G3BP1 Interact with JAK2 mRNA to Promote the Malignant Progression of Nasopharyngeal Carcinoma via Activating JAK2/STAT3 Signaling Pathway.

Ras-GTPase-activating protein (GAP)-binding protein 1 (G3BP1) is an RNA-binding protein implicated in various malignancies. However, its role in nasopharyngeal carcinoma (NPC) remains elusive. This study elucidates the potential regulation mechanisms of G3BP1 and its significance in NPC advancement. Through knockdown and overexpression approaches, we validate G3BP1's oncogenic role by promoting proliferation, migration, and invasion in vitro and in vivo. Moreover, G3BP1 emerges as a key regulator of the JAK2/STAT3 signaling pathway, augmenting JAK2 expression via mRNA binding. Notably, epigallocatechin gallate (EGCG), a green tea-derived antioxidant, counteracts G3BP1-mediated pathway activation. Clinical analysis reveals heightened G3BP1, JAK2, and p-STAT3 as powerful prognostic markers, with G3BP1's expression standing as an independent indicator of poorer outcomes for NPC patients. In conclusion, the study unveils the oncogenic prowess of G3BP1, its orchestration of the JAK2/STAT3 signaling pathway, and its pivotal role in NPC progression.

Suppression of the SLC7A11/glutathione axis causes ferroptosis and apoptosis and alters the mitogen-activated protein kinase pathway in nasopharyngeal carcinoma.

SLC7A11 is a unit of the glutamate cystine antiporter Xc- system. It functions to import cystine for glutathione biosynthesis and maintains the redox balance in cells. Sorafenib inhibits the transporter activity of SLC7A11. The use of sorafenib has been approved in the treatment of multiple cancers. However, at present, our understanding of the mechanism of SLC7A11 and sorafenib in nasopharyngeal carcinoma (NPC) remains limited. We found that the expression of SLC7A11 was upregulated in NPC. A high SLC7A11 expression was associated with poor prognosis, metastasis, and an advanced T stage, which can be used as an independent prognostic indicator of NPC. In vitro, we observed that NPC cells relied on cystine for survival. Targeting SLC7A11 resulted in glutathione biosynthesis limitation, intracellular reactive oxygen species accumulation, lipid peroxides, ferroptosis, and apoptosis. Meanwhile, it altered mitogen activated protein kinase pathway, including p38 activation but ERK inhibition in NPC. This limited the proliferation of NPC cells. Sorafenib inhibited the proliferation and induced the death of NPC cells in vivo. In conclusion, SLC7A11 plays an important role in the occurrence and progression of NPC and may be a novel target for NPC treatment.

Somatostatin receptor2 (SSTR2) expression, prognostic implications, modifications and potential therapeutic strategies associates with head and neck squamous cell carcinomas.

Head and neck squamous cell carcinomas (HNSCC) constitute a heterogeneous cluster of tumors celebrated for their predisposition to metastasize and exhibit local recurrence. Recent explorations have illuminated the intricate involvement of Somatostatin Receptor 2 (SSTR2), a growth-regulatory receptor traditionally classified as a tumor suppressor, yet concurrently implicated in bolstering specific tumor phenotypes. Advances in the realm of SSTR2 investigation within HNSCC, with a specific spotlight on laryngeal squamous cell carcinomas (LSCC), tongue squamous cell carcinomas (TSCC), and nasopharyngeal carcinomas (NPC), have been established. This study aims to provide a comprehensive overview of SSTR2 expression patterns, prognostic implications, distinctive signaling pathways, epigenetic modifications, and potential therapeutic strategies associated with SSTR2 in HNSCC.

Effects of donor-specific microvascular anatomy on hemodynamic perfusion in human choriocapillaris.

