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Abstract Hydrogel-based tissue expansion combined with mass spectrometry (MS) offers an emerging spatial proteomics approach. Here, we present a filter-aided expansion proteomics (FAXP) strategy for spatial proteomics analysis of archived formalin-fixed paraffin-embedded (FFPE) specimens. Compared to our previous ProteomEx method, FAXP employed a customized tip device to enhance both the stability and throughput of sample preparation, thus guaranteeing the reproducibility and robustness of the workflow. FAXP achieved a 14.5-fold increase in volumetric resolution. It generated over 8 times higher peptide yield and a 255% rise in protein identifications while reducing sample preparation time by 50%. We also demonstrated the applicability of FAXP using human colorectal FFPE tissue samples. Furthermore, for the first time, we achieved bona fide single-subcellular proteomics under image guidance by integrating FAXP with laser capture microdissection.

Abstract This article proposes a unilateral Adaptive update strategy based Interval Prediction (AIP) model for short‐term load prediction, which is developed based on lower and upper bound estimation (LUBE) architecture. In traditional LUBE interval prediction model, the model training is usually trained by heuristic algorithms. In this article, the model training is formulated as a bi‐level optimization problem with the help of proposed unilateral adaptive update strategy and cost function. In lower‐level problem, a simplified biased convex cost function is developed to supervise the learning direction of basic prediction engines. The basic prediction engine utilizes Gated Recurrent Unit (GRU) to extract features and Full connected Neural Network (FNN) to generate interval boundary. In upper‐level problem, a unilateral adaptive update strategy with unilateral coverage rate is put forward. It iteratively tunes hyper‐parameters of cost function during training process. Comprehensive experiments based on residential load data are implemented and the proposed interval prediction model outperforms the tested state‐of‐the‐art algorithms, achieving a 15% reduction in prediction error and a 20% decrease in computational time.

Flame temperature and spectral emissivity were the important parameters characterizing the sufficient degree of fuel combustion and the particle radiative characteristics in the Rocket Based Combined Cycle (RBCC) combustor. To investigate the combustion characteristics of the complex supersonic flame in the RBCC combustor, a new radiation thermometry combined with Levenberg-Marquardt (LM) algorithm and the least squares method was proposed to measure the temperature, emissivity and spectral radiative properties based on the flame emission spectrum. In-situ measurements of the flame temperature, emissivity and spectral radiative properties were carried out in the RBCC direct-connected test bench with laser-induced plasma combustion enhancement (LIPCE) and without LIPCE. The flame average temperatures at fuel global equivalence ratio (α) of 1.0b and 0.6 with LIPCE were 4.51% and 2.08% higher than those without LIPCE. The flame combustion oscillation of kerosene tended to be stable in the recirculation zone of cavity with the thermal and chemical effects of laser induced plasma. The differences of flame temperature at α = 1.0b and 0.6 were 503 K and 523 K with LIPCE, which were 20.07% and 42.64% lower than those without LIPCE. The flame emissivity with methane assisted ignition was 80.46% lower than that without methane assisted ignition, due to the carbon-hydrogen ratio of kerosene was higher than that of methane. The spectral emissivities at 600 nm with LIPCE were 1.25%, 22.2%, and 4.22% lower than those without LIPCE at α = 1.0a (with methane assisted ignition), 1.0b (without methane assisted ignition) and 0.6. The effect of concentration in the emissivity was removed by normalization to analyze the flame radiative properties in the RBCC combustor chamber. The maximum differences of flame normalized emissivity were 50.91% without LIPCE and 27.53% with LIPCE. The flame radiative properties were stabilized under the thermal and chemical effects of laser induced plasma at α = 0.6.

In response to the contradiction between the deep mobility control capability and near-well-bore area injectability of oil displacement agents， this paper proposed that an ideal oil displacement agent for mobility control should fulfill the technical requirements of low viscosity preparation/transportation， low adsorption in the near-well-bore area for long-term stable injection， and produced liquid with low concentrations of the component. Meanwhile， multi-level flow resistance peaks （Δpmax） at different positions in the deep reservoir should be established during the flow process， and flow resistance of fluid after displacing front should be maintained at a lower level. Based on the synergistic effect of the adsorption at the solid/liquid interface and the inter-molecular interaction， a hydrophobically associating water-soluble polymer/anionic surfactant binary system was designed with the characteristics of dynamically changing the system constituent and microscopic solution structure， thereby changing flow resistance. Compared with HP-1 （1 500 mg/L）， the binary systems HP-1 （1 500 mg/L）/SDSB （150 mg/L） and HP-1 （1 500 mg/L）/SDSB （200 mg/L）， with similar apparent viscosity and different constituents can construct dynamic flow resistance with higher values and better spatial distribution in the middle-rear position of the porous medium flow during the slug injection and subsequent water flooding processes. It verified that the binary system had the characteristics of viscosity increasing and delayed breakthrough during migration， and the mobility control capability in the displacing front was more powerful. In addition， the spatial distribution of flow resistance in the reservoir becomes more reasonable， which prolonged the overall breakthrough time of the slugs， thus expanding the swept volume and enhancing the oil displacement efficiency. Oil displacement experiments were conducted in a Bohai Oilfield with heavy oil， strong heterogeneity， and 80% water cut during water flooding， with chemical industrial products with basically the same dosage and similar cost adopted. The results show that the spatial dynamic distribution characteristics of the binary system before subsequent water flooding breakthrough are a crucial factor affecting oil displacement efficiency， and the binary system （AP-P4 （1 400 mg/L） + ZX-27（300 mg/L）， viscosity of 6.4 mPa·s） can improve the oil recovery by more than 10% compared with hydrophobically associating water-soluble polymer AP-P4 （1 750 mg/L， viscosity of 62.9 mPa·s）.

Abstract Ductal carcinoma in situ (DCIS) represents pre-invasive breast carcinoma. In untreated cases, 25–60% DCIS progress to invasive ductal carcinoma (IDC). The challenge lies in distinguishing between non-progressive and progressive DCIS, often resulting in over- or under-treatment in many cases. With increasing screen-detected DCIS in these years, the nature of DCIS has aroused worldwide attention. A deeper understanding of the biological nature of DCIS and the molecular journey of the DCIS-IDC transition is crucial for more effective clinical management. Here, we reviewed the key signaling pathways in breast cancer that may contribute to DCIS initiation and progression. We also explored the molecular features of DCIS and IDC, shedding light on the progression of DCIS through both inherent changes within tumor cells and alterations in the tumor microenvironment. In addition, valuable research tools utilized in studying DCIS including preclinical models and newer advanced technologies such as single-cell sequencing, spatial transcriptomics and artificial intelligence, have been systematically summarized. Further, we thoroughly discussed the clinical advancements in DCIS and IDC, including prognostic biomarkers and clinical managements, with the aim of facilitating more personalized treatment strategies in the future. Research on DCIS has already yielded significant insights into breast carcinogenesis and will continue to pave the way for practical clinical applications.

