Causal associations of cognition, intelligence, education, health and lifestyle factors with cervical spondylosis: a mendelian randomization study.

Background: Education, cognition, and intelligence are phenotypically and genetically related. Education has been shown to have a protective effect on the risk of developing cervical spondylosis. However, it is unclear whether cognition and intelligence have independent causal effects on cervical spondylosis, and whether health and lifestyle factors influence this association. Methods: We first assessed the independent effects of education, cognition, and intelligence on cervical spondylosis by two-sample Mendelian randomization and multivariable Mendelian randomization analysis, and evaluated 26 potential association mediators using two-step Mendelian randomization, and calculated the median proportion. Results: The results showed that only education had an independent causal effect on cervical spondylosis, and had a protective effect on the risk of cervical spondylosis (ß: 0.3395; se: 0.166; p < 0.05; OR:0.71; [95%CI: 0.481-0.943]. Of the 26 potential associated mediators, a factor was identified: SHBG (mediated proportion: 2.5%). Univariable Mendelian randomization results showed that the risk factors for cervical spondylosis were time spent watching TV (OR:1.96; [95%CI: 1.39-2.76]), smoking (OR:2.56; [95%CI: 1.061-1.486]), body mass index (OR:1.26; [95%CI: 1.124-1.418]), percentage of body fat (OR:1.32; [95%CI: 1.097-1.593]), major depression (OR:1.27; [95%CI: 1.017-1.587]) and sitting height (OR:1.15; [95%CI: 1.025-1.291]). Protective factors include computer using (OR:0.65; [95%CI: 0.418-0.995]), sex hormone binding globulin (OR:0.87; [95%CI: 0.7955-0.951]) and high-density lipoprotein (OR:0.90; [95%CI: 0.826-0.990]). Conclusion: Our findings demonstrate the causal and independent effects of education on cervical spondylosis and suggest that lifestyle media may be a priority target for the prevention of cervical spondylosis due to low educational attainment.

Sustained delivery of NT-3 and curcumin augments microenvironment modulation effects of decellularized spinal cord matrix hydrogel for spinal cord injury repair.

Decellularized extracellular matrix hydrogel, especially that derived from spinal cord (DSCM hydrogel), has been actively considered as a functional biomaterial for remodeling the extracellular matrix of the native tissue, due to its unique characteristics in constructing pro-regenerative microenvironment for neural stem cells (NSCs). Furthermore, DSCM hydrogel can provide multiple binding domains to growth factors and drugs. Therefore, both exogenous neurotrophic factors and anti-inflammatory drugs are highly desired to be incorporated into DSCM hydrogel, which may synergistically modulate the complex microenvironment at the lesion site after spinal cord injury (SCI). Herein, neurotrophin-3 (NT-3) and curcumin (Cur) were integrated into DSCM hydrogel for SCI therapy. Due to different affinities to the DSCM hydrogel, NT-3 underwent a controlled release manner, while curcumin released explosively within the first 24 h, followed by rather sustained but slower release. The integration of both NT-3 and curcumin significantly enhanced NSCs proliferation and their neuronal differentiation. Meanwhile, the release of curcumin promoted macrophages polarization into anti-inflammatory subtypes, which further facilitated NSCs differentiation into neurons. The in situ injected DSCM + NT3 + Cur hydrogel exerted superior capability in alleviating the inflammatory responses in rat contused spinal cord. Compared to DSCM hydrogel alone, DSCM + NT3 + Cur hydrogel more significantly promoted the recruitment of NSCs and their neuronal differentiation at the lesion site. These outcomes favored functional recovery, as evidenced by the improved hind limb movement. Overall, the bioactive DSCM hydrogel can serve as a multifunctional carrier for cooperatively release of growth factors and drugs, which significantly benefits microenvironment regulation and nerve regeneration after SCI.

Contribution of mechanoreceptors to spinal cord injury-induced mechanical allodynia.

