Designing a synthetic moss genome using GenoDesigner.

The de novo synthesis of genomes has made unprecedented progress and achieved milestones, particularly in bacteria and yeast. However, the process of synthesizing a multicellular plant genome has not progressed at the same pace, due to the complexity of multicellular plant genomes, technical difficulties associated with large genome size and structure, and the intricacies of gene regulation and expression in plants. Here we outline the bottom-up design principles for the de novo synthesis of the Physcomitrium patens (that is, earthmoss) genome. To facilitate international collaboration and accessibility, we have developed and launched a public online design platform called GenoDesigner. This platform offers an intuitive graphical interface enabling users to efficiently manipulate extensive genome sequences, even up to the gigabase level. This tool is poised to greatly expedite the synthesis of the P. patens genome, offering an essential reference and roadmap for the synthesis of plant genomes.

Effect of Chinese Medicine in Patients with COVID-19: A Multi-center Retrospective Cohort Study.

OBJECTIVE: To evaluate the effectiveness and safety of Chinese medicine (CM) in the treatment of coronavirus disease 2019 (COVID-19) in China. METHODS: A multi-center retrospective cohort study was carried out, with cumulative CM treatment period of ⩾3 days during hospitalization as exposure. Data came from consecutive inpatients from December 19, 2019 to May 16, 2020 in 4 medical centers in Wuhan, China. After data extraction, verification and cleaning, confounding factors were adjusted by inverse probability of treatment weighting (IPTW), and the Cox proportional hazards regression model was used for statistical analysis. RESULTS: A total of 2,272 COVID-19 patients were included. There were 1,684 patients in the CM group and 588 patients in the control group. Compared with the control group, the hazard ratio (HR) for the deterioration rate in the CM group was 0.52 [95% confidence interval (CI): 0.41 to 0.64, P<0.001]. The results were consistent across patients of varying severity at admission, and the robustness of the results were confirmed by 3 sensitivity analyses. In addition, the HR for all-cause mortality in the CM group was 0.29 (95% CI: 0.19 to 0.44, P<0.001). Regarding of safety, the proportion of patients with abnormal liver function or renal function in the CM group was smaller. CONCLUSION: This real-world study indicates that the combination of a full-course CM therapy on the basic conventional treatment, may safely reduce the deterioration rate and all-cause mortality of COVID-19 patients. This result can provide the new evidence to support the current treatment of COVID-19. Additional prospective clinical trial is needed to evaluate the efficacy and safety of specific CM interventions. (Registration No. ChiCTR2200062917).

A Naturally Inspired Extrusion-Based Microfluidic Approach for Manufacturing Tailorable Magnetic Soft Continuum Microrobotic Devices.

Soft materials play a crucial role in small-scale robotic applications by closely mimicking the complex motion and morphing behavior of organisms. However, conventional fabrication methods face challenges in creating highly integrated small-scale soft devices. In this study, microfluidics is leveraged to precisely control reaction-diffusion (RD) processes to generate multifunctional and compartmentalized calcium-cross-linkable alginate-based microfibers. Under RD conditions, sophisticated alginate-based fibers are produced for magnetic soft continuum robotics applications with customizable features, such as geometry (compact or hollow), degree of cross-linking, and the precise localization of magnetic nanoparticles (inside the core, surrounding the fiber, or on one side). This fine control allows for tuning the stiffness and magnetic responsiveness of the microfibers. Additionally, chemically cleavable regions within the fibers enable disassembly into smaller robotic units or roll-up structures under a rotating magnetic field. These findings demonstrate the versatility of microfluidics in processing highly integrated small-scale devices.

Outcomes of patients in nasopharyngeal adenoid cystic carcinoma in the IMRT era: a single-center experience.

