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Epithelial–mesenchymal transition (EMT) is defined as a cellular process during which epithelial cells acquire mesenchymal phenotypes and behavior following the downregulation of epithelial features. EMT and its reversed process, the mesenchymal-epithelial transition (MET), and the special form of EMT, the endothelial-mesenchymal transition (EndMT), have been considered as mainstream concepts and general rules driving developmental and pathological processes, particularly cancer. However, discrepancies and disputes over EMT and EMT research have also grown over time. EMT is defined as transition between two cellular states, but it is unanimously agreed by EMT researchers that (1) neither the epithelial and mesenchymal states nor their regulatory networks have been clearly defined, (2) no EMT markers or factors can represent universally epithelial and mesenchymal states, and thus (3) EMT cannot be assessed on the basis of one or a few EMT markers. In contrast to definition and proposed roles of EMT, loss of epithelial feature does not cause mesenchymal phenotype, and EMT does not contribute to embryonic mesenchyme and neural crest formation, the key developmental events from which the EMT concept was derived. EMT and MET, represented by change in cell shapes or adhesiveness, or symbolized by EMT factors, are biased interpretation of the overall change in cellular property and regulatory networks during development and cancer progression. Moreover, EMT and MET are consequences rather than driving factors of developmental and pathological processes. The true meaning of EMT in some developmental and pathological processes, such as fibrosis, needs re-evaluation. EMT is believed to endow malignant features, such as migration, stemness, etc., to cancer cells. However, the core property of cancer (tumorigenic) cells is neural stemness, and the core EMT factors are components of the regulatory networks of neural stemness. Thus, EMT in cancer progression is misattribution of the roles of neural stemness to the unknown mesenchymal state. Similarly, neural crest EMT is misattribution of intrinsic property of neural crest cells to the unknown mesenchymal state. Lack of basic rationale in EMT and related concepts urges re-evaluation of their significance as general rules for understanding developmental and pathological processes, and re-evaluation of their significance in scientific research.

Cancer is a complex disease without a unified explanation for its cause so far. Our recent work demonstrates that cancer cells share similar regulatory networks and characteristics with embryonic neural cells. Based on the study, I will address the relationship between tumor and neural cells in more details. I collected the evidence from various aspects of cancer development in many other studies, and integrated the information from studies on cancer cell properties, cell fate specification during embryonic development and evolution. Synthesis of the information strongly supports that cancer cells share much more similarities with neural progenitor/stem cells than with mesenchymal-type cells and that tumorigenesis represents a process of gradual loss of cell or lineage identity and gain of characteristics of neural cells. I also discuss cancer EMT, a concept having been under intense debate, and possibly the true meaning of EMT in cancer initiation and development. This synthesis provides fresh insights into a unified explanation for and a previously unrecognized nature of tumorigenesis, which might not be revealed by studies on individual molecular events. The review will also present some brief suggestions for cancer research based on the proposed model of tumorigenesis.

China is recognized as the largest energy consumer and is also the country with the largest and fastest-aging population. Ongoing demographic changes may reshape China’s household-based energy consumption patterns because of the large gap in consumption behavior between the elderly and the young as well as varying attitudes toward the environment among generations. However, when the impact of China’s aging population on energy consumption is projected, the heterogeneous cognitive norms of generations in the process of demographic transition are not well understood. In this study, we assessed the future impact of China’s demographic transition on energy consumption using a proposed theoretical framework to distinguish between age and generational effects. Specifically, we used age–period–cohort (APC) detrended analysis to estimate age and generational effects based on China’s urban household survey data from 1992 to 2015. The results indicated large differences in energy use propensity across ages and generations. The elderly and younger generations tended to be energy-intensive consumers, resulting in higher energy consumption in this aging society. Our results consequently show that future changes in China’s elderly population will result in a substantial increase in energy consumption. By 2050, the changing consumption share of the elderly population will account for ∼17 to 26% of total energy consumption in the residential sector, which is close to 115 million tons of standard coal (Mtce). These findings highlight the need to interlace environmental education policies and demographic transitions to promote energy conservation behavior in children and youth for low-carbon, sustainable development.