ABSTRACT: Evidence from previous studies supports the concept that spinal cord injury (SCI)-induced neuropathic pain (NP) has its neural roots in the peripheral nervous system. There is uncertainty about how and to which degree mechanoreceptors contribute. Sensorimotor activation-based interventions (eg, treadmill training) have been shown to reduce NP after experimental SCI, suggesting transmission of pain-alleviating signals through mechanoreceptors. The aim of the present study was to understand the contribution of mechanoreceptors with respect to mechanical allodynia in a moderate mouse contusion SCI model. After genetic ablation of tropomyosin receptor kinase B expressing mechanoreceptors before SCI, mechanical allodynia was reduced. The identical genetic ablation after SCI did not yield any change in pain behavior. Peptidergic nociceptor sprouting into lamina III/IV below injury level as a consequence of SCI was not altered by either mechanoreceptor ablation. However, skin-nerve preparations of contusion SCI mice 7 days after injury yielded hyperexcitability in nociceptors, not in mechanoreceptors, which makes a substantial direct contribution of mechanoreceptors to NP maintenance unlikely. Complementing animal data, quantitative sensory testing in human SCI subjects indicated reduced mechanical pain thresholds, whereas the mechanical detection threshold was not altered. Taken together, early mechanoreceptor ablation modulates pain behavior, most likely through indirect mechanisms. Hyperexcitable nociceptors seem to be the main drivers of SCI-induced NP. Future studies need to focus on injury-derived factors triggering early-onset nociceptor hyperexcitability, which could serve as targets for more effective therapeutic interventions.

Magnetic Seeding of SPIO-BMSCs Into a Biphasic Scaffold Can Promote Tendon-Bone Healing After Rotator Cuff Repair.

BACKGROUND: The tendon-bone interface (TBI) in the rotator cuff has a poor intrinsic capacity for healing, which increases the risk of retear after rotator cuff repair (RCR). However, facilitating regeneration of the TBI still remains a great clinical challenge. Herein, the authors established a novel strategy based on magnetic seeding to enhance the TBI regeneration. HYPOTHESIS: Magnetic seeding bone marrow mesenchymal stem cells labeled with superparamagnetic iron oxide (SPIO-BMSCs) into a biphasic scaffold can promote tendon-bone healing after RCR. STUDY DESIGN: Controlled laboratory study. METHODS: BMSCs were labeled with SPIOs. Prussian blue staining, CCK-8 tests, Western blot, and quantitative reverse transcription polymerase chain reaction (PCR) were used to determine the optimal effect concentration of SPIOs on cell bioactivities and abilities. Then SPIO-BMSCs were magnetically seeded into a biphasic scaffold under a magnetic field. The seeding efficacy was assessed by a scanning electron microscope, and the potential mechanism in chondrogenic differentiation after seeding SPIO-BMSCs into the scaffold was evaluated by Western blot and PCR. Furthermore, the effect of SPIO-BMSC/biphasic scaffold on tendon-bone healing after RCR using a rat model was examined using histological analysis, enzyme-linked immunosorbent assay, and biomechanical evaluation. RESULTS: BMSCs labeled with 100 µg/mL SPIO had no effect on cell bioactivities and the ability of chondrogenic differentiation. SPIO-BMSCs were magnetically seeded into a biphasic scaffold, which offered a high seeding efficacy to enhance chondrogenic differentiation of SPIO-BMSCs via the CDR1as/miR-7/FGF2 pathway for TBI formation in vitro. Furthermore, in vivo application of the biphasic scaffold with magnetically seeded SPIO-BMSCs showed their regenerative potential, indicating that they could significantly accelerate and promote TBI healing with superior biomechanical properties after RCR in a rat rotator cuff tear model. CONCLUSION: Magnetically seeding SPIO-BMSCs into a biphasic scaffold enhanced seeding efficacy to promote cell distribution and condensation. This construct enhanced the chondrogenesis process via the CDR1as/miR-7/FGF2 pathway and further promoted tendon-bone healing after RCR in a rat rotator cuff tear model. CLINICAL RELEVANCE: This study provides an alternative strategy for improving TBI healing after RCR.

Three-Dimensional Structure Light Robot-Assisted Frameless Stereotactic Brain Biopsy.