OBJECTIVE: Nasopharyngeal adenoid cystic carcinoma (NACC) is a rare malignancy with special biological features. Controversies exist regarding the treatment approach and prognostic factors in the IMRT era. This study aimed to evaluate the long-term outcomes and management approaches in NACC. METHODS: Fifty patients with NACC at our institution between 2010 and 2020 were reviewed. Sixteen patients received primary radiotherapy (RT), and 34 patients underwent primary surgery. RESULTS: Between January 2010 and October 2020, a total of 50 patients with pathologically proven NACC were included in our analysis. The median follow-up time was 58.5 months (range: 6.0-151.0 months). The 5-year overall survival rate (OS) and progression-free survival rate (PFS) were 83.9% and 67.5%, respectively. The 5-year OS rates of patients whose primary treatment was surgery and RT were 90.0% and 67.3%, respectively (log-rank P = 0.028). The 5-year PFS rates of patients whose primary treatment was surgery or RT were 80.8% and 40.7%, respectively (log-rank P = 0.024). Multivariate analyses showed that nerve invasion and the pattern of primary treatment were independent factors associated with PFS. CONCLUSIONS: Due to the relative insensitivity to radiation, primary surgery seemed to provide a better chance of disease control and improved survival in NACC. Meanwhile, postoperative radiotherapy should be performed for advanced stage or residual tumours. Cranial nerve invasion and treatment pattern might be important factors affecting the prognosis of patients with NACC.

Digital smart internal fixation surgery for coronal process basal fracture with normal joint spaces or radius-shortening: Occult factor of radius-ulna load sharing.

BACKGROUND: Reasonable postoperative humeroradial and humeroulnar joint spaces maybe an important indicator in biomechanical stability of smart internal fixation surgery for coronoid process basal fractures (CPBF). The aim of this study is to compare elbow articular stresses and elbow-forearm stability under smart internal fixations for the CPBF between normal elbow joint spaces and radius-shortening, and to determine the occult factor of radius-ulna load sharing. METHODS: CT images of 70 volunteers with intact elbow joints were retrospectively collected for accurate three-dimensional reconstruction to measure the longitudinal and transverse joint spaces. Two groups of ten finite element (FE) models were established prospectively between normal joint space and radius-shortening with 2.0 mm, including intact elbow joint and forearm, elbow-forearm with CPBF trauma, anterior or posterior double screws-cancellous bone fixation, mini-plate-cancellous bone fixation. Three sets of physiological loads (compression, valgus, varus) were used for FE intelligent calculation, FE model verification, and biomechanical and motion analysis. RESULTS: The stress distribution between coronoid process and radial head, compression displacements and valgus angles of elbow-forearm in the three smart fixation models of the normal joint spaces were close to those of corresponding intact elbow model, but were significantly different from those of preoperative CPBF models and fixed radius-shortening models. The maximum stresses of three smart fixation instrument models of normal joint spaces were significantly smaller than those of the corresponding fixed radius-shortening models. CONCLUSIONS: On the basis of the existing trauma of the elbow-forearm system in clinical practice, which is a dominant factor affecting radius-ulna load sharing, the elbow joint longitudinal space has been found to be the occult factor affecting radius-ulna load sharing. The stability and load sharing of radius and ulna after three kinds of smart fixations of the CPBF is not only related to the anatomical and biomechanical stability principles of smart internal fixations, but also closely related to postoperative elbow joint longitudinal space.

Novel Isoalantolactone-Based Derivatives as Potent NLRP3 Inflammasome Inhibitors: Design, Synthesis, and Biological Characterization.

The NLRP3 inflammasome has been recognized as a promising therapeutic target in drug discovery for inflammatory diseases. Our initial research identified a natural sesquiterpene isoalantolactone (IAL) as the active scaffold targeting NLRP3 inflammasome. To improve its activity and metabolic stability, a total of 64 IAL derivatives were designed and synthesized. Among them, compound 49 emerged as the optimal lead, displaying the most potent inhibitory efficacy on nigericin-induced IL-1ß release in THP-1 cells, with an IC50 value of 0.29 µM, approximately 27-fold more potent than that of IAL (IC50: 7.86 µM), and exhibiting higher metabolic stability. Importantly, 49 remarkably improved DSS-induced ulcerative colitis in vivo. Mechanistically, we demonstrated that 49 covalently bound to cysteine 279 in the NACHT domain of NLRP3, thereby inhibiting the assembly and activation of NLRP3 inflammasome. These results provided compelling evidence to further advance the development of more potent NLRP3 inhibitors based on this scaffold.

Identification of Transcriptomic Signatures of Pancreatic Ductal Adenocarcinoma-Derived Exosomes That Promote Macrophage M2 Polarization and Predict Prognosis: S100A9 Reveals Tumor Progression.

