Nesfatin-1 enhances vascular smooth muscle calcification through facilitating BMP-2 osteogenic signaling.

Vascular calcification (VC) arises from the accumulation of calcium salts in the intimal or tunica media layer of the aorta, contributing to higher risk of cardiovascular events and mortality. Despite this, the mechanisms driving VC remain incompletely understood. We previously described that nesfatin-1 functioned as a switch for vascular smooth muscle cells (VSMCs) plasticity in hypertension and neointimal hyperplasia. In this study, we sought to investigate the role and mechanism of nesfatin-1 in VC. The expression of nesfatin-1 was measured in calcified VSMCs and aortas, as well as in patients. Loss- and gain-of-function experiments were evaluated the roles of nesfatin-1 in VC pathogenesis. The transcription activation of nesfatin-1 was detected using a mass spectrometry. We found higher levels of nesfatin-1 in both calcified VSMCs and aortas, as well as in patients with coronary calcification. Loss-of-function and gain-of-function experiments revealed that nesfatin-1 was a key regulator of VC by facilitating the osteogenic transformation of VSMCs. Mechanistically, nesfatin-1 promoted the de-ubiquitination and stability of BMP-2 via inhibiting the E3 ligase SYTL4, and the interaction of nesfatin-1 with BMP-2 potentiated BMP-2 signaling and induced phosphorylation of Smad, followed by HDAC4 phosphorylation and nuclear exclusion. The dissociation of HDAC4 from RUNX2 elicited RUNX2 acetylation and subsequent nuclear translocation, leading to the transcription upregulation of OPN, a critical player in VC. From a small library of natural compounds, we identified that Curculigoside and Chebulagic acid reduced VC development via binding to and inhibiting nesfatin-1. Eventually, we designed a mass spectrometry-based DNA-protein interaction screening to identify that STAT3 mediated the transcription activation of nesfatin-1 in the context of VC. Overall, our study demonstrates that nesfatin-1 enhances BMP-2 signaling by inhibiting the E3 ligase SYTL4, thereby stabilizing BMP-2 and facilitating the downstream phosphorylation of SMAD1/5/9 and HDAC4. This signaling cascade leads to RUNX2 activation and the transcriptional upregulation of MSX2, driving VC. These insights position nesfatin-1 as a potential therapeutic target for preventing or treating VC, advancing our understanding of the molecular mechanisms underlying this critical cardiovascular condition.

Association between daily circulatory emergency ambulance dispatches and short-term PM2.5 exposure in a heavily polluted area.

Emergency ambulance dispatches (EAD) have been proven to be associated with ambient particulate matter with diameter < 2.5 µm (PM2.5) concentration, but the associations of circulatory EAD remained inconclusive, especially in heavily polluted areas. In this time series conducted in Shenyang City, Northeastern China, we explored the associations between circulatory EAD and ambient PM2.5 and its constituents. Data including 113,508 circulatory EAD records, five types of PM2.5 constituents, and meteorological information spanning from 2014 to 2019 were retrieved. Using generalized additive models (GAMs), we explored the association between circulatory EAD and calculated excess risks induced by a 10 µg/m3 increase (ERR10) in PM2.5 mass and its constituents. ERR by percentage change (ERRpc) to compare among the different constituents were also calculated. Positive associations between circulatory EAD and PM2.5 mass, sulfates, organic matters, and black carbon, were found particularly at lag0 and lag0-5, with the ERR10 of 3.8% (3.2%-4.4%), 6.5% (2.2%-10.8%), 4.2% (1.7%-6.6%), and 30.2% (17.2%-43.4%) at lag0-5, respectively. Similar associations were observed for cardiovascular EAD, while cerebrovascular EAD suggested a positive association with O3 rather than PM2.5 or its constituents. Notably, PM2.5 mass exhibited the largest ERRpc for circulatory and cardiovascular EAD, followed by sulfates and black carbon. Moreover, the risks were enhanced for circulatory and cardiovascular EAD in males compared to females and during warmer seasons compared to colder seasons. Our findings contribute new evidence on PM2.5 exposure and circulatory EAD in relatively polluted areas.

