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Prospective associated with genistein-induced autophagy within the management of neurodegenerative illnesses
Recent evidence supports the notion that mitochondrial metabolism is necessary for the determination of stem cell fate. Historically, mitochondrial metabolism is linked to the production of ATP and tricarboxylic acid (TCA) cycle metabolites to support stem cell survival and growth, respectively. However, it is now clear that beyond these canonical roles, mitochondria as signaling organelles dictate stem cell fate and function. In this review, we focus on key conceptual ideas on how mitochondria control mammalian stem cell fate and function through reactive oxygen species (ROS) generation, TCA cycle metabolite production, NAD+/NADH ratio regulation, pyruvate metabolism, and mitochondrial dynamics.Malignant stem cells have long been considered a key therapeutic target in leukemia. Therapeutic strategies designed to target the fundamental biology of leukemia stem cells while sparing normal hematopoietic cells may provide better outcomes for leukemia patients. One process in leukemia stem cell biology that has intriguing therapeutic potential is energy metabolism. In this article we discuss the metabolic properties of leukemia stem cells and how targeting energy metabolism may provide more effective therapeutic regimens for leukemia patients. In addition, we highlight the similarities and differences in energy metabolism between leukemia stem cells and malignant stem cells from solid tumors.The depth of quiescence in hematopoietic stem cells (HSCs) dictates their potency and is sensitive to metabolic perturbations. Recent evidence suggests that lysosomal functions distinct from autophagic processes are pivotal in regulating quiescence versus activation by potential control of the access to a nutrient reservoir required for HSC activation.In this forum piece, we review progress in exploiting diet and nutrition for enhancing tissue regeneration with a particular emphasis on how dietary composition and diet-induced physiology influence adult stem cell biology.COVID-19 has unfortunately halted lab work, conferences, and in-person networking, which is especially detrimental to researchers just starting their labs. Through social media and our reviewer networks, we met some early-career stem cell investigators impacted by the closures. Here, they introduce themselves and their research to our readers.In this issue of Cell Stem Cell, Ning et al. (2021) demonstrate that contractility in differentiating, suprabasally located keratinocytes acts non-cell-autonomously to regulate the replication and differentiation of the stem/progenitor keratinocytes in the basal layer of epidermis. This finding expands our understanding of the niche that regulates stem/progenitor cells in skin.By single-cell transcriptome profiling of human yolk sacs and fetal livers, Wang et al. (2021) (in this issue of Cell Stem Cell) track two alternative routes for differentiation of megakaryocytes. The authors have shown that these megakaryocytes have hemostatic- and HSC-supporting functions, and that hESC-derived thrombospondin1-positive endothelial cells are capable of generating megakaryocytes in vitro.Previous work demonstrating the existence of intermediate pluripotency states in post-implantation embryos had ignited a debate on whether "formative" pluripotency can be stabilized in pluripotent stem cell (PSC) lines. In this issue of Cell Stem Cell, two papers show that polarized epithelial and germ cell-competent formative PSCs can be maintained in modified activin-dependent conditions.Myeloproliferative neoplasms (MPNs) are hematological malignancies caused by somatic mutations originating from a single hematopoietic stem cell (HSC). In this issue of Cell Stem Cell,Van Egeren et al. (2021) used whole-genome sequencing of hematopoietic colonies to reconstruct the clonal history and time of acquisition of the disease-initiating gene mutation.This article shows an example of the peer review process for "Integrative Single-Cell RNA-Seq and ATAC-Seq Analysis of Human Developmental Hematopoiesis" (Ranzoni et al., 2021).Human monoclonal antibodies are safe, preventive, and therapeutic tools that can be rapidly developed to help restore the massive health and economic disruption caused by the coronavirus disease 2019 (COVID-19) pandemic. By single-cell sorting 4,277 SARS-CoV-2 spike protein-specific memory B cells from 14 COVID-19 survivors, 453 neutralizing antibodies were identified. The most potent neutralizing antibodies recognized the spike protein receptor-binding domain, followed in potency by antibodies that recognize the S1 domain, the spike protein trimer, and the S2 subunit. Only 1.4% of them neutralized the authentic virus with a potency of 1-10 ng/mL. The most potent monoclonal antibody, engineered to reduce the risk of antibody-dependent enhancement and prolong half-life, neutralized the authentic wild-type virus and emerging variants containing D614G, E484K, and N501Y substitutions. Prophylactic and therapeutic efficacy in the hamster model was observed at 0.25 and 4 mg/kg respectively in absence of Fc functions.Divergence of gene function is a hallmark of evolution, but assessing functional divergence over deep time is not trivial. The few alleles available for cross-species studies often fail to expose the entire functional spectrum of genes, potentially obscuring deeply conserved pleiotropic roles. Here, we explore the functional divergence of WUSCHEL HOMEOBOX9 (WOX9), suggested to have species-specific roles in embryo and inflorescence development. Using a cis-regulatory editing drive system, we generate a comprehensive allelic series in tomato, which revealed hidden pleiotropic roles for WOX9. Analysis of accessible chromatin and conserved cis-regulatory sequences identifies the regions responsible for this pleiotropic activity, the functions of which are conserved in groundcherry, a tomato relative. Mimicking these alleles in Arabidopsis, distantly related to tomato and groundcherry, reveals new inflorescence phenotypes, exposing a deeply conserved pleiotropy. We suggest that targeted cis-regulatory mutations can uncover conserved gene functions and reduce undesirable effects in crop improvement.
Extensive resection of skin carcinomas in the periorbital and forehead regions often results in complicated defects involving the upper eyelid, superciliary arch, and nasal dorsum. The aim of this study is to report our experience with the use of supraorbital artery perforator propeller flaps for primary repair of complicated forehead defects.

