The clinical implication and translational research of OSCC differentiation.

BACKGROUND: The clinical value and molecular characteristics of tumor differentiation in oral squamous cell carcinoma (OSCC) remain unclear. There is a lack of a related molecular classification prediction system based on pathological images for precision medicine. METHODS: Integration of epidemiology, genomics, experiments, and deep learning to clarify the clinical value and molecular characteristics, and develop a novel OSCC molecular classification prediction system. RESULTS: Large-scale epidemiology data (n = 118,817) demonstrated OSCC differentiation was a significant prognosis indicator (p < 0.001), and well-differentiated OSCC was more chemo-resistant than poorly differentiated OSCC. These results were confirmed in the TCGA database and in vitro. Furthermore, we found chemo-resistant related pathways and cell cycle-related pathways were up-regulated in well- and poorly differentiated OSCC, respectively. Based on the characteristics of OSCC differentiation, a molecular grade of OSCC was obtained and combined with pathological images to establish a novel prediction system through deep learning, named ShuffleNetV2-based Molecular Grade of OSCC (SMGO). Importantly, our independent multi-center cohort of OSCC (n = 340) confirmed the high accuracy of SMGO. CONCLUSIONS: OSCC differentiation was a significant indicator of prognosis and chemotherapy selection. Importantly, SMGO could be an indispensable reference for OSCC differentiation and assist the decision-making of chemotherapy.

ESCO2's oncogenic role in human tumors: a pan-cancer analysis and experimental validation.

PURPOSE: Establishment of sister chromatid cohesion N-acetyltransferase 2 (ESCO2) is involved in the mitotic S-phase adhesins acetylation and is responsible for bridging two sister chromatids. However, present ESCO2 cancer research is limited to a few cancers. No systematic pan-cancer analysis has been conducted to investigate its role in diagnosis, prognosis, and effector function. METHODS: We thoroughly examined the ESCO2 carcinogenesis in pan-cancer by combining public databases such as The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), UALCAN and Tumor Immune Single-cell Hub (TISCH). The analysis includes differential expression analysis, survival analysis, cellular effector function, gene mutation, single cell analysis, and tumor immune cell infiltration. Furthermore, we confirmed ESCO2's impacts on clear cell renal cell carcinoma (ccRCC) cells' proliferative and invasive capacities in vitro. RESULTS: In our study, 30 of 33 cancer types exhibited considerably greater levels of ESCO2 expression in tumor tissue using TCGA and GTEx databases, whereas acute myeloid leukemia (LAML) exhibited significantly lower levels. Kaplan-Meier survival analyses in adrenocortical carcinoma (ACC), kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), brain lower grade glioma (LGG), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), mesothelioma (MESO), and pancreatic adenocarcinoma (PAAD) demonstrated that tumor patients with high ESCO2 expression have short survival periods. However, in thymoma (THYM), colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ), ESCO2 was a favorable prognostic factor. Moreover, ESCO2 expression positively correlates with tumor stage and tumor size in several cancers, including LIHC, KIRC, KIRP and LUAD. Function analysis revealed that ESCO2 participates in mitosis, cell cycle, DNA damage repair, and other processes. CDK1 was identified as a downstream gene regulated by ESCO2. Furthermore, ESCO2 might also be implicated in immune cell infiltration. Finally, ESCO2'S knockdown significantly inhibited the A498 and T24 cells' proliferation, invasion, and migration. CONCLUSIONS: In conclusion, ESCO2 is a possible pan-cancer biomarker and oncogene that can reliably predict the prognosis of cancer patients. ESCO2 was also implicated in the cell cycle and proliferation regulation. In a nutshell, ESCO2 is a therapeutically viable and dependable target.

DNT cells mediate resistance to CAR-T cells therapy in a pediatric patient with relapsed and refractory B-ALL.