BACKGROUND AND OBJECTIVES: To assess the feasibility, accuracy, and safety of 3-dimensional (3D) structure light robot-assisted frameless stereotactic brain biopsy. METHODS: Five consecutive patients (3 males, 2 females) were included in this study. The patients' clinical, imaging, and histological data were analyzed, and all patients received a 3D structure light robot-assisted frameless stereotactic brain biopsy. The raw and/or analyzed data of the study are available from the corresponding author. RESULTS: The statistical results showed a mean age of 59.6 years (range 40-70 years), a mean target depth of 60.9 mm (range 53.5-65.8 mm), a mean radial error of 1.2 ± 0.7 mm (mean ± SD), a mean depth error of 0.7 ± 0.3 mm, and a mean absolute tip error of 1.5 ± 0.6 mm. The calculated Pearson product-moment correlation coefficient (r = 0.23) revealed no correlation between target depth and absolute tip error. All biopsy needles were placed in line with the planned trajectory successfully, and diagnostic specimens were harvested in all cases. Histopathological analysis revealed lymphoma (2 cases), lung adenocarcinoma (1 case), glioblastoma multiforme (1 case), and oligodendroglioma (1 case). CONCLUSION: Surface registration using the 3D structure light technique is fast and precise because of the achievable million-scale point cloud data of the head and face. 3D structure light robot-assisted frameless stereotactic brain biopsy is feasible, accurate, and safe.

Weak-Interaction Environment in a Composite Electrolyte Enabling Ultralong-Cycling High-Voltage Solid-State Lithium Batteries.

Poly(vinylidene fluoride) (PVDF)-based solid electrolytes with a Li salt-polymer-little residual solvent configuration are promising candidates for solid-state batteries. Herein, we clarify the microstructure of PVDF-based composite electrolyte at the atomic level and demonstrate that the Li+-interaction environment determines both interfacial stability and ion-transport capability. The polymer works as a "solid diluent" and the filler realizes a uniform solvent distribution. We propose a universal strategy of constructing a weak-interaction environment by replacing the conventional N,N-dimethylformamide (DMF) solvent with the designed 2,2,2-trifluoroacetamide (TFA). The lower Li+ binding energy of TFA forms abundant aggregates to generate inorganic-rich interphases for interfacial compatibility. The weaker interactions of TFA with PVDF and filler achieve high ionic conductivity (7.0 × 10-4 S cm-1) of the electrolyte. The solid-state Li||LiNi0.8Co0.1Mn0.1O2 cells stably cycle 4900 and 3000 times with cutoff voltages of 4.3 and 4.5 V, respectively, as well as deliver superior stability at -20 to 45 °C and a high energy density of 300 Wh kg-1 in pouch cells.

Fully Biodegradable Packaging Films for Fresh Food Storage Based on Oil-Infused Bacterial Cellulose.

Fully biodegradable packaging materials are demanded to resolve the issue of plastic pollution. However, the fresh food storage performance of biodegradable materials is generally much lower than that of plastics due to their high permeability, microbial friendliness, and limited stretchability and transparency. Here a biodegradable packaging material is reported with high fresh food storage performance based on an oil-infused bacterial cellulose (OBC) porous film. The oil infusion significantly improved cellulose's food-keeping performance by reducing its gas permeability, increasing its stretchability and transparency, and enabling the active release of green vapor-phase preservative molecules, while maintaining its intrinsically high degradability. Strawberries stored in a container with the OBC lid at 23 °C after 5 days exhibited a moldy rate of 0%, in contrast to the 100% moldy rate of those stored by poly(ethylene). Enhanced storage performance is also obtained on tomatoes, pork, and shrimp. The OBC film is naturally degraded after being buried in wet soil at 30 °C for 9 days, identical to the degradation rate of bacterial cellulose. The liquid seal strategy broadly applies to different celluloses, providing a general option for developing cellulose-based biodegradable packaging materials.

Precisely Engineering Asymmetric Atomic CoN4 by Electron Donating and Extracting for Oxygen Reduction Reaction.

