SIRT7 activates quiescent hair follicle stem cells to ensure hair growth in mice.

Hair follicle stem cells (HFSCs) are maintained in a quiescent state until activated to grow, but the mechanisms that reactivate the quiescent HFSC reservoir are unclear. Here, we find that loss of Sirt7 in mice impedes hair follicle life-cycle transition from telogen to anagen phase, resulting in delay of hair growth. Conversely, Sirt7 overexpression during telogen phase facilitated HSFC anagen entry and accelerated hair growth. Mechanistically, Sirt7 is upregulated in HFSCs during the telogen-to-anagen transition, and HFSC-specific Sirt7 knockout mice (Sirt7f/f ;K15-Cre) exhibit a similar hair growth delay. At the molecular level, Sirt7 interacts with and deacetylates the transcriptional regulator Nfatc1 at K612, causing PA28γ-dependent proteasomal degradation to terminate Nfatc1-mediated telogen quiescence and boost anagen entry. Cyclosporin A, a potent calcineurin inhibitor, suppresses nuclear retention of Nfatc1, abrogates hair follicle cycle delay, and promotes hair growth in Sirt7-/- mice. Furthermore, Sirt7 is downregulated in aged HFSCs, and exogenous Sirt7 overexpression promotes hair growth in aged animals. These data reveal that Sirt7 activates HFSCs by destabilizing Nfatc1 to ensure hair follicle cycle initiation.

Prophylactic Effect of Simultaneous Placement of Mesh on Incidence of Parastomal Hernia After Miles' Surgical Resection of Colorectal Cancer: A Prospective Study.

INTRODUCTION: To assess the prophylactic effect of simultaneous placement of mesh and the incidence of parastomal hernia (PSH) after abdominoperineal resection of rectal cancer. METHODS: This study included real-world data of 56 surgically resected patients with colorectal cancer who were consecutively assigned to two groups: control (no mesh, n = 32) and experimental (received mesh, n = 24). An artificial patch was placed under the tunica vaginalis of rectus abdominis for patients in the experimental group, whereas those in the control group received routine sigmoidostomy. The median follow-up time was >20 mo. The difference in hazards function was analyzed by cox regression analysis. The Kaplan-Meir analysis was used to determine the survival curves. A P value of <0.05 was considered as significant. RESULTS: The postoperative incidence rate of PSH was lower in the experimental (41.7%) group than in the control group (71.9%; P = 0.045). The PSH postoperative time in the experimental group was significantly delayed compared to the control group (48 mo versus 10 mo; P < 0.001). The risk of progression from H1 to H2 was less in the experimental group compared to the control group (49.28% versus 60.86%; P = 0.14). CONCLUSIONS: Prophylactic mesh placement significantly prolonged postoperative time for the recurrence of PSH. The incidence of recurrence of H2 (severe PSH) requiring secondary surgical repair was also reduced.

Deacetylase-independent function of SIRT6 couples GATA4 transcription factor and epigenetic activation against cardiomyocyte apoptosis.

SIRT6 deacetylase activity improves stress resistance via gene silencing and genome maintenance. Here, we reveal a deacetylase-independent function of SIRT6, which promotes anti-apoptotic gene expression via the transcription factor GATA4. SIRT6 recruits TIP60 acetyltransferase to acetylate GATA4 at K328/330, thus enhancing its chromatin binding capacity. In turn, GATA4 inhibits the deacetylase activity of SIRT6, thus ensuring the local chromatin accessibility via TIP60-promoted H3K9 acetylation. Significantly, the treatment of doxorubicin (DOX), an anti-cancer chemotherapeutic, impairs the SIRT6-TIP60-GATA4 trimeric complex, blocking GATA4 acetylation and causing cardiomyocyte apoptosis. While GATA4 hyperacetylation-mimic retains the protective effect against DOX, the hypoacetylation-mimic loses such ability. Thus, the data reveal a novel SIRT6-TIP60-GATA4 axis, which promotes the anti-apoptotic pathway to prevent DOX toxicity. Targeting the trimeric complex constitutes a new strategy to improve the safety of DOX chemotherapy in clinical application.

HDAC8 cooperates with SMAD3/4 complex to suppress SIRT7 and promote cell survival and migration.