Evidence from histopathology and clinical imaging suggest that choroidal anatomy and hemodynamic perfusion are among the earliest changes in retinal diseases such as age-related macular degeneration (AMD). However, how inner choroidal anatomy affects hemodynamic perfusion is not well understood. Therefore, we sought to understand the influences of choroidal microvascular architecture on the spatial distribution of hemodynamic parameters in choriocapillaris from human donor eyes using image-based computational hemodynamic (ICH) simulations. We subjected image-based inner choroid reconstructions from eight human donor eyes to ICH simulation using a kinetic-based volumetric lattice Boltzmann method to compute hemodynamic distributions of velocity, pressure, and endothelial shear stress. Here, we demonstrate that anatomic parameters, including arteriolar and venular arrangements and intercapillary pillar density and distribution exert profound influences on inner choroidal hemodynamic characteristics. Reductions in capillary, arteriolar, and venular density not only reduce the overall blood velocity within choriocapillaris, but also substantially increase its spatial heterogeneity. These first-ever findings improve understanding of how choroidal anatomy affects hemodynamics and may contribute to pathogenesis of retinal diseases such as AMD.

Occurrence, behavior and fate of liquid crystal monomers in municipal wastewater.

Liquid crystal monomers (LCMs), the essential substances used in the display screen of electronic devices, have been proposed as a class of emerging chemicals of concern. Despite their detection in various environmental matrices, little is known about the presence of LCMs in municipal sewage systems. This study aimed to investigate the occurrence, distribution, and fate of 64 LCMs released into the aqueous environment from a municipal wastewater treatment plant (WWTP) in Hong Kong, China. In total 14 LCMs were detected in WWTP samples. Specifically, the Σ14LCMs concentrations in crude influent, final effluent, and final sludge were found to be 16.8 ± 0.3 ng/L, 2.71 ± 0.05 ng/L, and 19.2 ± 1.0 ng/g dry weight, respectively. Among them, 10 fluorinated LCMs (F-LCMs) were determined to be present at concentrations of 8.90 ± 0.10 ng/L, 1.69 ± 0.05 ng/L, and 9.94 ± 1.00 ng/g dry weight, respectively. The predominant non-fluorinated LCMs (NF-LCMs) detected in all samples were 3OCB and EPhEMOB, while 2OdF3B was the dominant F-LCM. The overall removal rate of total LCMs was 83.8 ± 0.3 %, with 25.4 ± 4.8 % being removed by biodegradation and UV treatment. Compared to NF-LCMs, F-LCMs were more resistant to biodegradation. Despite the significant removal of LCMs through WWTP, the remaining LCMs in final effluent could result in an annual emission of 3.04 kg of total LCMs from the population of Hong Kong. This study provides the first evidence of LCMs contamination in municipal wastewater, possibly arising from routine electronic devices usage. Further investigation is needed to elucidate the potential impact of LCMs emission via WWTP effluent on the aquatic receiving ecosystem.

SSTR2 positively associates with EGFR and predicts poor prognosis in nasopharyngeal carcinoma.

AIMS: Epidermal growth factor receptor (EGFR) belongs to the receptor tyrosine kinases family and overexpression of EGFR has been linked to poor prognosis and cancer progression. Somatostatin receptor 2 (SSTR2) is a G-protein-coupled receptor (GPCR) with diverse biological functions in humans, and it is upregulated through the NF-KB signalling pathway in nasopharyngeal carcinomas (NPC). However, no studies have examined the EGFR and SSTR2 in NPC. This study aimed to investigate whether SSTR2 is associated with EGFR and clinicopathological features in NPC. METHODS: Bioinformatics analysis was performed to assess the correlation between EGFR and SSTR2 based on the GEO database. The expression of SSTR2 and EGFR was evaluated by immunohistochemistry (IHC) in 491 cases of NPC and 50 cases of non-cancerous nasopharyngeal epithelium. RESULTS: The bioinformatics analysis and IHC showed a positive correlation between SSTR2 and EGFR in NPC. High expression of SSTR2 and EGFR was significantly increased in NPC patients compared with non-cancerous nasopharyngeal epithelium. High expression of SSTR2 and/or EGFR was associated with a worse outcome and a higher risk of progression. The study found that patients receiving chemoradiotherapy (CR) with high expression of SSTR2, high expression of EGFR, and high coexpression of SSTR2 and EGFR had a poorer prognosis in both progression-free survival (PFS) and overall survival (OS). Interestingly, NPC patients with high expression of SSTR2, high expression of EGFR, high coexpression of EGFR and SSTR2, and EGFR/SSTR2 anyone high expression had a better prognosis with CR combined with targeted therapy. Cox multivariate analysis identified SSTR2 and EGFR as independent poor predictors of PFS. CONCLUSION: Our study is the first to shed light on the intricate relationship between SSTR2 and EGFR in NPC and provides new insights into the potential benefits of EGFR targeted therapy for patients with high SSTR2 expression. Additionally, SSTR2 has potential as a new biomarker for poor prognosis in NPC patients.

