Deep Learning with Pretrained Framework Unleashes the Power of Satellite-Based Global Fine-Mode Aerosol Retrieval.

Fine-mode aerosol optical depth (fAOD) is a vital proxy for the concentration of anthropogenic aerosols in the atmosphere. Currently, the limited data length and high uncertainty of the satellite-based data diminish the applicability of fAOD for climate research. Here, we propose a novel pretrained deep learning framework that can extract information underlying each satellite pixel and use it to create new latent features that can be employed for improving retrieval accuracy in regions without in situ data. With the proposed model, we developed a new global fAOD (at 0.5 µm) data from 2001 to 2020, resulting in a 10% improvement in the overall correlation coefficient (R) during site-based independent validation and a 15% enhancement in non-AERONET site areas validation. Over the past two decades, there has been a noticeable downward trend in global fAOD (-1.39 × 10-3/year). Compared to the general deep-learning model, our method reduces the global trend's previously overestimated magnitude by 7% per year. China has experienced the most significant decline (-5.07 × 10-3/year), which is 3 times greater than the global trend. Conversely, India has shown a significant increase (7.86 × 10-4/year). This study bridges the gap between sparse in situ observations and abundant satellite measurements, thereby improving predictive models for global patterns of fAOD and other climate factors.

Acute radiation skin injury in stage III-IV head and neck cancer: scale correlates and predictive model.

PURPOSE: Active radiation skin injury (ARSI) has the highest incidence of acute adverse reactions caused by radiotherapy (RT) in patients with head and neck cancer (HNC). This study aimed to screen risk factors that can facilitate the identification of HNC patients at high risk of ARSI. METHODS: Data from 255 stage III-IV HNC patients who underwent intensity-modulated radiation therapy (IMRT) were collected. The data from our medical records, including clinical characteristics and hematological indices before RT, were retrospectively collected and arranged. The Common Terminology Criteria for Adverse Events Criteria (CTCAE), Radiation Therapy Oncology Group Criteria (RTOG), World Health Organization Criteria (WHO), Oncology Nursing Society (ONS), Acute Radiation Dermatitis Graduation Scale, Douglas & Fowler and Radiation Dermatitis Severity Scale (RDSS) were used to assess ARSI. Of these, CTCAE was used for further analysis. Binary logistic regression analyses were used to identity risk factors. To establish the correction between each risk factor and the ARSI score, the odds ratio (OR) and 95% confidence interval (CI) were computed. RESULTS: The assessment results of the CTCAE with RTOG, WHO, ONS, Graduation Scale, Douglas & Fowler and RDSS have good consistency. After radiotherapy, 18.4% of patients had at least 3 (3 +) grade ARSI. Multivariate logistic regression analysis revealed that the KPS score, blood glucose level, white blood cell count, and plasma free thyroxine (FT4) concentration were independent risk factors for 3 + grade ARSI. A nomogram was constructed on the basis of these risk factors, which demonstrated good predictive power according to the area under the ROC curve (AUC). The satisfactory consistency and clinical efficacy of the nomogram were confirmed by calibration curves and decision curve analysis (DCA). CONCLUSION: A low KPS score, high blood glucose level, high white blood cell count, and high thyroid hormone prior to radiotherapy for stage III-IV HNC are independent risk factors for grade 3 + RSI.

Understanding the Role of Technology Anxiety in the Adoption of Digital Health Technologies (DHTs) by Older Adults with Chronic Diseases in Shanghai: An Extension of the Unified Theory of Acceptance and Use of Technology (UTAUT) Model.

The unprecedented rapid growth of digital health has brought new opportunities to the health field. However, elderly patients with chronic diseases, as an important potential beneficiary group, are affected by the digital divide, leading to unsatisfactory usage of digital health technologies (DHTs). Our study focused on the factors influencing the adoption of DHTs among this vulnerable group. To extend the UTAUT theory, technology anxiety and several demographic predictors were included to address the age characteristics of the respondents. An on-site survey was conducted in general, district, and community hospitals in Shanghai (n = 309). Facilitating conditions negatively influenced technology anxiety. Technology anxiety hindered behavioural intention. Social influence had a significant but negative impact on behavioural intention. Education, whether older adults have had experience with DHTs and previous smartphone usage experiences were significantly associated with technology anxiety. The findings provide valuable information for multiple stakeholders, including family members of elderly users, product designers, and policymakers. Ameliorating facilitating conditions, improving devices' usage experience, encouraging attempts and focusing on groups with lower educational levels can help to reduce technology anxiety and promote DHT acceptance and use in older age groups.

