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Abstract Anaplastic thyroid cancer (ATC) is among the most aggressive and metastatic malignancies, often resulting in fatal outcomes due to the lack of effective treatments. Prosapogenin A (PA), a bioactive compound prevalent in traditional Chinese herbs, has shown potential as an antineoplastic agent against various human tumors. However, its effects on ATC and the underlying mechanism remain unclear. Here, we demonstrate that PA exhibits significant anti-ATC activity both in vitro and in vivo by inducing GSDME-dependent pyroptosis in ATC cells. Mechanistically, PA promotes lysosomal membrane permeabilization (LMP), leading to the release of cathepsins that activate caspase 8/3 to cleave GSDME. Remarkably, PA significantly upregulates three key functional subunits of V-ATPase—ATP6V1A, ATP6V1B2, and ATP6V0C—resulting in lysosomal over-acidification. This over-acidification exacerbates LMP and subsequent lysosomal damage. Neutralization of lysosomal lumen acidification or inhibition/knockdown of these V-ATPase subunits attenuates PA-induced lysosomal damage, pyroptosis and growth inhibition of ATC cells, highlighting the critical role for lysosomal acidification and LMP in PA’s anticancer effects. In summary, our findings uncover a novel link between PA and lysosomal damage-dependent pyroptosis in cancer cells. PA may act as a V-ATPase agonist targeting lysosomal acidification, presenting a new potential therapeutic option for ATC treatment.

Abstract Hepatocellular carcinoma (HCC) is one of the most significant causes of cancer-related deaths in the worldwide. Currently, predicting the survival of patients with HCC and developing treatment drugs still remain a significant challenge. In this study, we employed prognosis-related genes to develop and externally validate a predictive risk model. Furthermore, the correlation between signaling pathways, immune cell infiltration, immunotherapy response, drug sensitivity, and risk score was investigated using different algorithm platforms in HCC. Our results showed that 11 differentially expressed genes including UBE2C, PTTG1, TOP2A, SPP1, FCN3, SLC22A1, ADH4, CYP2C8, SLC10A1, F9, and FBP1 were identified as being related to prognosis, which were integrated to construct a prediction model. Our model could accurately predict patients’ overall survival using both internal and external datasets. Moreover, a strong correlation was revealed between the signaling pathway, immune cell infiltration, immunotherapy response, and risk score. Importantly, a novel potential drug candidate for HCC treatment was discovered based on the risk score and also validated through ex vivo experiments. Our finds offer a novel perspective on prognosis prediction and drug exploration for cancer patients.

Abstract The alteration of metabolic processes has been found to have significant impacts on the development of hepatocellular carcinoma (HCC). Nevertheless, the effects of dysfunction of tyrosine metabolism on the development of HCC remains to be discovered. This research demonstrated that tyrosine hydroxylase (TH), which responsible for the initial and limiting step in the bio-generation of the neuro-transmitters dopamine and adrenaline, et al. was shown to be reduced in HCC. Increased expression of TH was found facilitates the survival of HCC patients. In addition, decreased TH indicated larger tumor size, much more numbers of tumor, higher level of AFP, and the presence of cirrhosis. TH effectively impairs the growth and metastasis of HCC cells, a process dependent on the phosphorylation of serine residues (S19/S40). TH directly binds to Smad2 and hinders the cascade activation of TGFβ/Smad signaling with the treatment of TGFβ1. In summary, our study uncovered the non-metabolic functions of TH in the development of HCC and proposes that TH might be a promising biomarker for diagnosis as well as an innovative target for metastatic HCC.