The development of nonpyrolytic catalysts featuring precisely defined active sites represents an effective strategy for investigating the fundamental relationship between the catalytic activity of oxygen reduction reaction (ORR) catalysts and their local coordination environments. In this study, we have synthesized a series of model electrocatalysts with well-defined CoN4 centers and nonplanar symmetric coordination structures. These catalysts were prepared by a sequential process involving the chelation of cobalt salts and 1,10-phenanthroline-based ligands with various substituent groups (phen(X), where X=OH, CH3, H, Br, Cl) onto covalent triazine frameworks (CTFs). By modulating the electron-donating or electron-withdrawing properties of the substituent groups on the phen-based ligands, the electron density surrounding the CoN4 centers was effectively controlled. Our results demonstrated a direct correlation between the catalytic activity of the CoN4 centers and the electron-donating ability of the substituent group on the phenanthroline ligands. Notably, the catalyst denoted as BCTF-Co-phen(OH), featuring the electron-donating OH group, exhibited the highest ORR catalytic activity. This custom-crafted catalyst achieved a remarkable half-wave potential of up to 0.80 V vs. RHE and an impressive turnover frequency (TOF) value of 47.4×10-3 Hz at 0.80 V vs. RHE in an alkaline environment.

Machine learning based peri-surgical risk calculator for abdominal related emergency general surgery: a multicenter retrospective study.

BACKGROUND: Currently, there is a lack of ideal risk prediction tools in the field of emergency general surgery (EGS). The American Association for the Surgery of Trauma recommends developing risk assessment tools specifically for EGS-related diseases. In this study, we sought to utilize machine learning (ML) algorithms to explore and develop a web-based calculator for predicting five perioperative risk events of eight common operations in EGS. METHOD: This study focused on patients with EGS and utilized electronic medical record systems to obtain data retrospectively from five centers in China. Five ML algorithms, including Random Forest (RF), Support Vector Machine, Naive Bayes, XGBoost, and Logistic Regression, were employed to construct predictive models for postoperative mortality, pneumonia, surgical site infection, thrombosis, and mechanical ventilation >48 h. The optimal models for each outcome event were determined based on metrics, including the value of the Area Under the Curve, F1 score, and sensitivity. A comparative analysis was conducted between the optimal models and Emergency Surgery Score (ESS), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and American Society of Anesthesiologists (ASA) classification. A web-based calculator was developed to determine corresponding risk probabilities. RESULT: Based on 10,993 patients with EGS, we determined the optimal RF model. The RF model also exhibited strong predictive performance compared with the ESS, APACHE II score, and ASA classification. Using this optimal model, we developed an online calculator with a questionnaire-guided interactive interface, catering to both the preoperative and postoperative application scenarios. CONCLUSIONS: We successfully developed an ML-based calculator for predicting the risk of postoperative adverse events in patients with EGS. This calculator accurately predicted the occurrence risk of five outcome events, providing quantified risk probabilities for clinical diagnosis and treatment.

TGF-ß1-triggered BMI1 and SMAD2 cooperatively regulate miR-191 to modulate bone formation.

Transforming growth factor ß 1 (TGF-ß1), as the most abundant signaling molecule in bone matrix, is essential for bone homeostasis. However, the signaling transduction of TGF-ß1 in the bone-forming microenvironment remains unknown. Here, we showed that microRNA-191 (miR-191) was downregulated during osteogenesis and further decreased by osteo-favoring TGF-ß1 in bone marrow mesenchymal stem cells (BMSCs). MiR-191 was lower in bone tissues from children than in those from middle-aged individuals and it was negatively correlated with collagen type I alpha 1 chain (COL1A1). MiR-191 depletion significantly increased osteogenesis and bone formation in vivo. Hydrogels embedded with miR-191-low BMSCs displayed a powerful bone repair effect. Mechanistically, transcription factors BMI1 and SMAD2 coordinately controlled miR-191 level. In detail, BMI1 and pSMAD2 were both upregulated by TGF-ß1 under osteogenic condition. SMAD2 activated miR-191 transcription, while BMI1 competed with SMAD2 for binding to miR-191 promoter region, thus disturbing the activation of SMAD2 on miR-191 and reducing miR-191 level. Altogether, our findings reveal that miR-191 regulated by TGF-ß1-induced BMI1 and SMAD2 negatively modulated bone formation and regeneration, and inhibition of miR-191 might be therapeutically useful to enhance bone repair in clinic.

