Intensive Ambulance-Delivered Blood-Pressure Reduction in Hyperacute Stroke.

BACKGROUND: Treatment of acute stroke, before a distinction can be made between ischemic and hemorrhagic types, is challenging. Whether very early blood-pressure control in the ambulance improves outcomes among patients with undifferentiated acute stroke is uncertain. METHODS: We randomly assigned patients with suspected acute stroke that caused a motor deficit and with elevated systolic blood pressure (≥150 mm Hg), who were assessed in the ambulance within 2 hours after the onset of symptoms, to receive immediate treatment to lower the systolic blood pressure (target range, 130 to 140 mm Hg) (intervention group) or usual blood-pressure management (usual-care group). The primary efficacy outcome was functional status as assessed by the score on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days after randomization. The primary safety outcome was any serious adverse event. RESULTS: A total of 2404 patients (mean age, 70 years) in China underwent randomization and provided consent for the trial: 1205 in the intervention group and 1199 in the usual-care group. The median time between symptom onset and randomization was 61 minutes (interquartile range, 41 to 93), and the mean blood pressure at randomization was 178/98 mm Hg. Stroke was subsequently confirmed by imaging in 2240 patients, of whom 1041 (46.5%) had a hemorrhagic stroke. At the time of patients' arrival at the hospital, the mean systolic blood pressure in the intervention group was 159 mm Hg, as compared with 170 mm Hg in the usual-care group. Overall, there was no difference in functional outcome between the two groups (common odds ratio, 1.00; 95% confidence interval [CI], 0.87 to 1.15), and the incidence of serious adverse events was similar in the two groups. Prehospital reduction of blood pressure was associated with a decrease in the odds of a poor functional outcome among patients with hemorrhagic stroke (common odds ratio, 0.75; 95% CI, 0.60 to 0.92) but an increase among patients with cerebral ischemia (common odds ratio, 1.30; 95% CI, 1.06 to 1.60). CONCLUSIONS: In this trial, prehospital blood-pressure reduction did not improve functional outcomes in a cohort of patients with undifferentiated acute stroke, of whom 46.5% subsequently received a diagnosis of hemorrhagic stroke. (Funded by the National Health and Medical Research Council of Australia and others; INTERACT4 ClinicalTrials.gov number, NCT03790800; Chinese Trial Registry number, ChiCTR1900020534.).

Comparison of clinical characteristics between patients with axial spondyloarthritis with and without acute anterior uveitis: a multicentre study of the Chinese Spondyloarthritis Registry.

OBJECTIVES: This study explores the clinical characteristics associated with the occurrence of acute anterior uveitis (AAU) in patients with axial spondyloarthritis (axSpA) within a large, multicentre database. METHODS: This observational, cross-sectional study of patients with axSpA used data from the Chinese Spondyloarthritis Registry between August 1, 2018, and March 31, 2020. The demographic and clinical features of patients with and without AAU were compared. Univariate and multivariate analyses were performed to determine the association between variables and uveitis. RESULTS: A total of 4304 patients were included in this study. The prevalence of AAU in patients with axSpA was 10.59%. Multivariate logistic regression analysis revealed a positive correlation between AAU and age at diagnosis (odds ratio [OR], 1.026; p<0.001), disease duration (OR, 2.117; p<0.001), current or past Achilles tendinitis (OR, 1.692; p<0.001), current or past dactylitis (OR, 1.687; p=0.002), current or past psoriasis (OR, 3.932; p<0.001), presence of human leukocyte antigen-B27 (HLA-B27) (OR, 2.787; p<0.001), and a good response to non-steroidal anti-inflammatory drugs (NSAIDs) (OR, 1.343; p=0.027). CONCLUSIONS: AAU was the most common extra-articular manifestation in the Chinese Spondyloarthritis Registry. In Chinese patients with axSpA, older age at diagnosis, longer disease duration, presence of HLA-B27, current or past Achilles tendinitis, current or past dactylitis, current or past psoriasis, and a good response to NSAIDs were positively associated with AAU.

