Oncogenic fatty acid oxidation senses circadian disruption in sleep-deficiency-enhanced tumorigenesis.

Circadian disruption predicts poor cancer prognosis, yet how circadian disruption is sensed in sleep-deficiency (SD)-enhanced tumorigenesis remains obscure. Here, we show fatty acid oxidation (FAO) as a circadian sensor relaying from clock disruption to oncogenic metabolic signal in SD-enhanced lung tumorigenesis. Both unbiased transcriptomic and metabolomic analyses reveal that FAO senses SD-induced circadian disruption, as illustrated by continuously increased palmitoyl-coenzyme A (PA-CoA) catalyzed by long-chain fatty acyl-CoA synthetase 1 (ACSL1). Mechanistically, SD-dysregulated CLOCK hypertransactivates ACSL1 to produce PA-CoA, which facilitates CLOCK-Cys194 S-palmitoylation in a ZDHHC5-dependent manner. This positive transcription-palmitoylation feedback loop prevents ubiquitin-proteasomal degradation of CLOCK, causing FAO-sensed circadian disruption to maintain SD-enhanced cancer stemness. Intriguingly, timed ß-endorphin resets rhythmic Clock and Acsl1 expression to alleviate SD-enhanced tumorigenesis. Sleep quality and serum ß-endorphin are negatively associated with both cancer development and CLOCK/ACSL1 expression in patients with cancer, suggesting dawn-supplemented ß-endorphin as a potential chronotherapeutic strategy for SD-related cancer.

The impact of information presentation on self-other risk decision-making.

To explore the impact of social distance and information presentation types on self-other risk preferences in monetary tasks. Risk preferences were examined in decision-making tasks and experiential information tasks within different frameworks when participants made decisions for themselves and others. Experiment 1 employed experiential decision tasks and revealed individual differences in decision-making for oneself and others. In gain situations, participants exhibited more risk aversion when deciding for others compared to themselves. Experiment 2 presented both types of information simultaneously to investigate whether risk decisions for oneself and others are influenced by information types. Results indicated that experiential information led participants to make more conservative choices for others, while descriptive information eliminated this effect. This study discovered the influence of social distance on self-other risk decisions and the role of information presentation types in self and other risk decision-making. Future research could further explore self-other decision-making from the perspectives of decision-makers' traits and culture.

Crosstalk between lipid metabolism and EMT: emerging mechanisms and cancer therapy.

Lipids are the key component of all membranes composed of a variety of molecules that transduce intracellular signaling and provide energy to the cells in the absence of nutrients. Alteration in lipid metabolism is a major factor for cancer heterogeneity and a newly identified cancer hallmark. Reprogramming of lipid metabolism affects the diverse cancer phenotypes, especially epithelial-mesenchymal transition (EMT). EMT activation is considered to be an essential step for tumor metastasis, which exhibits a crucial role in the biological processes including development, wound healing, and stem cell maintenance, and has been widely reported to contribute pathologically to cancer progression. Altered lipid metabolism triggers EMT and activates multiple EMT-associated oncogenic pathways. Although the role of lipid metabolism-induced EMT in tumorigenesis is an attractive field of research, there are still significant gaps in understanding the underlying mechanisms and the precise contributions of this interplay. Further study is needed to clarify the specific molecular mechanisms driving the crosstalk between lipid metabolism and EMT, as well as to determine the potential therapeutic implications. The increased dependency of tumor cells on lipid metabolism represents a novel therapeutic target, and targeting altered lipid metabolism holds promise as a strategy to suppress EMT and ultimately inhibit metastasis.

Pyrroline-5-carboxylate reductase 1 reprograms proline metabolism to drive breast cancer stemness under psychological stress.

Cancer stem-like cells (CSCs) contribute to cancer metastasis, drug resistance and tumor relapse, yet how amino acid metabolism promotes CSC maintenance remains exclusive. Here, we identify that proline synthetase PYCR1 is critical for breast cancer stemness and tumor growth. Mechanistically, PYCR1-synthesized proline activates cGMP-PKG signaling to enhance cancer stem-like traits. Importantly, cGMP-PKG signaling mediates psychological stress-induced cancer stem-like phenotypes and tumorigenesis. Ablation of PYCR1 markedly reverses psychological stress-induced proline synthesis, cGMP-PKG signaling activation and cancer progression. Clinically, PYCR1 and cGMP-PKG signaling components are highly expressed in breast tumor specimens, conferring poor survival in breast cancer patients. Targeting proline metabolism or cGMP-PKG signaling pathway provides a potential therapeutic strategy for breast patients undergoing psychological stress. Collectively, our findings unveil that PYCR1-enhanced proline synthesis displays a critical role in maintaining breast cancer stemness.

