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Abstract Autonomous mobile clinics (AMCs) have the potential to revolutionize healthcare delivery by bringing healthcare services to patients at the order of patient’s fingertips. Particularly, AMCs can act as an essential touch point of integrated care, which is a worldwide response to the fragmented delivery of health by focusing on more coordinated and integrated forms of care provision. However, the impact of AMCs on the health satisfaction outcome effectiveness still remains unknown. In this article, in collaboration with United Family Healthcare (UFH), we study the potential effectiveness improvement of integrated care delivery through AMCs.

Abstract Pseudouridine widely affects the stability and function of RNA. However, our knowledge of pseudouridine properties in tumors is incomplete. We systematically analyzed pseudouridine synthases (PUSs) expression, genomic aberrations, and prognostic features in 10907 samples from 33 tumors. We found that the pseudouridine-associated pathway was abnormal in tumors and affected patient prognosis. Dysregulation of the PUSs expression pattern may arise from copy number variation (CNV) mutations and aberrant DNA methylation. Functional enrichment analyses determined that the PUSs expression was closely associated with the MYC, E2F, and MTORC1 signaling pathways. In addition, PUSs are involved in the remodeling of the tumor microenvironment (TME) in solid tumors, such as kidney and lung cancers. Particularly in lung cancer, increased expression of PUSs is accompanied by increased immune checkpoint expression and Treg infiltration. The best signature model based on more than 112 machine learning combinations had good prognostic ability in ACC, DLBC, GBM, KICH, MESO, THYM, TGCT, and PRAD tumors, and is expected to guide immunotherapy for 19 tumor types. The model was also effective in identifying patients with tumors amenable to etoposide, camptothecin, cisplatin, or bexarotene treatment. In conclusion, our work highlights the dysregulated features of PUSs and their role in the TME and patient prognosis, providing an initial molecular basis for future exploration of pseudouridine. Studies targeting pseudouridine are expected to lead to the development of potential diagnostic strategies and the evaluation and improvement of antitumor therapies.

BackgroundTo investigate the effects of different hinge positions in the sagittal and axial planes on distal tibial rotation (DTR) during medial opening wedge high tibial osteotomy (MOWHTO) with three-dimensional tibial models.MethodsPreoperative CT data from 30 knee joints in 30 patients who underwent surgery for varus malalignment of knee were included. 1 standard hinge position (0°), 6 axial planes (±5°, ±10°, ±15°), and 6 sagittal planes (±5°, ±10°, ±15°) hinge positions were defined and virtual uniplanar osteotomy was performed. The correction angle of each model was generated using Fujisawa's point. Participants’ baseline characteristics, radiologic parameters and DTR were measured. One-Way Repeated Measures ANOVA and single factor linear regression analysis were used to analyze the association between tibial rotation and hinge position in the sagittal and axial planes.ResultsWe found a clear linear correlation between changes in hinge position in the sagittal plane and DTR. The changes in DTR were the smallest when the hinge position was at 5°, where internal or external rotation of the DTR may occur. When the front aspect of hinge axis rotated distally, DTR tended towards internal. Meanwhile, when the front aspect of hinge axis rotated proximally, DTR tended towards external. There were no correlations with every hinge axis position in the axial plane.ConclusionsIt is sagittal but not axial hinge axis affects DTR in uniplanar MOWHTO with three-dimensional tibial models. In the sagittal plane, every change in hinge position was significantly linearly correlated with DTR. However, no linear correlations were observed between every hinge position change in the axial plane.

Abstract Background Glomerular lesions are the main injuries of diabetic nephropathy (DN) and are used as a crucial index for pathologic classification. Manual quantification of these morphologic features currently used is semi-quantitative and time-consuming. Automatically quantifying glomerular morphologic features is urgently needed. Methods A series of convolutional neural networks (CNN) were designed to identify and classify glomerular morphologic features in DN patients. Associations of these digital features with pathologic classification and prognosis were further analyzed. Results Our CNN-based model achieved a 0.928 F1-score for global glomerulosclerosis and 0.953 F1-score for Kimmelstiel-Wilson lesion, further obtained a dice of 0.870 for the mesangial area and F1-score beyond 0.839 for three glomerular intrinsic cells. As the pathologic classes increased, mesangial cell numbers and mesangial area increased, and podocyte numbers decreased (p for all

Background Patients with idiopathic membranous nephropathy (IMN) are more likely to be complicated by venous thromboembolism (VTE). The aim of the study was to investigate the potential association between anti-phospholipase A2 receptor (PLA2R) antibodies and hypercoagulability in patients with IMN.Methods A total of 168 patients with biopsy-proven IMN and 36 patients with biopsy-proven minimal change disease (MCD) were enrolled in this study. The clinical data, serum anti-PLA2R antibodies and coagulation-related indices of the patients were retrospectively analyzed.Results Patients with IMN were categorized into glomerular PLA2R staining-positive (GAg+) IMN group and glomerular PLA2R staining-negative (GAg-) IMN group in the study. Patients with IMN who were GAg + had lower PT, APTT and R time than patients with IMN who were GAg-, while the CI value was higher in patients with IMN who were GAg+. Patients with IMN who were GAg + were divided into the SAb+/GAg + group and the SAb-/GAg + group. Patients with IMN who were SAb+/GAg + had higher Fib and MA values than patients with IMN who were SAb-/GAg+. Correlation analysis showed that serum anti-PLA2R antibodies were positively correlated with fibrinogen, D-dimer, K time, CI value, α-angle, and MA value. Multiple linear regression analysis indicated that anti-PLA2R antibodies were independently correlated with fibrinogen and MA value.Conclusion Our study provides a new perspective on the underlying mechanisms of hypercoagulability in patients with IMN. Anti-PLA2R antibodies are associated with hypercoagulability in patients with IMN and may affect coagulation in patients with IMN by affecting platelet aggregation function and fibrinogen counts.

Background The analytical renal pathology system (ARPS) based on convolutional neural networks has been used successfully in native IgA nephropathy (IgAN) patients. Considering the similarity of pathologic features, we aim to evaluate the performance of the ARPS in allograft IgAN patients and broaden its implementation.Methods Biopsy-proven allograft IgAN patients from two different centers were enrolled for internal and external validation. We implemented the ARPS to identify glomerular lesions and intrinsic glomerular cells, and then evaluated its performance. Consistency between the ARPS and pathologists was assessed using intraclass correlation coefficients. The association of digital pathological features with clinical and pathological data was measured. Kaplan-Meier survival curve and cox proportional hazards model were applied to investigate prognosis prediction.Results A total of 56 biopsy-proven allograft IgAN patients from the internal center and 17 biopsy-proven allograft IgAN patients from the external center were enrolled in this study. The ARPS was successfully applied to identify the glomerular lesions (F1-score, 0.696–0.959) and quantify intrinsic glomerular cells (F1-score, 0.888–0.968) in allograft IgAN patients rapidly and precisely. Furthermore, the mesangial hypercellularity score was positively correlated with all mesangial metrics provided by ARPS [Spearman’s correlation coefficient (r), 0.439–0.472, and all p values < 0.001]. Besides, a higher allograft survival was noticed among patients in the high-level groups of the maximum and ratio of endothelial cells, as well as the maximum and density of podocytes.Conclusion We propose that the ARPS could be implemented in future clinical practice with outstanding capability.

