Progress in the application of ultrasound in glioma surgery.

Brain glioma, which is highly invasive and has a poor prognosis, is the most common primary intracranial tumor. Several studies have verified that the extent of resection is a considerable prognostic factor for achieving the best results in neurosurgical oncology. To obtain gross total resection (GTR), neurosurgery relies heavily on generating continuous, real-time, intraoperative glioma descriptions based on image guidance. Given the limitations of existing devices, it is imperative to develop a real-time image-guided resection technique to offer reliable functional and anatomical information during surgery. At present, the application of intraoperative ultrasound (IOUS) has been indicated to enhance resection rates and maximize brain function preservation. IOUS, which is promising due to its lower cost, minimal operational flow interruptions, and lack of radiation exposure, can enable real-time localization and precise tumor size and form descriptions while assisting in discriminating residual tumors and solving brain tissue shifts. Moreover, the application of new advancements in ultrasound technology, such as contrast-enhanced ultrasound (CEUS), three-dimensional ultrasound (3DUS), noninvasive ultrasound (NUS), and ultrasound elastography (UE), could assist in achieving GTR in glioma surgery. This article reviews the advantages and disadvantages of IOUS in glioma surgery.

Repeatability and Agreement of Central Vault for Implantable Collamer Lens Obtained by the Tomey OA-2000 Biometer and Spectralis OCT.

Objective: To assess repeatability and agreement of central vault for implantable collamer lens (ICL) measured by the Tomey OA-2000 biometry and Spectralis optical coherence tomography (OCT). Methods: In this prospective study, the central vault was measured by the Tomey OA-2000 biometer and Spectralis OCT in 84 eyes (43 patients) after ICL implantation at six month follow-up. Three consecutive scans were obtained by one experienced technician using Tomey OA-2000 and the Spectralis OCT in the same day. The coefficient of variation (CoV), intraclass correlation coefficient (ICC), within-subject standard deviation (Sw), and 2.77 Sw were calculated to assess the repeatability and reproducibility. The paired t-test and Bland-Altman plots were used to analyze the differences and agreements of central vault measured by two devices. Results: Repeatability of the central vault measured by Tomey OA-2000 biometer and Spectralis OCT showed that the CoV was 2.71% and 1.66%, respectively. The ICC for both devices was 0.996 and 0.999, respectively. The paired t-test showed that central vault measured by Tomey OA-2000 biometer was -7.25 ± 23.57 microns lower than that measured by Spectralis OCT (P = 0.006). The mean difference between measurements for Tomey OA-2000 and ASM-OCT with 95% limits of agreement (LoAs) was -38.94 to 53.44 µm. Conclusion: Both Tomey OA-2000 biometer and Spectralis OCT displayed good repeatability for the measurement of central vault of ICL. Good reliability and agreement were observed between Tomey OA-2000 biometer and Spectralis OCT. Both instruments are useful but not replaced each other for central vault measurements.

Sub-femtomolar vertical graphene field effect immunosensor for detection of lung tumor markers.

Lung cancer is the main cancer that endangers human life worldwide, with the highest mortality rate. The detection of lung tumor markers is of great significance for the early diagnosis and subsequent treatment of lung cancer. In this study, a vertical graphene field effect transistor (VGFET) immunosensor based on graphene/C60 heterojunction was created to offer quantitative detections for the lung tumor markers carcinoembryonic antigen (CEA), cytokeratin 19 fragment (Cyfra21-1), and neuron-specific enolase (NSE). The experimental results showed that the sensitive range for standard antigen is between 1 pg/ml to 100 ng/ml, with a limit of detection (LOD) of 5.6 amol/ml for CEA, 33.3 amol/ml for Cyfra 21-1 and 12.8 amol/ml for NSE (1 pg/ml for all). The detection accuracy for these tumor markers was compared with the clinically used method for clinical patients on serum samples. Results are highly consistent with clinically used immunoassay in its efficient diagnosis concentration range. Subsequently, the mesoporous silica nanospheres (MSNs) with an average size of 90 nm were surface modified with glutaraldehyde, and a second antibody was assembled on MSNs, which fixes nanospheres on the antigen and amplified the field effect. The LODs for three markers are 100 fg/ml (0.56 amol/ml for CEA) under optimal circumstances of detection. This result indicates that specific binding to MSNs enhances local field effects and can achieve higher sensing efficiency for tumor marker detection at extremely low concentrations, providing effective assistance for the early diagnosis of lung cancer.