Design and characterization of a self-matching photonic lantern for all few-mode fiber laser systems.

We model and demonstrate a self-matching photonic lantern (SMPL) device, which is designed to address the constraint of limited transverse modes generated by fiber lasers. The SMPL incorporates a FMF into the array at the input end of a traditional photonic lantern. The few-mode fiber at the output end is specifically configured to align with the few-mode fiber at the input, therefore named as SMPL. This paper details the design and fabrication of the SMPL device, validated by both simulation and experiment. The 980nm fundamental mode, injected via 980nm single-mode fibers, selectively excites corresponding higher-order modes at the few-mode port of the SMPL. Additionally, 1550nm fundamental and higher-order modes injected at the input end into the SMPL device demonstrates mode preservation and low-loss transmission characteristics. The SMPL is well-suited for developing a ring laser system, enabling selective excitation of 980nm pump light modes and facilitating closed-loop oscillation and transmission of 1550nm laser.

[18F]AlF-NOTA-PCP2: a novel PET/CT tracer for enhanced PD-L1 heterogeneity imaging and comparative analysis with [18F]AlF-NOTA-WL12 in glioblastoma xenografts.

PURPOSE: The unsatisfactory efficacy of PD-L1 antibodies in glioblastoma (GBM) is largely due to the temporal and spatial heterogeneity of PD-L1 expression. Molecular imaging can enhance understanding of the tumor immune microenvironment and guide immunotherapy. However, highly sensitive imaging agents capable of effectively visualizing PD-L1 heterogeneity are limited. This study introduces a novel PET tracer, offering improved imaging of PD-L1 heterogeneity in GBM xenografts, with a comparative analysis to [18F]AlF-NOTA-WL12. METHODS: [18F]AlF-NOTA-PCP2 was synthesized with high purity and its affinity for PD-L1 was characterized using surface plasmon resonance (SPR) and cell binding assays. Its specificity for PD-L1 was evaluated both in vitro using various cell lines and in vivo with GBM xenograft models in NOD/SCID mice. PET/CT imaging was conducted to evaluate the tracer's biodistribution, pharmacokinetics, and ability to quantify tumoral spatial heterogeneity of PD-L1 expression. A focused comparative analysis between [18F]AlF-NOTA-PCP2 and [18F]AlF-NOTA-WL12 was conducted, examining binding affinity, biodistribution, pharmacokinetics, and imaging effectiveness in GBM xenografts. Additionally, human radiation dosimetry estimates compared the safety profiles of both tracers. RESULTS: [18F]AlF-NOTA-PCP2 demonstrated high radiochemical purity (> 95%) and a strong affinity for PD-L1, comparable to [18F]AlF-NOTA-WL12. In vitro and in vivo studies confirmed its specificity for PD-L1, with increased uptake in PD-L1 expressing cells and tumors. Toxicological profiles indicated no significant abnormalities in serum biochemical indicators or major organ tissues. MicroPET/CT imaging showed [18F]AlF-NOTA-PCP2's effectiveness in visualizing PD-L1 expression levels and spatial heterogeneity in GBM xenografts. Comparative studies revealed [18F]AlF-NOTA-PCP2's improved pharmacokinetic properties, including higher tumor-to-blood ratios and lower nonspecific liver uptake, as well as reduced radiation exposure compared to [18F]AlF-NOTA-WL12. CONCLUSION: [18F]AlF-NOTA-PCP2 distinguishes itself as an exceptionally sensitive PET/CT tracer, adept at non-invasively and accurately quantifying PD-L1 expression and its spatial heterogeneity in tumors, especially in GBM. Its favorable pharmacokinetic properties, safety profile, and high affinity for PD-L1 highlight its potential for enhancing the precision of cancer immunotherapy and guiding individualized treatment strategies. While promising, its clinical translation, especially in brain imaging, necessitates further validation in clinical trials.

Systematic investigation of TetR-family transcriptional regulators and their roles on lignocellulosic inhibitor acetate tolerance in Zymomonas mobilis.

