming of macrophage, T cells and tumor cells associated with ICI response and irAEs, elucidates divergent roles of TNF signaling in antitumor immunity and irAEs, and highlights the significance of TNF expression in irAE development in the LUSC setting.

Human perceptions represent the psychological experiences and feelings of individuals toward the surrounding environment. It is influenced by various physical elements (e.g., sky, tree, building, etc.) within the street canyon. However, prior research has predominantly relied on field surveys, high-cost methods, and restricted data sources, thereby limiting analyses of the impact of street canyon characteristics on human perceptions. Importantly, the nonlinear effects of street canyon characteristics on human perceptions have not been fully understood by existing studies. Thus, this study employed Baidu Street View images to evaluate street canyon characteristics and human perceptions at a visual level. A random forest regression was then utilized to uncover the nonlinear effects of street canyon characteristics on human perceptions. The results suggested that some street canyon characteristics nonlinearly affected human perceptions. Specifically, the optimal sky proportion within the individual visual field was 15%, and the appropriate thresholds for trees and grass were 17.5% and 1.0%, respectively. Overall, positive perceptions might be increased if the proportion of natural characteristics within street canyons was maintained below the optimal threshold. In addition, threshold effects have been observed in relation to the perception of beauty due to cars, the perception of vitality and security due to roads, and the perception of boredom due to walls. The findings of this study can serve as scientific evidence and inform urban renewal based on a people-oriented approach.

With the in-depth implementation of the strategy of maritime power, the state has gradually increased its financial input in marine survey and research, and the number of ocean observation instruments and equipment in maritime research institutes has increased substantially. At the same time, due to the particularity of the use of ocean observation instruments and equipment, damage or even loss of instruments and equipment sometimes occurs, which has brought new challenges to the management of instruments and equipment. Taking the ocean observation instruments related to physical oceanography as an example, this paper classified the ocean observation instruments and equipment, discussed their particularity, explored the establishment of management mechanisms in line with the characteristics of ocean observation instruments and equipment, further improved the scientific nature of asset management, to better serve the needs of teaching and scientific research.

Abstract Radiotherapy is the first‐line treatment for locally advanced cervical squamous cell cancer (CSCC). However, ≈50% of patients fail to respond to therapy and, in some cases, tumors progress after radical radiotherapy. Here, single‐nucleus RNA‐seq is performed to construct high‐resolution molecular landscapes of various cell types in CSCC before and during radiotherapy, to better understand radiotherapy related molecular responses within tumor microenvironment. The results show that expression levels of a neural‐like progenitor (NRP) program in tumor cells are significantly higher after radiotherapy and these are enriched in the tumors of nonresponding patients. The enrichment of the NRP program in malignant cells from the tumors of nonresponders in an independent cohort analyzed by bulk RNA‐seq is validated. In addition, an analysis of The Cancer Genome Atlas dataset shows that NRP expression is associated with poor prognosis in CSCC patients. In vitro experiments on the CSCC cell line demonstrate that downregulation of neuregulin 1 (NRG1), a key gene from NRP program, is associated with decreased cell growth and increased sensitivity to radiation. Immunohistochemistry staining in cohort 3 validated key genes, NRG1 and immediate early response 3 from immunomodulatory program, as radiosensitivity regulators. The findings reveal that the expression of NRP in CSCC can be used to predict the efficacy of radiotherapy.

The rapid spread of carbapenemase-producing Klebsiella pneumoniae (cpKP) poses serious threats to public health; however, the underlying genetic basis for its dissemination is still unknown. We conducted a comprehensive genomic epidemiology analysis on 420 cpKP isolates collected from 70 hospitals in 24 provinces/autonomous regions/municipalities of China during 2009–2017 by short-/long-read sequencing. The results showed that most cpKP isolates were categorized into clonal group 258 (CG258), in which ST11 was the dominant clone. Phylogenetic analysis revealed three major clades including the top one of Clade 3 for CG258 cpKP isolates. Additionally, carbapenemase gene analysis indicated that blaKPC was dominant in the cpKP isolates, and most blaKPC genes were located in five major incompatibility (Inc) groups of blaKPC-harboring plasmids. Importantly, three advantageous combinations of host–blaKPC-carrying plasmid (Clade 3.1+3.2–IncFIIpHN7A8, Clade 3.1+3.2–IncFIIpHN7A8:IncR, and Clade 3.3–IncFIIpHN7A8:IncpA1763-KPC) were identified to confer cpKP isolates the advantages in both genotypes (strong correlation/coevolution) and phenotypes (resistance/growth/competition) to facilitate the nationwide spread of ST11/CG258 cpKP. Intriguingly, Bayesian skyline analysis illustrated that the three advantageous combinations might be directly associated with the strong population expansion during 2007–2008 and subsequent maintenance of the population of ST11/CG258 cpKP after 2008. We then examined drug resistance profiles of these cpKP isolates and proposed combination treatment regimens for CG258/non-CG258 cpKP infections. Thus, the findings of our systematical analysis shed light on the molecular epidemiology and genetic basis for the dissemination of ST11/CG258 cpKP in China, and much emphasis should be given to the close monitoring of advantageous cpKP–plasmid combinations.

