Molecular basis of human noradrenaline transporter reuptake and inhibition.

Noradrenaline, also known as norepinephrine, has a wide range of activities and effects on most brain cell types1. Its reuptake from the synaptic cleft heavily relies on the noradrenaline transporter (NET) located in the presynaptic membrane2. Here we report the cryo-electron microscopy (cryo-EM) structures of the human NET in both its apo state and when bound to substrates or antidepressant drugs, with resolutions ranging from 2.5 Å to 3.5 Å. The two substrates, noradrenaline and dopamine, display a similar binding mode within the central substrate binding site (S1) and within a newly identified extracellular allosteric site (S2). Four distinct antidepressants, namely, atomoxetine, desipramine, bupropion and escitalopram, occupy the S1 site to obstruct substrate transport in distinct conformations. Moreover, a potassium ion was observed within sodium-binding site 1 in the structure of the NET bound to desipramine under the KCl condition. Complemented by structural-guided biochemical analyses, our studies reveal the mechanism of substrate recognition, the alternating access of NET, and elucidate the mode of action of the four antidepressants.

A three-dimensional liquid diode for soft, integrated permeable electronics.

Wearable electronics with great breathability enable a comfortable wearing experience and facilitate continuous biosignal monitoring over extended periods1-3. However, current research on permeable electronics is predominantly at the stage of electrode and substrate development, which is far behind practical applications with comprehensive integration with diverse electronic components (for example, circuitry, electronics, encapsulation)4-8. Achieving permeability and multifunctionality in a singular, integrated wearable electronic system remains a formidable challenge. Here we present a general strategy for integrated moisture-permeable wearable electronics based on three-dimensional liquid diode (3D LD) configurations. By constructing spatially heterogeneous wettability, the 3D LD unidirectionally self-pumps the sweat from the skin to the outlet at a maximum flow rate of 11.6 ml cm-2 min-1, 4,000 times greater than the physiological sweat rate during exercise, presenting exceptional skin-friendliness, user comfort and stable signal-reading behaviour even under sweating conditions. A detachable design incorporating a replaceable vapour/sweat-discharging substrate enables the reuse of soft circuitry/electronics, increasing its sustainability and cost-effectiveness. We demonstrated this fundamental technology in both advanced skin-integrated electronics and textile-integrated electronics, highlighting its potential for scalable, user-friendly wearable devices.

Skin-integrated wireless haptic interfaces for virtual and augmented reality.

Traditional technologies for virtual reality (VR) and augmented reality (AR) create human experiences through visual and auditory stimuli that replicate sensations associated with the physical world. The most widespread VR and AR systems use head-mounted displays, accelerometers and loudspeakers as the basis for three-dimensional, computer-generated environments that can exist in isolation or as overlays on actual scenery. In comparison to the eyes and the ears, the skin is a relatively underexplored sensory interface for VR and AR technology that could, nevertheless, greatly enhance experiences at a qualitative level, with direct relevance in areas such as communications, entertainment and medicine1,2. Here we present a wireless, battery-free platform of electronic systems and haptic (that is, touch-based) interfaces capable of softly laminating onto the curved surfaces of the skin to communicate information via spatio-temporally programmable patterns of localized mechanical vibrations. We describe the materials, device structures, power delivery strategies and communication schemes that serve as the foundations for such platforms. The resulting technology creates many opportunities for use where the skin provides an electronically programmable communication and sensory input channel to the body, as demonstrated through applications in social media and personal engagement, prosthetic control and feedback, and gaming and entertainment.

Regulating the Grain-Growth Surface for Efficient Near-Infrared Perovskite Light-Emitting Diodes.

Metal halide perovskites hold great potential for next-generation light-emitting diodes (PeLEDs). Despite significant progress, achieving high-performance PeLEDs hinges on optimizing the interface between the perovskite crystal film and the charge transport layers, especially the buried interface, which serves as the starting point for perovskite growth. Here, we develop a bottom-up perovskite film modulation strategy using formamidine acetate (FAAc) to enhance the buried interface. This multifaceted approach facilitates the vertical-oriented growth of high-quality perovskites with minimized defects. Meanwhile, the in situ deprotonation between FA+ and ZnO could eliminate the hydroxyl (-OH) defects and modulate the energy level of ZnO. The resulting FAPbI3-PeLED exhibits a champion EQE of 23.84% with enhanced operational stability and suppressed EQE roll-off. This strategy is also successfully extended to other mixed-halide PeLEDs (e.g., Cs0.17FA0.83Pb(I0.75Br0.25)3), demonstrating its versatility as an efficient and straightforward method for enhancing the PeLEDs' performance.

