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Background: Mesenchymal stem cells (MSCs) have been used to treat immunopathy, and three-dimensional (3D) cultured MSCs show enhanced immunomodulatory property compared with those in two-dimensional (2D) culture. However, both the regulatory mechanisms remain unclear. The aim of the study was to investigate the role of mechanical stress in maintaining the immunomodulatory function of 2D and 3D cultured MSCs.Methods: Umbilical cord mesenchymal stem cells (UC-MSCs) were plated on tissue culture plastic (TCP) as 2D culture and 3D cultured UC-MSCs were seeded in matrigel. Surface markers, clonogenicity, proliferation and immunoregulatory property of UC-MSCs were evaluated. Meanwhile, we established the mouse models of colitis and type 1 diabetes mellitus (T1DM) to reveal the pharmacotherapeutic effects of 3D cultured MSCs in vivo. The effect of changing mechanical stress by modulating Yes-associated protein (YAP) on immunomodulatory function of 2D and 3D cultured UC-MSCs was evaluated by immunofluorescent analysis, real-time quantitative polymerase chain reaction (qPCR) and western blot.Results: We verified early passage UC-MSCs in 2D and 3D cultures exhibited stemness, immunomodulatory property and therapeutic efficacy against immunopathy. However, these characteristics of 2D cultured UC-MSCs were impaired after extensive expansion, whereas 3D culture extended them for several passages by activating YAP. Moreover, prostaglandin E2 (PGE2) could up-regulate YAP to improve the immunomodulatory ability of 2D cultured UC-MSCs after extensive expansion. Conclusions: This work found for the first time that the significance of mechanical stress in maintaining immunoregulatory function of 2D and 3D cultured UC-MSCs, providing a new idea for improving the efficacy of MSCs-based immunotherapy.

Mitochondrial biogenesis and energy metabolism are essential for regulating the inflammatory state of monocytes. This state is partially controlled by peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), a coactivator that regulates mitochondrial biogenesis and energy metabolism. Disruption of these processes can also contribute to the initiation of chronic inflammatory diseases, such as pulmonary fibrosis, atherosclerosis, and rheumatoid arthritis. Methyltransferase-like 3 (METTL3)-dependent N6-methyladenosine (m6A) methylation has recently been shown to regulate a variety of inflammatory processes. However, the role of m6A mRNA methylation in affecting mitochondrial metabolism in monocytes under inflammation is unclear, nor is there an established relationship between m6A methylation and PGC-1α. In this study, we identified a novel mechanism by which METTL3 acts during oxidized low-density lipoprotein (oxLDL)-induced monocyte inflammation, where METTL3 and YTH N6-methyladenosine RNA binding protein 2 (YTHDF2) cooperatively modify PGC-1α mRNA, mediating its degradation, decreasing PGC-1α protein levels, and thereby enhancing the inflammatory response. METTL3 coordinated with YTHDF2 to suppress the expression of PGC-1α, as well as that of cytochrome c (CYCS) and NADH:ubiquinone oxidoreductase subunit C2 (NDUFC2) and reduced ATP production and oxygen consumption rate (OCR). This subsequently increased the accumulation of cellular and mitochondrial reactive oxygen species (ROS) and the levels of proinflammatory cytokines in inflammatory monocytes. These data may provide new insights into the role of METTL3-dependent m6A modification of PGC-1α mRNA in the monocyte inflammation response. These data also contribute to a more comprehensive understanding of the pathogenesis of monocyte-macrophage inflammation-associated diseases, such as pulmonary fibrosis, atherosclerosis, and rheumatoid arthritis.

Ruminants have a superficial implantation pattern. The extended conceptus attaches to the receptive endometrium to form the cotyledonary placenta. During the attachment, a large number of events occur at the maternal-fetal interface. However, the related molecular mechanisms have not been fully understood. Integrin beta8 (ITGB8) is a subunit of integrin beta involved in embryo implantation. In this study, we determined peri-implantation expression and regulation of ITGB8 in goat uterus. The mRNA and protein levels of ITGB8 were both high in goat endometrial luminal epithelium (LE) and superficial glandular epithelium (sGE) during the adhesion period (Days 16-19 of pregnancy). Such expression profile was opposite to that of microRNA-187 (miR-187). Then, we validated that miR-187 targeted the 3' untranslated region (UTR) of ITGB8 in primary goat endometrial epithelial cells (EECs). In EECs, inhibition of miR-187 resulted in not only up-regulated ITGB8 level but also reduced cell proliferation and focal adhesion kinase (FAK) activity. Moreover, ITGB8 and miR-187 were regulated by interferon tau (IFNT). Altogether, in goat, the miR-187/ITGB8 axis may be involved in conceptus attachment and is downstream of IFNT. Our results will help us better understand the mechanisms of ruminant implantation and may provide a useful tool to improve the reproduction ratio for ruminants.

Leader-following consensus is an essential problem for tracking control. However, the state trajectories of agents may be exposed because of frequent exchange of information. Hence, this paper considers the secure leader-following consensus with continuous-time dynamics over directed fixed topologies. For each follower, introduce a virtual node that forms a directed node pair combining with the real node, i.e., the information can only transmit from virtual node to real node in a node pair. In this case, we design a control law utilizing neighboring information, and analyze convergence and privacy preservation of the leader-following multi-agent systems. Finally, a numerical simulation is provided to illustrate our results.

