MXene-Induced Flexible, Water-Retention, Semi-Interpenetrating Network Hydrogel for Ultra-Stable Strain Sensors with Real-Time Gesture Recognition.

As water-saturated polymer networks, hydrogels are a growing family of soft materials that have recently become promising candidates for flexible electronics application. However, it remains still difficult for hydrogel-based strain sensors to achieve the organic unity of mechanical properties, electrical conductivity, and water retention. To address this challenge, based on the template, the excellent properties of MXene nanoflakes (rich surface functional groups, high specific surface area, hydrophilicity, and conductivity) are fully utilized in this study to prepare the P(AA-co-AM)/MXene@PDADMAC semi-interpenetrating network (semi-IPN) hydrogel. The proposed hydrogel continues to exhibit excellent strain response and flexibility after 30 days of storage at room temperature, and its performance do not decrease after 1100 cycles. Considering these characteristics, a hydrogel-based device for converting sign language into Chinese characters is successfully developed and optimized using machine learning. Therefore, this study provides novel insight and application directions for hydrogel families.

CCP5 and CCP6 retain CP110 and negatively regulate ciliogenesis.

BACKGROUND: The axonemal microtubules of primary cilium undergo a conserved protein posttranslational modification (PTM) - polyglutamylation. This reversible procedure is processed by tubulin tyrosine ligase-like polyglutamylases to form secondary polyglutamate side chains, which are metabolized by the 6-member cytosolic carboxypeptidase (CCP) family. Although polyglutamylation modifying enzymes have been linked to ciliary architecture and motility, it was unknown whether they also play a role in ciliogenesis. RESULTS: In this study, we found that CCP5 expression is transiently downregulated upon the initiation of ciliogenesis, but recovered after cilia are formed. Overexpression of CCP5 inhibited ciliogenesis, suggesting that a transient downregulation of CCP5 expression is required for ciliation initiation. Interestingly, the inhibitory effect of CCP5 on ciliogenesis does not rely on its enzyme activity. Among other 3 CCP members tested, only CCP6 can similarly suppress ciliogenesis. Using CoIP-MS analysis, we identified a protein that potentially interacts with CCP - CP110, a known negative regulator of ciliogenesis, whose degradation at the distal end of mother centriole permits cilia assembly. We found that both CCP5 and CCP6 can modulate CP110 level. Particularly, CCP5 interacts with CP110 through its N-terminus. Loss of CCP5 or CCP6 led to the disappearance of CP110 at the mother centriole and abnormally increased ciliation in cycling RPE-1 cells. Co-depletion of CCP5 and CCP6 synergized this abnormal ciliation, suggesting their partially overlapped function in suppressing cilia formation in cycling cells. In contrast, co-depletion of the two enzymes did not further increase the length of cilia, although CCP5 and CCP6 differentially regulate polyglutamate side-chain length of ciliary axoneme and both contribute to limiting cilia length, suggesting that they may share a common pathway in cilia length control. Through inducing the overexpression of CCP5 or CCP6 at different stages of ciliogenesis, we further demonstrated that CCP5 or CCP6 inhibited cilia formation before ciliogenesis, while shortened the length of cilia after cilia formation. CONCLUSION: These findings reveal the dual role of CCP5 and CCP6. In addition to regulating cilia length, they also retain CP110 level to suppress cilia formation in cycling cells, pointing to a novel regulatory mechanism for ciliogenesis mediated by demodifying enzymes of a conserved ciliary PTM, polyglutamylation.

Recent advances in cell-based and cell-free therapeutic approaches for sarcopenia.

Sarcopenia is a progressive loss of muscle mass and function that is connected with increased hospital expenditures, falls, fractures, and mortality. Although muscle loss has been related to aging, injury, hormonal imbalances, and diseases such as malignancies, chronic obstructive pulmonary disease, heart failure, and kidney failure, the underlying pathogenic mechanisms of sarcopenia are unclear. Exercise-based interventions and multimodal strategies are currently being considered as potential therapeutic approaches to prevent or treat these diseases. Although drug therapy research is ongoing, no drug has yet been proven to have a substantial safety and clinical value to be the first drug therapy to be licensed for sarcopenia. To better understand the molecular alterations underlying sarcopenia and effective treatments, we review leading research and available findings from the systemic change to the muscle-specific microenvironment. Furthermore, we explore possible mechanisms of sarcopenia and provide new knowledge for the development of novel cell-free and cell-based therapeutics. This review will assist researchers in developing better therapies to improve muscle health in the elderly.