Granulosa Cell-Layer Stiffening Prevents Escape of Mural Granulosa Cells from the Post-Ovulatory Follicle.

Ovulation is vital for successful reproduction. Following ovulation, cumulus cells and oocyte are released, while mural granulosa cells (mGCs) remain sequestered within the post-ovulatory follicle to form the corpus luteum. However, the mechanism underlying the confinement of mGCs has been a longstanding mystery. Here, in vitro and in vivo evidence is provided demonstrating that the stiffening of mGC-layer serves as an evolutionarily conserved mechanism that prevents mGCs from escaping the post-ovulatory follicles. The results from spatial transcriptome analysis and experiments reveal that focal adhesion assembly, triggered by the LH (hCG)-cAMP-PKA-CREB signaling cascade, is necessary for mGC-layer stiffening. Disrupting focal adhesion assembly through RNA interference results in stiffening failure, mGC escape, and the subsequent development of an abnormal corpus luteum characterized by decreased cell density or cavities. These findings introduce a novel concept of "mGC-layer stiffening", shedding light on the mechanism that prevents mGC escape from the post-ovulatory follicle.

Alterations of the bile microbiome is associated with progression-free survival in pancreatic ductal adenocarcinoma patients.

BACKGROUND: Patients with pancreatic ductal adenocarcinoma (PDAC) display an altered oral, gastrointestinal, and intra-pancreatic microbiome compared to healthy individuals. However, knowledge regarding the bile microbiome and its potential impact on progression-free survival in PDACs remains limited. METHODS: Patients with PDAC (n = 45), including 20 matched pairs before and after surgery, and benign controls (n = 16) were included prospectively. The characteristics of the microbiomes of the total 81 bile were revealed by 16  S-rRNA gene sequencing. PDAC patients were divided into distinct groups based on tumor marker levels, disease staging, before and after surgery, as well as progression free survival (PFS) for further analysis. Disease diagnostic model was formulated utilizing the random forest algorithm. RESULTS: PDAC patients harbor a unique and diverse bile microbiome (PCoA, weighted Unifrac, p = 0.038), and the increasing microbial diversity is correlated with dysbiosis according to key microbes and microbial functions. Aliihoeflea emerged as the genus displaying the most significant alteration among two groups (p < 0.01). Significant differences were found in beta diversity of the bile microbiome between long-term PFS and short-term PFS groups (PCoA, weighted Unifrac, p = 0.005). Bacillota and Actinomycetota were identified as altered phylum between two groups associated with progression-free survival in all PDAC patients. Additionally, we identified three biomarkers as the most suitable set for the random forest model, which indicated a significantly elevated likelihood of disease occurrence in the PDAC group (p < 0.0001). The area under the receiver operating characteristic (ROC) curve reached 80.8% with a 95% confidence interval ranging from 55.0 to 100%. Due to the scarcity of bile samples, we were unable to conduct further external verification. CONCLUSION: PDAC is characterized by an altered microbiome of bile ducts. Biliary dysbiosis is linked with progression-free survival in all PDACs. This study revealed the alteration of the bile microbiome in PDACs and successfully developed a diagnostic model for PDAC.

RNA modification gene WDR4 facilitates tumor progression and immunotherapy resistance in breast cancer.