NAD+-dependent SIRT7 deacylase plays essential roles in ribosome biogenesis, stress response, genome integrity, metabolism and aging, while how it is transcriptionally regulated is still largely unclear. TGF-ß signaling is highly conserved in multicellular organisms, regulating cell growth, cancer stemness, migration and invasion. Here, we demonstrate that histone deacetylase HDAC8 forms complex with SMAD3/4 heterotrimer and occupies SIRT7 promoter, wherein it deacetylates H4 and thus suppresses SIRT7 transcription. Treatment with HDAC8 inhibitor compromises TGF-ß signaling via SIRT7-SMAD4 axis and consequently, inhibits lung metastasis and improves chemotherapy efficacy in breast cancer. Our data establish a regulatory feedback loop of TGF-ß signaling, wherein HDAC8 as a novel cofactor of SMAD3/4 complex, transcriptionally suppresses SIRT7 via local chromatin remodeling and thus further activates TGF-ß signaling. Targeting HDAC8 exhibits therapeutic potential for TGF-ß signaling related diseases.

[A pace recognition method for exoskeleton wearers based on support vector machine-hidden Markov model].

In order to improve the motion fluency and coordination of lower extremity exoskeleton robots and wearers, a pace recognition method of exoskeleton wearer is proposed base on inertial sensors. Firstly, the triaxial acceleration and triaxial angular velocity signals at the thigh and calf were collected by inertial sensors. Then the signal segment of 0.5 seconds before the current time was extracted by the time window method. And the Fourier transform coefficients in the frequency domain signal were used as eigenvalues. Then the support vector machine (SVM) and hidden Markov model (HMM) were combined as a classification model, which was trained and tested for pace recognition. Finally, the pace change rule and the human-machine interaction force were combined in this model and the current pace was predicted by the model. The experimental results showed that the pace intention of the lower extremity exoskeleton wearer could be effectively identified by the method proposed in this article. And the recognition rate of the seven pace patterns could reach 92.14%. It provides a new way for the smooth control of the exoskeleton.

Selection of EMG Sensors Based on Motion Coordinated Analysis.

The intelligent prosthesis driven by electromyography (EMG) signal provides a solution for the movement of the disabled. The proper position of EMG sensors can improve the prosthesis's motion recognition ability. To exert the amputee's action-oriented ability and the prosthesis' control ability, the EMG spatial distribution and internal connection of the prosthetic wearer is analyzed in three kinds of movement conditions: appropriate angle, excessive angle, and angle too small. Firstly, the correlation characteristics between the EMG channels are analyzed by mutual information to construct a muscle functional network. Secondly, the network's features of different movement conditions are analyzed by calculating the characteristic of nodes and evaluating the importance of nodes. Finally, the convergent cross-mapping method is applied to construct a directed network, and the critical muscle groups which can reflect the user's movement intention are determined. Experiment shows that this method can accurately determine the EMG location and simplify the distribution of EMG sensors inside the prosthetic socket. The network characteristics of key muscle groups can distinguish different movements effectively and provide a new strategy for decoding the relationship between limb nerve control and body movement.

Bicycling Phase Recognition for Lower Limb Amputees Using Support Vector Machine Optimized by Particle Swarm Optimization.

A novel method for recognizing the phases in bicycling of lower limb amputees using support vector machine (SVM) optimized by particle swarm optimization (PSO) is proposed in this paper. The method is essential for enhanced prosthetic knee joint control for lower limb amputees in carrying out bicycling activity. Some wireless wearable accelerometers and a knee joint angle sensor are installed in the prosthesis to obtain data on the knee joint and ankle joint horizontal, vertical acceleration signal and knee joint angle. In order to overcome the problem of high noise content in the collected data, a soft-hard threshold filter was used to remove the noise caused by the vibration. The filtered information is then used to extract the multi-dimensional feature vector for the training of SVM for performing bicycling phase recognition. The SVM is optimized by PSO to enhance its classification accuracy. The recognition accuracy of the PSO-SVM classification model on testing data is 93%, which is much higher than those of BP, SVM and PSO-BP classification models.

Sirt6 deacetylase activity regulates circadian rhythms via Per2.