Highly sensitive and wide-range iontronic pressure sensors with a wheat awn-like hierarchical structure.

Flexible pressure sensors with high sensitivity and wide sensing range are highly desired in e-skins and wearable electronics. However, there is always a trade-off between high sensitivity and broad sensing range for most flexible pressure sensors. Herein, an artificial wheat awn-like hierarchical structure is designed onto the dielectric layer of the iontronic pressure sensor, realizing both high sensitivity and broad working range. The sensor is constructed by sandwiching a wheat awn-like polyvinyl alcohol/H3PO4 dielectric layer between two transparent electrodes of silver nanowires/thermoplastic polyurethane/ionic liquid. The obtained sensor exhibits a high precision of 1 Pa, a high sensitivity of 47.65 kPa-1 (1-200 Pa), a wide measurement range from 1 Pa to 238 kPa, short response/recovery time of 13 ms/12 ms, outstanding stability over 6000 cycles, as well as good transparency. Considering these excellent properties, the sensor shows promising potential in health monitoring, human-computer interaction, wearable electronics, etc.

Combination of anti-SSA/Ro60 and anti-dsDNA serotype is predictive of belimumab renal response in patients with lupus nephritis.

OBJECTIVES: To investigate the effectiveness of belimumab on active lupus nephritis (LN) and explore the predictors, including serological biomarkers, of renal response to belimumab in a real-world setting. METHODS: This multicentre, real-world observational study enrolled patients with active LN receiving intravenous belimumab as an add-on therapy with 24-hour urine protein≥1 g and estimated glomerular filtration rate≥30 mL/min/1.73 m2 at baseline. Complete renal response (CRR), partial renal response (PRR), no renal response (NRR) and primary efficacy renal response (PERR) were evaluated. Multivariable logistic regression was used to identify risk factors for NRR to belimumab at 6 months. RESULTS: Among the 122 patients enrolled, the proportions of patients achieving CRR, PRR, NRR and PERR were 35.9%, 17.1%, 47.0% and 44.4% at 6 months (n=117) and 55.6%, 19.4%, 26.4% and 58.3% at 12 months (n=72), respectively. Proteinuria, daily prednisone dosage and Systemic Lupus Erythematosus Disease Activity Index 2000 scores significantly decreased at 6 and 12 months (p<0.0001). NRR at 6 months (NRR6) was the strongest negative predictor of CRR at 12 months. Baseline anti-dsDNA positivity inversely predicted NRR6 (OR=0.32,95% CI=0.10 to 0.98, p=0.049), while anti-SSA/Ro60 positively predicted NRR6 (OR=3.16, 95% CI=1.14 to 8.74, p=0.027). The combination of anti-SSA/Ro60 and anti-dsDNA serotype quantitatively predicted belimumab renal response. CONCLUSION: The effectiveness of belimumab was reproducible in Chinese patients with active LN. The simple yet interesting serotype predictive model needs further validation and its possible underlying mechanistic relevance deserves further exploration.

Bilateral matching decision-making for rural homesteads withdrawal patterns and types of peasant households' welfare needs: Evidence from China in the context of land spatial planning regulation.

In order to solve the issue of idle rural homesteads and enhance the welfare of peasant households, the Chinese government has implemented various rural homestead withdrawal patterns. In the context of land spatial planning regulation, based on the field survey data from 210 peasant households in Xuzhou City and Ganzhou City, this study constructs a bilateral matching model between rural homestead withdrawal patterns and types of welfare needs of peasant households. This study uses a Discrete Particle Swarm Optimization algorithm improved on the 0-1 knapsack strategy to solve the matching model, aiming to find the optimal homestead withdrawal patterns that match the types of peasant households. The results show that: (1) The matching of rural homestead withdrawal patterns and types of peasant households conforms to the principle of comparative advantage. (2) In the case of "one-to-one matching" between peasant households and homestead withdrawal patterns, matching the "economic-material-oriented" peasant households with the withdrawal pattern of "monetary compensation", matching the "social-service-oriented" peasant households with withdrawal pattern of "indicator replacement", and matching the "welfare-assistance-oriented" peasant households with the withdrawal pattern of "asset replacement". (3) The bilateral overall preference of the combined rural homestead withdrawal patterns is higher than that of the single rural homestead withdrawal pattern, and satisfaction has increased by at least 8 %. The authors argue that the government should design and implement diversified withdrawal patterns based on a full understanding of the welfare needs of peasant households.