Molecular factors that drive metastasis in premenopausal patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2−), early breast cancer (EBC) are largely unknown. To identify markers/signatures contributing to metastasis, we analyzed molecular changes in tumors from premenopausal patients who developed metastasis (M1) and who did not (M0). Ninety-seven premenopausal patients with HR+/HER2− EBC were included (M1, n = 48, median distant metastasis-free survival (DMFS): 54 (7–184) months, M0, n = 49, median follow-up: 149 (121–191) months). Gene expression profiling on tumor RNA (Breast Cancer 360TM panel, Nanostring) was performed, followed by comprehensive bioinformatic and statistical analyses. Significantly enhanced ROR (risk of recurrence) scores and reduced signature scores of PGR (progesterone receptor), claudin-low, and mammary stemness were determined in M1. These differences were significantly associated with shorter DMFS in univariate survival analyses. Gene set enrichment analysis showed an enriched mTORC1 pathway in M1. Moreover, a metastasis signature of 19 differentially expressed genes (DEGs) that were DMFS-related was defined. Multivariate analysis including the four signatures, 19 DEGs, pN, and pT status, identified LRP2, IBSP, and SCUBE2 as independent prognostic factors. We identified prognostic gene signatures and single-gene markers for distant metastasis in premenopausal HR+/HER2− EBC potentially applicable in future clinical practice.

Developmental programmed cell death (dPCD) has multiple functions in plant growth and development, and is of great value for industrial production. Among them, wood formed by xylem dPCD is one of the most widely used natural materials. Therefore, it is crucial to explore the molecular mechanism of plant dPCD. The dPCD process is tightly regulated by genetic networks and is involved in the transduction of signaling molecules. Several key regulators have been identified in diverse organisms and individual PCD events. However, complex molecular networks controlling plant dPCD remain highly elusive, and the original triggers of this process are still unknown. This review summarizes the recent progress on the transcriptional regulation and signaling of dPCD during vegetative and reproductive development. It is hoped that this review will provide an overall view of the molecular regulation of dPCD in different developmental processes in plants and identify specific mechanisms for regulating these dPCD events. In addition, the application of plants in industrial production can be improved by manipulating dPCD in specific processes, such as xylogenesis.

This study explores food safety and sanitation-related competence, self-efficacy, overall behavioral motives, behavioral intentions, behaviors, and the effects of the organizational environment on foodservice employees. Significant positive correlations are found between food safety and sanitation-related competence, self-efficacy, overall behavioral motive, behavioral intention, and food safety-related behavior. A structural equation modeling analysis of those paramters indicated that competence positively affects self-efficacy and overall behavioral motive. The affect on the behavior applied for both self-efficacy and overall behavioral motive and positively influenced behavioral intention and behavior. Thus, the model we obtained a goodness of fit. Improving the organization environment can increase the influence of self-efficacy and behavioral intention on behavior.

Tantalum exhibits excellent biocompatibility and good chemical stability, which has been employed in dental and orthopedic applications. The local microenvironment of the surface of implants influence determines the surrounding cell responses. In this work, nano-dimpled structure on the surface of pure tantalum was fabricated by electrochemical anodization. The surface morphology of the nano-dimpled structure was observed, and the dimensions of the nano-dimpled structure were measured by scanning electron microscopy (SEM). The surface roughness of the sample with nano-dimpled structure was measured by atomic force microscopy (AFM). The results show that the diameter of nano-dimpled ranges from 40 to 180 nm, and the higher the applied voltage, the larger the diameter. Moreover, nano-dimpled structure has good hydrophilicity. In vitro results show that nano-dimpled structure can promote the adhesion and proliferation of mouse cranial anterior bone (MC-3T3-E1) cells. The filopodia of MC-3T3-E1 cells can be fully extended on this nano-dimpled structure. On the surface of the nano-dimpled structure with a dimple size of 40 nm, the cells have the longest aspect ratio. The small dimple size of the nano-dimpled structure is beneficial to cell proliferation and osteogenic differentiation.

Background Geraniol is an acyclic monoterpene alcohol, which is extracted from the ethereal oils of aromatic plants. A systematic analysis of its mechanism of action has not yet been carried out. Methods In this study, the druggability of geraniol was assessed via Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), and the potential targets of geraniol were identified using the Comparative Toxicogenomics Database (CTD). Additionally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using WebGestalt. Drug-target-pathway networks were constructed using Cytoscape to give a visual view. Results Our findings showed that geraniol has superb druggability with 38 putative identified target genes. GO, KEGG, and network analyses revealed that these targets were associated with cancer, inflammatory immunoreactions, and other physiological processes. Conclusion Geraniol is predicted to target multiple proteins and pathways that shape a network which can exert systematic pharmacological effects.

Resistance to cisplatin (DDP)-based chemotherapy is a major cause of treatment failure in human gastric cancer (GC). It is necessary to identify the drugs to re-sensitize GC cells to DDP. In our previous research, Zuo Jin Wan Formula (ZJW) has been proved could increase the mitochondrial apoptosis via cofilin-1 in a immortalized cell line, SGC-7901/DDP. Due to the immortalized cells may still difficult highly recapitulate the important molecular events in vivo, primary GC cells model derived from clinical patient was constructed in the present study to further evaluate the effect of ZJW and the underlying molecular mechanism. Immunofluorescent staining was used to indentify primary cultured human GC cells. Western blotting was carried out to detect the protein expression. Cell Counting Kit-8 (CCK-8) was used to evaluate cell proliferation. Flow cytometry analysis was performed to assess cell apoptosis. ZJW inhibited proliferation and induced apoptosis in primary DDP-resistant GC cells. Notably, the apoptosis in GC cells was mediated by inducing cofilin-1 mitochondrial translocation, down-regulating Bcl-2 and up-regulating Bax expression. Surprisingly, the level of p-AKT protein was higher in DDP-resistant GC cells than that of the DDP-sensitive GC cells, and the activation of AKT could attenuate ZJW-induced sensitivity to DDP. These data revealed that ZJW can increase the chemosensitivity in DDP-resistant primary GC cells by inducing mitochondrial apoptosis and AKT inactivation. The combining chemotherapy with ZJW may be an effective therapeutic strategy for GC chemoresistance patients.

