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Corona virus disease 2019 (COVID-19) has caused a global outbreak and severely posed threat to people’s health and social stability. Mounting evidence suggests that immunopathological changes, including diminished lymphocytes and elevated cytokines, are important drivers of disease progression and death in coronavirus infections. Cytokine storm not only limits further spread of virus in the body but also induces secondary tissue damage through the secretion of large amounts of active mediators and inflammatory factors. It has been determined that cytokine storm is a major cause of deaths in COVID-19; therefore, in order to reverse the deterioration of severe and critically ill patients from this disease, the cytokine storm has become a key therapeutic target. Although specific mechanisms of the occurrences of cytokine storms in COVID-19 have not been fully illuminated, hyper-activated innate immune responses, and dysregulation of ACE2 (angiotensin converting enzyme 2) expression and its downstream pathways might provide possibilities. Tailored immunoregulatory therapies have been applied to counteract cytokine storms, such as inhibition of cytokines, corticosteroids, blood purification therapy, and mesenchymal stem cell therapy. This review will summarize advances in the research of cytokine storms induced by COVID-19, as well as potential intervention strategies to control cytokine storms.

Internet gaming addiction (IGA), depression, and anxiety are significant issues among children and adolescents, with substantial social implications. Understanding the specific characteristics of this relationship is crucial for developing effective prevention and intervention strategies. The present study employed network analysis to explore the symptom network of IGA, depression, and anxiety among 1,548 Chinese children and adolescents. The results showed that the core symptoms of IGA among children and adolescents were “tolerance”, “withdrawal”, and “conflict”. There was no significant gender difference in the structure, global strength, and core symptoms of IGA. Although there were no significant differences in the structure of the symptom network of IGA among children and adolescents of different ages, there were significant differences in global strength and some core symptoms (“conflict”). The core symptoms of the comorbidity of IGA, depression, and anxiety in children and adolescents included “feeling downhearted and blue”, “breathing difficulty”, “difficult to work up the initiative to do things”, and “withdrawal”. The comorbidity network did not show significant gender and age differences in network structure, but there were significant gender differences in global strength. Furthermore, there were significant gender and age differences in some core symptoms. The social impact of these findings is profound, highlighting the need for targeted interventions in schools and communities to address IGA and its comorbidities. Our results also suggest that interventions should be tailored to consider gender and age differences to maximize effectiveness.

The immune-cell origin of hematologic malignancies provides a unique avenue for the understanding of both the mechanisms of immune responsiveness and immune escape, which has accelerated the progress of immunotherapy. Several categories of immunotherapies have been developed and are being further evaluated in clinical trials for the treatment of blood cancers, including stem cell transplantation, immune checkpoint inhibitors, antigen-targeted antibodies, antibody-drug conjugates, tumor vaccines, and adoptive cell therapies. These immunotherapies have shown the potential to induce long-term remission in refractory or relapsed patients and have led to a paradigm shift in cancer treatment with great clinical success. Different immunotherapeutic approaches have their advantages but also shortcomings that need to be addressed. To provide clinicians with timely information on these revolutionary therapeutic approaches, the comprehensive review provides historical perspectives on the applications and clinical considerations of the immunotherapy. Here, we first outline the recent advances that have been made in the understanding of the various categories of immunotherapies in the treatment of hematologic malignancies. We further discuss the specific mechanisms of action, summarize the clinical trials and outcomes of immunotherapies in hematologic malignancies, as well as the adverse effects and toxicity management and then provide novel insights into challenges and future directions.