TetR-family transcriptional regulators are widely distributed among bacteria and involved in various cellular processes such as multidrug and inhibitor resistance. Zymomonas mobilis is a industrial bacterium for lignocellulosic ethanol production. Although TetR-family regulators and their associated RND-family efflux pumps in Z. mobilis have been identified to be differentially expressed under various inhibitors and stressful conditions, there are no systematic investigation yet. In this study, bioinformatic analyses indicated that there are three TetR-family transcriptional regulators (ZMO0281, ZMO0963, ZMO1547) and two RND-family efflux pumps (ZMO0282-0285, ZMO0964-0966) adjacent to corresponding TetR-family regulators of ZMO0281 and ZMO0963 in Z. mobilis. Genetics studies were then carried out with various mutants of TetR-family regulators constructed, and ZMO0281 was characterized to be related to acetate tolerance. Combining transcriptomics and dual-reporter gene system, this study demonstrated that three TetR-family regulators repressed their adjacent genes specifically. Moreover, TetR-family regulator ZMO0281 might also be involved in other cellular processes in the presence of acetate. In addition, the upregulation of RND-family efflux pumps due to ZMO0281 deletion might lead to an energy imbalance and decreased cell growth in Z. mobilis under acetate stress. The systematic investigation of all three TetR-family regulators and their roles on a major lignocellulosic inhibitor acetate tolerance in Z. mobilis thus not only unravels the molecular mechanisms of TetR-family regulators and their potential cross-talks on regulating RND-family efflux pumps and other genes in Z. mobilis, but also provides guidance on understanding the roles of multiple regulators of same family in Z. mobilis and other microorganisms for efficient lignocellulosic biochemical production.

Dynamic network biomarker C1QTNF1 regulates tumor formation at the tipping point of hepatocellular carcinoma.

Identifying the precise moment before the onset of hepatocellular carcinoma (HCC) remains a significant challenge in the medical field. The existing biomarkers fall short of pinpointing the critical point preceding HCC formation. This study aimed to determine the exact tipping point for the transition from cirrhosis to HCC, identify the core Dynamic Network Biomarker (DNB), and elucidate its regulatory effects on HCC. A spontaneous HCC mouse model was established to mimic HCC formation in patients with chronic hepatitis. Using the DNB method, C1q and tumor necrosis factor (TNF) related 1 (C1QTNF1) protein was identified as the key DNB at the crucial tipping time of spontaneous HCC development. Both in vitro and in vivo studies showed that C1QTNF1 could inhibit tumor growth. Overexpression of C1QTNF1 before the tipping point effectively prevented HCC occurrence. Patients with elevated C1QTNF1 expression demonstrated improved overall survival (OS) (P = 0.03) and disease-free survival (DFS) (P = 0.03). The diagnostic value of C1QTNF1 was comparable to that of alpha-fetoprotein (AFP) (area under the curve [AUC] = 0.84; sensitivity 85%; specificity 80%). Furthermore, our research indicated that platelet-expressed C1QTNF1 is involved in cancer-associated signaling pathways. Our findings introduce a novel perspective by highlighting C1QTNF1 as the pivotal biomarker at the tipping point of primary HCC formation using DNB. We propose C1QTNF1 as a prognostic biomarker for HCC, potentially influencing tumor development through a platelet-related cancer signaling pathway.

Cell-free DNA methylation profile potential in the diagnosis of lung squamous cell carcinoma.

Background: Aberrant methylation plays an essential role in early cancer development. In this study, we investigated methylation patterns in lung squamous cell carcinoma (LUSC) and matched non-tumor tissue and plasma samples to evaluate the potential of these patterns in the diagnosis of LUSC. Methods: The study group included 49 patients with stage I-III LUSC. We collected resected tumor tissue, paired peritumoral tissue, distant normal tissue, and corresponding plasma samples. A bespoke lung cancer bisulfite sequencing panel was used to profile the methylation level. Another 48 healthy volunteers provided control plasma samples. Results: Peritumoral and distant normal tissues presented similar methylation signatures, distinct from those in tumor tissue samples. A comparison of methylation profiles led to the identification of 871 tumor-specific differentially methylated blocks, including 847 hypermethylated and 24 hypomethylated blocks (adjusted P value <0.05). All top-ranked blocks were tumor-related. Tissue samples were analyzed for field cancerization to identify progressively aggravating aberrant methylations during tumor initiation and development. The analysis revealed that 221 blocks presented a stepwise increase in methylation levels, while seven blocks presented a stepwise decrease in methylation pattern as the sampling drew nearer to the tumor. The malignant contaminated ratio (MCR) confirmed the presence of distinct methylation patterns between tumor and peritumoral tissue samples. We then constructed a diagnostic panel using a combined diagnostic score of cell-free DNA (cfDNA) that showed high sensitivity and specificity. The healthy controls had a significantly lower combined diagnostic score (cd-score) than LUSC patients. Additionally, based on the methylation profiles, LUSC could be classified into two subgroups, C1 and C2. The methylation profile of the C2 group was not distinct from the healthy controls, which had a significantly lower cd-score than did the C1 group. Conclusions: LUSC-specific methylation patterns could potentially discriminate between peritumoral tissue, distant normal tumor tissue, and tumor tissues. This preliminary study also supported the potential utility of cfDNA methylation analysis in diagnosing LUSC.

