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Background. The pathogenesis of slow transit constipation (STC) is associated with exosomal miR-34c-5p. Electroacupuncture (EA) improves gastrointestinal motility in gastrointestinal disorders, especially STC. Our study aimed to explore the mechanism by which EA improves intestinal motility by modulating the release of exosomes and the transmission of exosomal miR-34c-5p. Methods. Fifty rats were randomly divided into five groups. STC model rats were induced, and GW4869, the exosome release inhibitor, was used to inhibit the release of exosome. The serum exosomes were authenticated under a transmission electron microscope and nanoparticle tracking analysis. RT-qPCR detected the expression of miR-34c-5p in serum exosomes and colonic tissues. The fecal number in 24 hours, Bristol scores, and intestinal transit rates were used to assess intestinal motility. Subsequently, hematoxylin and eosin (H&E) staining was used to examine the colonic mucosal histology. Finally, the expression of stem cell factor (SCF) and receptor tyrosine kinase (c-Kit) protein was measured using immunohistochemistry staining. Results. We found that EA upregulated exosomal miR-34c-5p in serum and downregulated miR-34c-5p in colonic tissues ( P < 0.01 ). EA improved fecal numbers in 24 hours, Bristol scores, and intestinal transit rates in STC rats ( P < 0.01 ). EA recovered the colonic histological structure and enhanced the expression of SCF and c-Kit protein ( P < 0.01 ). The therapeutic effect of EA was attenuated after inhibiting the release of the exosome. Conclusion. Our results indicated that EA improves intestinal motility in STC rats by transporting of exosomal miR-34c-5p targeting the SCF/c-Kit signaling pathway.

Six new compounds, including one tetralone (1), two xanthones (2 and 3), one flavan derivative (4), and two nor-diterpenoids (7 and 8), with two known flavan derivatives (5 and 6) and one known olefine acid (9) were isolated from the whole bodies of Kromopolites svenhedini (Verhoeff). All the structures of new compounds were determined by 1D and 2D nuclear magnetic resonance (NMR) and other spectroscopic methods, as well as computational methods. Part of the compounds were evaluated for their biological properties against the mouse pancreatic cancer cell line and inhibitory effects on iNOS and COX-2.

A great increase in the number of patients needs critical care to the intensive care unit (ICU) due to improvements in oncology. The aim of the study was to explore risk factors affecting survival of critically ill patients with solid cancers in ICU.The study retrospectively reviewed patients between 2001 and 2012, which were collected by Medical Information Mart for Intensive Care III (MIMIC-III) from the Beth Israel Deaconess Medical Center in Boston, MA, USA.A total of 38,508 adult patients, who were admitted to ICUs and 8,308 (21.6%) were diagnosed as an underlying malignancy; 1,671 and 3,165 adult patients with sold cancer were admitted to surgical ICU (SICU) and medical ICU (MICU), respectively. Patients in SICU had a higher survival rate at the point of 28-, 90-day, and 1-, 3-year than patients in MICU (P0.001 for all). Multivariate analysis demonstrated that age ≥70, emergency admission, the presence of metastases, Oxford Acute Severity of Illness Score (OASIS) ≥30 and sepsis were independent risk factors affecting 28-day survival in SICU. In MICU, emergency admission, metastatic disease, Sequential Organ Failure Assessment (SOFA) ≥3, Simplified Acute Physiology Score II (SAPS II) ≥39, Acute Physiology Score III (APS III) ≥40, Oxford Acute Severity of Illness Score (OASIS) ≥30, Elixhauser comorbidity index ≥9 and sepsis were independent risk factors for 28-day survival rate. The area under curve (AUC) of the OASIS for predicting ICU mortality was 0.824 [95% confidence interval (CI): 0.805-0.842], which was obviously higher than other scores in SICU. The AUC of the SAPS II for predicting ICU mortality was 0.820 (95% CI: 0.806-0.833), which was slightly higher than other scores in MICU.Patients with cancer in SICU have longer survival time than patients with cancer in MICU. The prediction of prognosis of critically ill cancer patients can guide treatment and optimize medical resources.