Prognosis of LSPD versus TIPS for the treatment of esophagogastric variceal bleeding in cirrhosis.

BACKGROUND: This study aimed to compare postoperative complications in patients with esophagogastric variceal bleeding (EVB) who underwent laparoscopic splenectomy combined with pericardial devascularization (LSPD) versus transjugular intrahepatic portosystemic shunt (TIPS) procedures. METHODS: A retrospective collection of medical records was conducted from January 2014 to May 2020 at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. The study included patients from the departments of trauma surgery, interventional radiology, and general surgery who were diagnosed with EVB caused by portal hypertension and treated with LSPD or TIPS. Follow-up data were obtained to assess the occurrence of postoperative complications in both groups. RESULTS: A total of 201 patients were included in the study, with 104 cases in the LSPD group and 97 cases in the TIPS group. There was no significant difference in the 1-year and 3-year post-surgery survival rates between the TIPS and LSPD groups (P = 0.669, 0.066). The 3-year survival rate of Child-Pugh B patients in the LSPD group was higher than TIPS group (P = 0.041). The LSPD group also had a significantly higher rate of freedom from rebleeding at 3-year post-surgery compared to the TIPS group (P = 0.038). Stratified analysis showed no statistically significant difference in the rebleeding rate between the two groups. Furthermore, the LSPD group had a higher rate of freedom from overt hepatic encephalopathy at 1-year and 3-year post-surgery compared to the TIPS group (P = 0.007, < 0.001). The LSPD group also had a lower rate of severe complications at 3-year post-surgery compared to the TIPS group (P = 0.020). CONCLUSION: Compared to TIPS, LSPD does not increase the risk of mortality and rebleeding, while demonstrating fewer complications. In patients classified as Child-Pugh A and B, the use of LSPD for treating EVB is both safe and effective.

Trans-lesion synthesis and mismatch repair pathway crosstalk defines chemoresistance and hypermutation mechanisms in glioblastoma.

Almost all Glioblastoma (GBM) are either intrinsically resistant to the chemotherapeutical drug temozolomide (TMZ) or acquire therapy-induced mutations that cause chemoresistance and recurrence. The genome maintenance mechanisms responsible for GBM chemoresistance and hypermutation are unknown. We show that the E3 ubiquitin ligase RAD18 (a proximal regulator of TLS) is activated in a Mismatch repair (MMR)-dependent manner in TMZ-treated GBM cells, promoting post-replicative gap-filling and survival. An unbiased CRISPR screen provides an aerial map of RAD18-interacting DNA damage response (DDR) pathways deployed by GBM to tolerate TMZ genotoxicity. Analysis of mutation signatures from TMZ-treated GBM reveals a role for RAD18 in error-free bypass of O6mG (the most toxic TMZ-induced lesion), and error-prone bypass of other TMZ-induced lesions. Our analyses of recurrent GBM patient samples establishes a correlation between low RAD18 expression and hypermutation. Taken together we define molecular underpinnings for the hallmark tumorigenic phenotypes of TMZ-treated GBM.

Effects of polypropylene microplastics on carbon dioxide dynamics in intertidal mangrove sediments.

Microplastics (MPs) in soil can influence CO2 dynamics by altering organic carbon (OC) and microbial composition. Nevertheless, the fluctuation of CO2 response attributed to MPs in mangrove sediments is unclear. This study explores the impact of micro-sized polypropylene (mPP) particles on the carbon dynamics of intertidal mangrove sediments. In the high-tide level sediment, after 28 days, the cumulative CO2 levels for varying mPP dosages were as follows: 496.86 ± 2.07, 430.38 ± 3.84 and 447.09 ± 1.72 mg kg-1 for 0.1%, 1% and 10% (w/w) mPP, respectively. The CO2 emissions were found to be increased with a 0.1% (w/w) mPP level and decreased with 1% and 10% (w/w) mPP at high-tide level sediment, suggesting a tide level-specific dose dependence of the CO2 emission pattern in mangrove sediments. Overall, results indicated that the presence of mPP in mangrove sediments would potentially affect intertidal total CO2 storage under given experimental conditions.