Background Artificial intelligence (AI) technologies are transforming medicine and healthcare. Scholars and practitioners have debated the philosophical, ethical, legal, and regulatory implications of medical AI, and empirical research on stakeholders’ knowledge, attitude, and practices has started to emerge. This study is a systematic review of published empirical studies of medical AI ethics with the goal of mapping the main approaches, findings, and limitations of scholarship to inform future practice considerations. Methods We searched seven databases for published peer-reviewed empirical studies on medical AI ethics and evaluated them in terms of types of technologies studied, geographic locations, stakeholders involved, research methods used, ethical principles studied, and major findings. Findings Thirty-six studies were included (published 2013-2022). They typically belonged to one of the three topics: exploratory studies of stakeholder knowledge and attitude toward medical AI, theory-building studies testing hypotheses regarding factors contributing to stakeholders’ acceptance of medical AI, and studies identifying and correcting bias in medical AI. Interpretation There is a disconnect between high-level ethical principles and guidelines developed by ethicists and empirical research on the topic and a need to embed ethicists in tandem with AI developers, clinicians, patients, and scholars of innovation and technology adoption in studying medical AI ethics.

The overlapping metabolic reprogramming of cancer and immune cells is a putative determinant of the antitumor immune response in cancer. Increased evidence suggests that cancer metabolism not only plays a crucial role in cancer signaling for sustaining tumorigenesis and survival, but also has wider implications in the regulation of antitumor immune response through both the release of metabolites and affecting the expression of immune molecules, such as lactate, PGE 2 , arginine, etc. Actually, this energetic interplay between tumor and immune cells leads to metabolic competition in the tumor ecosystem, limiting nutrient availability and leading to microenvironmental acidosis, which hinders immune cell function. More interestingly, metabolic reprogramming is also indispensable in the process of maintaining self and body homeostasis by various types of immune cells. At present, more and more studies pointed out that immune cell would undergo metabolic reprogramming during the process of proliferation, differentiation, and execution of effector functions, which is essential to the immune response. Herein, we discuss how metabolic reprogramming of cancer cells and immune cells regulate antitumor immune response and the possible approaches to targeting metabolic pathways in the context of anticancer immunotherapy. We also describe hypothetical combination treatments between immunotherapy and metabolic intervening that could be used to better unleash the potential of anticancer therapies.

Post-translational modifications of proteins in malignant transformation and tumor maintenance of pancreatic ductal adenocarcinoma (PDAC) in the context of KRAS signaling remain poorly understood. Here, we use the KPC mouse model to examine the effect of palmitoylation on pancreatic cancer progression. ZDHHC20, upregulated by KRAS , is abnormally overexpressed and associated with poor prognosis in patients with pancreatic cancer. Dysregulation of ZDHHC20 promotes pancreatic cancer progression in a palmitoylation-dependent manner. ZDHHC20 inhibits the chaperone-mediated autophagic degradation of YTHDF3 through S-palmitoylation of Cys474, which can result in abnormal accumulation of the oncogenic product MYC and thereby promote the malignant phenotypes of cancer cells. Further, we design a biologically active YTHDF3-derived peptide to competitively inhibit YTHDF3 palmitoylation mediated by ZDHHC20, which in turn downregulates MYC expression and inhibits the progression of KRAS mutant pancreatic cancer. Thus, these findings highlight the therapeutic potential of targeting the ZDHHC20–YTHDF3–MYC signaling axis in pancreatic cancer. The relevance of post-translational modifications in pancreatic cancer remains insufficiently explored. Here, the authors report that ZDHHC20-mediated S-Palmitoylation of the m6A reader YTHDF3 stabilizes MYC mRNA to promote the progression of KRAS-mutant pancreatic cancer.

Abiotic stresses induced by climate change and soil pollution cause significant crop yield loss. Identifying stress-resistant genes for genetic improvement is urgent and necessary. Reticulon (RTN, also called RTNLB in plants) is a widely distributed endoplasmic reticulum-associated protein in eukaryotic cells, playing a crucial role in stress response activities, including autophagy, endoplasmic reticulum stress, and osmotic regulation. However, the diversity of RTNLBs in plants has hindered comprehensive analysis. This study identified 20 OsRTNLBs from Oryza sativa through a comprehensive whole-genome analysis. Detailed information on their chromosomal localization, protein motifs, phylogenetic relationships, and gene collinearity has been provided. The effects of five major abiotic stresses—cold, heat, heavy metals, salt, and drought—on rice seedling development have been assessed. The expression levels of RTNLBs under these abiotic stresses show significant changes, with an overall increase in transcription levels under simulated drought stress and a decrease under the other four stresses. Three OsRTNLBs (OsRTNLB4, OsRTNLB8 and OsRTNLB9) have been identified as key proteins contributing to abiotic stress.