Aberrant dynamic functional network connectivity in progressive supranuclear palsy.

BACKGROUND: The clinical symptoms of progressive supranuclear palsy (PSP) may be mediated by aberrant dynamic functional network connectivity (dFNC). While earlier research has found altered functional network connections in PSP patients, the majority of those studies have concentrated on static functional connectivity. Nevertheless, in this study, we sought to evaluate the modifications in dynamic characteristics and establish the correlation between these disease-related changes and clinical variables. METHODS: In our study, we conducted a study on 53 PSP patients and 65 normal controls. Initially, we employed a group independent component analysis (ICA) to derive resting-state networks (RSNs), while employing a sliding window correlation approach to produce dFNC matrices. The K-means algorithm was used to cluster these matrices into distinct dynamic states, and then state analysis was subsequently employed to analyze the dFNC and temporal metrics between the two groups. Finally, we made a correlation analysis. RESULTS: PSP patients showed increased connectivity strength between medulla oblongata (MO) and visual network (VN) /cerebellum network (CBN) and decreased connections were found between default mode network (DMN) and VN/CBN, subcortical cortex network (SCN) and CBN. In addition, PSP patients spend less fraction time and shorter dwell time in a diffused state, especially the MO and SCN. Finally, the fraction time and mean dwell time in the distributed connectivity state (state 2) is negatively correlated with duration, bulbar and oculomotor symptoms. DISCUSSION: Our findings were that the altered connectivity was mostly concentrated in the CBN and MO. In addition, PSP patients had different temporal dynamics, which were associated with bulbar and oculomotor symptoms in PSPRS. It suggest that variations in dynamic functional network connectivity properties may represent an essential neurological mechanism in PSP.

Single-test Ritchey-Common interferometry.

The Ritchey-Common test is widely adopted to measure large optical flats. The traditional Ritchey-Common test eliminates the defocus error with multiple tests by changing the position of the mirrors, which suffers from cumbersome steps, poor repeatability, coupled system error, extra mirror deformation, and potential overturning. The above problems increase the test time, decrease the reliability and accuracy, increase the test cost, and threaten manufacturing safety. We propose a single-test Ritchey-Common interferometry to avoid the obligatory position change in the traditional method. A sub-aperture of test flat is directly measured by a small-aperture interferometer before the test, which is easy to implement, to replace the extra system wavefront measurement in different positions. The defocus is calculated in sub-aperture at exactly the same position as the full-field measurement without the position change, then the surface form under test can be obtained with accurate optical path modeling. Measurement experiments for 100 mm and 2050 mm aperture flats were performed to demonstrate the feasibility of this method. Compared with a direct test in a standard Zygo interferometer, the peak to valley (PV) and root mean square (RMS) errors were 0.0889 λ and 0.0126 λ (λ=632.8 nm), respectively, which reaches the upper limit of accuracy of the interferometer. To the best of our knowledge, this is the first proposal of the Ritchey-Common test that can eliminate the defocus error and realize high accuracy measurement in a single test. Our work paves the way for reliable and practical optical metrology for large optical flats.

CT-guided radioactive 125I seeds brachytherapy for lung oligometastases from colorectal cancer: initial results.