Liquid crystal monomers in ventilation and air conditioning dust: Indoor characteristics, sources analysis and toxicity assessment.

Indoor dust contaminated with liquid crystal monomers (LCMs) released from various commercial liquid crystal display (LCD) screens may pose environmental health risks to humans. This study aimed to investigate the occurrence of 64 LCMs in ventilation and air conditioning filters (VACF) dust, characterize their composition profiles, potential sources, and associations with indoor characteristics, and assess their in vitro toxicity using the human lung bronchial epithelial cells (BEAS-2B). A total of 31 LCMs with concentrations (ΣLCMs) ranging from 43.7 ng/g to 448 ng/g were detected in the collected VACF dust. Additional analysis revealed the potential interactions between indoor environmental conditions and human exposure risks associated with the detected LCMs in VACF dust. The service area and working time of the ventilation and air conditioning system, and the number of indoor LCD screens were positively correlated with the fluorinated ΣLCMs in VACF dust (r = 0.355 âˆ¼ 0.511, p < 0.05), while the associations with the non-fluorinated ΣLCMs were not found (p > 0.05), suggesting different environmental behavior and fates of fluorinated and non-fluorinated LCMs in the indoor environment. Four main indoor sources of LCMs (i.e., computer (37.1%), television (28.3%), Brand A smartphone (21.2%) and Brand S smartphone (13.4%)) were identified by positive matrix factorization-multiple linear regression (PMF-MLR). Exposure to 14 relatively frequently detected LCMs, individually and in the mixture, induced significant oxidative stress in BEAS-2B cells. Among them, non-fluorinated LCMs, specifically 3cH2B and MeP3bcH, caused dominant decreased cell viability. This study provides new insights into the indoor LCMs pollution and the associated potential health risks due to the daily use of electronic devices.

Role of ß-catenin in PD-L1 expression of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a particular type of tumor connected to Epstein-Barr virus infection, genetic, and environmental factors. It is typically discovered late, with few therapeutic options and poor clinical outcomes. Cellular immune responses can be attenuated when programmed death ligand 1 (PD-L1) and programmed cell death protein 1 (PD-1) are combined. Although PD-1 inhibitors have a different anti-tumor response rate than chemotherapy alone, they can nevertheless considerably outperform chemotherapy in patients with metastatic or recurrent NPC. The nuclear ß-catenin can bind to the CD274 promoter region, promoting transcription and upregulating the expression of tumor-specific PD-L1. Separation of ß-catenin from E-cadherin and translocation it into nucleus were both aided by ß-catenin phosphorylates at the Tyr654 site. Its function in NPC and the expression of PD-L1 have not yet been investigated. This study investigated the predictive significance of PD-L1 and p-ß-cateninTyr654 expressions in NPC. Our findings indicated that patients with distant metastases or poor prognoses exhibited higher levels of PD-L1 and p-ß-cateninTyr654 expressions. According to Cox multivariate prognostic analysis, PD-L1 was also an effective indicator for predicting the survival status of patients with NPC. We subsequently demonstrated that PD-L1 transcription and protein production could be downregulated by targeting inhibition of the level of ß-catenin in NPC cells. This is for developing the ß-catenin or TCF4 inhibitor as a potential new option for immune checkpoint immunosuppression in NPC.

Release Behavior of Liquid Crystal Monomers from Waste Smartphone Screens: Occurrence, Distribution, and Mechanistic Modeling.