The present paper investigates the dynamic behaviors of a bubble restricted by two parallel plates near an elliptical wall. The typical experimental phenomena of the bubble are recorded employing the high-speed photography and a theoretical Kelvin impulse model is established. The impacts of the spatial position and the curvature of the wall on the bubble collapse behaviors are quantitatively investigated through the theoretical model and verified against the experimental results. The Kelvin impulse intensity and the direction during the bubble collapse process are compared and discussed for different elliptical-shaped walls. The main conclusions include: (1) During the bubble collapse process, the phenomenon of the bubble uneven splitting is discovered. (2) At different spatial positions and wall curvatures, the bubble collapse jet angle, movement distance, and velocity are in good agreement with the theoretical Kelvin impulse predictions. (3) As the short-to-long axis ratio increases, the differences in the distributions of the Kelvin impulse intensity and the direction near the elliptical wall gradually become larger, and the range of the influence of the impulse intensity expands.

Increasing penetration of distributed energy resources in the distribution network (DN) is threatening safe operation of the DN, which necessitates setup of the ancillary service market in the DN. In the ancillary service market, distribution system operator (DSO) is responsible for safety of the DN by procuring available capacities of aggregators. Unlike existing studies, this paper proposes a novel market mechanism composed of two parts: choice rule and payment rule. The proposed choice rule simultaneously considers social welfare and fairness, encouraging risk-averse aggregators to participate in the ancillary service market. It is then formulated as a linear programming problem, and a distributed solution using the multi-cut Benders decomposition is presented. Moreover, successful implementation of the choice rule depends on each aggregator's truthful adoption of private parameters. Therefore, a payment rule is also designed, which is proved to possess two properties: incentive compatibility and individual rationality. Simulation results demonstrate effectiveness of the proposed choice rule on improving fairness and verify properties of the payment rule.

Background: Src homology 2 domain-containing phosphatase 2 (SHP2) is hyper-activated in some solid tumors. Previous findings suggest that the expression of SHP2 in colorectal cancer (CRC) may be associated with prognosis. However, validation with large sample data is lacking. Materials and Methods: Tissue microarrays containing 860 CRCs and 197 mucosal tissues adjacent to the tumors were constructed. Immunohistochemistry was used to evaluate the expression of SHP2. Differences between SHP2 expression and clinicopathological parameters were evaluated. Kaplan–Meier survival curves and log-rank tests were used to analyze the relationships between SHP2 expression and the overall survival of patients. A Cox proportional hazard regression model was used for univariate and multivariate analyses of prognostic factors. Results: SHP2 expression in CRCs tissues was significantly higher than those in adjacent mucosal tissues (P < 0.001). SHP2 expression was related to tumor differentiation, depth of invasion, distant metastasis, vascular tumor thrombus, lymph node metastasis, and TNM classification (P < 0.05). The prognosis of the high-expression group of SHP2 was significantly better than that of the low-expression group (P = 0.008). Univariate analysis showed that the expression of SHP2 was a prognostic factor for CRC (P = 0.008). Multivariate analysis demonstrated that SHP2 remained an independent prognostic factor for CRC (P = 0.033). Conclusion: The expression of SHP2 was significantly higher in CRC tissues than in adjacent normal tissues. High expression of SHP2 was associated with a promising outcome, suggesting that SHP2 may be a favorable prognostic indicator of CRC.

With the enhancement of environmental protection and the incentive policies issued by governments, the choice of electric vehicles as a means of transportation has gradually become a new mode, so the establishment of a perfect charging station service network is a key link and an critical guarantee for accelerating the adoption of electric vehicles (EVs). In the early stage of EV charging station construction, reasonable and scientific planning is not only related to the convenient travel of users, but also related to the effective utilization of resources. To promote the development of low-carbon economy, this paper first propose a Voronoi diagram based charging station service division approach, followed by a M/G/K queuing model based approach for evaluating the charging capacity of the EV charging station. Finally, a location and volume model is constructed and solved to determine the optimal construction plan of the EV charging station with minimum total cost for the whole society. The experimental results show that the charging station planning method proposed in this paper is economical and effectively improves the charging convenience of electric vehicle users. The reasonable location setting and capacity configuration of charging stations promote the sustainable development of the power grid in the planning area, which has certain practical significance.

In this paper, a multistage reliability-constrained stochastic planning model is established for the diamond distribution network, a new type of distribution system grid structure, with the goal of optimizing the total cost of investment and operation. The uncertainty of load growth is simulated by generating multiple load growth scenarios, and the power supply loss caused by the reliability of components in the system is also considered. The multistage stochastic dynamic decision process is modeled by The Markov decision process. In order to solve the “curse of dimensionality” problem in multi-stage stochastic planning model, the approximate dynamic programming algorithm is used to solve it. The case study is based on the typical structure of the diamond distribution network and realistic data of an actual district in Shanghai, China. The planning results verify the effectiveness of the model and the solution algorithm, and demonstrate the reliability and economy of the diamond distribution network are superior to the traditional double-ring network.

The use of broadband laser technology is a novel approach for inhibiting processes related to laser plasma interactions (LPIs). In this study, several preliminary experiments into broadband-laser-driven LPIs are carried out using a newly established hundreds-of-joules broadband second-harmonic-generation laser facility. Through direct comparison with LPI results for a traditional narrowband laser, the actual LPI-suppression effect of the broadband laser is shown. The broadband laser had a clear suppressive effect on both back-stimulated Raman scattering and back-stimulated Brillouin scattering at laser intensities below 1 × 1015 W cm−2. An abnormal hot-electron phenomenon is also investigated, using targets of different thicknesses.

Abstract 360‐degree videos have drawn great attention from both the academia and the industry. For transmission and storage of 360‐degree video, the joint video exploration team proposed the Versatile Video Coding (VVC) standard. VVC can significantly reduce the bitrate while maintaining the same subjective visual quality compared to the preceding high efficiency video coding. However, the computational complexity of VVC is extremely high which hinders the interactive applications. This paper proposes a fast intra partition method and mode prediction algorithm for equirectangular projection 360‐degree video coding. First, a latitude‐based preprocessing is introduced to early terminate the Coding Unit (CU) partition in the polar region. Second, the support vector machine is used to predict the CU partition type. Third, the fast intra mode search method accelerates the intra mode prediction. Experimental results show that the proposed algorithm can significantly obtain an average time reduction rate of 60.40% and a Bjontegaard delta rate increase of 1.96%.

