Does the presence of systemic artery-pulmonary circulation shunt during bronchial arterial embolization increase the recurrence of noncancer-related hemoptysis? A retrospective cohort study.

BACKGROUND: The presence of systemic artery-pulmonary circulation shunt (SPS) during the bronchial arterial embolization (BAE) procedure, has been inferred to be a potential risk factor for recurrence. The aim of this study is to reveal the impact of SPS on the recurrence of noncancer-related hemoptysis after BAE. METHODS: In this study, 134 patients with SPS (SPS-present group) and 192 patients without SPS (SPS-absent group) who underwent BAE for noncancer-related hemoptysis from January 2015 to December 2020 were compared. Four different Cox proportional hazards regression models were used to clarify the impact of SPSs on hemoptysis recurrence after BAE. RESULTS: During the median follow-up time of 39.8 months, recurrence occurred in 75 (23.0%) patients, including 51 (38.1%) in the SPS-present group and 24 (12.5%) in the SPS-absent group. The 1-month, 1-year, 2-year, 3-year and 5-year hemoptysis-free survival rates in the SPS-present and SPS-absent groups were 91.8%, 79.7%, 70.6%, 62.3%, and 52.6% and 97.9%, 94.7%, 89.0%, 87.1%, and 82.3%, respectively (P < 0.001). The adjusted hazard ratios of SPSs in the four models were 3.37 [95% confidence intervals (CI), 2.07-5.47, P < 0.001 in model 1], 1.96 (95% CI, 1.11-3.49, P = 0.021 in model 2), 2.29 (95% CI, 1.34-3.92, P = 0.002 in model 3), and 2.39 (95% CI, 1.44-3.97, P = 0.001 in model 4). CONCLUSIONS: The presence of SPS during BAE increases the recurrence probability of noncancer-related hemoptysis after BAE.

Preparation and Characterization of GX-50 and Vitamin C Co-encapsulated Microcapsules by a Water-in-Oil-in-Water (W1/O/W2) Double Emulsion-Complex Coacervation Method.

Co-encapsulated xanthoxylin (GX-50) and vitamin C (Vc) microcapsules (GX-50-Vc-M) were prepared by the combination of a water-in-oil-in-water (W1/O/W2) double emulsion with complex coacervation. The W1/O/W2 double emulsion was prepared by two-step emulsification, and it has a uniform particle size of 8.388 µm and high encapsulation efficiencies of GX-50 (85.95%) and Vc (67.35%) under optimized process conditions. Complex coacervation occurs at pHs 4.0-4.7, which has the highest encapsulation efficiency of GX-50 and Vc at pH 4.5. The complex coacervate with tannic acid solidifying (namely, wet microcapsules) has better mechanical properties and also enhances the ability of co-encapsulation of active ingredients. The resulting microcapsules by freeze-drying of wet microcapsules were characterized by UV-vis absorbance spectroscopy (UV-vis), Fourier infrared spectroscopy (FI-IR), confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM), X-ray diffraction (XRD), 2,2-diphenyl-1-picrylhydrazyl (DPPH·) radical scavenging, and in vitro permeation measurements. Under optimal conditions, the encapsulation efficiency and drug loading of GX-50-Vc-M for GX-50 and Vc are, respectively, 78.38 ± 0.51 and 59.34 ± 0.56%, and 35.6 ± 0.68 and 29.8 ± 0.92%. A slight shift in the FTIR peak between single GX-50 or Vc and GX-50-Vc-M confirmed the successful co-encapsulation of GX-50 and Vc in microcapsules. GX-50-Vc-M has bridged irregular spherical aggregates, while GX-50 and Vc are, respectively, encapsulated in hydrophobic and hydrophilic cavities of microcapsules in an amorphous dissolved state. GX-50-Vc-M has the highest DPPH· radical scavenging rate of 62.51%, and the scavenging process of GX-50-Vc-M on DPPH· radicals is more in line with the pseudo-second-order kinetic equation model. Moreover, the in vitro permeation of GX-50 and Vc in GX-50-Vc-M can reach maximum values of 40 and 60%, respectively. This concludes that GX-50-Vc-M is a promising delivery system for the penetration of the antioxidant into the deeper layers of the skin for the antioxidant effect.

Simultaneous Enhancement of Magnetothermal and Photothermal Responses by Zn, Co Co-Doped Ferrite Nanoparticles.