OBJECTIVES: To evaluate the safety and effectiveness of computed tomography (CT)-guided radioactive 125I seeds brachytherapy (RISB) for lung oligometastases (LO) from colorectal cancer (CRC). METHODS: Data for 144 LOs from 70 CRC patients who underwent CT-guided RISB were retrospectively analyzed. The primary endpoints were progression-free survival (PFS) and overall survival (OS), and the secondary endpoints were technical success, local control rate (LCR), and complications. Kaplan-Meier method was used for survival analysis. Cox model was used to identify the independent predictors of poor prognosis. RESULTS: The RISB procedures were successfully performed in all patients, and the success rate was 100%. The median follow-up was 27.8 months. The median PFS was 10.0 months (95% CI: 8.9-11.1) and the 1- and 2-year PFS rates were 32.9% and 5.9%, respectively. On multivariate analysis, serum carcinoembryonic antigen (CEA) ≤ 15 ng/ml (P = 0.048), middle-high differentiated pathological classification (P = 0.015), primary TNM stages I-III (P = 0.001), LO number ≤ 2 (P < 0.001) and cumulative gross tumor volume (GTV) ≤ 40 cm3 (P < 0.001) showed superior PFS. The median OS was 30.8 months (95% CI: 27.1-34.4) and the 1-, 2-, and 3-year OS rates were 95.7%, 67.4%, and 42.5%, respectively. On multivariate analysis, serum CEA ≤ 15 ng/ml (P = 0.004), middle-high differentiated pathological classification (P < 0.001), primary TNM stages I-III (P < 0.001), LO number ≤ 2 (P < 0.001), cumulative GTV ≤ 40 cm3 (P < 0.001) and system treatments combined with chemotherapy and target therapy (P < 0.001) showed superior OS. The LCR for 3, 6, and 12 months was 97.9%, 91.0%, and 83.6%, respectively. There were 4 cases of pneumothorax at 5.7% that required drainage. CONCLUSIONS: RISB for LO from CRC is safe and effective, and serum CEA, TNM stage, LO number, cumulative GTV, and system treatments should be emphasized for long OS.

Associations Between Dietary Intake of Tomato and Lycopene with All-Cause and Cancer-Specific Mortality in US Adults with Diabetes: Results From a Cohort Study.

This study aimed to explore the association between dietary intake of tomatoes and lycopene with all-cause and cancer mortality among US adults with diabetes. We hypothesized that a higher intake of tomato and lycopene is related to a reduced risk of all-cause and cancer mortality among adults with diabetes. This prospective study was conducted among 9213 US adults with diabetes using data from the National Health and Nutrition Examination Survey (NHANES) 2007-2016. Data on dietary intake of tomatoes and lycopene were obtained from two 24-h dietary recalls. Multivariate Cox proportional hazard models determined the associations between tomato/lycopene intake and mortality. A higher intake of tomatoes and lycopene was significantly associated with a lower risk of all-cause mortality (tomato: Q5 vs. Q1: HR = 0.68, 95% CI = 0.54-0.86, p = 0.001, p for trend = 0.001; lycopene: Q5 vs. Q1: HR = 0.78, 95% CI = 0.64-0.95, p = 0.013, p for trend = 0.006) after adjusting for all covariates. Compared with the lowest quintile of tomato and lycopene intake, the highest quintile was associated with a lower risk of cancer mortality (tomato: HR = 0.58, 95% CI = 0.35-0.96, p = 0.035; lycopene: HR = 0.63, 95% CI = 0.40-0.98, p = 0.043). Our study demonstrated that dietary intake of tomatoes and lycopene was significantly associated with a lower risk of all-cause mortality in US adults with diabetes. High consumption of tomatoes and lycopene was also related to reduced cancer mortality in US adults with diabetes.

Efficacy and Safety of TACE Combined with Regorafenib versus TACE Combined with Camrelizumab in Hepatocellular Carcinoma With Untreatable Progression After TACE Combined with Sorafenib Therapy: A Case Control Study.

PURPOSE: To evaluate the efficacy and safety of transarterial chemoembolization (TACE) combined with regorafenib (hereafter, TACE-regorafenib) or camrelizumab (hereafter, TACE-camrelizumab) for treating hepatocellular carcinoma (HCC) with untreatable progression after TACE and sorafenib therapy. METHODS: The medical records of patients with HCC who received TACE-regorafenib or TACE-camrelizumab between September 2018 and December 2023 were retrospectively evaluated. Therapeutic response, overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were compared between the two groups. RESULTS: A total of 76 patients were enrolled in this study, with 41 and 35 patients in the TACE-regorafenib and TACE-camrelizumab groups, respectively. The objective response rates in the TACE-regorafenib and TACE-camrelizumab groups were 9.8% and 8.6%, respectively, with no statistically significant difference between the two groups (P = 0.859). Similarly, there was no statistically significant difference in disease control rates between the two groups (61.0% vs 68.6%, P = 0.838). The median OS was 11 months in the TACE-regorafenib group and 10 months in the TACE-camrelizumab group, with no significant difference between the two groups (P = 0.348). The TACE-regorafenib group had a median PFS of 7 months, which was significantly longer than that of the TACE-camrelizumab group (4 months, P = 0.004). There was no significant difference in the incidence of AEs between the two groups (P = 0.544). CONCLUSIONS: TACE-regorafenib was safe, well-tolerated, and showed promising efficacy in patients with sorafenib-refractory advanced HCC, whereas TACE-camrelizumab demonstrated similar survival benefits.