Immunohistochemical (IHC) assay is a commonly used auxiliary technique in pathological diagnosis. Compared to the conventional manual scoring methods that are complicated and time-consuming, automated scoring methods have been playing a more and more important role in the development of digital medicine due to their adaptability and consistency. This study proposes an automatic scoring model for tumor IHC images, which mainly consists of a module for extracting the regions of interest (ROI) and a feature fusion scoring network. The former module extracts the effective tissue regions and the nuclear regions as prior knowledge to exclude cytoplasmic staining interference. The feature fusion network includes two branches. The main branch network combines the structure of cross-block stitching feature maps and the frequency channel attention networks (FcaNet) to extract the features of the effective tissue region images. The other branch network extracts the color representation vector of the cell nucleus region images. The fully-connected layers combine the features from both branches to give a comprehensive final score as the result. We performed experiments on IHC images of P53 protein in colorectal cancer. The results show that the proposed P53Net achieves better classification results than the commonly used classification models, with 94.21% accuracy, 89.24% F1-Score, and 0.9136 kappa coefficient.

The increased deployment of electricity-based hydrogen production strengthens the coupling of power distribution system (PDS) and hydrogen energy system (HES). Considering that power to hydrogen (PtH) has great potential to facilitate the usage of renewable energy sources (RESs), the coordination of PDS and HES is important for planning purposes under high RES penetration. To this end, this paper proposes a multi-stage co-planning model for the PDS and HES. For the PDS, investment decisions on network assets and RES are optimized to supply the growing electric load and PtHs. For the HES, capacities of PtHs and hydrogen storages (HSs) are optimally determined to satisfy hydrogen load considering the hydrogen production, tube trailer transportation, and storage constraints. The overall planning problem is formulated as a multistage stochastic optimization model, in which the investment decisions are sequentially made as the uncertainties of electric and hydrogen load growth states are revealed gradually over periods. Case studies validate that the proposed co-planning model can reduce the total planning cost, promote RES consumption, and obtain more flexible decisions under long-term load growth uncertainties.

Abstract Determination of malignancy in thyroid nodules remains a major diagnostic challenge. Here we report the feasibility and clinical utility of developing an AI-defined protein-based biomarker panel for diagnostic classification of thyroid nodules: based initially on formalin-fixed paraffin-embedded (FFPE), and further refined for fine-needle aspiration (FNA) tissue specimens of minute amounts which pose technical challenges for other methods. We first developed a neural network model of 19 protein biomarkers based on the proteomes of 1724 FFPE thyroid tissue samples from a retrospective cohort. This classifier achieved over 91% accuracy in the discovery set for classifying malignant thyroid nodules. The classifier was externally validated by blinded analyses in a retrospective cohort of 288 nodules (89% accuracy; FFPE) and a prospective cohort of 294 FNA biopsies (85% accuracy) from twelve independent clinical centers. This study shows that integrating high-throughput proteomics and AI technology in multi-center retrospective and prospective clinical cohorts facilitates precise disease diagnosis which is otherwise difficult to achieve by other methods.

Abstract Colorectal cancer (CRC) is a major malignancy threatening the health of people in China and screening could be effective for preventing the occurrence and reducing the mortality of CRC. We conducted a multicenter, prospective clinical study which recruited 4,245 high‐risk CRC individuals defined as having positive risk‐adapted scores or fecal immunochemical test (FIT) results, to evaluate the clinical performance of the multitarget fecal immunochemical and stool DNA (FIT‐sDNA) test for CRC screening. Each participant was asked to provide a stool sample prior to bowel preparation, and FIT‐sDNA test and FIT were performed independently of colonoscopy. We found that 186 (4.4%) were confirmed to have CRC, and 375 (8.8%) had advanced precancerous neoplasia among the high CRC risk individuals. The sensitivity of detecting CRC for FIT‐sDNA test was 91.9% (95% CI, 86.8–95.3), compared with 62.4% (95% CI, 54.9–69.3) for FIT (P

Abstract Germline PALB2 pathogenic variants are associated with an increased lifetime risk for breast, pancreatic, and ovarian cancer. However, the interpretation of the pathogenicity of numerous PALB2 missense variants of uncertain significance (VUSs) identified in germline genetic testing remains a challenge. Here we selected ten potentially pathogenic PALB2 VUSs identified in 2279 Chinese patients with breast cancer and evaluated their impacts on PALB2 function by systematic functional assays. We showed that three PALB2 VUSs p.K16M [c.47 A > T], p.L24F [c.72 G > C], and p.L35F [c.103 C > T] in the coiled-coil domain impaired PALB2-mediated homologous recombination. The p.L24F and p.L35F variants partially disrupted BRCA1-PALB2 interactions, reduced RAD51 foci formation in response to DNA damage, abrogated ionizing radiation-induced G2/M checkpoint maintenance, and conferred increased sensitivity to olaparib and cisplatin. The p.K16M variant presented mild effects on BRCA1-PALB2 interactions and RAD51 foci formation. Altogether, we identify two novel PALB2 VUSs, p.L24F and p.L35F, that compromise PALB2 function and may increase cancer risk. These two variants display marked olaparib and cisplatin sensitivity and may help predict response to targeted therapy in the clinical treatment of patients with these variants.

Adenocarcinoma not otherwise specified (AC) and mucinous adenocarcinoma (MC) have different biological behaviors and clinical features. We utilized our previous proteomic data and public transcriptome, single-cell transcriptome, and spatial transcriptome databases to profile the molecular atlas of the tumor microenvironments of MC, AC, and normal colon tissues. By exploring the general and specific molecular features of AC and MC, we found that AC was immune-active but exposed to a hypoxic microenvironment. MC cells could protect against DNA damage, and the microenvironment was unfavorable to leukocyte transendothelial migration. We identified several potential molecular and cellular targets of AC and MC for future research. We also highlighted that the major difference between AC and MC was not the variety of cell types and functions but possibly cell interactions. Stromal and epithelial cell interactions play important roles in both MC and AC, but different regulatory pathways were involved.