Abstract Aims Neutrophil extracellular traps (NETs) have been implicated in thrombotic diseases. There is no definitive explanation for how NETs form during acute ischemic strokes (AIS). The purpose of our study was to investigate the potential mechanism and role of NETs formation in the AIS process. Methods As well as 45 healthy subjects, 45 patients with AIS had ELISA tests performed to detect NET markers. Expression of high-mobility group box 1 (HMGB1) on platelet microvesicles (PMVs) was analyzed by flow cytometry in healthy subjects and AIS patients’ blood samples. We established middle cerebral artery occlusion (MCAO) mice model to elucidate the interaction between PMPs and NETs. Results A significant elevation in NET markers was found in patient plasma in AIS patients, and neutrophils generated more NETs from patients’ neutrophils. HMGB1 expression was upregulated on PMVs from AIS patients and induced NET formation. NETs enhanced Procoagulant activity (PCA) through tissue factor and via platelet activation. Targeting lactadherin in genetical and in pharmacology could regulate the formation of NETs in MCAO model. Conclusions NETs mediated by PMVs derived HMGB1 exacerbate thrombosis and brain injury in AIS. Video Abstract

Unmanned aerial vehicles (UAVs) are equipped with various sensors to facilitate control and navigation. However, UAV sensors are highly susceptible to damage under complex flight environments, leading to severe accidents and economic losses. Although fault diagnosis methods based on deep neural networks have been widely applied in the mechanical field, these methods often fail to integrate multi-source information and overlook the importance of system prior knowledge. As a result, this study employs a spatial-temporal difference graph convolutional network (STDGCN) for the fault diagnosis of UAV sensors, where the graph structure naturally organizes the diverse sensors. Specifically, a difference layer enhances the feature extraction capability of the graph nodes, and the spatial-temporal graph convolutional modules are designed to extract spatial-temporal dependencies from sensor data. Moreover, to ensure the accuracy of the association graph, this research introduces the UAV’s dynamic model as prior knowledge for constructing the association graph. Finally, diagnostic accuracies of 94.93%, 98.71%, and 92.97% were achieved on three self-constructed datasets. In addition, compared to commonly used data-driven approaches, the proposed method demonstrates superior feature extraction capabilities and achieves the highest diagnostic accuracy.

Abstract As an efficient molecular engineering approach, on-surface synthesis (OSS) defines a special opportunity to investigate intermolecular coupling at the sub-molecular level and has delivered many appealing polymers. So far, all OSS is based on the lateral covalent bonding of molecular precursors within a single molecular layer; extending OSS from two to three dimensions is yet to be realized. Herein, we address this challenge by cycloaddition between C60 and an aromatic compound. The C60 layer is assembled on the well-defined molecular network, allowing appropriate molecular orbital hybridization. Upon thermal activation, covalent coupling perpendicular to the surface via [4 + 2] cycloaddition between C60 and the phenyl ring of the molecule is realized; the resultant adduct shows frozen orientation and distinct sub-molecular feature at room temperature and further enables lateral covalent bonding via [2 + 2] cycloaddition. This work unlocks an unconventional route for bottom-up precise synthesis of three-dimensional covalently-bonded organic architectures/devices on surfaces.

Abstract Background Accurately predicting the outcome of isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM) remains hitherto challenging. This study aims to Construct and Validate a Robust Prognostic Model for IDH wild-type GBM (COVPRIG) for the prediction of overall survival using a novel metric, gene–gene (G × G) interaction, and explore molecular and cellular underpinnings. Methods Univariate and multivariate Cox regression of four independent trans-ethnic cohorts containing a total of 800 samples. Prediction efficacy was comprehensively evaluated and compared with previous models by a systematic literature review. The molecular underpinnings of COVPRIG were elucidated by integrated analysis of bulk-tumor and single-cell based datasets. Results Using a Cox-ph model-based method, six of the 93,961 G × G interactions were screened to form an optimal combination which, together with age, comprised the COVPRIG model. COVPRIG was designed for RNA-seq and microarray, respectively, and effectively identified patients at high risk of mortality. The predictive performance of COVPRIG was satisfactory, with area under the curve (AUC) ranging from 0.56 (CGGA693, RNA-seq, 6-month survival) to 0.79 (TCGA RNAseq, 18-month survival), which can be further validated by decision curves. Nomograms were constructed for individual risk prediction for RNA-seq and microarray-based cohorts, respectively. Besides, the prognostic significance of COVPRIG was also validated in GBM including the IDH mutant samples. Notably, COVPRIG was comprehensively evaluated and externally validated, and a systemic review disclosed that COVPRIG outperformed current validated models with an integrated discrimination improvement (IDI) of 6–16%. Moreover, integrative bioinformatics analysis predicted an essential role of METTL1+ neural-progenitor-like (NPC-like) malignant cell in driving unfavorable outcome. Conclusion This study provided a powerful tool for the outcome prediction for IDH wild-type GBM, and preliminary molecular underpinnings for future research.

IntroductionThe type VI secretion system (T6SS) is a crucial virulence factor in the nosocomial pathogen Acinetobacter baumannii. However, its association with drug resistance is less well known. Notably, the roles that different T6SS components play in the process of antimicrobial resistance, as well as in virulence, have not been systematically revealed.MethodsThe importance of three representative T6SS core genes involved in the drug resistance and virulence of A. baumannii, namely, tssB, tssD (hcp), and tssM was elucidated.ResultsA higher ratio of the three core genes was detected in drug-resistant strains than in susceptible strains among our 114 A. baumannii clinical isolates. Upon deletion of tssB in AB795639, increased antimicrobial resistance to cefuroxime and ceftriaxone was observed, alongside reduced resistance to gentamicin. The ΔtssD mutant showed decreased resistance to ciprofloxacin, norfloxacin, ofloxacin, tetracycline, and doxycycline, but increased resistance to tobramycin and streptomycin. The tssM-lacking mutant showed an increased sensitivity to ofloxacin, polymyxin B, and furazolidone. In addition, a significant reduction in biofilm formation was observed only with the ΔtssM mutant. Moreover, the ΔtssM strain, followed by the ΔtssD mutant, showed decreased survival in human serum, with attenuated competition with Escherichia coli and impaired lethality in Galleria mellonella.DiscussionThe above results suggest that T6SS plays an important role, participating in the antibiotic resistance of A. baumannii, especially in terms of intrinsic resistance. Meanwhile, tssM and tssD contribute to bacterial virulence to a greater degree, with tssM being associated with greater importance.

As high-energy cathode materials, conversion-type metal fluorides provide a prospective pathway for developing next-generation lithium-ion batteries. However, they suffer from severe performance decay owing to continuous structural destruction and active material dissolution upon cycling, which worsen at elevated temperatures. Here, we design a novel FeF2 cathode with in situ polymerized solid-state electrolyte systems to enhance the cycling ability of metal fluorides at 60 ​°C. Novel FeF2 with a mesoporous structure (meso-FeF2) improves Li+ diffusion and relieves the volume change that typically occurs during the alternating conversion reactions. The structural stability of the meso-FeF2 cathode is strengthened by an in situ polymerized solid-state electrolyte, which prevents the pulverization and ion dissolution that are inevitable for conventional liquid electrolytes. Under the double action of this in situ polymerized solid-state electrolyte and the meso-FeF2's mesoporous structure, the active material maintains an intact SEI layer and part of the mesoporous structure after long charge–discharge cycling, showing excellent cycling stability at high temperatures.