Background/aim Gastric cancer (GC) is one of a most threatening cancer globally. Rhotekin (RTKN), a Rho effector, has been reported to be upregulated in GC tissues. This study aimed to investigate the underlying regulatory roles of RTKN in the biological behavior of GC. Methods Real-time PCR and Western blotting were carried out to detect the mRNA and protein expression, respectively. Cell Counting Kit-8 and xenograft nude mice model were used to evaluate cell proliferation. Flow cytometry analysis was performed to assess cell cycle distribution and cell apoptosis. Results RTKN had high expression level in GC compared with normal tissues. RTKN expression strongly associated with tumor size, TNM stage, lymphnode metastasis and the poor prognosis of patients with GC. Downregulation of RTKN significantly repressed GC cell proliferation, but increased cell population in G1/S phase and induced cell apoptosis. Moreover, the RTKN expression level was related to the p53 signaling pathway and histone deacetylase (HDAC) Class I pathway. RTKN knockdown caused a notable increment in the acetylation level of p53 (Lys382), and the expression of p53-target genes (p21, Bax, and PUMA), as well as a reduction in the expression of a potential deacetylase for p53, HDAC1. Notably, downregulation of HDAC1 had similar effects as RTKN knockdown, and RTKN overexpression could hardly abrogate the effects of HDAC1 knockdown on GC cells. Conclusion RTKN could work as an oncogene via regulating HDAC1/p53 and may become a promising treatment strategy for GC.

Advanced exfoliation techniques are crucial for exploring the intrinsic properties and applications of 2D materials. Though the recently discovered Au-enhanced exfoliation technique provides an effective strategy for the preparation of large-scale 2D crystals, the high cost of gold hinders this method from being widely adopted in industrial applications. In addition, direct Au contact could significantly quench photoluminescence (PL) emission in 2D semiconductors. It is therefore crucial to find alternative metals that can replace gold to achieve efficient exfoliation of 2D materials. Here, the authors present a one-step Ag-assisted method that can efficiently exfoliate many large-area 2D monolayers, where the yield ratio is comparable to Au-enhanced exfoliation method. Differing from Au film, however, the surface roughness of as-prepared Ag films on SiO

Thirty-five years ago, Sir Michael Berry and his collaborator Mondragon studied the behaviors of neutrino, a massless relativistic quantum particle, in a classically chaotic billiard—the neutrino billiard problem. To celebrate Sir Michael Berry’s eightieth birthday, here we report results on the role of geometric symmetries of the billiard system in relativistic quantum scarring. In particular, we investigate a Dirac billiard system with a four-fold rotational symmetry whose classical dynamics are fully chaotic. The system is described by the massless Dirac equation in the fundamental domain that consists of one fourth of the full billiard, with proper boundary conditions on the symmetry lines to preserve the physical properties under the symmetry operations. We show that the relativistic quantum characteristics of spin induced phase play a fundamental role in the quantum behaviors of the Dirac particle in the billiard. We find that the peaks in the length spectra are due to the interference of states circling the fundamental domain orbits (FDOs) in opposite propagating directions, which can be constructive or destructive depending on the accumulated phases. In addition, we derive the quantization conditions of the scarring states about the unstable periodic orbits within the fundamental domain from the phase along the FDOs. Our work is a vivid demonstration that relativistic quantum scarring, or more generally quantum manifestations of classical chaos, can be fully understood by analyzing the behaviors of the geometric phase—a powerful approach in modern physics pioneered by Sir Michael Berry.

Pregnancy success is closely related to the molecular mechanisms that control energy metabolism balance. However, the mechanisms have not been fully understood. Uncoupling protein 2 (UCP2) plays a physiological role by regulating energy metabolism in numerous tissues. In this study, we determined the expression and hormone regulation of UCP2 in goat uterus. UCP2 is expressed in the luminal and glandular epithelia of goat uterus during early pregnancy, as revealed by in situ hybridization and immunohistochemistry conducted on pregnant goats. The signals were detected from day 0 (D0) to D30 of pregnancy, though weak on D16 (the adhesion period). The low levels of UCP2 on D16 were confirmed by RT-qPCR and western blot. In goat uterus and endometrial epithelial cells (EECs), UCP2 was up-regulated by progesterone and estrogen. In addition, after goat EECs were treated with genipin (an inhibitor of UCP2), not only UCP2 expression but also cell proliferation was inhibited. Collectively, UCP2 is dynamically expressed in goat uterus and can affect EEC proliferation, suggesting that it may participate in regulating the energy metabolism balance of goat uterus during early pregnancy.