Autophagy has been typically associated with resistance to cancer therapy, and autophagy inhibitors have been explored in cancer. Here, the authors investigate autophagy signatures and their association with drug response in cancer, and find that autophagy induction can actually sensitise cancer cells to therapy.

The ChangKang (Heathy Bowel) project was established to collect molecular and clinical information of a thousand Chinese colorectal cancer patients. Here, the authors present the genomic landscape of the ChangKang cohort and find a subgroup of patients defined by abnormal mitochondrial copy numbers.

With the rapid development of high-speed railway (HSR), many scholars have studied the competition between HSR and aviation or inter-city coach, but few studies have discussed the supply-service relationship within the railway system. This paper explores the competition and cooperation between HSR and conventional railway (CR) at the city-pair level of 39 core cities in China from the temporal perspective. Comprehensive considering the departure time and arrival time between city pairs as the representation of train service quality, we find that the proportion of superior quality service of high-speed train (HST) is far higher than that of conventional train (CT). However, the time slots representing the competition degree show that CR with fewer superior quality trains is easier to be replaced than HSR. The supply-service relationships of the railway system indicate that HSR has become the main transportation mode between core cities, and the CR, as an auxiliary transportation, shows a certain complementary effect in the temporal perspective. Spatially, HSR and CR services are more likely to generate temporal competition on the mainline, but temporal complementarity between city pairs on non-arterial lines. This study can provide inspiration for regional spatial planning by better understanding the operation strategy of railway passenger transport system.

Abstract Background The carbapenem-resistance genes bla VIM are widely disseminated in Pseudomonas, and frequently harbored within class 1 integrons that reside within various mobile genetic elements (MGEs). However, there are few reports on detailed genetic dissection of bla VIM-carrying MGEs in Pseudomonas. Methods This study presented the complete sequences of five bla VIM-2/-4-carrying MGEs, including two plasmids, two chromosomal integrative and mobilizable elements (IMEs), and one chromosomal integrative and conjugative element (ICE) from five different Pseudomonas isolates. Results The two plasmids were assigned to a novel incompatibility (Inc) group IncpSTY, which included only seven available plasmids with determined complete sequences and could be further divided into three subgroups IncpSTY-1/2/3. A detailed sequence comparison was then applied to a collection of 15 MGEs belonging to four different groups: three representative IncpSTY plasmids, two Tn6916-related IMEs, two Tn6918-related IMEs, and eight Tn6417-related ICEs and ten of these 15 MGEs were first time identified. At least 22 genes involving resistance to seven different categories of antibiotics and heavy metals were identified within these 15 MGEs, and most of these resistance genes were located within the accessory modules integrated as exogenous DNA regions into these MGEs. Especially, eleven of these 15 MGEs carried the bla VIM genes, which were located within 11 different concise class 1 integrons. Conclusion These bla VIM-carrying integrons were further integrated into the above plasmids, IMEs/ICEs with intercellular mobility. These MGEs could transfer between Pseudomonas isolates, which resulted in the accumulation and spread of bla VIM among Pseudomonas and thus was helpful for the bacteria to survival from the stress of antibiotics. Data presented here provided a deeper insight into the genetic diversification and evolution of VIM-encoding MGEs in Pseudomonas.

The quinolone resistance crpP genes can mediate decreased susceptibility to quinolones. However, diversification and prevalence of crpP genes and crpP-carrying integrative and conjugative elements (ICEs) still need to be elucidated. In this study, genome sequencing was conducted for 200 Chinese Pseudomonas aeruginosa isolates, 16 of which were fully sequenced. All the 37 available CrpP variants were collected for phylogenetic analysis, 10 CrpP enzymes were chosen to conduct cloning and antimicrobial susceptibility test, and 22 crpP-carrying Tn6786-related ICEs were selected for detail genetic dissection analysis. Then, typing/nomenclature schemes for crpP variants and crpP-carrying ICEs were established for the first time. The 10 representative CrpP enzymes were confirmed to mediate decreased susceptibility to one to three quinolones. Tn6786-related ICEs displayed high-level diversification in both nucleotide sequences and modular structures. Mainly, massive gene acquisition/loss occurred across the whole genomes of Tn6786-related ICEs. 53.5% (107/200) of the tested clinical P. aeruginosa isolates from China carried crpP genes, which were exclusively located within chromosome-borne Tn6786-related ICEs. The crpP-carrying ICEs were at active stages of evolution and had the high potential to be an important vector for the dissemination of resistance genes besides crpP. The present study furthered the understanding of the bioinformatics and epidemiology of crpP genes and crpP-carrying ICEs.