We present the first detection in space of thionylimide (HNSO) toward the Galactic center molecular cloud G + 0.693-0.027, thanks to the superb sensitivity of an ultradeep molecular line survey carried out with the Yebes 40 m and IRAM 30 m telescopes. This molecule is the first species detected in the interstellar medium containing, simultaneously, N, S, and O. We have identified numerous K _a = 0, 1, and 2 transitions belonging to HNSO covering from J _up = 2 to J _up =10, including several completely unblended features. We derive a molecular column density of N = (8 ± 1)×10 ^13 cm ^−2 , yielding a fractional abundance relative to H _2 of ∼6 × 10 ^−10 , which is about ∼37 and ∼4.8 times less abundant than SO and SO _2 , respectively. Although there are still many unknowns in the interstellar chemistry of NSO-bearing molecules, we propose that HNSO is likely formed through the reaction of the NSO radical and atomic H on the surface of icy grains, with alternative routes also deserving exploration. Finally, HNSO appears as a promising link between N, S, and O interstellar chemistry, and its discovery paves the route to the detection of a new family of molecules in space.

IntroductionAutotrophic bacteria play an important role in carbon dioxide fixation and are widespread in terrestrial ecosystems. However, the biogeographic patterns of autotrophic bacteria and the driving factors still remain poorly understood.MethodsHerein, we conducted a 391-km north to south transect (mean annual precipitation

AbstractObjective To investigate the risk factors for deep vein thrombosis (DVT) in children with osteomyelitis and provide diagnostic and treatment strategies for the prevention, early detection and treatment of DVT.Study design The clinical data of nine children diagnosed with osteomyelitis and DVT between July 2012 and March 2021 were collected at our hospital, including age, sex, clinical manifestations, body temperature, coagulation function and other data, as well as the clinical data of 27 children diagnosed with osteomyelitis without DVT during the same period. Thirty-six children were divided into thrombus and thrombus-free groups. The clinical characteristics and risk factors for DVT in children with osteomyelitis were analysed.Results Among the 36 children in this study, nine cases of thrombus formation mainly occurred in the femoral vein, popliteal vein and iliac vein, all near the infection site. The main clinical manifestations were lower extremity pain, swelling and pulmonary embolism in three cases. Among them, intensive care unit (ICU) admission, sepsis, higher D-dimer, higher body temperature during hospitalization, and pathogen culture showed that methicillin-resistant Staphylococcus aureus (MRSA) was associated with DVT. MRSA was the independent risk factor for DVT.Conclusions Admission to ICU, sepsis, higher D-dimer, higher body temperature during hospitalization, and MRSA are risk factors for thrombosis. MRSA is the independent risk factor for DVT. For patients with related risk factors, timely ultrasound examination of the infected site should be considered to achieve early detection and treatment.

During the International Workshop on Soil Erosion and Riverine Sediment in Mountainous Regions held in November 2022, scientists from many countries shared their state-of-the-art knowledge and brainstormed to improve scientific understanding for coping with climate change and anthropogenic impacts. Information summarized in this discussion includes proposed key scientific questions and suggested joint actions to reduce soil erosion and riverine sediment problems in mountainous regions.

Abstract Carbon films have been considered suitable to be applied in water lubrication since they exhibit excellent friction-reducing and wear resistance, chemical inertness, etc. However, the basic understanding of tribological behaviors of carbon-based films under water lubrication still needs to be explored. In the present work, carbon films with different nanostructures were prepared by the electron cyclotron resonance (ECR) plasma nano-surface manufacturing system, and micro-textures with different sizes were prepared on the surface of carbon films by plasma etching. The influence of nanostructure and surface texture on the tribological properties of carbon films was investigated. The results show that different nanostructured carbon films can obtain lower friction coefficients and longer wear life under water lubrication than under dry condition. Due to low surface roughness, high hardness, and compact structure, the tribological properties of amorphous carbon (a-C) films under water lubrication are much better than those of graphene sheet-embedded carbon (GSEC) films. The prepared surface texture has a negative effect on the hard a-C film, but it can make the soft GSEC film generate soft wear debris at the initial stage. With the action of water, the soft wear debris is bonded on the surface of the contacting ball to form a silt-like transfer film, which increases the wear life by nearly three orders of magnitude. These results extend the basic understanding of the tribological behavior of carbon film under water lubrication, which is crucial in both fundamental and applied science.

Neoseiulus bicaudus is a predatory mite species that could potentially be used for the biological control of spider mites and thrips. Floral resources can provide excellent habitats and abundant nutrients for natural enemies. The objective of this experiment was to evaluate the effects of eight floral resources on the longevity, fecundity, and predation ability of N. bicaudus. Among the considered plants, Cnidium monnieri led to the highest longevity (24 days) and fecundity (13.8 eggs) of N. bicaudus, while Tagetes erecta resulted in the lowest longevity (7 days) and fecundity (0.1 eggs) observed in the predatory mites. By comparing the effects of three nectar and pollen plants on the predation of predatory mites, it was observed that N. bicaudus still exhibited a type II functional response to Tetranychus turkestani. In the presence of pollen, the predation efficacy (a/Th) of N. bicaudus exhibited a lower value, compared to that in the absence of pollen (Control: a/Th = 24.00). When pollen was supplied, the maximum consumption (1/Th) of predatory mites was higher than in its absence (Control: 1/Th = 9.90 d−1), with the highest value obtained in the presence of B. officinalis pollen (B. officinalis: 1/Th = 17.86 d−1). The influence coefficient of predation of N. bicaudus on T. turkestani in the presence of pollen was compared in the presence of three nectar and pollen plants: Cnidium monnieri, Centaurea cyanus, and Borago officinalis. At low prey densities, the influence coefficient of C. cyanus exceeded that of B. officinalis, and the overall influence coefficient values were negative (i.e., the presence of pollen reduced predatory mite feeding on T. turkestani). They exhibited similar values at high prey densities, and all of the influence coefficient values were close to 0 (i.e., the presence of pollen had no effect on predatory mite feeding on T. turkestani). The findings revealed that diverse plant species exert differential impacts on N. bicaudus, with some influencing its lifespan and others affecting its reproductive capabilities. Furthermore, the presence of nectar and pollen plants had a significant impact on predatory mite feeding on T. turkestani at low prey densities; however, this effect diminished as the prey density increased. Therefore, we recommend planting C. monnieri, C. cyanus, and B. officinalis in the field to ensure an ample population of predatory mites. The obtained results hold significant implications for the utilization of nectar and pollen plants in eco-friendly pest management strategies within agricultural contexts.

IntroductionThe gut microbiota closely relates to host health, whereas the relationship between gut microbiota and testosterone during the development of Meishan male pigs remains unclear. This study investigated the fecal microbiota composition and testosterone level during development in Meishan male pigs.MethodsFresh fecal samples of 20 healthy Meishan male pigs were individually collected at 10 and 22 weeks (wk) of age for testosterone content detection and bacteria pyrosequencing analysis. Anaerobic culture experiment of fecal bacteria in vitro was performed for bacteria pyrosequencing analysis.ResultsThe fecal testosterone content increased significantly from 10 weeks (wk) to 22 wk of age (P < 0.05). Meanwhile, the boars at 22 wk had a lower abundance of phylum Bacteroidetes and Proteobacteria, and genus Alloprevotella, Prevotella_1, Prevotellaceae_NK3B31_group, and Streptococcus in the fecal microbiota composition (P < 0.05). but higher proportions of the phylum Actinobacteria, Firmicutes, Kiritimatiellaeota, and Tenericutes, and genus Clostridium_sensu_stricto_1, Muribaculaceae and Terrisporobacter than that at 10 wk (P < 0.05), and the Firmicutes to Bacteroidetes ratio was higher at 22 wk than 10 wk (P < 0.05). Moreover, the fecal testosterone level significantly correlated with the relative abundance of the phylum Actinobacteria, Firmicutes, and Tencuteseri, and genus Alloprevotella, Clostridium_sensu_stricto_1, Muribaculaceae, Prevotella_1 and Streptococcus. Furthermore, the in vitro experiments indicated that the abundance of the phylum Proteobacteria and genus Escherichia-Shigella reduced with the increase of supplemental testosterone level. In contrast, the proportion of Firmicutes phylum increased with additional testosterone levels.DiscussionTestosterone could modulate the microflora structure. Meanwhile, the bacteria could degrade the testosterone in a dose testosterone-dependent manner. These results provide us with new insights into the relationship between the gut microbiome and testosterone and the contributions of the gut microbiome in physiological regulation in response to gonad development.