Femoral image segmentation based on two-stage convolutional network using 3D-DMFNet and 3D-ResUnet.

OBJECTIVE: The femur is a typical human long bone with an irregular spatial structure. Femoral fractures are the most common occurrence in middle-aged and older adults. The structure of human bone tissue is very complex, and there are significant differences between individuals. Segmenting bone tissue is a challenging task and of great practical significance. METHODS: Our research is based on segmenting and the three-dimensional reconstruction of femoral images using X-ray imaging. The currently commonly used two-dimensional fully convolutional network Unet has the problem of ignoring spatial position information and losing too much feature information. The commonly used three-dimensional fully convolutional network 3D Unet has the problem of ignoring spatial position information and losing too much feature information. For the problem of many model parameters, we proposes a two-stage network segmentation model composed of 3D-DMFNet and 3D-ResUnet networks and trains the network in stages to segment the femur. One stage is used to detect the coarse segmentation of the femur range, and one stage is used for the fine segmentation of the femur so that the training speed is fast and the segmentation accuracy is moderate, which is suitable for detecting the femur range. RESULTS: The experimental dataset used in this paper is from The Second Affiliated Hospital of Fujian Medical University, which consists of 30 sets of femur X-ray images. The experiment compares the accuracy and loss value of Unet and the two-stage convolutional network. The image shows that the two-stage convolutional network has higher accuracy. At the same time, this paper shows the effect of the two-stage coarse segmentation and fine segmentation of medical images. Subsequently, this paper applies the model to practice and obtains the model's Dice, Sensitivity, Specificity and Pixel Accuracy values. After comparative analysis, the experimental results show that the two-stage network segmentation model composed of 3D-DMFNet and 3D-ResUnet network designed in this paper has higher accuracy, intuitiveness, and more application value than traditional image segmentation algorithms. CONCLUSION: With the continuous application of X-ray images in clinical diagnosis using femoral images, the method in this paper is expected to become a diagnostic tool that can effectively improve the accuracy and loss of femoral image segmentation and the three-dimensional reconstruction.

MicroRNA-455-3p regulates proliferation and osteoclast differentiation of RAW264.7 cells by targeting PTEN.

BACKGROUND: Macrophages are one of the important cells in immune system. In this article, we aim to explore the regulatory role of miR-455-3p on proliferation and osteoblast differentiation of RAW264.7 cells. METHODS: Expression levels of genes and proteins in cells were tested via qRT-PCR and western blot. The targeted correlation between miR-455-3p and PTEN was identified by luciferase analysis. MTT assay and flow cytometry were applied to detect the proliferation and apoptosis of cells. Osteoclastogenesis was completed by stimulating RAW 264.7 cells with RANKL. Tartrate-resistant acid phosphatase (TRAP) activity in different groups of cells were assessed. RESULTS: Firstly, we determined that up-regulation of miR-455-3p promoted the proliferation and inhibited apoptosis of RAW 264.7 cells. MiR-455-3p deficiency played opposite effect in RAW 264.7 cells. Additionally, osteoclastogenesis-related factors (TRAP, CTSK and NFATc1) expression levels were remarkably up-regulated in miR-455-3p-mimic group of RAW264.7 cells treated with RANKL, but decreased in inhibitor group. Luciferase assay proved that miR-455-3p targeted PTEN. We took a further step and found overexpression of PTEN significantly inhibited the increased proliferation and osteoblast differentiation of RAW264.7 cells induced by miR-455-3p. CONCLUSIONS: Our findings supported basic to explore the molecular mechanism of proliferation and osteoblast differentiation of RAW264.7 cells.

Controlled Hypotension Combined with Femoral Nerve Block for Knee Replacement without Tourniquet.

In the process of knee replacement surgery, the use of tourniquet technology for hemostasis is the most common method. But the adverse reactions of tourniquets in knee replacement surgery have become more prominent in recent years. More and more scholars have begun to advocate the optimization of the use of tourniquet technology, thereby controlling the use of tourniquet technology. In this study, 125 patient cases were randomly divided into four experimental groups for comparative analysis. The two sets of variables are whether to use tourniquet during surgery and use intravenous analgesia or nerve block analgesia. Studies have shown that when using a tourniquet for knee replacement surgery, the chance of hidden blood loss increases after use. The tourniquet was not used during the operation, the patient's thighs were swollen, and postoperative pain was reduced. Compared with intravenous analgesia, knee joint replacement with uncontrolled tourniquet combined with femoral nerve block has a better analgesic effect and can effectively relieve pain after knee replacement. Therefore, under the method of controlled hypotension combined with femoral nerve block, TKA surgery without using tourniquet technology is more conducive to early health recovery and pain relief after TKA surgery, as well as functional exercise and knee joint recovery during postoperative recovery.