To evaluate longitudinal changes in subfoveal choroidal thickness (SFChT) among children receiving atropine 0.05%, 0.025%, or 0.01% over 2 years and their associations with treatment outcomes in myopia control.Double-blinded randomized controlled trial.SFChT was measured at 4-month intervals using spectral domain optical coherence tomography. Cycloplegic spherical equivalent (SE), axial length (AL), best-corrected visual acuity, parental SE, outdoor time, near work diopter hours, and treatment compliance were also measured.314 children were included with qualified choroidal data. The 2-year changes in SFChT from baseline were 21.15 ± 32.99 µm, 3.34 ± 25.30 µm, and -0.30 ± 27.15 µm for the atropine 0.05%, 0.025%, and 0.01% groups, respectively (P.001). A concentration-dependent response was observed, with thicker choroids at higher atropine concentrations (β = 0.89, P.001). Mean SFChT thickness significantly increased at 4 months in the atropine 0.025% (P = .001) and 0.05% groups (P.001) and then remained stable until the end of the second year (P.05 for all groups). Over 2 years, an increase in SFChT was associated with slower SE progression (β = 0.074, P.001) and reduced AL elongation (β = -0.045, P.001). In the mediation analysis, 18.45% of the effect on SE progression from atropine 0.05% was mediated via its choroidal thickening.Low concentration atropine induced a choroidal thickening effect along a concentration-dependent response throughout the treatment period. The choroidal thickening was associated with a slower SE progression and AL elongation among all the treatment groups. Choroidal response can be used for assessment of long-term treatment outcomes and as a guide for concentration titrations of atropine.

Searching for the maximum coordination number (CN) in planar species with novel bonding patterns has fascinated chemists for many years. Using the experimentally observed cyclo[18]carbon D9h C18 and theoretically predicted cyclo[14]carbon D7h C14 as effective ligands and based on extensive first-principles theory calculations, we predict herein their perfect planar alkaline-metal-doped complexes D9h Cs©C18+ (1) and D7h Na©C14+ (4) which, as the global minima of the systems with an alkaline metal atom located exactly at the center, possess the record coordination numbers of CN = 18 and 14 in planar species, respectively. More interestingly, detailed energy decomposition and adaptive natural density partitioning bonding analyses indicate that the hypercoordinate alkaline-metal centers in these σ + π dually aromatic complexes exhibit obvious transition metal behaviors, with effective in-plane (π-6s)σ, (π-7p)σ, and (π-5d)σ coordination bonds formed in Cs©C18+ (1) and (π-3s)σ, (π-3p)σ, and (π-3d)σ coordination interactions fabricated in Na©C14+ (4) to dominate the overall attractive interactions between the metal center and its cyclo[n]carbon ligand. Similar dually aromatic alkaline-metal-centered planar Cs Cs©C17B (2), C2v Cs©C17- (3), C2v Na©C13B (5), and C2v Na©C13- (6) have also been obtained with CN = 18, 17, 14, and 13, respectively.

This article shows a fast continuous 2π geometrical phase modulator based on the dynamic optical axis rotation of the short-pitch Ferroelectric Liquid Crystal (FLC). A continuous multi-level (8-bit) phase modulation, fast switching time (< 250 μs at 2 kHz), low operating voltage (< 7 V), and high diffraction efficiency (> 77%) is achieved using defect-free Deformed Helix Ferroelectric Liquid Crystal (DHFLC) for the first time. We showed a minimum feature size of 1 µm without fringe field effect (FFE). We also developed a new FLC with a cone angle of ~85˚ and a way to provide compensated half-wave condition (HW) during the entire electro-optical operational range. As a result, we achieve both spatial and time modulation with high frequency (1/3 μm-1 and 4 kHz, respectively), which can be used in applications such as a real-time hologram and dynamic beam steering in Light Ranging and Detector (LiDAR).

Hirudin variants are the most powerful thrombin inhibitors discovered to date, with a lower risk of bleeding than heparin. For anticoagulation, the C-termini of hirudin variants bind to the exocite I of thrombin. Anticoagulant effects of gene-recombinant hirudin are weaker than natural hirudin for the reason of lacking tyrosine O-sulfation at C-terminus.An integrative pharmacological study was carried out using molecular dynamic, molecular biological and in vivo and in vitro experiments to elucidate the anticoagulant effects of protein-engineered hirudins.Molecular dynamic analysis showed that modifications of the C-termini of hirudin variant 1 of Hirudo medicinalis (HV1) and hirudin variant 2 of Hirudinaria manillensis (HM2) changed the binding energy of the C-termini to human thrombin. The study indicated that Asp61 of HM2 that corresponds to sulfated Tyr63 of HV1 is critical for inhibiting thrombin activities. Further, the anticoagulant effects of HV1 and HM2 were improved when the amino acid residues adjacent to Asp61 were mutated to Asp. These improvements were prolongation of the activated partial thromboplastin time, prothrombin time and thrombin time of human blood, and decreased K

With helps of advancing CMOS technology, ISFETs have achieved great success. However, CMOS-based ISFETs are also suffering problems of scaling attenuation and threshold voltage offset. These problems mainly result from the architecture used to adapt standard CMOS process. To deal with these, we developed a novel CMOS ISFET configuration, namely, 3D-T-ISFET, by building a truncated architecture to expose CMOS process-inherent TiN thin film as the sensing interface. Due to the electrical conductivity of TiN, the signal from the environment can bypass the sensing dielectric and couple to the transistor effectively through the electrical double layer capacitance. Based on our experiments, as the footprint of 8.52 μm2, a 3.21-fold ΔID/pH improvement can be achieved by developed 3D-T-ISFET. At the same time, the 3D-T-ISFET has an about 1.65-fold improvement in SNR compared to the traditional 2D-ISFET. Compared to the 2D-ISFET in a state-of-the-art design, therefore, 3D-T-ISFET exhibits a scaling attenuation-free behavior and becomes less vulnerable to the non-idea effects brought by trapped charges.