Abstract Circulating tumor cells (CTCs) are tumor cells that have sloughed off the primary tumor and extravasate into and circulate in the blood. Understanding of the metastatic cascade of CTCs has tremendous potential for the identification of targets against cancer metastasis. Detecting these very rare CTCs among the massive blood cells is challenging. However, emerging technologies for CTCs detection have profoundly contributed to deepening investigation into the biology of CTCs and have facilitated their clinical application. Current technologies for the detection of CTCs are summarized herein, together with their advantages and disadvantages. The detection of CTCs is usually dependent on molecular markers, with the epithelial cell adhesion molecule being the most widely used, although molecular markers vary between different types of cancer. Properties associated with epithelial-to-mesenchymal transition and stemness have been identified in CTCs, indicating their increased metastatic capacity. Only a small proportion of CTCs can survive and eventually initiate metastases, suggesting that an interaction and modulation between CTCs and the hostile blood microenvironment is essential for CTC metastasis. Single-cell sequencing of CTCs has been extensively investigated, and has enabled researchers to reveal the genome and transcriptome of CTCs. Herein, we also review the clinical applications of CTCs, especially for monitoring response to cancer treatment and in evaluating prognosis. Hence, CTCs have and will continue to contribute to providing significant insights into metastatic processes and will open new avenues for useful clinical applications.

Abnormal ubiquitination is extensively associated with cancers. To investigate human lung cancer ubiquitination and its potential functions, quantitative ubiquitinomics was carried out between human lung squamous cell carcinoma (LSCC) and control tissues, which characterized a total of 627 ubiquitin-modified proteins (UPs) and 1209 ubiquitinated lysine sites. Those UPs were mainly involved in cell adhesion, signal transduction, and regulations of ribosome complex and proteasome complex. Thirty three UPs whose genes were also found in TCGA database were significantly related to overall survival of LSCC. Six significant networks and 234 hub molecules were obtained from the protein-protein interaction (PPI) analysis of those 627 UPs. KEGG pathway analysis of those UPs revealed 47 statistically significant pathways, and most of which were tumor-associated pathways such as mTOR, HIF-1, PI3K-Akt, and Ras signaling pathways, and intracellular protein turnover-related pathways such as ribosome complex, ubiquitin-mediated proteolysis, ER protein processing, and proteasome complex pathways. Further, the relationship analysis of ubiquitination and differentially expressed proteins shows that ubiquitination regulates two aspects of protein turnover - synthesis and degradation. This study provided the first profile of UPs and molecular networks in LSCC tissue, which is the important resource to insight into new mechanisms, and to identify new biomarkers and therapeutic targets/drugs to treat LSCC.

Human endogenous retroviruses (HERVs) originated from ancient retroviral infections of germline cells millions of years ago and have evolved as part of the host genome. HERVs not only retain the capacity as retroelements but also regulate host genes. The expansion of HERVs involves transcription by RNA polymerase II, reverse transcription, and re-integration into the host genome. Fast progress in deep sequencing and functional analysis has revealed the importance of domesticated copies of HERVs, including their regulatory sequences, transcripts, and proteins in normal cells. However, evidence also suggests the involvement of HERVs in the development and progression of many types of cancer. Here we summarize the current state of knowledge about the expression of HERVs, transcriptional regulation of host genes by HERVs, and the functions of HERVs in reverse transcription and gene editing with their reverse transcriptase.

Abstract Patients with right-sided colon cancer (RCC) generally have a poorer prognosis than those with left-sided colon cancer (LCC). We previously found that homeobox C6 (HOXC6) was the most significantly upregulated gene in RCC compared to LCC. However, it remains unclear whether HOXC6 plays a role in tumor proliferation and metastasis. Our study aimed to explore the potential oncogenic role and the detailed molecular mechanism of HOXC6 in RCC. In this study, HOXC6 was validated to be overexpressed in RCC and associated with poor prognosis. Furthermore, overexpression of HOXC6 promoted the migration and invasion of colon cancer cells through inducing EMT by activating the Wnt/β-catenin signaling pathway and inhibition of DKK1 secretion. Lastly, we preliminary explored the translational effect of HOXC6 and found that silencing of HOXC6 made HCT116 and HT29 cells more sensitive to irinotecan.

Abstract As the predominant modification in RNA, N6-methyladenosine (m6A) has attracted increasing attention in the past few years since it plays vital roles in many biological processes. This chemical modification is dynamic, reversible and regulated by several methyltransferases, demethylases and proteins that recognize m6A modification. M6A modification exists in messenger RNA and affects their splicing, nuclear export, stability, decay, and translation, thereby modulating gene expression. Besides, the existence of m6A in noncoding RNAs (ncRNAs) could also directly or indirectly regulated gene expression. Colorectal cancer (CRC) is a common cancer around the world and of high mortality. Increasing evidence have shown that the changes of m6A level and the dysregulation of m6A regulatory proteins have been implicated in CRC carcinogenesis and progression. However, the underlying regulation laws of m6A modification to CRC remain elusive and better understanding of these mechanisms will benefit the diagnosis and therapy. In the present review, the latest studies about the dysregulation of m6A and its regulators in CRC have been summarized. We will focus on the crucial roles of m6A modification in the carcinogenesis and development of CRC. Moreover, we will also discuss the potential applications of m6A modification in CRC diagnosis and therapeutics.

Abstract The emergence of SARS-CoV-2 has resulted in the COVID-19 pandemic, leading to millions of infections and hundreds of thousands of human deaths. The efficient replication and population spread of SARS-CoV-2 indicates an effective evasion of human innate immune responses, although the viral proteins responsible for this immune evasion are not clear. In this study, we identified SARS-CoV-2 structural proteins, accessory proteins, and the main viral protease as potent inhibitors of host innate immune responses of distinct pathways. In particular, the main viral protease was a potent inhibitor of both the RLR and cGAS-STING pathways. Viral accessory protein ORF3a had the unique ability to inhibit STING, but not the RLR response. On the other hand, structural protein N was a unique RLR inhibitor. ORF3a bound STING in a unique fashion and blocked the nuclear accumulation of p65 to inhibit nuclear factor-κB signaling. 3CL of SARS-CoV-2 inhibited K63-ubiquitin modification of STING to disrupt the assembly of the STING functional complex and downstream signaling. Diverse vertebrate STINGs, including those from humans, mice, and chickens, could be inhibited by ORF3a and 3CL of SARS-CoV-2. The existence of more effective innate immune suppressors in pathogenic coronaviruses may allow them to replicate more efficiently in vivo. Since evasion of host innate immune responses is essential for the survival of all viruses, our study provides insights into the design of therapeutic agents against SARS-CoV-2.