PFKFB3 controls acinar IP3R-mediated Ca2+ overload to regulate acute pancreatitis severity.

Acute Pancreatitis (AP) is among the most common hospital gastrointestinal diagnosis; understanding the mechanisms underlying the severity of AP are critical for development of new treatment options for this disease. Here, we evaluate the biological function of phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) in AP pathogenesis in two independent genetically engineered mouse models of AP. PFKFB3 is elevated in AP and severe AP (SAP) and knockout of Pfkfb3 abrogates the severity of alcoholic SAP (FAEE-SAP). Using a combination of genetic, pharmacological, and molecular studies we define the interaction of PFKFB3 with inositol 1,4,5-trisphosphate receptor (IP3R) as a key event mediating this phenomenon. Further analysis demonstrated that the interaction between PFKFB3 and IP3R promotes FAEE-SAP severity by altering intracellular calcium homeostasis in acinar cells. Together our results support a PFKFB3-driven mechanism controlling AP pathobiology and define this enzyme as a therapeutic target to ameliorate the severity of this dismal condition.

The Application of "Table Tennis Racquet" Random Skin Flap in the Treatment of Facial Skin Carcinoma.

BACKGROUND: The repair of facial skin and soft tissue defects remains a clinical challenge. The author introduced a novel "table tennis racquet" random skin flap for wound repair after facial skin cancer excision and discussed its survival mechanisms. METHODS: A lateral mandibular neck skin flap shaped like a table tennis racquet with no well-known blood vessels at the narrow pedicle was designed in 31 cases to repair tissue defects. Among them, there were 8 cases of skin carcinoma in the frontotemporal area and 23 cases of skin carcinoma in the cheek. The flap area was 8.0 × 7.0 cm at maximum and 3.0 × 2.5 cm at minimum, with a pedicle width of 1.0-2.0 cm and a pedicle length of 2.0-6.0 cm. RESULTS: All 31 "table tennis racquet" random skin flaps survived, although there were 3 cases with delayed healing of distal flap bruising. All of them had an ideal local shape after repair with a concealed donor area and inconspicuous scars. CONCLUSIONS: This flap has a "table tennis racquet" shape with a pedicle without well-known blood vessels and has a length-to-width ratio that exceeds that of conventional random flaps, making it unconventional. Because of its long and narrow pedicle, it not only has a large rotation and coverage area but also can be designed away from the defect area, avoiding the defect of no donor tissue being localized near the defect. Overall, this approach is an ideal option for repairing tissue defects after enlarged excision of facial skin carcinoma.

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.

Comparison of combined intravenous and inhalation anesthesia and total intravenous anesthesia in laparoscopic surgery and the identification of predictive factors influencing the delayed recovery of neurocognitive function.