This work shows a differential rotational thermal piezoresistive resonator (DR-TPR) design, fabrication, and characterization. The resonator uses silicon on insulator (SOI) microelectromechanical systems (SOI MEMS) technology. The sensing of carboxyl-polystyrene beads requires estimating the variation in the frequency of the resonator. It can serve as an alternative enabling technology to detect small molecules having wide implementations in clinical and industrial applications. The resonator uses a negative frequency shift to find the change in the mass due to the chemical absorption of the carboxyl-polystyrene beads on the DR-TPR surface. The method of using DR-TPR can attain label-free detection for many future biomarkers. The use of carboxyl-polystyrene beads to showcase the potential of DR-TPR as a mass sensor for future chemical/biosensing applications is the highlight of the paper. It includes the characterization in different concentrations of immobilization on the resonator surface. The work shows the operation of the resonator in an ionic buffer solution which is crucial for its future applications. The Q value of 80 with differential feedthrough cancellation is measured in phosphate-buffered saline (PBS) using DR-TPR.

Compared to the dynamics of the predominantly geostrophic along-shelf current, our understanding of the cross-shelf dynamics in the Sea of Okhotsk is inadequate despite their importance in water mixing and nutrient entrainment. We investigated the cross-shelf overturning circulation along the East Sakhalin Current, which is a source of nutrients such as iron for the western North Pacific. Here, we reveal that the cross-shelf circulation during winter is characterised by a nearshore upwelling and a shelf-break downwelling under a downwelling-favourable monsoon wind, contrary to a classical Ekman overturning (EOT). This reverse EOT is driven by the internal water stress, which is caused by intensive vertical mixing and geostrophic vertical shear in the shelf-break front produced by riverine discharges from the far-eastern Eurasian Continent. The EOT blocks the Ekman onshore transport from the open ocean, thereby producing a deep mixed layer at the shelf break. Scaling analyses indicate the applicability of this mechanism to various other shelf-break fronts.

Diclofenac (DCF), one of the most current and widely used nonsteroidal anti-inflammatory drugs (NSAIDs), has been frequently detected in aquatic environments worldwide. However, the ecotoxicological effects of DCF on freshwater invertebrates remain largely unknown. In the present study, Corbicula fluminea were exposed to environmentally relevant concentrations of DCF (0, 2, 20 and 200 µg/L) for 28 days, and the potential adverse effects of DCF on siphoning behavior, antioxidant responses and apoptosis were investigated. Our results showed that the siphon efficiencies of clams were significantly suppressed by DCF exposure. DCF exerted neurotoxicity via reducing the activity of acetylcholinesterase (AChE) in gills and digestive gland of C. fluminea. Exposure to DCF induced antioxidant stress and led to increased malondialdehyde (MDA) levels in both tissues of C. fluminea. Transcriptional alterations of apoptosis-related genes indicated that DCF might induce apoptosis by triggering mitochondrial apoptotic pathway. Our findings will help enhance our awareness of the negative effects of DCF on freshwater bivalves and highlight the ecological risks of DCF in freshwater ecosystems.