Chimeric antigen receptor T (CAR-T) cells therapy is a milestone achievement in the immunotherapy of relapsed and refractory (R/R) B cell acute lymphoblastic leukemia (B-ALL). However, some patients treated with CAR-T cells do not achieve complete remission, the mechanisms of which have not been elucidated. In the present study, we report a 9-year-old pediatric patient with refractory B-ALL received a triple infusion of autologous CD19 CAR-T cells therapy after the second relapse. CAR-T cells expanded in the peripheral blood and bone marrow. However, the patient did not achieve complete remission, indicating a lack of response to CAR-T cells therapy. Analysis of etiological factors revealed that the number of CD4 and CD8 double-negative T (DNT) cells was significantly upregulated in the peripheral blood, bone marrow, and autologous CAR-T cells products. In conclusiont, these findings indicate that DNT cells mediated resistance to CAR-T cells therapy in this pediatric patient with R/R B-ALL.

Colorectal cancer-derived extracellular vesicles containing HSP70 enhance macrophage phagocytosis by up-regulating MARCO expression.

In recent years, we have realized that extracellular vesicles (EVs) play a critical role in regulating the intercellular communication between tumor and immune cells in the tumor microenvironment (TME). Tumor-derived extracellular vesicles (TDEVs) profoundly affect the functional changes of tumor-associated macrophages (TAMs) and promote their M2 polarization. Meanwhile, macrophages have a strong phagocytic ability in phagocytosing apoptotic cells. Especially in the course of chemotherapy or radiotherapy, TAMs can phagocytose and remove apoptotic tumor cells, showing anti-inflammatory and pro-tumor effects. However, the underlying mechanisms by which TDEVs regulate macrophage phagocytosis of apoptotic tumor cells have not been fully elucidated. In this study, we focused on the effect of colorectal cancer-derived extracellular vesicles (CRC-EVs) on macrophages. We demonstrated that CRC-EVs enhanced macrophage phagocytosis of apoptotic CRC cells. We then determined that heat shock protein 70 (HSP70) carried in CRC-EVs was responsible for this effect by using mass spectrometry-based proteomic analysis and the CRISPR-Cas9 system. Through transcriptome sequencing of macrophages, we found that the enhanced phagocytosis of macrophages was mainly due to the up-regulation of the macrophage receptor with collagenous structure (MARCO). In addition, we confirmed that the up-regulation of MARCO was mediated by the AKT-STAT3 signaling pathway. Taken together, this study revealed a novel EVs-mediated macrophage phagocytosis mechanism involved in the clearance of apoptotic tumor cells in the TME. Targeting TDEVs may have potential therapeutic applications in tumor treatment.

Distributed Sensitivity and Critical Interference Power Analysis of Multi-Degree-of-Freedom Navigation Interference for Global Navigation Satellite System Array Antennas.

Current research on the interference of GNSS (Global Navigation Satellite System) array antennas focuses on the single interference effect and the improvement of interference hardware capability, while the multi-degree-of-freedom (DOF) interference model and mechanism remain to be fully studied. Aiming at this problem, this paper analyzes the preconditions for the definition of anti-jamming degrees of freedom and the characteristics of super-DOF interference through formula derivation and simulation. First, by analyzing the influence of the number of interfering signals on the angular resolution, the prerequisite of the definition of anti-interference degrees of freedom in the airspace is proposed. Second, the definition of anti-interference degrees of freedom is used to calculate the change rule of the critical power of the interference under different numbers of interfering signals. Finally, the influence of super-DOF interference on the array antenna is analyzed. The results show that the prerequisite for the anti-interference freedom of the array antenna is that the distribution interval of the interfering signal is greater than 15°, taking a four-array element uniform circular array antenna as an example. The critical interference power of the array antenna decreases by about 15 dB when the number of interfering signals exceeds the degrees of freedom of the array antenna's interference immunity, provided that the interference resolution is satisfied. The conclusions of this paper give the critical power change rule of multi-DOF interference and the effect of super-DOF interference, as well as the prerequisites for the setting of interference signals, which can be used, for example, in the deployment of distributed interference sources and the development of anti-jamming algorithms.

Development and validation of a nomogram for predicting osteoporosis in prostate cancer patients: A cross-sectional study from China.