Liquid crystal display (LCD) screens can release many organic pollutants into the indoor environment, including liquid crystal monomers (LCMs), which have been proposed as a novel class of emerging pollutants. Knowing the release pathways and mechanisms of LCMs from various components of LCD screens is important to accurately assess the LCM release and reveal their environmental transport behavior and fate in the ambient environment. A total of 47, 43, and 33 out of 64 target LCMs were detected in three disassembled parts of waste smartphone screens, including the LCM layer (LL), light guide plate (LGP), and screen protector (SP), respectively. Correlation analysis confirmed LL was the source of LCMs detected in LGP and SP. The emission factors of LCMs from waste screen, SP, and LGP parts were estimated as 2.38 × 10-3, 1.36 × 10-3, and 1.02 × 10-3, respectively. A mechanism model was developed to describe the release behaviors of LCMs from waste screens, where three characteristics parameters of released LCMs, including average mass proportion (AP), predicted subcooled vapor pressures (PL), and octanol-air partitioning coefficients (Koa), involving coexistence of absorption and adsorption mechanisms, could control the diffusion-partitioning. The released LCMs in LGP could reach diffusion-partition equilibrium more quickly than those in SP, indicating that LCM release could be mainly governed through SP diffusions.

YAP1 synergize with YY1 transcriptional co-repress DUSP1 to induce osimertinib resistant by activating the EGFR/MAPK pathway and abrogating autophagy in non-small cell lung cancer.

YAP1 is a well-known core effector of the Hippo pathway in tumors, but its potential role in osimertinib resistance remained unexplored. Our study provides evidence that YAP1 acts as a potent promoter of osimertinib resistance. By inhibiting YAP1 with a novel inhibitor, CA3, and combining it with osimertinib, we observed a significant suppression of cell proliferation and metastasis, induction of apoptosis and autophagy, and a delay in the emergence of osimertinib resistance. Interestingly, CA3 combined with osimertinib executed its anti-metastasis and pro-tumor apoptosis in part through autophagy. Mechanistically, we found that YAP1, in collaboration with YY1, transcriptionally represses DUSP1, leading to the dephosphorylation of the EGFR/MEK/ERK pathway and YAP1 phosphorylation in osimertinib-resistant cells. Our results also validate that CA3, in combination with osimertinib, executes its anti-metastasis and pro-tumor apoptosis partly through autophagy and the YAP1/DUSP1/EGFR/MEK/ERK regulatory feedback loop in osimertinib-resistant cells. Remarkably, our findings illustrate that YAP1 protein is upregulated in patients after osimertinib treatment and osimertinib resistance. Overall, our study confirms that the YAP1 inhibitor CA3 increases DUSP1 with concomitant activation of the EGFR/MAPK pathway and induces autophagy to enhance the efficacy of third-generation EGFR-TKI treatments for NSCLC patients.

Removing emerging e-waste pollutant DTFPB by synchronized oxidation-adsorption Fenton technology.

Liquid crystal monomers (LCMs), an emerging group of organic pollutants related to electronic waste, have been frequently detected from various environmental matrices, including landfill leachate. The persistence of LCMs requires robust technology for remediation. The objectives of this study were to evaluate the feasibility, performance and mechanism of the remediation of a typical LCM 4-[difluoro(3,4,5-trifluorophenoxy)methyl]- 3,5-difluoro-4'-propylbiphenyl (DTFPB) via synchronized oxidation-adsorption (SOA) Fenton technology and verify its application in DTFPB-contaminated leachate. The SOA Fenton system could effectively degrade 93.5% of DTFPB and 5.6% of its total organic carbon (TOCDTFPB) by hydroxyl radical oxidation (molar ratio of Fe2+ to H2O2 of 1/4 and pH 2.5-3.0) following a pseudo-first-order model under 0.378 h-1. Additionally, synchronized adsorption of DTFPB and its degradation intermediates by in situ resultant ferric particles via hydrophobic interaction, complexation, and coprecipitation contributed to almost 100% of DTFPB and 33.4% of TOCDTFPB removal. Three possible degradation pathways involving eight products were proposed, and hydrophobic interactions might drive the adsorption process. It was first confirmed that the SOA Fenton system exhibited good performance in eliminating DTFPB and byproducts from landfill leachate. This study provides new insights into the potential of the Fenton process for the treatment of emerging LCMs contamination in wastewater.

Structural insights into angiotensin receptor signaling modulation by balanced and biased agonists.