Abstract The large-scale vegetation restoration project on the Loess Plateau increased the ecosystem carbon (C) stocks and affected C budget in arid and semi-arid ecosystems. The specific details affecting the C stocks, their distribution, and dependence on land use and climate were never presented and generalized. We assessed the effects of climate factors and soil properties on ecosystem C stocks through field investigation across the Loess Plateau. The total C stocks in the four ecosystems: forestlands [0.36], shrublands [0.24], grasslands [1.18], and farmlands [1.05] was 2.84 Pg (1 Pg = 1015 g), among which 30% were stored in topsoil (0–20 cm), 53% in above-ground biomass, and 17% in roots. The total ecosystem C density decreased according to the climate from the southeast (warm dry) to the northwest (cold moist) of the Loess Plateau. The ecosystem C density decreased with increasing temperature (from 5 to 15 °C), but increased with precipitation (from 200 to 700 mm). Variation partitioning analysis and structural equation models indicated that ecosystem C density was more explained by climate compared with soil properties. This supports the theory and empirical findings that large scale pattern of ecosystem C density is predominantly regulated by climate on the Loess Plateau. Our results highlight that grasslands are more predestined to store C compared with the other ecosystems, and the C stored in roots is substantial and should be considered when assessing C stocks and strongly contributes to soil organic matter formation. We suggest that investing in roots can be an effective strategy for meeting part of Loess Plateau C reduction goals to mitigate climate change, which is necessary for validating and parameterizing C models worldwide.

Abstract Background Paeonia veitchii Lynch, a well-known herb from the Qinghai-Tibet Plateau south of the Himalayas, can synthesize specific monoterpene glycosides (PMGs) with multiple pharmacological activities, and its rhizome has become an indispensable ingredient in many clinical drugs. However, little is known about the molecular background of P. veitchii, especially the genes involved in the biosynthetic pathway of PMGs. Results A corrective full-length transcriptome with 30,827 unigenes was generated by combining next-generation sequencing (NGS) and single-molecule real-time sequencing (SMRT) of six tissues (leaf, stem, petal, ovary, phloem and xylem). The enzymes terpene synthase (TPS), cytochrome P450 (CYP), UDP-glycosyltransferase (UGT), and BAHD acyltransferase, which participate in the biosynthesis of PMGs, were systematically characterized, and their functions related to PMG biosynthesis were analysed. With further insight into TPSs, CYPs, UGTs and BAHDs involved in PMG biosynthesis, the weighted gene coexpression network analysis (WGCNA) method was used to identify the relationships between these genes and PMGs. Finally, 8 TPSs, 22 CYPs, 7 UGTs, and 2 BAHD genes were obtained, and these putative genes were very likely to be involved in the biosynthesis of PMGs. In addition, the expression patterns of the putative genes and the accumulation of PMGs in tissues suggested that all tissues are capable of biosynthesizing PMGs and that aerial plant parts could also be used to extract PMGs. Conclusion We generated a large-scale transcriptome database across the major tissues in P. veitchii, providing valuable support for further research investigating P. veitchii and understanding the genetic information of plants from the Qinghai-Tibet Plateau. TPSs, CYPs, UGTs and BAHDs further contribute to a better understanding of the biology and complexity of PMGs in P. veitchii. Our study will help reveal the mechanisms underlying the biosynthesis pathway of these specific monoterpene glycosides and aid in the comprehensive utilization of this multifunctional plant.

Abstract Background Protein p62 (sequestosome 1) encoded by gene SQSTM1 plays a vital role in mediating protectively selective autophagy in tumor cells under stressed conditions. CircSQSTM1 (hsa_circ_0075323) is a circular transcript generated from gene SQSTM1 (chr5:179260586–179260782) by back-splicing. However, the potential role of hsa_hsa_circ_0075323 in glioblastoma (GBM) remains unclear. Here, we aimed to explore the biological function of hsa_circ_0075323 in GBM and its relationship with autophagy regulation. Results Hsa_circ_0075323 is highly expressed in GBM cells and mainly locates in the cytoplasm. Inhibition of hsa_circ_0075323 in U87-MG and T98G cells attenuated proliferation and invasion ability significantly, while upregulation of has_ circ_0075323 enhanced proliferation and migration of U251-MG and A172 cells. Mechanistically, depletion of hsa_circ_0075323 in GBM cells resulted in impaired autophagy, as indicated by increased expression of p62 and decreased expression of LC3B. Conclusions Hsa_circ_0075323 regulates p62-mediated autophagy pathway to promote GBM progression and may serve as a prognostic biomarker potentially.

Abstract With the booming development of smart wearable devices, flexible multifunctional composites with high sensitivity and well health therapy have evoked great interest for next-generation healthcare electronics. However, the weak biocompatibility, low breathability, and narrow sensing range greatly hinder the development of healthcare sensors. Herein, a porous, flexible and conductive MXene/Polydimethylsiloxane/Polydopamine/Polyurethane Sponge (MXene/PDMS/PDA/PU) nanocomposite is developed as a promising motion-detecting device with good flexibility, breathability, sensing performance, photothermal therapy and antibacterial activity. Benefiting from the porous structure and biocompatible surface, this multifunctional sensor is further fabricated into a diagnostic and therapeutic system for monitoring human body motion and performing hot therapy/antibacterial treatment in the application of sports injury site. Moreover, both the wireless smart insole and cushion are constructed to gait monitoring and sit position detecting. This multifunctional hybrid sponge not only demonstrates great potential for motion monitoring sensors but also exhibits wide potential in wearable medical assistive and therapeutic systems.

Abstract Monoclonal gammopathy has emerged as an important cause of renal injury. Since the clinicopathologic features related to monotypic monoclonal gammopathy of renal significance with IgM monoclonal gammopathy (IgM-MGRS) are poorly described and it is uncertain if intervention improves renal survival and mortality, we report a series of such patients, characterizing their clinicopathologic spectrum and outcomes. We retrospectively analyzed 38 patients referred to one medical center between 2009 and 2019 with detectable serum monoclonal IgM by immunofixation, performance of a bone marrow biopsy and kidney biopsy-proven MGRS. Of the 38 patients identified, about half patients were amyloidosis, followed by cryoglobulinemic glomerulonephritis. Patients were divided into two groups on the basis of their kidney pathology: amyloid and non-amyloid. Patients with non-amyloidosis were more likely to have renal dysfunction, hematuria, anemia and hypocomplementemia and κ light chain was predominant in this sub-group. Amyloid patients were more often treated with chemotherapy than the non-amyloid patients (P = 0.002). There were no significant differences between amyloid and non-amyloid patients in mortality (48% vs 29%, P = 0.467) and incidence of ESRD (19% vs 59%, P = 0.103). The incidence of ESRD was lower in patients treated with chemotherapy and/or ASCT, compared to those without chemotherapy (25% vs 57%, P = 0.049), and it was also lower in the hematologic responders than non-responders (10% vs 40%, P = 0.047). Our study confirmed a diverse variety of clinicopathological features and outcomes in patients with IgM-MGRS. Chemotherapy and/or ASCT and deep hematologic responses might improve renal prognosis.