O-GlcNAcylation of RAB10 promotes hepatocellular carcinoma progression.

Ras-related protein Rab-10 (RAB10) is involved in tumorigenesis and progression of hepatocellular carcinoma (HCC). Here, we found RAB10, O-GlcNAc transferase (OGT), and O-GlcNAcylation were upregulated in HCC. In addition, RAB10 protein level was prominently positively correlated with the expression of OGT. O-GlcNAcylation modification of RAB10 was then investigated. Here we showed that RAB10 interacts directly with OGT in HCC cell lines, Meanwhile, O-GlcNAcylation enhanced RAB10 protein stability. Furthermore, knockdown of OGT suppressed aggressive behaviors of HCC in vitro and in vivo, while elevated RAB10 reversed these. Taken together, these results indicated that OGT mediated O-GlcNAcylation stabilized RAB10, thus accelerating HCC progression.

Differential effects of trichostatin A on mouse embryogenesis and development.

Trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, can significantly improve the reprogramming efficiency of somatic cells. However, whether TSA has a detrimental effect on other kinds of embryos is largely unknown because of the lack of integrated analysis of the TSA effect on natural fertilized embryos. To investigate the effect of TSA on mouse embryo development, we analyzed preimplantation and post-implantation development of in vivo, in vitro fertilized, and parthenogenetic embryos treated with TSA at different concentrations and durations. In vivo fertilized embryos appeared to be the most sensitive to TSA treatment among the three groups, and the blastocyst formation rate decreased sharply as TSA concentration and treatment time increased. TSA treatment also reduced the livebirth rate for in vivo fertilized embryos from 56.59 to 38.33% but did not significantly affect postnatal biological functions such as the pups' reproductive performance and their ability for spatial learning and memory. Further analysis indicated that the acetylation level of H3K9 and H4K5 was enhanced by TSA treatment at low concentrations, while DNA methylation appeared to be also disturbed by TSA treatment only at high concentration. Thus, our data indicates that TSA has different effects on preimplantation embryonic development depending on the nature of the embryo's reproductive origin, the TSA concentration and treatment time, whereas the effect of TSA at the indicated concentration on postnatal function was minor.

CT features and outcomes of newly developed pulmonary lesions in patients with Coronavirus Disease 2019 (COVID-19).

Background: In patients with coronavirus disease 2019 (COVID-19) pneumonia, whether new pulmonary lesions will continue to develop after treatment was unknown. This study aimed to determine whether new pulmonary lesions will develop after treatment in patients with COVID-19 pneumonia, and investigate their CT features and outcomes. Methods: This retrospective study included 56 consecutive patients with confirmed COVID-19 pneumonia from January 20 to March 5, 2020. Their initial and follow-up CT images and clinical data were reviewed. The CT manifestations of primary and newly developed pulmonary lesions and their changes after treatment were mainly evaluated. Results: Among the 56 patients (mean age: 48±15 years, 35 men) with COVID-19 pneumonia, 42 (75.0%) patients developed new pulmonary lesions during treatment. All new lesions developed before the nucleic acid test turned negative. Patients with new lesions were more likely to have lymphopenia (P=0.041) or increased C-reactive protein (CRP) levels (P<0.001) than those without new lesions. Of the 42 patients, 30 (71.4%) patients developed new lesions once, and 12 (28.6%) twice or thrice, which usually appeared when primary lesions were progressing (37, 88.1%) and 1-15 days after treatment. The newly developed lesions were usually multiple (38, 90.5%), distributed in the previously involved (39, 92.9%) or uninvolved (27, 64.3%) lobes, and manifested as ground-glass opacities (GGOs) with consolidation (23, 54.8%) or pure GGOs (19, 45.2%). After their occurrence, the new lesions in most patients (32, 76.2%) showed direct absorption, whereas those in some patients (10, 23.8%) progressed before absorption. Conclusion: During treatment, most patients with COVID-19 pneumonia will develop new pulmonary lesions, which usually manifest as multiple GGOs distributed around the primary lesions or in previously uninvolved lobes, and are subsequently absorbed directly.