Percutaneous Nephroureteral Stent Placement and Antegrade Forceps Biopsy of Ureteral Obstruction.

PURPOSE: To evaluate the feasibility of percutaneous transluminal ureteral biopsy (PTUB) combined with percutaneous nephroureteral stent placement for ureteral obstruction under fluoroscopy. MATERIALS AND METHODS: From September 2011 to July 2021, 37 patients (27 men and 10 women; median age, 65.0 years) who experienced ureteroscopic biopsy failure or refused or were unable to undergo ureteroscopic biopsy underwent PTUB for ureteral obstruction during nephroureteral stent placement under fluoroscopic guidance. Data on technical success, early adverse events, and radiation dose were collected. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy (OA) of PTUB were analyzed. RESULTS: The technical success of PTUB was 89.2%, with a mean irradiation dose of 76.9 mGy·cm2 ± 12.2. A total of 67.6% (25/37) of the cases were correctly diagnosed with malignancy, whereas 8 cases were confirmed to be true negatives. There were 4 false negatives and no false positives. PTUB had a sensitivity, specificity, PPV, NPV, and OA of 86.2% (25/29), 100% (8/8), 100% (25/25), 66.7% (8/12), and 89.2% (33/37), respectively. Eleven patients (29.7%) experienced Grade 1 adverse events (transient aggravated hematuria). CONCLUSIONS: PTUB appears to be a safe and effective alternative to ureteroscopic biopsy for ureteral obstruction.

Visceral adiposity index as a predictor of type 2 diabetes mellitus risk: A systematic review and dose-response meta-analysis.

AIMS: Considering the positive association between visceral adiposity index (VAI) and type 2 diabetes mellitus (T2DM), no comprehensive assessment on the summarized and dose-response relationship between VAI and T2DM has yet been reported. Therefore, we performed a meta-analysis, including dose-response analysis, to quantitively elucidate this association. DATA SYNTHESIS: MEDLINE via PubMed and Embase databases were searched for relevant articles up to December 14, 2021. Random-effects generalized least squares regression models were used to assess the quantitative association between VAI and T2DM risk across studies. Restricted cubic splines were used to model the dose-response association. A total of 9 prospective cohort studies and 5 cross sectional studies were included in our review. Based on the meta-analysis, the pooled RR of T2DM was 2.05 (95% CI 1.74-2.41) for the highest versus reference VAI category. We found that the risk of T2DM was increased by 44% (RR, 1.44; 95% CI, 1.23-1.68) with each 1-unit increment of VAI. While, we found no evidence of a nonlinear dose-response association of VAI and T2DM (Pnon-linearity = 0.428). With the linear cubic spline model, when compared to population with VAI at 0.6, for those with VAI at 2.0, the risk of T2DM was increased by 81% (RR, 1.81; 95% CI 1.55-2.12). CONCLUSIONS: Our meta-analysis provides quantitative data suggesting that VAI is associated with an increased risk of T2DM. Public health strategies focusing on weight loss among obesity, especially the people characterized by the thin-on-the-outside--fat-on-the-inside phenotype could possibly reduce a substantial risk of T2DM. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022372666.

Induced transparency by interference or polarization.

Polarization of optical fields is a crucial degree of freedom in the all-optical analogue of electromagnetically induced transparency (EIT). However, the physical origins of EIT and polarization-induced phenomena have not been well distinguished, which can lead to confusion in associated applications such as slow light and optical/quantum storage. Here we study the polarization effects in various optical EIT systems. We find that a polarization mismatch between whispering gallery modes in two indirectly coupled resonators can induce a narrow transparency window in the transmission spectrum resembling the EIT lineshape. However, such polarization-induced transparency (PIT) is distinct from EIT: It originates from strong polarization rotation effects and shows a unidirectional feature. The coexistence of PIT and EIT provides additional routes for the manipulation of light flow in optical resonator systems.