Reducing nanoparticle (NP) dosage for hyperthermia therapy has remained a great challenge. In this work, efficiencies of alternating current (AC) magnetic field and near-infrared (NIR) heating are simultaneously enhanced by Zn and Co co-doping of magnetite NPs. The optimum magnetic anisotropy for maximized loss power under each magnetic field is achieved by tuning the doping concentration. The specific loss power of Zn0.3 Co0.08 Fe2.62 O4 @SiO2 NPs reaches 2428 W g-1 under an AC field of 27 kA m-1 at 430 kHz; 12 296 W g-1 under NIR laser irradiation at 808 nm and 2.5 W cm-2 ; and an unprecedented value of 14 724 W g-1 under dual mode. These values far exceed what has been achieved previously in iron oxide NPs. Ex vivo experiments on sacrificial mice show that while the NP dosage is substantially reduced to that used for magnetic resonance imaging, the surface body temperature of the mice reaches 50 °C after exposure to both AC field and laser irradiation under field parameters and laser intensity below safety limits. This nanoplatform is thus promising for multi-modal local hyperthermia therapy.

Bronchial artery embolization for the management of frequent hemoptysis caused by bronchiectasis.

BACKGROUND: To retrospectively evaluate the effectiveness of bronchial artery embolization (BAE) compared with conservative therapy for the treatment of frequent hemoptysis caused by bronchiectasis. METHODS: From January 2015 to December 2019, consecutive patients who were admitted due to frequent (more than three times per year) bronchiectasis-related hemoptysis were retrospectively reviewed. Those who were treated with either BAE (n = 69) or conservative therapy (n = 47) were enrolled for analysis. The technical success, clinical success, and complications of the BAE procedure were evaluated. Long-term hemoptysis-free survival rates and clinical success were compared between patients in the BAE group and patients in the conservative group. A Cox proportional hazard regression model was used to identify the predictors of recurrent hemoptysis. RESULTS: The technical success rate was 100% for the BAE procedure, and clinical success was achieved in 92.8% (64 of 69) of cases. No major procedure-related complications occurred, and minor complications were observed in 16 cases (23.2%). The 1-, 2-, and 3-year hemoptysis-free survival rates were 88.3, 71.3, and 66.2%, respectively, for the BAE group and 31.9, 17.6, and 2.5%, respectively, for the conservative treatment group (P <  0.001). Multivariate analysis showed that BAE was a protective factor against recurrent hemoptysis in treated patients. In addition, the presence of cystic bronchiectasis was the only independent risk factor for rebleeding in the whole population and in the BAE group. CONCLUSIONS: BAE may provide an effective option for patients with frequent bronchiectasis-related hemoptysis, especially for those without cystic bronchiectasis.

Low p-SYN1 (Ser-553) Expression Leads to Abnormal Neurotransmitter Release of GABA Induced by Up-Regulated Cdk5 after Microwave Exposure: Insights on Protection and Treatment of Microwave-Induced Cognitive Dysfunction.

With the wide application of microwave technology, concerns about its health impact have arisen. The signal transmission mode of the central nervous system and neurons make it particularly sensitive to electromagnetic exposure. It has been reported that abnormal release of amino acid neurotransmitters is mediated by alteration of p-SYN1 after microwave exposure, which results in cognitive dysfunction. As the phosphorylation of SYN1 is regulated by different kinases, in this study we explored the regulatory mechanisms of SYN1 fluctuations following microwave exposure and its subsequent effect on GABA release, aiming to provide clues on the mechanism of cognitive impairment caused by microwave exposure. In vivo studies with Timm and H&E staining were adopted and the results showed abnormality in synapse formation and neuronal structure, explaining the previously-described deficiency in cognitive ability caused by microwave exposure. The observed alterations in SYN1 level, combined with the results of earlier studies, indicate that SYN1 and its phosphorylation status (ser-553 and ser62/67) may play a role in the abnormal release of neurotransmitters. Thus, the role of Cdk5, the upstream kinase regulating the formation of p-SYN1 (ser-553), as well as that of MEK, the regulator of p-SYN1 (ser-62/67), were investigated both in vivo and in vitro. The results showed that Cdk5 was a negative regulator of p-SYN1 (ser-553) and that its up-regulation caused a decrease in GABA release by reducing p-SYN1 (ser-553). While further exploration still needed to elaborate the role of p-SYN1 (ser-62/67) for neurotransmitter release, MEK inhibition had was no impact on p-Erk or p-SYN1 (ser-62/67) after microwave exposure. In conclusion, the decrease of p-SYN1 (ser-553) may result in abnormalities in vesicular anchoring and GABA release, which is caused by increased Cdk5 regulated through Calpain-p25 pathway after 30 mW/cm2 microwave exposure. This study provided a potential new strategy for the prevention and treatment of microwave-induced cognitive dysfunction.