Background: Exosomes play a role in intercellular communication and participate in the interaction between pancreatic ductal adenocarcinoma (PDAC) cells and immune cells. Macrophages can receive tumor cell-derived exosomes to polarize into M2-type macrophages, which can enhance the invasion and metastasis of pancreatic cancer, leading to poor prognosis. However, the mechanism by which pancreatic cancer cell-derived exosomes promote M2-type macrophages is still unclear. Methods: M2 macrophage-associated exosome-derived key module genes were identified by differentially expressed genes (DEGs) and weighted gene co-expression network analysis (WGCNA) analysis using exoRbase 2.0, The Cancer Genome Atlas (TCGA), and The International Cancer Genome Consortium (ICGC) databases. Multivariate Cox regression analysis was used to identify key prognostic genes and obtain regression coefficients to establish prognostic signature. Immune infiltration, tumor mutations, and GSEA among different risk groups were compared. exoRbase 2.0, Gene Expression Profiling Interactive Analysis 2 (GEPIA2), HPA, and TISCH2 databases were used to further analyze the expression pattern of S100A9 in pancreatic cancer. In vitro experiments, cell-derived exosome isolation, quantitative polymerase chain reaction (qPCR), western blot, flow cytometry analysis, cell transfection, transwell assay, and CCK-8 assay were applied to investigate the roles of S100A9 in macrophage M2 polarization and tumor progression. Results: The key genes of PDAC-derived exosomes promoting M2-type macrophage polarization were identified, and a risk score model was established. The risk score is related to the expression of common immune checkpoints, immune score, and stromal score, and the tumor mutational burden and biological function of high- and low-risk groups were also different. S100A9 was positively correlated with M2-type macrophage marker. In addition, scRNA-seq data from the TISCH2 database revealed that S100A9 is predominantly expressed in pancreatic cancer cells and mono/macrophage cells, suggesting that S100A9 in pancreatic cancer cells could be received by macrophages, thereby inducing macrophage polarization. In vitro, we used exosomes from BxPC-3 cell lines to coculture macrophages and found that macrophages were mainly polarized toward M2 type, which further promoted the proliferation and metastasis of PDAC. Conclusions: Our study established a reliable risk score model for PDAC-derived exosomes and M2 macrophages, identified the important role of S100A9 in macrophage M2 polarization, which provides a new strategy for the diagnosis and treatment of PDAC, and strengthened the understanding of the mechanism of tumor development and metastasis.

Achieving ultrahigh uranium/vanadium selectivity of poly(amidoxime) via coupling MXene-enabled strong intermolecular interaction and separated photothermal interface.

Poly(amidoxime) (PAO) has been recognized as the most potential candidate for extracting uranium from seawater, owing to its merits of outstanding uranium affinity, low cost, and large-scale production. Despite remarkable achievements, existing PAO sorbents suffer from unsatisfactory uranium extraction efficiency and selectivity, as imposed by the inherently sluggish uranium adsorption kinetics and inevitable spatial configuration transition of amidoxime, which diminishes uranium affinity. Herein, we discover a facile and integrated design to elaborate a PAO/MXene nanocomposite that delivers ultrahigh and durable uranium/vanadium (U/V) selectivity. The key to our design lies in harnessing MXene-enabled strong intermolecular interactions to PAO to minimize the spatial configuration transition of amidoxime and stabilizing its superior uranium affinity, as well as creating a separated photothermal interface to maximize temperature-strengthened affinity for uranium over vanadium. Such a synergetic effect allows the nanocomposite to acquire over a 4-fold improvement in U/V selectivity compared to that of pure PAO as well as an unprecedented distribution coefficient of uranium compared to most state-of-the-art sorbents. We further demonstrate that our nanocomposite exhibits durable U/V selectivity with negligible attenuation and good antibacterial ability even in long-term operation. The design concept and extraordinary performance in this study bring PAO-based sorbents a step closer to practical uranium extraction from seawater.

RBM24 Suppresses the Tumorigenesis of Glioblastoma by Stabilizing LATS1 mRNA.