In recent years, a huge number of individuals all over the world, elderly people, in particular, have been suffering from Alzheimer’s disease (AD), which has had a significant negative impact on their quality of life. To intervene early in the progression of the disease, accurate, convenient, and low-cost detection technologies are gaining increased attention. As a result of their multiple merits in the detection and assessment of AD, biosensors are being frequently utilized in this field. Behavioral detection is a prospective way to diagnose AD at an early stage, which is a more objective and quantitative approach than conventional neuropsychological scales. Furthermore, it provides a safer and more comfortable environment than those invasive methods (such as blood and cerebrospinal fluid tests) and is more economical than neuroimaging tests. Behavior detection is gaining increasing attention in AD diagnosis. In this review, cutting-edge biosensor-based devices for AD diagnosis together with their measurement parameters and diagnostic effectiveness have been discussed in four application subtopics: body movement behavior detection, eye movement behavior detection, speech behavior detection, and multi-behavior detection. Finally, the characteristics of behavior detection sensors in various application scenarios are summarized and the prospects of their application in AD diagnostics are presented as well.

The civil aviation industry plays an important role in advancing interregional socio-economic development. Investigating the competitiveness of civil aviation airports (CAAs) from the tempo-spatial change perspective aids in the optimization of airport layout towards balanced and coordinated regional development. This research assesses the overall competitiveness of 86 CAAs in 11 provinces or provincial-level municipalities of the Yangtze River Economic Belt (YREB) from 2009 to 2019 by the entropy weight approach, then characterizes their spatial-temporal evolution via Moran index of spatial auto-correlation analysis, and finally explores their dynamic changing tendency of the spatial variability based on Theil index measurement and decomposition. The findings are concluded: 1) From 2009 to 2019, the overall competitiveness of civil aviation airports is dramatically improved and an evidently hierarchical system is formed at the provincial level, with the spatial pattern of “strong in the east and west, weak in the middle”. 2) The global Moran indexes of civil aviation airport competitiveness in 2009, 2014, and 2019 are negative, indicating that superior and inferior airports are likely to be spatially clustered. 3) The local Moran Indexes show that the spatial agglomerations of civil aviation airports tend to be more evident in the recent decade. The high-high competitiveness clusters lie in the Yangtze River Delta Economic Zone for the long run, transforming from “Shanghai-Hangzhou” high-competitiveness pole to “Shanghai-Hangzhou-Nanjing” and further extending to central Jiangsu. Civil aviation airports in provincial capitals and secondary cities have formed clusters of high-low competitiveness. Moreover, clusters of low-low competitiveness stretch from the Yunnan-Guizhou Plateau to cities in the middle reaches of the Yangtze River. 4) The interprovincial Theil indexes of civil aviation airport competitiveness fluctuate, with the discrepancy increasing and then decreasing.

As a type of public land, park green spaces (PGSs) carry the daily recreation and social communication of urban residents, and the inequity of their space accessibility has been widely confirmed. However, the optimized suggestions based on evaluations of accessibility and equity in previous studies cannot guide actual planning effectively because the reasonable locations and scales of construction of PGSs were difficult to accurately identify. This study first constructed two equity objective functions: the minimum standard deviation (SD) and the minimum Gini coefficient (GC) in accessibility; then an improved two-step optimization method considering location-allocation was adopted to maximal accessibility equity (MAE) for optimizing the spatial layout of PGSs and doing comparisons of these two objectives for further analysis. The results showed that the improved method based on covering the accessibility blind area and preserving the existing PGSs could optimize the location selection and rationally determine the area. The two objective functions were both effective for optimization, but the GC minimization is more advantageous than the SD for achieving the MAE. The accessibility value increased significantly in a higher proportion of regions, and the overall accessibility median increased by 0.0445. It is worth mentioning that the MAE optimization would lead to a new imbalance between supply and demand in some regions. This indicated that the strictly restricted area standard may lead to the oversupply of PGSs in some areas, while the improvement of equity might not mean the improvement of accessibility. The proposed optimization framework could achieve the optimal layout of PGSs on the goal of MAE. Our findings also could provide inspiration for the equity allocation of other types of public facility lands and support decision-making for government departments regarding management and planning.

At the 75th session of the United Nations General Assembly, China formally proposed the goal of achieving carbon peak by 2030 and carbon neutrality by 2060, which is called the dual-carbon strategy. In this study, we incorporated the dual-carbon strategy perspective into ecological product value (EPV) evaluation. The EPV is the sum of the final product and service value provided by regional ecosystems for human production and life. A significant uncertainty exists in evaluating the EPV. To bridge this gap, we explored the quantitative evaluation index system of EPV based on the dual-carbon perspective and conducted an empirical analysis relating to four subindexes (ecological protection, ecological products carbon neutral capacity transformation, ecological value, and ecological product value realization safeguard mechanism). The EPV in nine provinces of the Yellow River basin in 2020 was measured. The results showed that the total evaluation score of EPV realization in the Yellow River basin was relatively low, and the average scores of ecological product protection level, carbon neutrality capacity, value transformation level, and value realization guarantee mechanism were all at a low level. Overall, the protection level of ecological products and the guarantee mechanism to realize the EPV were relatively good. However, the carbon neutrality capacity and the value transformation level were relatively poor. From the spatial perspective, the value realization level of ecological products was roughly upstream region > downstream region > midstream region in the Yellow River basin. Finally, corresponding countermeasures and suggestions are put forward according to the comprehensive evaluation index of EPV realization and analysis of the four subindexes.