INTRODUCTION: Growing interest toward RNA modification in cancer has inspired the exploration of gene sets related to multiple RNA modifications. However, a comprehensive elucidation of the clinical value of various RNA modifications in breast cancer is still lacking. OBJECTIVES: This study aimed to provide a strategy based on RNA modification-related genes for predicting therapy response and survival outcomes in breast cancer patients. METHODS: Genes related to thirteen RNA modification patterns were integrated for establishing a nine-gene-containing signature-RMscore. Alterations of tumor immune microenvironment and therapy response featured by different RMscore levels were assessed by bulk transcriptome, single-cell transcriptome and genomics analyses. The biological function of key RMscore-related molecules was investigated by cellular experiments in vitro and in vivo, using flow cytometry, immunohistochemistry and immunofluorescence staining. RESULTS: This study has raised an effective therapy strategy for breast cancer patients after a well-rounded investigation of RNA modification-related genes. With a great performance of predicting patient prognosis, high levels of the RMscore proposed in this study represented suppressive immune microenvironment and therapy resistance, including adjuvant chemotherapy and PD-L1 blockade treatment. As the key contributor of the RMscore, inhibition of WDR4 impaired breast cancer progression significantly in vitro and in vivo, as well as participated in regulating cell cycle and mTORC1 signaling pathway via m7G modification. CONCLUSION: Briefly, this study has developed promising and effective tactics to achieve the prediction of survival probabilities and treatment response in breast cancer patients.

Prediction of wheat SPAD using integrated multispectral and support vector machines.

Rapidly obtaining the chlorophyll content of crop leaves is of great significance for timely diagnosis of crop health and effective field management. Multispectral imagery obtained from unmanned aerial vehicles (UAV) is being used to remotely sense the SPAD (Soil and Plant Analyzer Development) values of wheat crops. However, existing research has not yet fully considered the impact of different growth stages and crop populations on the accuracy of SPAD estimation. In this study, 300 materials from winter wheat natural populations in Xinjiang, collected between 2020 to 2022, were analyzed. UAV multispectral images were obtained in the experimental area, and vegetation indices were extracted to analyze the correlation between the selected vegetation indices and SPAD values. The input variables for the model were screened, and a support vector machine (SVM) model was constructed to estimate SPAD values during the heading, flowering, and filling stages under different water stresses. The aim was to provide a method for the rapid acquisition of winter wheat SPAD values. The results showed that the SPAD values under normal irrigation were higher than those under water restriction. Multiple vegetation indices were significantly correlated with SPAD values. In the prediction model construction of SPAD, the different models had high estimation accuracy under both normal irrigation and water limitation treatments, with correlation coefficients of predicted and measured values under normal irrigation in different environments the value of r from 0.59 to 0.81 and RMSE from 2.15 to 11.64, compared to RE from 0.10% to 1.00%; and under drought stress in different environments, correlation coefficients of predicted and measured values of r was 0.69-0.79, RMSE was 2.30-12.94, and RE was 0.10%-1.30%. This study demonstrated that the optimal combination of feature selection methods and machine learning algorithms can lead to a more accurate estimation of winter wheat SPAD values. In summary, the SVM model based on UAV multispectral images can rapidly and accurately estimate winter wheat SPAD value.

Combined transcriptome and widely targeted metabolome analysis reveals the potential mechanism of HupA biosynthesis and antioxidant activity in Huperzia serrata.

Introduction: Huperzia serrata is a traditional Chinese herb that has gained much attention for its production of Huperzine A (HupA). HupA has shown promise on treating Alzheimer's disease (AD). However, the biosynthetic pathway and molecular mechanism of HupA in H. serrata are still not well understood. Methods: Integrated transcriptome and metabolome analysis was performed to reveal the molecular mechanisms related to HupA biosynthesis and antioxidant activity in Huperzia serrata. Results: HT (in vitro H. serrata thallus) exhibits higher antioxidant activity and lower cytotoxicity than WH (wild H. serrata). Through hierarchical clustering analysis and qRT-PCR verification, 7 important enzyme genes and 13 transcription factors (TFs) related to HupA biosynthesis were detected. Among them, the average |log2FC| value of CYP (Cytochrome P450) and CAO (Copper amine oxidase) was the largest. Metabolomic analysis identified 12 metabolites involved in the HupA biosynthesis and 29 metabolites related to antioxidant activity. KEGG co-enrichment analysis revealed that tropane, piperidine and pyridine alkaloid biosynthesis were involved in the HupA biosynthesis pathway. Furthermore, the phenylpropanoid, phenylalanine, and flavonoid biosynthesis pathway were found to regulate the antioxidant activity of H. serrata. The study also identified seven important genes related to the regulation of antioxidant activity, including PrAO (primary-amine oxidase). Based on the above joint analysis, the biosynthetic pathway of HupA and potential mechanisms of antioxidant in H. serrata was constructed. Discussion: Through differential transcriptome and metabolome analysis, DEGs and DAMs involved in HupA biosynthesis and antioxidant-related were identified, and the potential metabolic pathway related to HupA biosynthesis and antioxidant in Huperzia serrata were constructed. This study would provide valuable insights into the HupA biosynthesis mechanism and the H. serrata thallus medicinal value.