Emerging studies indicate that long noncoding RNAs (lncRNAs) play crucial roles in ovarian cancer (OC). By analyzing high-throughput data, we found that SNHG17 was highly expressed in multiple OC cohorts. However, its functions in OC were not explored. In this study, lncRNA expression in OC was analyzed by a series of microarray data. The functions of SNHG17 were investigated by various in vitro and in vivo assays. Fluorescence in situ hybridization (FISH), RNA pull-down, chromatin immunoprecipitation (ChIP), RNA immunoprecipitation (RIP), and luciferase reporter assays were used to reveal the potential mechanisms involved in the effects of SNHG17. We found that SNHG17 was overexpressed in OC and that the oncogenic transcription factor STAT3 was involved in promoting its expression. In addition, high SNHG17 expression was associated with a poor prognosis in OC. Functional analysis revealed that SNHG17 could promote OC cell growth. Mechanistically, SNHG17 was found to be located predominantly in the cytoplasm. It could regulate expression of CDK6, an important cell-cycle regulator, by acting as a molecular sponge for miR-214-3p. In summary, our study suggested that SNHG17 acted as an oncogene in OC, which might serve as a novel target for OC diagnosis and therapy.

BackgroundDue to the lack of large-scale clinical trials, the treatment strategies of small bowel adenocarcinoma (SBA) are controversial, especially for stage II patients. According to the National Comprehensive Cancer Network (NCCN) guideline, few lymph nodes (LNs) examined (

To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipeline and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to generate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.

Objective: Circulating tumor cells (CTCs) play a critical role in cancer metastasis, but their prevalence and significance remain unclear. This study attempted to track the epithelial-mesenchymal transition (EMT) status of CTCs in breast cancer patients and investigate their clinical relevance. Methods: In this study, the established negFACS-IF:E/M platform was applied to isolate rare CTCs and characterize their EMT status in breast cancer. A total of 89 breast cancer patients were recruited, including stage 0–III (n = 60) and late stage (n = 29) cases. Results: Using the negFACS-IF:E/M platform, it was found that in human epidermal growth factor receptor 2 (HER2)+ patients, mesenchymal CTCs usually exhibited a high percentage of HER2+ cells. Stage IV breast cancer patients had considerably more CTCs than stage 0–III patients. Among stage 0–III breast cancers, the HER2 subtype included a significantly higher percentage of mesenchymal and biphenotypic (epithelial and mesenchymal) CTCs than the luminal A or B subtypes. Among stage IV patients, CTCs were predominantly epithelial in cases with local recurrence and were more mesenchymal in cases with distant metastasis. By applying a support vector machine (SVM) algorithm, the EMT status of CTCs could distinguish between breast cancer cases with metastasis/local recurrence and those without recurrence. Conclusions: The negFACS-IF:E/M platform provides a flexible and generally acceptable method for the highly sensitive and specific detection of CTCs and their EMT traits in breast cancer. This study demonstrated that the EMT status of CTCs had high clinical relevance in breast cancer, especially in predicting the distant metastasis or local recurrence of breast cancer.

Abstract Background The role and mechanism of the nicotinamide adenine dinucleotide (NAD+) salvage pathway in cancer cell proliferation is poorly understood. Nicotinamide phosphoribosyltransferase (NAMPT), which converts nicotinamide into NAD+, is the rate-limiting enzyme in the NAD+ salvage pathway. Here, we assessed the role of NAMPT in the proliferation of colorectal cancer. Methods Real-time PCR, immunohistochemistry, western blotting, and analyses of datasets from Oncomine and Gene Expression Omnibus were conducted to assess the expression of NAMPT at the mRNA and protein levels in colorectal cancer. The Kaplan Meier plotter online tool was used to evaluate the prognostic role of NAMPT. Knockdown of NAMPT was performed to assess the role of NAMPT in colorectal cancer cell proliferation and tumorigenesis both in vitro and in vivo. Overexpression of NAMPT was used to evaluate impact of NAMPT on colorectal cancer cell proliferation in vitro. NAD+ quantitation, immunofluorescence, dual luciferase assay and western blot were used to explore the mechanism of colorectal cancer proliferation. Transwell migration and invasion assays were conducted to assess the role of NAMPT in cell migration and invasion abilities of colorectal cancer cells. Results Our study indicated that the inhibition of NAMPT decreased proliferation capacity of colorectal cancer cells both in vitro and in vivo. Conversely, overexpression of NAMPT could promote cell proliferation in vitro. NAMPT inhibition induced β-catenin degradation by increasing Axin expression levels; this resulted in the inhibition of Wnt/β-catenin signaling and cell proliferation in colorectal cancer. The addition of nicotinamide mononucleotide, the enzymatic product of NAMPT, effectively reversed β-catenin protein degradation and inhibited growth. Similarly, the knockdown of Axin also decreased the cell death induced by the inhibition of NAMPT. In addition, we showed that colorectal cancer tissues harbored significantly higher levels of NAMPT than the levels harbored by paired normal tissues, especially in colorectal cancer stages I and II. And the overexpression of NAMPT was associated with unfavorable survival results. Conclusions Our findings reveal that NAMPT plays an important role in colorectal cancer proliferation via Wnt/β-catenin pathway, which could have vital implications for the diagnosis, prognosis and treatment of colorectal cancer.

The mechanism of the active cochlea relies on a complex interaction between microstructures in the organ of Corti. A significant longitudinal vibration “hotspot” was recently observed in the high-frequency region of the living gerbil cochlea between the Deiters cells and the outer hair cells. A similar phenomenon was also found in guinea pigs with a relatively smaller magnitude. The cause is unknown, but one hypothesis is that this phenomenon is due to the structural constraints between different microstructures. It is not easy to explain the mechanism of hotspots directly from experimental observations. It may also be difficult to image or test if the hotspot will occur in the low-frequency region in the cochlea. We built two three-dimensional finite element models corresponding to the high- and low-frequency regions in the guinea pig cochlea. Responses of the organ of Corti to passive acoustic and outer hair cell electrical excitation were calculated. The two excitations were then superimposed to predict the active response of the organ of Corti. The hotspot phenomenon in the experiment was reproduced and analyzed in-depth about influencing factors. Our results indicate that hotspots appear in the low-frequency region of the cochlea as well. We hypothesize that the hotspot is a locally originated phenomenon in the cochlea, and the traveling wave further enhances the response to low-frequency excitation. The movement of outer hair cells inclined in the longitudinal direction is the leading cause of the hotspot.

