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The popularisation of autonomous vehicles will give rise to a new business model called shared autonomous vehicle (SAV). SAVs may attract a large number of passengers and lead to a decline in the share of buses, which can be interpreted by exploring passengers’ travel behaviour when confronting the SAV and bus modes. Thus, this paper addresses the SAV and bus passengers’ travel behaviour, aiming to examine the factors influencing travel behaviour and revealing the characteristics of SAV passengers. We classified passengers using latent class cluster analysis and modelled passengers’ travel behaviour based on confirmatory factor analysis and mixed logit model. The findings indicate a variation in travel preferences among different classes of travellers. Short-distance travellers pay less attention to travel time. Non-short-distance PT travellers are most likely to be affected by service attributes (waiting time, travel time and travel costs). Non-short-distance private car travellers are more likely to become early SAV adopters. Passengers travelling for short distances may be more likely to choose SAV, which reveals the potential of SAVs to become a first and last mile connection for public transport. Passengers lack trust in SAVs, which will affect their promotion.

Abstract TNFAIP8 family molecules have been recognized for their involvement in the progression of tumors across a range of cancer types. Emerging experimental data suggests a role for certain TNFAIP8 family molecules in the development of glioma. Nonetheless, the comprehensive understanding of the genomic alterations, prognostic significance, and immunological profiles of TNFAIP8 family molecules in glioma remains incomplete. In the study, using the comprehensive bioinformatics tools, we explored the unique functions of 4 TNFAIP8 members including TNFAIP8, TNFAIP8L1, TNFAIP8L2 and TNFAIP8L3 in glioma. The expressions of TNFAIP8, TNFAIP8L1, TNFAIP8L2, and TNFAIP8L3 were notably upregulated in glioma tissues compared to normal tissues. Furthermore, survival analysis indicated that elevated expression levels of TNFAIP8, TNFAIP8L1 and TNFAIP8L2 were correlated with unfavorable outcomes in terms of overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) among glioma patients. Genetic modifications, such as mutations and copy number alterations, within the TNFAIP8 family exhibited a significant association with extended OS, DSS and PFS in individuals diagnosed with glioma. The findings suggest a noteworthy correlation between TNFAIP8 family members and the age and 1p/19q codeletion status of glioma patients. We also found that there were significant relationships between TNFAIP8 family expression and tumor immunity in glioma. Furthermore, functional annotation of TNFAIP8 family members and their co-expressed genes in gliomas was carried out using GO and KEGG pathway analysis. The GO analysis revealed that the primary biological processes influenced by the TNFAIP8 family co-expressed genes included cell chemotaxis, temperature homeostasis, and endocytic vesicle formation. Additionally, the KEGG analysis demonstrated that TNFAIP8 family co-expressed genes are involved in regulating various pathways such as inflammatory mediator regulation of TRP channels, pathways in cancer, prolactin signaling pathway, and Fc gamma R-mediated phagocytosis. Overall, the findings suggest that TNFAIP8 family members may play a significant role in the development of glioma and have the potential to serve as prognostic indicators and therapeutic targets for individuals with glioma.

Abstract Background Medical research in complementary and alternative medicine (CAM) has increased recently, raising ethical concerns about the moral status of CAM. Medical academic journals are responsible for conducting ethical review (ER) of manuscripts to protect the interests of human subjects and to make ethical results available before deciding to publish. However, there has been no systematic analysis of the ER in CAM journals. This study is aim to evaluate the current status of ethical requirements and compliance in CAM journals. Methods This is a cross-sectional study. We reviewed instructions for authors (IFAs) of CAM journals included in the Journal Citation Reports (2021) ( https://jcr.clarivate.com ) for general information and requirements for ER. We also browsed the manuscripts regarding randomized controlled trials published by CAM journals in Q1 and Q2 section from January to June, 2023, to check the actual situation of ethical requirement. Descriptive statistics and Fisher’s exact test were used for statistical analysis. Results 27 journals and 68 manuscripts were ultimately included. 92.6% (25/27) IFAs included keywords of ER, indicating the presence of ethical considerations. However, no specific ER was required for CAM (n = 0). We categorized journals by Geographic origin, JCR section, Year of electronic JCR, Types of studies, % of OA Gold to explore the factors that could influence CAM journals to have certain ethical review policies. The results showed there was no statistical significance in certain ethical review policy in any classification of journals (p > 0.05). All RCT manuscripts included in the study generally met the requirements of the published journals for ethical review. Conclusions All IFAs discussed ER, but the content was scattered, unfocused, and there were no specific ER requirements regarding CAM. Although the manuscripts basically met the requirements of the journal, it was not possible to get closer to the process of ER in the manuscript. To ensure full implementation of these policies in the future, CAM journals should require authors to provide more details, or to form a list of items necessary for CAM ethical review.

Abstract Background and aim Traditional Chinese medicine (TCM) is widely used by patients with amyotrophic lateral sclerosis (ALS). However, their reasons and experience in using TCM have received insufficient attention. Therefore, we conducted a mixed method study to gain insights into this issue. Materials and methods This study was conducted on the basis of the China Amyotrophic Lateral Sclerosis Registry of Patients with Traditional Chinese Medicine (CARE-TCM). Data were collected from Dongzhimen Hospital through a mixed method approach, including a questionnaire and a semi-structured interview. Patients with ALS who were using TCM when they were initially registered with CARE-TCM and who had been followed-up for over six months were recruited. The questionnaires’ outcomes were statistically outlined, and the interview transcripts were thematically analysed to identify themes and sub-themes. Results Fifty-two and sixteen patients were included in the questionnaire and semi-structured interview groups, respectively. Patients used TCM with the hope of regulating their body holistically to improve nonmotor symptoms and quality of life (QOL). Those who recognised TCM as ineffective tended to discontinue it after a three-month trial period. Although quality was a major concern, herbal medicine (HM) was the most frequently used modality among all participants (n = 52), with the majority (n = 44, 84.6%) continuing to use it. Patients emphasised in-person consultations as a crucial part of TCM treatment. However, the disability caused by disease often made this interaction unattainable. Conclusion Nonmotor symptoms and QOL hold substantial importance for patients with ALS using TCM. HM is a more suitable modality than other TCM treatment modalities, but patients are facing challenges in seeking HM treatment. It is necessary to promote the implementation of hierarchical diagnosis and treatment, thus making TCM more accessible. Trial registration ClinicalTrials.gov identifier: NCT04885374 (registered on May 13, 2021).

Abstract To achieve the best management of the ecosystem and sustainable socioeconomic development, it is crucial to clarify the matching relationship between the supply and demand of ecosystem services (ESs). Four types of ESs were chosen for the Hexi region in this study: food supply, carbon sequestration, water yield, wind erosion control and sediment retention. We assessed the supply–demand and matching relationships of different ESs using the Integrated Valuation of Ecosystem Service and Tradeoffs (InVEST) model, the ESs supply–demand ratio and the four-quadrant model. Moreover, we also analyzed the supply–demand ratio of integrated ESs and their cold spots. The findings suggest that (1) from 2000 to 2020, the average supply of food supply, carbon sequestration, water yield, wind erosion control and sediment retention increased by 44.31 t/km2, 128.44 t/hm2, 14,545.94 m3/km2 and 0.14 kg/m2 respectively, which showed a spatial pattern of “high in the southeast and low in the northwest”. The average demand for food supply and carbon sequestration increased by 1.33 t/km2 and 0.32 t/hm2 respectively, while the average demand for water yield and wind erosion control and sediment retention decreased by 2997.25 m3/km2 and 1.19 kg/km2 respectively. The spatial distribution is consistent with the layout of population density, production and residential areas, and fragile ecological areas. (2) The supply–demand ratio of food supply, carbon sequestration and water yield is greater than 0.095, which is in a state of oversupply, and the supply–demand ratio of wind erosion control and sediment retention is less than 0, which is in a state of shortage; all ESs are mainly in low-low spatial matching areas, mainly concentrated in the desert areas of the northwest in the Hexi region. (3) The supply–demand ratio of integrated ESs increased by 0.024, and the proportion of cold spots and sub-cold spots was more than 50% and concentrated in the northwest, while hot spots and sub-hot spots accounted for only about 16%, mainly distributed in the southern Qilian Mountains and some oasis areas.