Immunotherapy, the reactivation of the immune system to recognize cancer cells, can be accompanied by severe adverse effects. Here, the authors use pharmacovigilance and genomic data to be able to predict which patients might be susceptible to such severe events.

ABSTRACT In this study, draft-genome sequencing was conducted for 60 Chinese Morganella isolates, and furthermore, 12 of them were fully sequenced. Then, a total of 166 global sequenced Morganella isolates, including the above 60, were collected to perform average nucleotide identity-based genomic classification and core single nucleotide polymorphism-based phylogenomic analysis. A genome sequence-based species classification scheme for Morganella was established, and accordingly, the two conventional Morganella species were redefined as two complexes and further divided into four and two genospecies, respectively. At least 88 acquired antimicrobial resistance genes (ARGs) were disseminated in these 166 isolates and were prevalent mostly in the isolates from hospital settings. IS26/IS15DI, IS10 and IS1R, and Tn3-, Tn21-, and Tn7-subfamily unit transposons were frequently presented in these 166 isolates. Furthermore, a detailed sequence comparison was applied to 18 Morganella chromosomal accessory genetic elements (AGEs) from the fully sequenced 12 isolates, together with 5 prototype AGEs from GenBank. These 23 AGEs were divided into eight different groups belonging to composite/unit transposons, transposable prophages, integrative and mobilizable elements, and integrative and conjugative elements, and they harbored at least 52 ARGs involved in resistance to 15 categories of antimicrobials. Eleven of these 23 AGEs acquired large accessory modules, which exhibited complex mosaic structures and contained many antimicrobial resistance loci and associated ARGs. Integration of ARG-containing AGEs into Morganella chromosomes would contribute to the accumulation and dissemination of ARGs in Morganella and enhance the adaption and survival of Morganella under complex and diverse antimicrobial selection pressures. IMPORTANCE This study presents a comprehensive genomic epidemiology analysis on global sequenced Morganella isolates. First, a genome sequence-based species classification scheme for Morganella is established with a higher resolution and accuracy than those of the conventional scheme. Second, the prevalence of accessory genetic elements (AGEs) and associated antimicrobial resistance genes (ARGs) among Morganella isolates is disclosed based on genome sequences. Finally, a detailed sequence comparison of eight groups of 23 AGEs (including 19 Morganella chromosomal AGEs) reveals that Morganella chromosomes have evolved to acquire diverse AGEs harboring different profiles of ARGs and that some of these AGEs harbor large accessory modules that exhibit complex mosaic structures and contain a large number of ARGs. Data presented here provide a deeper understanding of the classification and evolution of Morganella species and also those of ARG-containing AGEs in Morganella at the genomic scale.

Capillarity influences the long-term stability of the dam greatly and affects the sustainable development of tailings dam. The online monitoring capillary water rise test system was independently developed by SM3001B temperature and humidity sensor, SU9101B RS485 converter, SV3010 data acquisition system, and other equipment to carry out the whole process test of water absorption and water release of tailings with different particle sizes. The results show that the capillary rising trend of tailings with different particle sizes is basically consistent, the relationship between the rising height and the diameter are negatively correlated, and the logarithm function can better fit the height of capillary rising over time well enough. The water content of tailing capillary zone decreases with the height, and the smaller the size of tailings, the greater the change of water content. The water release process of tailings is an unsaturated permeability process, which largely depends on the saturation before water release. The larger the particle size of tailings is, the smaller the water content after water release. Based on the above results, the relationship between capillary diameter and tailings particle size was discussed, and the relationship formula between water content change and particle size was deduced. The research results systematically show the water migration law under the tailing capillaries. It is suggested that the unsaturated tailings water content index should be added in the monitoring of the saturated surface of tailings dam.

Abstract Emerging evidence has revealed significant roles for small nucleolar RNAs (snoRNAs) in tumorigenesis. However, the genetic and pharmacogenomic landscape of snoRNAs has not been characterized. Using the genotype and snoRNA expression data from The Cancer Genome Atlas, we characterized the effects of genetic variants on snoRNAs across 29 cancer types and further linked related alleles with patient survival as well as genome-wide association study risk loci. Furthermore, we characterized the impact of snoRNA expression on drug response in patients to facilitate the clinical utility of snoRNAs in cancer. We also developed a user-friendly data resource, GPSno ( http://hanlab.uth.edu/GPSno ), with multiple modules for researchers to visualize, browse, and download multi-dimensional data. Our study provides a comprehensive genetic and pharmacogenomic landscape of snoRNAs, which will shed light on future clinical considerations for the development of snoRNA-based targeted therapies.