Circadian clock relies on a transcription and translation feedback loop (TTFL). Two transcription factors, i.e. Bmal1 and Clock, activate the transcription of Period (Per) and Cryptochrome (Cry), which inhibit their own transcription when accumulated to a critical concentration. NAD+-dependent deacylase Sirt1 deacetylates Bmal1 and Per2 to regulate circadian rhythms. Sirt6 interacts with Bmal1 to regulate clock-controlled gene (CCG) expression by local chromatin remodeling. Whether Sirt6 directly modify clock components is elusive. Here, we found that loss of Sirt6 jeopardizes circadian phase. At molecular level, Sirt6 interacts with and deacetylates Per2, thus preventing its proteasomal degradation. These data highlight an important function of Sirt6 in the direct regulation of TTFL and circadian rhythms.

Wearable Sensor-Based Human Activity Recognition via Two-Layer Diversity-Enhanced Multiclassifier Recognition Method.

Sensor-based human activity recognition can benefit a variety of applications such as health care, fitness, smart homes, rehabilitation training, and so forth. In this paper, we propose a novel two-layer diversity-enhanced multiclassifier recognition method for single wearable accelerometer-based human activity recognition, which contains data-based and classifier-based diversity enhancement. Firstly, we introduce the kernel Fisher discriminant analysis (KFDA) technique to spatially transform the training samples and enhance the discrimination between activities. In addition, bootstrap resampling is utilized to increase the diversities of the dataset for training the base classifiers in the multiclassifier system. Secondly, a combined diversity measure for selecting the base classifiers with excellent performance and large diversity is proposed to optimize the performance of the multiclassifier system. Lastly, majority voting is utilized to combine the preferred base classifiers. Experiments showed that the data-based diversity enhancement can improve the discriminance of different activity samples and promote the generation of base classifiers with different structures and performances. Compared with random selection and traditional ensemble methods, including Bagging and Adaboost, the proposed method achieved 92.3% accuracy and 90.7% recall, which demonstrates better performance in activity recognition.

Hypoxia Inhibits Myogenic Differentiation through p53 Protein-dependent Induction of Bhlhe40 Protein.

Satellite cells are muscle-resident stem cells capable of self-renewal and differentiation to repair injured muscles. However, muscle injury often leads to an ischemic hypoxia environment that impedes satellite cell differentiation and reduces the efficiency of muscle regeneration. Here we performed microarray analyses and identified the basic helix-loop-helix family transcription factor Bhlhe40 as a candidate mediator of the myogenic inhibitory effect of hypoxia. Bhlhe40 is strongly induced by hypoxia in satellite cell-derived primary myoblasts. Overexpression of Bhlhe40 inhibits Myog expression and mimics the effect of hypoxia on myogenesis. Inhibition of Bhlhe40, conversely, up-regulates Myog expression and promotes myogenic differentiation. Importantly, Bhlhe40 knockdown rescues myogenic differentiation under hypoxia. Mechanistically, Bhlhe40 binds to the proximal E-boxes of the Myog promoter and reduces the binding affinity and transcriptional activity of MyoD on Myog. Interestingly, hypoxia induces Bhlhe40 expression independent of HIF1α but through a novel p53-dependent signaling pathway. Our study establishes a crucial role of Bhlhe40 in mediating the repressive effect of hypoxia on myogenic differentiation and suggests that inhibition of Bhlhe40 or p53 may facilitate muscle regeneration after ischemic injuries.

Bone marrow stromal cells induced activation of nuclear factor κB signaling protects non-Hodgkin's B lymphoma cells from apoptosis.

The microenvironment encompassing a variety of non-malignant cells in close proximity with malignant tumor cells has been well known to significantly affect the behavior of tumor cells. In this study, we therefore studied the mechanism of bone marrow stromal cells in protection of lymphoma cells from spontaneous apoptosis. We demonstrated that adhesion of the freshly isolated lymphoma B cells to bone marrow stromal cells or freshly isolated lymphoma stromal cells inhibited B cell spontaneous apoptosis in culture. This inhibition of apoptosis correlated with decreased cleavage of caspase-3/8 and increased activation of canonical and non-canonical NF-κB signaling pathway. In addition to BAFF signaling which has been reported as a functional determinant for B lymphoma cell survival in the bone marrow environment, we demonstrated RANKL from BMSCs works synergistically with BAFF to activate NF-κB signaling pathway and thus protects lymphoma B cells from spontaneous apoptosis.