Abstract The rigid hull encasing Tartary buckwheat seeds necessitates a laborious dehulling process before flour milling, resulting in considerable nutrient loss. Investigation of lignin composition is pivotal in understanding the structural properties of tartary buckwheat seeds hulls, as lignin is key determinant of rigidity in plant cell walls, thus directly impacting the dehulling process. Here, the lignin composition of seed hulls from 274 Tartary buckwheat accessions is analyzed, unveiling a unique lignin chemotype primarily consisting of G lignin, a common feature in gymnosperms. Furthermore, the hardness of the seed hull showed a strong negative correlation with the S lignin content. Genome‐wide detection of selective sweeps uncovered that genes governing the biosynthesis of S lignin, specifically two caffeic acid O‐methyltransferases (COMTs) and one ferulate 5‐hydroxylases, are selected during domestication. This likely contributed to the increased S lignin content and decreased hardness of seed hulls from more domesticated varieties. Genome‐wide association studies identified robust associations between FtCOMT1 and the accumulation of S lignin in seed hull. Transgenic Arabidopsis comt1 plants expressing FtCOMT1 successfully reinstated S lignin content, confirming its conserved function across plant species. These findings provide valuable metabolic and genetic insights for the potential redesign of Tartary buckwheat seed hulls.

Abstract Global gridded data sets of observed extremes indices underpin assessments of changes in climate extremes. However, similar efforts to enable the assessment of indices relevant to different sectors of society have been missing. Here we present a data set of sector‐specific indices, based on daily station data, that extends the HadEX3 data set of climate extremes indices. These additional indices, which can be used singly or in combinations, have been recommended by the World Meteorological Organization and are intended to empower decision makers in different sectors with accurate historical information about how sector‐relevant measures of the climate are changing, especially in regions where in situ daily temperature and rainfall data are hard to come by. The annual and/or monthly indices have been interpolated on to a 1.875° × 1.25° longitude‐latitude grid for 1901–2018. We show changes in globally‐averaged time series of these indices in comparison with reanalysis products. Changes in temperature‐based indices are consistent with global scale warming, with days with Tmax > 30°C (TXge30) increasing virtually everywhere with potential impacts on crop fertility. At the other end of the scale, the number of days with Tmin

Abstract Bergenia purpurascens is an important medicinal, edible and ornamental plant. It generally grows in high-altitude areas with complex climates. There have been no reports about how B. purpurascens survives under cold stress. Here, the B. purpurascens under low temperature were subjected to transcriptomics analysis to explore the candidate genes and pathways that involved in the cold tolerance of B. purpurascens. Compared with the control treatment, we found 9,600 up-regulated differentially expressed genes (DEGs) and 7,055 down-regulated DEGs. A significant number of DEGs were involved in the Ca2+ signaling pathway, mitogen-activated protein kinase (MAPK) cascade, plant hormone signaling pathway, and lipid metabolism. A total of 400 transcription factors were found to respond to cold stress, most of which belonged to the MYB and AP2/ERF families. Five novel genes were found to be potential candidate genes involved in the cold tolerance of B. purpurascens. The study provide insights into further investigation of the molecular mechanism of how B. purpurascens survives under cold stress.

Abstract Background While substantial placebos have been used in herbal medicine (HM) clinical trials for rare diseases, the use and quality of reporting of HM-placebo remain unclear. We aim to describe the use of HM-placebo in clinical trials for rare diseases and determine the quality of reporting in these trials. Methods This is a cross-sectional study. We searched PubMed, Embase, Web of Science, SinoMed, China National Knowledge Infrastructure, WanFang database, China Science and Technology Journal Database, National Institute of Informatics Support Academic Information Services, ClinicalTrials.gov and Chinese Clinical Trials Registry from their inception date to 14 February 2023 to identify registered and published trials that use placebos as a comparator in rare diseases. We collected data on placebo use reporting and the efficacy and safety of placebo. Descriptive statistics, the Chi-square test, and Binary multivariable logistic regression analysis were used to determine the placebo characteristics of the HM trial and its effect on reporting. Results Among the 55 studies, we included that with a median administration time of placebo of 84 days (IQR 42–180) and a median placebo sample size of 30 (IQR 24–54). About half of the trials (27, 49.1%) did not provide their ethical approvals, and one trial had details of informed consent. None of the studies were fully reported and more than half of the items reported less than 50%. A total of 10 trials (18.2%) of placebo has active ingredients even though none of them performed pharmacological inert tests. Of the 29 studies with available data on adverse events, 5 (17.2%) trials did not show a better safety profile in the placebo group. Under the context that a relatively high-quality report is defined as a report with more than 9 items, there was a statistically significant difference between the two groups in the rate of relatively high-quality reports of the administration time (p = 0.047, OR 0.10, 95% CI 0.01 to 0.90), but the results are not representative. Conclusion The overall situation of HM-placebo in the field of rare diseases was poor. In particular, the placebo is tied to the quality of trials, and poor placebo hinders the generation of high-quality evidence for herbal clinical trials in the field of rare diseases. We summarize the current methods of assessment involved in the use of placebos and propose various considerations for placebos in different contexts. Our study can greatly promote rare disease researchers to review the quality of their placebo and clinical trials. It is imperative to guarantee that meticulously conducted research generates clinical evidence of the highest caliber. We also expect that in the future, more rigorous relevant standards about the reporting and design of HM-placebo will be developed. High-quality clinical trials are the prerequisite for the wide clinical application of herbal medicines for rare diseases.

The effective utilization of medium-high temperature geothermal energy is pivotal in reducing carbon emissions and plays a crucial role in developing clean energy technologies. The MiDu geothermal field, situated in the southeastern region of Dali Prefecture, Yunnan Province, lies within the Mediterranean–Himalayan high-temperature geothermal belt and is characterized by abundant geothermal resources. However, due to its considerable depth, exploration poses significant risks, resulting in a total utilization rate of less than 0.5% of the total reserves. This study employs natural seismic data to perform a tomographic analysis of the geothermal system in the Midu basin. By examining the P-wave velocity (Vp) and the velocity ratio of P-waves and S-waves (Vp/Vs) at various depths, the findings reveal that the basin comprises two distinct structural layers: the thrust basement of the Mesozoic and Paleozoic eras and the strike–slip extensional sedimentary layer of the Cenozoic era. A low-velocity anomaly in the central basin corresponds to the loose Cenozoic sedimentary layer. In contrast, high-velocity anomalies at the basin edges correlate with boundary faults and the Mesozoic–Paleozoic strata. Below a depth of 4 km, the Red River Fault and MiDu Fault continue to dominate the basin’s structure, whereas the influence of the Malipo Fault diminishes. The MiDu Fault exhibits higher thermal conductivity than the Yinjie Fault. It interfaces with multiple carbonate and basalt formations characterized by well-developed pores and fractures, making it a crucial conduit for water and a control point for geothermal storage. Consequently, the existence of medium-high temperature (>90 °C) geothermal resources for power generation should be concentrated around the Midu fault on the western side of the basin, while the Yinjie fault area is more favorable for advancements in heating and wellness.

An aging population is one of the main features of China's current population structure, and it is a key area that needs attention to achieve high-quality population development. Because of its unique geographical environment, economic conditions, and sociocultural background, the study of population aging in the karst region of southwest China is particularly important. However, there is a lack of research exploring the regional differentiation of population aging and its influencing factors in the karst regions of southwest China. In light of this, we chose Anshun City, located in Guizhou Province's southwest area, as the case study area. We used the Lorenz curve and spatial autocorrelation to study the differences in the spatial distribution pattern of population aging and introduced multi-scale geographical weighted regression to explore its influencing factors. The results show that Anshun City's older people population proportion (OPP) is generally high with more than 7% of the older people there, making it part of an aging society. The OPP appeared high in the east and low in the west in spatial distribution; the older people population density (OPD) revealed a gradually increasing trend from south to north. At the township scale, both the OPP and the OPD showed significant spatial positive correlation, and the spatial agglomeration characteristics were obvious. OPD and OPP have a positive spatial correlation at the global level, and townships with similar OPP or OPD were spatially adjacent. The spatial distribution characteristics of population aging are the consequence of complex contributions such as natural, social, economic, and karst factors. Further, the spatial distribution pattern of aging is determined by a variety of influencing factors, which have different directions and intensities. Therefore, it is necessary to formulate and implement corresponding policies and strategies to deal with the aging problem in the future.

Abstract Rare precipitation events with return periods of multiple decades to hundreds of years are particularly damaging to natural and societal systems. Projections of such rare, damaging precipitation events in the future climate are, however, subject to large inter‐model variations. We show that a substantial portion of these differences can be ascribed to the projected warming uncertainty, and can be robustly reduced by using the warming observed during recent decades as an observational constraint, implemented either by directly constraining the projections with the observed warming or by conditioning them on constrained warming projections, as verified by extensive model‐based cross‐validation. The temperature constraint reduces >40% of the warming‐induced uncertainty in the projected intensification of future rare daily precipitation events for a climate that is 2°C warmer than preindustrial across most regions. This uncertainty reduction together with validation of the reliability of the projections should permit more confident adaptation planning at regional levels.