BACKGROUND: The specific risk factors contributing to the development of osteoporosis and the appropriate timing of treatment in Chinese prostate cancer (PCa) patients remain unclear. Our objective was to develop and validate a nomogram capable of predicting the occurrence of osteoporosis in PCa patients. METHODS: We conducted a cross-sectional study with PCa patients attending the Second Hospital of Tianjin Medical University, collecting data from June 2021 to February 2023. The patients were divided into training and validation sets in a 7:3 ratio. The LASSO regression was used to identify the most relevant predictive variables, and the multivariable logistic regression was used to construct the nomogram. The nomogram's performance was validated through receiver operating characteristic (ROC) curves, C-index, calibration curves, and decision curve analysis (DCA) in both the training and validation sets. RESULTS: We collected data from a total of 596 patients and then constructed the nomogram using age, body mass index, hemoglobin, vitamin D3, testosterone, and androgen deprivation therapy duration. The C-index of the nomogram was 0.923 in the training set and 0.859 in the validation set. The nomogram showed good consistency in both sets. DCA demonstrated the clinical benefit of the nomogram across various prediction thresholds. Furthermore, a separate nomogram was constructed to predict bone loss in patients undergoing ADT, exhibiting equally favorable diagnostic performance and clinical benefit. CONCLUSION: This study constructed two reliable nomograms to predict osteoporosis and bone loss, integrating personal health information and PCa-specific treatment data. These nomograms offer an easy and individualized approach to predict the occurrence of osteoporosis and bone loss in PCa patients.

Stereoselective Construction of Unsymmetrically Linked Heterocycles via Palladium-Catalyzed Alkyne Insertion/Cycloimidoylation Cascade.

A novel strategy to access unsymmetrically linked heterocycles via palladium-catalyzed acylcycloimidoylation of alkyne-tethered carbamoyl chlorides with isocyanides has been developed. Functionalized isocyanides were successfully applied as imine-containing heterocycle precursors to capture the vinyl-PdII intermediate, which was generated from a syn-carbopalladation of alkyne, followed by subsequent intramolecular C-H bond activation/imidoylative Heck reactions. Methylene oxindoles within Z-tetrasubstituted olefins were obtained in high yields with excellent stereoselectivities. Broad functional groups were well tolerated under mild reaction conditions.

SNAI2 promotes the malignant transformation of oral leukoplakia by modulating p-EMT.

OBJECTIVE: Snail family transcriptional repressor 2 (SNAI2) is a key regulator of partial epithelial-mesenchymal transition (p-EMT) and is associated with tumorigenesis. Whether SNAI2 promotes oral leukoplakia (OLK) malignant transformation by modulating p-EMT is unclear. MATERIALS AND METHODS: This study utilized two clinical datasets (GSE26549 and GSE85195) from the Gene Expression Omnibus database, cytological experiments, and a 4-nitroquinoline 1-oxide-induced mice model to explore the role of SNAI2 in OLK malignant transformation. RESULTS: The clinical cohort found SNAI2, as a risk factor (HR = 2.50, 95% CI: 1.08-5.79, p = 0.033), could promote OLK malignant transformation (p = 0.012). Cytological experiments indicated that SNAI2 overexpression promoted DOK cell proliferation, invasion, migration, and increase the protein expression of p-EMT relative signatures, whereas SNAI2 silencing has opposite effects. Furthermore, the mice model and clinical datasets demonstrated the expression of SNAI2 and p-EMT relative signatures were increased with OLK malignant transformation. And SNAI2 was strongly correlated with p-EMT. Besides, co-expressed genes of SNAI2 were also enriched in p-EMT relative biological processes and signaling pathways. CONCLUSIONS: p-EMT plays a significant role in promoting the OLK malignant transformation. As an important regulator of p-EMT, SNAI2 could be a target to block the OLK malignant transformation.

Comparative analysis of two arecoline-induced oral submucous fibrosis models.

OBJECTIVE: The limited understanding of the molecular mechanism for oral submucosal fibrosis (OSF) poses challenges to the development of effective prevention and treatment strategies. The lack of suitable animal models is a major hindrance. Therefore, this study aimed to address this issue by comparing commonly used arecoline-induced water drinking and injection mouse models. MATERIALS AND METHODS: The mice were subjected to two protocols: receiving 2 mg/mL arecoline in drinking water and 4 mg/mL arecoline saline solution injections every other day. Tissues were collected at regular 4-week intervals, with a final time point of 20 weeks. Stereo microscopy and histomorphological analysis were performed on live and harvested tissues, respectively. RESULTS: During arecoline treatment, collagen deposition and myofibroblast proliferation progressively increased in both models. Changes in the collagen I/III ratio indicated that both models exhibited characteristics of the early and intermediate stages of OSF after 20 weeks of arecoline induction. The water-drinking model also demonstrated multi-organ fibrosis involving the tongue, lungs, and small intestine. CONCLUSION: Both the water drinking and injection mouse models effectively induced OSF, but the water-drinking model better mirrored the observed pathogenesis in patients with OSF. These models provide valuable tools for investigating the mechanisms underlying OSF.

