JMJD3 regulate H3K27me3 modification via interacting directly with TET1 to affect spermatogonia self-renewal and proliferation.

BACKGROUND: In epigenetic modification, histone modification and DNA methylation coordinate the regulation of spermatogonium. Not only can methylcytosine dioxygenase 1 (TET1) function as a DNA demethylase, converting 5-methylcytosine to 5-hydroxymethylcytosine, it can also form complexes with other proteins to regulate gene expression. H3K27me3, one of the common histone modifications, is involved in the regulation of stem cell maintenance and tumorigenesis by inhibiting gene transcription. METHODS: we examined JMJD3 at both mRNA and protein levels and performed Chip-seq sequencing of H3K27me3 in TET1 overexpressing cells to search for target genes and signaling pathways of its action. RESULTS: This study has found that JMJD3 plays a leading role in spermatogonia self-renewal and proliferation: at one extreme, the expression of the self-renewal gene GFRA1 and the proliferation-promoting gene PCNA was upregulated following the overexpression of JMJD3 in spermatogonia; at the other end of the spectrum, the expression of differentiation-promoting gene DAZL was down-regulated. Furthermore, the fact that TET1 and JMJD3 can form a protein complex to interact with H3K27me3 has also been fully proven. Then, through analyzing the sequencing results of CHIP-Seq, we found that TET1 targeted Pramel3 when it interacted with H3K27me3. Besides, TET1 overexpression not only reduced H3K27me3 deposition at Pramel3, but promoted its transcriptional activation as well, and the up-regulation of Pramel3 expression was verified in JMJD3-overexpressing spermatogonia. CONCLUSION: In summary, our study identified a novel link between TET1 and H3K27me3 and established a Tet1-JMJD3-H3K27me3-Pramel3 axis to regulate spermatogonia self-renewal and proliferation. Judging from the evidence offered above, we can safely conclude that this study provides new ideas for further research regarding the mechanism of spermatogenesis and spermatogenesis disorders on an apparent spectrum.

Efficient cocrystal coformer screening based on a Machine learning Strategy: A case study for the preparation of imatinib cocrystal with enhanced physicochemical properties.

Cocrystal engineering, which involves the self-assembly of two or more components into a solid-state supramolecular structure through non-covalent interactions, has emerged as a promising approach to tailor the physicochemical properties of active pharmaceutical ingredient (API). Efficient coformer screening for cocrystal remains a challenge. Herein, a prediction strategy based on machine learning algorithms was employed to predict cocrystal formation and seven reliable models with accuracy over 0.890 were successfully constructed. Imatinib was selected as the model drug and the models established were applied to screen 31 potential coformers. Experimental verification results indicated RF-8 is the optimal model among seven models with an accuracy of 0.839. When the seven models were combined for coformer screening of Imatinib, the combinational model achieved an accuracy of 0.903, and eight new solid forms were observed and characterized. Benefiting from intermolecular interactions, the obtained multicomponent crystals displayed enhanced physicochemical properties. Dissolution and solubility experiments showed the prepared multicomponent crystals had higher cumulative dissolution rate and remarkably improved the solubility of imatinib, and IM-MC exhibited comparable solubility to Imatinib mesylate α form. Stability test and cytotoxicity results showed that multicomponent crystals exhibited excellent stability and the drug-drug cocrystal IM-5F exhibited higher cytotoxicity than pure API.

Stretchable, Self-Rolled, Microfluidic Electronics Enable Conformable Neural Interfaces of Brain and Vagus Neuromodulation.

Implantable neuroelectronic interfaces have gained significant importance in long-term brain-computer interfacing and neuroscience therapy. However, due to the mechanical and geometrical mismatches between the electrode-nerve interfaces, personalized and compatible neural interfaces remain serious issues for peripheral neuromodulation. This study introduces the stretchable and flexible electronics class as a self-rolled neural interface for neurological diagnosis and modulation. These stretchable electronics are made from liquid metal-polymer conductors with a high resolution of 30 µm using microfluidic printing technology. They exhibit high conformability and stretchability (over 600% strain) during body movements and have good biocompatibility during long-term implantation (over 8 weeks). These stretchable electronics offer real-time monitoring of epileptiform activities with excellent conformability to soft brain tissue. The study also develops self-rolled microfluidic electrodes that tightly wind the deforming nerves with minimal constraint (160 µm in diameter). The in vivo signal recording of the vagus and sciatic nerve demonstrates the potential of self-rolled cuff electrodes for sciatic and vagus neural modulation by recording action potential and reducing heart rate. The findings of this study suggest that the robust, easy-to-use self-rolled microfluidic electrodes may provide useful tools for compatible neuroelectronics and neural modulation.

