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Metabolic reprogramming plays a critical role in tumorigenesis and tumor progression. The metabolism and the proliferation of tumors are regulated by both intrinsic factors within the tumor and the availability of metabolites in the tumor microenvironment (TME). The metabolic niche within the TME is primarily orchestrated at 3 levels: 1) the regulation of tumor metabolism by factors intrinsic to the tumors, 2) the interaction between tumor cells and T cells, macrophages, and stromal cells, and 3) the metabolic heterogeneity of tumor cells within the tissue space. Herein, we provided a concise overview of the various metabolic regulatory modes observed in tumor cells. Additionally, we extensively analyzed the interaction between tumor cells and other cells within the TME, as well as the metabolic characteristics and functions of different types of cells. Ultimately, this review provides a theoretical basis and novel insights for the precision treatment of tumors.

Multi-biological functions of intermedin in diseases.

Intermedin (IMD) is a member of the calcitonin gene-related peptide (CGRP)/calcitonin (CT) superfamily, and it is expressed extensively throughout the body. The typical receptors for IMD are complexes composed of calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein (RAMP), which leads to a biased activation towards Gαs. As a diagnostic and prognostic biomarker, IMD regulates the initiation and metastasis of multiple tumors. Additionally, IMD functions as a proangiogenic factor that can restrain excessive vascular budding and facilitate the expansion of blood vessel lumen, ultimately resulting in the fusion of blood vessels. IMD has protective roles in various diseases, including ischemia-reperfusion injury, metabolic disease, cardiovascular diseases and inflammatory diseases. This review systematically elucidates IMD's expression, structure, related receptors and signal pathway, as well as its comprehensive functions in the context of acute kidney injury, obesity, diabetes, heart failure and sepsis. However, the precise formation process of IMD short peptides in vivo and their downstream signaling pathway have not been fully elucidated yet. Further in-depth studies are need to translate IMD research into clinical applications.

Preparation of MoS2/MXene/NC Porous Composite Microspheres with Wrinkled Surface and Their Microwave Absorption Performances.

In this paper, a MoS2/MXene/N-doped carbon (NC) porous composite microsphere with a wrinkled surface was designed and constructed. Lithium fluoride exfoliation and lithium-ion etching fabricated two types of 2D assembly elements, MXene (Ti3C2Tx) and MoS2 nanosheets. The two nanosheets were self-assembled by an ultrasonic spray technique with high-temperature reduction, and MoS2/MXene microspheres with 3Dwrinkled shapes were obtained. The coating of the surface NC layer was achieved by the carbonization of a polydopamine (PDA) precursor formed by the self-polymerization of dopamine. The amount of PDA coating and raw material ratio significantly affect the microstructure and electromagnetic wave absorption performance. The optimal MXene to MoS2 mass ratio is 5:1, and the optimal coating time and filler amount are 8 h and 40%. MoS2/MXene/NC composite microspheres exhibit excellent absorption performance with low reflection losses (RLmin) of -52.9 dB at 6.4 GHz and high adequate absorption bandwidths of 5.2 GHz. By adjusting the thickness of the absorber, the full coverage of the C-Ku band (4-18 GHz) can be achieved. As a new composite absorber, it has significant potential applications.

A novel prognostic signature contributes to precision treatment in colon adenocarcinoma with KRAS mutation.

BACKGROUND: Approximately 40% of colon cancer harbor Kirsten rat sarcoma viral oncogene ( KRAS ) mutations, but the prognostic value of KRAS mutations in colon cancer is still controversial. METHODS: We enrolled 412 colon adenocarcinoma (COAD) patients with KRAS mutations, 644 COAD patients with KRAS wild-type and 357 COAD patients lacking information on KRAS status from five independent cohorts. A random forest model was developed to estimate the KRAS status. The prognostic signature was established using least absolute shrinkage and selection operator-Cox regression and evaluated by Kaplan-Meier survival analysis, multivariate-Cox analysis, receiver operating characteristic curve and nomogram. The expression data of KRAS -mutant COAD cell lines from the Cancer Cell Line Encyclopedia database and the corresponding drug sensitivity data from the Genomics of Drug Sensitivity in Cancer database were used for potential target and agent exploration. RESULTS: We established a 36-gene prognostic signature classifying the KRAS -mutant COAD as high and low risk. High risk patients had inferior prognoses compared to those with low risk, while the signature failed to distinguish the prognosis of COAD with KRAS wild-type. The risk score was the independent prognostic factor for KRAS -mutant COAD and we further fabricated the nomograms with good predictive efficiency. Moreover, we suggested FMNL1 as a potential drug target and three drugs as potential therapeutic agents for KRAS -mutant COAD with high risk. CONCLUSION: We established a precise 36-gene prognostic signature with great performance in prognosis prediction of KRAS -mutant COAD providing a new strategy for personalized prognosis management and precision treatment for KRAS -mutant COAD.