Localized fine-tuning and clinical evaluation of deep-learning based auto-segmentation (DLAS) model for clinical target volume (CTV) and organs-at-risk (OAR) in rectal cancer radiotherapy.

BACKGROUND AND PURPOSE: Various deep learning auto-segmentation (DLAS) models have been proposed, some of which have been commercialized. However, the issue of performance degradation is notable when pretrained models are deployed in the clinic. This study aims to enhance precision of a popular commercial DLAS product in rectal cancer radiotherapy by localized fine-tuning, addressing challenges in practicality and generalizability in real-world clinical settings. MATERIALS AND METHODS: A total of 120 Stage II/III mid-low rectal cancer patients were retrospectively enrolled and divided into three datasets: training (n = 60), external validation (ExVal, n = 30), and generalizability evaluation (GenEva, n = 30) datasets respectively. The patients in the training and ExVal dataset were acquired on the same CT simulator, while those in GenEva were on a different CT simulator. The commercial DLAS software was first localized fine-tuned (LFT) for clinical target volume (CTV) and organs-at-risk (OAR) using the training data, and then validated on ExVal and GenEva respectively. Performance evaluation involved comparing the LFT model with the vendor-provided pretrained model (VPM) against ground truth contours, using metrics like Dice similarity coefficient (DSC), 95th Hausdorff distance (95HD), sensitivity and specificity. RESULTS: LFT significantly improved CTV delineation accuracy (p < 0.05) with LFT outperforming VPM in target volume, DSC, 95HD and specificity. Both models exhibited adequate accuracy for bladder and femoral heads, and LFT demonstrated significant enhancement in segmenting the more complex small intestine. We did not identify performance degradation when LFT and VPM models were applied in the GenEva dataset. CONCLUSIONS: The necessity and potential benefits of LFT DLAS towards institution-specific model adaption is underscored. The commercial DLAS software exhibits superior accuracy once localized fine-tuned, and is highly robust to imaging equipment changes.

Development and validation of a novel prediction model for Carbapenem-resistant organism infection in a large-scale hospitalized patients.

Carbapenem-resistant organism (CRO) are defined as gram-negative bacteria. The lack of safe and effective antibiotics has led to an increase in incidence rate. The purpose of this study is to establish and determine a risk nomogram to predict CRO infection in hospitalized patients. Hospitalized patients' information were collected from the electronic medical record system of hospital between January 2019 and December 2022. Based on the inclusion and exclusion criteria, we identified 131390 inpatients who met the criteria for this study. For the training cohort, the area under the curves (AUC) for predicting the CRO infection was 0.935. For the validation cohort, the AUC for predicting the CRO infection was 0.937. We have developed the first novel nomogram to predict CRO infection in hospitalized patients, which is reliable and high-performance. The nomogram performs well among hospitalized patients and has good predictive ability.

Unraveling the function of FGF signaling in human hypoblast specialization.

Dattani et al.1 developed a method for inducing hypoblast-like cells from human naive pluripotent stem cells. They elucidated the requirement for FGF signaling in human hypoblast specialization at a specific time window, which was previously controversial.

The association between circulating phenylalanine and the temporal risk of impaired insulin markers in gestational diabetes mellitus.