Screening of monoamine oxidase B inhibitors in Tibetan strawberry by ligand fishing based on enzyme functionalized cellulose filter paper.

Tibetan strawberry (Fragaria nubicola) is a wild medicinal and edible plant in Tibet possessing various health benefits such as neuroprotection and anti-oxidation. However, there has been little study reported on its chemical constituents. To investigate the inhibitors of monoamine oxidase B (MAO-B) in Tibetan strawberry, we immobilized the enzyme onto cellulose filter paper for the first time to develop a new screening method. Two known glycosides (compounds 1 and 2) and one new iridoid glucoside (Compound 3) were fished out by this method, which was found to effectively inhibit MAO-B with IC50 values of 16.95 ± 0.93, 24.69 ± 0.20, and 46.77 ± 0.78 µM, respectively. Molecular docking and kinetic analysis were performed to reveal the inhibition mechanism of these compounds. Furthermore, compound 1 exhibited neuroprotective effects against 6-OHDA-induced injury on PC12 cells. The developed method exhibits the advantages of rapidness and effectiveness in screening of MAO-B inhibitors from complex herbal extracts.

Spatial-temporal differentiation and control strategies of nitrogen environmental loss in China's coastal regions based on flow analysis.

Nitrogen pollution emissions from human production and living activities in coastal regions are important topics in the management of environmental pollution in coastal waters. However, to date, there has been relatively little research systematically assessing the environmental loss of nitrogen (NEL) from human activities that negatively affect marine ecosystems. This study categorised emission sources into five subsystems, namely livestock, farming, aquatic, industrial, and residential. Through flow analysis, the anthropogenic emissions of nitrogen in the gas, liquid, and solid phases from 11 coastal provinces in China in 2011, 2015, and 2020 were determined. A nitrogen cost index was constructed by combining the social indicators of each province. The effectiveness of nitrogen emission control since the land-sea coordination and the future challenges for the coastal region were discussed from various perspectives. The results of the study showed that the total NEL that poses a potential threat to marine ecosystems in coastal areas of China has decreased from 18.93 TgN to 14.66 TgN since the proposal of land-sea coordination, with livestock systems and aquatic systems emitting the most. The Bohai and Yellow Seas area were most threatened by nitrogen pollution. Among the three oceanic pathways, liquid-phase nitrogen discharge from each subsystem was effectively controlled, and the control of gas-phase nitrogen emissions is still the most numerous NEL state, although it has had a significant effect. The results of the correlation analysis suggest that NEL flow can characterize the regional management of nutrient-based organic pollutants. Past management tools and environmental investments in China have been more effective in controlling emissions from point and line sources involving artificial facilities, but less direct effect on mariculture. How to control surface source pollution from livestock and aquaculture will be an important challenge to reduce reactive nitrogen emissions in the future.

Analysis of extracellular and intracellular antibiotic resistance genes in commercial organic fertilizers reveals a non-negligible risk posed by extracellular genes.

Livestock manure is known to be a significant reservoir of antibiotic resistance genes (ARGs), posing a major threat to human health and animal safety. ARGs are found in both intracellular and extracellular DNA fractions. However, there has been no comprehensive analysis of these fractions in commercial organic fertilizers (COFs). The present study conducted a systematic survey of the profiles of intracellular ARGs (iARGs) and extracellular ARGs (eARGs) and their contributing factor in COFs in Northern China. Results showed that the ARG diversity in COFs (i.e., 57 iARGs and 53 eARGs) was significantly lower than that in cow dung (i.e., 68 iARGs and 69 eARGs). The total abundance of iARGs and eARGs decreased by 85.7% and 75.8%, respectively, after compost processing, and there were no significant differences between iARGs and eARGs in COFs (P > 0.05). Notably, the relative abundance of Campilobacterota decreased significantly (99.1-100.0%) after composting, while that of Actinobacteriota and Firmicutes increased by 21.1% and 29.7%, respectively, becoming the dominant bacteria in COFs. Co-occurrence analysis showed that microorganisms and mobile genetic elements (MGEs) were more closely related to eARGs than iARGs in COFs. And structural equation models (SEMs) further verified that microbial community was an essential factor regulating iARGs and eARGs variation in COFs, with a direct influence (λ = 0.74 and 0.62, P < 0.01), following by similar effects of MGEs (λ = 0.59 and 0.43, P < 0.05). These findings indicate the need to separate eARGs and iARGs when assessing the risk of dissemination and during removal management in the environment.