Abstract Background Glioblastoma (GBM) is an aggressive and malignant brain tumor with extremely poor prognosis. Despite advances in treatment, the pathogenesis of GBM remains elusive. Mounting studies have revealed the critical role of circular RNAs (circRNAs) in the development and progression of human cancers including GBM, but the comprehension of their functions is still insufficient. In this study, we investigated the expression profile of a circRNA derived from GLIS family zinc finger 3 (GLIS3) in GBM and normal astrocytes. CircGLIS3 expression was detected through quantitative real-time polymerase chain reaction (qRT-PCR) analysis. Functional experiments were performed to analyze the influence of circGLIS3 on GBM cell proliferation and apoptosis. In addition, mechanism assays were to uncover the potential regulatory mechanism of circGLIS3. Results CircGLIS3 was up-regulated in GBM cells and knockdown of circGLIS3 significantly hampered proliferation and promoted apoptosis of GBM cells. Furthermore, circGLIS3 positively regulated CAPG and GLIS3 by sponging miR-449c-5p to affect GBM cell proliferation and apoptosis. Conclusions In summary, our study identified that circGLIS3 could promote proliferation and inhibit apoptosis of GBM cells via targeting miR-449c-5p/GLIS3/CAPG axis in vitro. This study could offer a novel molecular perspective for further investigation into mechanisms essential to GBM progression.

BackgroundHumanistic care pertains to the abilities, attitudes, and behaviors central to patient-centered care, contributing to patients' sense of safety and wellbeing. This study aimed to assess the satisfaction of patients with humanistic nursing care in Chinese secondary and tertiary public hospitals.MethodsA national cross-sectional survey was conducted across 30 provinces and 83 hospitals in China. Patient satisfaction with humanistic care was assessed using the Methodist Health Care System Nurse Caring Instrument (NCI), which encompasses 20 items across 12 dimensions. Each item was rated on a 7-point Likert scale, yielding a total score of 140. Multiple linear regression analysis was employed to identify factors associated with patients' satisfaction.ResultsModerate satisfaction (mean score 91.26 ± 13.14) with humanistic nursing care was observed among the 17,593 participants. Factors significantly associated with patient satisfaction included age, hospital type, presence of children, educational attainment, place of residence, family monthly income, and medical insurance type.ConclusionThe study findings highlight the importance of tailored interventions, evidence-based practice guidelines, and patient-centered care in improving patients' satisfaction with humanistic nursing care. Continuous emphasis on nursing education and professional development is crucial for enhancing humanistic care and patient satisfaction.

Intra-tumoral necrosis (ITN) is reported to be an independent prognostic factor in glioma. However, knowledge of ITN is mainly limited to pseudopalisadwe, while its other aspects were neglected. Therefore, a deeper understanding of ITN could be valuable for understanding its exact role in glioma. The only reliable ITN model was time-dependently achieved with the GL261 syngeneic mouse model. The ITN-associated expression pattern was enriched from RNA sequencing. TCGA glioma samples were clustered into a high-expression group (HEG) and a low-expression group (LEG) based on their pattern and their association with prognosis, clinical status, immune status, and therapeutic responsiveness were compared. Mouse glioma with ITN demonstrated invasive histology. Cytokine signaling was significantly enriched in necrotic mouse glioma compared with non-necrotic glioma tissues. Nine pro-inflammatory (IL6, PPBP, IL1A, TNFSF11, CXCL11, CXCL9, CXCL10, CXCL3, and CCL8) and two anti-inflammatory cytokine (IL1RN and IL10) genes were found to be related to ITN-associated cytokine patterns. Comparative analysis showed that HEG had a significantly shorter survival time, five differentially distributed clinical statuses, more infiltrated immune cells, greater expression of immune checkpoints, and better therapeutic responsiveness than LEG. In conclusion, the ITN-associated cytokine pattern is characteristically expressed in glioma with ITN and might indicate necrosis missed in histology diagnosis. Its expression pattern could predict the prognosis, tumor grade, immune status, and therapeutic responsiveness of glioma patients.

BackgroundPhotodynamic therapy (PDT) promotes significant tumor regression and extends the lifetime of patients. The actual operation of PDT often relies on the subjective judgment of experienced neurosurgeons. Patients can benefit more from precisely targeting PDT’s key operating zones.MethodsWe used magnetic resonance imaging scans and created 3D digital models of patient anatomy. Multiple images are aligned and merged in STL format. Neurosurgeons use HoloLens to import reconstructions and assist in PDT execution. Also, immunohistochemistry was used to explore the association of hyperperfusion sites in PDT of glioma with patient survival.ResultsWe constructed satisfactory 3D visualization of glioma models and accurately localized the hyperperfused areas of the tumor. Tumor tissue taken in these areas was rich in CD31, VEGFA and EGFR that were associated with poor prognosis in glioma patients. We report the first study using MR technology combined with PDT in the treatment of glioma. Based on this model, neurosurgeons can focus PDT on the hyperperfused area of the glioma. A direct benefit was expected for the patients in this treatment.ConclusionUsing the Mixed Reality technique combines multimodal imaging signatures to adjuvant glioma PDT can better exploit the vascular sealing effect of PDT on glioma.

The modified carbapenem inactivation method (mCIM) recommended by the Clinical and Laboratory Standards Institute is not applicable for detecting carbapenemases in Acinetobacter baumannii. Four currently reported phenotypic detection methods, namely, the modified Hodge test, the mCIM, the adjusted mCIM, and the simplified carbapenem inactivation method (sCIM), did not perform well in our 90 clinical A. baumannii isolates. Thus, the minimal inhibitory concentrations (MICs) of carbapenems and the existence and expression of carbapenemase-encoding genes were detected to explain the results. According to the E-test, which was more accurate than the VITEK 2 system, 80.0 and 41.1% were resistant to imipenem (IPM) and meropenem (MEM), respectively, and 14.4 and 53.3% exhibited intermediate resistance, respectively. Five β-lactamase genes were found, of which blaOXA-51-like, blaTEM, and blaOXA-23-like were detected more frequently in 85 non-susceptible strains. The expression of blaOXA-23-like was positively correlated with the MIC values of IPM and MEM. Therefore, an improved approach based on the mCIM, designated the optimized CIM (oCIM), was developed in this study to detect carbapenemases more accurately and reproducibly. The condition was improved by evaluating the factors of A. baumannii inoculum, incubation broth volume, and MEM disk incubation time. Obvious high sensitivity (92.94%) and specificity (100.00%) were obtained using the oCIM, which was cost-effective and reproducible in routine laboratory work.

PurposeThis study aimed to explore the clinical value of non-invasive preoperative Edmondson-Steiner grade of hepatocellular carcinoma (HCC) using contrast-enhanced ultrasound (CEUS).Methods212 cases of HCCs were retrospectively included, including 83 cases of high-grade HCCs and 129 cases of low-grade HCCs. Three representative CEUS images were selected from the arterial phase, portal vein phase, and delayed phase and stored in a 3-dimensional array. ITK-SNAP was used to segment the tumor lesions manually. The Radiomics method was conducted to extract high-dimensional features on these contrast-enhanced ultrasound images. Then the independent sample T-test and the Least Absolute Shrinkage and Selection Operator (LASSO) were employed to reduce the feature dimensions. The optimized features were modeled by a classifier based on ensemble learning, and the Edmondson Steiner grading was predicted in an independent testing set using this model.ResultsA total of 1338 features were extracted from the 3D images. After the dimension reduction, 10 features were finally selected to establish the model. In the independent testing set, the integrated model performed best, with an AUC of 0.931.ConclusionThis study proposed an Edmondson-Steiner grading method for HCC with CEUS. The method has good classification performance on independent testing sets, which can provide quantitative analysis support for clinical decision-making.