Cancer cell employs a microenvironmental neural signal trans-activating nucleus-mitochondria coordination to acquire stemness.

Cancer cell receives extracellular signal inputs to obtain a stem-like status, yet how tumor microenvironmental (TME) neural signals steer cancer stemness to establish the hierarchical tumor architectures remains elusive. Here, a pan-cancer transcriptomic screening for 10852 samples of 33 TCGA cancer types reveals that cAMP-responsive element (CRE) transcription factors are convergent activators for cancer stemness. Deconvolution of transcriptomic profiles, specification of neural markers and illustration of norepinephrine dynamics uncover a bond between TME neural signals and cancer-cell CRE activity. Specifically, neural signal norepinephrine potentiates the stemness of proximal cancer cells by activating cAMP-CRE axis, where ATF1 serves as a conserved hub. Upon activation by norepinephrine, ATF1 potentiates cancer stemness by coordinated trans-activation of both nuclear pluripotency factors MYC/NANOG and mitochondrial biogenesis regulators NRF1/TFAM, thereby orchestrating nuclear reprograming and mitochondrial rejuvenating. Accordingly, single-cell transcriptomes confirm the coordinated activation of nuclear pluripotency with mitochondrial biogenesis in cancer stem-like cells. These findings elucidate that cancer cell acquires stemness via a norepinephrine-ATF1 driven nucleus-mitochondria collaborated program, suggesting a spatialized stemness acquisition by hijacking microenvironmental neural signals.

Fast Charge-Transport Interface on Primary Particles Boosts High-Rate Performance of Li-Rich Mn-Based Cathode Materials.

A Li-rich Mn-based layered oxide cathode (LLO) is one of the most promising cathode materials for achieving high-energy lithium-ion batteries. Nevertheless, the intrinsic problems including sluggish kinetics, oxygen evolution, and structural degradation lead to unsatisfactory performance in rate capability, initial Coulombic efficiency, and stability of LLO. Herein, different from the current typical surface modification, an interfacial optimization of primary particles is proposed to improve the simultaneous transport of ions and electrons. The modified interfaces containing AlPO4 and carbon can effectively increase the Li+ diffusion coefficient and decrease the interfacial charge-transfer resistance, thereby achieving fast charge-transport kinetics. Moreover, the in situ high-temperature X-ray diffraction confirms that the modified interface can improve the thermal stability of LLO by inhibiting the lattice oxygen release on the surface of the delithiated cathode material. In addition, the chemical and visual analysis of the cathode-electrolyte interface (CEI) composition clarifies that a highly stable and conductive CEI film generated on the modified electrode can facilitate interfacial kinetic transmission during cycling. As a result, the optimized LLO cathode exhibits a high initial Coulombic efficiency of 87.3% at a 0.2C rate and maintains superior high-rate stability with a capacity retention of 88.2% after 300 cycles at a 5C high rate.

Clinical analysis of 10 cases of multi-center tumor necrosis factor receptor-associated periodic syndrome / 中华儿科杂志

Objective: To summarize the clinical characteristics of tumour necrosis factor receptor-associated periodic syndrome (TRAPS) in children. Methods: The clinical manifestations, laboratory tests, genetic testing and follow-up of 10 children with TRAPS from May 2011 to May 2021 in 6 hospitals in China were retrospectively analyzed. Results: Among the 10 patients with TRAPS, including 8 boys and 2 girls. The age of onset was 2 (1, 5) years, the age of diagnosis was (8±4) years, and the time from onset to diagnosis was 3 (1, 7) years. A total of 7 types of TNFRSF1A gene variants were detected, including 5 paternal variations, 1 maternal variation and 4 de novo variations. Six children had a family history of related diseases. Clinical manifestations included recurrent fever in 10 cases, rash in 4 cases, abdominal pain in 6 cases, joint involvement in 6 cases, periorbital edema in 1 case, and myalgia in 4 cases. Two patients had hematological system involvement. The erythrocyte sedimentation rate and C-reactive protein were significantly increased in 10 cases. All patients were negative for autoantibodies. In the course of treatment, 5 cases were treated with glucocorticoids, 7 cases with immunosuppressants, and 7 cases with biological agents. Conclusions: TRAPS is clinically characterized by recurrent fever accompanied by joint, gastrointestinal, skin, and muscle involvement. Inflammatory markers are elevated, and autoantibodies are mostly negative. Treatment mainly involves glucocorticoids, immunosuppressants, and biological agents.

