One New Acid-Activated Hybrid Anticancer Peptide by Coupling with a Desirable pH-Sensitive Anionic Partner Peptide.

Anticancer peptides (ACPs) are promising antitumor resources, and developing acid-activated ACPs as more effective and selective antitumor drugs would represent new progress in cancer therapy. In this study, we designed a new class of acid-activated hybrid peptides LK-LE by altering the charge shielding position of the anionic binding partner LE based on the cationic ACP LK and investigated their pH response, cytotoxic activity, and serum stability, in hoping to achieve a desirable acid-activatable ACP. As expected, the obtained hybrid peptides could be activated and exhibit a remarkable antitumor activity by rapid membrane disruption at acidic pH, whereas its killing activity could be alleviated at normal pH, showing a significant pH response compared with LK. Importantly, this study found that the peptide LK-LE3 with the charge shielding in the N-terminal of LK displayed notably low cytotoxicity and more stability, demonstrating that the position of charge masking is extremely important for the improvement of peptide toxicity and stability. In short, our work opens a new avenue to design promising acid-activated ACPs as potential targeting agents for cancer treatment.

Social incentives foster cooperation through guilt aversion: An effect that diminishes with primary psychopathic traits.

The association between primary psychopathic traits and non-cooperative behaviors is well-identified. There is a lack of studies on how to motivate cooperative behaviors in individuals with primary psychopathic traits. This study investigated the effects of monetary incentives and social incentives on promoting cooperation in healthy adults with varying primary psychopathic traits. Participants played a one-shot public goods game (PGG) with other anonymous players in three different contexts: a social incentives context where participants' decisions would be judged by others, a monetary incentives context where participants' decisions would result in winning or losing money depending on their contributions, and a control condition where no additional incentives were implemented. We found that, compared to the control condition, both monetary and social incentives significantly improved participants' contributions to the public project-an indicator of cooperative behavior. However, the association between higher primary psychopathic traits and less cooperation was only observed in the context of social incentives. Computational modeling further revealed that this effect can be explained by the diminishing guilt aversion when participants deliberately violated their inferred expectations of themselves from others' perspectives. This study found that social incentives can encourage cooperative behaviors in non-clinical psychopathy, and identified the mental processes navigating this effect.

Association between Serum Iron, Blood Lead, Cadmium, Mercury, Selenium, Manganese and Low Cognitive Performance in Old Adults from National Health and Nutrition Examination Survey (NHANES): A Cross-Sectional Study.

Cognitive decline is a public health problem for the world's aging population. This study was to evaluate the relationships between serum iron, blood lead, cadmium, mercury, selenium, and manganese and cognitive decline in elderly Americans. Data of this cross-sectional study was extracted from the National Health and Nutritional Examination Survey (NHANES 2011-2014). Cognitive performance was measured by the consortium to establish a registry for Alzheimer's disease (CERAD), Animal fluency, and digit symbol substitution test (DSST) tests. Weighted univariable and multivariate logistic regression analyses were used to assess the associations between six trace elements and low cognitive performance, with odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses based on diabetes and hypertension history were further assess the associations. A total of 2,002 adults over 60 years old were included. After adjusting covariates, elevated serum iron levels were associated with the decreased risk of low cognitive performance (OR=0.995, 95%CI: 0.990-0.999), as well as in the elderly without diabetes history (OR=0.992, 95%CI: 0.988-0.997) and with hypertension history (OR=0.993, 95%CI: 0.988-0.997) in the Animal Fluency test. High blood cadmium and blood manganese levels were associated with the odds of low cognitive performance in old adults with diabetes (OR=2.900, 95%CI: 1.311-6.417) and hypertension (OR=1.037, 95%CI: 1.009-1.066) history, respectively. In the DSST test, high blood lead levels were related to the odds of low cognitive performance (OR=1.102, 95%CI: 1.019-1.192), as well as in the elderly without diabetes (OR=1.126, 95%CI: 1.026-1.235) and hypertension (OR=1.121, 95%CI: 1.002-1.255) history. Elevated blood cadmium levels were connected with low cognitive performance in diabetic (OR=3.177, 95%CI: 1.323-7.27) and hypertensive (OR=1.896, 95%CI: 1.056-3.403) old people. High blood selenium levels were linked to the decreased risk of low cognitive performance in all the elderly (OR=0.987, 95%CI: 0.981-0.993). Appropriate iron, selenium supplementation and iron-, selenium-rich foods intake, while reducing exposure to lead, cadmium and manganese may be beneficial for cognitive function in the elderly.

