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We develop a new type of pH-responsive amphiphilic small molecular prodrug by conjugating folic acid with anti-tumour doxorubicin via a hydrazone bond. This prodrug is featured by high and precise drug loading (55.4 wt%), which can self-assemble into micellar nanoparticles in neutral environment while disassemble in the presence of tumour cells expressing folic acid receptors or the acidic tumoral endosomal environment. The prodrug nanoparticles can effectively improve anticancer efficacy due to the features of pH-triggered drug release and targeted delivery. Moreover, in vitro cell study further indicated that the resulting prodrug nanoparticles had enhanced cytotoxicity for folic-acid-positive cells (HeLa) compared to folic-acid-negative cells (MCF-7). More importantly, the induced disassembly of prodrug nanoparticles can “switch on” the inherent fluorescence of the internalized doxorubicin drug in the tumour microenvironment, which can be used for the detection of tumour cells. We believe that this strategy can pave a new way for designing small molecular drug delivery systems and facilitate tumour diagnosis and treatment simultaneously. [ABSTRACT FROM AUTHOR]

It is an important way for realizing sustainable development of sweet corn production to stabilize and improve soil fertility of cultivated land in sweet corn production region. Through the test of sweet corn straw directly returning to the field after 6 seasons for 3 years, the results showed that continuous single application of chemical fertilizer is not conducive to the stability of soil fertility and yield improvement, and implementation of straw returning could receive fertility, improve soil acidic conditions, and enhance the yield of sweet corn. Compared with before the test, the single application of chemical fertilizer increased soil available phosphorus, while the contents of soil organic matter, available nitrogen and available potassium decreased by 1. 08, 1.18 and 2.47 mg/kg respectively, and the soil pH decreased by 0.15. Under the same fertilizer conditions, organic matter contents of single and double-season straw returning increased by 0.71 and 1. 29 g/kg, available nitrogen increased by 17.15 and 28.27 mg/kg, available phosphorus increased by 0.96 and 1.73 mg/kg, available potassium increased by 2.41 and 5.92 mg/kg, the soil pH increased by 0.16 and 0.2. Compared with the single application of chemical fertilizer, the average yields of single and double-season straw returning increased by 7. 5% and 11. 8%, and their average income increased by 87.3 and 117.1 yuan of per mu (667 m²) respectively. [ABSTRACT FROM AUTHOR]

Cultural ecosystem services (CES) in urban parks are associated with nature contact willingness and health outcomes of urban residents. However, practical knowledge on how to manage urban park features to enhance CES is still lacking, especially on more detailed scales. This study developed a practice-oriented workflow for exploring design-related indicators that affect CES by considering four aspects of urban park features, including distance to elements, density of elements, land cover proportion, and landscape diversity. Then the workflow was implemented in a case study by taking six urban parks in Beijing as study areas. Three CES types were identified with outdoor social media images, including recreation value, aesthetic value, and social interaction value. Statistical analyses indicated that a combination of the four aspects of urban park features within a specific service radius was the most significant factor in explaining CES. The importance of design-related indicators for enhancing different CES types was also identified. Density of facilities, proportion of tree canopy-shaded ground, and richness of land cover types were proved important for all the three CES types and therefore could be concerned in urban park design practices. Based on these findings, this study further proposed landscape site design strategies and three adaptive design cases for enhancing different CES types, which could provide evidence-based and practical solutions for managers and landscape architects. [Display omitted] • Three cultural ecosystem service (CES) types were mapped with outdoor social media. • Four aspects of urban park features were adopted for explaining CES. • Urban park features within a specific service radius can explain CES more thoroughly. • The importance of design-related indicators in explaining CES was identified. • Strategies and cases for urban park design practices to enhance CES were proposed. [ABSTRACT FROM AUTHOR]