The ribose nucleic acid (RNA)-binding motif protein 24 (RBM24) has been recognized as a critical regulatory protein in various types of tumors. However, its specific role in glioblastoma (GBM) has not been thoroughly investigated. The objective of this study is to uncover the role of RBM24 in GBM and understand the underlying mechanism. The expression of RBM24 in GBM was initially analyzed using the Gene Expression Profiling Interactive Analysis (GEPIA). Subsequently, the RBM24 expression levels in clinical samples of GBM were examined, and the survival curves of GBM patients were plotted based on high- and low-expression levels of RBM24 using Kaplan-Meier (KM) plotter. In addition, RBM24 knockdown cell lines and overexpression vectors were created to assess the effects on proliferation, apoptosis, and invasion abilities. Finally, the binding level of RBM24 protein to LATS1 messenger RNA (mRNA) was determined by RNA immunoprecipitation (RIP) assay, and the expression levels of RBM24 and LATS1 were measured through quantitative reverse-transcriptase-polymerase chain reaction (qRT-PCR) and Western blot (WB). Our data revealed a significant decrease in RBM24 mRNA and protein levels in GBM patients, indicating that those with low RBM24 expression had a worse prognosis. Overexpression of RBM24 led to inhibited cell proliferation, reduced invasion, and increased apoptosis in LN229 and U87 cells. In addition, knocking down LATS1 partially reversed the effects of RBM24 on cell proliferation, invasion, and apoptosis in GBM cells. In vivo xenograft model further demonstrated that RBM24 overexpression reduced the growth of subcutaneous tumors in nude mice, accompanied by a decrease in Ki-67 expression and an increase in apoptotic events in tumor tissues. There was also correlation between RBM24 and LATS1 protein expression in the xenograft tumors. RBM24 functions to stabilize LATS1 mRNA, thereby inhibiting the proliferation, suppressing invasion, and promoting apoptosis in GBM cells.

Pd-Catalyzed Cascade Cyclization/Thiocarbonylation with Thioformates: Synthesis of Thioester-Functionalized Oxindoles.

A Pd-catalyzed thiocarbonylative cyclization of N-(o-iodoaryl)acrylamides with easily accessible thioformates has been developed. The reaction has a wide substrate scope with good yields and represents a powerful route to the synthesis of thioester-functionalized oxindoles. Both S-aryl and alkyl thioformates as the thioester sources were well tolerated. The active Pd-CO intermediate may play an important role in the transformation process.

Hydroxysafflor Yellow A Inhibits Pyroptosis and Protecting HUVECs from OGD/R via NLRP3/Caspase-1/GSDMD Pathway.

OBJECTIVE: To observe the protective effect and mechanism of hydroxyl safflower yellow A (HSYA) from myocardial ischemia-reperfusion injury on human umbilical vein endothelial cells (HUVECs). METHODS: HUVECs were treated with oxygen-glucose deprivation reperfusion (OGD/R) to simulate the ischemia reperfusion model, and cell counting kit-8 was used to detect the protective effect of different concentrations (1.25-160 µ mol/L) of HSYA on HUVECs after OGD/R. HSYA 80 µ mol/L was used for follow-up experiments. The contents of inflammatory cytokines interleukin (IL)-18, IL-1 ß, monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor α (TNF-α) and IL-6 before and after administration were measured by enzyme-linked immunosorbent assay. The protein expressions of toll-like receptor, NOD-like receptor containing pyrin domain 3 (NLRP3), gasdermin D (GSDMD) and GSDMD-N-terminal domain (GSDMD-N) before and after administration were detected by Western blot. NLRP3 inflammasome inhibitor cytokine release inhibitory drug 3 sodium salt (CRID3 sodium salt, also known as MCC950) and agonist were added, and the changes of NLRP3, cysteine-aspartic acid protease 1 (Caspase-1), GSDMD and GSDMD-N protein expressions were detected by Western blot. RESULTS: HSYA inhibited OGD/R-induced inflammation and significantly decreased the contents of inflammatory cytokines IL-18, IL-1 ß, MCP-1, TNF-α and IL-6 (P<0.01 or P<0.05). At the same time, by inhibiting NLRP3/Caspase-1/GSDMD pathway, HSYA can reduce the occurrence of pyroptosis after OGD/R and reduce the expression of NLRP3, Caspase-1, GSDMD and GSDMD-N proteins (P<0.01). CONCLUSIONS: The protective effect of HSYA on HUVECs after OGD/R is related to down-regulating the expression of NLRP3 inflammasome and inhibiting pyroptosis.

On particle motion in a confined square domain filled with active fluids.