EVALUATING THE OUTCOMES OF MINIMALLY INVASIVE THERAPY VS SURGERY FOR ORAL MUCOCELES: A SYSTEMATIC REVIEW AND META-ANALYSIS.

OBJECTIVES: Oral mucoceles could be managed with minimally invasive therapy (MIT) or conventional surgery, and both modalities reportedly possess advantages and demerits. This review aims to investigate and compare the postoperative disease recurrence and complications of these interventions with each other. METHODS: Relevant studies were searched in 5 databases (PubMed, Embase, Scopus, Web of Science and Cochrane Library) from inception to December 17, 2022. The pooled relative risks (RRs) with 95% confidence intervals (CIs) of disease recurrence, overall complications, nerve injury and bleeding/hematoma in MIT vs conventional surgery were calculated in meta-analysis. Trial Sequential Analysis (TSA) was performed to confirm our conclusions and assess the need for future trials. RESULTS: Six studies (1 randomized controlled trial and 5 cohort studies) were included for systematic review and meta-analysis. The results showed no significant difference in recurrence between MIT and conventional surgery (RR=0.80; 95% CI, 0.39-1.64; P = .54; I2=17%), and the results of the subgroup analysis were consistent. The incidence of the overall complications (RR=0.15; 95% CI, 0.05-0.47; P = .001; I2=0%) and nerve injury (RR=0.22; 95% CI, 0.06-0.82; P = .02; I2=0%) was significantly lower in MIT than in conventional surgery, but the incidence of bleeding/hematoma presented no significant difference (RR=0.34; 95% CI, 0.06-2.07; P = .24; I2=0%). The results of TSA suggested that the conclusion of MIT significantly reducing the risk of overall complications was stable; and additional clinical trials were need in the future for confirming the conclusions regarding disease recurrence, nerve injury and bleeding/hematoma. CONCLUSIONS: For mucoceles in the oral cavity, MIT is less likely to induce complications (i.e., nerve injury) compared with surgical removal, and the control of disease recurrence is comparable to that of conventional surgery. Therefore, the application of MIT for mucoceles could be a promising alternative to conventional surgery when the latter is not applicable.

Mutagenesis and Resistance Development of Bacteria Challenged by Silver Nanoparticles.

Because of their extremely broad spectrum and strong biocidal power, nanoparticles of metals, especially silver (AgNPs), have been widely applied as effective antimicrobial agents against bacteria, fungi, and so on. However, the mutagenic effects of AgNPs and resistance mechanisms of target cells remain controversial. In this study, we discover that AgNPs do not speed up resistance mutation generation by accelerating genome-wide mutation rate of the target bacterium Escherichia coli. AgNPs-treated bacteria also show decreased expression in quorum sensing (QS), one of the major mechanisms leading to population-level drug resistance in microbes. Nonetheless, these nanomaterials are not immune to resistance development by bacteria. Gene expression analysis, experimental evolution in response to sublethal or bactericidal AgNPs treatments, and gene editing reveal that bacteria acquire resistance mainly through two-component regulatory systems, especially those involved in metal detoxification, osmoregulation, and energy metabolism. Although these findings imply low mutagenic risks of nanomaterial-based antimicrobial agents, they also highlight the capacity for bacteria to evolve resistance.

Trends and predictions of lung cancer incidence in Jiangsu Province, China, 2009-2030: a bayesian age-period-cohort modelling study.