The nutritious acorns produced by oak trees ( Quercus spp.) are attacked frequently by insects that feed on seed reserves. However, previous studies have partly considered the effects of insect infestations on animal seed dispersal and subsequent plant regeneration. In this study, we tested whether the effects of insect infestations on seed dispersal were frequency dependent (i.e., ratio of noninfested to infested acorns). We tracked the seed dispersal of plastic-tagged noninfested and insect-infested Q. aliena var. acuteserrata acorns with different frequencies in the Qinling Mountains in central China. Our results demonstrated that noninfested acorns were removed more rapidly, regardless of the infestation rates. Insect-infested acorns were also more likely to be eaten in situ, whereas noninfested acorns were more likely to be scatter-hoarded independent of infestation rates. Moreover, noninfested acorns were dispersed further and had higher survival rates than insect-infested acorns. Our findings suggest that the seed dispersal advantages of noninfested acorns compared with infested acorns was not frequency dependent, thereby indicating a consistently higher dispersal likelihood of noninfested acorns. [ABSTRACT FROM AUTHOR]

With the rapid development of database technologies, multiple data sources may be available for a given learning task (e.g. collaborative filtering). However, the data sources may contain different types of features. For example, users' profiles can be used to build recommendation systems. In addition, a model can also use users' historical behaviors and social networks to infer users' interests on related products. We argue that it is desirable to collectively use any available multiple heterogeneous data sources in order to build effective learning models. We call this framework heterogeneous learning. In our proposed setting, data sources can include (i) nonoverlapping features, (ii) nonoverlapping instances, and (iii) multiple networks (i.e. graphs) that connect instances. In this paper, we propose a general optimization framework for heterogeneous learning, and devise a corresponding learning model from gradient boosting. The idea is to minimize the empirical loss with two constraints: (1) there should be consensus among the predictions of overlapping instances (if any) from different data sources; (2) connected instances in graph datasets may have similar predictions. The objective function is solved by stochastic gradient boosting trees. Furthermore, a weighting strategy is designed to emphasize informative data sources, and deemphasize the noisy ones. We formally prove that the proposed strategy leads to a tighter error bound. This approach consistently outperforms a standard concatenation of data sources on movie rating prediction, number recognition, and terrorist attack detection tasks. Furthermore, the approach is evaluated on AT&T's distributed database with over 500 000 instances, 91 different data sources, and over 45 000 000 joined features. We observe that the proposed model can improve out-of-sample error rate substantially. [ABSTRACT FROM AUTHOR]

The Pinus armandii and Quercus aliena var. acuteserrata mixed forest is one of the major forest types in the Qinling Mountains, China. P. armandii is considered to be a pioneer species during succession and it is usually invaded by late successional Q. aliena var. acuteserrata. However, the mechanism that underlies its invasion remains unclear. In the present study, we tracked seed dispersal of P. armandii and Q. aliena var. acuteserrata using coded plastic tags in the western, middle and eastern Qinling Mountains to elucidate the invasion process in the mixed forests. Our results indicated that the seeds of both P. armandii and Q. aliena var. acuteserrata were removed rapidly in the Qinling Mountains, and there were no differences in the seed removal rates between the two species. There were significant differences in rodent seed-eating and caching strategies between the two tree species. For P. armandii, seeds were more likely to be eaten in situ than those of Q. aliena var. acuteserrata in all plots. By contrast, the acorns of Q. aliena var. acuteserrata were less frequently eaten in situ, but more likely to be removed and cached. Q. aliena var. acuteserrata acorns had significantly longer dispersal distances than P. armandii seeds in all plots. Although P. armandii seeds were less likely to be dispersed into the Q. aliena var. acuteserrata stands, over 30% of the released acorns were transported into the P. armandii stands where they established five seedlings. Based on the coupled recruitment patterns of P. armandii and Q. aliena var. acuteserrata, we suggest that the animal-mediated seed dispersal contributes to the formation of Pinus armandii-Quercus aliena var. acuteserrata forests. [ABSTRACT FROM AUTHOR]

• Unimolecule-based size-charge switchable nanomedicine is of importance for precision medicine. • Assembly and disassembly mechanism of unimolecular micelles for enhancing nanoparticle in tumor accumulation and penetration. • Acid-responsive unimolecular micelles with enhanced tumor penetration and dual immunization strategies for synergistic sono-immunotherapy. [Display omitted] Immune checkpoint inhibitor-based immunotherapy has been the most promising method for treating cancer patients. In this study, an anti-programmed death ligand 1 peptide inhibitor (APP) was engineered to act in the inner core of unimolecular polymers (Dex-PCR780- b -P(DPA- co -APP). The APP polymers had the capability of forming nano-micelles (PCR780-APP NMs) via self-assembly and featured controlled exposure in an acidic microenvironment while maintaining APP original bioactivity. Notably, in an acid tumor microenvironment, the PCR780-APP NMs (~ 121.1 nm, 2.3 mV) quickly switched into ultrasmall and positively charged PCR780-APP unimolecular micelles (PCR780-APP UMs; ~ 24.1 nm, 19.6 mV) with ultrastability, a narrow polydispersity index, and great fluorescence/photoacoustic (FL/PA) linearity due to its unique and definite unimolecular structure. Based on these advantages, under FL/PA imaging guidance, size-charge switchable PCR780-APP NMs could control exposure of APP and when combined with ultrasound, induce specific-dosage reactive oxygen species (ROS) that facilitates abundant immune T-cell recruitment and activation in deep solid tumors. [ABSTRACT FROM AUTHOR]