Ferroptosis is a nonapoptotic form of cell death characterized by iron dependence and lipid peroxidation. Ferroptosis is involved in a range of pathological processes, such as cancer. Many studies have confirmed that ferroptosis plays an essential role in inhibiting cancer cell proliferation. In addition, a series of small-molecule compounds have been developed, including erastin, RSL3, and FIN56, which can be used as ferroptosis inducers. The combination of ferroptosis inducers with anticancer drugs can produce a significant synergistic effect in cancer treatment, and patients treated with these combinations exhibit a better prognosis than patients receiving traditional therapy. Therefore, a thorough understanding of the roles of ferroptosis in cancer is of great significance for the treatment of cancer. This review mainly elaborates the molecular biological characteristics and mechanism of ferroptosis, summarizes the function of ferroptosis in cancer development and treatment,illustrates the application of ferroptosis in patient's prognosis prediction and drug discovery, and discusses the prospects of targeting ferroptosis.

Abstract Cancer metastasis is the leading cause of mortality in patients with hepatocellular carcinoma (HCC). To meet the rapid malignant growth and transformation, tumor cells dramatically increase the consumption of nutrients, such as amino acids. Peptide transporter 1 (PEPT1), a key transporter for small peptides, has been found to be an effective and energy‐saving intracellular source of amino acids that are required for the growth of tumor cells. Here, the role of PEPT1 in HCC metastasis and its underlying mechanisms is explored. PEPT1 is upregulated in HCC cells and tissues, and high PEPT1 expression is associated with poor prognosis in patients with HCC. PEPT1 overexpression dramatically promoted HCC cell migration, invasion, and lung metastasis, whereas its knockdown abolished these effects both in vitro and in vivo. Mechanistic analysis revealed that high PEPT1 expression increased cellular dipeptides in HCC cells that are responsible for activating the MAP4K4/G3BP2 signaling pathway, ultimately facilitating the phosphorylation of G3BP2 at Thr227 and enhancing HCC metastasis. Taken together, these findings suggest that PEPT1 acts as an oncogene in promoting HCC metastasis through dipeptide‐induced MAP4K4/G3BP2 signaling and that the PEPT1/MAP4K4/G3BP2 axis can serve as a promising therapeutic target for metastatic HCC.

Abstract Background One‐carbon (1C) metabolism is a metabolic network that plays essential roles in biological reactions. In 1C metabolism, a series of nutrients are used to fuel metabolic pathways, including nucleotide metabolism, amino acid metabolism, cellular redox defence and epigenetic maintenance. At present, 1C metabolism is considered the hallmark of cancer. The 1C units obtained from the metabolic pathways increase the proliferation rate of cancer cells. In addition, anticancer drugs, such as methotrexate, which target 1C metabolism, have long been used in the clinic. In terms of immunotherapy, 1C metabolism has been used to explore biomarkers connected with immunotherapy response and immune‐related adverse events in patients. Methods We collected numerous literatures to explain the roles of one‐carbon metabolism in cancer immunotherapy. Results In this review, we focus on the important pathways in 1C metabolism and the function of 1C metabolism enzymes in cancer immunotherapy. Then, we summarise the inhibitors acting on 1C metabolism and their potential application on cancer immunotherapy. Finally, we provide a viewpoint and conclusion regarding the opportunities and challenges of targeting 1C metabolism for cancer immunotherapy in clinical practicability in the future. Conclusion Targeting one‐carbon metabolism is useful for cancer immunotherapy.