Combination of co-pyrolyzed biomass-sludge biochar and ultrasound for persulfate activation in antibiotic degradation: efficiency, synergistic effect, and reaction mechanism.

A carbon material Cu-corn straw-sludge biochar (Cu-CSBC) was prepared by hydrothermally modifying sewage sludge and corn stover. The composite coupled to ultrasound can effectively catalyze the activation of PS for organic pollutants degradation, and the removal rate of 20 mg/L TC reached 89.15% in 5 min in the presence of 0.5 g/L Cu-CSBC and 3 mM PS. The synergistic effect between the factors in the system, the reaction mechanism, and the efficient removal of TC in the aqueous environment were explored in a Cu-CSBC/US/PS system established for that purpose. Quenching experiments and electron paramagnetic resonance analysis both demonstrated the Cu-CSBC/US/PS system generated •OH, SO4-•, 1O2, and O2- •, which involved in the reaction. The Cu, carboxyl, and hydroxyl groups on the Cu-CSBC surface promoted the generation of radicals and non-radicals for the degradation process, which was dominated by both radical and non-radical pathways. The degradation pathway is proposed by measuring the intermediate products with LC-MS. Finally, the stability of the Cu-CSBC/US/PS system was tested under various reaction conditions. This study not only prepared a novel biochar composite material for the active degradation of organic pollutants by PS but also provided an effective method for the resource utilization of solid waste and sludge treatment.

Spin-Frustrated Trisradical Trication of PrismCage.

Organic trisradicals featuring threefold symmetry have attracted significant interest because of their unique magnetic properties associated with spin frustration. Herein, we describe the synthesis and characterization of a triangular prism-shaped organic cage for which we have coined the name PrismCage6+ and its trisradical trication─TR3(•+). PrismCage6+ is composed of three 4,4'-bipyridinium dications and two 1,3,5-phenylene units bridged by six methylene groups. In the solid state, PrismCage6+ adopts a highly twisted conformation with close to C3 symmetry as a result of encapsulating one PF6- anion as a guest. PrismCage6+ undergoes stepwise reduction to its mono-, di-, and trisradical cations in MeCN on account of strong electronic communication between its 4,4'-bipyridinium units. TR3(•+), which is obtained by the reduction of PrismCage6+ employing CoCp2, adopts a triangular prism-shaped conformation with close to C2v symmetry in the solid state. Temperature-dependent continuous-wave and nutation-frequency-selective electron paramagnetic resonance spectra of TR3(•+) in frozen N,N-dimethylformamide indicate its doublet ground state. The doublet-quartet energy gap of TR3(•+) is estimated to be -0.08 kcal mol-1, and the critical temperature of spin-state conversion is found to be ca. 50 K, suggesting that it displays pronounced spin frustration at the molecular level. To the best of our knowledge, this example is the first organic radical cage to exhibit spin frustration. The trisradical trication of PrismCage6+ opens up new possibilities for fundamental investigations and potential applications in the fields of both organic cages and spin chemistry.

IFN-beta and EIF2AK2 are potential biomarkers for interstitial lung disease in anti-MDA5 positive dermatomyositis.