PET Imaging of Peptide Probe Al[18F]F-NOTA-PCP1 for Monitoring the Engagement of PD-L1 Antibodies in Tumors.

Immune checkpoint inhibitors (ICIs) are a powerful treatment modality for various types of cancer. The effectiveness of ICIs is intimately connected to the binding status of antibodies to receptors. However, validated means to accurately evaluate target specificity and predict antibody efficacy in vivo are lacking. A novel peptide-based probe called Al[18F]F-NOTA-PCP1 was developed and validated for its specificity to PD-L1 in A549, U87MG, GL261, and GL261-iPDL1 cell lines, as well as in xenograft models. Then the probe was used in PET/CT scans to determine the binding status of PD-L1 antibodies (atezolizumab, avelumab, and durvalumab) in U87MG xenograft model mice. Moreover, Al[18F]F-NOTA-PCP1 was used to evaluate the impact of different treatment times and doses. Al[18F]F-NOTA-PCP1 PET/CT can be used to evaluate the interaction between PD-L1 and antibodies to determine the effectiveness of immunotherapy. By quantifying target engagement, the probe has the potential to predict the efficacy of immunotherapy and optimize the dose and treatment schedules for PD-L1 immunotherapy. This imaging agent could be a valuable tool in guiding personalized treatment strategies and improving cancer patient outcomes.

Neo-adjuvant chemotherapy plus immunotherapy in resectable N1/N2 NSCLC.

BACKGROUND: Locally advanced non-small cell lung cancer (NSCLC) with N1/N2 lymph node metastasis is challenging with poor survival. Neo-adjuvant chemo-immunotherapy has gained benefits in a proportion of these patients. However no specific biomarker has been proved to predict the effect before therapy. In addition, the relationship of nodal status and survival after neo-adjuvant chemo-immunotherapy is still not well stated. METHODS: A total of 75 resectable NSCLC patients with N1/N2 stage who received neo-adjuvant chemo-immunotherapy plus surgery were retrospectively studied. The clinical characteristics, surgical information and safety parameters were collected. The correlations of major pathological response (MPR) and pathological complete response (pCR) with clinical data were analyzed. The progression free disease(PFS) and overall survival(OS) were evaluated with pathological response and nodal status. RESULTS: Of the 75 patients, 69 (92%) patients experienced treatment related adverse effects, while grade 3-4 adverse effects occurred in 8 (10%) patients. All the patients received surgical R0 resection with a MPR rate of 60% and a pCR rate of 36%. 67% of N1 patients and 77% of N2 patients had nodal clearance after neo-adjuvant treatment. A significant difference was observed between pathological response with age, histology and multiple lymph node metastasis. The PFS was better in the MPR cohort. The PFS was 90.1% and 83.6% at the nodal clearance group at the time of 12 and 18 months, compared with 70.1% and 63.7% at the nodal residual group. CONCLUSIONS: The neo-adjuvant chemo-immunotherapy for locally advanced NSCLC with nodal positive was safe and feasible. The patients with elder age and squamous-cell carcinoma (SCC) were more likely to have better pathological response, while multiple nodal metastasis was a negative predictor. The clearance of lymph node resulted in significantly longer PFS and OS.

Risk factor analysis and prediction model for papillary thyroid carcinoma with lymph node metastasis.