Abstract Background Anaplastic thyroid carcinoma (ATC) was a rare and extremely malignant endocrine cancer with the distinct hallmark of high proportion of cancer stem cell-like characteristics. Therapies aiming to cancer stem-like cells (CSCs) were emerging as a new direction in cancer treatment, but targeting ATC CSCs remained challenging, mainly due to incomplete insights of the regulatory mechanism of CSCs. Here, we unveiled a novel role of ISG15 in the modulation of ATC CSCs. Methods The expression of ubiquitin-like proteins were detected by bioinformatics and immunohistochemistry. The correlation between ISG15 expression and tumor stem cells and malignant progression of ATC was analyzed by single-cell RNA sequence from the Gene Expression Omnibus. Flow cytometry combined with immunofluorescence were used to verify the enrichment of ISG15 and ISGyaltion in cancer stem cells. The effect and mechanism of ISG15 and KPNA2 on cancer stem cell-like characteristics of ATC cells were determined by molecular biology experiments. Mass spectrometry combined with immunoprecipitation to screen the substrates of ISG15 and validate its ISGylation modification. Nude mice and zebrafish xenograft models were utilized to demonstrate that ISG15 regulates stem cell characteristics and promotes malignant progression of ATC. Results We found that among several ubiquitin proteins, only ISG15 was aberrantly expressed in ATC and enriched in CSCs. Single-cell sequencing analysis revealed that abnormal expression of ISG15 were intensely associated with stemness and malignant cells in ATC. Inhibition of ISG15 expression dramatically attenuated clone and sphere formation of ATC cells, and facilitated its sensitivity to doxorubicin. Notably, overexpression of ISGylation, but not the non-ISGylation mutant, effectively reinforced cancer stem cell-like characteristics. Mechanistically, ISG15 mediated the ISGylation of KPNA2 and impeded its ubiquitination to promote stability, further maintaining cancer stem cell-like characteristics. Finally, depletion of ISG15 inhibited ATC growth and metastasis in xenografted mouse and zebrafish models. Conclusion Our studies not only provided new insights into potential intervention strategies targeting ATC CSCs, but also uncovered the novel biological functions and mechanisms of ISG15 and ISGylation for maintaining ATC cancer stem cell-like characteristics. Graphical Abstract

Abstract Hexokinase 2 (HK2), a critical rate-limiting enzyme in the glycolytic pathway catalyzing hexose phosphorylation, is overexpressed in multiple human cancers and associated with poor clinicopathological features. Drugs targeting aerobic glycolysis regulators, including HK2, are in development. However, the physiological significance of HK2 inhibitors and mechanisms of HK2 inhibition in cancer cells remain largely unclear. Herein, we show that microRNA-let-7b-5p (let-7b-5p) represses HK2 expression by targeting its 3′-untranslated region. By suppressing HK2-mediated aerobic glycolysis, let-7b-5p restrains breast tumor growth and metastasis both in vitro and in vivo. In patients with breast cancer, let-7b-5p expression is significantly downregulated and is negatively correlated with HK2 expression. Our findings indicate that the let-7b-5p/HK2 axis plays a key role in aerobic glycolysis as well as breast tumor proliferation and metastasis, and targeting this axis is a potential therapeutic strategy for breast cancer.

Several types of modifications have been proven to participate in the metabolism and processing of different RNA types, including non-coding RNAs (ncRNAs). N-6-methyladenosine (m6A) is a dynamic and reversible RNA modification that is closely involved in the ncRNA homeostasis, and serves as a crucial regulator for multiple cancer-associated signaling pathways. The ncRNAs usually regulate the epigenetic modification, mRNA transcription and other biological processes, displaying enormous roles in human cancers. In this review, we summarized the significant implications of m6A-ncRNA interaction in various types of cancers. In particular, the interplay between m6A and ncRNAs in cancer pathogenesis and therapeutic resistance are being widely recognized. We also discussed the relevance of m6A-ncRNA interaction in immune regulation, followed by the interference on cancer immunotherapeutic procedures. In addition, we briefly highlighted the computation tools that could identify the accurate features of m6A methylome among ncRNAs. In summary, this review would pave the way for a better understanding of the biological functions of m6A-ncRNA crosstalk in cancer research and treatment.

Non-coding RNA are a class of RNA that lack the potential to encode proteins. CircRNAs, generated by a post-splicing mechanism, are a newly discovered type of non-coding RNA with multi-functional covalent loop structures. CircRNAs may play an important role in the occurrence and progression of tumors. Research has shown that circRNAs are aberrantly expressed in various types of human cancers, including leukemia. In this review, we summarize the expression and function of circRNAs and their impact on different types of leukemia. We also illustrate the function of circRNAs on immune modulation and chemoresistance in leukemia and their impact on its diagnosis and prognosis. Herein, we provide an understanding of recent advances in research that highlight the importance of circRNAs in proliferation, apoptosis, migration, and autophagy in different types of leukemia. Furthermore, circRNAs make an indispensable difference in the modulation of the immunity and chemoresistance of leukemia. Increasing evidence suggests that circRNAs may play a vital role in the diagnostic and prognostic markers of leukemia because of their prominent properties. More detailed preclinical studies on circRNAs are needed to explore effective ways in which they can serve as biomarkers for the diagnosis and prognosis of leukemia in vivo.