Background: Compare the anesthesia effects of combined intravenous and inhalation anesthesia (CIVIA) and total intravenous anesthesia (TIVA) in laparoscopic surgery. Furthermore, our objective is to examine the elements that contribute to the delay in postoperative recovery of neurocognitive function and anticipate the manifestation of delayed recovery by analyzing serum cytokines. Methods: The CIVIA group and the TIVA group both consisted of 130 patients who were scheduled to have elective major abdominal surgery through laparoscopy. The criteria taken into account by the observational and record-keeping study were the patients' ages, sexes, body masses, heights, and the presence or absence of any preexisting problems. Both groups also had their anesthetic depth, duration, and per-unit-of-time muscle relaxant and analgesic dosages recorded. Finally, the length of each patient's stay in the hospital as well as their overall length of stay were tracked. By using the Mini-Mental State Examination (MMSE) to measure cognitive function, we assessed the mental states of the subjects. Additionally, we wanted to identify any biomarkers that could be linked to postoperative cognitive decline or delays in neurocognitive recovery. Results: A total of 51 participants from the CIVIA group and 53 participants from the TIVA group satisfactorily completed the necessary neuropsychological exam for identifying delayed neurocognitive recovery at the study's completion. In the initial data of the two groups, no significant discrepancies were found (p > 0.05). The CIVIA group exhibited noteworthy reductions in the quantity of administered analgesics and muscle relaxants per unit of time in comparison to the TIVA group (p < 0.05). In addition to this, the duration from the sevoflurane tank being closed to the extubation period demonstrated a significant reduction in the CIVIA group compared to the TIVA group (p < 0.05). Moreover, no statistically notable distinction was observed in terms of postoperative hospitalization duration and overall hospitalization duration among both groups (p > 0.05). According to the study, both the CIVIA group and the TIVA group had a total of 7 (13.72%) and 17 (32.07%) individuals, respectively, who met the criteria for neurocognitive delayed recovery (Odds Ratio: 0.336; 95% CI: 0.134-0.864; p = 0.026). According to the research findings, it is indicated that there is a possibility for an increased presence of IL-6 in the bloodstream within 60 min following the incision made on the skin. This occurrence subsequently leads to the prolonged restoration of neurocognitive capabilities. Conclusion: The CIVIA technique outperforms the TIVA method in terms of overall assessment in the setting of laparoscopic surgery. It's also important to remember that an increased blood IL-6 level during laparoscopy may operate as a separate risk factor for a delay in the restoration of neurocognitive function.

Secondary-electron imaging of bulk crystalline specimens in an aberration corrected STEM.

Atomic-scale electron microscopy traditionally probes thin specimens, with thickness below 100 nm, and its feasibility for bulk samples has not been documented. In this study, we explore the practicality of scanning transmission electron microscope (STEM) imaging with secondary electrons (SE), using a silicon-wedge specimen having a maximum thickness of 18 µm. We find that the atomic structure is present in the entire thickness range of the SE images although the background intensity increases moderately with thickness. The consistent intensity of secondary electron (SE) images at atomic positions and the modest increase in background intensity observed in silicon suggest a limited contribution from SEs generated by backscattered electrons, a conclusion supported by our multislice calculations. We conclude that achieving atomic resolution in SE imaging for bulk specimens is indeed attainable using aberration-corrected STEM and an aberration-corrected scanning electron microscope (SEM) may have the capacity for atomic-level resolution, holding great promise for future strides in materials research.

2,4,6-trinitrotoluene causes mitochondrial toxicity in Caenorhabditis elegans by affecting electron transport.

As a typical energetic compound widely used in military activities, 2,4,6-trinitrotoluene (TNT) has attracted great attention in recent years due to its heavy pollution and wide distribution in and around the training facilities, firing ranges, and demolition sites. However, the subcellular targets and the underlying toxic mechanism of TNT remain largely unknown. In this study, we explored the toxic effects of TNT biological reduction on the mitochondrial function and homeostasis in Caenorhabditis elegans (C. elegans). With short-term exposure of L4 larvae, 10-1000 ng/mL TNT reduced mitochondrial membrane potential and adenosine triphosphate (ATP) content, which was associated with decreased expression of specific mitochondrial complex involving gas-1 and mev-1 genes. Using fluorescence-labeled transgenic nematodes, we found that fluorescence expression of sod-3 (muls84) and gst-4 (dvls19) was increased, suggesting that TNT disrupted the mitochondrial antioxidant defense system. Furthermore, 10 ng/mL TNT exposure increased the expression of the autophagy-related gene pink-1 and activated mitochondrial unfolded protein response (mt UPR), which was indicated by the increased expression of mitochondrial stress activated transcription factor atfs-1, ubiquitin-like protein ubl-5, and homeobox protein dve-1. Our findings demonstrated that TNT biological reduction caused mitochondrial dysfunction and the development of mt UPR protective stress responses, and provided a basis for determining the potential risks of energetic compounds to living organisms.