Background: We aimed to contrast plasma amino acid concentrations in pregnant women with Gestational Diabetes Mellitus (GDM) to those without, to analyze the link between plasma amino acid concentrations, GDM, insulin resistance, and insulin secretion at 24-28 weeks of gestation. Methods: The research employed a retrospective case-control study design at a single center. Basic demographic and laboratory data were procured from the hospital's case system. The study encompassed seventy women without gestational diabetes mellitus (GDM) and thirty-five women with GDM matched in a 1-to-2 ratio for age and pre-pregnancy BMI. Utilizing high-performance liquid chromatography-mass spectrometry (HPLC-MS), peripheral fasting plasma amino acid concentrations in these women, during mid-pregnancy, were duly measured. We carefully evaluated the significant differences in the quantitative data between the two groups and developed linear regression models to assess the independent risk factors affecting insulin resistance and insulin secretion. Results: Significant variations in insulin secretion and resistance levels distinguished GDM Group from the non-GDM group at three distinct time points, alongside relatively elevated serum Glycosylated Hemoglobin (HbA1c) levels. Triglycerides (TG) were also significantly increased in those with GDM during adipocytokine observations. Apart from glutamic acid and glutamine, the concentrations of the remaining 16 amino acids were notably increased in GDM patients, including all branched chain amino acids(BCAAs) and aromatic amino acids(AAAs). Ultimately, it was ascertained that fasting serum phenylalanine levels were independent risk factors affecting insulin resistance index and insulin secretion at various phases. Conclusions: Various fasting serum amino acid levels are markedly increased in patients with GDM, specifically phenylalanine, which may play role in insulin resistance and secretion.

Body composition characteristics and influencing factors of different parts of sarcopenia in elderly people: A community-based cross-sectional survey.

Objectives: This study aims to describe the differences in body composition among different body parts of the elderly in the community and its relationship with sarcopenia. Methods: Elderly people aged ≥65 underwent bioelectric impedance analysis testing and were categorized into a sarcopenia group, possible sarcopenia group, and control group. The characteristics of body composition indicators in different parts and their relationship with different stages of sarcopenia were analyzed. Results: The sarcopenia group illustrated the lowest values of FFM, FFM%, BFM, BFM%, ICW, and limb PhA, along with higher ECW/TBW in the trunk and left leg compared to the control group. The possible sarcopenia group showed lower FFM% in limbs and trunk, and higher BFM% compared to the control group. Gender differences in elderly body composition were observed, with an increase in BFM% in various body parts posing a risk factor for possible sarcopenia in elderly males, whereas an increase in BFM% except in the left arm was a protective factor for sarcopenia in elderly females. Conclusion: The body composition of the elderly in the community varied significantly in different stages of sarcopenia and genders, which correlated with sarcopenia.

Recent advances of biocompatible optical nanobiosensors in liquid biopsy: towards early non-invasive diagnosis.

Liquid biopsy is a non-invasive diagnostic method that can reduce the risk of complications and offers exceptional benefits in the dynamic monitoring and acquisition of heterogeneous cell population information. Optical nanomaterials with excellent light absorption, luminescence, and photoelectrochemical properties have accelerated the development of liquid biopsy technologies. Owing to the unique size effect of optical nanomaterials, their improved optical properties enable them to exhibit good sensitivity and specificity for mitigating signal interference from various molecules in body fluids. Nanomaterials with biocompatible and optical sensing properties play a crucial role in advancing the maturity and diversification of liquid biopsy technologies. This article offers a comprehensive review of recent advanced liquid biopsy technologies that utilize novel biocompatible optical nanomaterials, including fluorescence, colorimetric, photoelectrochemical, and Raman broad-spectrum-based biosensors. We focused on liquid biopsy for the most significant early biomarkers in clinical medicine, and specifically reviewed reports on the effectiveness of optical nanosensing technology in the detection of real patient samples, which may provide basic evidence for the transition of optical nanosensing technology from engineering design to clinical practice. Furthermore, we introduced the integration of optical nanosensing-based liquid biopsy with modern devices, such as smartphones, to demonstrate the potential of the technology in portable clinical diagnosis.

