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A practical Rh(iii)-catalyzed, redox-neutral C–H alkenylation of benzamides with gem-difluorohomoallylic silyl ethers enables the synthesis of 2-(3,3-difluoro-4-(silyloxy)but-1-en-1-yl)benzamides with a broad substrate scope and high regioselectivity.

Aging is a major risk factor for multiple diseases, including cardiovascular diseases, neurodegenerative disorders, osteoarthritis, and cancer. It is accompanied by the dysregulation of stem cells and other differentiated cells, and the impairment of their microenvironment. Cell therapies to replenish the abovementioned cells provide a promising approach to restore tissue homeostasis and alleviate aging and aging-related chronic diseases. Importantly, by leveraging gene editing technologies, genetic enhancement, an enhanced strategy for cell therapy, can be developed to improve the safety and efficacy of transplanted therapeutic cells. In this review, we provide an overview and discussion of the current progress in the genetic enhancement field, including genetic modifications of mesenchymal stem cells, neural stem cells, hematopoietic stem cells, vascular cells, and T cells to target aging and aging-associated diseases. We also outline questions regarding safety and current limitations that need to be addressed for the continued development of genetic enhancement strategies for cell therapy to enable its further applications in clinical trials to combat aging-related diseases.

β-Amylase (BAM)-mediated starch degradation is a main source of soluble sugars that help plants adapt to environmental stresses. Here, we demonstrate that dehydration-induced expression of PtrBAM3 in trifoliate orange (Poncirus trifoliata (L.) Raf.) functions positively in drought tolerance via modulation of starch catabolism. Two transcription factors, PtrABF4 (P. trifoliata abscisic acid-responsive element-binding factor 4) and PtrABR1 (P. trifoliata ABA repressor 1), were identified as upstream transcriptional activators of PtrBAM3 through yeast one-hybrid library screening and protein–DNA interaction assays. Both PtrABF4 and PtrABR1 played a positive role in plant drought tolerance by modulating soluble sugar accumulation derived from BAM3-mediated starch decomposition. In addition, PtrABF4 could directly regulate PtrABR1 expression by binding to its promoter, leading to a regulatory cascade to reinforce the activation of PtrBAM3. Moreover, PtrABF4 physically interacted with PtrABR1 to form a protein complex that further promoted the transcriptional regulation of PtrBAM3. Taken together, our finding reveals that a transcriptional cascade composed of ABF4 and ABR1 works synergistically to upregulate BAM3 expression and starch catabolism in response to drought condition. The results shed light on the understanding of the regulatory molecular mechanisms underlying BAM-mediated soluble sugar accumulation for rendering drought tolerance in plants.

Aging is characterized by a progressive deterioration of physiological integrity, leading to impaired functional ability and ultimately increased susceptibility to death. It is a major risk factor for chronic human diseases, including cardiovascular disease, diabetes, neurological degeneration, and cancer. Therefore, the growing emphasis on "healthy aging" raises a series of important questions in life and social sciences. In recent years, there has been unprecedented progress in aging research, particularly the discovery that the rate of aging is at least partly controlled by evolutionarily conserved genetic pathways and biological processes. In an attempt to bring full-fledged understanding to both the aging process and age-associated diseases, we review the descriptive, conceptual, and interventive aspects of the landscape of aging composed of a number of layers at the cellular, tissue, organ, organ system, and organismal levels.