The mitigation potential of synergistic quorum quenching and antibacterial properties for biofilm proliferation and membrane biofouling.

Biofouling has been a persistent problem hindering the application of membranes in water treatment, and quorum quenching has been identified as an effective method for mitigating biofouling, but surface accumulation of live bacteria still induces biofilm secretion, which poses a significant challenge for sustained prevention of membrane biofouling. In this study, we utilized quercetin, a typical flavonoid with the dual functions of quorum quenching and bacterial inactivation, to evaluate its role in preventing biofilm proliferation and against biofouling. Quercetin exhibited excellent antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), and the decreased bioactivity was positively correlated with the quercetin concentration, with inhibition rates of 53.1 % and 57.4 %, respectively, at the experimental concentrations. The RT-qPCR results demonstrated that quercetin inhibited AI-2 of E. coli and AGR of S. aureus mediated quorum sensing system, and reduced the expression of genes such as adhesion, virulence, biofilm secretion, and key regulatory proteases. As a result, the bacterial growth cycle was retarded and the biomass and biofilm maturation cycles were alleviated with the synergistic effect of quorum quenching and antibacterial activity. In addition, membrane biofouling was significantly declined in the dynamic operation experiments, dead cells in the biofilm overwhelmingly dominated, and the final normalized water fluxes were increased by more than 49.9 % and 34.5 % for E. coli and S. aureus, respectively. This work demonstrates the potential for mitigating biofouling using protocols that quorum quenching and inactivate bacteria, also provides a unique and long-lasting strategy to alleviate membrane fouling.

How public commuting stress promotes employee turnover intention: an examination through the lens of the transactional theory of stress.

BACKGROUND AND OBJECTIVES: The potential detrimental effects of commuting stress have gradually attracted scholars' interest in recent years. Going beyond the perspectives of prior studies (e.g., conservation of resources theory), this study offers a new explanatory framework for the relationship between employees' commuting stress and turnover intention based on the transactional theory of stress. Specifically, this study aims to investigate the mediating effect of hindrance appraisal and the moderating effect of trait mindfulness. DESIGN AND METHOD: To test the hypotheses, we collected two-wave data from 243 employees working in various Chinese firms. Path analysis was used for the analysis. RESULTS: The findings demonstrated that hindrance appraisal mediated the positive relationship between commuting stress and turnover intention. In addition, trait mindfulness buffered the relationship between commuting stress and turnover intention as well as the indirect effect of hindrance appraisal on this relationship. CONCLUSIONS: The findings highlight the stressor appraisal mechanism in the association between commuting stress and turnover intention and identify trait mindfulness as a key coping mechanism for reducing commuting stress.

Antiphospholipid antibodies as potential predictors of disease severity and poor prognosis in systemic lupus erythematosus-associated thrombocytopenia: results from a real-world CSTAR cohort study.