Land use/land cover changes (LULCCs) and biological invasions significantly impact coastal wetlands (CWs) and their ecosystem services and functions. The exact impacts, however, are difficult to quantify and are often neglected in policymaking. The evaluation of ecological service value (ESV) is conducive to clarifying the ecological and environmental changes caused by LULCCs and biological invasions. The objective of this study was to investigate their impact on CWs in Jiangsu Province, China, and provide useful information and advice for policymakers concerned with sustainable development. In this paper, basic data were obtained through geographic information system technology, and CW ecosystems’ services were calculated via the ESV coefficients per unit area of different wetland types. Accordingly, this study found the current land use methods responsible for significant ecosystem disruption and reductions in the area of natural vegetation. Currently, the area of natural vegetation only accounts for 43% of the total area recorded in 1987. In 2018, the total ESV of wetland vegetation (Spartina, Phragmites, and Suaeda) was estimated to be USD 14.10 million, while that of farmland was USD 8.58 million, and that of forests was USD 2.09 million. Natural vegetation only covered 9% of the total land area but produced 60% of the total ESV. Spartina alterniflora exhibited the highest ESV per unit area, with USD 1.35 million. However, the CWs of Jiangsu Province have recently shown a shift in vegetation composition due to the invasion of Spartina alterniflora. Currently, the dominant species in these CWs are Spartina alterniflora and Phragmites australis, while the local population of Suaeda salsa has significantly declined. Therefore, it is necessary to strengthen the preservation and restoration of wetland vegetation, control the invasive potential of Spartina alterniflora, and consider the implementation of suitable protective measures for native plants.

Intestinal inflammation is a key determinant of intestinal and systemic health, and when our intestines are damaged, there is disruption of the intestinal barrier, which in turn induces a systemic inflammatory response. However, the etiology and pathogenesis of inflammatory diseases of the intestine are still not fully understood. Artemether (ART), one of the artemisinin derivatives, has been widely used to treat malaria. Nevertheless, the effect of ART on intestinal inflammation remains unclear. The present study intended to elucidate the potential mechanism of ART in diet-induced intestinal injury. A high-fat and high-fructose (HFHF) diet-induced mouse model of intestinal injury was constructed, and the mice were treated with ART to examine their role in intestinal injury. RT-qPCR, Western blotting, immunohistochemical staining, and 16S rRNA gene sequencing were used to investigate the anti-intestinal inflammation effect and mechanism of ART. The results indicated that ART intervention may significantly ameliorate the intestinal flora imbalance caused by the HFHF diet and alleviate intestinal barrier function disorders and inflammatory responses by raising the expression of tight junction proteins ZO-1 and occludin and decreasing the expression of pro-inflammatory factors TNF-α and IL-1β. Moreover, ART intervention restrained HFHF-induced activation of the TLR4/NF-κB p65 pathway in colon tissue, which may be concerned with the potential protective effect of ART on intestinal inflammation. ART might provide new insights into further explaining the mechanism of action of other metabolic diseases caused by intestinal disorders.