Individual cells are basic units of life. Despite extensive efforts to characterize the cellular heterogeneity of different organisms, cross-species comparisons of landscape dynamics have not been achieved. Here, we applied single-cell RNA sequencing (scRNA-seq) to map organism-level cell landscapes at multiple life stages for mice, zebrafish and Drosophila. By integrating the comprehensive dataset of2.6 million single cells, we constructed a cross-species cell landscape and identified signatures and common pathways that changed throughout the life span. We identified structural inflammation and mitochondrial dysfunction as the most common hallmarks of organism aging, and found that pharmacological activation of mitochondrial metabolism alleviated aging phenotypes in mice. The cross-species cell landscape with other published datasets were stored in an integrated online portal-Cell Landscape. Our work provides a valuable resource for studying lineage development, maturation and aging.How many cell types are there in nature? How do they change during the life cycle? These are two fundamental questions that researchers have been trying to understand in the area of biology. In this study, single-cell mRNA sequencing data were used to profile over 2.6 million individual cells from mice, zebrafish and Drosophila at different life stages, 1.3 million of which were newly collected. The comprehensive datasets allow investigators to construct a cross-species cell landscape that helps to reveal the conservation and diversity of cell taxonomies at genetic and regulatory levels. The resources in this study are assembled into a publicly available website at http://bis.zju.edu.cn/cellatlas/.

A high-efficiency composite adsorbent was synthesized by mixing cellulose and graphene oxide (GO) in the lithium chloride/N,N-dimethyl-acetamide system. The cellulose/GO composite (D-RCGO) was characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, elemental analysis, and thermal gravimetric analysis. The influences of various parameters on the removal of Ce(III), such as the adsorbent dosage, temperature, initial Ce(III) concentration, contact time, and pH, were optimized using a range of batch adsorption experiments. Adsorption kinetics displayed adsorption behavior according to the Langmuir isotherm model and pseudo-second-order model. The X-ray photoelectron spectroscopy analysis showed that the two peaks of Ce-3d almost disappeared after the desorption in NaCl solution, which indicated that the adsorption belonged to the ion exchange adsorption mechanism. Furthermore, the theoretical maximum capacity of the adsorption of Ce(III) onto D-RCGO was 225.8 mg·g-1. This work suggested that the D-RCGO composite membranes could serve as an effective and eco-friendly adsorbent for rare earth pollutant removal in wastewater treatment.

Let [Formula: see text] be a connected graph where [Formula: see text] is the set of vertices of [Formula: see text] and [Formula: see text] is the set of edges of [Formula: see text]. The distance from the vertex [Formula: see text] to the edge [Formula: see text] is given by [Formula: see text]. A subset [Formula: see text] is called an edge metric generator for [Formula: see text] if for every two distinct edges [Formula: see text], there exists a vertex [Formula: see text] such that [Formula: see text]. The edge metric generator with the minimum number of vertices is called an edge metric basis for [Formula: see text] and the cardinality of the edge metric basis is called the edge metric dimension denoted by [Formula: see text]. A subset [Formula: see text] is called a mixed metric generator for [Formula: see text] if for every two distinct elements [Formula: see text], there exists a vertex [Formula: see text] such that [Formula: see text]. A mixed metric generator containing a minimum number of vertices is called a mixed metric basis for [Formula: see text] and the cardinality of a mixed metric basis is called the mixed metric dimension denoted by [Formula: see text]. In this paper, we study the edge metric dimension and the mixed metric dimension of a plane graph [Formula: see text].

A rapidly warming Arctic and mild cold mid-latitude continents have been one of the main characteristics of the Northern Hemisphere winter during the last two decades. However, the factors contributing this warm Arctic-cold continent (WACC) pattern remain unclear, although anomalies in blocking highs and the Arctic oscillation (AO) are possible factors. This study revealed that the mode with high-latitude concurrent blockings (HCBs) is more consistent with the WACC pattern than the AO. In the HCB mode, a strong anticyclonic anomalous circulation over the Arctic Circle, excited by the strong HCBs over the Ural Mountains and the North Pacific, changes the polar atmospheric circulation and redistributes both momentum and heat to give a warmer Arctic than in the AO mode. A weak polar night jet and a poleward shift in the subtropical westerly jet result in mild cold mid-latitude continents. However, these features are not seen in the AO mode, which is characterized by cool continents and a warm Greenland. Besides, human activities may also be contributed to the interdecadal WACC because there is an interdecadal increase in the WACC pattern with HCBs in the CMIP6 simulations with human activities. These results suggest that the role of HCBs should be highly paid attention in winter mid-high latitude extreme events in recent decades.