Background: The Delphi method has been extensively used to reach a consensus in traditional Chinese medicine (TCM) syndrome diagnosis research when subjective judgment is not uniform and objective evidence is lacking. The conduct and reporting of the Delphi method in TCM syndrome diagnosis research have never been critiqued. Our study aims to explore the consistency of using this technique and assess the reporting quality. Methods: A cross-sectional study was employed to scope articles reporting the conduct of the Delphi method in TCM syndrome diagnosis research. We searched the PubMed, Web of Science, CNKI, VIP, Wanfang and SinoMed databases with the restriction of Chinese and English language from their inception to March 25, 2023. A standardized extraction form was designed to collect demographics and methodological processes reflecting the rigor and transparency in TCM syndrome diagnosis research. Results: A total of 1832 studies were screened, and 50 were included. The median number of panels was 30 (IQR 20–34.5) and only 12 (24.0 %) studies were with a heterogeneous sample of panels. Two rounds was most common (37/50; 74.0 %), followed by three (7/50; 14.0 %), and only 13 (26.0 %) studies determined the number of rounds a priori. The reporting quality varied, with 18.0 % (9/50) reporting anonymity, 30.0 % (15/50) describing the controlled feedback, 20.0 % (10/50) reporting the procedure duration (7.14 ± 3.29 months) and 26.0 % (13/50) predefining the consensus. Conclusion: The Delphi method is inconsistently conducted and nontransparently reported in TCM syndrome diagnosis research. Standardized criteria are urgently needed for best practices in future research.

Constructing resistive layer with novel structure holds great potential in upgrading electromagnetic properties of soft magnetic materials in a wide frequency range. In this work, FeNi@SiO2 composites with controllable core–shell structures, including 2D-type laminar shell and 3D-type raspberry-like shell, were fabricated by modified Stöber method. The structure of SiO2 shell depends highly on the concentration of tetraethyl orthosilicate (TEOS). In detail, a laminar shell can be formed at low TEOS concentration, owing to slow condensation. While at high TEOS concentration, heterogeneous growth on powder surface and homogeneous growth in solution of silica networks are significantly accelerated, resulting in the formation of the raspberry-like shell. Improved electromagnetic performance of FeNi@SiO2 cores at 2 MHz, including high resistivity, low eddy current loss, and low loss factor, should be ascribed to the unique raspberry-like shell structure. Meanwhile, raspberry-like shell also contributes to enhanced attenuation and acceptable impedance matching in GHz range. Consequently, a wide effective absorption bandwidth of 8.92 GHz can be achieved at a thin thickness of 1.85 mm. This work provides deep insights into the growth mechanism of different SiO2 shells and sheds new light on the design of high-performance soft magnetic composites working in different frequency bands.

Abstract The unique dumbbell-shape of grass guard cells (GCs) is controlled by their cell walls which enable their rapid responses to the environment. The molecular mechanisms regulating the synthesis and assembly of GC walls are as yet unknown. Here we have identified BZU3, a maize gene encoding UDP-glucose 4-epimerase that regulates the supply of UDP-glucose during GC wall synthesis. The BZU3 mutation leads to significant decreases in cellular UDP-glucose levels. Immunofluorescence intensities reporting levels of cellulose and mixed-linkage glucans are reduced in the GCs, resulting in impaired local wall thickening. BZU3 also catalyzes the epimerization of UDP-N-acetylgalactosamine to UDP-N-acetylglucosamine, and the BZU3 mutation affects N-glycosylation of proteins that may be involved in cell wall synthesis and signaling. Our results suggest that the spatiotemporal modulation of BZU3 plays a dual role in controlling cell wall synthesis and glycosylation via controlling UDP-glucose/N-acetylglucosamine homeostasis during stomatal morphogenesis. These findings provide insights into the mechanisms controlling formation of the unique morphology of grass stomata.

Abstract Temozolomide (TMZ) therapy offers minimal clinical benefits in patients with glioblastoma multiforme (GBM) with high EGFR activity, underscoring the need for effective combination therapy. Here, we show that tonicity-responsive enhancer binding protein (NFAT5) lysine methylation, is a determinant of TMZ response. Mechanistically, EGFR activation induces phosphorylated EZH2 (Ser21) binding and triggers NFAT5 methylation at K668. Methylation prevents NFAT5 cytoplasm interaction with E3 ligase TRAF6, thus blocks NFAT5 lysosomal degradation and cytosol localization restriction, which was mediated by TRAF6 induced K63-linked ubiquitination, resulting in NFAT5 protein stabilization, nuclear accumulation and activation. Methylated NFAT5 leads to the upregulation of MGMT, a transcriptional target of NFAT5, which is responsible for unfavorable TMZ response. Inhibition of NFAT5 K668 methylation improved TMZ efficacy in orthotopic xenografts and patient-derived xenografts (PDX) models. Notably, NFAT5 K668 methylation levels are elevated in TMZ-refractory specimens and confer poor prognosis. Our findings suggest targeting NFAT5 methylation is a promising therapeutic strategy to improve TMZ response in tumors with EGFR activation.

Human activities have caused different degrees of land-use change on different topographic gradients, with impacts on the landscape and ecosystem. Effectively preventing and addressing ecological risk (ER) and achieving harmonious coexistence between humans and nature are important aspects of sustainable development. In this study, we used Gansu Province as an example, adopted five periods of land-use data in 1980, 1990, 2000, 2010 and 2020, and used the geoinformatic Tupu method and the terrain distribution index to study land-use changes under different topographic gradients, and then constructed the landscape ecological risk assessment (LERA) model based on the landscape pattern index to analyze landscape ecological risk (LER) spatiotemporal changes under different topographic gradients, and finally explored the LER driving factors using the geodetector model. The results showed that (1) the dominant land-use types were unused land and grassland, accounting for approximately 74% of the land. The situation of transferring and changing each type was more drastic. The distribution and changes in cropland and built-up land were easily found in low topographic gradient areas with low elevations and small slopes; the distribution and changes in woodland, grassland and water areas were easily found in high topographic gradient areas with high elevations and large slopes. (2) The landscape ecological risk index (LERI) was 0.018, 0.019, 0.019, 0.019 and 0.020, respectively, with spatial expressions of high in the northwest and low in the southeast. Low LER was concentrated in high topographic gradient ecological reserves; high LER was concentrated in low topographic gradient human interference areas and high topographic gradient natural environmental complex areas. (3) Natural factors mainly acted on the LER on moderate and high topographic position gradients; socioeconomic factors mainly acted on the LER on low topographic position gradients. Human interference interacted with natural factors more than human interference alone on LER. This study can provide a scientific basis for ensuring ecological security and sustainable development in areas with complex topography and geomorphology.

Ecological management zoning plays a significant role in optimizing resource utilization, improving ecosystem service function, and promoting coordinated regional development. Taking Hexi Corridor as a representative region of the Mountain–Oasis–Desert composite system in arid regions of Asia, this study analyzed the spatial and temporal evolution of ecosystem service values and explored the influencing mechanism based on the optimal parameters-based geographical detector model. We have comprehensively divided ecological management zones and proposed corresponding control strategies. The results show that (1) the Hexi Corridor is characterized by regional differentiation, which is composed of three systems: The southern mountain system, central oasis system, and northern desert system. The mountain system is mainly composed of forestland and grassland, the oasis system is mainly composed of cropland, and the desert system is mainly composed of unused land. The conversion of land use mainly involves the conversion of unused land to cropland and grassland, while grassland is mainly converted to cropland. (2) The ecosystem service value of the Hexi Corridor increased significantly and demonstrated agglomeration characteristics in space. The highest value areas are mainly distributed in the southern mountain, with higher value and medium areas mainly distributed in the central oasis, and the lowest value areas are mainly located in the northern desert. (3) Socio-economic factors greatly influence the spatial differentiation of ecosystem service values in the Hexi Corridor, with natural environmental factors having less impact. Additionally, the internal interaction of natural environmental factors is the most significant. (4) The Hexi Corridor is divided into three ecological management zones: Ecological function protection zone, ecological and agricultural coordinated development zone, and ecological and urbanization coordinated development zone. This research has important reference value for global ecological management in arid regions.

With the widespread adoption of ultrasound guidance, Seldinger puncture techniques, and intracardiac electrical positioning technology for the placement of peripherally inserted central catheters in recent years, an increasing number of medical staff and patients now accept peripheral placement of totally implantable venous access devices (TIVADs) in the upper arm. This approach has the advantage of completely avoiding the risks of hemothorax, pneumothorax, and neck and chest scarring. Medical specialties presently engaged in this study in China include internal medicine, surgery, anesthesiology, and interventional departments. However, command over implantation techniques, treatment of complications, and proper use and maintenance of TIVAD remain uneven among different medical units. Moreover, currently, there are no established quality control standards for implantation techniques or specifications for handling complications. Thus, this expert consensus is proposed to improve the success rate of TIVAD implantation via the upper-arm approach, reduce complication rates, and ensure patient safety. This consensus elaborates on the technical indications and contraindications, procedures and technical points, treatment of complications, and the use and maintenance of upper-arm TIVAD, thus providing a practical reference for medical staff.