Atovaquone enhances doxorubicin's efficacy via inhibiting mitochondrial respiration and STAT3 in aggressive thyroid cancer.

The clinical management of anaplastic thyroid carcinoma and follicular thyroid carcinoma is challenging and requires an alternative therapeutic strategy. Although atovaquone is an FDA-approved anti-malarial drug, studies has recently demonstrated its anti-cancer activities. In line with these efforts, our study shows that atovaquone is an attractive candidate for thyroid cancer treatment. We show that atovaquone significantly inhibits growth, migration and survival in a concentration-dependent manner in 8505C and FTC113 cells. Mechanistically, atovaquone inhibits mitochondrial complex III activity, leading to mitochondrial respiration inhibition and reduction of ATP production in thyroid cancer cells. The inhibitory effects of atovaquone is reversed in mitochondrial respiration-deficient 8505C ρ0 cells, confirming mitochondrial respiration as the mechanism of atovaquone's action in thyroid cancer. In addition, atovaquone suppresses phosphorylation of STAT3 in thyroid cancer wildype but not ρ0 cells, demonstrating that STAT3 phosphorylation inhibition by atovaquone is a consequence of mitochondrial respiration inhibition. Notably, we further demonstrate that atovaquone significantly augments doxorubicin's inhibitory effects via suppressing mitochondrial respiration and STAT3. Our findings suggest that atovaquone can be repurposed for thyroid cancer treatment. Our work also highlights that targeting mitochondrial respiration may represent potential therapeutic strategy in thyroid cancer.

Synthetic and immunological studies of N-acyl modified S-linked STn derivatives as anticancer vaccine candidates.

It is well known that tumor cells express some aberrant glycans, termed tumor-associated carbohydrate antigens (TACAs). TACAs are good targets for the development of carbohydrate-based anticancer vaccines. However, one of the major problems is that carbohydrate antigens possess a weak immunogenicity. To tackle this problem, a number of unnatural N-modified S-linked STn analogues were designed and prepared. Reaction of the modified STn disaccharides with bifunctional adipic acid p-nitrophenyl diester provided the corresponding activated esters, which was followed by the conjugation with keyhole limpet hemocyanin (KLH), affording the corresponding protein conjugates. The immunological properties of these glycoconjugates were evaluated in a mouse model. The results showed that the modified glycoconjugates stimulated the production of IgG antibodies that are capable of recognizing the naturally occurring STn antigen, helping the discovery of carbohydrate-based anticancer vaccine candidates.

iPS cells produce viable mice through tetraploid complementation.

Since the initial description of induced pluripotent stem (iPS) cells created by forced expression of four transcription factors in mouse fibroblasts, the technique has been used to generate embryonic stem (ES)-cell-like pluripotent cells from a variety of cell types in other species, including primates and rat. It has become a popular means to reprogram somatic genomes into an embryonic-like pluripotent state, and a preferred alternative to somatic-cell nuclear transfer and somatic-cell fusion with ES cells. However, iPS cell reprogramming remains slow and inefficient. Notably, no live animals have been produced by the most stringent tetraploid complementation assay, indicative of a failure to create fully pluripotent cells. Here we report the generation of several iPS cell lines that are capable of generating viable, fertile live-born progeny by tetraploid complementation. These iPS cells maintain a pluripotent potential that is very close to ES cells generated from in vivo or nuclear transfer embryos. We demonstrate the practicality of using iPS cells as useful tools for the characterization of cellular reprogramming and developmental potency, and confirm that iPS cells can attain true pluripotency that is similar to that of ES cells.

Blastomere biopsy influences epigenetic reprogramming during early embryo development, which impacts neural development and function in resulting mice.