Necroptosis is a programmed form of necrotic cell death that serves as a host gatekeeper for defense against invasion by certain pathogens. Previous studies have uncovered the essential role of necroptosis in tumor progression and implied the potential for novel therapies targeting necroptosis. However, no comprehensive analysis of multi-omics data has been conducted to better understand the relationship between necroptosis and tumor. We developed the necroptosis index (NI) to uncover the effect of necroptosis in most cancers. NI not only correlated with clinical characteristics of multiple tumors, but also could influence drug sensitivity in glioma. Based on necroptosis-related differentially expressed genes, the consensus clustering was used to classify glioma patients into two NI subgroups. Then, we revealed NI subgroup I were more sensitive to immunotherapy, particularly anti-PD1 therapy. This new NI-based classification may have prospective predictive factors for prognosis and guide physicians in prioritizing immunotherapy for potential responders.

Pancreatic ductal adenocarcinoma (PDAC) presents a formidable challenge with high lethality and limited effective drug treatments. Its heightened metastatic potential further complicates the prognosis. Owing to the significant toxicity of current chemotherapeutics, compounds like [Met5]-enkephalin, known as opioid growth factor (OGF), have emerged in oncology clinical trials. OGF, an endogenous peptide interacting with the OGF receptor (OGFr), plays a crucial role in inhibiting cell proliferation across various cancer types. This in vitro study explores the potential anticancer efficacy of a newly synthesized OGF bioconjugate in synergy with the classic chemotherapeutic agent, gemcitabine (OGF-Gem). The study delves into assessing the impact of the OGF-Gem conjugate on cell proliferation inhibition, cell cycle regulation, the induction of cellular senescence, and apoptosis. Furthermore, the antimetastatic potential of the OGF-Gem conjugate was demonstrated through evaluations using blood platelets and AsPC-1 cells with a light aggregometer. In summary, this article demonstrates the cytotoxic impact of the innovative OGF-Gem conjugate on pancreatic cancer cells in both 2D and 3D models. We highlight the potential of both the OGF-Gem conjugate and OGF alone in effectively inhibiting the ex vivo pancreatic tumor cell-induced platelet aggregation (TCIPA) process, a phenomenon not observed with Gem alone. Furthermore, the confirmed hemocompatibility of OGF-Gem with platelets reinforces its promising potential. We anticipate that this conjugation strategy will open avenues for the development of potent anticancer agents.

Deuterium fractionation in the closest vicinity of a protostar is important in understanding its potential heritage to a planetary system. Here, we have detected the spectral line emission of CH _3 OH and its three deuterated species, CH _2 DOH, CHD _2 OH, and CH _3 OD, toward the low-mass protostellar source B335 at a resolution of 0.″03 (5 au) with Atacama Large Millimeter/submillimeter Array. They have a ring distribution within the radius of 24 au with the intensity depression at the continuum peak. We derive the column densities and abundance ratios of the above species at six positions in the disk/envelope system as well as the continuum peak. The D/H ratio of CH _3 OH is ∼[0.03–0.13], which is derived by correcting the statistical weight of 3 for CH _2 DOH. The [CHD _2 OH]/[CH _2 DOH] ratio is derived to be higher ([0.14–0.29]). On the other hand, the [CH _2 DOH]/[CH _3 OD] ratio ([4.9–15]) is higher than the statistical ratio of 3 and is comparable to those reported for other low-mass sources. We study the physical structure on a few astronomical unit scales in B335 by analyzing the CH _3 OH (18 _3,15 − 18 _2,16 , A) and HCOOH (12 _0,12 − 11 _0,11 ) line emission. Velocity structures of these lines are reasonably explained as the infalling-rotating motion. The protostellar mass and the upper limit to the centrifugal barrier are thus derived to be 0.03–0.07 M _⊙ and

We report the first detection in the interstellar medium of N -cyanomethanimine (H _2 CNCN), the stable dimer of HCN of highest energy and the most complex organic molecule identified in space containing the prebiotically relevant NCN backbone. We have identified a plethora of a -type rotational transitions with 3 ≤ J _up ≤ 11 and K _a ≤ 2 that belong to this species toward the Galactic center G+0.693-0.027 molecular cloud, the only interstellar source showing the three cyanomethanimine isomers (including the Z - and E -isomers of C -cyanomethanimine, HNCHCN). We have derived a total column density for H _2 CNCN of (2.9 ± 0.1) × 10 ^12 cm ^−2 , which translates into a total molecular abundance with respect to H _2 of (2.1 ± 0.3) × 10 ^−11 . We have also revisited the previous detection of E - and Z -HNCHCN and found a total C / N -cyanomethanimine abundance ratio of 31.8 ± 1.8 and a Z / E -HNCHCN ratio of 4.5 ± 0.2. While the latter can be explained on the basis of thermodynamic equilibrium, chemical kinetics are more likely responsible for the observed C / N -cyanomethanimine abundance ratio, where the gas-phase reaction between methanimine (CH _2 NH) and the cyanogen radical (CN) arises as the primary formation route.

We present the first detection in space of O-protonated carbonyl sulfide (HOCS ^+ ), in the midst of an ultradeep molecular line survey toward the G+0.693-0.027 molecular cloud. From the observation of all K _a = 0 transitions ranging from J _lo = 2 to J _lo = 13 of HOCS ^+ covered by our survey, we derive a column density of N = (9 ± 2) × 10 ^12 cm ^−2 , translating into a fractional abundance relative to H _2 of ∼7 × 10 ^−11 . Conversely, the S-protonated HSCO ^+ isomer remains undetected, and we derive an upper limit to its abundance with respect to H _2 of ≤3 × 10 ^−11 , a factor of ≥2.3 less abundant than HOCS ^+ . We obtain an HOCS ^+ /OCS ratio of ∼2.5 × 10 ^−3 , in good agreement with the prediction of astrochemical models. These models show that one of the main chemical routes to the interstellar formation of HOCS ^+ is likely the protonation of OCS, which appears to be more efficient at the oxygen end. Also, we find that high values of cosmic-ray ionization rates (10 ^−15 –10 ^−14 s ^−1 ) are needed to reproduce the observed abundance of HOCS ^+ . In addition, we compare the O/S ratio across different interstellar environments. G+0.693-0.027 appears as the source with the lowest O/S ratio. We find an HOCO ^+ /HOCS ^+ ratio of ∼31, in accordance with other O/S molecular pairs detected toward this region and also close to the O/S solar value (∼37). This fact indicates that S is not significantly depleted within this cloud due to the action of large-scale shocks, unlike in other sources where S-bearing species remain trapped on icy dust grains.