Safety and efficacy of postoperative adjuvant therapy with atezolizumab and bevacizumab after radical resection of hepatocellular carcinoma.

BACKGROUND: The effects of postoperative adjuvant therapy for high-risk recurrent hepatocellular carcinoma (HCC) in immunotherapy are still under investigation. This study evaluated the preventive effects and safety of postoperative adjuvant therapy, including atezolizumab, and bevacizumab, against the early recurrence of HCC with high-risk factors. METHODS: The complete data of HCC patients who underwent radical hepatectomy with or without postoperative adjuvant therapy after two-year follow-up were analyzed retrospectively. The patients were divided into high-risk or low-risk groups based on HCC pathological characteristics. High-risk recurrence patients were divided into postoperative adjuvant treatment and control groups. Due to the difference in approaches in postoperative adjuvant therapies, they were divided into transarterial chemoembolization (TACE), atezolizumab, and bevacizumab (T + A), and combination (TACE+T + A) groups. The two-year recurrence-free survival rate (RFS), overall survival rate (OS), and associated factors were analyzed. RESULTS: The RFS in the high-risk group was significantly lower than that in the low-risk group (P = 0.0029), and the two-year RFS in the postoperative adjuvant treatment group was significantly higher than that in the control group (P = 0.040). No severe complications were observed in those who received atezolizumab and bevacizumab or other therapy. CONCLUSION: Postoperative adjuvant therapy was related to two-year RFS. TACE, T + A, and the combination of these two approaches were comparable in reducing the early recurrence of HCC without severe complications.

UPLC-MS/MS simultaneous quantification of urinary circadian rhythm hormones and related metabolites: Application to air traffic controllers.

Civil aviation flight crew and civil aviation air traffic controllers are prone to circadian rhythm abnormalities, which can lead to a slew of other maladies. It could endanger people's health and provide a serious threat to the safety of civil aviation flights if it is not appropriately evaluated and addressed. Early detection of rhythm irregularities and prompt treatment for particular populations that are vulnerable to rhythm disorders are crucial for enhancing civil aviation safety. In general, monitoring of the classical circadian rhythm biomarkers (melatonin or cortisol) in plasma or saliva is an effective way to evaluate the rhythm status. Due to the challenging sample procedure and the trauma of plasma, urine sample testing has received an increasing amount of attention. While, urine circadian rhythm biomarkers have seldom been examined, and the relationship between urinary steroid hormones and melatonin is still poorly understood. In most cases, hormones are determined by immunoassays respectively, mainly enzyme-linked immunosorbent assay (ELISA) or radioimmunoassay (RIA). There are also reports describing the liquid chromatography with tandem mass spectrometry (LC-MS/MS) technique as a method of melatonin or few steroid hormones quantification, however, the simultaneous detection of multiple rhythmic hormones in human urine is rarely reported. For the quantification of the rhythmic hormones in human urine, an accurate approach using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was devised in this work. Nine endogenous hormones (melatonin, 6-hydroxymelatonin, 6-sulfatoxymelatonin, cortisol, corticosterone, cortisone, testosterone, epitestosterone and androsterone), in human overnight urine, were quantified after solid phase extraction (SPE). A reverse phase HSS C18 column was used for chromatographic separation with a 9-minute gradient elution and deuterated analogues of each analyte were applied as internal standards. This method was successfully applied to the analysis of 596 overnight urine samples (23:00-9:00) collected from 84 air traffic controllers in the Beijing area during shift work. This study's findings showed a clear correlation not only between melatonin and its metabolites; cortisol-related metabolites, but also between melatonin metabolites and endogenous metabolites upstream and downstream of cortisol, implying that these two categories of hormones can be used as potential biological rhythm indicators to provide circadian rhythm data support for future studies on circadian rhythm disorders.

3-D tissue-engineered epidermis against human primary keratinocytes apoptosis via relieving mitochondrial oxidative stress in wound healing.

