Explore the vast range of titles available.

Pancreatic cancer has a dismal prognosis due to the early development of systemic metastatic disease. Chemotherapeutic agents are the only systemic therapy that offers patients meaningful benefit. This study reviewed the literature for recently published Phase III clinical trials whose results have guided the current standards of chemotherapy for pancreatic cancer. Although combination chemotherapy regimens are shown to be superior to gemcitabine monotherapy for both metastatic pancreatic cancer and adjuvant chemotherapy after surgical resection, it should be recognized that all combination chemotherapy regimens offer only limited benefits. In addition, there is a paucity of clinical trials that directly compare the various combination chemotherapy regimens. With the advancement of systemic cancer treatment beyond chemotherapy, it is important to devote more investigation into better understanding the biology of these chemotherapy regimens, such that we combine them with targeted therapeutics and immunotherapeutics in a rational and scientific manner. For the current treatment of pancreatic cancer, the available chemotherapy regimens have shown modest but statistically significant improvements in survival. However, it is important to avoid cross-comparisons of trials and choose regimens based on patient characteristics and the side-effect profiles of the regimen.

Summary Ligand‐receptor pairs play important roles in cell–cell communication for multicellular organisms in response to environmental cues. Recently, the emergence of single‐cell RNA‐sequencing (scRNA‐seq) provides unprecedented opportunities to investigate cellular communication based on ligand‐receptor expression. However, so far, no reliable ligand‐receptor interaction database is available for plant species. In this study, we developed PlantPhoneDB (https://jasonxu.shinyapps.io/PlantPhoneDB/), a pan‐plant database comprising a large number of high‐confidence ligand‐receptor pairs manually curated from seven resources. Also, we developed a PlantPhoneDB R package, which not only provided optional four scoring approaches that calculate interaction scores of ligand‐receptor pairs between cell types but also provided visualization functions to present analysis results. At the PlantPhoneDB web interface, the processed datasets and results can be searched, browsed, and downloaded. To uncover novel cell–cell communication events in plants, we applied the PlantPhoneDB R package on GSE121619 dataset to infer significant cell–cell interactions of heat‐shocked root cells in Arabidopsis thaliana. As a result, the PlantPhoneDB predicted the actively communicating AT1G28290‐AT2G14890 ligand‐receptor pair in atrichoblast–cortex cell pair in Arabidopsis thaliana. Importantly, the downstream target genes of this ligand‐receptor pair were significantly enriched in the ribosome pathway, which facilitated plants adapting to environmental changes. In conclusion, PlantPhoneDB provided researchers with integrated resources to infer cell–cell communication from scRNA‐seq datasets.

Epigenetic regulation of gene expression in cancer cells has been extensively studied in recent decades, resulting in the FDA approval of multiple epigenetic agents for treating different cancer types. Recent studies have revealed novel roles of epigenetic dysregulation in altering the phenotypes of immune cells and tumor-associated stromal cells, including fibroblasts and endothelial cells. As a result, epigenetic dysregulation of these cells reshapes the tumor microenvironment (TME), changing it from an antitumor environment to an immunosuppressive environment. Here, we review recent studies demonstrating how specific epigenetic mechanisms drive aspects of stromal and immune cell differentiation with implications for the development of solid tumor therapeutics, focusing on the pancreatic ductal adenocarcinoma (PDA) TME as a representative of solid tumors. Due to their unique ability to reprogram the TME into a more immunopermissive environment, epigenetic agents have great potential for sensitizing cancer immunotherapy to augment the antitumor response, as an immunopermissive TME is a prerequisite for the success of cancer immunotherapy but is often not developed with solid tumors. The idea of combining epigenetic agents with cancer immunotherapy has been tested both in preclinical settings and in multiple clinical trials. In this review, we highlight the basic biological mechanisms underlying the synergy between epigenetic therapy and immunotherapy and discuss current efforts to translate this knowledge into clinical benefits for patients.