Immunotherapy has tremendous potential to treat many patients with cancer. In this study, the authors investigate the impact of gender on the response to therapy, highlighting the importance to include omics profiling in clinical studies.

BackgroundAdrenocorticotropic hormone (ACTH) is widely used in adrenal vein sampling (AVS) and can be administered as a bolus injection or continuous infusion. The optimal administration method has not been determined. We aimed to compare the effects of ACTH bolus with infusion on cannulation success, lateralization assessment and adverse events (AEs).MethodsRetrospectively collected data from patients with primary aldosteronism who underwent AVS with ACTH at a tertiary hospital in China. Rate of successful cannulation, lateralization index (LI), complete biochemical remission and AEs related to AVS were analyzed.ResultsThe study included 80 patients receiving ACTH bolus and 94 receiving infusions. The rate of successful cannulation was comparable between bolus and infusion groups (75/80, 93.4% vs 88/94, 93.6%). In those with successful cannulation, the bolus group had a higher selectivity index than the infusion group, while LI [6.4(1.8-17.5) vs. 7.6(2.0-27.8), P=0.48] and rate of complete biochemical remission (43/44, 97.7% vs 53/53, 100%, P=0.45) did not significantly differ between the two groups. One in the bolus and one patient in the infusion group had adrenal vein rupture but they recovered with conservative treatment. The bolus group reported more transient AEs such as palpitation (52.9% vs 2.2%) and abdominal discomfort (40.0% vs 2.2%) than the infusion group.ConclusionsDue to their similar effects on cannulation success and lateralization, but a lower rate of transient AEs in the infusion group, the continuous infusion method should be recommended for ACTH stimulation in AVS.

More and more tourists tend to seek cultural enjoyment while taking trips based on their satisfied socio-economic needs. The spatiality of cultural tourism determines the feasibility and convenience of the access to cultural tourism resources. Given that spatial research on cultural tourism rarely involves the underdeveloped regions in China, especially via Baidu Index data, this study aims to explore the dynamic spatial pattern of cultural tourism Internet attention based on Baidu Index through social network analysis (i.e., network density, centrality analysis, core–periphery model, etc.) in the Western Triangle Economic Zone (WTEZ), China. Research findings are as follows. (1) Temporally, the centrality is increasingly enhanced in terms of the core cities with high cultural tourism Internet attention, as well as their radiation effect. (2) Spatially, the distribution pattern of cultural tourism Internet attention is shifting from polarization to equilibrium. However, the overall network density still presents a mode of loose connection and fails to extend from the core triangle structure in the planar dimension. (3) The cultural tourism Internet attention in WTEZ presents an obvious core–periphery pattern. Xi’an–Chengdu–Chongqing is in a dominant position, and the core area spreads from south to north. (4) The spatial-temporal pattern of cultural tourism Internet attention in WTEZ is influenced by transportation, reception facilities, consumption ability, and political environment, and the main driving factors are the number of hotels, per capita income, total highway mileage, and cultural tourism policy indicators. This study is conducive to sustainable spatial planning of cultural tourism through smart data governance.

Data-driven deep neural networks have demonstrated their superiority in high-resolution remote-sensing image (HRSI) classification based on superpixel-based objects. Currently, most HRSI classification methods that combine deep learning and superpixel object segmentation use multiple scales of stacking to satisfy the contextual semantic-information extraction of one analyzed object. However, this approach does not consider the long-distance dependencies between objects, which not only weakens the representation of feature information but also increases computational redundancy. To solve this problem, a superpixel-based long-range dependent network is proposed for HRSI classification. First, a superpixel segmentation algorithm is used to segment HRSI into homogeneous analysis objects as input. Secondly, a multi-channel deep convolutional neural network is proposed for the feature mapping of the analysis objects. Finally, we design a long-range dependent framework based on a long short-term memory (LSTM) network for obtaining contextual relationships and outputting classes of analysis objects. Additionally, we define the semantic range and investigate how it affects classification accuracy. A test is conducted by using two HRSI with overall accuracy (0.79, 0.76) and kappa coefficients (κ) (0.92, 0.89). Both qualitative and quantitative comparisons are adopted to test the proposed method’s efficacy. Findings concluded that the proposed method is competitive and consistently superior to the benchmark comparison method.

In the aviation industry, foreign object debris (FOD) on airport runways is a serious threat to aircraft during takeoff and landing. Therefore, FOD detection is important for improving the safety of aircraft flight. In this paper, an unsupervised anomaly detection method called Multi-Scale Feature Inpainting (MSFI) is proposed to perform FOD detection in images, in which FOD is defined as an anomaly. This method adopts a pre-trained deep convolutional neural network (CNN) to generate multi-scale features for the input images. Based on the multi-scale features, a deep feature inpainting module is designed and trained to learn how to reconstruct the missing region masked by the multi-scale grid masks. During the inference stage, an anomaly map for the test image is obtained by computing the difference between the original feature and its reconstruction. Based on the anomaly map, the abnormal regions are identified and located. The performance of the proposed method is demonstrated on a newly collected FOD dataset and the public benchmark dataset MVTec AD. The results show that the proposed method is superior to other methods.