The tissue-engineered epidermal (TEE), composed of biocompatible vectors and autogenous functional cells, is a novel strategy to solve the problem of shortage of donor skin sources. The human primary keratinocyte (HPK), the major skin components, are self-evident vital in wound healing and was considered as one of the preferred seed cells for TEEs. Since the process of separating HPKs from the skin triggers a stress state of the cells, achieving its rapid adhesion and proliferation on biomaterials remains challenging. The key to the clinical application is to ensure the normal function of cells while improving the proliferation ability in vitro, and to complete the complex mesenchymal epithelialization to achieve tissue remodeling after vivo implantation. Herein, in order to aid HPKs adhesion and proliferation in vitro and promoting wound healing, we developed a three dimensional collagen scaffold with Y-27632 sustainedly released from the nanoplatform, hollow mesoporous organosilica nanoparticles (HMON). The results showed that the porous structure within the TEE supports the implanted HPKs expanding in a three-dimensional mode to jointly construct the tissue-engineered epidermis in vitro and inhibited the mitochondria-mediated cell apoptosis. It was confirmed that the TEEs with suitable degradation rate could maintain drug release after implantation and could accelerate vascularization of wound base and further revealed the involvement of mesenchymal transformation of transplanted HPKs during skin regeneration in a nude mouse model with full-thickness skin resection. In conclusion, our study highlights the great potential of constructing TEE using a nanoparticle platform for the treatment of large-area skin defects.

Mental time travel ability influences the representation of events and emotional expressions: evidence from microblogs.

Mental time travel (MTT) ability allows people to project themselves mentally into the past and future. It is associated with people's mental representation of events and objects. Using text analysis methods, we explore the linguistic representation and emotional expression of people with various MTT abilities. In Study 1, we assessed the users' MTT distances, text lengths, visual perspectives, priming effects of temporal words, and emotional valences by analyzing 2973 users' microblog texts. From our statistical analysis findings, users with far MTT incorporated longer text length and more third-person pronouns in their microblogs and are more likely to relate the future and past with the present than people with near MTT. However, the study showed no significant difference in emotional valence between people with different MTT distances. In Study 2, we explored the relationship between emotional valence and MTT ability by analyzing the comments of 1112 users on "procrastination." We found the users with far MTT more positive toward procrastination than those with near MTT. By analyzing users' social media platform data, this study re-examined and verified previous findings indicating that users who mentally travel different temporal distances represent events and emotional expressions differently. This study serves as an important reference for MTT studies.

The Promoting Role of HK II in Tumor Development and the Research Progress of Its Inhibitors.

Increased glycolysis is a key characteristic of malignant cells that contributes to their high proliferation rates and ability to develop drug resistance. The glycolysis rate-limiting enzyme hexokinase II (HK II) is overexpressed in most tumor cells and significantly affects tumor development. This paper examines the structure of HK II and the specific biological factors that influence its role in tumor development, as well as the potential of HK II inhibitors in antitumor therapy. Furthermore, we identify and discuss the inhibitors of HK II that have been reported in the literature.

RAB27A promotes the proliferation and invasion of colorectal cancer cells.

Colorectal cancer (CRC) is one of the most commonly diagnosed cancer types worldwide. Despite significant advances in prevention and diagnosis, CRC is still one of the leading causes of cancer-related mortality globally. RAB27A, the member of RAB27 family of small GTPases, is the critical protein for intracellular secretion and has been reported to promote tumor progression. However, it is controversial for the role of RAB27A in CRC progression, so we explored the exact function of RAB27A in CRC development in this study. Based on the stable colon cancer cell lines of RAB27A knockdown and ectopic expression, we found that RAB27A knockdown inhibited proliferation and clone formation of SW480 colon cancer cells, whereas ectopic expression of RAB27A in RKO colon cancer cells facilitated cell proliferation and clone formation, indicating that RAB27A is critical for colon cancer cell growth. In addition, our data demonstrated that the migration and invasion of colon cancer cells were suppressed by RAB27A knockdown, but promoted by RAB27A ectopic expression. Therefore, RAB27A is identified as an onco-protein in mediating CRC development, which may be a valuable prognostic indicator and potential therapeutic target for CRC.

Reforming Magnet Waste to Prussian Blue for Sustainable Sodium-Ion Batteries.