BACKGROUND: To investigate the role of antiphospholipid antibodies (aPLs) in the disease severity and prognosis of SLE-related thrombocytopenia (SLE-TP). METHODS: This multicenter prospective study was conducted based on data from the CSTAR registry. TP was defined as a platelet count<100 × 109/L. Demographic characteristics, platelet count, clinical manifestations, disease activity, and autoantibody profiles were collected at baseline. Relapse was defined as the loss of remission. Bone marrow aspirate reports were also collected. RESULTS: A total of 350 SLE-TP patients with complete follow-up data, 194 (55.4%) were aPLs positive. At baseline, SLE-TP patients with aPLs had lower baseline platelet counts (61.0 × 109/L vs. 76.5 × 109/L, P<0.001), and a higher proportion of moderate to severe cases (24.2% vs. 14.1% ; 18.0% vs. 8.3%, P<0.001). SLE-TP patients with aPLs also had lower platelet counts at their lowest point (37.0 × 109/L vs. 51.0 × 109/L, P = 0.002). In addition, thean increasing number of aPLs types was associated with a decrease in the baseline and minimum values of platelets ( P<0.001, P = 0.001). During follow-up, SLE-TP carrying aPLs had a higher relapse rate (58.2% vs. 44.2%, P = 0.009) and a lower complete response (CR) rate. As the types of aPLs increased, the relapse rate increased, and the CR rate decreased. Furthermore, there was no significant difference in the ratio of granulocytes to red blood cells (G/E), the total number of megakaryocyte and categories. CONCLUSION: SLE-TP patients with positive aPLs had more severe disease a lower remission rate but a higher relapse rate.

Silver nanoparticles facilitate phage-borne resistance gene transfer in planktonic and microplastic-attached bacteria.

The spread of bacteriophage-borne antibiotic resistance genes (ARGs) poses a realistic threat to human health. Nanomaterials, as important emerging pollutants, have potential impacts on ARGs dissemination in aquatic environments. However, little is known about its role in transductive transfer of ARGs mediated by bacteriophage in the presence of microplastics. Therefore, this study comprehensively investigated the influence of silver nanoparticles (AgNPs) on the transfer of bacteriophage-encoded ARGs in planktonic Escherichia coli and microplastic-attached biofilm. AgNPs exposure facilitated the phage transduction in planktonic and microplastic-attached bacteria at ambient concentration of 0.1 mg/L. Biological binding mediated by phage-specific recognition, rather than physical aggregation conducted by hydrophilicity and ζ-potential, dominated the bacterial adhesion of AgNPs. The aggregated AgNPs in turn resulted in elevated oxidative stress and membrane destabilization, which promoted the bacteriophage infection to planktonic bacteria. AgNPs exposure could disrupt colanic acid biosynthesis and then reduce the thickness of biofilm on microplastics, contributing to the transfer of phage-encoded ARGs. Moreover, the roughness of microplastics also affected the performance of AgNPs on the transductive transfer of ARGs in biofilms. This study reveals the compound risks of nanomaterials and microplastics in phage-borne ARGs dissemination and highlights the complexity in various environmental scenarios.

Assessment of cellular senescence potential of PM2.5 using 3D human lung fibroblast spheroids in vitro model.

Background: Epidemiological studies demonstrate that particulate matter 2.5 (PM2.5) exposure closely related to chronic respiratory diseases. Cellular senescence plays an important role in many diseases. However, it is not fully clear whether PM2.5 exposure could induce cellular senescence in the human lung. In this study, we generated a three-dimensional (3D) spheroid model using isolated primary human lung fibroblasts (HLFs) to investigate the effects of PM2.5 on cellular senescence at the 3D level. Methods: 3D spheroids were exposed to 25-100 µg/ml of PM2.5 in order to evaluate the impact on cellular senescence. SA-ß-galactosidase activity, cell proliferation, and the expression of key genes and proteins were detected. Results: Exposure of the HLF spheroids to PM2.5 yielded a more sensitive cytotoxicity than 2D HLF cell culture. Importantly, PM2.5 exposure induced the rapid progression of cellular senescence in 3D HLF spheroids, with a dramatically increased SA-ß-Gal activity. In exploiting the mechanism underlying the effect of PM2.5 on senescence, we found a significant increase of DNA damage, upregulation of p21 protein levels, and suppression of cell proliferation in PM2.5-treated HLF spheroids. Moreover, PM2.5 exposure created a significant inflammatory response, which may be at least partially associated with the activation of TGF-ß1/Smad3 axis and HMGB1 pathway. Conclusions: Our results indicate that PM2.5 could induce DNA damage, inflammation, and cellular senescence in 3D HLF spheroids, which may provide a new evidence for PM2.5 toxicity based on a 3D model which has been shown to be more in vivo-like in their phenotype and physiology than 2D cultures.