Objective: We aimed to identify the clinical factors associated with lymph node metastasis (LNM) based on ultrasound characteristics and clinical data, and develop a nomogram for personalized clinical decision-making. Methods: A retrospective analysis was performed on 252 patients with papillary thyroid carcinoma (PTC). The patient's information was subjected to univariate and multivariate logistic regression analyses to identify risk factors. A nomogram to predict LNM was established combining the risk factors. The performance of the nomogram was evaluated using receiver operating characteristic (ROC) curve, calibration curve, cross-validation, decision curve analysis (DCA), and clinical impact curve. Results: There are significant differences between LNM and non-LNM groups in terms of age, sex, tumor size, hypoechoic halo around the nodule, thyroid capsule invasion, lymph node microcalcification, lymph node hyperechoic area, peak intensity of contrast (PI), and area under the curve (AUC) of the time intensity curve of contrast (P<0.05). Age, sex, thyroid capsule invasion, lymph node microcalcification were independent predictors of LNM and were used to establish the predictive nomogram. The ROC was 0.800, with excellent discrimination and calibration. The predictive accuracy of 0.757 and the Kappa value was 0.508. The calibration curve, DCA and calibration curve demonstrated that the prediction model had excellent net benefits and clinical practicability. Conclusion: Age, sex, thyroid capsule invasion, and lymph node microcalcification were identified as significant risk factors for predicting LNM in patients with PTC. The visualized nomogram model may assist clinicians in predicting the likelihood of LNM in patients with PTC prior to surgery.

N6 -methyladenosine-modified circSTX6 promotes hepatocellular carcinoma progression by regulating the HNRNPD/ATF3 axis and encoding a 144 amino acid polypeptide.

BACKGROUND: Circular RNAs (circRNAs) play a significant role in the initiation and progression of various cancers, including hepatocellular carcinoma (HCC). Circular syntaxin 6 (circSTX6, also known as hsa_circ_0007905) has been identified as a microRNA (miRNA) sponge in pancreatic adenocarcinoma. However, its full range of functions in terms of protein scaffold and translation remain largely unexplored in the context of HCC. METHODS: The expression of circSTX6 and its encoded protein was examined in HCC tumour tissues. N6 -methyladenosine (m6 A) on circSTX6 was verified and quantified by methylated RNA immunoprecipitation (Me-RIP), RIP and dual luciferase reporter assays. The biological functions of circSTX6 and its encoded protein in HCC were clarified by in vitro and in vivo experiments. Mechanistically, the interaction between circSTX6 and heterogeneous nuclear ribonucleoprotein D (HNRNPD) was investigated by RNA pull-down, RIP and fluorescence in situ hybridization (FISH)/IF. The regulatory effects of circSTX6 and HNRNPD on activating transcription factor 3 (ATF3) mRNA were determined by mRNA stability and RIP assays. Furthermore, the presence of circSTX6-encoded protein was verified by mass spectrometry. RESULTS: CircSTX6 and its encoded 144 amino acid polypeptide, circSTX6-144aa, were highly expressed in HCC tumour tissues and served as independent risk factors for overall survival in HCC patients. The expression of circSTX6 was regulated by METTL14 in an m6 A-dependent manner. Functionally, circSTX6 accelerated HCC proliferation and tumourigenicity and reinforced tumour metastasis in vitro and in vivo. Mechanistically, circSTX6 acted as a sponge for HNRNPD protein, facilitating its binding to ATF3 mRNA, consequently promoting ATF3 mRNA decay. Meanwhile, circSTX6-144aa promoted HCC proliferation, migration and invasion independent of circSTX6 itself. CONCLUSION: Collectively, our study reveals that m6 A-modified circSTX6 drives malignancy in HCC through the HNRNPD/ATF3 axis, while its encoded circSTX6-144aa contributes to HCC progression independent of circSTX6. CirSTX6 and its encoded protein hold promise as potential biomarkers and therapeutic targets in HCC.

Time course of changes in the transcriptome during russet induction in apple fruit.

