New clinical trial design in precision medicine: discovery, development and direction.

In the era of precision medicine, it has been increasingly recognized that individuals with a certain disease are complex and different from each other. Due to the underestimation of the significant heterogeneity across participants in traditional "one-size-fits-all" trials, patient-centered trials that could provide optimal therapy customization to individuals with specific biomarkers were developed including the basket, umbrella, and platform trial designs under the master protocol framework. In recent years, the successive FDA approval of indications based on biomarker-guided master protocol designs has demonstrated that these new clinical trials are ushering in tremendous opportunities. Despite the rapid increase in the number of basket, umbrella, and platform trials, the current clinical and research understanding of these new trial designs, as compared with traditional trial designs, remains limited. The majority of the research focuses on methodologies, and there is a lack of in-depth insight concerning the underlying biological logic of these new clinical trial designs. Therefore, we provide this comprehensive review of the discovery and development of basket, umbrella, and platform trials and their underlying logic from the perspective of precision medicine. Meanwhile, we discuss future directions on the potential development of these new clinical design in view of the "Precision Pro", "Dynamic Precision", and "Intelligent Precision". This review would assist trial-related researchers to enhance the innovation and feasibility of clinical trial designs by expounding the underlying logic, which be essential to accelerate the progression of precision medicine.

Solid Additive Dual-Regulates Spectral Response Enabling High-Performance Semitransparent Organic Solar Cells.

Semi-transparent organic solar cells (ST-OSCs) possess significant potential for applications in vehicles and buildings due to their distinctive visual transparency. Conventional device engineering strategies are typically used to optimize photon selection and utilization at the expense of power conversion efficiency (PCE); moreover, the fixed spectral utilization range always imposes an unsatisfactory upper limit to its light utilization efficiency (LUE). Herein, a novel solid additive named 1,3-diphenoxybenzene (DB) is employed to dual-regulate donor/acceptor molecular aggregation and crystallinity, which effectively broadens the spectral response of ST-OSCs in near-infrared region. Besides, more visible light is allowed to pass through the devices, which enables ST-OSCs to possess satisfactory photocurrent and high average visible transmittance (AVT) simultaneously. Consequently, the optimal ST-OSC based on PP2+DB/BTP-eC9+DB achieves a superior LUE of 4.77%, representing the highest value within AVT range of 40-50%, which also correlates with the formation of multi-scale phase-separated morphology. Such results indicate that the ST-OSCs can simultaneously meet the requirements for minimum commercial efficiency and plant photosynthesis when integrated with the roofs of agricultural greenhouses. This work emphasizes the significance of additives to tune the spectral response in ST-OSCs, and charts the way for organic photovoltaics in economically sustainable agricultural development.

Preparation of superhydrophobic sponge and its application in oil-water separation and treatment of polymer-containing wastewater.

At present, the application prospect of superhydrophobic materials in oil-water separation, an-tibacterial and other aspects have attracted more and more attention. However, preparing a simple and low-cost superhydrophobic material remains a challenge. Using acetone as solvent, candle soot, silver/silica nanoparticles and polydimethylsiloxane were uniformly mixed to form a mixed solution, and the superhydrophobic sponge was successfully prepared by spraying method. The results show that the superhydrophobic sponge has high water contact Angle (162°) and excellent oil-water separation efficiency, which can realize effective treatment of polymerized wastewater. In addition, the superhydrophobic sponge showed better antibacterial properties on the surface of Escherichia coli and Staphylococcus aureus. In this work, a simple way to prepare superhydro-phobic oil-water separation material is proposed. The preparation process is green, the material is easy to obtain, and it is expected to be widely used in practical production.

Green-Processed Non-Fullerene Organic Solar Cells Based on Y-Series Acceptors.

The development of environmentally friendly and sustainable processes for the production of high-performance organic solar cells (OSCs) has become a critical research area. Currently, Y-series electron acceptors are widely used in high-performance OSCs, achieving power conversion efficiencies above 19%. However, these acceptors have large fused conjugated backbones that are well-soluble in halogenated solvents, such as chloroform and chlorobenzene, but have poor solubility in non-halogenated green solvents. To overcome this challenge, recent studies have focused on developing green-processed OSCs that use non-chlorinated and non-aromatic solvents to dissolve bulk-heterojunction photoactive layers based on Y-series electron acceptors, enabling environmentally friendly fabrication. In this comprehensive review, an overview of recent progress in green-processed OSCs based on Y-series acceptors is provided, covering the determination of Hansen solubility parameters, the use of non-chlorinated solvents, and the dispersion of conjugated nanoparticles in water/alcohol. It is hoped that the timely review will inspire researchers to develop new ideas and approaches in this important field, ultimately leading to the practical application of OSCs.