Polar Organic Charge-Transfer Complex of the Asymmetrical Component for Flexible Piezoelectric Energy Harvesting and Self-Powered Wearable Sensors.

Organic piezomaterials have attracted much attention because of their easy processing, lightweight, and mechanic flexibility properties. Developing new smart organic piezomaterials is highly required for new-generation electronic applications. Here, we found a novel organic piezomaterial of organic charge-transfer complex (CTC) consisting of dibenzcarbazole analogue (DBCz) and tetracyanoquinodimethane (TCNQ) in the molecular-level heterojunction stacking mode. The DBCz-TCNQ complex exhibited ferroelectric properties (the saturated polarization of ∼1.23 µC/cm2) at room temperature with a low coercive field. The noncentrosymmetric alignment (Pc space group) led to a spontaneous polarization of this architecture and thus was the origin of the piezoelectric behavior. Lateral piezoelectric nanogenerators (PENGs) based on the thermal evaporated CTC thin-film exhibited significant energy conversion behavior under mechanical agitation with a calculated piezoelectric coefficient (d31) of ∼33 pC/N. Furthermore, such a binary CTC thin-film constructed single-electrode PENG could show steady-state sensing performance to external stimuli as this flexible wearable device precisely detected physiological signals (e.g., finger bending, blink movement, carotid artery, etc.) with a self-powered supply. This work provides that the polar CTCs can act as efficient piezomaterials for flexible energy harvesting, conversion, and wearable sensing devices with a self-powered supply, enabling great potential in healthcare, motion detection, human-machine interfaces, etc.

The effects and predictive value of calcium and magnesium concentrations on nutritional improvement, inflammatory response and diagnosis in patients with Crohn's disease.

BACKGROUND: Crohn's disease (CD) is a progressive inflammatory disease of the gastrointestinal tract associated with malnutrition, high levels of inflammation and calcium and magnesium deficiencies. However, the relationships between these symptoms are poorly defined. METHOD: Seventy-six adult CD patients who had not yet started treatment and 83 healthy volunteers were recruited. The dietary intakes, serum calcium and magnesium levels, nutritional indicators and biochemical markers of disease activity were measured. RESULTS: Most participants had inadequate magnesium and calcium intake. The serum magnesium and calcium levels, as well as nutritional and inflammatory indicators, differed significantly between CD patients and controls, especially in the active phase. Serum levels of magnesium and calcium correlated with both nutritional status and inflammation. The cut-off values for CD development were 0.835 mmol/L (magnesium) and 2.315 mmol/L (calcium), whereas those for the active phase were 0.785 and 2.28 mmol/L, respectively. CONCLUSION: Adequate intake of magnesium and calcium may both improve the nutritional status of CD patients and reduce inflammation, benefiting disease relief. As both magnesium and calcium reflect CD status, they may be useful markers for CD diagnosis and disease activity.

A study of targeted mutation of l-rhamnose isomerase to improve the conversion efficiency of D-allose.

D-Allose is a rare cis-caprose with a wide range of physiological functions, which has a wide range of applications in medicine, food, and other industries. L-Rhamnose isomerase (L-Rhi) is the earliest enzyme found to catalyze the production of D-allose from D-psicose. This catalyst has a high conversion rate, but its specificity for substrates is limited; thus, it cannot fulfill the requirements of industrial production of D-allose. In this study, L-Rhi derived from Bacillus subtilis was employed as the research subject, and D-psicose as the conversion substrate. Two mutant libraries were constructed through alanine scanning, saturation mutation, and rational design based on the analysis of the secondary structure, tertiary structure, and interactions with ligands of the enzyme. The yield of D-allose produced by these mutants was assessed; it was found that the conversion rate of mutant D325M to D-allose was increased by 55.73 %, and the D325S improved by 15.34 %, while mutant W184H increased by 10.37 % at 55 °C, respectively. According to modeling analysis, manganese (Mn2+) had no significant effect on the production of D-psicose from D-psicose by L-Rhi. The results of molecular dynamics simulation demonstrated that the mutants W184H, D325M, and D325S had more stable protein structures while binding with the substrate D-psicose, as evidenced by its root mean square deviation (RMSD), root mean square fluctuation (RMSF), and binding free energy values. It was more conducive to binding D-psicose and facilitating its conversion to D-allose, providing the basis for the production of D-allose.