N-Phenyl-2-Pyridone-Derived Endoperoxide Suppressing both Lung Cancer and Idiopathic Pulmonary Fibrosis Progression by Three-Pronged Action.

We report an endoperoxide compound (E5) which can deliver three therapeutic components by a thermal cycloreversion, namely, singlet oxygen, triplet oxygen and 3-methyl-N-phenyl-2-pyridone, thus targeting multiple mechanisms for treating non-small cell lung cancer and idiopathic pulmonary fibrosis. In aqueous environment, E5 undergoes clean reaction to afford three therapeutic components with a half-life of 8.3 hours without the generation of other by-products, which not only achieves good cytotoxicity toward lung cancer cells and decreases the levels of HIF-1α protein, but also inhibits the TGF-ß1 induced fibrosis in vitro. In vivo experiments also demonstrated the efficacy of E5 in inhibiting tumor growth and relieving idiopathic pulmonary fibrosis, while exhibiting good biocompatibility. Many lines of evidence reveal the therapeutic efficacy of singlet oxygen and 3-methyl-N-phenyl-2-pyridone, and triplet oxygen could downregulate HIF-1α and relieve tumor hypoxia which is a critical issue in conventional PDT. Unlike other combination therapies, in which multiple therapeutic agents are given in independent formulations, our work demonstrates single molecule endoperoxide prodrugs could be developed as new platforms for treatment of cancers and related diseases.

Regulatory role of exosome-derived miRNAs and other contents in adipogenesis.

Intramuscular fat (IMF) content significantly impacts meat quality. influenced by complex interactions between skeletal muscle cells and adipocytes. Adipogenesis plays a pivotal role in IMF formation. Exosomes, extracellular membranous nanovesicles, facilitate intercellular communication by transporting proteins, nucleic acids (DNA and RNA), and other biomolecules into target cells, thereby modulating cellular behaviors. Recent studies have linked exosome-derived microRNAs (miRNAs) and other cargo to adipogenic processes. Various cell types, including skeletal muscle cells, interact with adipocytes via exosome secretion and uptake. Exosomes entering adipocytes regulate adipogenesis by modulating key signaling pathways, thereby influencing the extent and distribution of IMF deposition.This review comprehensively explores the origin, formation, and mechanisms of exosome action, along with current research and their applications in adipogenesis. Emphasis is placed on exosome-mediated regulation of miRNAs, non-coding RNAs (ncRNAs), proteins, lipids, and other biomolecules during adipogenesis. Leveraging exosomal contents for genetic breeding and treating obesity-related disorders is discussed. Insights gathered contribute to advancing understanding and potential therapeutic applications of exosome-regulated adipogenesis mechanisms.

Enhanced Hydrogen Peroxide Decomposition in a Continuous-Flow Reactor over Immobilized Catalase with PAES-C.

Due to the specificity, high efficiency, and gentleness of enzyme catalysis, the industrial utilization of enzymes has attracted more and more attention. Immobilized enzymes can be recovered/recycled easily compared to their free forms. The primary benefit of immobilization is protection of the enzymes from harsh environmental conditions (e.g., elevated temperatures, extreme pH values, etc.). In this paper, catalase was successfully immobilized in a poly(aryl ether sulfone) carrier (PAES-C) with tunable pore structure as well as carboxylic acid side chains. Moreover, immobilization factors like temperature, time, and free-enzyme dosage were optimized to maximize the value of the carrier and enzyme. Compared with free enzyme, the immobilized-enzyme exhibited higher enzymatic activity (188.75 U g-1, at 30 °C and pH 7) and better thermal stability (at 60 °C). The adsorption capacity of enzyme protein per unit mass carrier was 4.685 mg. Hydrogen peroxide decomposition carried out in a continuous-flow reactor was selected as a model reaction to investigate the performance of immobilized catalase. Immobilized-enzymes showed a higher conversion rate (90% at 8 mL/min, 1 h and 0.2 g) compared to intermittent operation. In addition, PAES-C has been synthesized using dichlorodiphenyl sulfone and the renewable resource bisphenolic acid, which meets the requirements of green chemistry. These results suggest that PAES-C as a carrier for immobilized catalase could improve the catalytic activity and stability of catalase, simplify the separation of enzymes, and exhibit good stability and reusability.