BACKGROUND: Lung cancer is currently the most frequent cancer in Jiangsu Province, China, and the features of cancer distribution have changed continuously in the last decade. The aim of this study was to analyse the trend of the incidence of lung cancer in Jiangsu from 2009 to 2018 and predict the incidence from 2019 to 2030. METHODS: Data on lung cancer incidence in Jiangsu from 2009 to 2018 were retrieved from the Jiangsu Cancer Registry. The average annual percentage change (AAPC) was used to quantify the trend of the lung cancer age-standardized rate (ASR) using Joinpoint software. Bayesian age-period-cohort models were used to predict lung cancer incidence up to 2030. RESULTS: In Jiangsu, the lung cancer crude rate increased from 45.73 per 100,000 in 2009 to 69.93 per 100,000 in 2018. The lung cancer ASR increased from 29.03 per 100,000 to 34.22 per 100,000 during the same period (AAPC = 2.17%, 95% confidence interval [CI], 1.54%, 2.80%). Between 2019 and 2030, the lung cancer ASR is predicted to decrease slightly to 32.14 per 100,000 (95% highest density interval [HDI], 24.99, 40.22). Meanwhile, the ASR showed a downward trend in males and rural regions while remaining stable in females and urban regions. CONCLUSION: We predict that the incidence of lung cancer in Jiangsu will decrease in the next 12 years, mainly due to the decrease in males and rural areas. Therefore, future lung cancer prevention and control efforts should be focused on females and urban regions.

Association between physical activity and cancer risk among Chinese adults: a 10-year prospective study.

BACKGROUND: In China, the quantity of physical activity differs from that in Western countries. Substantial uncertainty remains about the relevance of physical activity for cancer subtypes among Chinese adults. OBJECTIVE: This study aimed to investigate the association between total daily physical activity and the incidence of common types of cancer. METHODS: A total of 53,269 participants aged 30-79 years were derived from the Wuzhong subcohort of the China Kadoorie Biobank study during 2004-2008. We included 52,938 cancer-free participants in the final analysis. Incident cancers were identified through linkage with the health insurance system and death registries. Cox proportional hazard models were introduced to assess the associations of total daily physical activity with the incidence of 6 common types of cancer. RESULTS: During a follow-up of 10.1 years, 3,674 cases of cancer were identified, including 794 (21.6%) from stomach cancer, 722 (19.7%) from lung cancer, 458 (12.5%) from colorectal cancer, 338 (9.2%) from liver cancer, 250 (6.8%) from breast cancer, and 231 (6.3%) from oesophageal cancer. Compared to the participants in the lowest quartile of physical activity levels, those in the highest quartile had an 11% lower risk for total cancer incidence (hazard ratio [HR]: 0.89, 95% confidence interval [CI]: 0.81-0.99), 25% lower risk for lung cancer incidence (HR: 0.75, 95% CI: 0.60-0.94), and 26% lower risk for colorectal cancer incidence (HR: 0.74, 95% CI: 0.55-1.00). There were significant interactions of physical activity with sex and smoking on total cancer (both P for interaction < 0.005), showing a lower risk for females and never smokers (HR: 0.92, 95% CI: 0.87-0.98 and HR: 0.93, 95% CI: 0.87-0.98, respectively). CONCLUSIONS: Higher physical activity levels are associated with a reduced risk of total, lung, and colorectal cancer.

Management of epistaxis in hereditary haemorrhagic telangiectasia (HHT) patients using pulsed dye laser and the effect of withholding treatment during the COVID pandemic.

Using a patient survey, pulsed dye laser (PDL) treatment of epistaxis for hereditary haemorrhagic telangiectasia (HHT) patients was evaluated after initial referral. Subsequently, due to the COVID pandemic, a natural experimental set-up allowed assessment of an enforced withdrawal of treatment. A total of 34 subjects were identified as undergoing PDL for HHT-related epistaxis. They were surveyed to look at the effectiveness of PDL treatment after initial referral and at the effect of delay to treatment during COVID on epistaxis and the associated quality of life. The survey also examined the comparison to other available treatments. Retrospective pre-COVID Epistaxis Severity Scores (ESS) were compared to post-COVID data to assess the effect of treatment withdrawal. The patients were then followed up after resumption of their treatment to assess the ensuing change in ESS. After initial referral, frequency and severity of epistaxis decreased. Fifty-six percent of patients experienced several bleeds per day before treatment, compared to 12% after. 88% of patients had episodes of epistaxis longer than 5 min, which was halved to 44% after treatment. Average ESS pre-COVID was 4.42 compared to 5.43 post-COVID delay, with a significant statistical difference (p = 0.02). On resumption of treatment, average ESS reduced to below pre-COVID levels at 4.39 after only 2 sessions. Seventy-six percent of patients found that withdrawal of PDL during COVID diminished their quality of life. PDL treatment of nasal mucosal telangiectasia reduces the frequency and duration of epistaxis. The ESS is reduced following treatment with PDL and quality of life subjectively improved.