Skeletal-muscle index predicts survival after percutaneous transhepatic biliary drainage for obstructive jaundice due to perihilar cholangiocarcinoma.

BACKGROUND: Sarcopenia is emerging as a prognostic factor in patients with malignant diseases. The prognostication of perihilar cholangiocarcinoma (PHC) with obstructive jaundice was complex, because these patients suffered compete mortality events beyond cancer itself. Our study was to investigate the association between low skeletal-muscle index and overall survival (OS) after percutaneous transhepatic biliary drainage (PTBD) for obstructive jaundice due to PHC. METHODS: We performed a retrospective survival analysis of patients undergoing PTBD for PHC-related obstructive jaundice between January 2016 and March 2019. Using computed tomography, we measured skeletal-muscle mass at the third lumbar vertebra (L3) to obtain a skeletal-muscle index (SMI). Then, we compared OS between low- and high-SMI groups. Furthermore, factors that could potentially affect OS were assessed. RESULTS: One hundred and four patients (56 males; mean age 66 ± 12 years) were analyzed. Median OS after PTBD was 150 days. OS was shorter in patients with low SMI than in those with high SMI (median OS, 120 vs. 270 days; P < 0.001). Multivariate analysis indicated that low SMI (hazard ratio [HR] 3.46; 95% confidence interval [CI] 1.14-5.60; P < 0.001), intrahepatic metastasis (HR 2.98; 95% CI 1.89-4.69; P < 0.001) and elevated carbohydrate antigen (CA) 19-9 level (HR 1.00; 95% CI 1.00-1.00; P = 0.04) were significantly associated with OS. CONCLUSION: Low SMI was a predictor of dismal OS after PTBD for patients with PHC-related obstructive jaundice.

Cantilever deflection optical fiber sensor based on a chirped fiber grating Fabry-Perot cavity.

A cantilever deflection fiber-optic sensor based on chirped fiber grating (CFG) Fabry-Perot (FP) cavity had been proposed and experimental demonstrated. Two CFBGs with the same chirped coefficient direction and grating parameters are written in one single-mode fiber by UV mask exposure to form the CFG-FP cavity. The central wavelength of two CFGs is 1549.6072 nm, the 3 dB bandwidth is 2.9897 nm, and the physical cavity length of two CFGs is 1 cm. The grating region of two CFGs are straightness fixed on a cantilever beam, forming a sensor. Then the optical properties of this sensor are tested with different stresses at different positions of the cantilever beam. The experimental results show that this sensor can obtain linear displacement of a cantilever beam, overcoming the abilities of the FBG sensor, which only performed point measurement defect. The wavelength drift sensitivity of the sensor is 2.31 pm/g, and linearity is 0.99916. This sensor has great application value in the precise measurement of cantilever beam type and two-dimensional scale strain.

Development of a model to predict recurrence after bronchial artery embolization for non-cancer related hemoptysis.

BACKGROUND: Relapse after effective bronchial arterial embolization (BAE) for controlling hemoptysis is not uncommon. Studies reported diverse predictors of recurrence. However, a model to assess the probability of recurrence in non-cancer related hemoptysis patients after BAE has not been reported. This study was to develop a model to predict recurrence after BAE for non-cancer related hemoptysis. METHODS: The study cohort included 487 patients who underwent BAE for non-cancer-related hemoptysis between January 2015 and December 2019. We derived the model's variables from univariate and multivariate Cox regression analyses. The model presented as a nomogram scaled by the proportional regression coefficient of each predictor. Model performance was assessed with respect to discrimination and calibration. RESULTS: One-month and 1-, 2-, 3- and 5-year recurrence-free rates were 94.5%, 88.0%, 81.4%, 76.2% and 73.8%, respectively. Risk factors for recurrence were underlying lung diseases and the presence of systemic arterial-pulmonary circulation shunts. This risk prediction model with two risk factors provided good discrimination (area under curve, 0.69; 95% confidence interval, 0.62-0.76), and lower prediction error (integrated Brier score, 0.143). CONCLUSION: The proposed model based on routinely available clinical and imaging features demonstrates good performance for predicting recurrence of non-cancer-related hemoptysis after BAE. The model may assist clinicians in identifying higher-risk patients to improve the long-term efficacy of BAE.