The COVID-19 pandemic has affected city dwellers’ physical and mental health and has raised concerns about the health of urban public spaces. This field investigation research in Dalian, China, examined the perceived audio-visual environment characteristics of urban pedestrian streets with traffic noise and their influences on the environmental health of the pedestrian streets. Five indicators reflecting psychological responses to environmental characteristics (willingness to walk, relaxation, safety, beauty, and comprehensive comfort) were used to measure environmental health of pedestrian streets with traffic noise. The results showed that safety was rated the highest, and willingness to walk was evaluated as the lowest among health evaluation indicators. The imageability and openness of the streetscape were associated with each health evaluation indicator. In contrast, the rhythm and continuity of the street buildings had a greater effect on willingness to walk than the other health indicators. There were negative correlations between LAeq for traffic noise and health evaluations. Positive health evaluations were observed when LAeq was less than 55 dBA. In contrast, soundscape indicators showed positive correlations with health evaluations, and acoustic comfort and noise annoyance, rather than sound preference and subjective loudness were associated with each health evaluation indicator. In terms of the combined audio-visual factors, acoustic comfort, the quantity of greening, annoyance, sky visibility, spatial scale, and building distance were examined as the determining factors affecting health evaluations, and 55.40% of the variance in health evaluations was explained by the soundscape and streetscape indicators. The findings provide references for better understanding the relationships between healthy experience and audio-visual perceptions. Moreover, they enable environmental health quality optimisation of pedestrian spaces considering audio-visual indicators and approaches in the post-epidemic era.

Artificial intelligence (AI) is a general term that refers to the use of a machine to imitate intelligent behavior for performing complex tasks with minimal human intervention, such as machine learning; this technology is revolutionizing and reshaping medicine. AI has considerable potential to perfect health-care systems in areas such as diagnostics, risk analysis, health information administration, lifestyle supervision, and virtual health assistance. In terms of immunotherapy, AI has been applied to the prediction of immunotherapy responses based on immune signatures, medical imaging and histological analysis. These features could also be highly useful in the management of cancer immunotherapy given their ever-increasing performance in improving diagnostic accuracy, optimizing treatment planning, predicting outcomes of care and reducing human resource costs. In this review, we present the details of AI and the current progression and state of the art in employing AI for cancer immunotherapy. Furthermore, we discuss the challenges, opportunities and corresponding strategies in applying the technology for widespread clinical deployment. Finally, we summarize the impact of AI on cancer immunotherapy and provide our perspectives about underlying applications of AI in the future.

Macronaria is a clade of gigantic body-sized sauropod dinosaurs widely distributed from the Late Jurassic to the Late Cretaceous globally. However, its origin, early diversification, and dispersal are still controversial. Here, we report a new macronarian Yuzhoulong qurenensis gen. et sp. nov. excavated from the Middle Jurassic (Bathonian) Lower Shaximiao Formation. Yuzhoulong qurenensis bears a unique combination of features, such as two accessory fossae that exist on the posterior surface of dorsal diapophyses of anterior dorsal vertebrae. Results of phylogenetic analyses demonstrate it is one of the earliest-diverging macronarians. This new material represents a Middle Jurassic fossil record of macronarian sauropod worldwide and improves the understanding of the early diversity and dispersal of the Neosauropoda. This discovery further supports that sauropods achieved a more rapid and varied morphological diversity and palaeogeographical dispersal in the Middle Jurassic.