OBJECTIVE: DM with positive anti-melanoma differentiation-related gene 5 (MDA5) antibody is an autoimmune disease with multiple complications. Interstitial lung diseases (ILDs) are significantly associated with DM and are particularly related to MDA5+ DM. This article aims to explore potential molecular mechanisms and develop new diagnostic biomarkers for MDA5+ DM-ILD. METHODS: The series matrix files of DM and non-specific interstitial pneumonia (NSIP) were downloaded from the Gene Expression Omnibus (GEO) database to identify the differentially expressed genes (DEGs). Gene set enrichment analysis (GSEA) was used to screen the common enriched pathways related to DM and NSIP. Next, the co-expressed differential expressed genes (co-DEGs) between MDA5+, MDA5- and NSIP groups were identified by Venn plots, and then selected for different enrichment analyses and protein-protein interaction (PPI) network construction. The mRNA expression levels of IFN-beta and EIF2AK2 were measured by RT-qPCR. The protein expression levels of IFN-beta were measured by ELISA. RESULTS: Using GSEA, the enriched pathway 'herpes simplex virus 1 infection' was both up-regulated in DM and NSIP. Enrichment analysis in MDA5+ DM, MDA5- DM and NSIP reported that the IFN-beta signalling pathway was an important influencing factor in the MDA5+ DM-ILD. We also identified that eukaryotic translation initiation factor 2 alpha kinase 2 (EIF2AK2) was an important gene signature in the MDA5+ DM-ILD by PPI analysis. The expression levels of IFN-beta and EIF2AK2 were significantly increased in MDA5+ DM-ILD patients. CONCLUSIONS: IFN-beta and EIF2AK2 contributed to the pathogenesis of MDA5+ DM-ILD, which could be used as potential therapeutic targets.

Synthesis of Hierarchical CdS/NiS Photocatalysts Using Ni-MOF-74 as Template for Efficient Ethanol Conversion and Hydrogen Production under Visible Light.

The conversion of ethanol into high-valuable chemicals and H2 by photocatalytic process provides a sustainable approach to produce carbon-chain-prolonged chemicals and hydrogen energy. In this article, Ni-MOF-74 was added to fabricate the hierarchical CdS/NiS-N composites with an elevated specific surface area during the hydrothermal synthesis of CdS microsphere, and the Ni-MOF-74 facilitate the self-assemble growth of CdS and provide a source of Ni for the formation of NiS. The as-prepared photocatalyst was subjected to photocatalytic ethanol conversion, and the hierarchical composite material CdS/NiS-N (100) formed by adding 100 mg of Ni-MOF-74 exhibits the highest photocatalytic activity and stability in an ethanol aqueous solution with a water content of 10 %. Under visible light irradiation, the conversion rate of ethanol reached 15.2 % at the photocatalytic reaction of 5 h. The selectivity of 2,3-butanediol(2,3-BDO) was 25 %, and the selectivity of acetaldehyde(AA) was 63 %. Through various characterizations, it has been proven that a large specific surface area and the coupling interface between CdS and NiS are key factors in improving photocatalytic performance. This work provides an effective strategy for constructing photocatalysts with coupled cocatalysts/semiconductors and large specific surface areas.

Biliary drainage combined with simultaneous 125I seed strand brachytherapy for the treatment of hilar cholangiocarcinoma.

BACKGROUND: To evaluate the clinical efficacy of percutaneous biliary drainage (PBD) combined with 125I seed strand brachytherapy (ISSB) for the treatment of hilar cholangiocarcinoma (HCCA). METHODS: The clinical data of 64 patients with HCCA (median age 62.5, male 29, female 35) treated in our department from April 2017 to April 2021 were retrospectively analyzed. Thirty-four patients in the experimental group (EG) were treated with PBD combined with ISSB, while 30 patients in the control group (CG) were treated with PBD alone. The primary study endpoints were technical success, clinical success and the 2-month local tumor control (LTC) rate. Secondary endpoints were early/late complications, median progression-free survival (mPFS) and overall survival (mOS). RESULTS: The technical and clinical success in the EG and CG showed no significant differences (100 vs. 100%, 94.1 vs. 93.3%, P > 0.05). Both early and late complications showed no significant differences between the two groups (P > 0.05). The 2-month LTC rates were significantly better in the EG versus the CG (94.1% vs. 26.7%, 157.7 ± 115.3 vs. 478.1 ± 235.3 U/ml), respectively (P < 0.05). The mPFS and mOS were 4.3 (95% CI 3.9-4.7) months and 2.8 (95% CI 2.5-3.1) months and 13.5 (95% CI 10.7-16.3) months and 8.8 (95% CI 7.8-9.8) months, respectively, with significant differences (P < 0.05). CONCLUSION: PBD combined with ISSB is a safe and effective treatment for HCCA that can inhibit local tumors and prolong PFS and OS.