Tailoring Coherent Microwave Emission from a Solid-State Hybrid System for Room-Temperature Microwave Quantum Electronics.

Quantum electronics operating in the microwave domain are burgeoning and becoming essential building blocks of quantum computers, sensors, and communication devices. However, the field of microwave quantum electronics has long been dominated by the need for cryogenic conditions to maintain delicate quantum characteristics. Here, a solid-state hybrid system, constituted by a photo-excited pentacene triplet spin ensemble coupled to a dielectric resonator, is reported for the first time capable of both coherent microwave quantum amplification and oscillation at X band via the masing process at room temperature. By incorporating external driving and active dissipation control into the hybrid system, efficient tuning of the maser emission characteristics at ≈9.4 GHz is achieved, which is key to optimizing the performance of the maser device. The work not only pushes the boundaries of the operating frequency and functionality of the existing pentacene masers but also demonstrates a universal route for controlling the masing process at room temperature, highlighting opportunities for optimizing emerging solid-state masers for quantum information processing and communication.

The origin and spread of HIV-1 CRF59_01B epidemic in China: A molecular network and phylogeographic analysis.

Human immunodeficiency virus type 1 CRF59_01B, identified in China in 2013, has been detected nationwide, exhibiting notably high prevalence in Guangzhou and its vicinity. This study aimed to unravel its origin and migration. A data set was established, incorporating all available CRF59_01B pol gene sequences and their metadata from Guangzhou and the public database. Bayesian phylogeographic analysis demonstrated that CRF59_01B originated in Shenzhen, the neighboring city of Guangzhou, around 1998 with posterior probability of 0.937. Molecular network analysis detected 1131 transmission links and showed a remarkably high clustering rate (78.9%). Substantial inter-city transmissions (26.5%, 300/1131) were observed between Shenzhen and Guangzhou while inter-region transmissions linked Guangzhou with South (46) and Southwest (64) China. The centre of Guangzhou was the hub of CRF59_01B transmission, including the inflow from Shenzhen (3.57 events/year) and outflow to the outskirts of Guangzhou (>2 events/year). The large-scale analysis revealed significant migration from Shenzhen to Guangzhou (5.08 events/year) and North China (0.59 events/year), and spread from Guangzhou to Central (0.47 events/year), East (0.42 events/year), South (0.76 events/year), Southwest China (0.76 events/year) and Shenzhen (1.89 events/year). Shenzhen and Guangzhou served as the origin and the hub of CRF59_01B circulation, emphasizing inter-city cooperation and data sharing to confine its nationwide diffusion.

YTH domain family protein 3 accelerates non-small cell lung cancer immune evasion through targeting CD8+ T lymphocytes.

Immune evasion is one of the critical hallmarks of malignant tumors, especially non-small cell lung cancer (NSCLC). Emerging findings have illustrated the roles of N6-methyladenosine (m6A) on NSCLC immune evasion. Here, this study investigated the function and underlying mechanism of m6A reader YTH domain family protein 3 (YTHDF3) on NSCLC immune evasion. YTHDF3 was found to be highly expressed in NSCLC tissue and act as an independent prognostic factor for overall survival. Functionally, up-regulation of YTHDF3 impaired the CD8+ T antitumor activity to deteriorate NSCLC immune evasion, while YTHDF3 silencing recovered the CD8+ T antitumor activity to inhibit immune evasion. Besides, YTHDF3 up-regulation reduced the apoptosis of NSCLC cells. Mechanistically, PD-L1 acted as the downstream target for YTHDF3, and YTHDF3 could upregulate the transcription stability of PD-L1 mRNA. Overall, YTHDF3 targeted PD-L1 to promote NSCLC immune evasion partially through escaping effector cell cytotoxicity CD8+ T mediated killing and antitumor immunity. In summary, this study provides an essential insight for m6A modification on CD8+ T cell-mediated antitumor immunity in NSCLC, which might inspire an innovation for lung cancer tumor immunotherapy.