Hypoxia-inducible factor (HIF-1α), a core transcription factor responding to changes in cellular oxygen levels, is closely associated with a wide range of physiological and pathological conditions. However, its differential impacts on vascular cells types and molecular programs modulating human vascular homeostasis and regeneration remain largely elusive. Here, we applied CRISPR/Cas9-mediated gene editing of human embryonic stem cells (hESCs) and directed differentiation to generate HIF-1α-deficient human vascular cells including vascular endothelial cells (VECs), vascular smooth muscle cells (VSMCs), and mesenchymal stem cells (MSCs), as a platform for discovering cell type-specific hypoxia-induced response mechanisms. Through comparative molecular profiling across cell types under normoxic and hypoxic conditions, we provide insight into the indispensable role of HIF-1α in the promotion of ischemic vascular regeneration. We found human MSCs to be the vascular cell type most susceptible to HIF-1α deficiency, and that transcriptional inactivation of ANKZF1, an effector of HIF-1α, impaired pro-angiogenic processes. Altogether, our findings deepen the understanding of HIF-1α in human angiogenesis and support further explorations of novel therapeutic strategies of vascular regeneration against ischemic damage.

Let [Formula: see text] be a finite undirected simple connected graph with vertex set [Formula: see text] and edge set [Formula: see text]. A vertex [Formula: see text] resolves two elements (vertices or edges) [Formula: see text] if [Formula: see text]. A subset [Formula: see text] of vertices in [Formula: see text] is called a mixed metric generator for [Formula: see text] if every two distinct elements (vertices and edges) of [Formula: see text] are resolved by some vertices of [Formula: see text]. The minimum cardinality of a mixed metric generator for [Formula: see text] is called the mixed metric dimension and is denoted by [Formula: see text]. In this paper, we study the mixed metric dimension for the plane graph of web graph [Formula: see text] and convex polytope [Formula: see text].

Homeostasis is essential for muscle repair and regeneration after skeletal muscle exercise. This study investigated the role of methyltransferase-like 21C (METTL21C) in skeletal muscle of mice after exercise and the potential mechanism. First, muscle samples were collected at 2, 4, and 6 weeks after exercise, liver glycogen, muscle glycogen, blood lactic acid (BLA) and triglyceride (TG) were assessed. Moreover, the expression levels of autophagy markers and METTL21C in skeletal muscle were analyzed. The results showed that the expressions of METTL21C and MYH7 in the gastrocnemius muscle of mice in the exercise group were significantly higher than that in the control group after exercise, which suggested that long-term exercise promoted the formation of slow-twitch muscle fibers in mouse skeletal muscle. Likewise, the autophagy capacity is enhanced with the extension of exercise in muscles. The findings were further verified in mouse C2C12 cells. We discovered that knockdown of Mettl21c reduced the expression of MYH7 and autophagy level in mouse myoblasts. These findings indicate that METTL21C mediates autophagy in skeletal muscle after exercise, maintains skeletal muscle homeostasis, and promotes differentiation of myogenic and formation of slow muscle fiber.

Background Patients with developmental dysplasia of the hip (DDH) have complex proximal femoral deformities, and orthopedic surgery lacks objectivity. Expectations for surgical outcomes are often not achieved, and postoperative problems are common. Using 3D-printed technology in orthopedics offers a novel approach to precise and individualized treatment in modern orthopedics. The aim of this study was to investigate the value of the application of 3D-printed osteotomy guide plates in femoral osteotomy. The clinical indices of femoral osteotomy in children with DDH using 3D-printed osteotomy guide plates were compared with those of traditional osteotomy. Methods The clinical data of children with DDH who underwent open reduction and Salter pelvic osteotomy combined with femoral osteotomy from September 2010 to September 2020 were retrospectively collected and analyzed. Based on the inclusion and exclusion criteria, a total of 36 patients were included in the study: 16 in the guide plate group and 20 in the conventional group. Operation time (total), operation time (femoral side), X-ray fluoroscopy times (total), X-ray fluoroscopy times (femoral side) and intraoperative blood loss were analyzed and compared between the two groups. Comparison of treatment-related indicators such as postoperative neck-shaft angle, postoperative anteversion angle, hospitalization time, and hospitalization expenses is made between the two groups. The two groups of patients were evaluated at the last follow-up using the McKay clinical evaluation criteria. Results Between the two groups, there were significant differences in operation time (total), operation time (femoral side), X-ray fluoroscopy times (total), X-ray fluoroscopy times (femoral side) and intraoperative blood loss (P P > 0.05). The MacKay clinical evaluation did not significantly differ at the most recent follow-up (P > 0.05). Conclusions Children with DDH undergoing proximal femoral osteotomy using 3D-printed osteotomy guide plates benefit from a simpler surgical procedure, shorter operative time, less bleeding and less radiation exposure during surgery. This technique is of great clinical value.