The peptide hormone angiotensin II regulates blood pressure mainly through the type 1 angiotensin II receptor AT1 R and its downstream signaling proteins Gq and ß-arrestin. AT1 R blockers, clinically used as antihypertensive drugs, inhibit both signaling pathways, whereas AT1 R ß-arrestin-biased agonists have shown great potential for the treatment of acute heart failure. Here, we present a cryo-electron microscopy (cryo-EM) structure of the human AT1 R in complex with a balanced agonist, Sar1 -AngII, and Gq protein at 2.9 Å resolution. This structure, together with extensive functional assays and computational modeling, reveals the molecular mechanisms for AT1 R signaling modulation and suggests that a major hydrogen bond network (MHN) inside the receptor serves as a key regulator of AT1 R signal transduction from the ligand-binding pocket to both Gq and ß-arrestin pathways. Specifically, we found that the MHN mutations N1113.35 A and N2947.45 A induce biased signaling to Gq and ß-arrestin, respectively. These insights should facilitate AT1 R structure-based drug discovery for the treatment of cardiovascular diseases.

BRD7 inhibits enhancer activity and expression of BIRC2 to suppress tumor growth and metastasis in nasopharyngeal carcinoma.

BRD7 functions as a crucial tumor suppressor in numerous malignancies including nasopharyngeal carcinoma (NPC). However, its function and exact mechanisms involved in tumor progression are not well understood. Here, we found that the B7BS was a potential enhancer region of BIRC2, and BRD7 negatively regulated the transcriptional activity and expression of BIRC2 by targeting the activation of the BIRC2 enhancer. Moreover, BIRC2 promoted cell proliferation, migration, invasion as well as xenograft tumor growth and metastasis in vivo, thus functioning as an oncogene in NPC. Furthermore, the recovery of BIRC2 expression could rescue the inhibitory effect of BRD7 on cell proliferation, migration, invasion and xenograft tumor growth and metastasis. In addition, BIRC2 was highly-expressed in NPC tissues, and positively correlated with the TNM stage and negatively correlated with the expression of BRD7. Therefore, these results suggest that BRD7 suppresses tumor growth and metastasis thus functioning as a tumor suppressor at least partially by negatively regulating the enhancer activity and expression of BIRC2, and targeting the BRD7/BIRC2 regulation axis might be a potential strategy for the diagnosis and treatment of NPC.

Structures of human gastrin-releasing peptide receptors bound to antagonist and agonist for cancer and itch therapy.

Gastrin releasing peptide receptor (GRPR), a member of the bombesin (BBN) G protein-coupled receptors, is aberrantly overexpressed in several malignant tumors, including those of the breast, prostate, pancreas, lung, and central nervous system. Additionally, it also mediates non-histaminergic itch and pathological itch conditions in mice. Thus, GRPR could be an attractive target for cancer and itch therapy. Here, we report the inactive state crystal structure of human GRPR in complex with the non-peptide antagonist PD176252, as well as two active state cryo-electron microscopy (cryo-EM) structures of GRPR bound to the endogenous peptide agonist gastrin-releasing peptide and the synthetic BBN analog [D-Phe6, ß-Ala11, Phe13, Nle14] Bn (6-14), in complex with Gq heterotrimers. These structures revealed the molecular mechanisms for the ligand binding, receptor activation, and Gq proteins signaling of GRPR, which are expected to accelerate the structure-based design of GRPR antagonists and agonists for the treatments of cancer and pruritus.

Increased expression of FAT4 suppress metastasis of lung adenocarcinoma through regulating MAPK pathway and associated with immune cells infiltration.