• Mindfulness has significant effects on construction safety performance. • Psychological contract and coping behaviors play the mediating roles. • Errors, violations and safety participation have different antecedents. This research developed and tested an integrative model regarding the effects of mindfulness on construction workers' safety performance. Both psychological contract of safety and coping behaviors were examined as mediators. Empirical data were collected from 498 construction workers in China using a detailed questionnaire. Structural equation modeling was performed to analyze the data using AMOS and Mplus. The results showed that mindful workers were likely to have higher safety performance. Psychological contract of safety had stronger mediating effects on the relationship between mindfulness and safety performance than the coping behaviors. Furthermore, this research found that mindfulness was more related to errors and violations than safety participation. Problem-focused coping primarily mediated the effect of mindfulness on safety participation, while emotion-focused coping primarily mediated the effects on errors and violations. In addition, married workers reported more operational errors; older workers were more reluctant to follow safety rules; and workers with low education level were less likely to engage in voluntary safety activities. Theoretical and practical implications and associated research limitations are also discussed in this paper. [ABSTRACT FROM AUTHOR]

• Perceived communication, perceived controllability, and perceived responsiveness predict relationship quality. • Perceived communication and perceived controllability predict psychological ownership. • Relationship quality and psychological ownership predict solver engagement. • Different configurations of antecedents are associated with high and low levels of solver engagement. • Perceived interactivity and relationship quality jointly nourish solver engagement. • Perceived interactivity and psychological ownership jointly nourish solver engagement. Crowdsourcing has attracted significant attention from organizations seeking to capture new ideas and solutions, finance new projects, and obtain market feedback about product concepts. The success of online crowdsourcing communities relies on the engagement of solvers that participate in crowdsourcing activities. In line with the Stimulus-Organism-Response (S-O-R) model, this study aims to examine the relationships between the dimensions of perceived interactivity, relationship quality, psychological ownership, and solver engagement. The resulting relationships are examined using both symmetric (PLS-SEM) and asymmetric (fsQCA) approaches, applying survey data from 423 active solvers on two online crowdsourcing communities, Epwk.com and Zbj.com. PLS-SEM identified that high levels of perceived interactivity increased relationship quality. In contrast, the influence of perceived responsiveness on psychological ownership was not statistically significant. Finally, relationship quality and psychological ownership significantly influences solver engagement. The fsQCA results reinforced the PLS-SEM findings and revealed five alternative causal configurations that are sufficient for higher levels of solver engagement. [ABSTRACT FROM AUTHOR]

• Li 4 Mo 5 O 17 was first investigated for lithium-ion battery anode. • Li 4 Mo 5 O 17 micron particles were prepared by citric acid aid sol-gel method. • Li 4 Mo 5 O 17 electrode shows stable long cycle life. Herein, the micron-sized lithium molybdenum oxide (Li 4 Mo 5 O 17 , LMO) is first investigated as a new anode material for lithium secondary battery. LMO was obtained through citric acid aid sol–gel method and subsequently characterized by X-ray diffraction, X-ray photo-electron spectrometer and scanning electron microscopy. When tested as anode materials for lithium-ion batteries, the LMO electrode demonstrates excellent electrochemical performance. The initial discharge and charge specific capacities were 1470 mAh g−1 and 845 mAh g−1 at the current density of 100 mA g−1, respectively. The electrode provides a reversible charge capacity of 507 mAh g−1 even after 600 cycles long life test. These data show that LMO is very promising for the next generation of lithium-ion batteries. [ABSTRACT FROM AUTHOR]