Pancreatic cancer, notorious for its grim 10% five-year survival rate, poses significant clinical challenges, largely due to late-stage diagnosis and limited therapeutic options. This review delves into the generation of organoids, including those derived from resected tissues, biopsies, pluripotent stem cells, and adult stem cells, as well as the advancements in 3D printing. It explores the complexities of the tumor microenvironment, emphasizing culture media, the integration of non-neoplastic cells, and angiogenesis. Additionally, the review examines the multifaceted properties of graphene oxide (GO), such as its mechanical, thermal, electrical, chemical, and optical attributes, and their implications in cancer diagnostics and therapeutics. GO’s unique properties facilitate its interaction with tumors, allowing targeted drug delivery and enhanced imaging for early detection and treatment. The integration of GO with 3D cultured organoid systems, particularly in pancreatic cancer research, is critically analyzed, highlighting current limitations and future potential. This innovative approach has the promise to transform personalized medicine, improve drug screening efficiency, and aid biomarker discovery in this aggressive disease. Through this review, we offer a balanced perspective on the advancements and future prospects in pancreatic cancer research, harnessing the potential of organoids and GO.

Abstract Background Neutrophil extracellular traps (NETs) contribute to the creation of a coagulation state in various diseases. Currently, it is not clear whether NETs are present in the thrombi and plasma of patients with cerebral venous sinus thrombosis (CVST). This study aimed to investigate the presence of NETs in thrombi and blood samples from CVST patients and the procoagulant activity (PCA) of NETs during the progression of CVST. Results Thrombi obtained from CVST patients undergoing thrombectomy were examined by immunochemistry using neutrophil elastase (NE), CD66b and citrullinated histone H3(citH3). The presence of NET markers in samples from 37 CVST patients and 32 healthy people was evaluated by ELISA. NET-producing neutrophils and neutrophil-platelet (PLT) aggregates were examined in samples obtained from CVST patients and healthy people by flow cytometry. The TAT complex in plasma sample from each group was detected by ELISA to evaluate the procoagulant activity of NETs in CVST patients. Neutrophils from healthy subjects were treated with PLT-rich plasma in the presence of anti-PF4 antibodies or an autophagy inhibitor and analyzed by flow cytometry and confocal microscopy. After treatment with NETs, the expression of von Willebrand factor (VWF), tissue factor (TF) and CD31 in human brain microvascular endothelial cells (HBMECs) was measured by confocal microscopy and western blotting. Our results showed that NETs were abundant in the plasma and thrombi from CVST patients. Platelet factor 4 (PF4) from CVST PLTs induced NET generation through autophagy. NETs could induce PCA by modulating TF and phosphatidylserine (PS) in CVST. NETs also disrupted the endothelial barrier and transformed ECs into a procoagulant phenotype to exacerbate thrombogenicity. Conclusions NET generation was mediated by PF4 from PLTs through autophagy and contribute to thrombosis in CVST patients.

Abstract Objectives To evaluate the usefulness of Contrast-enhanced ultrasound (CEUS) in the diagnosis and differential diagnosis of Polypoid lesions of gallbladder (PLGs) ≥ 1 cm. Methods A prospective analysis was performed on 180 patients with PLGs ≥ 1 cm. 175 cases were confirmed by pathological diagnosis and the remaining were confirmed by other imaging findings. The characteristics of lesions on conventional Ultrasonography (US) and CEUS were recorded. Results Significant differences were observed in enhancement patterns between benign and malignant PLGs during both arterial (P

Abstract Background The purpose of this retrospective study aimed to assess the accuracy of detection of remnant common bile duct (CBD) stones by injecting saline through endoscopic nasobiliary drainage (ENBD) tubes under transabdominal ultrasound (US) guidance. Method Stone extraction and ENBD are regularly achieved through endoscopic retrograde cholangiopancreatography (ERCP) in patients with CBD stones. At 1–3 days thereafter, routine US studies were performed and repeated, using ENBD tubal saline injections (20–100 mL). Results A total of 302 patients underwent standard ERCP stone extractions in conjunction with occlusion cholangiograms, routine US testing, and ENBD-based saline-injection US exams. By occlusion cholangiogram, remnant stones were suspected in 31 (10.3%) patients in total of 302, and 26 (83.8%) were verified as true positives (sensitivity, 50.9%; specificity, 98.0%). Routine US studies proved suspicious in 13 (4.3%) patients in total of 302, and 12 (92.3%) were verified as true positives (sensitivity, 23.5%; specificity, 99.6%). Using ENBD-based saline-injection US, suspected stones were identified in 50 (16.6%) patients in total of 302, and 46 (92%) were verified as true positives (sensitivity, 90.1%; specificity, 98.4%). The sensitivity of ENBD-based saline-injection US significantly surpassed that of occlusion cholangiogram (p

Coagulopathy contributes to the majority of deaths and disabilities associated with traumatic brain injury (TBI). Whether neutrophil extracellular traps (NETs) contribute to an abnormal coagulation state in the acute phase of TBI remains unknown. Our objectives were to demonstrate the definitive role of NETs in coagulopathy in TBI. We detected NET markers in 128 TBI patients and 34 healthy individuals. Neutrophil-platelet aggregates were detected in blood samples from TBI patients and healthy individuals using flow cytometry and staining for CD41 and CD66b. Endothelial cells were incubated with isolated NETs and we detected the expression of vascular endothelial cadherin, syndecan-1, thrombomodulin, von Willebrand factor, phosphatidylserine, and tissue factor. In addition, we established a TBI mouse model to determine the potential role of NETs in TBI-associated coagulopathy. NET generation was mediated by high mobility group box 1 (HMGB1) from activated platelets and contributed to procoagulant activity in TBI. Furthermore, coculture experiments indicated that NETs damaged the endothelial barrier and caused these cells to assume a procoagulant phenotype. Moreover, the administration of DNase I before or after brain trauma markedly reduced coagulopathy and improved the survival and clinical outcome of mice with TBI.

BackgroundEarly tumor recurrence is one of the most significant poor prognostic factors for patients with HCC after R0 resection. The aim of this study is to identify risk factors of early recurrence, in addition, to develop a nomogram model predicting early recurrence of HCC patients.MethodsA total of 481 HCC patients after R0 resection were enrolled and divided into a training cohort (n = 337) and a validation cohort (n = 144). Risk factors for early recurrence were determined based on Cox regression analysis in the training cohort. A nomogram incorporating independent risk predictors was established and validated.ResultsEarly recurrence occurred in 37.8% of the 481 patients who underwent curative liver resection of HCC. AFP ≥ 400 ng/mL (HR: 1.662; P = 0.008), VEGF-A among 127.8 to 240.3 pg/mL (HR: 1.781, P = 0.012), VEGF-A > 240.3 pg/mL (HR: 2.552, P < 0.001), M1 subgroup of MVI (HR: 2.221, P = 0.002), M2 subgroup of MVI (HR: 3.120, P < 0.001), intratumor necrosis (HR: 1.666, P = 0.011), surgical margin among 5.0 to 10.0 mm (HR: 1.601, P = 0.043) and surgical margin < 5.0 mm (HR: 1.790, P = 0.012) were found to be independent risk factors for recurrence-free survival in the training cohort and were used for constructing the nomogram. The nomogram indicated good predictive performance with an AUC of 0.781 (95% CI: 0.729-0.832) and 0.808 (95% CI: 0.731-0.886) in the training and validation cohorts, respectively.ConclusionsElevated serum concentrations of AFP and VEGF-A, microvascular invasion, intratumor necrosis, surgical margin were independent risk factors of early intrahepatic recurrence. A reliable nomogram model which incorporated blood biomarkers and pathological variables was established and validated. The nomogram achieved desirable effectiveness in predicting early recurrence in HCC patients.