Flexible Self-Powered Integrated Sensing System with 3D Periodic Ordered Black Phosphorus@MXene Thin-Films.

Accurate and continuous detection of physiological signals without the need for an external power supply is a key technology for realizing wearable electronics as next-generation biomedical devices. Herein, it is shown that a MXene/black phosphorus (BP)-based self-powered smart sensor system can be designed by integrating a flexible pressure sensor with direct-laser-writing micro-supercapacitors and solar cells. Using a layer-by-layer (LbL) self-assembly process to form a periodic interleaving MXene/BP lamellar structure results in a high energy-storage capacity in a direct-laser-writing micro-supercapacitor to drive the operation of sensors and compensate the intermittency of light illumination. Meanwhile, with MXene/BP as the sensitive layer in a flexible pressure sensor, the pressure sensitivity of the device can be improved to 77.61 kPa-1 at an optimized elastic modulus of 0.45 MPa. Furthermore, the smart sensor system with fast response time (10.9 ms) shows a real-time detection capability for the state of the human heart under physiological conditions. It is believed that the proposed study based on the design and integration of MXene materials will provide a general platform for next-generation self-powered electronics.

Effects of lysine 2-hydroxyisobutyrylation on bacterial FabI activity and resistance to triclosan.

Lysine 2-hydroxyisobutyrylation (Khib) is a novel protein posttranslational modification conserved in eukaryotes and prokaryotes. However, the biological significance of Khib remains largely unknown. Here, through screening the proteome-wide Khib modification sites in bacteria using a bioinformatic method, we identified a potential Khib site (K201hib) targeted by de-2-hyroxyisobutyrylase CobB at the substrate-binding site of FabI, an enoyl-acyl carry protein reductase (EnvM or FabI) in fatty acid biosynthesis pathway. First, we confirmed that the previously identified de-2-hyroxyisobutyrylase CobB can remove Khib of FabI in an in vitro experiment. To investigate the biological effects of the Khib on FabI's activity, amino acid substitutes were introduced to the modification sites of the protein of E. coli origin to mimic modified/unmodified status. We found that the mutant mimicking K201hib reduced FabI activity with decreased Michaelis constant (Km) and catalytic turnover number (kcat), while the mutant mimicking the unmodified form and the recombinant wild-type protein treated with CobB exhibited increased activity. However, the dissociation constant (KD) between FabI and NADH was not affected by the mutation mimicking the modification, suggesting that K201hib didn't alter the binding between NADH and FabI. We also found that K201hib tended to increase the resistance of E. coli to triclosan (TCL), a widely-used antibiotics targeting FabI. Taken together, this study identified the regulatory role of Khib on FabI activity and pointed to a novel mechanism related to antibiotic resistance.

Identification of 2-PMPA as a novel inhibitor of cytosolic carboxypeptidases.

Cytosolic carboxypeptidases (CCPs) comprise a unique subfamily of M14 carboxypeptidases and are erasers of the reversible protein posttranslational modification- polyglutamylation. Potent inhibitors for CCPs may serve as leading compounds targeting imbalanced polyglutamylation. However, no efficient CCP inhibitor has yet been reported. Here, we showed that 2-phosphonomethylpentanedioic acid (2-PMPA), a potent inhibitor of the distant M28 family member glutamate carboxypeptidase II (GCPII), rather than the typical M14 inhibitor 2-benzylsuccinic acid, could efficiently inhibit CCP activities. 2-PMPA inhibited the recombinant Nna1 (a.k.a. CCP1) for hydrolyzing a synthetic peptide in a mixed manner, with Ki and Ki' being 0.11 µM and 0.24 µM respectively. It inhibited Nna1 for deglutamylating tubulin, the best-known polyglutamylated protein, with an IC50 of 0.21 mM. Homology modeling predicted that the R-form of 2-PMPA is more favorable to bind Nna1, unlike that GCPII prefers to S-form. This work for the first time identified a potent inhibitor for CCP family.

Assessing the effects of modeling the spectrum of clinical symptoms on the dynamics and control of Ebola.