Reducing the pollution risk of pesticide using nano networks induced by irradiation and hydrothermal treatment.

Traditional pesticides (TP) often do not adhere tightly to crop foliage. They can easily enter the surrounding environment through precipitation and volatilization. This can result in the pollution of the surrounding soil, water, and air. To reduce pesticide pollution, we developed a loss-control pesticide (LCP) by adding attapulgite with a nano networks structure fabricated using high energy electron beam (HEEB) irradiation and hydrothermal treatment to TP. HEEB irradiation effectively dispersed originally aggregated attapulgite through modified thermal, charge, and physical effects. Hydrothermal treatment further enhanced the dispersion of attapulgite to form nano porous networks via thermal and wet expansion effects, which are beneficial for pesticide binding. An LCP has improved retention on crop leaf surfaces. It has a higher adhesion capacity, reduced leaching and volatilization, and extended residual activity compared with the TP formulation. The treatment increases the residual activity of pesticides on crop foliage and decreases environmental pollution.

[A prospective multicenter clinical trial of extralevator abdominoperineal excision for locally advanced low rectal cancer].

OBJECTIVE: To demonstrate the feasibility of extralevator abdominoperineal excision (ELAPE) for locally advanced low cancer in China. METHODS: A prospective multicenter clinical trial was carried out by 7 general hospitals across China from August 2008 to October 2011. A total of 102 patients underwent ELAPE for primary locally advanced low rectal cancer. There were 60 male and 42 female patients. The patients' characteristics, complications and prognosis were recorded. RESULTS: All patients underwent the ELAPE procedure successfully. The median operating time was 180 minutes (range 110-495 minutes) and median intraoperative blood loss was 200 ml (range 50-1000 ml). The rates of sexual dysfunction, perineal complications, urinary retention, and chronic perineal pain were 40.5%, 23.5%, 18.6% and 13.7%, respectively. Chronic perineal pain was associated with coccygectomy (12 months postoperatively, t = 8.06, P < 0.01), and the pain might gradually ease over time. Reconstruction of pelvic floor with biologic mesh was associated with lower rate of perineal dehiscence (χ(2) = 13.502, P = 0.006) and overall perineal wound complications (χ(2) = 5.836, P = 0.016) compared with primary closure. A positive circumferential margin (CRM) was demonstrated in 6 (5.9%) patients, and intraoperative perforations occurred in 4 (3.9%) patients. All CRM involvement and intraoperative perforation located at anteriorly and anterolaterally. The local recurrence was 4.9% at a median follow-up of 35 months (range, 18-58 months). CONCLUSIONS: ELAPE performed in the prone position for low rectal cancer leads to a reduction in CRM involvement, intraoperative perforations, and local recurrence, but it might result in a little high rate of perineal wound related complications. Reconstruction of pelvic floor with biologic mesh might lower the rate of perineal wound complications.

Regulation of opsin and circadian clock genes on mate-finding behavior of the day-flying red moth, Phauda flammans (Walker).

First, significantly higher mate-finding success was found under light condition than under constant darkness condition in Phauda flammans, a typical diurnal moth. We speculate that mate-finding behavior in P. flammans may be influenced by the light-sensitive opsin genes Long wavelength opsin (PfLW), Ultraviolet opsin (PfUV) and Blue opsin (PfBL), which are potentially regulated by both light-cues and endogenous circadian rhythms. Second, the circadian clock genes Period (PfPer), Timeless (PfTim), Cryptochrome1 (PfCry1), Cryptochrome2 (PfCRY2), Cryptochrome3 (PfCry-like), Clock (PfClk), Cycle (PfCyc), Vrille (PfVri), and Slimb (PfSli) were identified in P. flammans. Third, circadian rhythms in the relative expression levels of opsin and circadian clock genes were demonstrated via quantitative real-time PCR analysis, with peak expression coinciding with the mate-finding peak. Notably, the relative expression of PfLW in males P. flammans was significantly higher than that in females P. flammans at the mate-finding peaks Zeitgeber time (ZT) 8 and ZT 10 under light, while the expression of the opsin gene PfBL showed a similar pattern at ZT 10 under light. Additionally, the expression of the clock gene PfCry-like was significantly higher in males than in females at ZT 8 and ZT 10 under light, while PfPer, PfTim, PfClk and PfCyc exhibited similar male-biased expression patterns at ZT 10 under light. Conversely, PfCry1 and PfVri expression was significantly higher in females than in male at ZT 8 under light. In conclusion, sex differences were detected in the expression of opsin and circadian clock genes, which indicated that light-mediated regulation of these genes may contribute to the daytime mate-finding behavior of P. flammans.