Hydroxyapatite-Based Coatings on Silicon Wafers and Printed Zirconia.

Dental surgery needs a biocompatible implant design that can ensure both osseointegration and soft tissue integration. This study aims to investigate the behavior of a hydroxyapatite-based coating, specifically designed to be deposited onto a zirconia substrate that was intentionally made porous through additive manufacturing for the purpose of reducing the cost of material. Layers were made via sol-gel dip coating by immersing the porous substrates into solutions of hydroxyapatite that were mixed with polyethyleneimine to improve the adhesion of hydroxyapatite to the substrate. The microstructure was determined by using X-ray diffraction, which showed the adhesion of hydroxyapatite; and atomic force microscopy was used to highlight the homogeneity of the coating repartition. Thermogravimetric analysis, differential scanning calorimetry, and Fourier transform infrared spectroscopy showed successful, selective removal of the polymer and a preserved hydroxyapatite coating. Finally, scanning electron microscopy pictures of the printed zirconia ceramics, which were obtained through the digital light processing additive manufacturing method, revealed that the mixed coating leads to a thicker, more uniform layer in comparison with a pure hydroxyapatite coating. Therefore, homogeneous coatings can be added to porous zirconia by combining polyethyleneimine with hydroxyapatite. This result has implications for improving global access to dental care.

Serum dual-specificity phosphatase 1 reflects decreased exacerbation risk, correlates with less advanced exacerbation severity and lower inflammatory cytokines in children with asthma

Background It is as fact that dual-specificity phosphatase 1 (DUSP1) regulates the T cell activation, pro-allergic response, and inflammation to engage with the pathogenesis of asthma, but its clinical role in children with asthma is unclear. The present study aimed to explore the expression of DUSP1, its association with exacerbation risk, severity, and inflammatory cytokines in children with asthma. Method Around 52 children with asthma-exacerbation, 50 children in asthma-remission, and 50 healthy children were chosen for the study. The serum levels of DUSP1, as well as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-17 were detected by the enzyme-linked immunosorbent assay. Results The levels of DUSP1 was the highest in healthy children (median (IQR)=34.305 (25.892– 43.693) ng/mL), the second highest in children in asthma-remission (median (IQR)=21.471 (18.581–27.934) ng/mL), and the lowest in children with asthma-exacerbation (median (IQR)=13.982 (7.901–21.624) ng/mL) (P<0.001). At the same time, DUSP1 was also related to decreased asthma risk with area under curve (AUC) (95%CI) of 0.847 (0.780–0.914), and correlated with its lower exacerbation risk with AUC (95%CI) of 0.755 (0.661–0.849). Besides, DUSP1 was negatively linked with exacerbation severity (rs=–0.338, P=0.014), immunoglobulin E (rs=-0.277, P=0.047), TNF-α (rs=-0.423, P=0.002), IL-1β (rs=-0.389, P=0.004), and IL-17 (rs=-0.293, P=0.035), but not related with other disease features in children with asthma-exacerbation. Meanwhile, DUSP1 was only negatively associated with TNF-α (rs=-0.300, P=0.034) and IL-1β (rs=-0.309, P=0.029) in children in asthma-remission. However, no correlation was found in DUSP1 with inflammatory cytokines or other disease features in healthy children (all P>0.05). Conclusion DUSP1 reflects the reduced exacerbation risk, and associates with lower (AU)

A broken circadian clock: The emerging neuro-immune link connecting depression to cancer.