In this study, a detailed genetic dissection of the huge and complex blaNDM-carrying genetic elements and their related mobile genetic elements was performed in Enterobacteriaceae. An extensive comparison was applied to 12 chromosomal genetic elements, including six sequenced in this study and the other six from GenBank. These 12 genetic elements were divided into five groups: a novel IME Tn6588; two related IMEs Tn6523 (SGI1) and Tn6589; four related ICEs Tn6512 (R391), Tn6575 (ICEPvuChnBC22), Tn6576, and Tn6577; Tn7 and its derivatives Tn6726 and 40.7-kb Tn7-related element; and two related IMEs Tn6591 (GIsul2) and Tn6590. At least 51 resistance genes, involved in resistance to 18 different categories of antibiotics and heavy metals, were found in these 12 genetic elements. Notably, Tn6576 carried another ICE Tn6582. In particular, the six blaNDM-carrying genetic elements Tn6588, Tn6589, Tn6575, Tn6576, Tn6726, and 40.7-kb Tn7-related element contained large accessory multidrug resistance (MDR) regions, each of which had a very complex mosaic structure that comprised intact or residual mobile genetic elements including insertion sequences, unit or composite transposons, integrons, and putative resistance units. Core blaNDM genetic environments manifested as four different Tn125 derivatives and, notably, two or more copies of relevant Tn125 derivatives were found in each of Tn6576, Tn6588, Tn6589, and 40.7-kb Tn7-related element. The huge and complex blaNDM-carrying genetic elements were assembled from complex transposition and homolog recombination. Firstly identified were eight novel mobile elements, including three ICEs Tn6576, Tn6577, and Tn6582, two IMEs, Tn6588 and Tn6589, two composite transposons Tn6580a and Tn6580b, and one integron In1718.

Abstract Background Human cancer cell lines are fundamental models for cancer research and therapeutic strategy development. However, there is no characterization of circular RNAs (circRNAs) in a large number of cancer cell lines. Methods Here, we apply four circRNA identification algorithms to heuristically characterize the expression landscape of circRNAs across ~ 1000 human cancer cell lines from CCLE polyA-enriched RNA-seq data. By using integrative analysis and experimental approaches, we explore the expression landscape, biogenesis, functional consequences, and drug response of circRNAs across different cancer lineages. Results We revealed highly lineage-specific expression patterns of circRNAs, suggesting that circRNAs may be powerful diagnostic and/or prognostic markers in cancer treatment. We also identified key genes involved in circRNA biogenesis and confirmed that TGF-β signaling may promote biogenesis of circRNAs. Strikingly, we showed that clinically actionable genes are more likely to generate circRNAs, potentially due to the enrichment of RNA-binding protein (RBP) binding sites. Among these, circMYC can promote cell proliferation. We observed strong association between the expression of circRNAs and the response to drugs, especially those targeting chromatin histone acetylation. Finally, we developed a user-friendly data portal, CircRNAs in cancer cell lines (CircRiC, https://hanlab.uth.edu/cRic), to benefit the biomedical research community. Conclusions Our study provides the characterization of circRNAs in cancer cell lines and explored the potential mechanism of circRNA biogenesis as well as its therapeutic implications. We also provide a data portal to facilitate the related biomedical researches.

As the key tool for land use management in China, land use planning (LUP) is characterized by the advantage of being state-led, quota-oriented, and easily monitored. Nevertheless, increasing research has doubted its effectiveness, particularly in controlling urban expansion, while few studies have empirically confirmed it. To this end, we construct a planning constraint index (PCI), supported by land use quota, for evaluating the pressure from LUP on urban expansion, and then analyze the spatial equilibrium of PCI. We also explore the spatial effects of PCI on urban expansion via the geographically weighted regression model (GWR) by collecting the spatial data of 280 prefecture-level cities in China from 2009 to 2016. The results show that: (1) most cities present a shortage of urban land quotas, and spatial disequilibrium exist among regions; (2) PCI has significant negative effects on urban expansion for all of the 280 cities, and spatial disparity of these effects occurs as well; (3) PCI has a stronger influence in southwest China where the economy is relatively backward. This study aims to provide a reference for land use planners and policymakers to help improve the effectiveness of LUP.