Despite the exciting breakthroughs in medical technology, cancer still accounts for one of the principle triggers of death and conventional therapeutic modalities often fail to attain an effective cure. Recently, nanobiotechnology has made huge advancement in cancer therapy with gigantic application potential because of their ability in achieving precise and controlled drug release, elevating drug solubility and reducing adverse effects. Carbon nanotubes (CNTs), one of the most promising carbon-related nanomaterials, have already achieved much success in biomedical field. Due to their excellent optical property, thermal and electronic conductivity, easy functionalization ability and high drug loading capacity, CNTs can be applied in a multifunctional way for cancer treatment and diagnosis. In this review, we will give an overview of the recent progress of CNT-based drug delivery systems in cancer theranostics, which emphasizes their targetability to intracellular components of tumor cells and extracellular elements in tumor microenvironment. Moreover, a detailed introduction on how CNTs penetrate inside the tumor cells to reach their sites of action and achieve the therapeutic effects, as well as their diagnostic applications will be highlighted. Graphic Abstract

Precipitation extremes are expected to intensify due to an increased moisture holding capacity in the atmosphere with higher temperatures; according to the Clausius-Clapeyron (CC) relation this increase is approximately 7% for every degree increase in temperature. Contrary to expectation, the relationship between precipitation extremes and surface temperature often differs from 7%/°C. Here, we explore this relationship further by estimating the sensitivity of precipitation with both dry-bulb temperature and dew point temperature across Australia. A much better correspondence to the CC relation is obtained when surface dew point temperature is used for the calculation of precipitation-temperature sensitivities instead of surface dry-bulb temperature with most sites exhibiting sensitivities close to, or in excess of, the CC relation. The sensitivity obtained using dew point temperature is more consistent across climatic region, precipitation duration, and precipitation percentile. We conclude that dew point temperature is a better measure of precipitation changes due to increases in atmospheric moisture than dry-bulb temperature.

Wilson’s disease (WD) is an autosomal recessive disease caused by mutation of the ATPase copper transporting β (ATP7B) gene, resulting in abnormal copper metabolism. We aimed to investigate the protective effect of GanDouLing (GDL) on neural stem cell (NSC) function in a mouse model of WD. NSCs were treated with different concentrations of GDL alone or in combination with penicillamine, following which we evaluated cellular growth, apoptosis, and differentiation. Nuclear factor E2-related factor 2 (Nrf2) pathway and NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation were analyzed via Western blotting. Treatment with GDL alone or in combination with penicillamine significantly increased proliferation and inhibited apoptosis of NSCs in a dose-dependent manner. In addition, GDL treatment remarkably promoted differentiation of NSCs. Consistently, levels of class III β-tubulin (Tuj1) and microtubule-associated protein 2 (MAP2) were significantly elevated, whereas glial fibrillary acidic protein (GFAP) levels were obviously suppressed in the presence of GDL or penicillamine. In vivo assays confirmed that GDL increased the ratio of Ki67+, Tuj1+, and MAP2+ cells and suppressed apoptosis in the hippocampal region in WD mice. Behavioral assays revealed that both GDL and penicillamine improved memory ability in WD models. Mechanistically, GDL treatment led to activation of Nrf2 signaling and suppression of the NLRP3 inflammasome in WD mice. Notably, inhibition of Nrf2 signaling reversed the protective effects of GDL on hippocampal NSCs. Collectively, these findings demonstrate that GDL exerts a protective effect on NSCs and promotes neurogenesis by targeting Nrf2 signaling and the NLRP3 inflammasome in WD.