A total of 6 patients underwent carcinoma resection with primary surgical reconstruction using supraorbital propeller flap at the Peking University School and Hospital of Stomatology from December 2015 to December 2018. We describe the technique and retrospectively review the outcomes.

A single propeller flap was used in 5 patients and 2 propeller flaps (supraorbital and nasolabial artery propeller flaps) in 1 patient. Two patients developed venous congestion of the flap on the first postoperative day; however, in both cases it was relieved by multiple needle punctures. All flaps had survived well at 1-year follow-up. Five patients had a normal eyelid closure, but 1 patient presented with lagophthalmos, which required correction by secondary surgery.

Propeller flap based on the supraorbital artery is a feasible option for primary reconstruction of supraorbital-forehead defect.
Propeller flap based on the supraorbital artery is a feasible option for primary reconstruction of supraorbital-forehead defect.Sensory dysfunction is the most serious complication that occurs after extracting lower third molars in close proximity to the inferior alveolar nerve (IAN). Even experienced surgeons have difficulties in avoiding nerve damage when the root is anatomically adjacent to the nerve canal. A useful method for reducing nerve damage during extraction is to perform orthodontic extrusion, in which the distance between the nerve and the root increased after applying an orthodontic force on the third molar while extruding the tooth. Here, we report the case of a 37-year-old female who presented with a partially erupted left lower third molar and risk of IAN nerve damage because of close anatomical proximity between the nerve and root. She underwent extraction using a miniscrew placed in the maxilla and a routine orthodontic mechanism using a cross-arch elastic band that induced a 3-mm vertical eruption in the impacted third molar without using complex orthodontic devices. In addition, tilting the dental axis to the lingual side resolved the proximity between the IAN and the tooth, thereby allowing extraction to proceed without major complications.Loss of insulin-secreting pancreatic β cells through apoptosis contributes to the progression of type 2 diabetes, but underlying mechanisms remain elusive. Here, we identify a pathway in which the cell death inhibitor ARC paradoxically becomes a killer during diabetes. While cytoplasmic ARC maintains β cell viability and pancreatic architecture, a pool of ARC relocates to the nucleus to induce β cell apoptosis in humans with diabetes and several pathophysiologically distinct mouse models. β cell death results through the coordinate downregulation of serpins (serine protease inhibitors) not previously known to be synthesized and secreted by β cells. Loss of the serpin α1-antitrypsin from the extracellular space unleashes elastase, triggering the disruption of β cell anchorage and subsequent cell death. Administration of α1-antitrypsin to mice with diabetes prevents β cell death and metabolic abnormalities. These data uncover a pathway for β cell loss in type 2 diabetes and identify an FDA-approved drug that may impede progression of this syndrome.Peripheral nerve injury induces long-term pro-inflammatory responses in spinal cord glial cells that facilitate neuropathic pain, but the identity of endogenous cells that resolve spinal inflammation has not been determined. Guided by single-cell RNA sequencing (scRNA-seq), we found that MRC1+ spinal cord macrophages proliferated and upregulated the anti-inflammatory mediator Cd163 in mice following superficial injury (SI; nerve intact), but this response was blunted in nerve-injured animals. Depleting spinal macrophages in SI animals promoted microgliosis and caused mechanical hypersensitivity to persist. Conversely, expressing Cd163 in spinal macrophages increased Interleukin 10 expression, attenuated micro- and astrogliosis, and enduringly alleviated mechanical and thermal hypersensitivity in nerve-injured animals. Our data indicate that MRC1+ spinal macrophages actively restrain glia to limit neuroinflammation and resolve mechanical pain following a superficial injury. Doramapimod Moreover, we show that spinal macrophages from nerve-injured animals mount a dampened anti-inflammatory response but can be therapeutically coaxed to promote long-lasting recovery of neuropathic pain.Perception improves by repeated practice with visual stimuli, a phenomenon known as visual perceptual learning (VPL). The interplay of attentional and neuromodulatory reward signals is hypothesized to cause these behavioral and associated neuronal changes, although VPL can occur without attention (i.e., task-irrelevant VPL). In addition, task-relevant VPL can be category-selective for simple attended oriented stimuli. Yet, it is unclear whether category-selective task-irrelevant VPL occurs and which brain centers mediate underlying forms of adult cortical plasticity. Here, we show that pairing subliminal complex visual stimuli (faces and bodies) with electrical microstimulation of the ventral tegmental area (VTA-EM) causes category-selective task-irrelevant VPL. These perceptual improvements are accompanied by fMRI signal changes in early and late visual and frontal areas, as well as the cerebellum, hippocampus, claustrum, and putamen. In conclusion, Pavlovian pairing of unattended complex stimuli with VTA-EM causes category-selective learning accompanied by changes of cortical and subcortical neural representations in macaques.
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