BACKGROUND: Russeting is a major problem in many fruit crops. Russeting is caused by environmental factors such as wounding or moisture exposure of the fruit surface. Despite extensive research, the molecular sequence that triggers russet initiation remains unclear. Here, we present high-resolution transcriptomic data by controlled russet induction at very early stages of fruit development. During Phase I, a patch of the fruit surface is exposed to surface moisture. For Phase II, moisture exposure is terminated, and the formerly exposed surface remains dry. We targeted differentially expressed transcripts as soon as 24 h after russet induction. RESULTS: During moisture exposure (Phase I) of 'Pinova' apple, transcripts associated with the cell cycle, cell wall, and cuticle synthesis (SHN3) decrease, while those related to abiotic stress increase. NAC35 and MYB17 were the earliest induced genes during Phase I. They are therefore linked to the initial processes of cuticle microcracking. After moisture removal (Phase II), the expression of genes related to meristematic activity increased (WOX4 within 24 h, MYB84 within 48 h). Genes related to lignin synthesis (MYB52) and suberin synthesis (MYB93, WRKY56) were upregulated within 3 d after moisture removal. WOX4 and AP2B3 are the earliest differentially expressed genes induced in Phase II. They are therefore linked to early events in periderm formation. The expression profiles were consistent between two different seasons and mirrored differences in russet susceptibility in a comparison of cultivars. Furthermore, expression profiles during Phase II of moisture induction were largely identical to those following wounding. CONCLUSIONS: The combination of a unique controlled russet induction technique with high-resolution transcriptomic data allowed for the very first time to analyse the formation of cuticular microcracks and periderm in apple fruit immediately after the onset of triggering factors. This data provides valuable insights into the spatial-temporal dynamics of russeting, including the synthesis of cuticles, dedifferentiation of cells, and impregnation of cell walls with suberin and lignin.

Grading surface urban heat island and investigating factor weight based on interpretable deep learning model across global cities.

Significant urbanization resulted in increasing surface urban heat island (SUHI) that caused negative impacts on urban ecological environment, and residential comfort. Accurately monitoring the spatiotemporal variations and understanding controls of SUHI were essential to propose effective mitigation measurements. However, SUHI grades across global cities remained unknown, which cloud greatly support for global mitigations. Additionally, quantitative evaluating factor weights for different SUHI indicators and grades worldwide remained further investigations. Therefore, this paper proposed SUHI grading based on agglomerative hierarchical clustering, and further quantified factor weights for different indicators and grades based on an interoperable machine learning named TabNet. There were three major findings. (1) Global cities were grouped into five grades, including SUCI (surface urban cool island), insignificant, low-value, medium-value, and high-value SUHI grades, indicating significant differences among different grades. SUHI grades showed significant climate-based variations, wherein the arid climate was dominated by the SUCI grade at daytime but the high-value grade at nighttime. (2) Vegetation difference was an important factor for daytime SUHII accounting for 27%. Daytime frequency of SUHI was controlled by vegetation difference, temperature, evaporation and nighttime light, accounting for 78%. The major factors for nighttime frequency were albedo differences and nighttime light, accounting for 45%. (3) Related factors contributed differently to various SUHI grades. The weight of △EVI for daytime SUHII gradually increased with grades, while it for daytime frequency and maximum duration of SUHI decreased with grades. The nighttime SUHII of the low-value grade was greatly affected by the background climate, while that of the medium-value and high-value grades were strongly impacted by anthropogenic heat flux. The diurnal contrast of grades and coupling effects with heat wave were further discussed. This paper aimed to provide information on grades and controls of SUHI for further mitigation proposal.

An overview of current advances of PD-L1 targeting immuno-imaging in cancers.

The programmed death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) pathway plays a significant role in immune evasion. PD-1 or PD-L1 immune checkpoint inhibitors (ICIs) have become a standard treatment for multiple types of cancer. To date, PD-L1 has served as a biomarker for predicting the efficacy of ICIs in several cancers. The need to establish an effective detection method that could visualize PD-L1 expression and predict the efficacy of PD-1/PD-L1 ICIs has promoted a search for new imaging strategies. PD-L1-targeting immuno-imaging could provide a noninvasive, real-time, repeatable, dynamic, and quantitative assessment of the characteristics of all tumor lesions in individual patients. This study analyzed the existing evidence in the literature on PD-L1-based immuno-imaging (2015-2022). Original English-language articles were searched using PubMed and Google Scholar. Keywords, such as "PD-L1," "PET," "SPECT," "PET/CT," and "SPECT/CT," were used in various combinations. A total of nearly 50 preclinical and clinical studies of PD-L1-targeting immuno-imaging were selected, reviewed, and included in this study. Therefore, in this review, we conducted a study of the advances in PD-L1-targeting immuno-imaging for detecting the expression of PD-L1 and the efficacy of ICIs. We focused on the different types of PD-L1-targeting agents, including antibodies and small PD-L1-binding agents, and illustrated the strength and weakness of these probes. Furthermore, we summarized the trends in the development of PD-L1-targeting immuno-imaging, as well as the current challenges and future directions for clinical workflow.

The current advances and future directions of PD-1/PD-L1 blockade in head and neck squamous cell carcinoma (HNSCC) in the era of immunotherapy.