Optimized spatial and temporal pattern for coral bleaching heat stress alerts for China's coral reefs.

Most studies on coral bleaching alerts use common Degree Heating Week (DHW) thresholds; however, these may underestimate historical patterns of heat stress for coral reef ecosystems. Taking an optimized DHW threshold for coral bleaching alerts for Coral Reef Watch (CRW) and Coral Reef Temperature Anomaly Database (CoRTAD) products, we analyzed the precise spatial and temporal pattern of heat stress on China's coral reefs from 2010 to 2021 in the South China Sea (SCS) and the Beibu Gulf (BG). We compared acute heat stress using common and optimized thresholds. Results indicated that the ocean warming rate in 2010-2021 was approximately 0.43 ± 0.22 °C/10a, showing a significant increase in the northern SCS and the BG. More severe bleaching events were predicted by the optimized thresholds and the high-frequency areas were mainly in the northern SCS. The number and intensity of years with severe heat stress anomalies was in the order 2020 > 2014 > 2010 > 2015. Heat stress duration was the longest in the Xisha Islands among offshore archipelagos, and longest in 2020-2021 in Weizhou Island in BG in the relative high-latitude inshore reefs. These abnormal events were mainly caused by El Niño, but La Niña was also involved in 2020.

The Regulation Network of Glycerolipid Metabolism as Coregulators of Immunotherapy-Related Myocarditis.

Background: To date, immunotherapy for patients with malignant tumors has shown a significant association with myocarditis. However, the mechanism of metabolic reprogramming changes for immunotherapy-related cardiotoxicity is still not well understood. Methods: The CD45+ single-cell RNA sequencing (scRNA-seq) of the Pdcd1-/-Ctla4+/- and wild-type mouse heart in GSE213486 was downloaded to demonstrate the heterogeneity of immunocyte atlas in immunotherapy-related myocarditis. The liquid chromatography-tandem mass spectrometry (LC-MS/MS) spectrum metabolomics analysis detects the metabolic network differences. The drug prediction, organelle level interaction, mitochondrial level regulatory network, and phosphorylation site prediction for key regulators have also been screened via multibioinformatics analysis methods. Results: The scRNA analysis shows that the T cell is the main regulatory cell subpopulation in the pathological progress of immunotherapy-related myocarditis. Mitochondrial regulation pathway significantly participated in pseudotime trajectory- (PTT-) related differential expressed genes (DEGs) in the T cell subpopulation. Additionally, both the gene set enrichment analysis (GSEA) of PTT-related DEGs and LC-MS/MS metabolomics analysis showed that mitochondrial-regulated glycerolipid metabolism plays a central role in metabolic reprogramming changes for immunotherapy-related cardiotoxicity. Finally, the hub-regulated protease of diacylglycerol kinase zeta (Dgkz) was significantly identified and widely played various roles in glycerolipid metabolism, oxidative phosphorylation, and lipid kinase activation. Conclusion: Mitochondrial-regulated glycerolipid metabolism, especially the DGKZ protein, plays a key role in the metabolic reprogramming of immunotherapy-related myocarditis.

Directly Cross-Linked Conjugated Polymer Donor Enables Efficient Polymer Solar Cells with Extraordinary Mechanical Robustness.

A cross-linking strategy can result in a three-dimensional network of interconnected chains for the copolymers, thereby improving their mechanical performance. In this work, a series of cross-linked conjugated copolymers, named PC2, PC5, and PC8, constructed with different ratios of monomers are designed and synthesized. For comparison, a random linear copolymer, PR2 is also synthesized based on the similar monomers. When blended with Y6 acceptor, the cross-linked polymers PC2, PC5, and PC8-based polymer solar cells (PSCs) achieve superior power conversion efficiencies (PCEs) of 17.58%, 17.02%, and 16.12%, respectively, which are higher than that (15.84%) of the random copolymer PR2-based devices. Moreover, the PCE of PC2:Y6-based flexible PSC retains ≈88% of the initial efficiency value after 2000 bending cycles, overwhelming the PR2:Y6-based device with the remaining 12.8% of the initial PCE. These results demonstrate that the cross-linking strategy is a feasible and facile approach to developing high-performance polymer donors for the fabrication of flexible PSCs.