Blastomere biopsy is used in preimplantation genetic diagnosis; however, the long-term implications on the offspring are poorly characterized. We previously reported a high risk of memory defects in adult biopsied mice. Here, we assessed nervous function of aged biopsied mice and further investigated the mechanism of neural impairment after biopsy. We found that aged biopsied mice had poorer spatial learning ability, increased neuron degeneration, and altered expression of proteins involved in neural degeneration or dysfunction in the brain compared to aged control mice. Furthermore, the MeDIP assay indicated a genome-wide low methylation in the brains of adult biopsied mice when compared to the controls, and most of the genes containing differentially methylated loci in promoter regions were associated with neural disorders. When we further compared the genomic DNA methylation profiles of 7.5-days postconception (dpc) embryos between the biopsy and control group, we found the whole genome low methylation in the biopsied group, suggesting that blastomere biopsy was an obstacle to de novo methylation during early embryo development. Further analysis on mRNA profiles of 4.5-dpc embryos indicated that reduced expression of de novo methylation genes in biopsied embryos may impact de novo methylation. In conclusion, we demonstrate an abnormal neural development and function in mice generated after blastomere biopsy. The impaired epigenetic reprogramming during early embryo development may be the latent mechanism contributing to the impairment of the nervous system in the biopsied mice, which results in a hypomethylation status in their brains.

Removal of Cu(II) and Ni(II) ions from an aqueous solution using α-Fe2O3nanoparticle-coated volcanic rocks.

An adsorbent, volcanic rocks coated with α-Fe2O3nanoparticles, was prepared and utilized for the removal of Cu(II) and Ni(II) ions from an aqueous solution. Characterization of the coated volcanic rocks indicated that the α-Fe2O3nanoparticles were successfully and homogeneously distributed on the volcanic rocks, including penetration into rock pores. Batch experiments were conducted to investigate adsorption performance. The adsorption behavior of both ions was found to best fit a pseudo second-order model and Langmuir isotherm. The maximum adsorption capacities of Cu(II) and Ni(II) ions were 58.14 mg g⁻¹ and 56.50 mg g⁻¹ at 293 K, respectively, and increased with rising temperature. The loaded α-Fe2O3nanoparticles onto volcanic rock significantly increased removal of Cu(II) and Ni(II) ions. The adsorption process was combined control of film diffusion and intra-particle diffusion. Adsorption thermodynamics indicated the adsorption process was spontaneous and occurred mainly through chemisorption. The results confirmed that the volcanic rocks coated with α-Fe2O3nanoparticles acted as a high-efficiency and low-cost absorbent, and effectively removed Cu(II) and Ni(II) from wastewater.

The development of nanocarriers for natural products.

Natural bioactive compounds from plants exhibit substantial pharmacological potency and therapeutic value. However, the development of most plant bioactive compounds is hindered by low solubility and instability. Conventional pharmaceutical forms, such as tablets and capsules, only partially overcome these limitations, restricting their efficacy. With the recent development of nanotechnology, nanocarriers can enhance the bioavailability, stability, and precise intracellular transport of plant bioactive compounds. Researchers are increasingly integrating nanocarrier-based drug delivery systems (NDDS) into the development of natural plant compounds with significant success. Moreover, natural products benefit from nanotechnological enhancement and contribute to the innovation and optimization of nanocarriers via self-assembly, grafting modifications, and biomimetic designs. This review aims to elucidate the collaborative and reciprocal advancement achieved by integrating nanocarriers with botanical products, such as bioactive compounds, polysaccharides, proteins, and extracellular vesicles. This review underscores the salient challenges in nanomedicine, encompassing long-term safety evaluations of nanomedicine formulations, precise targeting mechanisms, biodistribution complexities, and hurdles in clinical translation. Further, this study provides new perspectives to leverage nanotechnology in promoting the development and optimization of natural plant products for nanomedical applications and guiding the progression of NDDS toward enhanced efficiency, precision, and safety. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

Pharmacology of bioactive compounds from plant extracts for improving non-alcoholic fatty liver disease through endoplasmic reticulum stress modulation: A comprehensive review.