Increasing generation of permanent magnet waste has resulted in an urgent need to preserve finite resources. Reforming these wastes as feedstock to produce renewables is an ideal strategy for addressing waste and energy challenges. Herein, our work reports a smart and sustainable strategy to convert iron in magnet wastes into Prussian blue analogues that can serve as cathode materials for sodium-ion batteries. Moreover, a method to control feed rates is proposed to generate high-quality materials with fewer [Fe(CN)6] vacancies at a feed rate of 3 mL min-1. The recycled Na1.46Fe[Fe(CN)6]0.85·â–¡0.15 shows low vacancies and excellent cycling stability over 300 cycles (89% capacity retention at 50 mA g-1). In operando, evidence indicates that high-quality Prussian blue allows fast sodium-ion mobility and a high degree of reversibility over the course of cycling, although with a three-phase-transition mechanism. This study opens up a future direction for magnet waste created with the expectation of being environmentally reused.

Maturation of subtilisin-like protease NbSLP1 from microsporidia Nosema bombycis.

Microsporidia are obligate intracellular parasites and possess a unique way of invading hosts, namely germination. Microsporidia are able to infect almost all animal cells by germination. During the process, the polar tube extrudes from the spores within, thus injecting infectious sporoplasm into the host cells. Previous studies indicated that subtilisin-like protease 1 (NbSLP1) of microsporidia Nosema bombycis were located at the polar cap of germinated spores where the polar tube extrusion. We hypothesized that NbSLP1 is an essential player in the germination process. Normally, SLP need to be activated by autoproteolysis under conditions. In this study, we found that the signal peptide of NbSLP1 affected the activation of protease, two self-cleavage sites were involved in NbSLP1 maturation between Ala104Asp105 and Ala124Asp125 respectively. Mutants at catalytic triad of NbSLP1 confirmed the decreasing of autoproteolysis. This study demonstrates that intramolecular proteolysis is required for NbSLP1 maturation. The protease undergoes a series of sequential N-terminal cleavage events to generate the mature enzyme. Like other subtilisin-like enzymes, catalytic triad of NbSLP1 are significant for the self-activation of NbSLP1. In conclusion, clarifying the maturation of NbSLP1 will be valuable for understanding the polar tube ejection mechanism of germination.

Improving astaxanthin production in Escherichia coli by co-utilizing CrtZ enzymes with different substrate preference.

BACKGROUND: The bifunctional enzyme ß-carotene hydroxylase (CrtZ) catalyzes the hydroxylation of carotenoid ß-ionone rings at the 3, 3' position regardless of the presence of keto group at 4, 4' position, which is an important step in the synthesis of astaxanthin. The level and substrate preference of CrtZ may have great effect on the amount of astaxanthin and the accumulation of intermediates. RESULTS: In this study, the substrate preference of PCcrtZ from Paracoccus sp. PC1 and PAcrtZ from Pantoea Agglomerans were certified and were combined utilization for increase astaxanthin production. Firstly, PCcrtZ from Paracoccus sp. PC1 and PAcrtZ from P. Agglomerans were expressed in platform strains CAR032 (ß-carotene producing strain) and Can004 (canthaxanthin producing strain) separately to identify their substrate preference for carotenoids with keto groups at 4,4' position or not. The results showed that PCcrtZ led to a lower zeaxanthin yield in CAR032 compared to that of PAcrtZ. On the contrary, higher astaxanthin production was obtained in Can004 by PCcrtZ than that of PAcrtZ. This demonstrated that PCCrtZ has higher canthaxanthin to astaxanthin conversion ability than PACrtZ, while PACrtZ prefer using ß-carotene as substrate. Finally, Ast010, which has two copies of PAcrtZ and one copy of PCcrtZ produced 1.82 g/L of astaxanthin after 70 h of fed-batch fermentation. CONCLUSIONS: Combined utilization of crtZ genes, which have ß-carotene and canthaxanthin substrate preference respectively, can greatly enhance the production of astaxanthin and increase the ratio of astaxanthin among total carotenoids.

Metabolic engineering of Saccharomyces cerevisiae for gram-scale diosgenin production.