[Corrigendum] Crocetin induces apoptosis of BGC­823 human gastric cancer cells.

Following the publication of the above article, an interested reader drew to the authors' attention that Fig. 2 (showing morphological characteristics of cultured BGC­823 cells as visualized by microscopic analysis) and Fig. 3 (showing crocetin­induced apoptosis of the BGC­823 cells) on p. 523 appeared to feature panels containing overlapping data. The authors re­examined their original data, and realized that inadvertent errors were made during the compilation of these figures; specifically, the data shown in Fig. 2C (for the the 5­µM docetaxel group) and Fig. 3D (for the DMSO group) were selected incorrectly. The corrected versions of Figs. 2 and 3 are shown below and on the next page, now featuring the correct data for Figs. 2C and 3D. All the authors agree with the publication of this corrigendum, and are grateful of the Editor of Molecular Medicine Reports for granting them the opportunity to publish this. Furthermore, they regret that these errors were introduced into the paper, even though they did not substantially alter any of the major conclusions reported in the paper, and apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 9: 521­526, 2014; DOI: 10.3892/mmr.2013.1851].

Pan-cancer efficacy and safety of anlotinib plus PD-1 inhibitor in refractory solid tumor: A single-arm, open-label, phase II trial.

The combination of immunotherapy and antiangiogenic agents for the treatment of refractory solid tumor has not been well investigated. Thus, our study aimed to evaluate the efficacy and safety of a new regimen of anlotinib plus PD-1 inhibitor to treat refractory solid tumor. APICAL-RST is an investigator-initiated, open-label, single-arm, phase II trial in patients with heavily treated, refractory, metastatic solid tumor. Eligible patients experienced disease progression during prior therapy without further effective regimen. All patients received anlotinib and PD-1 inhibitor. The primary endpoints were objective response and disease control rates. The secondary endpoints included the ratio of progression-free survival 2 (PFS2)/PFS1, overall survival (OS) and safety. Forty-one patients were recruited in our study; 9 patients achieved a confirmed partial response and 21 patients had stable disease. Objective response rate and disease control rate were 22.0% and 73.2% in the intention-to-treat cohort, and 24.3% and 81.1% in the efficacy-evaluable cohort, respectively. A total of 63.4% (95% confidence interval [CI]: 46.9%-77.4%) of the patients (26/41) presented PFS2/PFS1 >1.3. The median OS was 16.8 months (range: 8.23-24.4), and the 12- and 36-month OS rates were 62.8% and 28.9%, respectively. No significant association was observed between concomitant mutation and efficacy. Thirty-one (75.6%) patients experienced at least one treatment-related adverse event. The most common adverse events were hypothyroidism, hand-foot syndrome and malaise. This phase II trial showed that anlotinib plus PD-1 inhibitor exhibits favorable efficacy and tolerability in patients with refractory solid tumor.

Longitudinal Through-Hole Architecture for Efficient and Thickness-Insensitive Semitransparent Organic Solar Cells.

Semi-transparent organic solar cells (ST-OSCs) have great potential for application in vehicle- or building-integrated solar energy harvesting. Ultrathin active layers and electrodes are typically utilized to guarantee high power conversion efficiency (PCE) and high average visible transmittance (AVT) simultaneously; however, such ultrathin parts are unsuitable for industrial high-throughput manufacturing. In this study, ST-OSCs are fabricated using a longitudinal through-hole architecture to achieve functional region division and to eliminate the dependence on ultrathin films. A complete circuit that vertically corresponds to the silver grid is responsible for obtaining high PCE, and the longitudinal through-holes embedded in it allow most of the light to pass through,where the overall transparency is associated with the through-hole specification rather than the thicknesses of active layer and electrode. Excellent photovoltaic performance over a wide range of transparency (9.80-60.03%), with PCEs ranging from 6.04% to 15.34% is achieved. More critically, this architecture allows printable 300-nm-thick devices to achieve a record-breaking light utilization efficiency (LUE) of 3.25%, and enables flexible ST-OSCs to exhibit better flexural endurance by dispersing the extrusion stress into the through-holes. This study paves the way for fabricating high-performance ST-OSCs and shows great promise for the commercialization of organic photovoltaics.