OBJECTIVE: To study the clinical effect of multi-oil fat emulsion for parenteral nutrition support in extremely low birth weight (ELBW) infants. METHODS: A retrospective analysis was performed for 49 ELBW infants who were admitted from January 1, 2018 to July 30, 2020, with an age of ≤14 days on admission and a duration of parenteral nutrition of > 14 days. According to the type of lipid emulsion received, the ELBW infants were divided into two groups: soybean oil, medium-chain triglycerides, olive oil, and fish oil (SMOF) (n=26) and medium-chain triglycerides/long-chain triglycerides (MCT/LCT) (n=23). The two groups were compared in terms of clinical features, complications, nutrition support therapy, and outcome. RESULTS: The 49 ELBW infants had a mean birth weight of (892±83) g and a mean gestational age of (28.2±2.3) weeks. There was no significant difference between the two groups in the incidence rates of hemodynamically significant patent ductus arteriosus, intraventricular hemorrhage, neonatal necrotizing enterocolitis, retinopathy of prematurity, bronchopulmonary dysplasia (BPD), grade Ⅲ BPD, sepsis, and pneumonia (P > 0.05). There was also no significant difference in the duration of parenteral nutrition, the age of total enteral nutrition, and head circumference/body length/body weight at discharge between the two groups (P > 0.05). Of all the infants, 22 (45%) had parenteral nutrition-associated cholestasis (PNAC), with 13 (50%) in the SMOF group and 9 (39%) in the MCT/LCT group but there was no significant difference in the incidence of PNAC between the two groups (P > 0.05); however, the infants with PNAC in the SMOF group had significantly lower peak values of direct bilirubin and alanine aminotransferase than those in the MCT/LCT group (P < 0.05). CONCLUSIONS: The application of multi-oil fat emulsion in ELBW infants does not reduce the incidence rate of complications, but compared with MCT/LCT emulsion, SMOF can reduce the severity of PNAC in ELBW infants.

Background Hepatic steatosis is a big hurdle to treat type 2 diabetes (T2D). Fasting-mimicking diet (FMD) has been shown to be an effective intervention in dyslipidemia of T2D. However, fasting might impair the normal glucose metabolism. Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) transplantation has been discovered to regulate immune reactions and reduce hyperglycemia in diabetes. However, the effects of UC-MSCs on improving the lipid metabolism disorder are not quite satisfactory. We have investigated the efficacy comparison and interaction between two typical therapies of FMD and UC-MSC infusion, aiming to pave an avenue for their synergistic use, establish effective T2D therapies and explore its mechanism.Methods C57/BL6 mice were fed with high-fat diet (HFD) for 16 weeks to induce a diet-induced obese (DIO) mouse model. Six-week-old leptin-receptor-deficient (db/db) mice were used for follow-up experiments. DIO or db/db mice were divided into 4 groups: PBS, UC-MSCs (1*106), FMD (entails 4-day FMD and 7-day of refeeding (RF)) and UC-MSCs + FMD. At the end of the study period, mice were fasted for 6 h with the measurement of blood glucose and body weight, and then sacrificed. Blood was collected to determine levels of HbA1c, serum insulin, and cytokines. In addition, the fresh liver, skin and white adipose tissue were analyzed by histology.Results FMD restored the lipid metabolism in DIO mice, whereas its capacity to rescue hyperglycemia was uncertain. Infusion of UC-MSCs was effective in T2D glycemic control but the impact on dyslipidemia was insufficient. Furthermore, both the glucose and the lipid alterations of DIO and db/db mice recovered after UC-MSCs combined with FMD. It was proved that UC-MSCs promoted FMD effects on ameliorating hyperglycemia and restoring the lipid metabolism in T2D mice, while FMD had little promotion effect on UC-MSCs. Mechanistically, we discovered that UC-MSC infusion significantly modulated systematic inflammatory microenvironment, which contributed to concerted actions with FMD.Conclusions We established a strategy that combined UC-MSC infusion and FMD were effective in treating T2D, which synergistically attenuated hyperglycemia and improved the lipid metabolism through immunoregulation. The significance of the work is to provide potential approaches for developing novel clinical T2D therapies.

The first atmospheric window of 3–5 μm in the mid-infrared (MIR) spectral range pertains to crucial application fields, with particular scientific and technological importance. However, conventional narrow-bandgap semiconductors operating at this band, represented by mercury cadmium telluride and indium antimonide, suffer from limited specific detectivity at room temperature and hindered optoelectronic integration. In this study, a plasmonic hot electron-empowered MIR photodetector based on Al-doped ZnO (AZO)/bi-layer graphene heterostructure is demonstrated. Free electrons oscillate coherently in AZO disk arrays, resulting in strong localized surface plasmon resonance (LSPR) in the MIR region. The photoelectric conversion efficiency at 3–5 μm is significantly improved due to plasmon-induced hot-electron extraction and LSPR-enhanced light absorption. The specific detectivity reaches about 1.4 × 1011 Jones and responsivity is up to 4712.3 A/W at wavelength of 3 μm at room temperature. The device’s specific detectivity is among the highest performance of commercial state-of-the-art photodetectors and superior to most of the other 2D materials based photodetectors in the MIR region. These results demonstrate that a plasmonic heavily doped metal oxides/2D material heterostructure is a suitable architecture for constructing highly sensitive room-temperature MIR photodetectors.