Background: Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver condition with significant clinical implications. Emerging research indicates endoplasmic reticulum (ER) stress as a critical pathogenic factor governing inflammatory responses, lipid metabolism and insulin signal transduction in patients with NAFLD. ER stress-associated activation of multiple signal transduction pathways, including the unfolded protein response, disrupts lipid homeostasis and substantially contributes to NAFLD development and progression. Targeting ER stress for liver function enhancement presents an innovative therapeutic strategy. Notably, the natural bioactive compounds of plant extracts have shown potential for treating NAFLD by reducing the level of ER stress marker proteins and mitigating inflammation, stress responses, and de novo lipogenesis. However, owing to limited comprehensive reviews, the effectiveness and pharmacology of these bioactive compounds remain uncertain. Objectives: To address the abovementioned challenges, the current review categorizes the bioactive compounds of plant extracts by chemical structures and properties into flavonoids, phenols, terpenoids, glycosides, lipids and quinones and examines their ameliorative potential for NAFLD under ER stress. Methods: This review systematically analyses the literature on the interactions of bioactive compounds from plant extracts with molecular targets under ER stress, providing a holistic view of NAFLD therapy. Results: Bioactive compounds from plant extracts may improve NAFLD by alleviating ER stress; reducing lipid synthesis, inflammation, oxidative stress and apoptosis and enhancing fatty acid metabolism. This provides a multifaceted approach for treating NAFLD. Conclusion: This review underscores the role of ER stress in NAFLD and the potential of plant bioactive compounds in treating this condition. The molecular mechanisms by which plant bioactive compounds interact with their ER stress targets provide a basis for further exploration in NAFLD management.

Anatomical Mechanisms of Leaf Blade Morphogenesis in Sasaella kogasensis 'Aureostriatus'.

There are limited studies on the cytology of bamboo leaf development from primordium to maturity. This study delves into the leaf morphological characteristics and growth patterns of Sasaella kogasensis 'Aureostriatus' and provides a three-dimensional anatomical analysis of cell division, expansion, and degradation. Leaves on the same branch develop bottom-up, while individual leaves develop the other way around. Like bamboo shoots and culms, the leaves follow a "slow-fast-slow" growth pattern, with longitudinal growth being predominant during their development. The growth zones of individual leaves included division, elongation, and maturation zones based on the distribution of growth space. By measuring 13,303 epidermal long cells and 3293 mesophyll cells in longitudinal sections of rapidly elongating leaves, we observed that in the rapid elongation phase (S4-S5), the division zone was located in the 1-2 cm segment at the bottom of the leaf blade and maintained a constant size, continuously providing new cells for leaf elongation, whereas in the late rapid elongation phase (S6), when the length of the leaf blade was approaching that of a mature leaf, its cells at the bottom of the blade no longer divided and were replaced by the ability to elongate. Furthermore, to gain an insight into the dynamic changes in the growth of the S. kogasensis 'Aureostriatus' leaves in the lateral and periclinal directions, the width and thickness of 1459 epidermal and 2719 mesophyll cells were counted in the mid-cross section of leaves at different developmental stages. The results showed that during the early stages of development (S1-S3), young leaves maintained vigorous division in the lateral direction, while periplasmic division gradually expanded from the bottom to the top of the leaf blade and the number of cell layers stabilized at S4. The meristematic tissues on both sides of the leaf were still able to divide at S4 but the frequency of the division gradually decreased, while cell division and expansion occurred simultaneously between the veins. At S6, the cells at the leaf margins and between the veins were completely differentiated and the width of the leaf blade no longer expanded. These findings revealed changes in cell growth anisotropically during the leaf development of S. kogasensis 'Aureostriatus' and demonstrated that leaf elongation was closely related to the longitudinal expansion of epidermal cells and proliferative growth of mesophyll cells, whereas the cell division of meristematic tissues and expansion of post-divisional cells contributed to the increases in blade width and thickness. The presented framework will facilitate a further exploration of the molecular regulatory mechanisms of leaf development in S. kogasensis 'Aureostriatus' and provide relevant information for developmental and taxonomic studies of bamboo plants.

Advances in Single-Cell Transcriptome Sequencing and Spatial Transcriptome Sequencing in Plants.