The genus Orthonairovirus , which is part of the family Nairoviridae , includes the important tick-transmitted pathogens Crimean–Congo hemorrhagic fever virus and Nairobi sheep disease virus, as well as many other poorly characterized viruses found in ticks, birds and mammals 1 , 2 . In this study, we identified a new orthonairovirus, Songling virus (SGLV), from patients who reported being bitten by ticks in Heilongjiang Province in northeastern China. SGLV shared similar genomic and morphological features with orthonairoviruses and phylogenetically formed a unique clade in Tamdy orthonairovirus of the Nairoviridae family. The isolated SGLV induced cytopathic effects in human hepatoma cells in vitro. SGLV infection was confirmed in 42 hospitalized patients analyzed between 2017 and 2018, with the main clinical manifestations being headache, fever, depression, fatigue and dizziness. More than two-thirds (69%) of patients generated virus-specific antibody responses in the acute phase. Taken together, these results suggest that this newly discovered orthonairovirus is associated with human febrile illness in China. Songling virus is a newly discovered orthonairovirus found in the blood of patients hospitalized with febrile illness and having a history of tick bites.

Immunotherapies such as immune checkpoint blockade (ICB) and adoptive cell therapy (ACT) have revolutionized cancer treatment, especially in patients whose disease was otherwise considered incurable. However, primary and secondary resistance to single agent immunotherapy often results in treatment failure, and only a minority of patients experience long-term benefits. This review article will discuss the relationship between cancer immune response and mechanisms of resistance to immunotherapy. It will also provide a comprehensive review on the latest clinical status of combination therapies (e.g., immunotherapy with chemotherapy, radiation therapy and targeted therapy), and discuss combination therapies approved by the US Food and Drug Administration. It will provide an overview of therapies targeting cytokines and other soluble immunoregulatory factors, ACT, virotherapy, innate immune modifiers and cancer vaccines, as well as combination therapies that exploit alternative immune targets and other therapeutic modalities. Finally, this review will include the stimulating insights from the 2020 China Immuno-Oncology Workshop co-organized by the Chinese American Hematologist and Oncologist Network (CAHON), the China National Medical Product Administration (NMPA) and Tsinghua University School of Medicine.

Abstract Anti-cancer therapies usually focus on tumor cells, but non-tumor stromal components in the tumor microenvironment also play vital roles in tumor initiation and progression, which may be the prognostic factors and potential therapeutic targets. Cancer-associated fibroblasts (CAFs) are the essential component in the tumor environment, exhibiting high heterogeneity in their cell origin and phenotype with diverse functions that influence tumor angiogenesis, immune systems, and metabolism. Single-cell RNA sequencing and genetically engineered mouse models have increased our understanding of CAF diversity, and many subtypes have been defined. However, the precise functions of these subtypes need to be studied and validated. Studies of signaling pathways and epigenetic changes in CAFs facilitate understanding of the phenotypes of CAFs and the crosstalk between tumor cells and CAFs to provide potential therapeutic targets. Some clinical trials, including phase III trials targeting CAFs, have been performed recently. However, few of these trials have generated promising results, which indicates that the complexity of CAFs in the tumor microenvironment remains largely unknown, and in-depth investigations of CAFs should be performed. This review summarizes the research on CAFs, focusing on the heterogeneity of their phenotypes and functions, specific signaling pathways, and the therapeutic strategies involving CAFs. Additionally, we briefly discuss the current technologies commonly used in CAF studies and describe the challenges and future perspectives of CAF research.