To study the miR-184 level in the seminal plasma exosome of male infertility patients and its clinical significance.Between 2015 and 2019, we collected 285 seminal plasma samples from 97 azoospermia (AS) and 96 asthenospermia (AZS) patients and 92 age-matched normal fertile controls in Jiangsu Provincial Hospital of Traditional Chinese Medicine, General Hospital of Eastern Theater Command and the First Hospital Affiliated to Wenzhou Medical University, identified the isolated seminal plasma exosomes by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM) and Western blot, and detected the miR-184 level in the seminal plasma exosomes by quantitative real-time PCR (qRT-PCR). We determined the clinical value of the miR-184 level and its correlation with semen parameters by multiple statistics, predicted the target genes and involved pathways of miR-184 by bioinformatic algorithms, and analyzed their relationship with male infertility.NTA, TEM and Western blot exhibited plenty of exosomes in the seminal plasma of the patients. The results of qRT-PCR showed that the miR-184 level in the seminal plasma exosome was dramatically decreased in the AS patients compared with that in the normal fertile controls (0.227 ［0.092, 0.790］ vs 0.650 ［0.408, 1.061］, P0.01), but increased in AZS males in comparison with that in the control group (1.176 ［0.661, 1.946］ vs 0.650 ［0.408, 1.061］, P0.01). The areas under the ROC curve (AUC) for differentiating the AS and AZS patients from the controls were 0.866 (95% CI: 0.815－0.916) and 0.724 (95% CI: 0.653－0.795), respectively, and that for differentiating the AS from the AZS group was 0.964 (95% CI: 0.943－0.985). The miR-184 level in the seminal plasma exosome of the AZS patients was correlated positively with the sperm count (r = 0.243, P = 0.017) but negatively with the percentage of progressively motile sperm (r = －0.407, P = 0.006). Bioinformatics analysis indicated that the downstream target genes of miR-184 were significantly enriched in the protein regulatory pathways closely related to male reproduction and spermatogenesis.The miR-184 level in the seminal plasma exosome of infertility patients is significantly different from that of normal fertile males, which may serve as a potential auxiliary marker for the diagnosis of and participate in the development and progression of male infertility.

Background: Esophageal squamous cell carcinoma (ESCC) is the eighth most common cancer in the world. Protein arginine methyltransferase 5 (PRMT5), an enzyme that catalyzes symmetric and asymmetric methylation on arginine residues of histone and non-histone proteins, is overexpressed in many cancers. However, whether or not PRMT5 participates in the regulation of ESCC remains largely unclear.Methods: PRMT5 mRNA and protein expression in ESCC tissues and cell lines were examined by RT-PCR, western blotting, and immunohistochemistry assays. Cell proliferation was examined by RT-PCR, western blotting, immunohistochemistry assays, MTT, and EdU assays. Cell apoptosis and cell cycle were examined by RT-PCR, western blotting, immunohistochemistry assays, and flow cytometry. Cell migration and invasion were examined by RT-PCR, western blotting, immunohistochemistry assays, and wound-healing and transwell assays. Tumor volume, tumors, and mouse weight were measured in different groups. Lung tissues with metastatic foci, the number of nodules, and lung/total weight were measured in different groups.Results: In the present study, the PRMT5 expression level was dramatically upregulated in ESCC clinical tissues as well as ESCC cell lines (ECA109 and KYSE150). Furthermore, knocking down PRMT5 obviously suppressed cell migration, invasion, proliferation, and cell arrest in G1 phase and promoted cell apoptosis in ESCC cells. Meanwhile, downregulating PRMT5 also increased the expression levels of Bax, caspase-3, and caspase-9, while expression levels of Bax-2, MMP-2, MMP-9, and p21 were decreased, which are members of the cyclin-dependent kinase family. Furthermore, knocking down PRMT5 could increase the expression of LKB1 and the phosphorylation (p)-AMPK expression and decrease the p-mTOR level. Additionally, overexpression of LKB1 could reveal anti-tumor effects in ESCC cell lines by inhibiting ESCC cell, migration, invasion, and proliferation and accelerating cell apoptosis. Besides, upregulating LKB1 expression could increase the levels of Bax, caspase-3, and caspase-9 and weaken the levels of Bax-2, MMP-2, and MMP-9. Moreover, knocking down PRMT5 could weaken the tumor growth and lung metastasis in vivo with upregulating the LKB1 expression and the p-AMPK level and downregulating the p-mTOR expression.Conclusion: PRMT5 may act as a tumor-inducing agent in ESCC by modulating LKB1/AMPK/mTOR pathway signaling.

BACKGROUND Peripheral regional block combined with general anesthesia might be a preferable anesthetic regimen for elderly patients undergoing total hip arthroplasty. AIM To investigate whether ultrasound-guided, direct suprainguinal injection for fascia iliaca block accelerated recovery after general anesthesia and relieved postoperative pain after total hip arthroplasty. METHODS Patients who underwent total hip arthroplasty under general anesthesia in 2015 or 2019 at The Second Affiliated Hospital of Xuzhou Medical University were retrospectively analyzed. The patients were grouped based on whether preoperative suprainguinal fascia iliaca block was performed or not. The time to tracheal extubation and time spent in the post-anesthesia care unit (PACU), intraoperative remifentanil dosage, fentanyl consumption in the PACU, postoperative cumulative fentanyl consumption within 48 h after operation, visual analogue scale at rest and during movement on the first and second days after surgery, and adverse reactions were compared. RESULTS Thirty-one elderly patients who underwent total hip arthroplasty were included in the study (block group, n = 16; no-block group, n = 15). The visual analog scale scores at rest and during movement on the first and second days were significantly lower in the block group than in the no-block group (all P < 0.05). Compared with the no-block group, the intraoperative remifentanil dosage was lower, the time to tracheal extubation and the time spent in the PACU were shorter in the block group (all P < 0.01). Fentanyl consumption in the PACU and postoperative cumulative fentanyl consumption in 48 h after operation were lower in the block group (all P < 0.01). The incidence of dizziness was higher in the no-block group than in the block group (P = 0.037). CONCLUSION Ultrasound-guided, direct suprainguinal injection for fascia iliaca block led to faster recovery after general anesthesia and early postoperative pain relief in elderly patients undergoing total hip arthroplasty.