Acquired EML4-ALK fusion and EGFR C797S in cis mutation as resistance mechanisms to osimertinib in a non-small cell lung cancer patient with EGFR L858R/T790M.

The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) dramatically improve the clinical outcomes of non-small cell lung cancer (NSCLC) patients harboring EGFR -sensitive mutations. Despite the remarkable efficacy of first-and second-generation EGFR TKIs, disease relapse is inevitable. EGFR T790M mutation is a primary contributor to the acquired resistance to first- and second-generation EGFR TKIs. Osimertinib, which is an irreversible third-generation EGFR TKI, was designed for EGFR -activating mutations as well as the EGFR T790M mutation in patients with advanced NSCLC and has demonstrated a convincing efficacy. However, acquired resistance to osimertinib after treatment inevitably occurs. The acquired resistance mechanisms to osimertinib are highly complicated and not fully understood, encompassing EGFR -dependent as well as EGFR -independent mechanisms. Treatment approaches for patients progressing from osimertinib have not been established. We present a case of a stage IV lung adenocarcinoma patient harboring EGFR L858R, acquired T790M after treatment with first-line gefitinib. She then acquired a new EML4-ALK gene fusion after treatment with osimertinib. A combination targeted therapy of osimertinib plus alectinib was initiated, with a progression-free survival of 5 months without any serious adverse reaction. After disease progression, EGFR C797S in cis was detected with a loss of the EML4-ALK fusion by targeted next-generation sequencing. Then therapy was changed to pemetrexed combined with bevacizumab plus camrelizumab, but no obvious effect was observed. The patient had achieved an overall survival of 31 months. As far as we know, this was the first reported case that an EGFR -mutant NSCLC patient-acquired ALK fusion mediating resistance to osimertinib, and sequential EGFR C797S mutation mediating resistance to combined targeted therapy with osimertinib and alectinib. Our case shows that EML4-ALK fusion is a rare but critical resistance mechanism to osimertinib, and C797S mutation in cis may be an underlying mechanism of acquired resistance mutation in double TKIs therapy. Furthermore, molecular detection and rebiopsy play important roles in the selection of therapeutic strategies when the disease progresses.

Distinct binding pattern of EZH2 and JARID2 on RNAs and DNAs in hepatocellular carcinoma development.

Hepatocellular carcinoma (HCC) is one of the most malignant cancers worldwide, with high mortality. However, the molecular regulatory mechanisms of liver cancer, especially transcriptional and post-transcriptional mechanisms, should be further studied. Here we used chromatin and cross-linking immunoprecipitation with high throughput sequencing methods (ChIP-seq and CLIP-seq) to capture the global binding profiles on RNAs and DNAs of Enhancer of zeste homolog 2 (EZH2) and its partner Jumonji And AT-Rich Interaction Domain Containing 2 (JARID2) in liver carcinoma cell lines (HepG2) and normal liver cell line (THLE-2), respectively. We also integrated HCC transcriptome data from the TCGA to analyze the expression pattern of bound genes. We found that EZH2 and JARID2 both showed distinct binding profiles between HepG2 and THLE-2 cells. By binding to the primary RNAs, bound transcripts of EZH2 and JARID2 in HepG2 showed significantly increased transcriptional levels in HCC patients. By performing gene set enrichment analysis (GSEA), the bound transcripts were also highly related to HCC development. We also found EZH2 and JARID2 could specifically bind to several long noncoding RNAs (lncRNAs), including H19. By exploring the DNA binding profile, we detected a dramatically repressed DNA binding ability of EZH2 in HepG2 cells. We also found that the EZH2-bound genes showed slightly increased transcriptional levels in HepG2 cells. Integrating analysis of the RNA and DNA binding profiles suggests EZH2 and JARID2 shift their binding ability from DNA to RNA in HepG2 cells to promote cancer development in HCC. Our study provided a comprehensive and distinct binding profile on RNAs and DNAs of EZH2 and JARID2 in liver cancer cell lines, suggesting their potential novel functional manners to promote HCC development.