Tutin, an established toxic natural product that causes epilepsy in rodents, is often used as a tool to develop animal model of acute epileptic seizures. However, the molecular target and toxic mechanism of tutin were unclear. In this study, for the first time, we conducted experiments to clarify the targets in tutin-induced epilepsy using thermal proteome profiling. Our studies showed that calcineurin (CN) was a target of tutin, and that tutin activated CN, leading to seizures. Binding site studies further established that tutin bound within the active site of CN catalytic subunit. CN inhibitor and calcineurin A (CNA) knockdown experiments in vivo proved that tutin induced epilepsy by activating CN, and produced obvious nerve damage. Together, these findings revealed that tutin caused epileptic seizures by activating CN. Moreover, further mechanism studies found that N-methyl-D-aspartate (NMDA) receptors, gamma-aminobutyric acid (GABA) receptors and voltage- and Ca2+- activated K+ (BK) channels might be involved in related signaling pathways. Our study fully explains the convulsive mechanism of tutin, which provides new ideas for epilepsy treatment and drug development.

Maintaining metabolic homeostasis is essential for cellular and organismal health throughout life. Multiple signaling pathways that regulate metabolism also play critical roles in aging, such as PI3K/AKT, mTOR, AMPK, and sirtuins (SIRTs). Among them, sirtuins are known as a protein family with versatile functions, such as metabolic control, epigenetic modification and lifespan extension. Therefore, by understanding how sirtuins regulate metabolic processes, we can start to understand how they slow down or accelerate biological aging from the perspectives of metabolic regulation. Here, we review the biology of SIRT3, SIRT4, and SIRT5, known as the mitochondrial sirtuins due to their localization in the mitochondrial matrix. First, we will discuss canonical pathways that regulate metabolism more broadly and how these are integrated with aging regulation. Then, we will summarize the current knowledge about functional differences between SIRT3, SIRT4, and SIRT5 in metabolic control and integration in signaling networks. Finally, we will discuss how mitochondrial sirtuins regulate processes associated with aging and aging-related diseases.

As a key area in word reading, the left ventral occipitotemporal cortex is proposed for abstract orthographic processing, and its middle part has even been labeled as the visual word form area. Because the definition of the VWFA largely varies and the reading task differs across studies, the function of the left ventral occipitotemporal cortex in word reading is continuingly debated on whether this region is specific for orthographic processing or be involved in an interactive framework. By using representational similarity analysis (RSA), this study examined information representation in the VWFA at the individual level and the modulatory effect of reading task. Twenty-four subjects were scanned while performing the explicit (i.e., the naming task) and implicit (i.e., the perceptual task) reading tasks. Activation analysis showed that the naming task elicited greater activation in regions related to phonological processing (e.g., the bilateral prefrontal cortex and temporoparietal cortex), while the perceptual task recruited greater activation in visual cortex and default mode network (e.g., the bilateral middle frontal gyrus, angular gyrus, and the right middle temporal gyrus). More importantly, RSA also showed that task modulated information representation in the bilateral anterior occipitotemporal cortex and VWFA. Specifically, ROI-based RSA revealed enhanced orthographic and phonological representations in the bilateral anterior fusiform cortex and VWFA in the naming task relative to the perceptual task. These results suggest that lexical representation in the VWFA is influenced by the demand of phonological processing, which supports the interactive account of the VWFA.