Nanoscale Channel Length MoS2 Vertical Field-Effect Transistor Arrays with Side-Wall Source/Drain Electrodes.

Two-dimensional transition metal dichalcogenides (TMDCs) have natural advantages in overcoming the short-channel effect in field-effect transistors (FETs) and in fabricating three-dimensional FETs, which benefit in increasing device density. However, so far, most reported works related to MoS2 FETs with a sub-100 nm channel employ mechanically exfoliated materials and all of the works involve electron beam lithography (EBL), which may limit their application in fabricating wafer-scale device arrays as demanded in integrated circuits (ICs). In this work, MoS2 FET arrays with a side-wall source and drain electrodes vertically distributed are designed and fabricated. The channel length of the as-fabricated FET is basically determined by the thickness of an insulating layer between the source and drain electrodes. The vertically distributed source and drain electrodes enable to reduce the electrode-occupied area and increase in the device density. The as-fabricated vertical FETs exhibit on/off ratios comparable to those of mechanically exfoliated MoS2 FETs with a nanoscale channel length under identical VDS. In addition, the as-fabricated FETs can work at a VDS as low as 10 mV with a desirable on/off ratio (1.9 × 107), which benefits in developing low-power devices. Moreover, the fabrication process is free from EBL and can be applied to wafer-scale device arrays. The statistical results show that the fabricated FET arrays have a device yield of 87.5% and an average on/off ratio of about 1.7 × 106 at a VDS of 10 mV, with the lowest and highest ones to be about 1.3 × 104 and 1.9 × 107, respectively, demonstrating the good reliability of our fabrication process. Our work promises a bright future for TMDCs in realizing high-density and low-power nanoelectronic devices in ICs.

Circulating cell-free DNA as a biomarker for diagnosis of Schistosomiasis japonica.

BACKGROUND: Schistosomiasis, a neglected tropical disease, remains an important public health problem. Although there are various methods for diagnosing schistosomiasis, many limitations still exist. Early diagnosis and treatment of schistosomiasis can significantly improve survival and prognosis of patients. METHODOLOGY: Circulating cell-free (cf)DNA has been widely used in the diagnosis of various diseases. In our study, we evaluated the diagnostic value of circulating cfDNA for schistosomiasis caused by Schistosoma japonicum. We focused on the tandem sequences and mitochondrial genes of S. japonicum to identify highly sensitive and specific targets for diagnosis of Schistosomiasis japonica. RESULTS: Through data screening and analysis, we ultimately identified four specific tandem sequences (TD-1, TD-2, TD-3. and TD-4) and six mitochondrial genes (COX1(1), COX1(2), CYTB, ATP6, COX3, and ND5). We designed specific primers to detect the amount of circulating cfDNA in S. japonicum-infected mouse and chronic schistosomiasis patients. Our results showed that the number of tandem sequences was significantly higher than that of the mitochondrial genes. A S. japonicum infection model in mice suggested that infection of S. japonicum can be diagnosed by detecting circulating cfDNA as early as the first week. We measured the expression levels of circulating cfDNA (TD-1, TD-2, and TD-3) at different time points and found that TD-3 expression was significantly higher than that of TD-1 or TD-2. We also infected mice with different quantities of cercariae (20 s and 80 s). The level of cfDNA (TD-3) in the 80 s infection group was significantly higher than in the 20 s infection group. Additionally, cfDNA (TD-3) levels increased after egg deposition. Meanwhile, we tested 42 patients with chronic Schistosomiasis japonica and circulating cfDNA (TD-3) was detected in nine patients. CONCLUSIONS: We have screened highly sensitive targets for the diagnosis of Schistosomiasis japonica, and the detection of circulating cfDNA is a rapid and effective method for the diagnosis of Schistosomiasis japonica. The levels of cfDNA is correlated with cercariae infection severity. Early detection and diagnosis of schistosomiasis is crucial for patient treatment and improving prognosis.

Nobiletin alleviates atherosclerosis by inhibiting lipid uptake via the PPARG/CD36 pathway.