Circadian clocks orchestrate daily rhythms in many organisms and are essential for optimal health. Circadian rhythm disrupting events, such as jet-lag, shift-work, night-light exposure and clock gene alterations, give rise to pathologic conditions that include cancer and clinical depression. This review systemically describes the fundamental mechanisms of circadian clocks and the interacting relationships among a broken circadian clock, cancer and depression. We propose that this broken clock is an emerging link that connects depression and cancer development. Importantly, broken circadian clocks, cancer and depression form a vicious feedback loop that threatens systemic fitness. Arresting this harmful loop by restoring normal circadian rhythms is a potential therapeutic strategy for treating both cancer and depression.

[Difference in soil water holding capacity and the influencing factors under different land use types in the alpine region of Tibet, China]. / è¥¿è—é«˜å¯’åŒºä¸åŒåœŸåœ°åˆ©ç”¨æ–¹å¼ä¸‹åœŸå£¤æŒæ°´èƒ½åŠ›å·®å¼‚åŠå ¶å½±å“å› ç´ .

To investigate the variation of soil water holding capacity under different land use types can provide scientific basis for evaluating the change characteristics and regulation mechanism of water conservation capacity in alpine ecosystems. We collected soil samples at different depth intervals (0-10, 10-20 and 20-30 cm) under three land use types (farmland, forest, and grassland) in Tibet alpine region to measure the maximum water holding capacity, capillary water holding capacity, field capacity, and basic soil physicochemical properties. The associated environmental factors (mean annual precipitation, normalized difference vegetation index, altitude, slope gradient and surface roughness) were extracted to analyze the change characteristics and influencing factors of soil water holding capacity under different land use types. The results showed that soil water holding capacity (the maximum water holding capacity, capillary water holding capacity, and field capacity) of farmland, forest, and grassland all decreased with increasing soil depth. The mean values of the maximum water holding capacity, capillary water holding capacity, and field capacity in the 0-30 cm soil layer of grassland were 379.79, 329.57 and 194.39 g·kg-1, respectively, which were significantly higher than that of farmland (301.15, 259.67, and 154.91 g·kg-1) and forest (293.09, 251.49, and 117.01 g·kg-1). Results of the redundancy analysis showed that soil properties significantly influenced soil water holding capacity, with explanation rate of 44.6%, 42.7%, 37.6% and 35.8% for total porosity, soil organic matter, capillary porosity and soil bulk density, respectively. Results of the principal component analysis showed that mean annual precipitation, normalized difference vegetation index, altitude, slope gradient, and surface roughness were the main environmental factors affecting the spatial variation of soil water holding capacity, with a cumulative contribution of 72.4%. The grassland in the alpine region of Tibet had the highest water holding capacity and could effectively prevent soil erosion. Therefore, the implementation of returning farmland to grassland and the enclosure management of degraded grassland would be conducive to improve soil water conservation capacity in the alpine regions.

Recent advances in the study of a novel Omicron variant of SARS-CoV-2 / 中国热带医学

@#Abstract: Due to the continued emergence of multiple variants of SARS-CoV-2, the ongoing pandemic has resulted in severe mortality over the past two years. After the Alpha, Beta, Gamma and Delta variants, the most recent new variant of concern (VOC) strain to emerge is Omicron (B.1.1.529), which evolved as a result of the accumulation of a large number of mutations. The Omicron variant, which has a much higher transmission rate than the Delta variant, soon replaced the Delta variant and others, is now the dominant variant worldwide. The emergence of Omicron poses new challenges for the prevention and control of COVID-19 and has raised a number of concerns worldwide. Recently, cases of Omicron infection have been reported in several parts of China, and therefore this paper provides a comprehensive analysis and summary of the epidemiology and immune escape mechanisms of the Omicron variant. We also suggest some therapeutic strategies against the Omicron variant, including rapid diagnosis, genome analysis of emerging variants, ramping up of vaccination drives and receiving booster doses, updating the available vaccines, designing of multivalent vaccines able to generate hybrid immunity, up-gradation of medical facilities and strict implementation of adequate prevention and control measures need to be given high priority to handle the on-going COVID-19 pandemic successfully.

Diversity and function of culturable actinobacteria in the root-associated of Salvia miltiorrhiza Bunge.