Background: Non-alcoholic fatty liver disease (NAFLD) is a widespread disease, but no recognized drug treatment exists. Previous studies have shown that artemether (Art) can ameliorate carbon tetrachloride (CCl4)–induced liver fibrosis in mice. This study sets out to observe the therapeutic impact of Art on non-alcoholic steatohepatitis (NASH).Methods: Model mice were provided with a methionine- and choline-deficient (MCD) diet for 4 weeks or a high-fat diet (HFD) for 28 weeks, respectively, and then treated with Art. RNA sequencing (RNA-Seq) analyzed gene expression changes caused by Art treatment. The molecular mechanism of the therapeutic effects of Art on NASH was studied in the mouse liver and HepG2 cells.Results: Art treatment significantly attenuated hepatic lipid accumulation and liver damage in MCD diet– or HFD-induced NASH mice. The RNA-Seq analysis revealed lipid metabolism as a major pathway suppressed by Art administration, in addition to the regulation of inflammation pathways. Mechanistically, Art reduced lipid accumulation by repressing de novo lipogenesis of sterol regulatory element-binding protein-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), fatty acid synthase (FASN), stearoyl-CoA desaturase (SCD1), promoting lipolysis of peroxisome proliferator–activated receptor-γ co-activator-1α (PGC1α), adipose triglyceride lipase (ATGL), and carnitine palmitoyltransferase I (CPT-1a) in NASH mouse liver and HepG2 cells. In addition, Art inhibited the secretion of pro-inflammatory factors and reduced inflammatory infiltration by effectively inhibiting M1 macrophage activation. Furthermore, Art inhibited transforming growth factor-beta 1 (TGF-β), and the SMAD signaling pathway mediates the development of liver fibrosis.Inclusion: Art improved fat deposition by repressing de novo lipogenesis and promoting lipolysis in vivo and in vitro. Furthermore, Art improved inflammation and fibrosis with a significant effect. It is a prospective therapeutic agent for NASH.

Chemoresistance, especially temozolomide (TMZ) resistance, is a major clinical challenge in the treatment of glioblastoma (GBM). Exploring the mechanisms of TMZ resistance could help us identify effective therapies. Adenosine deaminases acting on RNA (ADARs) are very important in RNA modification through regulating the A-to-I RNA editing. Recent studies have shown that ADARs regulate multiple neurotransmitter receptors, which have been linked with the occurrence and progress of GBM. Here, data from several bioinformatics databases demonstrated that adenosine deaminase RNA specific B1 (ADARB1), also named ADAR2, was upregulated in both GBM tissues and cells, and had the prognostic value in GBM patients. Moreover, ADARB1 was found to be involved in AKT-mediated TMZ resistance in GBM cells. The KEGG analysis of ADARB1-associated co-expressed genes showed that ADARB1 was potentially involved in the mitochondrial respiratory chain complex. TISIDB and GEPIA databases were further used to analyze the role of ADARB1 in tumor-immune system interactions in GBM. These findings deepened our understanding of the function of ADARB1 in tumorigenesis and therapeutic response in GBM.

Pancreatic ductal adenocarcinoma (PDAC) is a highly heterogeneous malignancy. Single-cell sequencing (scRNA-seq) technology enables quantitative gene expression measurements that underlie the phenotypic diversity of cells within a tumor. By integrating PDAC scRNA-seq and bulk sequencing data, we aim to extract relevant biological insights into the ductal cell features that lead to different prognoses. Firstly, differentially expressed genes (DEGs) of ductal cells between normal and tumor tissues were identified through scRNA-seq data analysis. The effect of DEGs on PDAC survival was then assessed in the bulk sequencing data. Based on these DEGs (LY6D, EPS8, DDIT4, TNFSF10, RBP4, NPY1R, MYADM, SLC12A2, SPCS3, NBPF15) affecting PDAC survival, a risk score model was developed to classify patients into high-risk and low-risk groups. The results showed that the overall survival was significantly longer in the low-risk group (p < 0.05). The model also revealed reliable predictive power in different subgroups of patients. The high-risk group had a higher tumor mutational burden (TMB) (p < 0.05), with significantly higher mutation frequencies in KRAS and ADAMTS12 (p < 0.05). Meanwhile, the high-risk group had a higher tumor stemness score (p < 0.05). However, there was no significant difference in the immune cell infiltration scores between the two groups. Lastly, drug candidates targeting risk model genes were identified, and seven compounds might act against PDAC through different mechanisms. In conclusion, we have developed a validated survival assessment model, which acted as an independent risk factor for PDAC.