Diosgenin (DSG) is a naturally occurring steroidal saponin with a variety of biological activities that is also an important precursor for the synthesis of various steroidal drugs. The traditional industrial production of DSG is based on natural plant extraction and chemical processing. However, the whole process is time-consuming, laborious, and accompanied by severe environmental pollution. Therefore, it is necessary to develop a more convenient and environmentally-friendly process to realize the green production of DSG. In our previous work, we achieved de novo synthesis of DSG in Saccharomyces cerevisiae using glucose as the carbon source. However, DSG production was only at the milligram level, which is too low for industrial production. In this work, we further developed yeast strains for DSG overproduction by optimizing the synthesis pathway, fine-tuning pathway gene expression, and eliminating competing pathways. Cholesterol 22-hydroxylase was used to construct the DSG biosynthesis pathway. The optimal ratio of cytochrome P450 (CYP) to cytochrome P450 reductase (CPR) associated with DSG synthesis was screened to increase DSG production. Weakening the expression of the ERG6 gene further increased DSG synthesis and reduced the formation of by-products. In addition, we investigated the impact of DSG accumulation on yeast cell physiology and growth by transcriptome analysis and found that the multidrug transporter PDR5 and the sterol-binding protein PRY1 contributed to DSG production. Finally, we obtained a DSG titer of 2.03 g/L after 288 h of high-cell-density fed-batch fermentation using the engineered strain LP118, which represents the highest DSG titer reported to date for a yeast de novo synthesis system.

[Advances in microbial synthesis of plant natural products].

Plant natural products are one of the main sources of small molecule drugs, nutraceuticals, cosmetics and fragrances, and play an important role in economy development. At present, the way of obtaining plant natural products mainly depends on direct extraction from plants, which is farm land occupying and time consuming. The contents of active ingredients in plants are usually low, and thus the production cost is high. By elucidating the biosynthetic pathways and reconstructing the pathways in microbial cells, plant natural products can be produced by fermentation using renewable raw materials. Microbial biosynthesis provides a new route for the supply of plant natural products. This review summarizes the research progress of microbial synthesis of terpenoids, flavonoids, phenylpropanoids and other important natural products of plants in Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences. Current research challenges and future prospects are also briefly discussed.

Ampelopsin Inhibits Cell Viability and Metastasis in Renal Cell Carcinoma by Negatively Regulating the PI3K/AKT Signaling Pathway.

BACKGROUND: Previous studies have shown that Ampelopsin has an inhibitory effect on human tumors. However, the effect of Ampelopsin on renal cell carcinoma (RCC) is rarely reported. Therefore, this study aims to explain the role of Ampelopsin in RCC. METHODS: Different concentrations of Ampelopsin (0, 10, 25, 50, and 100 µM) were used to treat 786-O cells. Cell viability was detected by MTT assay, colony formation assay, and flow cytometry assay. Transwell assay and Wound healing assay were used to detect cell migration and invasion. Western blot analysis was applied to detect protein expression. RESULTS: Ampelopsin inhibited cell proliferation and induced apoptosis in RCC. And Ampelopsin can inhibit cell migration and invasion in RCC. All these results changed in a dose-dependent manner. Ampelopsin (100 uM) had the strongest inhibitory effect on cell viability and metastasis. In addition, Ampelopsin negatively regulated the PI3K/AKT signaling pathway in RCC cells. Moreover, Ampelopsin was only cytotoxic to RCC cells. CONCLUSION: Ampelopsin inhibits cell viability and metastasis in RCC by negatively regulating the PI3K/AKT signaling pathway.

Tunable graphene-based metasurface for an ultra-low sidelobe terahertz phased array antenna.

In this paper, we propose an all-solid-state, electrically tunable, and reflective graphene metasurface array that can generate a specific phase or continuous scanning between 0° and 352.5° in the terahertz band. By optimizing the structural parameters of the metasurface, the average reflectivity can reach 68.3%, and the maximum reflectivity variation range is only 30%. We also simulate the results that an electrically tunable terahertz phased array can be achieved by adjusting the Fermi levels of a monolayer graphene resonator. The maximum deflection of the reflected beam is 46.05°, and the resolution can be improved to 1.10°. It should be noted that the sidelobe energy only accounts for 1.06% of the main lobe energy, due to the slight change in reflectivity with the phase gradient.

Ultralow sidelobe midinfrared optical phased array based on a broadband metasurface.

In this paper, we propose an all-solid-state and ultralow sidelobe optical phased array (OPA) through designing a broadband angle-insensitive reflective metasurface in the midinfrared. The simulation results show that the metasurface can realize the wide-frequency metareflection characteristics in the range of 4.3∼5.0µm. Notably, the metasurface array can almost generate a continuous sweep between 0° and 342°, while the variation of reflectivity amplitude is only 10.2%, by changing the corresponding structural parameters. Then, we design and simulate an OPA based on these excellent characteristics of the broadband metasurface. By simply changing the periodicity of the OPA structure, the continuous deflection angles can be achieved within 29.41°, which can increase to 44.06° by changing the angle of the incident beam. A key feature of our design is that the sidelobe energy is less than 3.10% of the main lobe energy.