Immune checkpoint inhibitors (ICIs) have previously demonstrated their efficacy and safety in various solid tumors, and with the growing interest in the application of ICIs in head and neck squamous cell carcinoma (HNSCC), various data have been reported. Mechanistically, HNSCC cells express programmed death ligand 1 (PD-L1), which binds to its receptor programmed death 1 (PD-1). Immune escape plays a key role in disease initiation and progression. Studying the abnormal activation of related pathways of PD-1/PD-L1 will help to understand the way of immunotherapy and find the advantageous population of immunotherapy. How to reduce HNSCC-related mortality and morbidity in this process has promoted the search for new therapeutic strategies, especially in the era of immunotherapy. PD-1 inhibitors have demonstrated significant prolongation of survival in recurrent/metastatic (R/M) HNSCC with a favorable safety profile. It also holds great promise in locally advanced (LA) HNSCC, where numerous studies are underway. Although immunotherapy has made great progress in HNSCC research, there are still many challenges. Therefore, in the review, we conducted an in-depth study on the expression of PD-L1 and the regulatory, immunosuppressive mechanisms caused by PD-L1, especially in head and neck squamous cell carcinoma, which is different from other tumors. And further summarize the situation, challenges and development trends of PD-1 and PD-L1 blockade in clinical practice.

m6A-modification regulated circ-CCT3 acts as the sponge of miR-378a-3p to promote hepatocellular carcinoma progression.

Background: Circular RNA (circRNA) plays a critical role in tumour progression. Circ-CCT3, a particularly abundant circRNA, was proposed to be involved in tumorigenesis. However, the role of circ-CCT3 in hepatocellular carcinoma remains elusive.Methods: Here, circ-CCT3 (a circRNA derived from exons 3, 4 and 5 of the CCT3 gene, hsa_circ_0004680) was identified by circRNA microarray and validated by qRT-PCR. RNA immunoprecipitation (RIP) was performed to confirm the binding between ALKBH5 along with METTL3 and circ-CCT3. Methylated RNA Immunoprecipitation (MeRIP) was used to detect the N6-methyladenosine (m 2A) levels of circ-CCT3. CircRNAs in vivo precipitation, luciferase reporter assay, biotin-coupled microRNA capture, and fluorescence in situ hybridization were conducted to assess the interaction between circ-CCT3 and miR-378a-3p. The functions of circ-CCT3 in HCC were evaluated both in vitro and in vivo.Results: We demonstrated that circ-CCT3 was highly expressed in HCC which indicated the poor prognosis. Circ-CCT3 expression served as an independent risk factor for overall survival in patients with HCC. Knocking-down of circ-CCT3 inhibited the proliferation, invasion and migration of HCC cells, and angiogenesis of HUVEC. Mechanistically, ALKBH5 and METTL3 could bind and regulate m A-modification of circ-CCT3. Further, circ-CCT3 upregulated the expression of FLT-1 by sponging miR-378a-3p.Conclusions: Circ-CCT3 was significantly up-regulated in HCC and promoted liver cancer development via miR-378a-3p-FLT1 axis. It was also found that circ-CCT3 was under m A-modification mediated by ALKBH5 and METTL3. Our study highlights circ-CCT3 as a potential therapeutic target of HCC treatment, which provides a novel understanding on mechanisms of circRNAs in HCC progression.

Adaptive Laboratory Evolution and Metabolic Engineering of Zymomonas mobilis for Bioethanol Production Using Molasses.

Molasses with abundant sugars is widely used for bioethanol production. Although the ethanologenic bacterium Zymomonas mobilis can use glucose, fructose, and sucrose for ethanol production, levan production from sucrose reduces the ethanol yield of molasses fermentation. To increase ethanol production from sucrose-rich molasses, Z. mobilis was adapted in molasses, sucrose, and fructose in parallel. Adaptation in fructose is the most effective route to generate an evolved strain F74 with improved molasses utilization, which is majorly due to a G99S mutation in Glf for enhanced fructose import. Subsequent sacB deletion and sacC overexpression in F74 to divert sucrose metabolism from levan production to ethanol production further enhanced ethanol productivity 28.6% to 1.35 g/L/h. The efficient utilization of molasses by diverting sucrose metabolic flux through adaptation and genome engineering not only generated an excellent ethanol producer using molasses but also provided the strategy for developing microbial cell factories.