Pseudomonas aeruginosa is noted for its intrinsic antibiotic resistance and capacity of acquiring additional resistance genes. In this study, the genomes of nine clinical P. aeruginosa isolates were fully sequenced. An extensive genetic comparison was applied to 18 P. aeruginosa accessory genetic elements (AGEs; 13 of them were sequenced in this study and located within P. aeruginosa chromosomes) that were divided into four groups: five related integrative and conjugative elements (ICEs), four related integrative and mobilizable elements (IMEs), five related unit transposons, and two related IMEs and their two derivatives. At least 45 resistance genes, involved in resistance to 10 different categories of antibiotics and heavy metals, were identified from these 18 AGEs. A total of 10 β-lactamase genes were identified from 10 AGEs sequenced herein, and nine of them were captured within class 1 integrons, which were further integrated into ICEs and IMEs with intercellular mobility, and also unit transposons with intracellular mobility. Through this study, we identified for the first time 20 novel MGEs, including four ICEs Tn6584, Tn6585, Tn6586, and Tn6587; three IMEs Tn6853, Tn6854, and Tn6878; five unit transposons Tn6846, Tn6847, Tn6848, Tn6849, and Tn6883; and eight integrons In1795, In1778, In1820, In1784, In1775, In1774, In1789, and In1799. This was also the first report of two resistance gene variants blaCARB-53 and catB3s, and a novel ST3405 isolate of P. aeruginosa. The data presented here denoted that complex transposition and homologous recombination promoted the assembly and integration of AGEs with mosaic structures into P. aeruginosa chromosomes.

ObjectivesTo investigate the serum level of osteocalcin (OC), also known as bone Gla protein, in maintenance hemodialysis (MHD) patients and its correlation with abdominal aortic calcification (AAC).MethodsFrom July 2017 to February 2020, we enrolled 108 adult MHD patients. Routine fasting blood laboratory tests were performed before the start of the second hemodialysis in a week. Abdominal aortic calcification score (AACs) was assessed within 1 month. Pearson correlation and Logistic regression were used to analyze the data.ResultsThe OC level was 231.56 (25.92,361.33) ng/ml, elevating significantly in this group of MHD patients. It had a positive correlation with serum phosphorus (r = 0.511, P = 0.001), intact parathyroid hormone(iPTH) (r = 0.594, P = 0.0001), fibroblast growth factor 23(FGF23) (r = 0.485, P = 0.003) and a negative correlation with age(r = -0.356, P = 0.039). Based on the AACs, patients were divided into two groups. Serum OC level were higher in patients with AACs≥5 (p=0.032). A multiple logistics regression analysis revealed that age (odds ratio [OR]1.14, P=0.005) and OC(OR=1.10, P=0.008)were risk factors for high AACs(≥5).ConclusionThe study implicated that OC elevated significantly in this group of MHD patients.OC is positively correlated with phosphorus, iPTH, FGF23, and a negative correlation with age. OC was a risk factor for vascular calcification in this study, but this study did not classify osteocalcin as c-OC and unOC. Whether unOC is associated more directly with vascular calcification requires further study.

In recent years, aviation security has become an important area of concern as foreign object debris (FOD) on the airport pavement has a huge potential risk to aircraft during takeoff and landing. Therefore, accurate detection of FOD is important to ensure aircraft flight safety. This paper proposes a novel method to detect FOD based on random forest. The complexity of information in airfield pavement images and the variability of FOD make FOD features difficult to design manually. To overcome this challenge, this study designs the pixel visual feature (PVF), in which weight and receptive field are determined through learning to obtain the optimal PVF. Then, the framework of random forest employing the optimal PVF to segment FOD is proposed. The effectiveness of the proposed method is demonstrated on the FOD dataset. The results show that compared with the original random forest and the deep learning method of Deeplabv3+, the proposed method is superior in precision and recall for FOD detection. This work aims to improve the accuracy of FOD detection and provide a reference for researchers interested in FOD detection in aviation.

Aldosterone-producing adenoma (APA) is a main cause of primary aldosteronism (PA). Given that a large benign-appearing unilateral masse (>1 cm in diameter) may represent an aldosterone and cortisol-co-secreting adenoma, dexamethasone suppression testing is required in such patients to exclude or confirm the diagnosis of hypercortisolism. Tuberculosis is highly prevalent in China, and rifamycins are often used in these patients. Rifapentine belongs to the rifamycin family, and we herein for the first time report a case of misdiagnosis of hypercortisolism due to rifapentine use in a patient with APA. Thus, in patients treated with rifapentine, diagnosis of hypercortisolism based on dexamethasone suppression tests can be very misleading.