Effect of acupuncture at Xinwu acupoint combined with loratadine and fluticasone propionate on symptom alleviation, nasal function, and serum histamine level in patients with allergic rhinitis.

OBJECTIVE: To determine the influence of acupuncture at the Xinwu acupoint combined with western medicine (loratadine and fluticasone propionate) on symptom alleviation, nasal mucociliary clearance velocity (MCV), and serum histamine level of patients with allergic rhinitis (AR). METHODS: A total of 122 patients with AR treated in Gansu province hospital of TCM and The Third People's Hospital of Gansu Province from April 2019 to April 2021 were retrospectively analyzed. Among them, 54 patients treated with loratadine and fluticasone propionate were assigned to the control group, and 68 patients treated with additional acupuncture at the Xinwu acupoint based on treatment of the control group were assigned to the observation group. The treatment efficacy of the two groups was compared, and the scores of main symptoms and nasal function were also compared before and after therapy. Additionally, the two groups were compared in the levels of histamine, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and immunoglobulin E (IgE) before and after therapy. RESULTS: After therapy, the observation group yielded a higher total effective rate than the control group (P=0.006) and had lower symptom scores than the control group (P<0.001). Additionally, the MCV of the two groups increased (P<0.001), and the nasal mucociliary transit time (MTT) and nasal resistance (NR) of both groups decreased (P<0.001) after therapy. The observation group showed a greatly better improvement of nasal function than the control group (P<0.001). Moreover, after therapy, the observation group showed lower histamine and IgE levels than the control group (P<0.01) and the observation group presented significantly lower levels than the control group, and had lower rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) scores than the control group (P<0.001). The two groups were not different in the incidence of adverse reactions (P=0.886). CONCLUSION: Acupuncture at Xinwu acupoint combined with loratadine and fluticasone propionate can deliver a powerful efficacy on AR and alleviate the clinical symptoms, without increasing adverse reactions.

Association between healthy sleep patterns and depressive trajectories among college students: a prospective cohort study.

BACKGROUND: The purpose of this study was to identify different develpment trajectories of depression symptoms during college period, and prospectively investigate the associations healthy sleep patterns with trajectories of depression symptoms among college students from freshman through junior year. METHODS: A total of 999 participants from the College Student Behavior and Health Cohort Study were included between April 2019 and June 2021. Healthy sleep patterns were defined by chronotype, sleep duration, insomnia, snoring, and daytime sleepiness. Latent growth curve model was used to identify trajectories of depression symptoms. Then binary logistic regression was used to examine association of the healthy sleep patterns with these trajectories. RESULTS: In baseline survey, we found that a total of 100 (10.0%) participants had healthy sleep patterns' score equal to 5. Then, we used 5 surveys' data to identify 2 distinct trajectories of depression symptoms during college (decreasing: 82.5%; increasing: 17.5%). The healthy sleep patterns were associated with these trajectories, the better healthy sleep patterns significantly decrease the risk of increasing trajectories of depression symptoms in males (OR: 0.72, 95%CI: 0.54 ~ 0.97, P = 0.031). Moreover, we found out that the healthy sleep patterns of college students can predict the future depressive symptoms in this study (all P < 0.001). CONCLUSION: Our findings indicate that the better healthy sleep patterns may significantly decrease the risk of increasing trajectory of depression symptoms only in male college students. The results speak to a need for college student with depression symptoms to identify and address sleep problems when present, which could prevent or reduce depression detriments in later life.