Abstract Background Microvascular complications are associated with an overtly increased risk of adverse outcomes in patients with diabetes including coronary microvascular injury which manifested as disruption of adherens junctions between cardiac microvascular endothelial cells (CMECs). However, particular mechanism leading to diabetic coronary microvascular hyperpermeability remains elusive. Methods Experimental diabetes was induced in mice with adipose tissue-specific Adipsin overexpression (AdipsinLSL/LSL-Cre) and their respective control (AdipsinLSL/LSL). In addition, cultured CMECs were subjected to high glucose/palmitic acid (HG + PA) treatment to simulate diabetes for a mechanistic approach. Results The results showed that Adipsin overexpression significantly reduced cardiac microvascular permeability, preserved coronary microvascular integrity, and increased coronary microvascular density. Adipsin overexpression also attenuated cardiac dysfunction in diabetic mice. E/A ratio, an indicator of cardiac diastolic function, was improved by Adipsin. Adipsin overexpression retarded left ventricular adverse remodeling, enhanced LVEF, and improved cardiac systolic function. Adipsin-enriched exosomes were taken up by CMECs, inhibited CMECs apoptosis, and increased CMECs proliferation under HG + PA treatment. Adipsin-enriched exosomes also accelerated wound healing, rescued cell migration defects, and promoted tube formation in response to HG + PA challenge. Furthermore, Adipsin-enriched exosomes maintained adherens junctions at endothelial cell borders and reversed endothelial hyperpermeability disrupted by HG + PA insult. Mechanistically, Adipsin blocked HG + PA-induced Src phosphorylation (Tyr416), VE-cadherin phosphorylation (Tyr685 and Tyr731), and VE-cadherin internalization, thus maintaining CMECs adherens junctions integrity. LC-MS/MS analysis and co-immunoprecipitation analysis (Co-IP) unveiled Csk as a direct downstream regulator of Adipsin. Csk knockdown increased Src phosphorylation (Tyr416) and VE-cadherin phosphorylation (Tyr685 and Tyr731), while abolishing Adipsin-induced inhibition of VE-cadherin internalization. Furthermore, Csk knockdown counteracted Adipsin-induced protective effects on endothelial hyperpermeability in vitro and endothelial barrier integrity of coronary microvessels in vivo. Conclusions Together, these findings favor the vital role of Adipsin in the regulation of CMECs adherens junctions integrity, revealing its promises as a treatment target against diabetic coronary microvascular dysfunction. Graphical Abstract Graphical abstract depicting the mechanisms of action behind Adipsin-induced regulation of diabetic coronary microvascular dysfunction.

Abstract To describe the clinical spectrum and prognosis of atypical tumefactive demyelinating lesions (TDLs), which were confirmed by pathology. A total of 11 patients were diagnosed with atypical TDLs confirmed by brain biopsy and surgery between January 2006 and December 2017. The clinical spectrum and prognosis in these patients were analyzed. The patients’ ages ranged from 29 to 62 years, with a mean age of 48.9 years; 72.7% were males. The Expanded Disability Status Scale (EDSS) of the patients with first onset was 2.36. Most of the patients started with limb numbness and weakness (45.5%) or alalia (27.2%). The mean time from symptom onset to biopsy or surgery was 12.9 days (3–30 days). Most of the patients had solitary lesions (72.7%), supratentorial lesions (90.9%, particularly predominant in the frontal, temporal, and parietal lobes), moderate edema (63.6%), mild mass effect (54.5%), and patchy lesions (54.5%). Among them, three patients were positive for myelin basic protein (MBP) and one patient was positive for myelin oligodendrocyte glycoprotein (MOG). The patients were followed up for an average of 6.9 years (2–14 years), and recurrent TDLs were observed in 2 patients. Except for the 2 patients who relapsed, only 1 of the 9 patients died; the other 8 patients improved or maintained the status quo (the EDSS scores were lower or unchanged). The patients did not have any serious nervous system injury at onset, and the main presentation included extremity weakness, headache or dizziness, and alalia. The most common form was patchy on MRI enhancement. Cerebrospinal fluid and demyelination test can be an indicator of TDLs, and seizures may be a poor prognostic indicator. Most atypical TDLs have monophasic courses and good outcomes. The effect of neurosurgery alone was good in our group, and the effect of surgery on atypical TDLs can be further studied.

Background: Stroke is the major cause of mortality and permanent disability and is associated with an astonishing economic burden worldwide. In the past few decades, accumulated evidence has indicated that Xuesaitong (XST) has therapeutic benefits in cases of acute ischemic stroke (AIS). Our study aimed to provide the best current body of evidence of the efficacy and safety of XST for patients with AIS.Methods: This is a systematic review and meta-analysis of randomized controlled trials (RCTs). We searched eight electronic databases from inception to 17 July 2023 for relevant RCTs. The investigators independently screened trials, extracted data, and assessed the risk of bias. A meta-analysis was conducted using RevMan 5.3 and STATA 16.0 software.Results: In total, 46 RCTs involving 7,957 patients were included. The results showed that XST improved the long-term functional outcomes with lower modified Rankin Scale (mRS) scores (MD = −0.67; 95% CI [−0.92 to −0.42]; p < 0.00001) and a higher proportion of functional independence (mRS ≤2) (RR = 1.08; 95% CI [1.05 to 1.12]; p < 0.00001). Low-quality evidence indicated that XST improved the activities of daily living (MD = 10.17; 95% CI [7.28 to 13.06]; p < 0.00001), improved the neurological impairment (MD = −3.39; 95% CI [−3.94 to −2.84]; p < 0.00001), and enhanced the total efficiency rate (RR = 1.19; 95% CI [1.15 to 1.23]; p < 0.00001). No significant difference was found in the all-cause mortality or incidence of adverse events between the XST and control groups. The certainty of evidence was estimated as moderate to very low.Conclusion: Presently, the administration of XST within 14 days of AIS is associated with favorable long-term functional outcomes. In addition, XST can improve activities of daily living, alleviate neurological deficits, and has shown good tolerability. However, the current evidence is too weak, and the confidence of evidence synthesis was restricted by the high risk of bias. Given the insufficient evidence, appropriately sized and powered RCTs investigating the efficacy and safety of XST for patients with AIS are warranted.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=446208, CRD42023446208.

As the highest plateau on the Earth, the Tibetan Plateau (TP) has experienced rapid warming in the last decades, affecting natural ecosystem and water resources extending far beyond the plateau itself. A distinctive characteristic known as elevation-dependent warming (EDW) in the high mountain regions was particularly pronounced in the TP, whereby the magnitude of temperature warming was amplified with increasing altitudes. Different mechanisms have been proposed to explain this phenomenon, however, the link between the root cause of warming, human activities, and the EDW remains poorly understood. Here we used the homogenized observation and simulations by the newest climate models to discern human influence on both mean and extreme temperatures within the region. An optimal fingerprinting method was applied in a vertical space rather than in traditional horizontal space. We found that the long-term trends in mean and extreme temperature amplified with increasing elevation, with larger magnitude of trends at higher elevations. The response to external forcing, primarily driven by human activities, was robustly detected in altitudinal amplification of temperature increase, providing clear evidence of human causes of EDW. As warming increases, the EDW in the region will continue, with more pronounced EDW corresponding to larger magnitude of warming under a high emission scenario. These findings mark the first evidence of human influence on temperature across different vertical altitudes of climate system.

Ball-milled Fe-Si-Al soft magnetic powder cores with the particle compositions away from the classical Sendust point were prepared in this work. The influences of alloy composition on the metallographic structure, density, hardness, and resistivity of Fe-Si-Al alloy, as well as the frequency-dependent permeability, loss, and the anti-saturation performance of Fe-Si-Al powder cores, were investigated systematically. It was found that the hardness of Fe-Si-Al alloy increases with the Si mass ratio and the saturation magnetization (Ms) increases with the Fe mass ratio. The alloy hardness affects the particle size after the ball-milling process and, thus, influences the porosity of the powder core. Together with adjusting the demagnetization field by controlling the particle size and the core’s porosity, changing the alloy composition to drive K and λ deviating from zero can effectively improve the anti-saturation performance of Fe-Si-Al powder cores at the expense of hysteresis loss, to some extent. In this work, good comprehensive magnetic properties were obtained in the Fe85.5-Si12-Al2.5 powder core. Its effective permeability percentage at 100 Oe and Ms were 59.12% and 132.23 emu/g, respectively, which are higher than those of the classical Sendust core. This work provides a feasible idea for optimizing the overall performance of the high-power magnetic device.