The root-associated actinobacteria play important roles in plant growth, nutrient use, and disease resistance due to their functional diversity. Salvia miltiorrhiza is a critical medicinal plant in China. The root actinobacterial community structure has been studied; however, the functions of root-associated actinobacteria of S. miltiorrhiza have not been elucidated. This study aimed to decipher the diversity and function of the culturable root-associated actinobacteria in plant growth using culture-dependent technology and culturable microbe metagenomes. We isolated 369 strains from the root-associated actinobacteria, belonging to four genera, among which Streptomyces was dominant. Besides, the functional prediction revealed some pathways related to plant growth, nitrogen and phosphorus metabolism, and antagonistic pathogens. We systematically described the diversity and functions of the culturable root-associated actinobacteria community. Our results demonstrated that the culturable root-associated actinobacteria of S. miltiorrhiza have rich functionalities, explaining the possible contribution of culturable root-associated actinobacteria to S. miltiorrhiza's growth and development. This study provides new insights into understanding the function of the culturable root-associated actinobacteria and can be used as a knowledge base for plant growth promoters and biological control agent development in agriculture.

"Felodipine-indomethacin" co-amorphous supersaturating drug delivery systems: "Spring-parachute" process, stability, in vivo bioavailability, and underlying molecular mechanisms.

Amorphous solid dispersions (ASD) are one of most commonly used supersaturating drug delivery systems (SDDS) to formulate insoluble active pharmaceutical ingredients. However, the development of polymer-guided stabilization of ASD systems faces many obstacles. To overcome these shortcomings, co-amorphous supersaturable formulations have emerged as an alternative formulation strategy for poorly soluble compounds. Noteworthily, current researches around co-amorphous system (CAS) are mostly focused on preparation and characterization of these systems, but more detailed investigations of their supersaturation ("spring-parachute" process), stability, in vivo bioavailability and molecular mechanisms are inadequate and need to be clarified. In present study, we chose pharmacological relevant BCS II drugs to fabricate and characterize "felodipine-indomethacin" CAS. To enrich the current inadequate but key knowledge on CAS studies, we carried out following highlighted investigations including dissolution/solubility, semi-continuous "spring-parachute" process, long-term stability profile of amorphous state, in vivo bioavailability and underlying molecular mechanisms (molecular interaction, molecular miscibility and crystallization inhibition). Generally, the research provides some key information in the field of current "drug-drug" CAS supersaturable formulations.

Spontaneous formation of multilayer refractory carbide coatings in a molten salt media.

Refractory materials hold great promise to develop functional multilayer coating for extreme environments and temperature applications but require high temperature and complex synthesis to overcome their strong atomic bonding and form a multilayer structure. Here, a spontaneous reaction producing sophisticated multilayer refractory carbide coatings on carbon fiber (CF) is reported. This approach utilizes a relatively low-temperature (950 °C) molten-salt process for forming refractory carbides. The reaction of titanium (Ti), chromium (Cr), and CF yields a complex, high-quality multilayer carbide coating composed of 1) Cr carbide (Cr3C2), 2) Ti carbide, and 3) Cr3C2 layers. The layered sequence arises from a difference in metal dissolutions, reactions, and diffusion rates in the salt media. The multilayer-coated CFs act as a permeable oxidation barrier with no crystalline degradation of the CFs after extreme temperature (1,200 °C) and environment (oxyacetylene flame) exposure. The synthesis of high-quality multilayer refractory coating in a fast, efficient, easy, and clean manner may answer the need for industrial applications that develop cheap and reliable extreme environment protection barriers.

[Study on liver diseases with zebrafish as an important tool].

With the increasing incidence of hepatobiliary diseases, it is particularly important to understand the role of molecular, cellular and physiological factors in the clinical diagnosis and treatment with traditional Chinese medicine(TCM) in the development of liver disease. Appropriate animal models can help us identify the possible mechanisms of relevant diseases. Danio rerio(zebrafish) model was traditionally used to study embryonic development, and has been gradually used in screening and evaluation of liver diseases and relevant drug in recent years. Zebrafish embryos develop rapidly and the digestive organs of 5-day-old juvenile fish are all mature. At this stage, they may develop hepatobiliary diseases induced by developmental defects or compounds. Zebrafish liver is similar to human liver in cell composition, function, signal transduction, response to injury and cell process mediating liver disease. Furthermore, due to the high conservation of genes and proteins between humans and zebrafish, zebrafish becomes an alternative system for studying basic mechanisms of liver disease. Therefore, genetic screening could be performed to identify new genes involving specific disease processes, and chemical screening could be made for drugs in specific processes. This paper briefly introduced the experimental properties of zebrafish as model system, emphasized the study progress of zebrafish models for pathological mechanism of liver diseases, especially fatty liver, and drug screening and evaluation, so as to provide ideas and techniques for the future liver toxicity assessment of TCM.