"Omics" typically involves exploration of the structure and function of the entire composition of a biological system at a specific level using high-throughput analytical methods to probe and analyze large amounts of data, including genomics, transcriptomics, proteomics, and metabolomics, among other types. Genomics characterizes and quantifies all genes of an organism collectively, studying their interrelationships and their impacts on the organism. However, conventional transcriptomic sequencing techniques target population cells, and their results only reflect the average expression levels of genes in population cells, as they are unable to reveal the gene expression heterogeneity and spatial heterogeneity among individual cells, thus masking the expression specificity between different cells. Single-cell transcriptomic sequencing and spatial transcriptomic sequencing techniques analyze the transcriptome of individual cells in plant or animal tissues, enabling the understanding of each cell's metabolites and expressed genes. Consequently, statistical analysis of the corresponding tissues can be performed, with the purpose of achieving cell classification, evolutionary growth, and physiological and pathological analyses. This article provides an overview of the research progress in plant single-cell and spatial transcriptomics, as well as their applications and challenges in plants. Furthermore, prospects for the development of single-cell and spatial transcriptomics are proposed.

Slow-Release Effect Assisted Crystallization for Sequential Deposition Realizes Efficient Inverted Perovskite Solar Cells.

The two-step sequential deposition strategy has been widely recognized in promoting the research and application of perovskite solar cells, but the rapid reaction of organic salts with lead iodide inevitably affects the growth of perovskite crystals, accompanied by the generation of more defects. In this study, the regulation of crystal growth was achieved in a two-step deposition method by mixing 1-naphthylmethylammonium bromide (NMABr) with organic salts. The results show that the addition of NMABr effectively delays the aggregation and crystallization behavior of organic salts; thereby, the growth of the optimal crystal (001) orientation of perovskite is promoted. Based on this phenomenon of delaying the crystallization process of perovskite, the "slow-release effect assisted crystallization" is defined. Moreover, the incorporation of the Br element expands the band gap of perovskite and mitigates material defects as nonradiative recombination centers. Consequently, the power conversion efficiency (PCE) of the enhanced perovskite solar cells (PSCs) reaches 20.20%. It is noteworthy that the hydrophobic nature of the naphthalene moiety in NMABr can enhance the humidity resistance of PSCs, and the perovskite phase does not decompose for more than 3000 h (30-40% RH), enabling it to retain 90% of its initial efficiency even after exposure to a nitrogen environment for 1200 h.

Gut microbiome and metabolites mediate the benefits of caloric restriction in mice after acute kidney injury.

The role of gut microbiome in acute kidney injury (AKI) is increasing recognized. Caloric restriction (CR) has been shown to enhance the resistance to ischemia/reperfusion injury to the kidneys in rodents. Nonetheless, it is unknown whether intestinal microbiota mediated CR protection against ischemic/reperfusion-induced injury (IRI) in the kidneys. Herein, we showed that CR ameliorated IRI-elicited renal dysfunction, oxidative stress, apoptosis, and inflammation, along with enhanced intestinal barrier function. In addition, gut microbiota depletion blocked the favorable effects of CR in AKI mice. 16S rRNA and metabolomics analysis showed that CR enriched the gut commensal Parabacteroides goldsteinii (P. goldsteinii) and upregulated the level of serum metabolite dodecafluorpentan. Intestinal colonization of P. goldsteinii and oral administration of dodecafluorpentan showed the similar beneficial effects as CR in AKI mice. RNA sequencing and experimental data revealed that dodecafluorpentan protected against AKI-induced renal injury by antagonizing oxidative burst and NFκB-induced NLRP3 inflammasome activation. In addition, we screened and found that Hamaudol improved renal insufficiency by boosting the growth of P. goldsteinii. Our results shed light on the role of intestinal microbiota P. goldsteinii and serum metabolites dodecafluorpentan in CR benefits to AKI.

Preimplantation genetic diagnosis (PGD) influences adrenal development and response to cold stress in resulting mice.