The motion of passive particles in a confined square domain filled with active fluids has been numerically simulated using a direct-fictitious domain method. The ratio of particle diameter to the side length of the square domain (dp/L) is adopted to classify the degree of confinement (i.e., strong or weak confinement). The translational mean-squared displacement (MSDT) of weakly-confined particles scales well with the reported theoretical and experimental results in a short time and eventually reaches a plateau because of the confined environment. Additionally, the radial probability densities of the particle positions gradually increase with increasing distance from the center of the square domain at relatively high activity levels, displaying an apparent rise near the boundary and maximize near the corner. Conversely, the strongly confined particles migrate toward the center of the square domain or approach the corner with continuous rotation. In addition, the localized minima of the angular velocity of the particles show a periodic behavior, with the vortices periodically becoming more organized. Moreover, with increasing activity, two distinct linearly correlated regimes emerge in the relationship between the particle's rotational velocity and the activity. A comprehensive analysis of the collective dynamics reveals that the cutoff length is Rc ≈ 0.19(2.375dp), pointing to the distance at which the velocities of two particles are uncorrelated. Moreover, the spatial correlation function (Ip) shows a small peak at Rr ≈ 0.12(1.5dp), suggesting a relatively strong correlation between a given particle and another particle located at a distance Rr from it. Interestingly, both Rc and Rr are smaller than those observed in an unbounded flow, which indicates that boundary confinement significantly influences the ability of the particles to form coherent structures.

Maternal fiber-rich diet promotes early-life intestinal development in offspring through milk-derived extracellular vesicles carrying miR-146a-5p.

BACKGROUNDS: The intestinal development in early life is profoundly influenced by multiple biological components of breast milk, in which milk-derived extracellular vesicles (mEVs) contain a large amount of vertically transmitted signal from the mother. However, little is known about how maternal fiber-rich diet regulates offspring intestinal development by influencing the mEVs. RESULTS: In this study, we found that maternal resistant starch (RS) consumption during late gestation and lactation improved the growth and intestinal health of offspring. The mEVs in breast milk are the primary factor driving these beneficial effects, especially enhancing intestinal cell proliferation and migration. To be specific, administration of mEVs after maternal RS intake enhanced intestinal cell proliferation and migration in vivo (performed in mice model and indicated by intestinal histological observation, EdU assay, and the quantification of cyclin proteins) and in vitro (indicated by CCK8, MTT, EdU, and wound healing experiments). Noteworthily, miR-146a-5p was found to be highly expressed in the mEVs from maternal RS group, which also promotes intestinal cell proliferation in cells and mice models. Mechanically, miR-146a-5p target to silence the expression of ubiquitin ligase 3 gene NEDD4L, thereby inhibiting DVL2 ubiquitination, activating the Wnt pathway, and promoting intestinal development. CONCLUSION: These findings demonstrated the beneficial role of mEVs in the connection between maternal fiber rich diet and offspring intestinal growth. In addition, we identified a novel miRNA-146a-5p-NEDD4L-ß-catenin/Wnt signaling axis in regulating early intestinal development. This work provided a new perspective for studying the influence of maternal diet on offspring development.

Effects of Resistant Starch Infusion, Solely and Mixed with Xylan or Cellulose, on Gut Microbiota Composition in Ileum-Cannulated Pigs.

Fermentation of dietary fiber (DF) is beneficial for gut health, but its prebiotic effects are often impeded in the distal large intestine because of the fast degradation of fermentable substrates. One way to enhance the prebiotic effect of DF is to deliver fibers to the lower parts of the gut, which can be achieved by mixing different kinds of fiber. Therefore, in the present study, an ileum-cannulated pig model was employed to investigate the fermentation influence in the large intestine by infusing resistant starch solely (RS, fast fermentable fiber) and mixing with other fibers (xylan or cellulose). Twenty-four ileum-cannulated growing pigs were divided into four groups: one control group receiving saline ileal infusions and three experimental groups infused with RS, RS with xylan, or RS with cellulose. Fecal and plasma samples were analyzed for gut microbiota composition, short-chain fatty acids (SCFAs), and blood biochemistry. Results indicated no significant differences between the RS and control group for the microbiome and SCFA concentration (p > 0.05). However, RS combined with fibers, particularly xylan, resulted in enhanced and prolonged fermentation, marked by an increase in Blautia and higher lactate and acetate production (p < 0.05). In contrast, RS with cellulose infusion enriched bacterial diversity in feces (p < 0.05). Blood biochemistry parameters showed no significant differences across groups (p > 0.05), though a trend of increased glucose levels was noted in the treatment groups (p < 0.1). Overall, RS alone had a limited impact on the distal hindgut microbiota due to rapid fermentation in the proximal gut, whereas combining RS with other fibers notably improved gut microecology by extending the fermentation process.