The treatment outcomes of nanomedicines against colorectal cancer are severely restricted by their insufficient accumulation in the tumor tissues, unsatisfactory antitumor effect, and weak immunometabolic modulation. To address these issues, flying‐saucer‐shaped nanoheterojunctions by coating copper oxide (CuxO) onto the surface of PEGylated zinc oxide (ZnO) nanoparticles are constructed. When exposed to ultrasound, the resultant CuxO@ZnO nanoheterojunctions exhibit increased locomotor activities, facilitating colorectal mucus infiltration, deep tumor penetration, and tumor cell internalization. The decoration of CuxO suppresses the rapid recombination of electrons and holes in CuxO@ZnO exposed to ultrasound, promoting the production of singlet oxygen and hydroxyl radical, which are generated by CuxO through a Fenton‐like chemodynamic reaction and CuxO@ZnO through sonodynamic reaction. After rectal administration, the sono‐chemodynamic CuxO@ZnO plus PD‐L1 antibodies effectively inhibit the growth of orthotopic and distant tumors. It elicits immunometabolic responses by inducing immunogenic cell death, activating the interferon genes signaling pathway stimulator, and inhibiting glucose transport and the glycolytic signaling pathways. This combined modality also increases the proportion of beneficial microbes (e.g., Bifidobacterium) and decreases the abundance of harmful microorganisms (e.g., Romboutsia) in the intestine. This treatment modality (CuxO@ZnO plus ultrasound and PD‐L1 antibodies) is a promising strategy for the synergistic treatment of colorectal cancer. [ABSTRACT FROM AUTHOR]

Photorespiration, or C2 photosynthesis, is generally considered a futile cycle that potentially decreases photosynthetic carbon fixation by more than 25%. Nonetheless, many essential processes, such as nitrogen assimilation, C1 metabolism, and sulfur assimilation, depend on photorespiration. Most studies of photosynthetic and photorespiratory reactions are conducted with magnesium as the sole metal cofactor despite many of the enzymes involved in these reactions readily associating with manganese. Indeed, when manganese is present, the energy efficiency of these reactions may improve. This review summarizes some commonly used methods to quantify photorespiration, outlines the influence of metal cofactors on photorespiratory enzymes, and discusses why photorespiration may not be as wasteful as previously believed. [ABSTRACT FROM AUTHOR]

The first generation of nanomedicine exhibits superior performance in the clinical treatment of various cancers compared to free conventional anticancer therapeutics. However, poor tumor penetration has been considered a major obstacle in the cancer treatment process and substantially impairs the overall therapeutic efficacy. Recently, this situation has been effectively improved through a great variety of smart size-shrinkable drug delivery nanosystems (SSDDNs), which remains stable with relatively large size in the circulation system for a prolonged plasma half-life and enhanced tumor accumulation, then specifically turn into smaller particles at the tumor site by an appropriate stimulus to promote tumor penetration for uniform drug distribution throughout the whole tumor. In this review, we systematically summarize the intelligent size-shrinkable strategies mediated by different response modes, including endogenous and external stimuli. In addition to offering enhanced penetration, the size-shrinkable strategy can companion imaging probes for specific diagnoses and image-guided therapy. The challenges and prospects are discussed, and several proposals for promoting SSDDNs clinical translation are supplied. It is anticipated that such smart SSDDNs will provide a guideline for next-generation clinical translation. ga1 • SSDDNs is a golden strategy for addressing the paradox of nanoparticle size in tumor accumulation and penetration. • Maintain larger size in the circulation system for a prolonged half-life and enhanced high tumor retention. • Stimulus response size-shrinkage to promote deep penetration for uniform drug distribution throughout the whole tumor. • The resultant small-sized nanoparticles can also promote phagocytosis and the drug release rate. [ABSTRACT FROM AUTHOR]