Electroconductive hydrogels are very attractive candidates for accelerated spinal cord injury (SCI) repair because they match the electrical and mechanical properties of neural tissue. However, electroconductive hydrogel implantation can potentially aggravate inflammation, and hinder its repair efficacy. Bone marrow stem cell‐derived exosomes (BMSC‐exosomes) have shown immunomodulatory and tissue regeneration effects, therefore, neural tissue‐like electroconductive hydrogels loaded with BMSC‐exosomes are developed for the synergistic treatment of SCI. These exosomes‐loaded electroconductive hydrogels modulate microglial M2 polarization via the NF‐κB pathway, and synergistically enhance neuronal and oligodendrocyte differentiation of neural stem cells (NSCs) while inhibiting astrocyte differentiation, and also increase axon outgrowth via the PTEN/PI3K/AKT/mTOR pathway. Furthermore, exosomes combined electroconductive hydrogels significantly decrease the number of CD68‐positive microglia, enhance local NSCs recruitment, and promote neuronal and axonal regeneration, resulting in significant functional recovery at the early stage in an SCI mouse model. Hence, the findings of this study demonstrate that the combination of electroconductive hydrogels and BMSC‐exosomes is a promising therapeutic strategy for SCI repair. Neural tissue‐like electroconductive hydrogels loaded with bone marrow stem cell‐derived exosomes are developed. The mechanism of the exosomes‐loaded electroconductive hydrogel synergistically regulating neural stem cell differentiation is explored. The exosomes‐combined electroconductive hydrogels significantly decrease inflammation reaction, enhance local neurogenesis, and promote axonal regeneration, resulting in significant functional recovery at the early stage in a spinal cord injury mouse model.

CONFLICT OF INTEREST Prof. Lei Zheng is the Editor-in-Chief of Interdisciplinary Medicine. Editor-in-Chief Lei Zheng, Nanfang Hospital, Southern Medical University, Guangzhou, China. Honorary Editors-in-Chief Ben Zhong Tang, The Chinese University of Hong Kong, Shenzhen, China Qian Wang, Zhujiang Hospital, Southern Medical University, Guangzhou, China Associate Editors Sai Kiang Lim, Institute for Molecular and Cell Biology, A*STAR, Singapore, Singapore Jiashu Sun, National Center for Nanoscience and Technology, Beijing, China.

Gastric cancer (GC) is one of the leading causes of cancer-related death in both men and women due to delayed diagnosis and high metastatic frequency. Extracellular vesicles (EVs) are membrane-bound nanovesicles which are released by cells into body fluids such as plasma, saliva, breast milk, cerebrospinal fluid, semen, urine, lymphatic fluid, amniotic fluid, sputum and synovial fluid. EVs deliver almost all types of biomolecules such as proteins, nucleic acids, metabolites, and even pharmacological compounds. These bioactive molecules can be delivered to recipient cells to influence their biological properties, modify surrounding microenvironment and distant targets. The extensive exploration of EVs enhances our comprehension of GC biology referring to tumor growth, metastasis, immune response and evasion, chemoresistance and treatment. In this review, we will sum up the effects of GC-derived EVs to the tumor microenvironment. Moreover, we will also summarize the function of microenvironment-derived EVs in GC and discuss how the bidirectional communication between tumor and microenvironment affect GC growth, metastatic behavior, immune response, and drug resistance. At last, we prospect the clinical application viewpoint of EVs in GC.

To achieve zero-carbon economy, advanced anode catalysts are desirable for hydrogen production and biomass upgrading powered by renewable energy. Ni-based non-precious electrocatalysts are considered as potential candidates because of intrinsic redox attributes, but in-depth understanding and rational design of Ni site coordination still remain challenging. Here, we perform anodic electrochemical oxidation of Ni-metalloids (NiP x , NiS x , and NiSe x ) to in-situ construct different oxyanion-coordinated amorphous nickel oxyhydroxides (NiOOH-TO x ), among which NiOOH-PO x shows optimal local coordination environment and boosts electrocatalytic activity of Ni sites towards selective oxidation of methanol to formate. Experiments and theoretical results demonstrate that NiOOH-PO x possesses improved adsorption of OH* and methanol, and favors the formation of CH 3 O* intermediates. The coordinated phosphate oxyanions effectively tailor the d band center of Ni sites and increases Ni-O covalency, promoting the catalytic activity. This study provides additional insights into modulation of active-center coordination environment via oxyanions for organic molecules transformation. Coordination environments around metal sites are important in electrocatalysis. Here, Ni metalloid oxidation produces oxyanion doped amorphous Ni-oxyhydroxides where substitution with phosphorus is found to boost methanol electrooxidation activity.