Oncogenic AURKA-enhanced N6-methyladenosine modification increases DROSHA mRNA stability to transactivate STC1 in breast cancer stem-like cells.

RNase III DROSHA is upregulated in multiple cancers and contributes to tumor progression by hitherto unclear mechanisms. Here, we demonstrate that DROSHA interacts with ß-Catenin to transactivate STC1 in an RNA cleavage-independent manner, contributing to breast cancer stem-like cell (BCSC) properties. DROSHA mRNA stability is enhanced by N6-methyladenosine (m6A) modification which is activated by AURKA in BCSCs. AURKA stabilizes METTL14 by inhibiting its ubiquitylation and degradation to promote DROSHA mRNA methylation. Moreover, binding of AURKA to DROSHA transcript further strengthens the binding of the m6A reader IGF2BP2 to stabilize m6A-modified DROSHA. In addition, wild-type DROSHA, but not an m6A methylation-deficient mutant, enhances BCSC stemness maintenance, while inhibition of DROSHA m6A modification attenuates BCSC traits. Our study unveils the AURKA-induced oncogenic m6A modification as a key regulator of DROSHA in breast cancer and identifies a novel DROSHA transcriptional function in promoting the BCSC phenotype.

Cancer and stress: NextGen strategies.

Chronic stress is well-known to cause physiological distress that leads to body balance perturbations by altering signaling pathways in the neuroendocrine and sympathetic nervous systems. This increases allostatic load, which is the cost of physiological fluctuations that are required to cope with psychological challenges as well as changes in the physical environment. Recent studies have enriched our knowledge about the role of chronic stress in disease development, especially carcinogenesis. Stress stimulates the hypothalamic-pituitaryadrenal (HPA) axis and the sympathetic nervous system (SNS), resulting in an abnormal release of hormones. These activate signaling pathways that elevate expression of downstream oncogenes. This occurs by activation of specific receptors that promote numerous cancer biological processes, including proliferation, genomic instability, angiogenesis, metastasis, immune evasion and metabolic disorders. Moreover, accumulating evidence has revealed that ß-adrenergic receptor (ADRB) antagonists and downstream target inhibitors exhibit remarkable anti-tumor effects. Psychosomatic behavioral interventions (PBI) and traditional Chinese medicine (TCM) also effectively relieve the impact of stress in cancer patients. In this review, we discuss recent advances in the underlying mechanisms that are responsible for stress in promoting malignancies. Collectively, these data provide approaches for NextGen pharmacological therapies, PBI and TCM to reduce the burden of tumorigenesis.

Study on liver diseases with zebrafish as an important tool / 中国中药杂志

With the increasing incidence of hepatobiliary diseases, it is particularly important to understand the role of molecular, cellular and physiological factors in the clinical diagnosis and treatment with traditional Chinese medicine(TCM) in the development of liver disease. Appropriate animal models can help us identify the possible mechanisms of relevant diseases. Danio rerio(zebrafish) model was traditionally used to study embryonic development, and has been gradually used in screening and evaluation of liver diseases and relevant drug in recent years. Zebrafish embryos develop rapidly and the digestive organs of 5-day-old juvenile fish are all mature. At this stage, they may develop hepatobiliary diseases induced by developmental defects or compounds. Zebrafish liver is similar to human liver in cell composition, function, signal transduction, response to injury and cell process mediating liver disease. Furthermore, due to the high conservation of genes and proteins between humans and zebrafish, zebrafish becomes an alternative system for studying basic mechanisms of liver disease. Therefore, genetic screening could be performed to identify new genes involving specific disease processes, and chemical screening could be made for drugs in specific processes. This paper briefly introduced the experimental properties of zebrafish as model system, emphasized the study progress of zebrafish models for pathological mechanism of liver diseases, especially fatty liver, and drug screening and evaluation, so as to provide ideas and techniques for the future liver toxicity assessment of TCM.