LncRNA CRNDE is involved in radiation resistance in hepatocellular carcinoma via modulating the SP1/PDK1 axis.

Hepatocellular carcinoma (HCC) is defined as a universal malignancy while radiation therapy is the effective treatment for it. This study validated the mechanism of long non-coding RNA (lncRNA) colorectal neoplasia differentially expressed gene (CRNDE) in radiation resistance in HCC. LncRNA CRNDE upregulation was detected in HCC cells. The radiation-resistant cell strains Huh7R and SNU-387R were established. After silencing lncRNA CRNDE, the cell colony formation ability, cell activity, apoptosis, cell cycles, and γ-H2AX positive rate in Huh7R and SNU-387R were detected. Silencing lncRNA CRNDE decreased the cell activity, colony formation ability, and cell number in the G2 phase and facilitated DNA damage and apoptosis. The binding relations of specificity protein 1 (SP1) with lncRNA CRNDE and 3-phosphoinositide dependent protein kinase 1 (PDK1) were verified. LncRNA CRNDE regulated PDK1 transcription by binding to transcription factor SP1. PDK1 overexpression partially reversed the inhibition of silencing lncRNA CRNDE on radiation resistance in HCC cells. The transplanted tumor mouse model was established and showed that silencing lncRNA CRNDE decreased tumor volume and weight and Ki67-positive cells in HCC mice in vivo. Collectively, lncRNA CRNDE was upregulated in HCC cells and promoted PDK1 transcription by binding to SP1, thus enhancing radiation resistance in HCC cells.

MiR-132-3p inhibits proliferation, invasion and migration of colorectal cancer cells via down-regulating FOXP2 expression.

OBJECTIVE: colorectal cancer (CRC) is a common cancer with high mortality. This study aimed to investigate the role of microRNA (miR)-132-3p on proliferation, invasion and migration of CRC cells. MATERIALS AND METHODS: qRT-PCR and Western blot analyses were used to determine the expression of miR-132-3p and forking box (FOX) protein 2 (FOXP2) in CRC cell line CACO-2. The expression of miR-132-3p and FOX was regulated using miR inhibitor and siRNA, and the viability and migration ability of the transfected cells were assessed. Cell cycle dependent kinase (CDK) 1, cyclin D1, matrix metalloproteinase (MMP)-2 and MMP-9 were detected using Western blots. The dual luciferase reporter gene assays were used to verify the targeting of miR-132-3p to FOXP2. RESULTS: Compared with control cells, FOXP2 and miR-132-3p expressions were decreased or increased significantly (P<0.05), respectively in CACO-2 cells. Up-regulation of miR-132-3p effectively inhibited the proliferation, migration and invasion of CACO-2 cells, and suppressed the expression of FORX2, cyclin-dependent kinase 1 (CDK1), cyclin D1, MMP-2 and MMP-9. Luciferase reporter gene assays reveled that FOXP2 expression was negatively regulated by miR-132-3p. Knockdown of FOXP2 using siRNA significantly reduced the proliferation and migration of CACO-2 cells, down-regulated the expression FOXP2 as well as CDK1, cyclin D1, MMP-2 and MMP-9. Since FOXP2 is targeted by miR-132-3p, it is likely that miR-132-3p-mediated reduction of proliferation and migration of CACO-2 cells was achieved via reduced translation of FOXP2 mRNA. CONCLUSIONS: miR-132-3p inhibits the proliferation, migration and invasion of CRC cells. This is likely achieved via negative regulation of the targeted FOXP2 expression. This role may be further explored for therapeutic applications in CRC.

Changes of Intestinal Microflora in Colorectal Cancer Patients after Surgical Resection and Chemotherapy.