Ovarian cancer (OC) is typically diagnosed at an advanced stage and poses a significant challenge to treatment and recovery. Rencently, Adenosine deaminase RNA-specific B1 (ADARB1), an adenosine-to-inosine (A-to-I) RNA-editing enzyme, has been found to play an essential role in the development of cancer. However, the specific function of ADARB1 in ovarian cancer is still not fully understood. Here, we investigated the effects of ADARB1 on OC biology. By conducting bioinformatics analyses of several public databases, we found significantly decreased ADARB1 expression in OC cells and tissues. Moreover, RT-PCR and western blot showed lower ADARB1 expression in OVCAR3, HO8910pm and A2780 OC cells compared to human normal ovarian epithelial cell IOSE. Cell proliferation assay and clone formation assay showed that overexpression of ADARB1 (ADARB1-OE) inhibited the proliferation of tumor cells. Wound healing and transwell assay indicated that ADARB1-OE could suppress OC cell invasion and metastasis. Kaplan-Meier methods revealed that the patients with low level of ADARB1 displayed poor prognosis. TISIDB databases were further used to analyze the roles of ADARB1 in tumor-immune system interactions in OC patients. Furthermore, ADARB1-OE down-regulated the expression of phosphorylated AKT. Combination of ADARB1-OE and AKT inhibitor MK2206 exerted stronger cell growth inhibition. Thus, our investigation demonstrated that low levels of ADARB1 might be a potential target in the tumorigenesis and prognostic evaluation of OC patients.

The excellent luminescence properties of perovskite quantum dots (PQDs), including wide excitation wavelength range, adjustable emission wavelength, narrow full width at half maximum (FWHM), and high photoluminescence quantum yield (PLQY), highly match the application requirements in emerging displays. Starting from the fundamental structure and the related optical properties, this paper first introduces the existing synthesis approaches of PQDs that have been and will potentially be used for display devices, and then summarizes the stability improving approaches with high retention of PQDs’ optical performance. Based on the above, the recent research progress of PQDs in displays is further elaborated. For photoluminescent display applications, the PQDs can be embedded in the backlighting device or color filter for liquid crystal displays (LCD), or they may function as the color conversion layer for blue organic light-emitting diodes (OLED) and blue micro-scale light-emitting diodes (μLED). In terms of next-generation electroluminescent displays, notable progress in perovskite quantum-dot light emitting diodes (PeQLED) has been achieved within the past decade, especially the maximum external quantum efficiency (EQE). To conclude, the key directions for future PQD development are summarized for promising prospects and widespread applications in display fields.

Circadian rhythms are physical, behavioral and environmental cycles that respond primarily to light and dark, with a period of time of approximately 24 h. The most essential physiological functions of mammals are manifested in circadian rhythm patterns, including the sleep-wake cycle and nutrient and energy metabolism. Autophagy is a conserved biological process contributing to nutrient and cellular homeostasis. The factors affecting autophagy are numerous, such as diet, drugs, and aging. Recent studies have indicated that autophagy is activated rhythmically in a clock-dependent manner whether the organism is healthy or has certain diseases. In addition, autophagy can affect circadian rhythm by degrading circadian proteins. This review discusses the interaction and mechanisms between autophagy and circadian rhythm. Moreover, we introduce the molecules influencing both autophagy and circadian rhythm. We then discuss the drugs affecting the circadian rhythm of autophagy. Finally, we present the role of rhythmic autophagy in nutrient and energy metabolism and its significance in physiology and metabolic disease.

Neurotrophic receptor tyrosine kinase 2 (NTRK2) is a member of the tropomyosin receptor kinase family associated with the tumor development. However, the detailed function of NTRK2 in lung cancer, especially in lung adenocarcinoma (LUAD), is still not fully understood. Here, we investigated the effects of NTRK2 on LUAD biology. Through analyzing bioinformatics data derived from several databases, such as Oncomine, Gene Expression Profiling Interactive Analysis and UALCAN, we found that NTRK2 expression was significantly decreased in LUAD tissues. Clinical data acquired from Wanderer database, which is linked to The Cancer Genome Atlas database, demonstrated that the expression and methylation site of NTRK2 were significantly related to the clinical characteristics and prognosis of LUAD. Furthermore, NTRK2 expression was increased remarkably after treatment with the protein kinase B (AKT) inhibitor MK2206 and the anticancer agent actinomycin D. Functional enrichment analysis of NTRK2-associated coexpression genes was further conducted. Together, our results suggested that downregulated NTRK2 might be used in the diagnostic and prognostic evaluation of LUAD patients, or as a potential therapeutic target for the treatment of LUAD.