Abstract Background As the main pathological basis for various cardiovascular and cerebrovascular diseases, atherosclerosis has become one of the leading causes of death and disability worldwide. Emerging evidence has suggested that Rho GTPase Rnd3 plays an indisputable role in cardiovascular diseases, although its function in atherosclerosis remains unclear. Here, we found a significant correlation between Rnd3 and pyroptosis of aortic endothelial cells (ECs). Methods ApoeKO mice were utilized as a model for atherosclerosis. Endothelium‐specific transgenic mice were employed to disrupt the expression level of Rnd3 in vivo. Mechanistic investigation of the impact of Rnd3 on endothelial cell pyroptosis was carried out using liquid chromatography tandem mass spectrometry (LC‐MS/MS), co‐immunoprecipitation (Co‐IP) assays, and molecular docking. Results Evidence from gain‐of‐function and loss‐of‐function studies denoted a protective role for Rnd3 against ECs pyroptosis. Downregulation of Rnd3 sensitized ECs to pyroptosis under oxidized low density lipoprotein (oxLDL) challenge and exacerbated atherosclerosis, while overexpression of Rnd3 effectively prevented these effects. LC‐MS/MS, Co‐IP assay, and molecular docking revealed that Rnd3 negatively regulated pyroptosis signaling by direct interaction with the ring finger domain of tumor necrosis factor receptor‐associated factor 6 (TRAF6). This leads to the suppression of K63‐linked TRAF6 ubiquitination and the promotion of K48‐linked TRAF6 ubiquitination, inhibiting the activation of NF‐κB and promoting the degradation of TRAF6. Moreover, TRAF6 knockdown countered Rnd3 knockout‐evoked exacerbation of EC pyroptosis in vivo and vitro. Conclusions These findings establish a critical functional connection between Rnd3 and the TRAF6/NF‐κB/NLRP3 signaling pathway in ECs, indicating the essential role of Rnd3 in preventing pyroptosis of ECs.

Agrobacterium-mediated soybean transformation is the simplest method of gene transfer. However, the low transformation due to the intractable nature of soybean genotypes hinders this process. The use of biochemicals (acetosyringone, cinnamic acid, flavonoids, etc.) plays an important role in increasing soybean transformation. These biochemicals induce chemotaxis and virulence gene activation during the infection process. Here we identified a biochemical, aztreonam (a monobactam), for high agrobacterium-mediated transformation in soybean. The soybean explants from three genotypes were inoculated with A. tumefaciens (GV3101) harboring the pMDC32 vector containing hpt or the GmUbi-35S-GUS vector containing the GUS gene during two separate events. High transient GUS expression was obtained during cotyledon explant culture on MS media supplemented with 2.5 mg/L aztreonam. The aztreonam-treated explants showed high efficiency in transient and stable transformation as compared to the untreated control. The transformation of aztreonam-treated explants during seed imbibition resulted in an average of 21.1% as compared to 13.2% in control by using the pMDC32 vector and 28.5 and 20.7% while using the GUS gene cassette, respectively. Based on these findings, the metabolic analysis of the explant after aztreonam treatment was assessed. The high accumulation of flavonoids was identified during an untargeted metabolic analysis. The quantification results showed a significantly high accumulation of the four compounds, i.e., genistein, apigenin, naringenin, and genistin, in cotyledon explants after 18 hours of aztreonam treatment. Alongside this, aztreonam also had some surprising effects on root elongation and lateral root formation when compared to indole-3-butyric acid (IBA). Our findings were limited to soybeans. However, the discovery of aztreonam and its effect on triggering flavonoids could lead to the potential role of aztreonam in the agrobacterium-mediated transformation of different crops.

Pancreatic cancer is one of the leading causes of cancer-related mortality in both developed and developing countries. The incidence of pancreatic cancer in China accounts for about a quater of the global incidence, and the epidemiological characteristics and therapeutic strategies differ due to social, economic, cultural, environmental, and public health factors. Non-domestic guidelines do not reflect the clinicopathologic characteristics and treatment patterns of Chinese patients. Thus, in 2018, the Chinese Society of Clinical Oncology (CSCO) organized a panel of senior experts from all sub-specialties within the field of pancreatic oncology to compile the Chinese guidelines for the diagnosis and treatment of pancreatic cancer. The guidelines were made based on both the Western and Eastern clinical evidence and updated every one or two years. The experts made consensus judgments and classified evidence-based recommendations into various grades according to the regional differences, the accessibility of diagnostic and treatment resources, and health economic indexes in China. Here we present the latest version of the guidelines, which covers the diagnosis, treatment, and follow-up of pancreatic cancer. The guidelines might standardize the diagnosis and treatment of pancreatic cancer in China and will encourage oncologists to design and conduct more clinical trials about pancreatic cancer.

Climate impacts and risks involve climatic impact drivers, the exposure and vulnerability of natural and socioeconomic systems, and a strong interdependency exists between climate, nature and human society. Effective climate change adaptation requires effective knowledge sharing and co-creation between communities of climate research and its users. This pilot project of the World Climate Research Programme, supported by the Asia-Pacific Network for Global Change Research and other funders, brought together experts and future leaders from the two communities to familiarise themselves with the aspects of the other discipline. The project demonstrated that knowledge-sharing and co-creation benefit everyone involved and good progress in bridging the gap between the two communities can be made. We also learned that going beyond one’s own training is challenging and fixing the gap requires both communities’ long-term and sustained commitment.

Introduction: Type 2 diabetes (T2D) is a multifactorial complex chronic disease with a high prevalence worldwide, and Type 2 diabetes patients with different comorbidities often present multiple phenotypes in the clinic. Thus, there is a pressing need to improve understanding of the complexity of the clinical Type 2 diabetes population to help identify more accurate disease subtypes for personalized treatment.Methods: Here, utilizing the traditional Chinese medicine (TCM) clinical electronic medical records (EMRs) of 2137 Type 2 diabetes inpatients, we followed a heterogeneous medical record network (HEMnet) framework to construct heterogeneous medical record networks by integrating the clinical features from the electronic medical records, molecular interaction networks and domain knowledge.Results: Of the 2137 Type 2 diabetes patients, 1347 were male (63.03%), and 790 were female (36.97%). Using the HEMnet method, we obtained eight non-overlapping patient subgroups. For example, in H3, Poria, Astragali Radix, Glycyrrhizae Radix et Rhizoma, Cinnamomi Ramulus, and Liriopes Radix were identified as significant botanical drugs. Cardiovascular diseases (CVDs) were found to be significant comorbidities. Furthermore, enrichment analysis showed that there were six overlapping pathways and eight overlapping Gene Ontology terms among the herbs, comorbidities, and Type 2 diabetes in H3.Discussion: Our results demonstrate that identification of the Type 2 diabetes subgroup based on the HEMnet method can provide important guidance for the clinical use of herbal prescriptions and that this method can be used for other complex diseases.

Background: Acute Ischemic stroke (AIS) has been a leading cause of long-term disability and even death, accounting for significant economic costs and leading to heavy care and financial burdens for patients and their families. Ginkgo biloba extract is highly valued for its efficacy and broad implementation into clinical practice. Therefore, a Bayesian network meta-analysis (BNMA) was conducted to determine the differences in efficacy and safety among various ginkgo biloba-related agents and to prescribe the optimal medication for decision-making. Methods: Inclusion and exclusion eligibility criteria were determined in advance. From the inception of the literature until December 2022, a systematic literature search was conducted in seven electronic databases. An assessment of the methodological quality of the included studies was carried out according to the Cochrane Collaborations tool. A previous registration (PROSPERO CRD42022319301) of this review protocol was undertaken. Results: There were 94 eligible studies included in the NMA involving 10,071 patients, with the experimental control group of 5,063 and the control group of 5,008, involving five ginkgo biloba-related agents included in the NMA. Findings of the studies revealed that supplementation with ginkgo biloba-related agents significantly improved the clinical effective rate, functional independence, neurological function impairments and activities of daily living function compared with the conventional western medicine (WM) group in a relatively safe manner. Comprehensive therapeutic efficacy analysis of neurological function impairments and activities of daily living function showed that GI+WM and GDLM+WM manifest at the first grade among these five therapeutic strategies. Conclusion: This Bayesian network meta-analysis results showed that the combination of ginkgo biloba-related agents and WM was more effective for AIS patients than WM alone. GI+WM and GDLM+WM stand out for the comprehensive therapeutic efficacy of patients with stroke through comparisons among various therapeutic approaches. Moreover, SXN+WM, GK+WM and GDLM+WM might be among the most effective in improving the functional efficacy outcome, while GI+WM might be among the least effective. GI+WM, GDLM+WM, SXN+WM and GK+WM might be among the most effective in improving neurofunctional deficits, while GNT+WM might be among the least effective. In terms of improving activities of daily living function, five ginkgo biloba-related agents might be among the most effective. However, well-designed researches with standardized functional outcome measures for AIS, further adequately powered, blinding and suitable comparators are still required to contribute to the current clinical practice.