ImportanceSecondhand smoke (SHS) exposure potentially threatens ocular health; however, its association with myopia is unknown.ObjectiveTo examine the association between SHS exposure and childhood myopia.Design, Setting, and ParticipantsCross-sectional data from the population-based Hong Kong Children Eye Study were used. Data were collected from March 5, 2015, to September 12, 2021, at The Chinese University of Hong Kong Eye Center. Participants included children aged 6 to 8 years. Secondhand smoke exposure was evaluated using a validated questionnaire. All participants underwent comprehensive ophthalmic and physical examinations.ExposureSecondhand smoke exposure.Main Outcomes and MeasuresGeneralized estimating equations were constructed to examine the association of SHS exposure with spherical equivalent and axial length; logistic regression models, with myopia rate; and linear regression models, with myopia onset.ResultsA total of 12 630 children (mean [SD] age, 7.37 [0.88] years; 53.2% boys) were included in the analysis. Among the participants, 4092 (32.4%) had SHS exposure. After adjusting for age, sex, parental myopia, body mass index, near-work time, outdoor time, and family income, SHS exposure was associated with greater myopic refraction (β = −0.09 [95% CI, −0.14 to −0.03]) and longer axial length (β = 0.05 [95% CI, 0.02-0.08]). Children with SHS exposure were more likely to develop moderate (odds ratio [OR], 1.30 [95% CI, 1.06-1.59]) and high myopia (OR, 2.64 [95% CI, 1.48-4.69]). The association of SHS exposure with spherical equivalence and axial length was magnified in younger children. For each younger year of a child’s exposure to SHS, SHS exposure was associated with a 0.07-D decrease in spherical equivalence (β = 0.07 [95% CI, 0.01-0.13]) and a 0.05-mm increase in axial length (β = −0.05 [95% CI, −0.08 to −0.01]). Exposure to SHS was associated with an earlier mean (SD) age at onset of myopia (72.8 [0.9] vs 74.6 [0.6] months; P = .01). Every increase in SHS exposure in units of 10 cigarettes per day was associated with greater myopic refraction (β = −0.07 [95% CI, −0.11 to −0.02]), axial length (β = 0.04 [95% CI, 0.01-0.06]), and likelihood of developing moderate (OR, 1.23 [95% CI, 1.05-1.44]) and high myopia (OR, 1.75 [95% CI, 1.20-2.56]), and earlier myopia onset (β = −1.30 [95% CI, −2.32 to −0.27]).Conclusions and RelevanceThe findings of this cross-sectional study suggest that SHS exposure was associated with greater myopic refraction, longer axial length, greater likelihood of developing moderate and high myopia, and earlier myopia onset. The larger the quantity of SHS exposure and the younger the child, the more advanced myopia development and progression with which SHS exposure is associated.

Background: Nervonic acid (C24:1Δ15, 24:1 ω-9, cis-tetracos-15-enoic acid; NA), a long-chain monounsaturated fatty acid, plays an essential role in prevention of metabolic diseases, and immune regulation, and has anti-inflammatory properties. As a chronic, immune-mediated inflammatory disease, ulcerative colitis (UC) can affect the large intestine. The influences of NA on UC are largely unknown. Purpose: The present study aimed to decipher the anti-UC effect of NA in the mouse colitis model. Specifically, we wanted to explore whether NA can regulate the levels of inflammatory factors in RAW264.7 cells and mouse colitis model. Methods: To address the above issues, the RAW264.7 cell inflammation model was established by lipopolysaccharide (LPS), then the inflammatory factors tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), Interleukin-1β (IL-1β), and Interleukin-10 (IL-10) were detected by Enzyme-linked immunosorbent assay (ELISA). The therapeutic effects of NA for UC were evaluated using C57BL/6 mice gavaged dextran sodium sulfate (DSS). Hematoxylin and eosin (H&E) staining, Myeloperoxidase (MPO) kit assay, ELISA, immunofluorescence assay, and LC-MS/MS were used to assess histological changes, MPO levels, inflammatory factors release, expression and distribution of intestinal tight junction (TJ) protein ZO-1, and metabolic pathways, respectively. The levels of proteins involved in the nuclear factor kappa-B (NF-κB) pathway in the UC were investigated by western blotting and RT-qPCR. Results: In vitro experiments verified that NA could reduce inflammatory response and inhibit the activation of key signal pathways associated with inflammation in LPS-induced RAW264.7 cells. Further, results from the mouse colitis model suggested that NA could restore intestinal barrier function and suppress NF-κB signal pathways to ameliorate DSS-induced colitis. In addition, untargeted metabolomics analysis of NA protection against UC found that NA protected mice from colitis by regulating citrate cycle, amino acid metabolism, pyrimidine and purine metabolism. Conclusion: These results suggested that NA could ameliorate the secretion of inflammatory factors, suppress the NF-κB signaling pathway, and protect the integrity of colon tissue, thereby having a novel role in prevention or treatment therapy for UC. This work for the first time indicated that NA might be a potential functional food ingredient for preventing and treating inflammatory bowel disease (IBD). National Key Research and Development, China | Ref. 2021YFE0109200 Universidade de Vigo/CISUG The Provincial Major Scientific and Technological Innovation Project of Shandong | Ref. 2022TZXD0029 The Provincial Major Scientific and Technological Innovation Project of Shandong | Ref. 2022TZXD0032 The Provincial Major Scientific and Technological Innovation Project of Shandong | Ref. 2021SFGC0904 The Provincial Major Scientific and Technological Innovation Project of Shandong | Ref. 2021TZX D004 The Natural Science Foundation of Shandong | Ref. ZR2020MH401 The Natural Science Foundation of Shandong | Ref. ZR2021QH351 National Wheat Industry Technology System of China | Ref. CARS-03–22