Influence of Soil Organic Carbon on the Aroma of Tobacco Leaves and the Structure of Microbial Communities.

The soil organic carbon is associated with the plant quality and the microbial community structure. In the present study, carbon fertilizers were applied to paddy soil to elucidate the relationship between soil carbon and neutral aroma substances in both tobacco and soil microbiome by transcriptome sequencing and 16S rDNA-based analysis, respectively. Our results showed that (1) the increase in soil carbon content was closely correlated with the abundance of microorganisms belonging to two classes (which could potentially affect tobacco plants), namely Gammaproteobacteria and Chloroflexia, (2) soil carbon apparently affected tobacco neutral aroma substances, and (3) soil carbon improved neutral aroma substances by affecting the transcriptional processes of sesquiterpenoid and chlorophyll biosyntheses. These results suggest that increased soil carbon-especially active organic carbon-resulted in desirable improvements in aroma substances in tobacco leaves.

Design, Synthesis and Biological Evaluation of 1-Phenyl-2-(phenylamino) Ethanone Derivatives as Novel MCR-1 Inhibitors.

Polymyxins are considered to be the last-line antibiotics that are used to treat infections caused by multidrug-resistant (MDR) gram-negative bacteria; however, the plasmid-mediated transferable colistin resistance gene (mcr-1) has rendered polymyxins ineffective. Therefore, the protein encoded by mcr-1, MCR-1, could be a target for structure-based design of inhibitors to tackle polymyxins resistance. Here, we identified racemic compound 3 as a potential MCR-1 inhibitor by virtual screening, and 26 compound 3 derivatives were synthesized and evaluated in vitro. In the cell-based assay, compound 6g, 6h, 6i, 6n, 6p, 6q, and 6r displayed more potent activity than compound 3. Notably, 25 µΜ of compound 6p or 6q combined with 2 µg·mL-1 colistin could completely inhibit the growth of BL21(DE3) expressing mcr-1, which exhibited the most potent activity. In the enzymatic assay, we elucidate that 6p and 6q could target the MCR-1 to inhibit the activity of the protein. Additionally, a molecular docking study showed that 6p and 6q could interact with Glu246 and Thr285 via hydrogen bonds and occupy well the cavity of the MCR-1 protein. These results may provide a potential avenue to overcome colistin resistance, and provide some valuable information for further investigation on MCR-1 inhibitors.

P7, a novel antagonist of corticotropin releasing factor receptor type 1 (CRFR1) screened from phage display library.

The corticotropin releasing factor (CRF) plays a central role in regulating the activities of hypothalamic-pituitary-adrenal (HPA) axis in the presence of a variety of stressful stimuli via binding to its type 1 receptors (CRFR1). Despite that many peptidic or non-peptidic antagonists of CRFR1 have been developed to serve as therapeutic tools to CRF-related pathologies, none of them have been utilized clinically. Targeting the extracellular domain 1 (EC1) of CRFR1, the CRF-binding site, represents a new strategy to inhibit the function of the receptor. However, no such agents have been identified up to now. Herein, by using an 87-amino acid fragment corresponding to the EC1 region as the bait, we screened the binding polypeptides from a phage display (Ph.D.-12) peptide library. After 3-round biopanning, positive clones were selected and the polypeptides carried by them were identified. 5 polypeptides were found to bind with the target specifically. Among them, the P7 exhibited the highest affinity. By evaluating the cAMP accumulation in the CRFR1 or CRFR2-expressing HEK293 cells, we demonstrated that P7 blocking the function of CRFR1, but not CRFR2. In addition, we also found that P7 and CRF act on CRFR1 competitively. Taken together, we reveal that P7, a novel polypeptide identified from phage display library, inhibits the function of CRFR1 effectively and specifically by binding at its EC1 domain. The new polypeptide might provide a promising agent for diagnostic or therapeutic utilities in CRF-related disorders.

Green finance and corporate environmental investment: "Scale Up" or "Efficiency Up"?