Stem cell therapies, including stem cell transplantation and rejuvenation of stem cells in situ, are promising avenues for tackling a broad range of diseases. Stem cells can both self-renew and differentiate into other cell types, and play a significant role in the regulation of tissue homeostasis and regeneration after cell degeneration or injury. However, stem cell exhaustion or dysfunction increases with age and impedes the normal function of multiple tissues and systems. Thus, stem cell therapies could provide a solution to aging and age-associated diseases. Here, we discuss recent advances in understanding the mechanisms that regulate stem cell regeneration. We also summarize potential strategies for rejuvenating stem cells that leverage intrinsic and extrinsic factors. These approaches may pave the way toward therapeutic interventions aiming at extending both health and life span.

Ageing populations are becoming a global issue. Against this background, the assessment and treatment of geriatric conditions have become increasingly important. This study draws on the multisensory integration of virtual reality (VR) devices in the field of rehabilitation to assess brain function in young and old people. The study is based on multimodal data generated by combining high temporal resolution electroencephalogram (EEG) and subjective scales and behavioural indicators reflecting motor abilities. The phase locking value (PLV) was chosen as an indicator of functional connectivity (FC), and six brain regions, namely LPFC, RPFC, LOL, ROL, LMC and RMC, were analysed. The results showed a significant difference in the alpha band on comparing the resting and task states in the younger group. A significant difference between the two states in the alpha and beta bands was observed when comparing task states in the younger and older groups. Meanwhile, this study affirms that advancing age significantly affects human locomotor performance and also has a correlation with cognitive level. The study proposes a novel accurate and valid assessment method that offers new possibilities for assessing and rehabilitating geriatric diseases. Thus, this method has the potential to contribute to the field of rehabilitation medicine.

A one-step solvothermal method is demonstrated to synthesize layered Co9S8 intercalated with Co cations. The as-prepared electrocatalyst exhibits outstanding performance for the hydrogen evolution reaction as well as remarkable long-term catalytic durability.

An efficient, sustainable and straightforward method is reported for the synthesis of a series of α,α-difluoromethyl carbinols via K2CO3-triggered Friedel–Crafts reaction of electron-rich arenes using the stable and easily affordable 2,2-difluorovinyl arylsulfonate.

SARS-CoV-2 binds to microplastics which facilitates viral host infection with enhanced inflammatory responses.

The recently developed strategies for the degradation and functionalization of lignin enable it to be converted into a wide variety of value-added -chemicals, -and advanced materials.

COVID-19 pandemic continues to spread throughout the world with an urgent demand for a safe and protective vaccine to effectuate herd protection and control the spread of SARS-CoV-2. Here, we report the development of a bacterial vector COVID-19 vaccine (aPA-RBD) that carries the gene for the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. Live-attenuated strains of Pseudomonas aeruginosa (aPA) were constructed which express the recombinant RBD and effectively deliver RBD protein into various antigen presenting cells through bacterial type 3 secretion system (T3SS) in vitro. In mice, two-dose of intranasal aPA-RBD vaccinations elicited the development of RBD-specific serum IgG and IgM. Importantly, the sera from the immunized mice were able to neutralize host cell infections by SARS-CoV-2 pseudovirus as well as the authentic virus variants potently. T-cell responses of immunized mice were assessed by enzyme-linked immunospot (ELISPOT) and intracellular cytokine staining (ICS) assays. aPA-RBD vaccinations can elicit RBD-specific CD4+and CD8+T cell responses. T3SS-based RBD intracellular delivery heightens the efficiency of antigen presentation and enables the aPA-RBD vaccine to elicit CD8+T cell response. Thus, aPA vector has the potential as an inexpensive, readily manufactured, and respiratory tract vaccination route vaccine platform for other pathogens