OBJECTIVE: The change of bacterial flora structure in colorectal cancer (CRC) patients after treatment is not clear. The aim of this study was to explore the change and function of intestinal microflora in CRC before and after treatment. METHOD: The 16S conserved region V3+V4 of intestinal flora obtained from CRC patients was sequenced and analyzed. Alpha and beta diversity indices were used to analyze the abundance and structure of gut flora. FAPROTAX, BugBase, and Tax4Fun software were used to analyze the species phenotypes and Kyoto Encyclopedia of Genes and Genomes Ontology (KO) function pathways. RESULTS: Total abundance and structure of species in CRC patients were significantly increased compared with healthy people (control group) (P < 0.05), but there was no significant difference between CRC patients before and after treatment (P > 0.05). There was significant difference in relative abundance of bacteria at different levels (phylum, class, order, family, genus, and species) between the CRC group with after operation (CRC_O group) and chemotherapy (CRC_C group) treatment, particularly Prevotellaceae_UCG-001, Akkermansia, Fusicatenibacter, Tyzzerella_4, Megamonas, etc. in genus level. The KO function analysis showed that most of the bacteria with differences were mainly involved in the biosynthesis of lipopolysaccharide (Megamonas, Megasphaera, and Ruminococcus torques_group), protein digestion and absorption, renin-angiotensin system pathway (Akkermansia, Eubacterium_ruminantium_group, and Eubacterium_nodatum_group genus), adipocytokine signaling pathway and peroxisome pathway (Tyzzerella_4, Phascolarctobacterium, Ruminococcus_gnavus_group), and so on. CONCLUSION: The abundance of intestinal microflora in CRC patients was increased significantly contrasted to healthy people, and surgery and chemotherapy were hard to reduce this phenomenon. Megamonas was involved in lipopolysaccharide biosynthesis and carcinogenesis in colorectal cancer. Surgery and drug treatment did not reduced lipopolysaccharide biosynthesis but increased the number of probiotic Akkermansia population and reduced the pathogenic bacteria Tyzzerella_4, participate in adipocytokine signaling pathway, and affect metabolism.

Defect Passivation Effect of Chemical Groups on Perovskite Solar Cells.

Defect passivation is a key strategy to prepare high-performance perovskite solar cells (PVSCs). Even though abundant passivation molecules have been applied, the absence of detailed researches with regard to different functional groups in polymer additives may inevitably impede the establishment of passivation molecules selection rules. In this work, three passivation molecules including poly(vinyl alcohol) (PVA), polymethyl acrylate (PMA), and poly(acrylic acid) (PAA) are employed to systematically analyze the passivation effect from hydroxyl, carbonyl, and carboxyl groups. In general, PVA (-OH) can form hydrogen bonds with perovskite and PMA (-C═O) can complex with uncoordinated Pb2+. Specifically, PAA (-COOH) can interact selectively with MA+ and I- ions via hydrogen bonding and complex with uncoordinated Pb2+ to passivate defects more effectively. Hence, the PAA-incorporated PVSCs based on MAPbI3 achieve the champion power conversion efficiency (PCE) of 20.29% with open-circuit voltage up to 1.13 V. In addition, PAA cross-linking perovskite grains can relieve mechanical stress, as well as occupy the major channels to suppress ion migration and water/oxygen erosion. The corresponding unencapsulated devices demonstrate a superior light soaking stability, retaining more than 80% of the original PCE under one sun illumination for 1000 h.

Prognostic value of tumor mutation burden in patients with advanced gastric cancer receiving first-line chemotherapy.

Background: Tumor mutation burden (TMB) is a promising biomarker positively associated with the benefit of immunotherapy and that might predict the outcome of chemotherapy. We described the prognostic value of TMB in advanced gastric cancer and explored the underlying mechanism. Methods: We enrolled 155 TMB-evaluated advanced gastric cancer patients and analyzed the relationship between clinicopathological characteristics and both overall survival (OS) and progression-free survival (PFS) among 40 patients treated with first-line chemotherapy. We further verified the distribution of TMB and analyzed the potential mechanism underlying the prognosis based on The Cancer Genome Atlas (TCGA) database. Results: Among the 155 patients, 29 (18.7%) were TMB-high (TMB ≥ 10), roughly the same as the proportion in the TCGA data. Of the 40 patients receiving first-line chemotherapy, the median OS (7.9 vs. 12.1 months; HR 3.18; p = 0.0056) and PFS (4.4 vs. 6.2 months; HR 2.94; p = 0.0099) of the tissue-tested TMB (tTMB)-high patients were inferior to those of the tTMB-low patients. Similarly, unfavorable median OS (9.9 vs. 12.1 months; HR 2.11; p = 0.028) and PFS (5.3 vs. 6.5 months; HR 2.49; p = 0.0054) were shown in the blood-tested TMB (bTMB)-high than in the bTMB-low patients. The Cox analysis demonstrated that both tTMB-high and bTMB-high were significant independent predictors of dreadful OS and PFS. The differentially expressed genes (DEGs) according to TMB status were most significantly enriched in the downregulated metabolic pathway among the TMB-high patients. Conclusions: TMB-high advanced gastric cancer patients accounted for around one-sixth and had a poorer prognosis than TMB-low patients when treated with first-line chemotherapy. The potential mechanism might be the downregulated metabolic activity in TMB-high patients.