The aims of this study were to explore the significant chemical changes in functional components induced by the traditional processing method and evaluate whether this method based on nine cycles of steaming and drying can effectively enhance the medicinal effects of Polygonatum cyrtonema rhizome. A global analysis on dynamic changes in secondary metabolites during nine processing cycles was performed, and the significantly differentially accumulated secondary metabolites were initially identified based on the secondary metabolome. Unsupervised principal component analysis (PCA), hierarchical clustering analysis (HCA), and orthogonal partial least squares discriminant analysis (OPLA-DA) on secondary metabolites clearly showed that processing significantly increased the global accumulation of secondary metabolites in processed P. cyrtonema rhizomes compared to unprocessed crude rhizomes. The first six processing cycles induced drastic changes in the accumulation of functional components, while the last three did not induce further changes. The accumulations of most functional components were significantly enhanced after the first three cycles and stabilized after six cycles; meanwhile, the first three cycles also led to numerous new components. However, the enhancing effects were unavoidably reversed or weakened under continued processing lasting 6–9 cycles. Furthermore, continued processing also reduced the contents of a small number of original components to undetectable levels. Processing induced some significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, among which the first three processing cycles enhanced the synthesis of various secondary metabolites and significantly affected the metabolisms of amino acids. In conclusion, this study not only reveals that processing can effectively enhance the medicinal effects, by two main mechanisms including enhancing chemical synthesis and inducing structural transformation of functional components, but also provides theoretical guidance for the optimization of the traditional processing method based on nine cycles of steaming and drying for achieving optimal effects on enhancing the medicinal effects of P. cyrtonema rhizome. [ABSTRACT FROM AUTHOR]

Introduction: Thrombosis in ANCA-associated vasculitis (AAV) was prevalent and has been neglected in Chinese patients. This study tried to describe the clinical characteristics, identify the risk factors, and investigate the causal relationship between AAV and venous thromboembolism (VTE) by two-sample Mendelian randomization (MR) analysis. Methods: In this retrospective, observational study, we included all hospitalized AAV patients from Jan 2013 to Apr 2022 in Peking Union Medical College Hospital. We collected their clinical data for multivariate regression analysis to determine the risk factors for thrombosis. The nomogram was constructed by applying these risk factors to predict thrombosis in AAV patients. As for MR analysis, we selected single nucleotide polymorphisms (SNPs) related to AAV from published genome-wide association studies and extracted the outcome data containing deep vein thrombosis (DVT) and pulmonary embolism (PE) from the UK biobank. Results: 1203 primary AAV patients were enrolled, and thrombosis occurred in 11.3%. Multivariate regression suggested that older than 65 years, EGPA, neurological involvement, lung involvement, significantly elevated serum creatinine (> 500µmol/L), and elevated D-dimer were associated with thrombosis in AAV patients. The model demonstrated satisfied discrimination with an AUC of 0.769 (95% CI, 0.726–0.812). MR analysis showed that EGPA could increase the risk of developing DVT and PE (OR = 1.0038, 95%CI = 1.0035–1.0041, P = 0.009). Conclusion: Thrombosis was not rare in Chinese patients with AAV. Renal damage and old age emerged as critical risk factors for thrombosis. EGPA might have a potential causal relationship with DVT and PE. [ABSTRACT FROM AUTHOR]

Background For decades, description of renal function has been of interest to clinicians and researchers. Serum creatinine (Scr) and estimated glomerular filtration rate (eGFR) are familiar but also limited in many circumstances. Meanwhile, the physiological volumes of the kidney cortex and medulla are presumed to change with age and have been proven to change with decreasing kidney function. Methods We recruited 182 patients with normal Scr levels between October 2021 and February 2022 in Peking Union Medical College Hospital (PUMCH) with demographic and clinical data. A 3D U-Net architecture is used for both cortex and medullary separation, and volume calculation. In addition, we included patients with the same inclusion criteria but with diabetes (PUMCH-DM test set) and diabetic nephropathy (PUMCH-DN test set) for internal comparison to verify the possible clinical value of "kidney age" (K-AGE). Results The PUMCH training set included 146 participants with a mean age of 47.5 ± 7.4 years and mean Scr 63.5 ± 12.3 μmol/L. The PUMCH test set included 36 participants with a mean age of 47.1 ± 7.9 years and mean Scr 66.9 ± 13.0 μmol/L. The multimodal method predicted K-AGE approximately close to the patient's actual physiological age, with 92% prediction within the 95% confidential interval. The mean absolute error increases with disease progression (PUMCH 5.00, PUMCH-DM 6.99, PUMCH-DN 9.32). Conclusion We established a machine learning model for predicting the K-AGE, which offered the possibility of evaluating the whole kidney health in normal kidney aging and in disease conditions. [ABSTRACT FROM AUTHOR]