Land degradation has become a catastrophic global environmental issue. The current status of land degradation and changing trends of land remain unclear on the Qinghai-Tibet Plateau (QTP). This study integrated an Optimal Land Degradation Index (OLDI) and spatial footprints of three land degradation pathways (i.e., salinization, desertification and soil erosion) to investigate changing trends and degradation risks from 2001 to 2021 on the QTP. The results showed that land improvements were the dominant changing trends on the QTP compared to land degradation, accounting for 18.83% of the whole plateau. The regions with land improvements were mainly distributed in the northeastern QTP. High-risk degraded land covered an area of 0.55 million km2, and low-risk degraded land covered 0.78 million km2. The spatial distribution of high-risk degraded land varied gradually from scattered small areas to increasingly frequent connected patches from southeast to northwest. Potential driving factor analysis illustrated that land degradation resulted from multidimensional driving forcings, including topography, climatic factors, and human activities. The findings in this study can provide great insight for alpine ecosystem development and make adaption to achieve carbon neutrality with global warming.

China’s Loess Plateau is both the largest and deepest loess deposit in the world, and it has long been one of the most severely eroded areas on Earth. With the implementation of the Grain-for-Green Project in 1999, the Loess Plateau has become the most successful ecological restoration zone, and soil organic carbon (SOC) sequestration has greatly increased. However, little is known about the balance of SOC sequestration and vegetation restoration on the Loess Plateau. Thus, this review focused on the SOC sequestration from vegetation restoration in this region. Firstly, the current situations and principal aspects of vegetation restoration processes were reviewed, and the effects of vegetation restoration on SOC sequestration were summarized. Secondly, based on the new technologies and methods for soil carbon (C) sequestration, the mechanism of soil microbial C sequestration was described from the molecular level of genes, and some management measures for SOC sequestration were summarized. Finally, we pointed out the main directions in C sequestration mechanisms for vegetation restoration depending on the basic process of the C cycle, which should integrate into physics, chemistry, and biology. Overall, this review will help us understand the SOC sequestration function and the ecological benefits of vegetation restoration on the Loess Plateau.

Abstract The complex interaction between cancer cells and the immune microenvironment is a central regulator of tumor growth and the treatment response. Chemotherapy-induced senescence is accompanied by the senescence-associated secretion phenotype (SASP). However, the mechanisms underlying the regulation of the SASP remain the most poorly understood element of senescence. Here, we show that nuclear erythroid factor 2-like factor 2 (Nrf2), a master antioxidative transcription factor, accumulates upon doxorubicin-induced senescence. This is due to the increased cytoplasmic Inhibitor of Apoptosis Stimulating Protein of P53, iASPP, which binds with Keap1, interrupting Keap1/Nrf2 interaction and promoting Nrf2 stabilization and activation. Activated Nrf2 transactivates a novel target gene of SASP factor, macrophage colony-stimulating factor (M-CSF), which subsequently acts on macrophages and induces polarization from M1 to M2 via a paracrine mechanism. Genetic inhibition of iASPP-Nrf2 suppresses the growth of apoptosis-resistant xenografts, with further analysis revealing that M-CSF/M-CSFR-regulated macrophage polarization is critical for the functional outcomes delineated above. Overall, our data uncover a novel function of iASPP-Nrf2 in skewing the immune microenvironment under treatment-induced senescence. Targeting the iASPP-Nrf2 axis could be a powerful strategy for the implementation of new chemotherapy-based therapeutic opportunities.

Abstract In macroecology, the concept of r‐ and K‐strategy has been widely applied, yet, there have been limited studies on microbial life‐history strategies in temperate grasslands using multiple sequencing approaches. Total phospholipid fatty acid (PLFA) analysis, high‐throughput meta‐genomic sequencing, and GeoChip technologies were used to examine the changes in microbial life‐history traits in a chronosequence of restored grasslands (1, 5, 10, 15, 25, and 30 years since restoration). Grassland restoration increased the relative abundances of Actinobacteria, Proteobacteria, and Bacteroidetes but reduced the relative abundances of Acidobacteria, Planctomycetes, and Chloroflexi. PLFA analysis revealed that grassland restoration reduced the fungi:bacteria and Gram‐positive:Gram‐negative bacteria ratios. Combined with the meta‐genomic data, we found that grassland restoration shifted microorganisms from oligotrophic (K‐) to copiotrophic (r‐) groups, consistent with the increased rRNA operon copy number of the microbial community. Structural equation modeling showed that soil properties positively (p

We report the first detection in the interstellar medium (ISM) of a C _2 H _5 O _2 N isomer: syn -glycolamide (NH _2 C(O)CH _2 OH). The exquisite sensitivity at sub-mK levels of an ultradeep spectral survey carried out with the Yebes 40 m and IRAM 30 m telescopes toward the G+0.693–0.027 molecular cloud has allowed us to unambiguously identify multiple transitions of this species. We derived a column density of (7.4 ± 0.7) × 10 ^12 cm ^−2 , which implies a molecular abundance with respect to H _2 of 5.5 × 10 ^−11 . The other C _2 H _5 O _2 N isomers, including the higher-energy anti conformer of glycolamide and two conformers of glycine, were not detected. The upper limit derived for the abundance of glycine indicates that this amino acid is surely less abundant than its isomer glycolamide in the ISM. The abundances of the C _2 H _5 O _2 N isomers cannot be explained in terms of thermodynamic equilibrium; thus, chemical kinetics need to be invoked. While the low abundance of glycine might not be surprising, based on the relative low abundances of acids in the ISM compared to other compounds (e.g., alcohols, aldehydes, or amines), several chemical pathways can favor the formation of its isomer glycolamide. It can be formed through radical–radical reactions on the surface of dust grains. The abundances of these radicals can be significantly boosted in an environment affected by a strong ultraviolet field induced by cosmic rays, such as that expected in G+0.693–0.027. Therefore, as shown by several recent molecular detections toward this molecular cloud, it stands out as the best target to discover new species with carbon, oxygen, and nitrogen with increasing chemical complexity.

Extra-neural spread of glioblastoma (GBM) is extremely rare. We report a case of postoperative intracranial GBM spreading to the subcutaneous tissue via the channel of craniotomy defect in a 73-year-old woman. Radiological images and histopathology indicate that the tumor microenvironment of the subcutaneous tumor is clearly different from the intracranial tumor. We also model the invasion of GBM cells through the dura-skull defect in mouse. The retrospective analysis of GBM with scalp metastases suggests that craniectomy is a direct cause of subcutaneous metastasis in patients with GBM. Imaging examinations of other sites for systemic screening is also recommended to look for metastases outside the brain when GBM invades the scalp or metastasizes to it.

Abstract Cartilage regeneration after injury is still a great challenge in clinics, which suffers from its avascularity and poor proliferative ability. Herein we designed a novel biocompatible cellulose nanocrystal/GelMA (gelatin‐methacrylate anhydride)/HAMA (hyaluronic acid‐methacrylate anhydride)‐blended hydrogel scaffold system, loaded with synthetic melanin nanoparticles (SMNP) and a bioactive drug kartogenin (KGN) for theranostic purpose. We found that the SMNP‐KGN/Gel showed favorable mechanical property, thermal stability, and distinct magnetic resonance imaging (MRI) contrast enhancement. Meanwhile, the sustained release of KGN could recruit bone‐derived mesenchymal stem cells to proliferate and differentiate into chondrocytes, which promoted cartilage regeneration in vitro and in vivo. The hydrogel degradation and cartilage restoration were simultaneously monitored by multiparametric MRI for 12 weeks, and further confirmed by histological analysis. Together, these results validated the multifunctional hydrogel as a promising tissue engineering platform for noninvasive imaging‐guided precision therapy in cartilage regenerative medicine.