In this paper, we will briefly introduce the recent progress on machine learning based on the dynamical perspective. By combining machine learning with the dynamics, we get many continuous time algorithms. By discretizing the continuous time dynamic equations, we can not only review the existing algorithms, but also get new discrete-time algorithms. Firstly, gradient based algorithms is presented, which include the accelerated algorithm, policy gradient algorithm and stochastic gradient algorithm. Then, we come to the non-gradient algorithms, including the Pontryagins maximum principle based successive approximation algorithm and the optimal tensor algorithm. Next, continuous-time perspective of machine learning is reviewed, which to some extent establish a theoretical basis for machine learning. And in the end, we propose the advantage and the disadvantage of the above achievements, and try to give our own opinion about the application prospect and the development direction.

In recent years, with the rapid development of unmanned surface vessel (USV), a real-time collision avoidance system is required to guarantee its safety navigation in the practical marine engineering. Therefore, this paper firstly uses wavelet transform technology to decompose and reconstruct the image collected by USV, so as to achieve the effect of denoising, and mark the foreground and background information. Then, the improved watershed segmentation method is used to segment the target object. Finally, a vector field histogram (VFH) method is proposed, which can solve the collision avoidance problem of USV from high dimension to low dimension based on the segmented image. The calculation burden is greatly low, and the real-time collision avoidance can be realized at the same time.

Background: Peripheral regional block combined with general anesthesia might be a preferable anesthetic regimen for elderly patients receiving total hip arthroplasty. To investigate whether suprainguinal fascia iliaca block accelerates recovery after general anesthesia and relieves early postoperative pain in elderly patients undergoing total hip arthroplasty. Methods: Patients who underwent total hip arthroplasty under general anesthesia in 2015 or 2019 at the Second Affiliated Hospital of Xuzhou Medical University were retrospectively analyzed. The patients were grouped based on whether preoperative suprainguinal fascia iliaca block was performed. The time to tracheal extubation and spent in the post anesthesia care unit (PACU), intraoperative remifentanil dosage, fentanyl consumption in PACU, postoperative cumulative fentanyl consumption within 48 h after operation, visual analog scale (VAS) at rest and during movement on the first and second days after surgery, and adverse reactions were compared.Results: Thirty-one patients were included in the study (block group:16, no-block group: 15). The VAS at rest and during movement on the first and second days were significantly lower in the block group than in the no-block group (all PConclusion: Suprainguinal fascia iliaca block led to faster recovery after general anesthesia and early postoperative pain relief in elderly patients undergoing total hip arthroplasty.

Streptococcus suis serotype 2 (S. suis 2) is an important swine pathogen and also an emerging zoonotic agent. HtpsA has been reported as an immunogenic cell surface protein on the bacterium. In the present study, we constructed an isogenic mutant strain of htpsA, namely ΔhtpsA, to study its role in the development and virulence of S. suis 2. Our results showed that the mutant strain lost its typical encapsulated structure with decreased concentrations of sialic acid. Furthermore, the survival rate in whole blood, the anti-phagocytosis by RAW264.7 murine macrophage, and the adherence ability to HEp-2 cells were all significantly affected in the ΔhtpsA. In addition, the deletion of htpsA sharply attenuated the virulence of S. suis 2 in an infection model of mouse. RNA-seq analysis revealed that 126 genes were differentially expressed between the ΔhtpsA and the wild-type strains, including 28 upregulated and 98 downregulated genes. Among the downregulated genes, many were involved in carbohydrate metabolism and synthesis of virulence-associated factors. Taken together, htpsA was demonstrated to play a role in the morphological development and pathogenesis of the highly virulent S. suis 2 05ZYH33 strain.

Driven by the advancement of science and technology, the issue of marine ship Internet of Things (IoT) users' assignment of computing tasks offloading has become more and more challenging. When faced with the complex and dynamic marine environment, considering the different quality requirements of maritime applications, we have addressed this issue in this paper. We first propose the space-air-ground-edge (SAGE) maritime communication network architecture. This novel architecture is used to offload computing-intensive applications and services for IoT users in the marine environment. At the same time, based on the Multi-Armed Bandits (MAB) problem, considering budget constraints and other marine environmental conditions such as delay and energy consumption, we propose an algorithm for selecting an edge server strategy. Simulation results of this paper show that the scheme has a better performance under different quality of service (QoS) requirements, which proves that the scheme is effective.