Abstract Background The dorsolateral prefrontal cortex (DLPFC) is the standard stimulation target for the repetitive transcranial magnetic stimulation (rTMS) treatment of major depression disorder (MDD). A retrospective study by Fox and colleagues found that a more negative resting‐state functional magnetic resonance imaging (RS‐fMRI) functional connectivity (FC) between left DLPFC and the subgenual anterior cingulate cortex (sgACC) in a large group of healthy participants is associated with a better curative effects of rTMS in MDD, suggesting that the sgACC may be an effective region. However, a recent meta‐analysis on RS‐fMRI studies found that the pregenual ACC (pgACC), rather than the sgACC, of MDD patients showed increased local activity. Methods We used the stimulation coordinates in the left DLPFC analyzed by Fox et al. to perform RS‐fMRI FC between the stimulation targets obtained from previous rTMS MDD studies and the potential effective regions (sgACC and pgACC, respectively) on the RS‐fMRI data from 88 heathy participants. Results (a) Both the pgACC and the sgACC were negatively connected to the left DLPFC; (b) both FCs of sgACC‐DLPFC and pgACC‐DLPFC were more negative in responders than in nonresponders; and (c) the associations between DLPFC‐sgACC functional connectivity and clinical efficacy were clustered around the midline sgACC. Conclusions Both the pgACC and the sgACC may be potential effective regions for rTMS on the left DLPFC for treatment of MDD. However, individualized ACC‐DLPFC FC‐based rTMS on depression should be performed in the future to test the pgACC or the sgACC as effective regions.

Functional magnetic resonance imaging (fMRI) studies have shown that the effect of repetitive transcranial magnetic stimulation (rTMS) can induce changes in remote brain regions. In the stimulated regions, low-frequency (≤1 Hz) rTMS induces inhibitory effects, while high-frequency (≥5 Hz) stimulation induces excitatory effects. However, these stereotypical effects arising from low- and high-frequency stimulation are based on measurements of motor evoked potentials (MEPs) induced by pulsed stimulation. To test the effects of rTMS on remote brain regions, the current study recruited 31 young healthy adults who participated in three rTMS sessions (10 Hz high frequency, 1 Hz low frequency, and sham) on three separate days. The stimulation target was based on individual fMRI activation in the motor cortex evoked by a finger movement task. Pre- and post-rTMS resting-state fMRI (RS-fMRI) were acquired. Regional homogeneity (ReHo) and degree centrality (DC) were calculated to measure the local and global connectivity, respectively. Compared with the sham session, high-frequency (10 Hz) rTMS significantly increased ReHo and DC in the right cerebellum, while low-frequency (1 Hz) stimulation did not significantly alter ReHo or DC. Then, using a newly developed PAIR support vector machine (SVM) method, we achieved accuracy of 93.18–97.24% by split-half validation for pairwise comparisons between conditions for ReHo or DC. While the univariate analyses suggest that high-frequency rTMS of the left motor cortex could affect distant brain activity in the right cerebellum, the multivariate SVM results suggest that both high- and low-frequency rTMS significantly modulated widespread brain activity. The current findings are useful for increasing the understanding of the mechanisms of rTMS, as well as guiding precise individualized rTMS treatment of movement disorders.

MCL1, a pro-survival BCL-2 related protein with rapid turnover rate, is often dysregulated in cancers. Here, the authors show that MCL1’s stability is regulated by deubiquitinase USP13, and its inhibition sensitises tumor cells to BH3 mimetic inhibitors.

Across cancer types tumor heterogeneity has been observed, but how this relates to tumor evolution is unclear. Here, the authors sequence multiple synchronous lung cancers, highlighting the evolutionary pressures that simultaneously shape the expansion and constraint of genomic heterogeneity.

Schools are an important food environment to cultivate and promote healthy food choices and practices among children and adolescents. The aim of the present study was to assess the type and quality of food and beverages sold in school canteens in public primary and secondary schools in Kelantan, Malaysia. Eligible schools were randomly selected from the list of all schools and detailed information of all food and beverage items sold in the school canteens were collected during school days. Food and beverages were classified based on food groups derived from the Malaysian Food Dietary Guideline and the Recommended Foods for Healthy Cafeteria Guideline. An assessment of the traffic-light nutrition food-labelling system of the total sugar content in all pre-packaged foods was also undertaken. A total of 568 food items were identified, with secondary school canteens selling a greater proportion of food items than the primary schools (55.5% vs. 44.5%). In terms of the main food groups, grains and cereal products represented the largest food group served (33–36%), followed by beverages (21–25%) and confectionary and sweet foods (12–13%). In contrast, the vegetable and fruit group represented the smallest proportion of food items sold (1–3%). Comparisons between primary and secondary schools showed a similar trend and pattern of food types and quality of foods sold, except for animal-based foods. A greater percentage of food items in this category was found among secondary schools (12.1%) versus primary schools (6.7%). When total sugar content of all pre-packaged foods was quantified based on the traffic-light nutrition-labelling system, almost one-third of foods and beverages were classified as high (29.1%). Confectionary (19.1%) and flavoured milk and fruit drinks (10.0%) both exceeded the recommended sugar levels of >22.5 g per 100 g and >11.25 mL per 100 m L, respectively. Only one of these packaged foods and beverages (0.9%) was classified as a healthy food choice. About a quarter of the food items available in school canteens were classified as prohibited based on a new revised list of prohibited food and beverage items. These findings indicate that, despite the Guidelines, a large number of unhealthy food items are being sold in school canteens. Hence, interventions such as sustainable healthy school canteen menus should be implemented to promote healthy food choices amongst school-aged children.