Mathematical modelers have attempted to capture the dynamics of Ebola transmission and to evaluate the effectiveness of control measures, as well as to make predictions about ongoing outbreaks. Many of their models consider only infections with typical symptoms, but Ebola presents clinically in a more complicated way. Even the most common symptom, fever, is not experienced by 13% of patients. This suggests that infected individuals could be asymptomatic or have moderately symptomatic infections as reported during previous Ebola outbreaks. To account crudely for the spectrum of clinical symptoms that characterizes Ebola infection, we developed a model including moderate and severe symptoms. Our model captures the dynamics of the recent outbreak of Ebola in Liberia. Our estimate of the basic reproduction number is 1.83 (CI: 1.72, 1.86), consistent with the WHO response team's estimate using early outbreak case data. We also estimate the effectiveness of interventions using observations before and after their introduction. As the final epidemic size is linked to the timing of interventions in an exponential fashion, a simple empirical formula is provided to guide policy-making. It suggests that early implementation could significantly decrease final size. We also compare our model to one with typical symptoms by excluding moderate ones. The model with only typical symptoms overestimates the basic reproduction number and effectiveness of control measures, and exaggerates changes in peak size attributable to the timing of interventions. In addition, uncertainty about how moderate symptoms affect the basic reproduction number is considered, and PRCC (Partial rank correlation coefficient) is used to analyze the global sensitivity of relevant parameters. Possible control strategies are evaluated through numerical simulations and sensitivity analysis, indicating that simultaneously strengthening contact-tracing and effectiveness of isolation in hospital would be most effective. In this study, we show that asymptomatic Ebola infections may have implications for policy-making.

Bifurcation analysis and global dynamics of a mathematical model of antibiotic resistance in hospitals.

Antibiotic-resistant bacteria have posed a grave threat to public health by causing a number of nosocomial infections in hospitals. Mathematical models have been used to study transmission dynamics of antibiotic-resistant bacteria within a hospital and the measures to control antibiotic resistance in nosocomial pathogens. Studies presented in Lipstich et al. (Proc Natl Acad Sci 97(4):1938-1943, 2000) and Lipstich and Bergstrom (Infection control in the ICU environment. Kluwer, Boston, 2002) have provided valuable insights in understanding the transmission of antibiotic-resistant bacteria in a hospital. However, their results are limited to numerical simulations of a few different scenarios without analytical analyses of the models in broader parameter regions that are biologically feasible. Bifurcation analysis and identification of the global stability conditions can be very helpful for assessing interventions that are aimed at limiting nosocomial infections and stemming the spread of antibiotic-resistant bacteria. In this paper we study the global dynamics of the mathematical model of antibiotic resistance in hospitals considered in Lipstich et al. (2000) and Lipstich and Bergstrom (2002). The invasion reproduction number [Formula: see text] of antibiotic-resistant bacteria is derived, and the relationship between [Formula: see text] and two control reproduction numbers of sensitive bacteria and resistant bacteria ([Formula: see text] and [Formula: see text]) is established. More importantly, we prove that a backward bifurcation may occur at [Formula: see text] when the model includes superinfection, which is not mentioned in Lipstich and Bergstrom (2002). More specifically, there exists a new threshold [Formula: see text], such that if [Formula: see text], then the system can have two positive interior equilibria, which leads to an interesting bistable phenomenon. This may have critical implications for controlling the antibiotic-resistance in a hospital.

Mathematical models of Ebola-Consequences of underlying assumptions.

Mathematical models have been used to study Ebola disease transmission dynamics and control for the recent epidemics in West Africa. Many of the models used in these studies are based on the model of Legrand et al. (2007), and most failed to accurately project the outbreak's course (Butler, 2014). Although there could be many reasons for this, including incomplete and unreliable data on Ebola epidemiology and lack of empirical data on how disease-control measures quantitatively affect Ebola transmission, we examine the underlying assumptions of the Legrand model, and provide alternate formulations that are simpler and provide additional information regarding the epidemiology of Ebola during an outbreak. We developed three models with different assumptions about disease stage durations, one of which simplifies to the Legrand model while the others have more realistic distributions. Control and basic reproduction numbers for all three models are derived and shown to provide threshold conditions for outbreak control and prevention.

A county-level analysis of persons living with HIV in the southern United States.

This study uses county-level surveillance data to systematically analyze geographic variation and clustering of persons living with diagnosed HIV (PLWH) in the southern United States in 2011. Clusters corresponding to large metropolitan areas - including Miami, Atlanta, and Baltimore - had HIV prevalence rates higher (p < .001) than the regional rate. Regression analysis within the counties included in these clusters determined that race was a significant indicator for PLWH. These results provide a general picture of the distribution of PLWH in the southern United States at the county level and provide insights for identifying local geographic areas with a high number of PLWH, as well as subpopulations that may have an increased risk of infection.