To make early predictions of preeclampsia before diagnosis, we developed and validated a new nomogram for the early prediction of preeclampsia in pregnant Chinese women. A stepwise regression model was used for feature selection. Multivariable logistic regression analysis was used to develop the prediction model. We incorporated BMI, blood pressure, uterine artery ultrasound parameters, and serological indicator risk factors, and this was presented with a nomogram. The performance of the nomogram was assessed with respect to its calibration, discrimination, and clinical usefulness. Internal validation was assessed. The signature, which consisted of 11 selected features, was associated with preeclampsia status (P < 0.1) for the development dataset. Predictors contained in the individualized prediction nomogram included BMI, blood pressure, uterine artery ultrasound parameters, and serological indicator levels. The model showed good discrimination, with an area under the ROC curve of 0.8563 (95% CI: 0.8364-0.8761) and good calibration. The nomogram still had good discrimination and good calibration when applied to the validation dataset (area under ROC curve of 0.8324, 95% CI: 0.7873-0.8775). Decision curve analysis demonstrated that the nomogram was clinically useful. The nomogram presented in this study incorporates BMI, blood pressure, uterine artery ultrasound parameters, and serological indicators and can be conveniently used to facilitate the individualized prediction of preeclampsia.

Depression in older population is more common now. Due to increasing numbers of older patients in hospitals, nurses have more opportunities to care for these patients. Therefore, nurses should have correct knowledge of late-life depression and more favorable attitudes about depression. The study aimed to understand hospital nurses’ knowledge level of late-life depression and attitudes about depression. A cross-sectional research design was used. A convenience sample of 307 nurses from 3 hospitals in Taiwan was recruited. Nurses scored 55.15% in the Late-Life Depression Quiz. The average score of the Revised Depression Attitude Questionnaire was 71.76 (SD = 6.13). The study also found that hospital nurses had more favorable attitudes about depression when their late-life depression knowledge was higher; their interest level in providing care for older patients with depression was greater; they had ever taken care of older patients with depressive symptoms or depression; they had never received in-service training on depression in the past year; and they had ever attended lectures about depression in school. Hospital nurses’ knowledge about late-life depression was limited, and they had neutral to slightly favorable attitudes about depression in Taiwan. It is suggested to carefully examine and evaluate in-service training related to depression for nurses in hospitals. In addition, developing appropriate interventions to increase hospital nurses’ knowledge level of late-life depression and attitudes toward depression is recommended.

Objective During pregnancy, inhibin A is mainly derived from the placenta and regulates the implantation and differentiation of embryos. Our aim was to assess whether second trimester serum inhibin A was associated with an increased risk of adverse pregnancy outcomes. Methods We investigated the serum levels of Inhibin A during the second trimester in pregnancy, and analyzed associations between the Inhibin A and the risk of adverse pregnancy outcome. 12,124 pregnant women were enrolled in this study between January 2017 and July 2019 at the Obstetrics & Gynecology Hospital of Fudan University. Multivariate logistic regression analysis was conducted to estimate the relative risk between Inhibin A and adverse pregnancy outcome. Results Compared with the group without adverse pregnancy outcome, during the second trimester of pregnancy, age and Inhibin A were risk factors for pre-eclampsia, gestational diabetes mellitus and preterm delivery; Inhibin A was risk factors for low birth weight. Gravidity and Inhibin A were risk factors for macrosomia; while parity was a protective factor against pre-eclampsia, gestational hypertension and low birth weight. Conclusion Elevated Inhibin A levels in pregnancy are significantly associated with pre-eclampsia, GDM, macrosomia, low birth weight and preterm delivery.

Embryo implantation is crucial for a successful pregnancy. Although many essential molecular modulators and pathways have been identified, the precise mechanisms of the process in goat remain largely unknown. CCN2 is a connective tissue growth factor participating in many biological processes; however, its presence or function in goat uterus has not yet been reported. In this study, we determined the expression and regulation of CCN2 in goat uterus. CCN2 was not detected by in situ hybridization at ED0 (Day 0 of the estrous cycle), but at ED6 (metestrus), ED12 (dioestrus), and ED16 (proestrus), with high signals in luminal epithelium, superficial glands, and caruncula matrix. During early pregnancy, CCN2 was also detected in these locations on D0 and D6 (pre-receptive uterus). The signals significantly increased on D16 and D19 (receptive uterus), and remained at high levels on D25 and D30. Similarly, the RT-qPCR assays showed that the mRNA level of CCN2 was relatively low on D0 and D6, increased on D16, peaked on D19, and kept high thereafter. Moreover, CCN2 was up-regulated not only in ovariectomized ewes subcutaneously injected with 17β-estradiol and progesterone (separately or together), but also in cultured goat uterine epithelial cells treated with the two hormones or interferon tau (IFNτ). In conclusion, CCN2 expression may be induced by 17β-estradiol, progesterone, and IFNτ in the luminal epithelium of goat receptive uterus, suggesting that CCN2 is involved in goat embryo adhesion during early pregnancy.

This paper deals with a class of one element n-degree polynomial differential equations. By the fixed point theory, we obtain n periodic solutions of the equation. This paper generalizes some related conclusions of some papers.