Sr2BN2Cl:Eu2+-Based Narrow-Band Blue-Emitting Phosphor: A Potential Color Converter for Illumination and Displays.

Due to the wide range of uses for phosphors in lighting and displays, research on narrow-band luminescent phosphors has recently received significant interest. In this work, Eu2+-activated Sr2BN2Cl phosphor has been successfully synthesized. Sr2BN2Cl:Eu2+ shows a wide absorption band in the UV region and exhibits a narrow-band emission peaking at 450 nm with a full width at half-maximum of ∼60 nm. More significantly, excellent thermal stability was discovered, which showed it still retained 87.4 and 100% of room-temperature intensity at 150 and 250 °C, respectively. The rigid skeleton formed by the co-edge connection of Sr(N, Cl)6 octahedra and defects in the crystal are responsible for the excellent thermal stability of the phosphor. In addition, two types of white-led devices have been prepared to test this phosphor for illumination and display applications. The former shows low correlated color temperature (CCT = 3190 K) and a high color rendering index (CRI = 92.0). The latter shows that using Sr2BN2Cl:Eu2+, ß-sialon:Eu2+, and K2SiF6:Mn4+ together for backlit displays can cover 73.3% of the NTSC area, which is comparable to commercial BaMgAl10O17:Eu2+ phosphors. These findings suggest that the blue phosphor Sr2BN2Cl:Eu2+ will be a promising choice for lighting and backlight displays.

Multifaceted Roles of Retromer in EGFR Trafficking and Signaling Activation.

Mammalian retromer complex contributes to multiple early endosome-associated trafficking pathways whose origins are dependent on which sorting nexin (SNX) they are complexed with. In an attempt to dissect out the contribution of individual retromer-SNX complexes, we examined the trafficking of EGFR in detail within a series of KO cell line models. We demonstrated that the depletion of retromer subunit Vps35 leads to decreased EGFR protein levels in resting cells with enhanced association of EGFR with lysosomal compartments. Compared to control cells, the addition of EGF to Vps35 KO cells resulted in a reduced rate of EGFR degradation; AKT activation and cell prolferation rates were elevated, while ERK activation remained relatively unchanged. These observations are consistent with a prolonged temporal association of EGFR within early endosomes due to the inefficiency of early endosome-associated protein trafficking pathways or organelle maturation due to retromer absence. We did not fully delineate the discrete contributions from retromer-associated SNXs to the phenotypes observed from retromer Vps35 depletion. While each of the knock-outs of SNX1/2, SNX3, or SNX27 promotes the enhanced association of EGFR with early endosomal compartments, only the decreased EGF-mediated EGFR degradation was observed in SNX1/2 dKO cells, while the enhanced AKT activation was only increased in SNX3 KO or SNX27 KO cells. Despite this, each of the knock-outs showed increased EGF-stimulated cell proliferation rates.

TEM Investigation of Asymmetric Deposition-Driven Crystalline-to-Amorphous Transition in Silicon Nanowires.

Controlling the shape and internal strain of nanowires (NWs) is critical for their safe and reliable use and for the exploration of novel functionalities of nanodevices. In this work, transmission electron microscopy was employed to examine bent Si NWs prepared by asymmetric electron-beam evaporation. The asymmetric deposition of Cr caused the formation of nanosized amorphous-Si domains; the non-crystallinity of the Si NWs was controlled by the bending radius. No other intermediate crystalline phase was present during the crystalline-to-amorphous transition, indicating a direct phase transition from the original crystalline phase to the amorphous phase. Moreover, amorphous microstructures caused by compressive stress, such as amorphous Cr domains and boxes, were also observed in the asymmetric Cr layer used to induce bending, and the local non-crystallinity of Cr was lower than that of Si under the same bending radius.