Background Telehealth rapidly expanded since the outbreak of the COVID-19 pandemic. This study aims to understand how telehealth can substitute in-person services by 1) estimating the changes in non-COVID emergency department (ED) visits, hospitalizations, and care costs among US Medicare beneficiaries by visit modality (telehealth vs. in-person) during the COVID-19 pandemic relative to the previous year; 2) comparing the follow-up time and patterns between telehealth and in-person care. Methods A retrospective and longitudinal study design using US Medicare patients 65 years or older from an Accountable Care Organization (ACO). The study period was April-December 2020, and the baseline period was March 2019 – February 2020. The sample included 16,222 patients, 338,872 patient-month records and 134,375 outpatient encounters. Patients were categorized as non-users, telehealth only, in-person care only and users of both types. Outcomes included the number of unplanned events and costs per month at the patient level; number of days until the next visit and whether the next visit happened within 3-, 7-, 14- and 30-days at the encounter level. All analyses were adjusted for patient characteristics and seasonal trends. Results Beneficiaries who used only telehealth or in-person care had comparable baseline health conditions but were healthier than those who used both types of services. During the study period, the telehealth only group had significantly fewer ED visits/hospitalizations and lower Medicare payments than the baseline (ED 13.2, 95% CI [11.6, 14.7] vs. 24.6 per 1,000 patients per month and hospitalization 8.1 [6.7, 9.4] vs. 12.7); the in-person only group had significantly fewer ED visits (21.9 [20.3, 23.5] vs. 26.1) and lower Medicare payments, but not hospitalizations; the both-types group had significantly more hospitalizations (23.0 [21.4, 24.6] vs. 17.8). Telehealth was not significantly different from in-person encounters in number of days until the next visit (33.4 vs. 31.2 days) or the probabilities of 3- and 7-day follow-up visits (9.2 vs. 9.3% and 21.8 vs.23.5%). Conclusions Patients and providers treated telehealth and in-person visits as substitutes and used either depending on medical needs and availability. Telehealth did not lead to sooner or more follow-up visits than in-person services.

The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the world is still expanding. Thus, there is an urgent need to better understand this novel virus and find a way to control its spread. Like other coronaviruses, the nucleocapsid (N) protein is one of the most crucial structural components of SARS-CoV-2. This protein shares 90% homology with the severe acute respiratory syndrome coronavirus N protein, implying functional significance. Based on the evolutionary conservation of the N protein in coronavirus, we reviewed the currently available knowledge regarding the SARS-CoV-2 N protein in terms of structure, biological functions, and clinical application as a drug target or vaccine candidate.

Transforming growth factor-β (TGF-β) signaling is initiated by activation of transmembrane TGF-β receptors (TGFBR), which deploys Smad2/3 transcription factors to control cellular responses. Failure or dysregulation in the TGF-β signaling pathways leads to pathological conditions. TGF-β signaling is regulated at different levels along the pathways and begins with the liberation of TGF-β ligand from its latent form. The mechanisms of TGFBR activation display selectivity to cell types, agonists, and TGF-β isoforms, enabling precise control of TGF-β signals. In addition, the cell surface compartments used to release active TGF-β are surprisingly vibrant, using thrombospondins, integrins, matrix metalloproteinases and reactive oxygen species. The scope of TGFBR activation is further unfolded with the discovery of TGFBR activation initiated by other signaling pathways. The unique combination of mechanisms works in series to trigger TGFBR activation, which can be explored as therapeutic targets. This comprehensive review provides valuable insights into the diverse mechanisms underpinning TGFBR activation, shedding light on potential avenues for therapeutic exploration.

Gene expression can be regulated through transcriptional and post-transcriptional mechanisms. Transcription in eukaryotes produces pre-mRNA molecules, which are processed and spliced post-transcriptionally to create translatable mRNAs. More than one mRNA may be produced from a single pre-mRNA by alternative splicing (AS); thus, AS serves to diversify an organism’s transcriptome and proteome. Previous studies of gene expression in plants have focused on the role of transcriptional regulation in response to environmental changes. However, recent data suggest that post-transcriptional regulation, especially AS, is necessary for plants to adapt to a changing environment. In this review, we summarize recent advances in our understanding of AS during plant development in response to environmental changes. We suggest that alternative gene splicing is a novel means of regulating the environmental fitness of plants.