Curcumin Derivative C66 Suppresses Pancreatic Cancer Progression through the Inhibition of JNK-Mediated Inflammation.

Pancreatic adenocarcinoma is by far the deadliest type of cancer. Inflammation is one of the important risk factors in tumor development. However, it is not yet clear whether deterioration in pancreatic cancer patients is related to inflammation, as well as the underlying mechanism. In addition, JNK is abnormally activated in pancreatic cancer cells and the JNK inhibitor C66 reduces the inflammatory microenvironment in the tumor. Therefore, the aim of this study was to evaluate the role of C66 in the proliferation and migration of pancreatic cancer. Our results showed that various inflammatory cytokines, such as IL-1ß, IL-6, IL-8, and IL-15, were more expressed in pancreatic cancer than in the matching normal tissue. Furthermore, C66, a curcumin analogue with good anti-inflammatory activity, inhibited the proliferation and migration of pancreatic cancer cells in a dose-dependent manner, and effectively inhibited the expression of the above inflammatory factors. Our previous research demonstrated that C66 prevents the inflammatory response by targeting JNK. Therefore, in this study, JNK activity in pancreatic cancer cells was investigated, revealing that JNK was highly activated, and the treatment with C66 inhibited the phosphorylation of JNK. Next, shJNK was used to knockdown JNK expression in pancreatic cancer cells to further confirm the role of JNK in the proliferation and migration of this tumor, as well as in the inflammatory tumor microenvironment (TME). The results demonstrated that JNK knockdown could significantly inhibit the proliferation and migration of pancreatic cancer. Moreover, the low JNK expression in pancreatic cancer cells significantly inhibited the expression of various inflammatory factors. These results indicated that C66 inhibited the progression of pancreatic cancer through the inhibition of JNK-mediated inflammation.

Follicular lymphoma manifests as multiple erosive and proliferative lesions of the oral mucosa: case report and brief literature review.

BACKGROUND: Erosion is one of the most common and basic lesions of oral mucosal diseases. Long-term refractory oral erosions, induced by autoimmune blistering diseases, infectious diseases, malignant diseases, and some rare conditions, may substantially reduce the quality of life of patients or even constitute a life-threatening condition, resulting in a clinical dilemma regarding the accurate diagnosis and precise management of these diseases. As a special type of malignant lymphoma, most lesions of follicular lymphoma (FL) in the oral mucosa present as masses or swelling of the oral mucosa, while emerging novel presentations lead to intractable diagnoses. Hence, diagnostic algorithms for such diseases are clinically required.  CASE PRESENTATION: A 55-year-old female patient presented to the clinic with long-lasting oral mucosal erosions and proliferative lesions. Blood tests, pathological examinations of oral lesions including haematoxylin-eosin (HE) staining, and direct immunofluorescence precluded all of the potential diagnoses described previously. Unexpectedly, positron emission tomography/computed tomography (PET/CT) and abdominal CT of the patient revealed a dense mass in the retroperitoneal area, and the final diagnosis of the retroperitoneal mass was FL. After three courses of chemotherapy conducted by the haematologist, the erosion and proliferative lesions in the patient's oral mucosa had significantly improved. HE and immunohistochemical staining results of intraoral lesions also confirmed it as oral FL. The successful diagnosis of FL in this case is of great clinical significance, as the oral and abdominal FL were treated in a timely manner to avoid unfavourable outcomes. CONCLUSIONS: To the best of our knowledge, this is the first case of FL that exhibited widespread erosions interspersed with proliferative lesions. Clinicians should be aware of oral FL or seek systemic factors in the presence of similar refractory oral erosions when treatment is non-responsive and the diagnosis is intractable.

Explainable multi-instance and multi-task learning for COVID-19 diagnosis and lesion segmentation in CT images.