Obesity has become one of the major threats to human health across the globe. The rhizomes of Polygonatum sibiricum have shown promising anti-obesity effect. However, the metabolic and genetic basis mediating this beneficial effect are not fully resolved. It is well known that older rhizomes of P. sibiricum exert stronger pharmacological effects. Here, we performed high-resolution metabolome profiling of P. sibiricum rhizomes at different growth stages, and identified that three candidate anti-obesity metabolites, namely phloretin, linoleic acid and α-linolenic acid, accumulated more in adult rhizomes. To elucidate the genetic basis controlling the accumulation of these metabolites, we performed transcriptome profiling of rhizomes from juvenile and adult P. sibiricum. Through third-generation long-read sequencing, we built a high-quality transcript pool of P. sibiricum, and resolved the genetic pathways involved in the biosynthesis and metabolism of phloretin, linoleic acid and α-linolenic acid. Comparative transcriptome analysis revealed altered expression of the genetic pathways in adult rhizomes, which likely lead to higher accumulation of these candidate metabolites. Overall, we identified several metabolic and genetic signatures related to the anti-obesity effect of P. sibiricum. The metabolic and transcriptional datasets generated in this work could also facilitate future research on other beneficial effects of this medicinal plant.

Glioblastoma is one of the most dangerous tumors for patients in clinical practice at present, and since glioblastoma originates from the brain, it will have a serious impact on patients. Therefore, more effective clinical therapeutic targets are still needed at this stage. Kinesin family member 15 (KIF15) promotes proliferation in several cancers, but its effect on glioblastoma is unclear. In this study, differentially expressed gene analysis and network analysis were performed to identify critical genes affecting glioma progression. The samples were divided into a KIF15 high-expression group and KIF15 low-expression group, and the association between FIK15 expression level and clinical characteristics was summarized and analyzed by performing medical data analysis; the effect of KIF15 on glioblastoma cell proliferation was detected by employing colony formation and MTT assays. The effect of KIF15 on tumor growth in mice was determined. It was found that KIF15 was a potential gene affecting the progression of glioblastoma. In addition, KIF15 was highly expressed in glioblastoma tumor tissues, and KIF15 was correlated with tumor size, clinical stage and other clinical characteristics. After the KIF15 gene was knocked out, the proliferation ability of glioblastoma was significantly inhibited. KIF15 also contributed to the growth of glioblastoma tumors in mice. Therefore, we found KIF15 to be a promising clinical therapeutic target.

Background and purposeThe best method for selecting patients with acute vertebrobasilar artery occlusion (VBAO) who would benefit from endovascular treatment (EVT) is still the key question. This study aimed to assess the efficacy of magnetic resonance imaging (MRI) for selecting patients with acute VBAO for EVT.Materials and methodsA total of 14 patients with suspected acute VBAO on MR angiography (MRA) in the EVT database (from April 2016 to August 2019) were enrolled. Acute Stroke Prognosis Early Computed Tomography Score (ASPECTS) and pons–midbrain index were assessed on diffusion-weighted imaging (DWI). EVT included a stent retriever and a rescue treatment (angioplasty and/or stenting). The proportion of successful reperfusion and favorable functional outcomes (modified Rankin Scale ≤ 3) at 90 days was documented.ResultsA total of 11 patients were included in the final analysis. The median DWI-ASPECTS and pons–midbrain index were 7 and 2, respectively. Underlying stenosis was detected in 10 of 11 (90.9%) patients. Balloon angioplasty and/or stenting were used as rescue therapy for five patients and two patients, respectively. A total of nine patients (81.8%) achieved successful reperfusion (mTICI, 2b, or 3). The 90-day mRS score of 0–3 was achieved in six (54.5%) patients. The mortality rate within 90 days was 18.2% (two of 11 patients).ConclusionDWI plus MRA could help select the patients with acute VBAO for EVT by assessing ASPECTS and the pons–midbrain index. Patients could achieve good reperfusion and favorable functional outcomes.

BackgroundThe burden of cardiovascular disease (CVD) on the current aging society in China is substantial. Climate change, including extreme temperatures and humidity, has a detrimental influence on health. However, epidemiological studies have been unable to fully identify the association between climate change and CVD among older adults. Therefore, we investigated the associations between temperature and relative humidity and CVD among older adults in China.MethodsWe used cohort data from the China Longitudinal Health and Longevity Survey (CLHLS) conducted in 2002, 2005, 2008, 2011, 2014, and 2018. A total of 39,278 Chinese adults 65 years and older participated in the analyses. The average annual temperatures and relative humidity during 2001 and 2017 (before the survey year) at the city level in China were used as the exposure measures. We selected patients with hypertension, heart disease, and stroke to create a sample of CVD patients. The associations between temperature and relative humidity and CVD were analyzed using the generalized estimation equation (GEE) model. Covariates included sociodemographic factors, health status, lifestyle, and cognitive function.ResultsThe average annual temperature was negatively correlated with the prevalence of CVD. Every 1°C increase in the average annual temperature reduced the rates of hypertension by 3% [odds ratio (OR): 0.97; 95% confidence interval (CI): 0.96–0.97], heart disease by 6% (OR: 0.94; 95% CI: 0.92–0.95), and stroke by 5% (OR: 0.95; 95% CI: 0.94–0.97). The results of the analyses stratified by sex, urban/rural residence, and educational level were robust. The average annual relative humidity was inversely associated with the likelihood of CVD among older adults. Every 1% increase in the average annual relative humidity reduced the rates of hypertension by 0.4% (OR: 0.996; 95% CI: 0.99–1.00), heart disease by 0.6% (OR: 0.994; 95% CI: 0.99–1.00), and stroke by 0.08% (OR: 0.992; 95% CI: 0.98–1.00). However, the effects were more obvious with higher humidity levels (>70).ConclusionOur findings suggest that higher temperatures and relative humidity may reduce the risk of CVD among older adults.

Bladder cancer (BC) is the predominant neoplasm affecting the urinary system and ranks among the most widespread malignancies globally. The causes of bladder cancer include genetic factors; age; sex; and lifestyle factors, such as imbalanced nutrition, obesity, and metabolic disorders. The lack of proper nutrient intake leads to the development of bladder cancer because insufficient nutrients are consumed to prevent this disease. The purpose of this review was to analyze the nutrients closely linked to the onset and advancement of bladder cancer and to explore the relationship between dietary nutrients and bladder cancer. Particular emphasis was placed on nutrients that are frequently ingested in daily life, including sugar, fat, protein, and others. The focus of this research was to analyze how nutritional intake before and after surgery affects the recovery process of patients who have been diagnosed with bladder cancer. This article seeks to increase awareness among both society and the medical community about the significance of implementing appropriate dietary nutrition to reduce the chances of developing bladder cancer, enhance perioperative care for patients with bladder cancer, and aid in their recuperation.

Ecological security evaluation and land space governance are effective ways to ensure regional ecological security and realize sustainable development. This study evaluated the ecological security status at the raster scale and conducted research on the restoration and governance of the national territory, with the aim of implementing accurate restoration, reducing ecological restoration costs, and increasing ecological restoration benefits. Taking the typical arid inland river Shule River Basin as an example, this study selected evaluation factors from production, living, and ecological perspectives, obtained the influencing factors of regional ecological security by spatial principal component analysis, and calculated the ecological security index on the grid scale of production, life and ecological space. The macro-scale national parks, ecological protection red line and other realistic constraints are combined with the grid-scale ecological security evaluation results to achieve accurate land space restoration and governance. The results show that the ecological space accounts for 79.23%, and the production space only accounts for 7.47%, which is similar to other inland river basins in arid areas. The study found that per capita GDP and distance to the road have a significant impact on the ecological security of the study area from the perspectives of production and life, while distance to the water, vegetation coverage, and land cover have a significant impact on ecological security from the ecological perspective. Moderate, moderate low and low ecological security zones account for 72.09% of the total area of the basin, indicating that the ecological security guarantee ability of the Shule River Basin is low. The ecological security level of the living space was the lowest, and the ecological security pattern of the basin area as a whole presented a “higher in the north and south and lower in the middle” characteristic. The land restoration and governance of the Shule River Basin area was divided into five types of ecological control, ecological conservation, ecological enhancement, ecological restoration and ecological management, of which the ecological control area accounted for as much as 35.86%, implying that ecological security in the Shule River Basin has attracted sufficient attention from the government. It is considered that the management of production and living space is more difficult, complex and important, and the proportion of space is relatively small, so it is necessary to focus on the comprehensive management project of ecological protection and restoration. However, the ecological endowment conditions of ecological space in the Shule River Basin are relatively poor, and the distribution area is vast, so natural restoration should be given priority, supplemented by artificial restoration. This study provides a reference for regional ecological security evaluation, ecological civilization construction, and national ecological security research and practice.