Lactation body condition loss impaired conceptus development and plasma progesterone concentration at day 8 post-ovulation in primiparous sows.

The current study investigated effects of dietary amino acid (AA) availability on lactational body condition loss and metabolic status, in relation to reproductive parameters after weaning up to Day 8 post-ovulation. Primiparous sows (n = 35) were allocated to one of two lactation diets containing either low crude protein (CP, 140 g/kg) with a low percentage (8%) of slow protein in total protein (LL, n = 18) or high CP (180 g/kg) with a high (16%) percentage of slow protein (HH, n = 17). The HH diet was expected to improve AA utilization by supplying more AA, in a more gradual fashion. The diets did not affect sow body condition loss during lactation, while the HH diet tended to increase litter weight gain during the week 3 of lactation (Δ = 1.3 kg, P = 0.09). On Day 14 post-farrowing, HH diet led to higher plasma urea both pre-feeding and post-feeding (Δ = 2.3 mmol/L, P < 0.01, Δ = 2.4 mmol/L, P < 0.01, respectively), whilst plasma creatinine, NEFA and IGF-1 were similar. No dietary effects on reproductive parameters were found, however several relationships were found between body condition and reproductive parameters. Sows with higher body weight on Day 1 or Day 21 post-farrowing had greater follicle size on Day 3 post-weaning (ß = 0.03 mm/kg, P < 0.01, ß = 0.04 mm/kg, P < 0.01, respectively). At Day 8 post-ovulation, plasma progesterone concentration was negatively related to loin muscle loss (ß = -0.67 ng/ml · mm-1, P = 0.02), backfat loss (ß = -2.33 ng/ml · mm-1, P = 0.02), and estimated body fat loss (ß = -0.67 ng/ml · mm-1, P = 0.02). Both plasma progesterone and the number of corpora lutea were positively related to the energy balance during lactation (ß = 0.03 ng/ml · ME MJ-1, P = 0.01, ß = 0.01 CL/ME MJ, P = 0.02, respectively). The conceptus size at Day 8 post-ovulation was negatively related to body weight loss (ß = -0.01 mm/kg, P = 0.01), estimated body fat loss (ß = -0.02 mm/kg, P = 0.03) and estimated body protein loss (ß = -0.06 mm/kg, P = 0.04), and was positively related to the energy balance during lactation (ß = 5.2*10-4 mm/ME MJ, P = 0.01). In conclusion, body protein and fat losses during lactation reduced subsequent plasma progesterone concentration and conceptus development at Day 8 post-ovulation.

Effect of bone mass density and alveolar bone resorption on stress in implant restoration of free-end edentulous posterior mandible: Finite element analysis of double-factor sensitivity.