A comparison of contributions of individual muscle and combination muscles to interaction force prediction using KPCA-DRSN model.

Rapid and accurate prediction of interaction force is an effective way to enhance the compliant control performance. However, whether individual muscles or a combination of muscles is more suitable for interaction force prediction under different contraction tasks is of great importance in the compliant control of the wearable assisted robot. In this article, a novel algorithm that is based on sEMG and KPCA-DRSN is proposed to explore the relationship between interaction force prediction and sEMG signals. Furthermore, the contribution of each muscle to the interaction force is assessed based on the predicted results. First of all, the experimental platform for obtaining the sEMG is described. Then, the raw sEMG signal of different muscles is collected from the upper arm during different contractions. Meanwhile, the output force is collected by the force sensor. The Kernel Principal Component Analysis (KPCA) method is adopted to remove the invalid components of the raw sEMG signal. After that, the processed sequence is fed into the Deep Residual Shrinkage Network (DRSN) to predict the interaction force. Finally, based on the prediction results, the contribution of each sEMG signal from different muscles to the interaction force is evaluated by the mean impact value (MIV) indicator. The experimental results demonstrate that our methods can automatically extract the valid features of sEMG signal and provided fast and efficient prediction. In addition, the single muscle with the largest MIV index could predict the interaction force faster and more accurately than the muscle combination in different contraction tasks. The finding of our research provides a solid evidence base for the compliant control of the wearable robot.

Association Between Non-Suicidal Self-Injury and Gut Microbial Characteristics in Chinese Adolescent.

Purpose: By exploring the gut-related microbiota differences of adolescents with non-suicidal self-injury (NSSI) and depression (without NSSI) and healthy volunteers, we provide a theoretical basis for the prevention and control of NSSI in adolescents through intestinal microecological regulation. Patients and Methods: A total of 99 subjects were recruited in Guangdong Province, China, including 51 adolescents with NSSI (KD), 24 healthy adolescents (NOR1), and 24 depression adolescents without NSSI (NOR2). General clinical data and fecal samples were collected from all subjects, who were assessed using the NSSI Behavioral Questionnaire and the 24-item Hamilton Depression Scale. The taxonomic composition of the gut microbiota was determined using the 16S rDNA gene sequencing method. Results: There were significant differences in diversity between the KD and NOR1, and the species uniformity index of the KD according to the Shannon and Simpson indices was significantly reduced compared with that of the NOR1 (4.81 vs 5.21, p<0.01; 0.02 vs 0.01, p<0.05). The relative abundances were different among the KD, NOR1 and NOR2, as reflected at the taxonomic levels of class, order, family, genus, and species. Bacteroides were the dominant flora of the KD and NOR2, while Mitsuokella was the dominant flora that distinguished the KD from the NOR2. Conclusion: We found that gut microbiota diversity was decreased in adolescents with NSSI, and the relative abundance was altered at different taxonomic levels. These results enrich the understanding of the relationship between NSSI and depression and the gut microbiota, Supporting that NSSI and depression are not homologous disorders. What is more, it establishes the basis for exploring the mechanisms of flora action in NSSI, providing a possible direction for NSSI to achieve a better prognosis and prevent relapse.

Estimation of Knee Extension Force Using Mechanomyography Signals Based on GRA and ICS-SVR.

During lower-extremity rehabilitation training, muscle activity status needs to be monitored in real time to adjust the assisted force appropriately, but it is a challenging task to obtain muscle force noninvasively. Mechanomyography (MMG) signals offer unparalleled advantages over sEMG, reflecting the intention of human movement while being noninvasive. Therefore, in this paper, based on MMG, a combined scheme of gray relational analysis (GRA) and support vector regression optimized by an improved cuckoo search algorithm (ICS-SVR) is proposed to estimate the knee joint extension force. Firstly, the features reflecting muscle activity comprehensively, such as time-domain features, frequency-domain features, time-frequency-domain features, and nonlinear dynamics features, were extracted from MMG signals, and the relational degree was calculated using the GRA method to obtain the correlation features with high relatedness to the knee joint extension force sequence. Then, a combination of correlated features with high relational degree was input into the designed ICS-SVR model for muscle force estimation. The experimental results show that the evaluation indices of the knee joint extension force estimation obtained by the combined scheme of GRA and ICS-SVR were superior to other regression models and could estimate the muscle force with higher estimation accuracy. It is further demonstrated that the proposed scheme can meet the need of muscle force estimation required for rehabilitation devices, powered prostheses, etc.