As a vital adipokine, Adipsin is closely associated with cardiovascular risks. Nevertheless, its role in the onset and development of cardiovascular diseases remains elusive. This study was designed to examine the effect of Adipsin on survival, cardiac dysfunction and adverse remodeling in the face of myocardial infarction (MI) injury. In vitro experiments were conducted to evaluate the effects of Adipsin on cardiomyocyte function in the face of hypoxic challenge and the mechanisms involved. Our results showed that Adipsin dramatically altered expression of proteins associated with iron metabolism and ferroptosis. In vivo results demonstrated that Adipsin upregulated levels of Ferritin Heavy Chain (FTH) while downregulating that of Transferrin Receptor (TFRC) in peri-infarct regions 1 month following MI. Adipsin also relieved post-MI-associated lipid oxidative stress as evidenced by decreased expression of COX2 and increased GPX4 level. Co-immunoprecipitation and immunofluorescence imaging prove a direct interaction between Adipsin and IRP2. As expected, cardioprotection provided by Adipsin depends on the key molecule of IRP2. These findings revealed that Adipsin could be efficiently delivered to the heart by exosomes derived from pericardial adipose tissues. In addition, Adipsin interacted with IRP2 to protect cardiomyocytes against ferroptosis and maintain iron homeostasis. Therefore, Adipsin-overexpressed exosomes derived from pericardial adipose tissues may be a promising therapeutic strategy to prevent adverse cardiac remodeling following ischemic heart injury.

Zanthoxylum armatum is a prominent plant for food industries. Its male flowers often occur in gynogenesis plants; however, the potential mechanism remains poorly understood. Herein, a total of 26 floral sex differentiation stages were observed to select four vital phases to reveal key factors by using RNA-seq, phytohormones and carbohydrates investigation. The results showed that a selective abortion of stamen or pistil primordia could result in the floral sex differentiation in Z. armatum. Carbohydrates might collaborate with cytokinin to effect the male floral differentiation, whereas female floral differentiation was involved in SA, GA1, and ABA biosynthesis and signal transduction pathways. Meanwhile, these endogenous regulators associated with reproductive growth might be integrated into ABCDE model to regulate the floral organ differentiation in Z. armatum. Furthermore, the 21 crucial candidates were identified in co-expression network, which would contribute to uncovering their roles in floral sex differentiation of Z. armatum in further studies. To the best of our knowledge, this study was the first comprehensive investigation to link floral sex differentiation with multi-level endogenous regulatory factors in Z. armatum. It also provided new insights to explore the regulatory mechanism of floral sex differentiation, which would be benefited to cultivate high-yield varieties in Z. armatum.

In this study, we train a convolutional neural network (CNN) model using a selection of Coupled Model Intercomparison Project (CMIP) phase 5 and 6 models to investigate the predictability of the sea surface temperature (SST) variability off the Sumatra-Java coast in the tropical southeast Indian Ocean, the eastern pole of the Indian Ocean Dipole (IOD). Results show that the CNN model can beat the persistence of the interannual SST variability, such that the eastern IOD (EIOD) SST variability can be forecast up to 6 months in advance. Visualizing the CNN model using a gradient weighted class activation map shows that the strong positive IOD events (cold EIOD SST anomalies) can stem from different processes: internal Indian Ocean dynamics were associated with the 1994 positive IOD, teleconnection from the equatorial Pacific was important in 1997, and cooling off the Australian coast in the southeast Indian Ocean contributed to the 2019 positive IOD. The CNN model overcomes the winter prediction barrier of the IOD, to a large extent due to the frequent transition from a warm state of the Indian Ocean to a negative IOD condition (warm EIOD SST anomalies) over the boreal winter to the following spring period. The forecasting skills of the CNN model are on par with predictions from a coupled seasonal forecasting model (ACCESS-S2), even outperforming this dynamic model in seasons leading to the IOD peaks. The ability of the CNN model to identify key dynamic drivers of the EIOD SST variability suggests that the CMIP models can capture the internal Indian Ocean variability and its teleconnection with the Pacific climate variability.

Background: Acute ischemic stroke (AIS) is a common cause of death and long-term disability worldwide. Recent trials of platelet-activating factor receptor antagonists (PAFRA) appeared to indicate that they could play a neuroprotective role in the treatment of AIS; therefore, we conducted a systematic literature review to evaluate the clinical efficacy and safety of PAFRA in patients with AIS.Methods: A systematic literature search was performed in seven electronic databases from inception to 11 March 2022. All randomized controlled trials (RCTs) in which patients were treated with PAFRA strategies within 7 days of stroke onset were included. Modified Rankin Scale (mRS) was selected as the primary outcome of this systematic review. The methodological quality of included studies was assessed based on the Cochrane Collaborations tool. The review protocol was previously registered (PROSPERO CRD42020182075).Results: Fifteen RCTs comprising a total of 3,907 participants were included in this study. The PAFRA-related compounds included natural preparations of terpenoids, flavonoids, and saponins, namely, ginkgo endoterpene diester meglumine (GEDM, seven RCTs), ginkgo biloba dropping pill (GBDP, one RCT), ginkgolide injection (GDI, four RCTs), hesperidin (HES, one RCT), ginsenoside Rd injection (GSRI, one RCT), and hydroxysafflor yellow A (HSYA, one RCT). All studies were conducted in China between 2017 and 2021, employing a two-arm parallel design with sample sizes ranging from 40 to 1,113. Eight studies (53.3%) provided no information on their method of randomization, and only two studies (13.3%) utilized the double-blind design. Treatment was associated with improved clinical outcomes for (1) GEDM, GDI, and GBDP in patients treated with conventional treatment (CM) [GEDM + CM for AIS on mRS: MDmRS = −0.42, 95% CI (−0.47, −0.37), five trials, p < 0.00001; GEDM + CM for AIS on NIHSS: MDNIHSS = −1.02, 95% CI (−1.51, −0.52), four trials, p < 0.0001]; (2) GEDM and GDI in patients treated with neuroprotective agent (NPA) [GEDM + NPA + CM for AIS on mRS: MDmRS = −0.40, 95% CI (−0.54, −0.26), p < 0.00001; GEDM + NPA + CM for AIS on NIHSS: MDNIHSS = −3.93, 95%CI (−7.72, −0.14), p = 0.04]; (3) GBDP in patients treated with CM; (4) GDI and GSRI in patients treated with IV rt-PA therapy (IVT); and (5) HSYA in patients compared with Dengzhan Xixin injection (DZXXI). No access to improved clinical outcome was associated with HES in patients treated with IVT. Seven RCTs reported adverse events (AEs) but found that taking PAFRA-related preparations was not associated with an increased incidence of AEs.Conclusions: This systematic review not only makes an important contribution to the existing body of current evidence but also lays a well-conducted basis for providing opinions and recommendation on the evaluation of PAFRA-based medicine, which could also highlight the need for well-designed clinical trials of PAFRA for AIS to increase the quality of available evidence. Further research is required, using standardized functional outcome measures for AIS, adequate blinding and suitable comparator groups reflecting current best practice.

Background and PurposeDiagnosing cervical artery dissection (CAD) is still a challenge based on the current radiographic criteria. This study aimed to assess the value of three-dimensional high-resolution magnetic resonance imaging (3D HRMRI) in the detection of the signs of CAD and its diagnosis.Materials and MethodsPatients with CAD from January 2016 to January 2021 were recruited from our 3D HRMRI database. The signs of dissection (intramural hematomas, intimal flap, double lumen), length and location of the dissection, thickness of the intramural hematoma, intraluminal thrombus, and percentage of dilation of the outer contour of the dissection on 3D HRMRI were assessed.ResultsFourteen patients with 16 CADs, including 12 carotid CADs and 4 vertebral CADs, were finally diagnosed in this study. On 3D HRMRI, intramural hematomas were detected in 13/16 (81.3%) lesions with high sensitivity (100%) and high specificity (100%). Intimal flaps were found in 9/16 (56.3%) lesions with moderate sensitivity (64.3%) and high specificity (88.9%). Double lumen signs were observed in 4/16 (25.0%) lesions with high sensitivity (80.0%) and high specificity (100%). In addition, concomitant intraluminal thrombus were detected in 4/16 (25.0%) lesions with high sensitivity (80.0%) and high specificity (100%). The mean length of dissection was (25.1 ± 13.7) mm. The mean thickness of the intramural hematoma was (4.3 ± 2.3) mm. The mean percentage of dilation for the outer contour of the dissection was (151.3 ± 28.6)%.ConclusionThe 3D HRMRI enables detection of the dissecting signs, such as intramural hematoma, intimal flap, double lumen, and intraluminal thrombus with high sensitivity and specificity, suggesting a useful, and non-invasive tool for definitively diagnosing CAD.