BACKGROUND: Osseous condition of the mandible was regarded as a key factor influencing stability of implants in the early stage. Finite element analysis was used to assess the effect of bone mass density and alveolar bone resorption (double factors) on stress in a four-unit implant restoration of a free-end edentulous posterior mandible. METHODS: A 3D finite element model was constructed for a single-sided free-end edentulous mandible (from mandibular first premolar to mandibular second molar) containing threaded dental implants. Mandible sensitivity modes were constructed with different alveolar bone resorption levels for normal conditions as well as mild, moderate and severe periodontitis, respectively. Based on the mass density of cancellous bone for four types of bones as the sensitivity parameter, two implant design modes were constructed: Model A (four-unit fixed bridge supported by three implants, implant positions were 34, 36 and 37) and model B: 34 × 36, 37 (37: a single implant crown) (34 × 36: three-unit fixed bridge supported by two implants, implant positions were 34 and 36). A total of 32 sensitivity-based finite element models, grouped in two groups, were constructed. Stress distribution and maximum von Mises stress on cortical bone and cancellous bone around the implant, as well as the surface of implant were investigated by using ABAQUS when vertical loading and 45° oblique loading were applied, respectively. RESULTS: When vertical loading was applied on the implant, maximum von Mises stress on the cortical bone around the implant was assessed to be 4.726 MPa - 13.15 MPa and 6.254 MPa - 13.79 MPa for groups A and B, respectively; maximum stress on the cancellous bone around the implant was 2.641 MPa - 3.773 MPa and 2.864 MPa - 4.605 MPa, respectively; maximum stress on the surface of implant was 14.7 MPa - 21.17 MPa and 21.64 MPa - 30.70 MPa, respectively. When 45° oblique loading was applied on the implant restoration, maximum von Mises stress on the cortical bone around the implant was assessed to be 42.08 MPa - 92.71 MPa and 50.84 MPa - 102.5 MPa for groups A and B, respectively; maximum stress on the cancellous bone around the implant was 4.88 MPa - 25.95 MPa and 5.227 MPa - 28.43 MPa, respectively; maximum stress on the surface of implant was 77.91 MPa - 124.8 MPa and 109.2 MPa - 150.7 MPa, respectively. Stress peak on the cortical bone and that on cancellous bone around the implant increased and decreased with the decrease in bone mass density, respectively. Stress peak on alveolar bone increased with alveolar bone resorption when oblique loading was applied. CONCLUSION: 1. Both alveolar bone resorption and bone mass density (double factors) are critical to implant restoration. Bone mass density may exhibit a more pronounced impact than alveolar bone resorption. 2. From the biomechanical perspective, types I and II bones are preferred for implant restoration, while implantation should be considered carefully in the case of type III bones, or those with less bone mass density accompanied by moderate to severe alveolar bone loss. 3. Splinting crowns restoration is biomechanically superior to single crown restoration.

microRNA profilings identify plasma biomarkers and targets associated with pediatric epilepsy patients.

BACKGROUND: Although previous studies show that microRNAs (miRNAs) can potentially be used as diagnostic markers for epilepsy, there are very few analyses of pediatric epilepsy patients. METHODS: miRNA profiles using miRNA-seq was performed on plasma samples from 14 pediatric epileptic patients and 14 healthy children. miRNA miR-27a-3p that were significantly changed between two groups were further evaluated. The potential target genes of miR-27a-3p were screened through unbiased mRNA-seq and further validated using Western blot and immunohistochemistry in HEK-293T cells and in the brains of mice with epilepsy induced by lithium chloride-pilocarpine. RESULTS: We found 82 upregulated and 76 downregulated miRNAs in the plasma from pediatric patients compared with controls (p < 0.01), of which miR-27a-3p exhibited a very low p value (p < 0.0001) and validated in additional plasma samples. Two genes, GOLM1 and LIMK1, whose mRNA levels were decreased (p < 0.001) with the increase of miR-27a-3p were further validated in both HEK-293T cells and in epileptic mice. CONCLUSIONS: MiR-27a-3p exhibits potential as a diagnostic and therapeutic marker for epilepsy. We postulate that additional studies on the downstream targets of miR-27a-3p will unravel its roles in epileptogenesis or disease progression. IMPACT: A total of 158 differentially expressed miRNAs were detected in plasma between epileptic and control children. Plasma miR-27a-3p was one of the miRNAs with a low p value. GOLM1 and LIMK1 were validated as downstream target genes of miR-27a-3p. miR-27a-3p has potential as a diagnostic and therapeutic marker for epilepsy.

Tailored Design of a Water-Based Nanoreactor Technology for Producing Processable Sub-40 Nm 3D COF Nanoparticles at Atmospheric Conditions.

Covalent organic frameworks (COFs) are crystalline materials with intrinsic porosity that offer a wide range of potential applications spanning diverse fields. Yet, the main goal in the COF research area is to achieve the most stable thermodynamic product while simultaneously targeting the desired size and structure crucial for enabling specific functions. While significant progress is made in the synthesis and processing of 2D COFs, the development of processable 3D COF nanocrystals remains challenging. Here, a water-based nanoreactor technology for producing processable sub-40 nm 3D COF nanoparticles at ambient conditions is presented. Significantly, this technology not only improves the processability of the synthesized 3D COF, but also unveils exciting possibilities for their utilization in previously unexplored domains, such as nano/microrobotics and biomedicine, which are limited by larger crystallites.