High glucose inhibits the osteogenic differentiation of periodontal ligament stem cells in periodontitis by activating endoplasmic reticulum stress.

Background: Periodontitis is a highly prevalent dental disease which is associated with diabetes and is challenging to cure in diabetic patients. However, the mechanism of comorbid diabetes and periodontitis is still unclear. This study aimed to uncover the role of endoplasmic reticulum (ER) stress in high glucose-associated periodontitis. Methods: Periodontal tissues were obtained from diabetic patients with periodontitis, periodontitis patients without systemic disease, and healthy teeth. The expressions of ER stress-related factors GRP78, ATF6, PERK and XBP1 were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and immumohistochemical staining. Periodontal ligament stem cells (PDLSCs) from three states of periodontal tissues were isolated and cultured as diabetic PDLSCs (dPDLSCs), inflamed PDLSCs (iPDLSCs) and healthy PDLSCs (hPDLSCs), and the cell stemness was assayed. Different concentrations (8, 11, and 25 mmol/L) of D-glucose were used on hPDLSCs to simulate high glucose microenvironment. The changes of osteogenic ability of PDLSCs were observed, and the expressions of ER stress-related factors in different time point (6, 12, 24, and 72 h) were detected. Finally, GRP78 shRNA lentivirus was used to block ER stress on PDLSCs in the 25 mmol/L D-glucose microenvironment, and the osteogenic ability of PDLSCs was observed. Results: The results showed that the expressions of GRP78, ATF6, PERK, and XBP1 were highest in the diabetic periodontitis group and lowest in the healthy periodontal tissue group (P<0.05). The clone formation, osteogenic and lipogenic differentiation abilities were lowest in dPDLSCs and highest in hPDLSCs. With the increase of glucose concentration, the osteogensis ability of PDLSCs decreased. After 6 hours of stimulation with D-glucose 25 mmol/L, the ER stress pathways in PDLSCs were effectively activated, and the peak value was reached at 12 hours. The decrease in the osteogensis ability of PDLSCs in a high glucose microenvironment reversed when ER stress was blocked. Conclusions: The osteogenic differentiation ability of PDLSCs cells is inhibited in a high glucose microenvironment, and this effect is realized by ER stress activation. Blocking ER stress can partially restore the reduced osteogenic ability of PDLSCs. These results suggest that high glucose inhibits the osteogenic differentiation ability of PDLSCs by activating ER stress, which ultimately exacerbates periodontitis.

Quantifying the CVD-grown two-dimensional materials via image clustering.

Machine learning (ML) techniques have been recently employed to facilitate the development of novel two-dimensional (2D) materials. Among various synthesis approaches, chemical vapor deposition (CVD) has demonstrated tremendous potential in producing high-quality 2D flakes with good controllability, enabling large-scale production at a relatively low cost. Traditionally, the quality of CVD-grown samples can be manually evaluated based on optical images which is labor-intensive and time-consuming. In this paper, we explored a data-driven unsupervised quality assessment strategy based on image clustering via integrating self-organizing map (SOM) and k-means methods for optical image analysis of CVD-grown 2D materials. The high matching rate between the clustering results and material experts' labels indicated a good accuracy of the proposed clustering algorithm. The proposed unsupervised ML methodology will provide materials scientists with an effective tool kit for efficient evaluation of CVD-grown materials' quality and has a broad applicability for various material systems.

Retromer dependent changes in cellular homeostasis and Parkinson's disease.