BackgroundThe homeobox (HOX) gene family encodes highly conserved transcription factors, that play important roles in the morphogenesis and embryonic development of vertebrates. Mammals have four similar HOX gene clusters, HOXA, HOXB, HOXC, and HOXD, which are located on chromosomes 7, 17,12 and 2 and consist of 38 genes. Some of these genes were found to be significantly related to a variety of tumors; however, it remains unknown whether abnormal expression of the HOX gene family affects prognosis and the tumor microenvironment (TME) reshaping in colorectal cancer (CRC). Therefore, we conducted this systematic exploration to provide additional information for the above questions.MethodsRNA sequencing data from The Cancer Genome Atlas (TCGA) and mRNA expression data from Gene Expression Omnibus (GEO) combined with online tumor analysis databases (UALCAN, TIMER, PrognoScan) were utilized to explore the relationship among abnormal expression of HOX family genes, prognosis and the tumor immune microenvironment in CRC.Results1. Differential expression and prognosis analysis: 24 genes were significantly differentially expressed in CRC compared to adjacent normal tissues, and seven upregulated genes were significantly associated with poor survival. Among these seven genes, univariate and multivariate Cox regression analysis revealed that only high expression of HOXC6 significantly contributed to poor prognosis; 2. The influence of overexpressed HOXC6 on the pathway and TME: High HOXC6 expression was significantly related to the cytokine pathway and expression of T cell attraction chemokines, the infiltration ratio of immune cells, expression of immune checkpoint markers, tumor mutation burden (TMB) scores and microsatellite instability-high (MSI-H) scores; 3. Stratified analysis based on stages: In stage IV, HOXC6 overexpression had no significant impact on TMB, MSI-H, infiltration ratio of immune cells and response prediction of immune checkpoint blockers (ICBs), which contributed to significantly poor overall survival (OS).ConclusionSeven differentially expressed HOX family genes had significantly worse prognoses. Among them, overexpressed HOXC6 contributed the most to poor OS. High expression of HOXC6 was significantly associated with high immunogenicity in nonmetastatic CRC. Further research on HOXC6 is therefore worthwhile to provide potential alternatives in CRC immunotherapy.

Optical coherence tomography (OCT) has become a novel approach to noninvasive imaging in the past three decades, bringing a significant potential to biological research and medical biopsy in situ, particularly in three-dimensional (3D) in vivo conditions. Specifically, OCT systems using broad bandwidth sources, mainly centered at near-infrared-II, allow significantly higher imaging depth, as well as maintain a high-resolution and better signal-to-noise ratio than the traditional microscope, which avoids the scattering blur and thus obtains more details from delicate biological structures not just limited to the surface. Furthermore, OCT systems combined the spectrometer with novel light sources, such as multiplexed superluminescent diodes or ultra-broadband supercontinuum laser sources, to obtain sub-micron resolution imaging with high-speed achieve widespread clinical applications. Besides improving OCT performance, the functional extensions of OCT with other designs and instrumentations, taking polarization state or birefringence into account, have further improved OCT properties and functions. We summarized the conventional principle of OCT systems, including time-domain OCT, Fourier-domain OCT, and several typical OCT extensions, compared their different components and properties, and analyzed factors that affect OCT performance. We also reviewed current applications of OCT in the biomedical field, especially in hearing science, discussed existing limitations and challenges, and looked forward to future development, which may provide a guideline for those with 3D in vivo imaging desires.

RNA methylation plays a vital role in the pathogenesis of a variety of diseases including cancer, and aberrant levels of modified nucleosides in RNA were revealed to be related to cancer. Urine is a favored source for biomarker discovery due to the non-invasion to patients. Herein, we developed a sensitive hydrophilic interaction liquid chromatography tandem mass spectrometry (HILIC–MS/MS) method combined with stable isotope dilution for accurate quantification of methylated nucleosides in human urine. With this method, we successfully quantified ten methylated nucleosides in urine samples collected from healthy controls and breast cancer patients. We found N6-methyladenosine (m6A), 2′-O-methyladenosine (Am), N1-methyladenosine (m1A), N6,2′-O-dimethyladenosine (m6Am), N1-methylguanosine (m1G), 2′-O-methylguanosine (Gm), 5-methylcytidine (m5C) and 2′-O-methylcytidine (Cm) were all decreased in early-stage breast cancer patients, and a nomogram prediction model was constructed. Locally advanced breast cancer patients exhibited elevated levels of urinary 2′-O-methylated nucleosides in comparison to early-stage breast cancer patients. Together, we developed a robust method for the simultaneous determination of methylated nucleosides in human urine, and the results revealed an association between the contents of urinary methylated nucleosides and the occurrence of breast cancer, which may stimulate future studies about the regulatory roles of these methylated nucleosides in the initiation and progression of breast cancer.

RNA methylation plays a significant regulatory role in various of physiological activities and it has gradually become a hotspot of epigenetics in the past decade. 2′-O-methyladenosine (Am), 2′-O-methylguanosine (Gm), 2′-O-methylcytidine (Cm), 2′-O-methyluridine (Um), N6-methyladenosine (m6A), N1-methylguanosine (m1G), 5-methylcytidine (m5C), and 5-methyluridine (m5U) are representative 2′-O-methylation and base-methylation modified epigenetic marks of RNA. Abnormal levels of these ribonucleosides were found to be related to various diseases including cancer. Serum is an important source of biofluid for the discovery of biomarkers, and novel tumor biomarkers can be explored by measuring these ribonucleoside modifications in human serum. Herein, we developed and applied a hydrophilic interaction liquid chromatography tandem mass spectrometry (HILIC-MS/MS) method to determine the content of monomethylated ribonucleosides in human serum. The developed method enabled sensitive and accurate determination of these monomethylated ribonucleosides. By applying this robust method, we demonstrated the presence of Gm and Um in human serum for the first time, and we successfully quantified m6A, Gm, m1G, Cm, Um and m5U in serum samples collected from 61 patients with breast cancer and 69 healthy controls. We discovered that the levels of Gm, m1G, Cm, Um and m5U in serum were all significantly decreased in breast cancer patients whereas m6A was increased. We performed receiver operating characteristic (ROC) curve analysis, and obtained highest area under curve (AUC) value when combining these six monomethylated ribonucleosides together. These results suggest that m6A, Gm, m1G, Cm, Um and m5U might have great potential to be novel biomarkers for detection of breast cancer in the early stage. In addition, this study may stimulate future investigations about the regulatory roles of monomethylated ribonucleosides on the initiation and development of breast cancer.