BACKGROUND: Atherosclerosis (AS) is a persistent inflammatory condition triggered and exacerbated by several factors including lipid accumulation, endothelial dysfunction and macrophages infiltration. Nobiletin (NOB) has been reported to alleviate atherosclerosis; however, the underlying mechanism remains incompletely understood. METHODS: This study involved comprehensive bioinformatic analysis, including multidatabase target prediction; GO and KEGG enrichment analyses for function and pathway exploration; DeepSite and AutoDock for drug binding site prediction; and CIBERSORT for immune cell involvement. In addition, target intervention was verified via cell scratch assays, oil red O staining, ELISA, flow cytometry, qRT‒PCR and Western blotting. In addition, by establishing a mouse model of AS, it was demonstrated that NOB attenuated lipid accumulation and the extent of atherosclerotic lesions. RESULTS: (1) Altogether, 141 potentially targetable genes were identified through which NOB could intervene in atherosclerosis. (2) Lipid and atherosclerosis, fluid shear stress and atherosclerosis may be the dominant pathways and potential mechanisms. (3) ALB, AKT1, CASP3 and 7 other genes were identified as the top 10 target genes. (4) Six genes, including PPARG, MMP9, SRC and 3 other genes, were related to the M0 fraction. (5) CD36 and PPARG were upregulated in atherosclerosis samples compared to the normal control. (6) By inhibiting lipid uptake in RAW264.7 cells, NOB prevents the formation of foam cell. (7) In RAW264.7 cells, the inhibitory effect of oxidized low-density lipoprotein on foam cells formation and lipid accumulation was closely associated with the PPARG signaling pathway. (8) In vivo validation showed that NOB significantly attenuated intra-arterial lipid accumulation and macrophage infiltration and reduced CD36 expression. CONCLUSIONS: Nobiletin alleviates atherosclerosis by inhibiting lipid uptake via the PPARG/CD36 pathway.

A hydrodynamic-based dual-function microfluidic chip for high throughput discriminating tumor cells.

A hydrodynamic-based microfluidic chip consisted of two function units that could not only separate tumor cells (TCs) from whole blood but also remove residual blood cells was designed. The separation of TCs was achieved by a straight contraction-expansion array (CEA) microchannel on the front end of the chip. The addition of contractive structure brought a micro-vortex like Dean vortex that promoted cell focusing in the channel, while when cells entered the dilated region, the wall-induced lift force generated by the channel wall gave cells a push away from the wall. As the wall-induced lift force is proportional to the third power of the cell diameter, TCs with larger diameter will have a larger lateral migration under the wall-induced lift force, realizing the separation of TCs from blood sample. Fluorescent particles with diameters of 19.3 µm and 4.5 µm were used to simulate TCs and red blood cells, respectively, to verify the separation capacity of the proposed CEA microchannel for particles with different diameter. And a separation efficiency 98.7% for 19.3 µm particles and a removal rate 96.2% for 4.5 µm particles was observed at sample flow rate of 10 µL min-1 and sheath flow rate of 190 µL min-1. In addition, a separation efficiency about 96.1% for MCF-7 cells (stained with DiI) and removal rates of 96.2% for red blood cells (RBCs) and 98.7% for white blood cells (WBCs) were also obtained under the same condition. However, on account of the large number of blood cells in the blood, there will be a large number of blood cells remained in the isolated TCs, so a purification unit based on hydrodynamic filtration (HDF) was added after the separation microchannel. The purification channel is a size-dictated cell filter that can remove residual blood cells but retain TCs, thus achieving the purification of TCs. Combined the CEA microchannel and the purifier, the microchip facilitates sorting of MCF-7 cells from whole blood with a separation rate about 95.3% and a removal rate over 99.99% for blood cells at a sample flow rate of 10 µL min-1, sheath flow rate of 190 µL min-1 and washing flow rate of 63 µL min-1.

Elaborate Modulating Binding Strength of Intermediates via Three-component Covalent Organic Frameworks for CO2 Reduction Reaction.