To date, mechanistic treatments targeting the initial cause of Parkinson's disease (PD) are limited due to the underlying biological cause(s) been unclear. Endosomes and their associated cellular homeostasis processes have emerged to have a significant role in the pathophysiology associated with PD. Several variants within retromer complex have been identified and characterised within familial PD patients. The retromer complex represents a key sorting platform within the endosomal system that regulates cargo sorting that maintains cellular homeostasis. In this review, we summarise the current understandings of how PD-associated retromer variants disrupt cellular trafficking and how the retromer complex can interact with other PD-associated genes to contribute to the disease progression.

New phenomena of photo-luminescence and persistent luminescence of a Eu2+,Tb3+ codoped Ca6BaP4O17 phosphor under high hydrostatic pressure.

In this study, we present a photo-luminescence (PL) and persistent luminescence (PersL) investigation of Ca6BaP4O17:Eu2+,Tb3+ (CBPO:Eu,Tb) at high hydrostatic pressure in the range of 0-11.04 GPa. More importantly, there is a significant increase of PL intensity and extension of PersL duration time at a pressure point of ∼0.15 GPa.

A Brief Review of OPT101 Sensor Application in Near-Infrared Spectroscopy Instrumentation for Intensive Care Unit Clinics.

The optoelectronic sensor OPT101 have merits in advanced optoelectronic response characteristics at wavelength range for medical near-infrared spectroscopy and small-size chip design with build-in trans-impedance amplifier. Our lab is devoted to developing a series of portable near-infrared spectroscopy (NIRS) devices embedded with OPT101 for applications in intensive care unit clinics, based on NIRS principle. Here we review the characteristics and advantages of OPT101 relative to clinical NIRS instrumentation, and the most recent achievements, including early-diagnosis and therapeutic effect evaluation of thrombus, noninvasive monitoring of patients' shock severity, and fatigue evaluation. The future prospect on OPT101 improvements in noninvasive clinical applications is also discussed.

[Effects of different intakes of protein on nutritional status in severe stroke patients].

OBJECTIVE: To investigate the effects of different intake of protein on nutritional indicators in severe stroke patients. METHODS: 89 patients with severe stroke and NRS-2002 scores not less than 3 were enrolled. The patients were divided into group A, group B and group C by random, and 28 cases were in group A with protein intake at 0.9 g/kg, 30 cases were in group B with protein intake at 1.2 g/kg and 31 cases were in group C with protein intake at 1.6 g/kg, all patients were given the same calories support (25 kcal/kg). On the day of pre-intervention, the 7th and 14th day of post-intervention, fasting blood samples were collected from every subjects. The total protein (TP), albumin (ALB), hemoglobin (Hb), creatinine (Cr), blood urea nitrogen (BUN), midarm circumference (MAC) and calf circumference (CC) were recorded. RESULTS: (1) The MAC and CC of health side body decreased on the 14th day post-intervention in group A and group B, the differences were significant compared with pre-intervention and on the 7th day post-intervention (P < 0.05), but there were no statistical differences between group A and group B. The index of group C had no significant changes from pre-intervention to the 14th day post-intervention. The differences among the three groups were statistically significant on the 14th day post-intervention (P < 0.05). (2) TP, ALB and Hb in group A were decreased from pre-intervention to the 14th day post-intervention, the differences were statistically significant. The levels of TP and Hb decreased in group B during the observation period, the differences were statistically significant. ALB in group B was decreased on the 7th day post-intervention, but it was increased on the 14th day post-intervention, there was no statistical difference compared with pre-intervention. The levels of TP, ALB and Hb in group C had no significant differences on the 7th day post-intervention, but they all increased on the 14th day post-intervention. The differences of ALB and Hb in group C were statistically significant on the 14th day post-intervention compared with pre-intervention and on the 7th day post-intervention. The differences of TP, ALB and Hb among the three groups were statistically significant on the 14th day post-intervention. (3) Cr in the three groups did not have significant differences during the observation period. BUN of group A and group B were both increased post-interventinon, the differences were statistically significant compared with pre-intervention and there were statistically significant differences between group A and group B (P < 0.05). BUN in group C did not have significant changes during the observation period. On the 14th day post-intervention, the differences of BUN were statistically significant among the three groups (P < 0.05). CONCLUSION: The nutritional effect of protein intake at 1.6 g/kg is better than 0.9 g/kg and 1.2 g/kg on improving the nutritional status in severe stroke patients.