The slow rate of extracellular electron transfer (EET) of electroactive microorganisms remains a primary bottleneck that restricts the practical applications of bioelectrochemical systems. Intracellular NAD(H/ + ) (i.e., the total level of NADH and NAD + ) is a crucial source of the intracellular electron pool from which intracellular electrons are transferred to extracellular electron acceptors via EET pathways. However, how the total level of intracellular NAD(H/ + ) impacts the EET rate in Shewanella oneidensis has not been established. Here, we use a modular synthetic biology strategy to redirect metabolic flux towards NAD + biosynthesis via three modules: de novo, salvage, and universal biosynthesis modules in S. oneidensis MR-1. The results demonstrate that an increase in intracellular NAD(H/ + ) results in the transfer of more electrons from the increased oxidation of the electron donor to the EET pathways of S. oneidensis , thereby enhancing intracellular electron flux and the EET rate. A bottleneck for the application of bioelectrochemical systems is the slow rate of extracellular electron transfer. Here the authors use a synthetic biology approach to redirect metabolic flux to NAD + biosynthesis, which enhances the intracellular electron flux and the extracellular electron transfer rate.

Astrocytes are one of the key glial types of the central nervous system (CNS), accounting for over 20% of total glial cells in the brain. Extensive evidence has established their indispensable functions in the maintenance of CNS homeostasis, as well as their broad involvement in neurological conditions. In particular, astrocytes can participate in various neuroinflammatory processes, e.g., releasing a repertoire of cytokines and chemokines or specific neurotrophic factors, which result in both beneficial and detrimental effects. It has become increasingly clear that such astrocyte-mediated neuroinflammation, together with its complex crosstalk with other glial cells or immune cells, designates neuronal survival and the functional integrity of neurocircuits, thus critically contributing to disease onset and progression. In this review, we focus on the current knowledge of the neuroinflammatory responses of astrocytes, summarizing their common features in neurological conditions. Moreover, we highlight several vital questions for future research that promise novel insights into diagnostic or therapeutic strategies against those debilitating CNS diseases.

Characterization of cancer cells and neural stem cells indicates that tumorigenicity and pluripotency are coupled cell properties determined by neural stemness, and tumorigenesis represents a process of progressive loss of original cell identity and gain of neural stemness. This reminds of a most fundamental process required for the development of the nervous system and body axis during embryogenesis, i.e., embryonic neural induction. Neural induction is that, in response to extracellular signals that are secreted by the Spemann-Mangold organizer in amphibians or the node in mammals and inhibit epidermal fate in ectoderm, the ectodermal cells lose their epidermal fate and assume the neural default fate and consequently, turn into neuroectodermal cells. They further differentiate into the nervous system and also some non-neural cells via interaction with adjacent tissues. Failure in neural induction leads to failure of embryogenesis, and ectopic neural induction due to ectopic organizer or node activity or activation of embryonic neural genes causes a formation of secondary body axis or a conjoined twin. During tumorigenesis, cells progressively lose their original cell identity and gain of neural stemness, and consequently, gain of tumorigenicity and pluripotency, due to various intra-/extracellular insults in cells of a postnatal animal. Tumorigenic cells can be induced to differentiation into normal cells and integrate into normal embryonic development within an embryo. However, they form tumors and cannot integrate into animal tissues/organs in a postnatal animal because of lack of embryonic inducing signals. Combination of studies of developmental and cancer biology indicates that neural induction drives embryogenesis in gastrulating embryos but a similar process drives tumorigenesis in a postnatal animal. Tumorigenicity is by nature the manifestation of aberrant occurrence of pluripotent state in a postnatal animal. Pluripotency and tumorigenicity are both but different manifestations of neural stemness in pre- and postnatal stages of animal life, respectively. Based on these findings, I discuss about some confusion in cancer research, propose to distinguish the causality and associations and discriminate causal and supporting factors involved in tumorigenesis, and suggest revisiting the focus of cancer research.