Preimplantation genetic diagnosis (PGD) has gained widespread application in clinical medicine and hence the health of PGD offspring needs to be systematically assessed. Given the critical role of the stress response in growth and health, assessments of the development and function of the stress system might help to clarify the health outcomes of PGD. In this study, we constructed a PGD-conceived mouse model and used naturally conceived mice as controls; we used this model to evaluate the potential effect of PGD procedures on the stress system of the offspring. Serum and tissues of stress organs, namely the hypothalamus, locus coeruleus and adrenal gland, were collected from 5-week-old mice in the basal state or after cold stress. The serum levels of stress-related hormones and the structural and functional indices of the stress organs were then examined. In the basal state, ultrastructural abnormalities and low expression of genes involved in steroid hormone synthesis were found in the adrenals of the PGD mice, which had low corticosterone and high epinephrine levels compared with those of control mice. After acute cold stress, the PGD mice continued to show structural and glucocorticoid secretion abnormalities resulting in a late response to the environmental change. Thus, our study indicates that PGD manipulations affect adrenal development, result in structural and functional abnormalities of the adrenals in the offspring and influence their reactivity and adaptability to cold stress.

Nitrogen removal through different pathways in an aged refuse bioreactor treating mature landfill leachate.

In this study, an aged refuse bioreactor was constructed to remove nitrogen in a mature landfill leachate. The nitrogen removal efficiency and the microbial community composition in the bioreactor were investigated. The results showed that the aged refuse bioreactor removed more than 90 % of total nitrogen in the leachate under the nitrogen loading rate (NLR) of 0.74 g/kg (vs) day, and the total nitrogen removal rate decreased to 62.2 % when NLR increased up to 2.03 g/kg (vs) day. Quantitative polymerase chain reaction results showed that the average cell number of ammonia-oxidizing bacteria in the bioreactor was 1.58 × 10(8) cells/g, which accounted for 0.41 % of total bacteria. The number of anammox bacteria in the reactor was 1.09 × 10(8) cells/g, which accounted for 0.27 % of total bacteria. Isotopic (15)N tracing experiments showed that nearly 10 % of nitrogen was removed by anammox. High-throughout 454 pyrosequencing revealed that the predominant bacteria in the bioreactor were Proteobacteria, Chloroflexi, Actinobacteria, Bacteroidetes, and Gemmatimonadetes, including various nitrifiers and denitrifiers with diverse heterotrophic and autotrophic metabolic pathways, supporting that nitrogen was removed through different pathways in this aged refuse bioreactor.

Research Progress on Stimulus-Responsive Polymer Nanocarriers for Cancer Treatment.

As drug carriers for cancer treatment, stimulus-responsive polymer nanomaterials are a major research focus. These nanocarriers respond to specific stimulus signals (e.g., pH, redox, hypoxia, enzymes, temperature, and light) to precisely control drug release, thereby improving drug uptake rates in cancer cells and reducing drug damage to normal cells. Therefore, we reviewed the research progress in the past 6 years and the mechanisms underpinning single and multiple stimulus-responsive polymer nanocarriers in tumour therapy. The advantages and disadvantages of various stimulus-responsive polymeric nanomaterials are summarised, and the future outlook is provided to provide a scientific and theoretical rationale for further research, development, and utilisation of stimulus-responsive nanocarriers.

Impact of Meritocratic Beliefs of Newcomers on Creativity: A Career Construction Perspective.

Recent research suggests that meritocratic beliefs impact future-oriented activities. However, relatively little attention has been given to concomitant work outcomes, such as employee creativity. This study examines how the meritocratic beliefs of newcomers relate to employee creativity. We explore a serial mediation model where the meritocratic beliefs of newcomers heighten their meaning of work and learning adaptability, which increases employee creativity. We use questionnaires to survey 212 full-time employees from 10 manufacturing enterprises in China, who had joined their companies for less than a year. The results show that positive serial indirect effects of the meritocratic beliefs of newcomers on employee creativity via increased meaning of work and learning adaptability. Overall, the results provide new insight that may advance theoretical and practical implications on the pathways in which meritocratic beliefs may enhance employee creativity.