Colorectal cancer and gastric cancer are the most prevalent gastrointestinal malignancies worldwide, and early detection of these cancers is crucial to reduce their incidence and mortality. RNA methylation plays an important regulatory role in a variety of physiological activities, and it has drawn great attention in recent years. Methylated adenosine (A) modifications such as N6-methyladenosine (m6A), N1-methyladenosine (m1A), 2′-O-methyladenosine (Am), N6,2′-O-dimethyladenosine (m6Am), and N6,N6-dimethyladenosine (m62A) are typical epigenetic markers of RNA, and they are closely correlated to various diseases including cancer. Serum is a valuable source of biofluid for biomarker discovery, and determination of these adenosine modifications in human serum is desirable since they are emerging biomarkers for detection of diseases. In this work, a targeted quantitative analysis method using hydrophilic interaction liquid chromatography–tandem mass spectrometry (HILIC-MS/MS) was developed and utilized to analyze these methylated adenosine modifications in serum samples. The concentration differences between the healthy volunteers and cancer patients were evaluated by Mann–Whitney test, and receiver operator characteristic (ROC) curve analysis was performed to access the potential of these nucleosides as biomarkers. We demonstrated the presence of the m6Am in human serum for the first time, and we successfully quantified the concentrations of A, m6A, m1A, and m6Am in serum samples from 99 healthy controls, 51 colorectal cancer patients, and 27 gastric cancer patients. We found that the levels of m6A and m6Am in serum were both increased in colorectal cancer or gastric cancer patients, compared to that in healthy controls. These results indicate that m6A and m6Am in serum may act as potential biomarkers for early detection and prognosis of colorectal cancer and gastric cancer. In addition, the present work will stimulate investigations on the effects of adenosine methylation on the initiation and progression of colorectal cancer and gastric cancer.

Background: This multicenter study aimed to reveal the genetic spectrum of colorectal cancer (CRC) with deficient mismatch repair (dMMR) and build a screening model for Lynch syndrome (LS). Methods: Through the immunohistochemical (IHC) screening of mismatch repair protein results in postoperative CRC patients, 311 dMMR cases, whose germline and somatic variants were detected using the ColonCore panel, were collected. Univariate and multivariate logistic regression analysis was performed on the clinical characteristics of these dMMR individuals, and a clinical nomogram, incorporating statistically significant factors identified using multivariate logistic regression analysis, was constructed to predict the probability of LS. The model was validated externally by an independent cohort. Results: In total, 311 CRC patients with IHC dMMR included 95 identified MMR germline variant (LS) cases and 216 cases without pathogenic or likely pathogenic variants in MMR genes (non-Lynch-associated dMMR). Of the 95 individuals, approximately 51.6%, 28.4%, 14.7%, and 5.3% cases carried germline MLH1 , MSH2 , MSH6 , and PMS2 pathogenic or likely pathogenic variants, respectively. A novel nomogram was then built to predict the probability of LS for CRC patients with dMMR intuitively. The receiver operating characteristic (ROC) curve informed that this nomogram-based screening model could identify LS with a higher specificity and sensitivity with an area under curve (AUC) of 0.87 than current screening criteria based on family history. In the external validation cohort, the AUC of the ROC curve reached 0.804, inferring the screening model’s universal applicability. We recommend that dMMR-CRC patients with a probability of LS greater than 0.435 should receive a further germline sequencing. Conclusion: This novel screening model based on the clinical characteristic differences between LS and non-Lynch-associated dMMR may assist clinicians to preliminarily screen LS and refer susceptible patients to experienced specialists.

Abstract Background Patients with microsatellite instability-high (MSI-H) colorectal cancer (CRC) generally have a better prognosis than patients with microsatellite stable (MSS) CRC. However, some MSI-H CRC patients do not gain overall survival benefits from immune checkpoint-blockade treatment. In other words, heterogeneity within the subgroup of MSI-H tumors remains poorly understood. Thus, an in-depth molecular characterization of MSI-H tumors is urgently required. Methods Here, we use nonnegative matrix factorization (NMF)-based consensus clustering to define CRC MSI-H subtypes in The Cancer Genome Atlas and a French multicenter cohort GSE39582. CIBERSORT was used to calculate the proportions of 22 lymphocytes in tumor tissue in MSI-H subtypes. Results MSI-H CRC samples basically clustered into two subgroups (MSI-H1 and MSI-H2). MSI-H1 was characterized by a lower BRAF mutational status, higher frequency of chromosomal instability, global hypomethylation, and worse survival than MSI-H2. Further examination of the immune landscape showed that macrophages of the M2 phenotype were enriched in MSI-H1, which may be associated with poor prognosis in this subgroup. Conclusions Our results illustrate the genetic heterogeneity in MSI-H CRCs and macrophages may serve as good targets for anticancer therapy in MSI-H1. Graphical abstract

Abstract The lungs are the second most common site of metastasis for colorectal cancer (CRC) after the liver. Rectal cancer is associated with a higher incidence of lung metastases compared to colon cancer. In China, the proportion of rectal cancer cases is around 50%, much higher than that in Western countries (nearly 30%). However, there is no available consensus or guideline focusing on CRC with lung metastases. We conducted an extensive discussion and reached a consensus of management for lung metastases in CRC based on current research reports and the experts’ clinical experiences and knowledge. This consensus provided detailed approaches of diagnosis and differential diagnosis and provided general guidelines for multidisciplinary therapy (MDT) of lung metastases. We also focused on recommendations of MDT management of synchronous lung metastases and initial metachronous lung metastases. This consensus might improve clinical practice of CRC with lung metastases in China and will encourage oncologists to conduct more clinical trials to obtain high-level evidences about managing lung metastases.

Abstract Background To date, no single colorectal cancer (CRC) screening strategy has been determined to be applicable worldwide. In China, a CRC screening protocol that combines double fecal immunochemical tests (FITs) and a high-risk factor questionnaire (HRFQ) as the first stage of screening and colonoscopy as the second stage of screening (scenario A) was adapted by the Chinese Ministry of Health in 2006. However, applying this CRC screening protocol nationally remains difficult because its effectiveness and convenience are controversial. This study evaluated the effects of subitems of the CRC screening protocol in China. Methods CRC screening results (scenario A) from Jiashan County, China, (2007–2009) were used to analyze the detection rates of CRC and advanced neoplasms as well as the cost-effectiveness of the protocol. Scenario A was divided into scenarios B–G (by selecting some items at the first stage of screening) for analysis. Results Compared with scenario A, removing the whole HRFQ (scenario F) reduced advanced neoplasm and adenoma detections by 29.8 and 41.2%, respectively, whereas the whole HRFQ accounted for 10.1% of the total screening cost. Removing FITs (scenario G) reduced CRC, advanced neoplasm and adenoma detections by 71.8, 56.9 and 47.7%, respectively, and the costs per case of CRC and advanced neoplasm were 82.0 and 19.1% higher, respectively, than those in scenario A. In scenarios B–E (deleting some high-risk factor questions on the HRFQ), the odds ratios (ORs) of the detection rates and costs per CRC, advanced neoplasm, adenoma, and neoplasm case were near 1.00. Scenarios C and D reduced the high-risk population and total screening costs by less than 6.0 and 4.1%, respectively. Scenarios E and B (FITs and a personal history of cancer or colorectal adenoma were reserved) reduced the high-risk population by 17.6 and 24.2% and the total screening costs by 11.2 and 15.4%, respectively, while the numbers of CRC cases were not missed, and advanced neoplasms detected decreased by only 5 and 11%, respectively. Conclusion The results of this study demonstrate that FITs and a personal history of colorectal adenoma are the most effective items in the Chinese CRC screening protocol.