The catalytic performance for electrocatalytic CO2 reduction reaction (CO2RR) depends on the binding strength of the reactants and intermediates. Covalent organic frameworks (COFs) have been adopted to catalyze CO2RR, and their binding abilities are tuned via constructing donor-acceptor (DA) systems. However, most DA COFs have single donor and acceptor units, which caused wide-range but lacking accuracy in modulating the binding strength of intermediates. More elaborate regulation of the interactions with intermediates are necessary and challenge to construct high-efficiency catalysts. Herein, the three-component COF with D-A-A units was first constructed by introducing electron-rich diarylamine unit, electron-deficient benzothiazole and Co-porphyrin units. Compared with two-component COFs, the designed COF exhibit elevated electronic conductivity, enhanced reducibility, high efficiency charge transfer, further improving the electrocatalytic CO2RR performance with the faradic efficiency of 97.2 % at -0.8 V and high activity with the partial current density of 27.85 mA cm-2 at -1.0 V which exceed other two-component COFs. Theoretical calculations demonstrate that catalytic sites in three-component COF have suitable binding ability of the intermediates, which are benefit for formation of *COOH and desorption of *CO. This work offers valuable insights for the advancement of multi-component COFs, enabling modulated charge transfer to improve the CO2RR activity.

Inhibition of pathogenic microbes in oral infectious diseases by natural products: Sources, mechanisms, and challenges.

The maintenance of oral health is of utmost importance for an individual's holistic well-being and standard of living. Within the oral cavity, symbiotic microorganisms actively safeguard themselves against potential foreign diseases by upholding a multifaceted equilibrium. Nevertheless, the occurrence of an imbalance can give rise to a range of oral infectious ailments, such as dental caries, periodontitis, and oral candidiasis. Presently, clinical interventions encompass the physical elimination of pathogens and the administration of antibiotics to regulate bacterial and fungal infections. Given the limitations of various antimicrobial drugs frequently employed in dental practice, the rising incidence of oral inflammation, and the escalating bacterial resistance to antibiotics, it is imperative to explore alternative remedies that are dependable, efficacious, and affordable for the prevention and management of oral infectious ailments. There is an increasing interest in the creation of novel antimicrobial agents derived from natural sources, which possess attributes such as safety, cost-effectiveness, and minimal adverse effects. This review provides a comprehensive overview of the impact of natural products on the development and progression of oral infectious diseases. Specifically, these products exert their influences by mitigating dental biofilm formation, impeding the proliferation of oral pathogens, and hindering bacterial adhesion to tooth surfaces. The review also encompasses an examination of the various classes of natural products, their antimicrobial mechanisms, and their potential therapeutic applications and limitations in the context of oral infections. The insights garnered from this review can support the promising application of natural products as viable therapeutic options for managing oral infectious diseases.

Relationship between parasitism and morphology of Trichogramma (Hymenoptera: Trichogrammatidae) on Spodoptera frugiperda (Lepidoptera: Noctuidae).

In this study, 5 species of Trichogramma Westwood were evaluated for the biological control of Spodoptera frugiperda (JE Smith), concerning the physical characteristics of female Trichogramma. The results showed that Trichogramma chilonis Ishii, Trichogramma dendrolimi Matsumura, and Trichogramma ostriniae Pang et Chen exhibited high parasitism rates, emergence rates, and offspring numbers, with the highest values observed for T. ostriniae. The ovipositor length of Trichogramma japonicum Ashmead and T. dendrolimi were longer than those of other species, and the hind tibia length was the shortest in Trichogramma cacoeciae Marchal. We further evaluated relationships between the parasitism ability of Trichogramma and various morphological indexes based on Spearman's rank correlation coefficients. A positive correlation was found between the parasitism rate and hind tibia length of T. cacoeciae. In T. dendrolimi, the parasitism rate was negatively correlated with ovipositor width and positively correlated with the length-width ratio of the ovipositor. A significant positive correlation was observed between the proportion of female offspring and the mother's ovipositor length in T. japonicum. However, there were no significant correlations between morphological indexes and indexes of parasitism in T. ostriniae. Overall, the parasitic abilities of T. chilonis on S. frugiperda eggs were significantly correlated with the morphology of the female ovipositors.