FAT4 is an extremely large atypical cadherin with crucial roles in the control of planar cell polarity (PCP) and regulation of the Hippo signaling pathway. Our study aims to clarify the FAT4 expression patterns, as well as the significance of FAT4 in predicting the prognosis and cancer immunity to non-small cell lung cancer (NSCLC). FAT4 mRNA and protein expressions were both underregulated in NSCLC and associated with poor prognosis in both lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). In addition, overexpress FAT4 with jujuboside A (JUA) or knockdown FAT4 with siRNA regulated the metastasis of LUAD through MAPK pathways. Moreover, the FAT4 expression included multiple immunological components to promote an immunosuppressive tumor microenvironment (TME). Furthermore, a study of the TCGA-LUAD cohort's DNA methylation results showed that most FAT4 DNA CpG sites were typically hypermethylated in NSCLC relative to the normal lung tissue. The DNA CpG sites cg25879360 and cg26389756 of FAT4 were found to be strongly associated with FAT4 expression in LUAD through the correlation study. In conclusion, this is the first to report the potential function of FAT4 in NSCLC. Hence, FAT4 could be used as a promising prognostic and immunological biomarker for NSCLC.

Targeting ALDH1A1 to induce Necroptosis in Nasopharyngeal Carcinoma.

ALDH1A1 is one of the highly conserved isoenzymes of the aldehyde dehydrogenase family. It is mainly involved in the metabolism of intracellular aldehydes and forms transcriptional regulators, which are essential for growth and differentiation of normal cells. Overexpression of ALDH1A1 in many malignancies and cancer stem cells (CSCs) is closely associated with poor prognosis and promotes tumor aggressiveness and drug resistance during conventional cancer chemotherapy. In this study, we found that ALDH1A1 had tumor suppressor effects in BRCA, CESC, LIHC, Lung cancer, renal cell carcinoma and PAAD, but tumor-promoting effects in SKCM, GBM, THCA and BLCA. As for the nasopharyngeal carcinoma, ALDH1A1 mainly played a carcinogenic role. We found that although the expression of ALDH1A1 in NPC tissue was lower than that in normal nasopharyngeal mucosal tissue, it was upregulated in patients with higher clinical stages, and correlated with poor patient outcomes. Therefore, we further analyzed the main possible role of ALDH1A1 in NPC by taking GSE12452 dataset. The GSEA enrichment analysis showed that it could inhibit the necroptosis of nasopharyngeal carcinoma cells. Therefore, we used the targeted inhibitor NCT-501 and found that it could inhibit the proliferation and stem cell spheroidization of NPC cells, and induce necroptosis. This study explored the possible role of ALDH1A1 in various tumors and focused on its potential role as a target in NPC. Meanwhile, ALDH1A1 inhibitor preferentially has potential therapeutic value in NPC.

The Emerging Roles and Clinical Potential of circSMARCA5 in Cancer.

Circular RNAs (circRNAs) are a type of endogenous non-coding RNA and a critical epigenetic regulation way that have a closed-loop structure and are highly stable, conserved, and tissue-specific, and they play an important role in the development of many diseases, including tumors, neurological diseases, and cardiovascular diseases. CircSMARCA5 is a circRNA formed by its parental gene SMARCA5 via back splicing which is dysregulated in expression in a variety of tumors and is involved in tumor development with dual functions as an oncogene or tumor suppressor. It not only serves as a competing endogenous RNA (ceRNA) by binding to various miRNAs, but it also interacts with RNA binding protein (RBP), regulating downstream gene expression; it also aids in DNA damage repair by regulating the transcription and expression of its parental gene. This review systematically summarized the expression and characteristics, dual biological functions, and molecular regulatory mechanisms of circSMARCA5 involved in carcinogenesis and tumor progression as well as the potential applications in early diagnosis and gene targeting therapy in tumors.

Clinical implications of the interaction between PD-1/PD-L1 and PI3K/AKT/mTOR pathway in progression and treatment of non-small cell lung cancer.