The establishment of green finance reform and innovation (GFRI) pilot zone is an important measure of the Chinese government to urge enterprises to develop green transformation. This paper explores the impact of pilot policies in the GFRI pilot zone on corporate environmental investment. Based on 819 A-share listed enterprises from 2010 to 2020, our staggered difference-in-differences (staggered DID) estimation documents revealed that enterprises in the GFRI pilot zone significantly increased the corporate environmental investment efficiency but reduced the scale of corporate environmental investment.This conclusion remained robust after Propensity Scores Matching difference-in-differences (PSM-DID), replacing dependent variables, and shortening the time window. We contend that the increased research and development (R&D) expenditure and technological innovation are the potential mechanisms at work. Heterogeneity analysis showed that the establishment of GFRI improved the environmental investment efficiency of polluting enterprises but had no effect on green enterprises.Meanwhile, the effect of GFRI exhibited heterogeneity in the type of enterprise ownership. This paper evaluates the implementation effect of GFRI from the perspective of corporate environmental investment, and provides theoretical support and an empirical basis for green finance policy to serve China's green economy.

Rearing behaviour in the mouse behavioural pattern monitor distinguishes the effects of psychedelics from those of lisuride and TBG.

Psychedelics alter consciousness and may have potential for drug development. As psychedelics are likely therapeutically active, it is important to study their effects and mechanisms using preclinical models. Here, we examined the effects of phenylalkylamine and indoleamine psychedelics on locomotor activity and exploratory behaviour using the mouse Behavioural Pattern Monitor (BPM). DOM, mescaline, and psilocin reduced locomotor activity at high doses and influenced rearings, an exploratory behaviour, in a characteristic inverted U-shaped dose-response function. Pretreatment with the selective 5-HT2A antagonist M100907 reversed the drug-induced alterations in locomotor activity, rearings, and jumps after systemic administration of DOM at low doses. However, holepoking at the full range of doses tested was not blocked by M100907. Administration of the hallucinogenic 5-HT2A agonist 25CN-NBOH induced striking similarities in response to that to psychedelics; these alterations were significantly diminished by M100907, whereas the putatively non-hallucinogenic 5-HT2A agonist TBG did not affect locomotor activity, rearings, or jumps at the most effective doses. The nonhallucinogenic 5-HT2A agonist lisuride failed to increase rearing. The results of these experiments provide strong evidence that DOM-elicited increases in rearing are due to mediation by the 5-HT2A receptor. Finally, discriminant analysis was able to distinguish all four psychedelics from lisuride and TBG based on behavioural performance alone. Thus, increased rearing in mice could provide additional evidence of behavioural differences between hallucinogenic and nonhallucinogenic 5-HT2A agonists.

Construction and Validation of a Novel Nomogram for Predicting the Recurrence of Diffuse Large B Cell Lymphoma Treated with R-CHOP.

Purpose: To explore recurrence-risk factors of diffuse large B cell lymphoma (DLBCL) and construct a risk nomogram for predicting recurrence. Patients and Methods: A retrospective analysis was performed on 228 DLBCL patients who achieved complete remission after R-CHOP treatment between January 2015 and December 2019. Univariate and multivariate analyses were applied to identify recurrence-related risk factors from the pretreatment evaluation factors covering patients' demographic characteristics, clinical manifestations, serological indicators, pathological and immunohistochemical results. A nomogram was developed based on the above results and validated by the concordance index (C-index), the receiver operating characteristic (ROC) curve, and the calibration curve. Results: The training and validation cohorts consisted of 160 and 68 patients (randomized by 7:3). Of the whole cohort, 50 of 228 (21.9%) cases recurred during follow-up. Three recurrence-risk factors including BCL2 expression (P = 0.027), CD10 expression (P = 0.021), LDH level (P = 0.004) were identified from multivariate analysis and entered the final nomogram. The C-index of the nomogram was 0.815 in training cohort and 0.797 in the validation cohort, higher than that of IPI system (0.699) and NCCN-IPI system (0.709). And the 1-year, 2-year, 3-year, and 4-year areas under ROC (AUC) were 0.812, 0.850, 0.837, and 0.801, respectively. The calibration curves also showed a good discrimination capability and accuracy. Conclusion: The novel nomogram incorporating the three independent risk factors (BCL2 expression, CD10 expression and LDH level) provided a valuable tool for predicting DLBCL recurrence.