Synergy between nanoplastics and benzo[a]pyrene promotes senescence by aggravating ferroptosis and impairing mitochondria integrity in Caenorhabditis elegans.

Micro-nano plastics have been reported as important carriers of polycyclic aromatic hydrocarbons (PAHs) for long-distance migration in the environment. However, the combined toxicity from long-term chronic exposure beyond the vehicle-release mechanism remains elusive. In this study, we investigated the synergistic action of Benzo[a]pyrene (BaP) and Polystyrene nanoparticles (PS) in Caenorhabditis elegans (C. elegans) as a combined exposure model with environmental concentrations. We found that the combined exposure to BaP and PS, as opposed to single exposures at low concentrations, significantly shortened the lifespan of C. elegans, leading to the occurrence of multiple senescence phenotypes. Multi-omics data indicated that the combined exposure to BaP and PS is associated with the disruption of glutathione homeostasis. Consequently, the accumulated reactive oxygen species (ROS) cannot be effectively cleared, which is highly correlated with mitochondrial dysfunction. Moreover, the increase in ROS promoted lipid peroxidation in C. elegans and downregulated Ferritin-1 (Ftn-1), resulting in ferroptosis and ultimately accelerating the aging process of C. elegans. Collectively, our study provides a new perspective to explain the long-term compound toxicity caused by BaP and PS at real-world exposure concentrations.

Comparative transcriptome analysis of sensory genes from the antenna and abdomen of Quadrastichus mendeli Kim.

Quadrastichus mendeli Kim is one of the most important parasitoids of Leptocybe invasa Fisher et La Salle, which is an invasive gall-making pest in eucalyptus plantations in the world. Gall-inducing insects live within plant tissues and induce tumor-like growths that provide the insects with food, shelter, and protection from natural enemies. Empirical evidences showed that sensory genes play a key role in the host location of parasitoids. So far, what kind of sensory genes regulate parasitoids to locate gall-inducing insects has not been uncovered. In this study, sensory genes in the antenna and abdomen of Q. mendeli were studied using high-throughput sequencing. In total, 181,543 contigs was obtained from the antenna and abdomen transcriptome of Q. mendeli. The major sensory genes (chemosensory proteins, CSPs; gustatory receptors, GRs; ionotropic receptors, IRs; odorant binding proteins, OBPs; odorant receptors, ORs; and sensory neuron membrane proteins, SNMPs) were identified, and phylogenetic analyses were performed with these genes from Q. mendeli and other model insect species. The gene co-expression network constructed by WGCNA method is robust and reliable. There were 10,314 differentially expressed genes (DEGs), and among them, 99 genes were DEGs. A comprehensive sequence resource with desirable quality was built by comparative transcriptome of the antenna and abdomen of Q. mendeli, enriching the genomic platform of Q. mendeli.

N-acetyltransferase 10 promotes cutaneous wound repair via the NF-κB-IL-6 axis.

Cutaneous wound healing, an integral part for protection of skin barrier, is a complex biological process and intimately associated with keratinocyte migration. However, mechanisms regulating keratinocyte migration in the process of cutaneous wound repair remain largely unknown. Here, we found that N-acetyltransferase 10 (NAT10) is essential for cutaneous wound repair in an in vivo skin wound healing model-a significant delay of wound repair in Nat10 haploinsufficient mice and a remarkable inhibition of keratinocyte migration by NAT10 knockdown in an in vitro keratinocyte migration model. We further demonstrate that loss of NAT10 expression attenuates the wound-induced IL-6/IL-8 expression through inhibiting NF-κB/p65 activity in keratinocytes. By deeply digging, silencing NAT10 compromises the level of nuclear p65 by facilitating its poly-ubiquitination, thus accelerates its degradation in the nucleus. Notably, we detected a strong positive correlation between the expression of NAT10 and relevant NF-kB/p65-IL6 signaling activity in mouse wound skin tissues. Overall, our study reveals an important role of NAT10 on cutaneous wound repair by potentiating NF-κB/p65-IL-6/8-STAT3 signaling. Targeting NAT10 might be a potential strategy for the treatment of skin wound dysfunctions and related diseases.