The discovery of immune checkpoints has been well known to provide novel clues for cancer treatments. Immunotherapy against the programmed cell death protein-1 (PD-1) /programmed death-ligand-1 (PD-L1), one of the most popular auxiliary treatments in recent years, has been applied in various tumor treatments, including non-small cell lung cancer (NSCLC). However, inevitable issues such as side effects and drug resistance emerge following the use of immune checkpoint inhibitors. The PI3K/AKT/mTOR pathway may participate in the regulation of PD-L1 expression. Abnormal PI3K/AKT/mTOR pathway activation results in increased PD-L1 protein translation, whereas PD-L1 overexpression can activate the PI3K/AKT/mTOR pathway inversely. Via downstream proteins, including 4E-BP1, STAT3, NF-κB, c-MYC, and AMPK in aberrant energy status, the PI3K/AKT/mTOR pathway can regulate PD-L1 post-transcription and translation. Besides, the regulation of the PI3K pathway by the PD-1/PD-L1 axis involves both tumor cells and the tumor immune microenvironment. Inhibitors targeting the PD-1/PD-L1 have been successfully applied in the treatment of gastrointestinal cancer and breast cancer. Meanwhile, drug resistance from alternative pathway activation also evidently affects clinical progress. To achieve a better therapeutic effect and quality of survival, the combination of multiple treatment modalities presents great research value. Here we reviewed the interaction between PD-1/PD-L1 and PI3K/AKT/mTOR pathway in the progression and treatment of NSCLC and summarized its clinical implications. The intracellular interactions between PD-1/PD-L1 and the PI3K/AKT/mTOR pathway indicate that PD-1/PD-L1 inhibitors have a wide range of potential applications. And we presented the mechanism for combining therapy with monoclonal antibody PD-1/PD-L1 and PI3K/AKT/mTOR inhibitors in this review, to broaden the therapies for NSCLC.

Overexpression of p-4EBP1 associates with p-eIF4E and predicts poor prognosis for non-small cell lung cancer patients with resection.

Eukaryotic initiation factor 4E (eIF4E) and its phosphorylated form (p-eIF4E) play a crucial role in the protein synthesis, both are under regulation of eIF4E-binding protein 1 (4EBP1) and mitogen-activated protein kinase (MAPK)-interacting kinases (MNKs). This study aims to explore the potential prognostic significance of p-4EBP1 and p-eIF4E in NSCLC patients. The expression of p-4EBP1 and p-eIF4E in NSCLC patients was detected by immunohistochemistry (IHC) staining in tissue microarrays (TMAs) containing 354 NSCLC and 53 non-cancerous lung tissues (Non-CLT). The overexpression percentage of p-4EBP1 and p-eIF4E in lung squamous cell carcinoma (SCC) and adenocarcinoma (ADC) was significantly higher than that of Non-CLT. P-4EBP1 expression in patients with advanced clinical stage was higher than that in early stage. Expression of p-4EBP1 had a positive relationship with p-eIF4E expression both in lung SCC and ADC. NSCLC patients with high expression of p-4EBP1 and p-eIF4E alone or in combination had a lower survival rate than that of other phenotypes. For NSCLC patients, p-4EBP1 is an independent poor prognostic factor as well as clinical stage, LNM and pathological grade. Overexpression of p-4EBP1 and p-eIF4E might be novel prognostic marker for NSCLC, who possesses potential application value for NSCLC targeted therapy.

Widespread occurrence of emerging E-waste contaminants - Liquid crystal monomers in sediments of the Pearl River Estuary, China.

Liquid crystal monomers (LCMs), commonly used in screens of electronic devices, have recently been identified as a group of emerging chemicals of concern associated with e-waste. They are potentially persistent, bioaccumulative, and toxic substances, and may pose a threat to the marine ecosystem. The Pearl River Estuary (PRE) receives organic contaminants discharged from the Pearl River Delta region, where primitive handling of e-waste is widespread. However, information on the pollution status of LCMs in the PRE is absent. Herein, a rapid and robust analytical method was established using ultrasonic extraction, solid phase extraction cleanup, and GC-Orbitrap-MS analysis. The spatial distribution of 39 target LCMs was investigated in 45 surface sediment samples from the PRE. Ten LCMs were detected, with ΣLCMs ranged from 0.9 to 31.1 ng/g dry weight. Our results demonstrated a widespread occurrence of LCMs in the sediments of the PRE, and a gradient of their contamination from inshore to offshore regions, indicating land-based origins. Our reported ΣLCMs concentrations were relatively higher compared to many other legacy and emerging pollutants found in the same investigated area. Preliminary risk assessment showed 3VbcH, Pe3bcH and tFMeO-3bcHP might be the top 3 risk contributors in the PRE. Further investigation on the ecological impact of LCMs on marine benthic ecosystems, as well as identification of their sources and control measures are warranted.