Acute psilocybin increased cortical activities in rats.

Psilocybin, a naturally occurring hallucinogenic component of magic mushrooms, has significant psychoactive effects in both humans and rodents. But the underlying mechanisms are not fully understood. Blood-oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is a useful tool in many preclinical and clinical trials to investigate psilocybin-induced changes of brain activity and functional connectivity (FC) due to its noninvasive nature and widespread availability. However, fMRI effects of psilocybin on rats have not been carefully investigated. This study aimed to explore how psilocybin affects resting-state brain activity and FC, through a combination of BOLD fMRI and immunofluorescence (IF) of EGR1, an immediate early gene (IEG) closely related to depressive symptoms. Ten minutes after psilocybin hydrochloride injection (2.0 mg/kg, i.p.), positive brain activities were observed in the frontal, temporal, and parietal cortex (including the cingulate cortex and retrosplenial cortex), hippocampus, and striatum. And a region-of-interest (ROI) -wise FC analysis matrix suggested increased interconnectivity of several regions, such as the cingulate cortex, dorsal striatum, prelimbic, and limbic regions. Further seed-based analyses revealed increased FC of cingulate cortex within the cortical and striatal areas. Consistently, acute psilocybin increased the EGR1 level throughout the brain, indicating a consistent activation thought the cortical and striatal areas. In conclusion, the psilocybin-induced hyperactive state of rats is congruent to that of humans, and may be responsible for its pharmacological effects.

Comparison of Bronchial Artery Embolisation Versus Conservative Treatment for Bronchiectasis-Related Nonmassive Haemoptysis: A Single-Centre Retrospective Study.

OBJECTIVE: To compare the safety and effectiveness between bronchial artery embolisation (BAE) and conservative treatment for bronchiectasis-related nonmassive haemoptysis patients. MATERIALS AND METHODS: From January 2015 to December 2020, consecutive bronchiectasis-related nonmassive haemoptysis patients who underwent either BAE (n = 98) or conservative treatment (n = 118) were included. Treatment-related complications, length of hospital stays, clinical success rate, patient satisfaction, and recurrence-free survival rates were compared between groups. Prognostic factors related to recurrence were also analysed. RESULTS: During a median follow-up time of 44.8 months (range, 2.4-83.6 months), 34 and 66 patients in the BAE and conservative treatment groups suffered relapse. The 1-year, 2-year, 3-year and 5-year haemoptysis-free survival rates in the BAE and conservative treatment groups were 79.2%, 68.1%, 62.8%, and 57.6% and 64.0%, 52.8%, 44.1%, and 37.0%, respectively (P = 0.007). The minor complication rate after BAE was higher than that after conservative treatment (23/98 vs. 12/118, P = 0.008). BAE was associated with shorter hospital stays (5.0 vs. 7.0 days, P = 0.042) and higher patient satisfaction (88.8% vs. 74.6%, P = 0.008) than those for conservative treatment and with comparable clinical success rates (95.9% vs. 91.5%, P = 0.192). Treatment type, haemoptysis duration, and bronchiectasis severity were independently significant predictors of recurrence for these patients. CONCLUSIONS: BAE could be another option for bronchiectasis-related nonmassive haemoptysis patients. In the patients with longer duration and more severe bronchiectasis, BAE still appeared to have better long-term haemoptysis control than conservative therapy.

External Ba2+ block of the two-pore domain potassium channel TREK-1 defines conformational transition in its selectivity filter.

TREK-1 is a member of the two-pore domain potassium channel family that is known as a leak channel and plays a key role in many physiological and pathological processes. The conformational transition of the selectivity filter is considered as an effective strategy for potassium channels to control the course of potassium efflux. It is well known that TREK-1 is regulated by a large volume of extracellular and intracellular signals. However, until now, little was known about the selectivity filter gating mechanism of the channel. In this research, it was found that Ba(2+) blocked the TREK-1 channel in a concentration- and time-dependent manner. A mutagenesis analysis showed that overlapped binding of Ba(2+) at the assumed K(+) binding site 4 (S4) within the selectivity filter was responsible for the inhibitory effects on TREK-1. Then, Ba(2+) was used as a probe to explore the conformational transition in the selectivity filter of the channel. It was confirmed that collapsed conformations were induced by extracellular K(+)-free and acidification at the selectivity filters, leading to nonconductive to permeable ions. Further detailed characterization demonstrated that the two conformations presented different properties. Additionally, the N-terminal truncated isoform (ΔN41), a product derived from alternative translation initiation, was identified as a constitutively nonconductive variant. Together, these results illustrate the important role of selectivity filter gating in the regulation of TREK-1 by the extracellular K(+) and proton.