Adenosine deaminase RNA-specific B1 (ADARB1), an adenosine-to-inosine (A-to-I) RNA-editing enzyme, has been found to play an essential role in the development of cancer. However, the specific function of ADARB1 in lung cancer, especially in lung adenocarcinoma (LUAD), is still not fully understood and requires further study. In our study, integrative bioinformatics were used to analyze the detailed function of ADARB1 in LUAD. By conducting bioinformatics analyses of several public databases, such as Gene Expression Profiling Interactive Analysis (GEPIA), GE-mini, and Oncomine, we found significantly decreased ADARB1 expression in LUAD cells and tissues. Moreover, RT-PCR and Western blot showed lower ADARB1 expression in H358 and A549 LUAD cells compared to human bronchial epithelial Beas-2B cells. Wound Healing Assay indicated that knockdown ADARB1 could promote LUAD cell metastasis. By using the Kaplan-Meier Plotter tool, we found that downregulation of ADARB1 was related to shorter first progression (FP), overall survival time (OS) and post-progression survival time (PPS). The relevant clinical data acquired from the Wanderer database indicated that the expression and methylation values of ADARB1 were significantly associated with the clinical characteristics of LUAD. Using DNA methylation inhibitor, we found DNMT inhibitor 5-aza-2-deoxycytidine (5-azaD) could promote the expression of ADARB1 and reverse the inhibition effect of ADARB1 in migration. In addition, functional enrichment analysis of ADARB1-associated coexpression genes was further conducted. Our investigation demonstrated that low levels of ADARB1 were specifically found in LUAD, and this gene might be a potential target in the diagnostic and prognostic evaluation of LUAD patients.

Objective. To establish and validate a simple, sensitive, and rapid liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the determination of methotrexate (MTX) and its major metabolite 7-hydroxy-methotrexate (7-OH-MTX) in human plasma. Method. The chromatographic separation was achieved on a Zorbax C18 column (3.5 μm, 2.1 × 100 mm) using a gradient elution with methanol (phase B) and 0.2% formic acid aqueous solution (phase A). The flow rate was 0.3 mL/min with analytical time of 3.5 min. Mass spectrometry detection was performed in a triple-quadruple tandem mass spectrometer under positive ion mode with the following mass transitions: m/z 455.1/308.1 for MTX, 471.0/324.1 for 7-OH-MTX, and 458.2/311.1 for internal standard. The pretreatment procedure was optimized with dilution after one-step protein precipitation. Results. The calibration range of methotrexate and 7-OH-MTX was 5.0-10000.0 ng/mL. The intraday and interday precision and accuracy were less than 15% and within ±15% for both analytes. The recovery for MTX and 7-OH-MTX was more than 90% and the matrix effect ranged from 97.90% to 117.60%. Conclusion. The method was successfully developed and applied to the routine therapeutic drug monitoring of MTX and 7-OH-MTX in human plasma.

Marsdenia tenacissima (MT), a traditional Chinese herbal medicine, has long been used for thousands of years to treat asthma, tracheitis, rheumatism, etc. An increasing number of recent studies have focused on the antitumor effects of MT. The effects of MT on cancer are the result of various activated signaling pathways and inhibiting factors and the high expression levels of regulatory proteins. MT can inhibit different cancer types including non-small cell lung cancer (NSCLC), malignant tumors, hepatic carcinoma, and so on. This article mainly focuses on the activities and mechanisms of MT. In addition, the efficacy and toxicity of MT are also discussed. Further studies of MT are required for improved medicinal utilization.