Offshore wind power has developed rapidly in recent years, but its scale still lags far behind onshore wind power. Offshore wind power still has great development potential. One of the key factors restricting the development of offshore wind power is the unsatisfactory control effect of offshore wind farms, and the reason is that the adjustable capacity of the wind farm cannot be obtained accurately and quickly. Aims to meet the high precision requirements for adjustable capacity evaluation of offshore wind farms, this paper establishes a step-by-step power mapping framework based on the division of power transmission processes in offshore wind farms, considering the loss of each transmission process in detail. By establishing a step-by-step mapping from the wind turbine power to the injected power at the grid connection point of the offshore wind farm, the adjustable capacity of the offshore wind farm can be estimated based on the maximum theoretical power of the wind turbines. The performance of proposed method has been demonstrated in a real offshore wind farm.

Coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally and rapidly developed into a worldwide pandemic. The sudden outburst and rapid dissemination of SARS-CoV-2, with overwhelming public health and economic burdens, highlight an urgent need to develop effective strategies for the diagnosis and treatment of infected patients. In this review, we focus on the current advances in the diagnostics and treatment for SARS-CoV-2 infection. Notably, we also summarize some antineoplastic drugs repurposed for COVID-19 treatment and address the diagnostic and therapeutic challenges for oncologists to manage cancer patients in this COVID-19 era. In addition, we emphasize the importance of organoid technology as a valuable experimental virology platform to better understand the pathogenesis of COVID-19 and assist rapid screening of drugs against COVID-19.

BackgroundColorectal cancer (CRC) is one of the leading causes of cancer-related death. Early detection is critical to reduce CRC morbidity and mortality. In order to meet this need, we developed a molecular clamping assay called the ColoScape TM assay for early colorectal cancer diagnostics.MethodsNineteen mutations in four genes (APC, KRAS, BRAF and CTNNB1) associated with early events in CRC pathogenesis are targeted in the ColoScapeTM assay. Xenonucleic Acid (XNA)-mediated qPCR clamping technology was applied to minimize the wild-type background amplification in order to improve assay sensitivity of CRC mutation detection. The assay analytical performance was verified and validated, cfDNA and FFPE CRC patient samples were evaluated, and an ROC curve was applied to evaluate its performance.ResultsThe data showed that the assay analytical sensitivity was 0.5% Variant Allele Frequency, corresponding to ~7-8 copies of mutant DNA with 5 ng total DNA input per test. This assay is highly reproducible with intra-assay CV of ConclusionsThe XNA-mediated molecular clamping assay is a rapid, precise, and sensitive assay for the detection of precancerous lesions cfDNA and CRC cfDNA or FFPE samples.

Immunoscore can accurately predict the prognosis of patients with stage I–III colorectal cancer. However, whether it can be used to predict the prognosis of colorectal cancer peritoneal metastases (CRCPM) remains to be validated. We analyzed peritoneal and ovarian metastases in 68 patients with CRCPM. The immunoscore (IS) was based on the infiltration level of CD3+ and CD8+ T cells, whereas the TBM score was derived from the infiltration level of CD3+, CD8+, CD20+ and CD163+ cells to tumor microenvironment (TME). The predictive value of IS and TBM scores for relapse-free survival (RFS) and overall survival (OS) of patients with CRCPM was analyzed using Kaplan Meier curve and Cox multivariate models. Significant difference in the infiltration levels of different immune cell subtypes in primary lesions, peritoneal metastasis and ovarian metastasis were compared using t-test.CRCPM patients with high IS (>1), high TBM1 score (≥2) or high TBM2 score (≥2) had a significantly longer OS (IS: median OS, not reached vs 23 months, p = .0078; TBM1: not reached vs 21.5 months, p = .013; TBM2: 39.3 months vs 15.2 months, p = .001). On the other hand, patients with high IS had a trend of improved RFS (13.4 months vs 11.0 months, p = .067). However, TBM1 and TBM2 score has no predictive utility for RFS. Multivariate analysis revealed that IS, TBM1 and TBM2 can accurately predict OS, but not RFS. Finally, the infiltration level of CD3+ T cells, CD8+ T cells, CD20+ B cells, and CD68+ macrophage was significantly higher in peritoneal metastatic tissue and ovarian metastatic tissue, relative to primary tumor tissues.The IS and TBM score of peritoneal metastases could effectively predict OS of patients with CRCPM. Peritoneal metastasis of colorectal cancer decreased the infiltration level of T and B cells.

Reports indicate that most metastatic ovarian cancer (MOC) originates from gastrointestinal cancer (GIC). Notably, GICs metastasize to the ovary frequently via 3 main routes including hematogenous spread, lymphogenous spread, and transcoelomic spread. Nonetheless, the mechanism of the progression remains unknown, and only a handful of literature exists on the molecular alteration implicated in MOC from GIC. This work collected existing evidence and literature on the vital molecules of the metastatic pathway and systematically analyzed them geared toward exploring the mechanism of the metastatic pathway of MOC. Further, this review described dominating molecular alteration in the metastatic process from cancer cells detaching away from lesions to arrive at the ovary, including factors for regulating signaling pathways in epithelial-interstitial transformation, invading, and surviving in the circulatory system or abdominal cavity. We interrogated the basis of the ovary as a distant metastatic site. This article provides new insights into the metastatic pathway and generates novel therapeutic targets for effective treatment and satisfactory outcomes in GIC patients.

Since the beginning of the COVID-19 global pandemic, there has been insufficient evidence and experience to help oncologists understand how to deal with infected and non-infected cancer patients. Many hospitals worldwide have shared their experiences of managing such patients by using the internet to reach non-infected cancer patients. However, for infected or suspected infected cancer patients, their experiences in terms COVID-19 diagnosis, anticancer treatment and prognosis are largely unknown and controversial. Here, we summarize the incidence, severe illness rate and mortality according to the published clinical data of COVID-19 in cancer patients and discuss the diagnostic difficulties, anticancer treatment and prognosis of COVID-19-infected cancer patients.