MSLF-Net: A Multi-Scale and Multi-Level Feature Fusion Net for Diabetic Retinopathy Segmentation.

Diabetic Retinopathy (DR) is a diabetic complication that predisposes patients to visual impairments that could lead to blindness. Lesion segmentation using deep learning algorithms is an effective measure to screen and prevent early DR. However, there are several types of DR with varying sizes and high inter-class similarity, making segmentation difficult. In this paper, we propose a supervised segmentation method (MSLF-Net) based on multi-scale-multi-level feature fusion to achieve accurate end-to-end DR lesion segmentation. MSLF-Net builds a Multi-Scale Feature Extraction (MSFE) module to extract multi-scale information and provide more comprehensive features for segmentation. This paper further introduces the Multi-Level Feature Fusion (MLFF) module to improve feature fusion using a cross-layer structure. This structure only fuses low- and high-level features of the same class based on category supervision, avoiding feature contamination. Moreover, this paper produces additional masked images for the dataset and performs image enhancement operations to ensure that the proposed method is trainable and functional on small datasets. The extensive experiments are conducted on public datasets IDRID and e_ophtha. The results showed that our proposed feature enhancement method can perform feature fusion more effectively. Therefore, In the end-to-end DR segmentation neural network model, MSLF Net is superior to other similar models in segmentation, and can effectively improve the DR lesion segmentation performance.

Low Psoas-Muscle index is associated with decreased survival in hepatocellular carcinoma treated with transarterial chemoembolization.

PURPOSE: Skeletal muscle index (SMI) is a promising predictor of clinical outcomes in patients with malignant diseases. As a simpler surrogate of sarcopenia-psoas muscle index (PMI), its predict value for overall survival (OS) after transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) has not been reported. To determine if changes in the PMI predicted OS in individuals with HCC treated with TACE. PATIENTS AND METHODS: A retrospective analysis was performed in HCC patients treated with TACE between January 2018 and March 2019. The survival curve according to PMI was estimated by the Kaplan-Meier method and then compared by the log-rank test. Cox proportional hazards models were conducted to identify the prognostic factors for OS. Furthermore, the predictive abilities of PMI and SMI were compared by using Harrell's concordance index (C-index). RESULTS: Two hundred and twenty-eight patients (175 men, mean age 59 ± 11 years) were analysed. The OS was less in patients with low PMI than those with high PMI (median OS: 16.9 vs. 38.5 months, p < .001). Multivariate analysis found that either PMI (hazard ratio [HR] = 0.64; 95% confidence interval [CI], 0.45-0.91; p < .001) or SMI (HR = 0.51; 95% CI, 0.36-0.72; p < .001) was significantly associated with OS. In the multivariate analysis, the C-index for PMI was 0.78 and 0.79 for SMI (p = .985). CONCLUSION: PMI is a simple tool to predict OS in HCC patients treated with TACE. The predictive ability of PMI is comparable to that of SMI. Key messagesLow psoas-muscle index is associated with decreased overall survival in hepatocellular carcinoma treated with transarterial chemoembolization (TACE).Psoas-muscle index has advantages of being faster and easier to acquire, which thus makes it more likely to achieve widespread clinical application.

[Research on clouds affecting the spectra of solar ultraviolet radiation].

In the present paper, using UV CCD optical multi-channel analyzer, the solar ultraviolet radiation spectra under the conditions of cloud cover were measured, and the impact of clouds on the solar ultraviolet radiation spectra were studied mostly. The results of spectral analysis showed that the intensity of solar ultraviolet radiation spectra was weakened by the clouds. The solar ultraviolet radiation spectral intensity attenuation depended on the wavelength and decreased with decreasing wavelength. The greater the cloud cover, the stronger the attenuation, The solar ultraviolet radiation spectral intensity at wavelengths below 315 nm was affected relatively less by the cloud cover. These results have more important practical applications. When we use solar ultraviolet radiation spectrum to study the atmospheric composition, we should choose the spectral band that is less affected by the atmospheric environment.