Background. Grip-force performance can be affected by aging, and hand-grip weakness is associated with functional limitations of dasily living. However, using an appropriate digital hand-held dynamometer with continuous hand-grip force data collection shows age-related changes in the quality of hand-grip force control may provide more valuable information for clinical diagnoses rather than merely recording instantaneous maximal hand-grip force in frail elderly adults or people with a disability. Therefore, the purpose of this study was to indicate the construct validity of the digital MicroFET3 dynamometer with Jamar values for maximal grip-force assessments in elderly and young adults and confirmed age-related changes in the maximal and the quality of grip-force performance using the MicroFET3 dynamometer in elderly people. Methods. Sixty-five healthy young (23.3±4.5 years) and 50 elderly (69.5±5.8 years) adults were recruited and asked to perform a validity test of the grip-force maximum voluntary contraction (MVC) using both the dominant and nondominant hands with a Jamar dynamometer and a MicroFET3 dynamometer. Results. A strong correlation of maximal grip-force measurements was found between the MicroFET3 dynamometer and Jamar standard dynamometer for both hands in all participants (p<0.05). Although, the results showed that a lower grip force was measured in both hands by the MicroFET3 dynamometer than with the Jamar dynamometer by 49.9%~57% (p<0.05), but confidently conversion formulae were also developed to convert MicroFET3 dynamometer values to equivalent Jamar values for both hands. Both dynamometers indicated age-related declines in the maximum grip-force performance by 36.7%~44.3% (p<0.05). We also found that the maximal hand-grip force values generated in both hand by the elderly adults were slower and more inconsistent than those of the young adults when using the MicroFET3 dynamometer. Conclusions. This study demonstrated that the digital MicroFET3 dynamometer has good validity when used to measure the maximal grip force of both hands, and conversion formulae were also developed to convert MicroFET3 dynamometer force values to Jamar values in both hands. Comparing with the Jamar dynamometer for measuring grip force, the MicroFET3 dynamometer not only indicated age-related declines in the maximum grip-force performance but also showed slower and more inconsistent maximal hand-grip strength generation by the elderly.

The existence of two periodic solutions of the Riccati’s equation when the coefficients areω-periodic and have different signs is obtained. One of these solutions is unstable onRand the other one is attractive on some region. Finally, an example is presented.

The use of highly corrosive chemicals to remove nano-particles on the surface of the wafer, results in substrate losses. This has resulted in the use of megasonics which provides acoustic cavitation to remove small particles. The megasonic wave does generate bubble cavitation which applies mechanical force to wafer structure, the violent cavitation such as transit cavitation or micro jet will damage the patterned structures [1,2]. A new megasonic technology is proposed in this paper, this technology provides stable control of bubble cavitation, without pattern damage at the different modes. The technology shows better particle performance when compared with the industry standard two-fluid nozzle cleaning technology. This Timely Energized Bubble Oscillation mode provides stable cavitation with a wide power window. It is unlike conventional megasonic which creates transit cavitation and damage when the bubble implodes. This new megasonic technology can be used to clean “sensitive” structures at 28nm and below without any pattern damage.

Depression is one of the most frequent psychiatric symptoms observed in people during the development of Alzheimer's disease (AD). We hypothesized that genetic factors conferring risk of depression might affect AD development. In this study, we screened 31 genes, which were located in 19 risk loci for major depressive disorder (MDD) identified by two recent large genome-wide association studies (GWAS), in AD patients at the genomic and transcriptomic levels. Association analysis of common variants was performed by using summary statistics of the International Genomics of Alzheimer's Project (IGAP), and association analysis of rare variants was conducted by sequencing the entire coding region of the 31 MDD risk genes in 107 Han Chinese patients with early-onset and/or familial AD. We also quantified the mRNA expression alterations of these MDD risk genes in brain tissues of AD patients and AD mouse models, followed by protein-protein interaction network prediction to show their potential effects in AD pathways. We found that common and rare variants of L3MBTL2 were significantly associated with AD. mRNA expression levels of 18 MDD risk genes, in particular SORCS3 and OAT, were differentially expressed in AD brain tissues. 13 MDD risk genes were predicted to physically interact with core AD genes. The involvement of HACE1, NEGR1, and SLC6A15 in AD was supported by convergent lines of evidence. Taken together, our results showed that MDD risk genes might play an active role in AD pathology and supported the notion that depression might be the "common cold" of psychiatry.

In order to study the effect of laser spot superposition on aluminum alloy sheet forming by laser peening, the finite element analysis method was introduced to simulating the forming of 7075 aluminum alloy with different spot superposition case. The results showed that the forming effect and stress distribution of the metal sheet was effected by the laser spot superposition modes. The forming effect of transverse spot superposition mode was better than the other three spot superposition modes.

Objective: Percutaneous coronary intervention (PCI) via the radial artery access has more advantages than that of femoral artery access, while radial or (and) brachial artery have tendency to be spasmodic. We sought to investigate the effectiveness and safety of guiding catheter crossing over spasmodic radial or (and) brachial artery segments by the aid of PCI wire and balloon compared with traditional anti-spasmodic approach. Methods: The clinical data of 168 patients with coronary artery disease (CAD) (group A), whose PCI was performed via radial artery access with radial or (and) brachial artery spasm or (and) dissection and guiding catheter passing through spasmodic segments successfully by the aid of PCI guiding wire and balloon were analyzed retrospectively, simultaneously, the other 73 patients (group B) who used conventional approach to cross over the spasmodic radial or (and) brachial artery segments were treated as the control. The success rate, the time consumption and the complication were compared between the two groups. Findings: There was no significant difference in the spasmodic site between the two groups (all p value > 0.05). The success rate in group A was significantly higher than that in group B (168(100%) vs 28 (38.4%), p < 0.0001). As for those of successful crossover in the two groups, the time consumption of guiding catheter crossing over spasmodic segment in group A was shorter than that in group B (p < 0.0001). The incidence of forearm hematoma in group A was lower than that in group B (7(4.2%) vs 14 (19.2%), p < 0.0001). Conclusions: It is more effective and safer for guiding catheter crossing over spasmodic or (and) dissected radial or (and) brachial artery segments by the aid of PCI guiding wire and balloon than using the routine approach of administration of anti-spasm drugs for trans-radial PCI.