Biomarkers of aging.

Aging biomarkers are a combination of biological parameters to (i) assess age-related changes, (ii) track the physiological aging process, and (iii) predict the transition into a pathological status. Although a broad spectrum of aging biomarkers has been developed, their potential uses and limitations remain poorly characterized. An immediate goal of biomarkers is to help us answer the following three fundamental questions in aging research: How old are we? Why do we get old? And how can we age slower? This review aims to address this need. Here, we summarize our current knowledge of biomarkers developed for cellular, organ, and organismal levels of aging, comprising six pillars: physiological characteristics, medical imaging, histological features, cellular alterations, molecular changes, and secretory factors. To fulfill all these requisites, we propose that aging biomarkers should qualify for being specific, systemic, and clinically relevant.

SKP1 is involved in abscisic acid signalling to regulate seed germination, stomatal opening and root growth in Arabidopsis thaliana.

Abscisic acid (ABA) regulates many aspects of plant development, including seed dormancy and germination, root growth and stomatal closure. Plant SKP1 proteins are subunits of the SCF complex E3 ligases, which regulate several phytohormone signalling pathways through protein degradation. However, little is known about SKP1 proteins participating in ABA signalling. Here, we report that the overexpression of Triticum aestivum SKP1-like 1 (TSK1) in Arabidopsis thaliana (Arabidopsis) resulted in delayed seed germination and hypersensitivity to ABA. The opening of stomatal guard cells and the transcription of several ABA-responsive genes were affected in transgenic plants. In contrast, Arabidopsis skp1-like 1 (ask1)/ask1 ASK2/ask2 seedlings exhibited reduced ABA sensitivity. Furthermore, the transcription of ASK1 and ASK2 was down-regulated in abi1-1 and abi5-1 mutants compared with that in wild type. ASK1 or ASK2 overexpression could rescue or partially rescue the ABA insensitivity of abi5-1 mutants, respectively. Our work demonstrates that SKP1 is involved in ABA signalling and that SKP1-like genes may positively regulate ABA signalling by SCF-mediated protein degradation.

Electroantennographic and olfactory responses of Quadrastichus mendeli to eucalyptus volatiles induced by the gall-forming insect Leptocybe invasa.

BACKGROUND: Although parasitoids can precisely locate hidden gall-inducing insects, the host location mechanism is unknown. In this study, our aim was to clarify the olfactory responses of the parasitoid Quadrastichus mendeli to eucalyptus volatiles induced by the gall wasp Leptocybe invasa. RESULTS: Q. mendeli preferred volatiles from gall-damaged plants compared with those produced by mechanically damaged and undamaged plants. Coupled gas chromatographic-electroantennographic detection results demonstrated that 3-carene, decanal, d-limonene, ethanone,1-(4-ethylphenyl)-, p-cymene and benzene,1-methyl-4-(1-methylpropyl)- from DH 201-2 (Eucalyptus grandis × Eucalyptus tereticornis) elicited significant antennal responses in Q. mendeli in all treatments. Q. mendeli was repelled by decanal and d-limonene and was attracted to 3-carene, benzene,1-methyl-4-(1-methylpropyl)-, ethanone,1-(4-ethylphenyl) and p-cymene. Quaternary blends containing 3-carene, p-cymene, benzene,1-methyl-4-(1-methylpropyl)- and ethanone,1-(4-ethylphenyl)- at a ratio of 1:1:1:1 were attractive to Q. mendeli. However, quaternary blends with added decanal and d-limonene alone or both together induced significant repellence in Q. mendeli. CONCLUSION: Our report is the first to demonstrate that volatiles produced by galls induced by L. invasa are attractive to Q. mendeli, which suggests that this parasitoid could utilize herbivore-induced plant volatiles to locate its host. The results are beneficial for understanding the function of plant volatiles in host searching by parasitoids of gall-forming insect pests. © 2022 Society of Chemical Industry.