Coronavirus Disease 2019 (COVID-19) still presents a pandemic trend globally. Detecting infected individuals and analyzing their status can provide patients with proper healthcare while protecting the normal population. Chest CT (computed tomography) is an effective tool for screening of COVID-19. It displays detailed pathology-related information. To achieve automated COVID-19 diagnosis and lung CT image segmentation, convolutional neural networks (CNNs) have become mainstream methods. However, most of the previous works consider automated diagnosis and image segmentation as two independent tasks, in which some focus on lung fields segmentation and the others focus on single-lesion segmentation. Moreover, lack of clinical explainability is a common problem for CNN-based methods. In such context, we develop a multi-task learning framework in which the diagnosis of COVID-19 and multi-lesion recognition (segmentation of CT images) are achieved simultaneously. The core of the proposed framework is an explainable multi-instance multi-task network. The network learns task-related features adaptively with learnable weights, and gives explicable diagnosis results by suggesting local CT images with lesions as additional evidence. Then, severity assessment of COVID-19 and lesion quantification are performed to analyze patient status. Extensive experimental results on real-world datasets show that the proposed framework outperforms all the compared approaches for COVID-19 diagnosis and multi-lesion segmentation.

The functions of autophagy at the tumour-immune interface.

Autophagy is frequently induced in the hypoxic tumour microenvironment. Accumulating evidence reveals important functions of autophagy at the tumour-immune interface. Herein, we propose an update on the roles of autophagy in modulating tumour immunity. Autophagy promotes adaptive resistance of established tumours to the cytotoxic effects of natural killer cells (NKs), macrophages and effector T cells. Increased autophagic flux in tumours dampen their immunogenicity and inhibits the expansion of cytotoxic T lymphocytes (CTLs) by suppressing the activation of STING type I interferon signalling (IFN-I) innate immune sensing pathway. Autophagy in suppressive tumour-infiltrating immune subsets maintains their survival through metabolic remodelling. On the other hand, autophagy is involved in the antigen processing and presentation process, which is essential for anti-tumour immune responses. Genetic deletion of autophagy induces spontaneous tumours in some models. Thus, the role of autophagy is context-dependent. In summary, our review has revealed the dichotomous roles of autophagy in modulating tumour immunity. Broad targeting of autophagy may not yield maximal benefits. The characterization of specific genes regulating tumour immunogenicity and innovation in targeted delivery of autophagy inhibitors into certain tumours are among the most urgent tasks to sensitize cold cancers to immunotherapy.

Anionic Biopolymer Assisted Preparation of MoO2@C Heterostructure Nanoparticles with Oxygen Vacancies for Ambient Electrocatalytic Ammonia Synthesis.

Recently, Mo-based metal catalysts are widely applied in the electrocatalytic nitrogen reduction reaction (NRR) due to the lower binding energy between the Mo atom and N atom. The design of a Mo-based catalyst@carbon heterostructure and the introduction of anion vacancies are effective measures to improve their NRR performance. In this research, the cross-linked Vo-MoO2@C (Vo means oxygen vacancies) heterostructure nanoparticles with rich oxygen vacancies are first synthesized via pectin assisted hydrothermal reaction followed by calcination and treating with NaBH4 solution. Vo-MoO2@C exhibits good electrocatalytic NRR performance with an ammonia yield rate of 9.75 µg h-1 mg-1 at -0.5 V (RHE) and a Faraday efficiency (FE) of 3.24% at -0.3 V (RHE) under ambient conditions.

Industrial applications of digital twins.

A digital twin (DT) is classically defined as the virtual replica of a real-world product, system, being, communities, even cities that are continuously updated with data from its physical counterpart, as well as its environment. It bridges the virtual cyberspace with the physical entities and, as such, is considered to be the pillar of Industry 4.0 and the innovation backbone of the future. A DT is created and used throughout the whole life cycle of the entity it replicates, from cradle to grave, so to speak. This article focuses on the present state of the art of DTs, concentrating on the use of DTs in industry in the context of smart manufacturing, especially from the point of view of plantwide optimization. The main capabilities of DTs (mirroring, shadowing and threading) are discussed in this context. The article concludes with a perspective on the future. This article is part of the theme issue 'Towards symbiotic autonomous systems'.