Electromagnetically induced transparency enabled by quasi-bound states in the continuum modulated by epsilon-near-zero materials.

Highly tunable electromagnetically induced transparency (EIT) with high-quality-factor (Q-factor) excited by combining with the quasi-bound states in the continuum (quasi-BIC) resonances is crucial for many applications. This paper describes all-dielectric metasurface composed of silicon cuboid etched with two rectangular holes into a unit cell and periodically arranged on a SiO2 substrate. By breaking the C2 rotational symmetry of the unit cell, a high-Q factor EIT and double quasi-BIC resonant modes are excited at 1224.3, 1251.9 and 1299.6 nm with quality factors of 7604, 10064 and 15503, respectively. We show that the EIT resonance is caused by destructive interference between magnetic dipole resonances and quasi-BIC dominated by electric quadrupole. Toroidal dipole (TD) and electric quadrupole (EQ) dominate the other two quasi-BICs. The EIT window can be successfully modulated with transmission intensity from 90% to 5% and modulation depths ranging from -17 to 24 dB at 1200-1250 nm by integrating the metasurface with an epsilon-near-zero (ENZ) material indium tin oxide (ITO) film. Our findings pave the way for the development of applications such as optical switches and modulators with many potential applications in nonlinear optics, filters, and multichannel biosensors.

ASB3 promotes hepatocellular carcinoma progression by mediating DR5 ubiquitination in TRAIL resistance.

Ankyrin-repeat proteins with a suppressor of cytokine signaling box (ASB) proteins belong to the E3 ubiquitin ligase family. 18 ASB members have been identified whose biological functions are mostly unexplored. Here, we discovered that ASB3 was essential for hepatocellular carcinoma (HCC) development and high ASB3 expression predicted poor clinical outcomes. ASB3 silencing induced HCC cell growth arrest and apoptosis in vitro and in vivo. Liver-specific deletion of Asb3 gene suppressed diethylnitrosamine (DEN)-induced liver cancer development. Mechanistically, ASB3 interacted with death receptor 5 (DR5), which promoted ubiquitination and degradation of DR5. We further showed that ASB3 knockdown stabilized DR5 and increased the sensitivity of liver cancer cells to the treatment of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in a DR5-dependent manner in cellular and in animal models. In summary, we demonstrated that ASB3 promoted ubiquitination and degradation of DR5 in HCC, suggesting the potential of targeting ASB3 to HCC treatment and overcome TRAIL resistance.

Randomness Regularization with Simple Consistency Training for Neural Networks.

Randomness is widely introduced in neural network training to simplify model optimization or avoid the over-fitting problem. Among them, dropout and its variations in different aspects (e.g., data, model structure) are prevalent in regularizing the training of deep neural networks. Though effective and performing well, the randomness introduced by these dropout-based methods causes nonnegligible inconsistency between training and inference. In this paper, we introduce a simple consistency training strategy to regularize such randomness, namely R-Drop, which forces two output distributions sampled by each type of randomness to be consistent. Specifically, R-Drop minimizes the bidirectional KL-divergence between two output distributions produced by dropout-based randomness for each training sample. Theoretical analysis reveals that R-Drop can reduce the above inconsistency by reducing the inconsistency among the sampled sub structures and bridging the gap between the loss calculated by the full model and sub structures. Experiments on 7 widely-used deep learning tasks ( 23 datasets in total) demonstrate that R-Drop is universally effective for different types of neural networks (i.e., feed-forward, recurrent, and graph neural networks) and different learning paradigms (supervised, parameter-efficient, and semi-supervised). In particular, it achieves state-of-the-art performances with the vanilla Transformer model on WMT14 English → German translation ( 30.91 BLEU) and WMT14 English → French translation ( 43.95 BLEU), even surpassing models trained with extra large-scale data and expert-designed advanced variants of Transformer models. Our code is available at GitHub https://github.com/dropreg/R-Drop.