Low microRNA150 expression is associated with activated carcinogenic pathways and a poor prognosis in patients with breast cancer.

Breast cancer is the most common type of cancer amongst women worldwide, and numerous microRNAs (miRNAs/miRs) are involved in the initiation and progression of breast cancer. The aim of the present study was to identify hub miRNAs and determine the underlying mechanisms regulated by these miRNAs in breast cancer. Breast invasive carcinoma transcriptome data (including mRNAs and miRNAs), and clinical data were acquired from The Cancer Genome Atlas database. Differential gene expression analysis, co­expression network analysis, gene set enrichment analysis (GSEA) and prognosis analysis were used to screen the hub miRNAs and explore their functions. Functional experiments were used to determine the underlying mechanisms of the hub miRNAs in breast cancer cells. The results revealed that low miR150 expression predicted a more advanced disease stage, and was associated with a less favorable prognosis. Through the combined use of five miRNA­target gene prediction tools, 31 potential miR150 target genes were identified. GSEA revealed that low miR150 expression was associated with the upregulation of several cancer­associated signaling pathways, and the downregulation of several tumor suppressor genes. Furthermore, miR150 independently affected overall survival in patients, and interacted with its target genes to indirectly affect overall and disease­free survival. Functional experiments demonstrated that miR150 positively regulated B and T lymphocyte attenuator (BTLA), and the downregulation of miR150 and BTLA combined promoted cell migration. In conclusion, the present study revealed that low miR150 expression was associated with less favorable clinical features, upregulation of several carcinogenic signaling pathways, and poor patient survival. Additionally, a miR150­BTLA axis was suggested to regulate cell viability and migration.

Retinal Vessel Segmentation by Deep Residual Learning with Wide Activation.

PURPOSE: Retinal blood vessel image segmentation is an important step in ophthalmological analysis. However, it is difficult to segment small vessels accurately because of low contrast and complex feature information of blood vessels. The objective of this study is to develop an improved retinal blood vessel segmentation structure (WA-Net) to overcome these challenges. METHODS: This paper mainly focuses on the width of deep learning. The channels of the ResNet block were broadened to propagate more low-level features, and the identity mapping pathway was slimmed to maintain parameter complexity. A residual atrous spatial pyramid module was used to capture the retinal vessels at various scales. We applied weight normalization to eliminate the impacts of the mini-batch and improve segmentation accuracy. The experiments were performed on the DRIVE and STARE datasets. To show the generalizability of WA-Net, we performed cross-training between datasets. RESULTS: The global accuracy and specificity within datasets were 95.66% and 96.45% and 98.13% and 98.71%, respectively. The accuracy and area under the curve of the interdataset diverged only by 1%∼2% compared with the performance of the corresponding intradataset. CONCLUSION: All the results show that WA-Net extracts more detailed blood vessels and shows superior performance on retinal blood vessel segmentation tasks.

Controlling Crystal Growth via an Autonomously Longitudinal Scaffold for Planar Perovskite Solar Cells.

Sequential deposition is certified as an effective technology to obtain high-performance perovskite solar cells (PVSCs), which can be derivatized into large-scale industrial production. However, dense lead iodide (PbI2 ) causes incomplete reaction and unsatisfactory solution utilization of perovskite in planar PVSCs without mesoporous titanium dioxide as a support. Here, a novel autonomously longitudinal scaffold constructed by the interspersion of in situ self-polymerized methyl methacrylate (sMMA) in PbI2 is introduced to fabricate efficient PVSCs with excellent flexural endurance and environmental adaptability. By this strategy perovskite solution can be confined within an organic scaffold with vertical crystal growth promoted, effectively inhibiting exciton accumulation and recombination at grain boundaries. Additionally, sMMA cross-linked perovskite network can release mechanical stress and occupy the main channels for ion migration and water/oxygen permeation to significantly improve operational stability, which opens up a new strategy for the commercial development of large-area PVSCs in flexible electronics.