At the intersection of the Qinghai–Tibet Plateau and Loess Plateau, topographic factors often profoundly affect the evolution of the regional land use pattern and ecological risk. This paper takes the Lanzhou–Xining urban agglomeration as the research area, divides the topographic gradient based on the topographic index, analyzes the characteristics of the land use pattern using the land use transfer matrix model, dynamic attitude and state degree model, and analyzes the influence of topographic factors on the land use pattern using the distribution model. At the same time, an ecological risk evaluation index system is constructed, the spatial principal component method is used to evaluate the ecological risk, and the influence of topography on the regional ecological risk is discussed. The results show that from 1990 to 2020, the area of construction land in the study area increased by 1045.807 km2 and the area of ecological land increased by 587.41 km2, with the most significant changes occurring in the attitude and state of construction land and unused land. It is found that cultivated land, water area and construction land are dominant in low terrain, while woodland, grassland and unused land are mainly distributed in middle and high terrain. During the study period, the ecological risk in the midwest and southeast of the Lanzhou–Xining urban agglomeration decreased, while the ecological risk in the northeast increased first and then decreased, although generally there was an increasing trend. Moran’s I varied from 0.942 to 0.955 from 1990 to 2020, indicating that the ecological risk index in the study area was highly positively correlated in space, while the spatial aggregation effect of the ecological risk was obvious. Low and moderately low risk areas are mainly distributed in high terrain, while high and moderately high risk areas are dominant in low terrain. The research results of this paper can make a lot of sense for ecological protection, land resource utilization and sustainable development of the Lanzhou–Xining urban agglomeration.

A strong atmospheric river made landfall in southwestern British Columbia, Canada on November 14th, 2021, bringing two days of intense precipitation to the region. The resulting floods and landslides led to the loss of at least five lives, cut Vancouver off entirely from the rest of Canada by road and rail, and made this the costliest natural disaster in the province's history. Here we show that when characterised in terms of storm-averaged water vapour transport, the variable typically used to characterise the intensity of atmospheric rivers, westerly atmospheric river events of this magnitude are approximately one in ten year events in the current climate of this region, and that such events have been made at least 60% more likely by the effects of human-induced climate change. Characterised in terms of the associated two-day precipitation, the event is substantially more extreme, approximately a one in fifty to one in a hundred year event, and the probability of events at least this large has been increased by a best estimate of 45% by human-induced climate change. The effects of this precipitation on streamflow were exacerbated by already wet conditions preceding the event, and by rising temperatures during the event that led to significant snowmelt, which led to streamflow maxima exceeding estimated one in a hundred year events in several basins in the region. Based on a large ensemble of simulations with a hydrological model which integrates the effects of multiple climatic drivers, we find that the probability of such extreme streamflow events in October to December has been increased by human-induced climate change by a best estimate of 120–330%. Together these results demonstrate the substantial human influence on this compound extreme event, and help motivate efforts to increase resiliency in the face of more frequent events of this kind in the future.

Extreme event attribution is used to evaluate the role of anthropogenic climate change in the occurrence or characteristics of extreme events. To be most useful, event attribution should be interpreted in the proper context and one part of this is understanding when event attribution results are robust. We investigate some factors contributing to the robustness of event attribution, by evaluating the roles of model choice, spatial scales, and ensemble sizes. We compare six single-model large ensembles to determine for which regions and variables there is agreement on at least two-fold changes in likelihood. As attribution of increases in the likelihood of daily temperature extremes is widespread by a 1 °C global warming level, we focus on precipitation extremes. In some regions, low signal to noise contributes to a lack of agreement on at least two-fold increases in likelihood in the current climate, but more model agreement in a 3 °C climate. In other regions, however, model differences remain, even at larger warming levels. Understanding where and when models do or do not agree on changes in large-scale precipitation extremes can be used to inform the design and interpretation of the local-scale analysis of specific events.

Verticillium wilt, caused by the soil-borne fungus Verticillium dahliae, is one of the most devastating diseases in cotton (Gossypium spp.). Lignin in the cell wall forms a physical barrier to inhibit pathogen invasion, and defense-induced lignification reinforces secondary cell wall to prevent pathogens from further spreading. Cinnamyl alcohol dehydrogenases (CADs) catalyze the production of three main monolignols, p-coumaryl- (H), coniferyl- (G), and sinapyl-alcohols (S), which are the fundamental blocks of lignin. Here, we identified CAD genes in G. hirsutum, analyzed their expression profiles in cotton leaf, stem, and root from different developmental stages, and selected GhCAD35, GhCAD45, and GhCAD43, which were consistently induced by V. dahliae inoculation in G. hirsutum cultivars resistant or susceptible to V. dahliae. On the basis of confirmation of the in vitro enzymatic activity of the three proteins in generation of the three monolignols, we used virus-induced gene silencing (VIGS) to investigate the effects of silencing of GhCAD35, GhCAD45, or GhCAD43 on resistance to V. dahliae as well as on deposition and the composition of lignin. Silencing each of the three CADs impaired the defense-induced lignification and salicylic acid biosynthesis in stem, and compromised resistance to V. dahliae. Moreover, our study showed that silencing the three GhCADs severely affected the biosynthesis of S-lignin, leading to a decrease of the syringyl/guaiacyl (S/G) ratio. Heterogeneous overexpression of GhCAD35, GhCAD45, or GhCAD43 in Arabidopsis enhanced disease resistance. Taken together, our study demonstrates a role of the three GhCADs in defense-induced lignin biosynthesis and resistance to V. dahliae in G. hirsutum.

Evaluating sea-level projections used by the IPCC is challenging due to the short overlap with measurements. Here, the authors show that observed global and regional sea-level trends confirm projections and that the acceleration of sea-level rise is between the one expected from the scenarios RCP4.5 and RCP8.5.

Abstract Background To compare robot-assisted simple enucleation with renal arterial cold perfusion (RACP-RASE) and RASE alone in complex renal tumors with regard to perioperative, functional and oncologic outcomes by propensity score-matched analysis. Methods Data from 351 patients who underwent RACP-RASE or RASE for complex renal tumors were recorded between September 2014 and December 2017. Propensity score-matched analysis was performed on age, sex, BMI, ECOG score, tumor side and size, preoperative estimated glomerular filtration rate (eGFR), RENAL score and PADUA score. Results The study included 31 RACP-RASE and 320 RASE procedures. RENAL score and PADUA score were higher and tumor diameter was greater under RACP-RASE than RASE. After matching, the two groups were similar in estimated blood loss (208.3 vs 230.7 ml; p = 0.696) and ischemic time (34.8 vs 32.8 min; p = 0.342). The RACP-RASE group had significantly longer operative time than the RASE group (264.1 ± 55.7 vs 206.9 ± 64.0 min, p = 0.001). There was no difference in the incidence of postoperative complications between the two groups (13.8% vs 24.1%; p = 0.315), as was the overall incidence of positive surgical margins (3.4 vs 0%; p = 1.000). The changes in eGFR significantly differed between the two groups at 3 months (p = 0.018) and 12 months (p = 0.038). More patients in the RASE group were CKD upstaged (p = 0.043). At multivariable analysis, preoperative eGFR and the type of procedure were significant predictive factors for a change of more than 10% in eGFR at 3 months postoperatively. There was no local recurrence or distant metastasis during follow-up. Conclusions RACP-RASE is an effective and safe technique for complex renal tumors that can provide appropriate temporary arterial occlusion and renal hypothermic perfusion. Renal arterial cold perfusion may be helpful in protecting renal function in RASE as compared with warm ischemia.

Daylily (Hemerocallis citrina Baroni) is an edible plant widely distributed worldwide, especially in Asia. It has traditionally been considered a potential anti-constipation vegetable. This study aimed to investigate the anti-constipation effects of daylily from the perspective of gastro-intestinal transit, defecation parameters, short-chain organic acids, gut microbiome, transcriptomes and network pharmacology. The results show that dried daylily (DHC) intake accelerated the defecation frequency of mice, while it did not significantly alter the levels of short-chain organic acids in the cecum. The 16S rRNA sequencing showed that DHC elevated the abundance of Akkermansia, Bifidobacterium and Flavonifractor, while it reduced the level of pathogens (such as Helicobacter and Vibrio). Furthermore, a transcriptomics analysis revealed 736 differentially expressed genes (DEGs) after DHC treatment, which are mainly enriched in the olfactory transduction pathway. The integration of transcriptomes and network pharmacology revealed seven overlapping targets (Alb, Drd2, Igf2, Pon1, Tshr, Mc2r and Nalcn). A qPCR analysis further showed that DHC reduced the expression of Alb, Pon1 and Cnr1 in the colon of constipated mice. Our findings provide a novel insight into the anti-constipation effects of DHC.