Increased clonal dissemination of OXA-232-producing ST15 Klebsiella pneumoniae in Zhejiang, China from 2018 to 2021.

BACKGROUND: OXA-232-producing Klebsiella pneumoniae was first identified in China in 2016, and its clonal transmission was reported in 2019. However, there are no prevalence and genotypic surveillance data available for OXA-232 in China. Therefore, we investigated the trends and characteristics of OXA-232 type carbapenemase in Zhejiang Province, China from 2018 to 2021. METHODS: A total of 3278 samples from 1666 patients in the intensive care units were collected from hospitals in Zhejiang Province from 2018 to 2021. Carbapenem-resistant isolates were initially selected by China Blue agar plates supplemented with 0.3 µg/ml meropenem, and further analyzed by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry identification, immune colloidal gold technique, conjugation experiment, antimicrobial susceptibility testing and whole genome sequencing. RESULTS: A total of 79 OXA-producing strains were recovered, with the prevalence increased from 1.8% [95% confidence interval (CI): 0.7-3.7%] in 2018 to 6.0% (95% CI: 4.4-7.9%) in 2021. Seventy-eight strains produced OXA-232 and one produced OXA-181. The blaOXA-232 gene in all strains was located in a 6141-bp ColKP3-type non-conjugative plasmid and the blaOXA-181 gene was located in a 51,391-bp ColKP3/IncX3-type non-conjugative plasmid. The blaOXA-232-producing K. pneumoniae was dominated (75/76) by isolates of sequence type 15 (ST15) that differed by less than 80 SNPs. All OXA-producing strains (100%, 95% CI: 95.4-100.0%) were multidrug-resistant. CONCLUSIONS: From 2018 to 2021, OXA-232 is the most prevalent OXA-48-like derivative in Zhejiang Province, and ST15 K. pneumoniae isolates belonging to the same clone are the major carriers. The transmission of ColKP3-type plasmid to E. coli highlighted that understanding the transmission mechanism is of great importance to delay or arrest the propagation of OXA-232 to other species.

All-cause mortality risk with different metabolic abdominal obesity phenotypes: the Rural Chinese Cohort Study.

We aimed to investigate the association of metabolic obesity phenotypes with all-cause mortality risk in a rural Chinese population. This prospective cohort study enrolled 15,704 Chinese adults (38.86% men) with a median age of 51.00 (IQR: 41.00-60.00) at baseline (2007-2008) and followed up during 2013-2014. Obesity was defined by waist circumference (WC: ≥90 cm for men and ≥80 cm for women) or waist-to-height ratio (WHtR: ≥0.5). The hazard ratio (HR) and 95% confidence interval (CI) for risk of all-cause mortality related to metabolic obesity phenotypes were calculated using the Cox hazards regression model. During a median follow-up of 6.01 years, 864 deaths were identified. When obesity was defined by WC, the prevalence of participants with metabolically healthy non-obesity (MHNO), metabolically healthy obesity (MHO), metabolically unhealthy non-obesity (MUNO), and metabolically unhealthy obesity (MUO) at baseline was 12.12%, 2.80%, 41.93%, and 43.15%, respectively. After adjusting for age, sex, alcohol drinking, smoking, physical activity, and education, the risk of all-cause mortality was higher with both MUNO (HR = 1.20, 95% CI 1.14-1.26) and MUO (HR = 1.20, 95% CI 1.13-1.27) versus MHNO, but the risk was not statistically significant with MHO (HR = 0.99, 95% CI 0.89-1.10), this result remained consistent when stratified by sex. Defining obesity by WHtR gave similar results. MHO does not suggest a greater risk of all-cause mortality compared to MHNO, but participants with metabolic abnormality, with or without obesity, have a higher risk of all-cause mortality. These results should be cautiously interpreted as the representation of MHO is small.

Partial Substitution of Urea with Biochar Induced Improvements in Soil Enzymes Activity, Ammonia-Nitrite Oxidizers, and Nitrogen Uptake in the Double-Cropping Rice System.

Biochar is an important soil amendment that can enhance the biological properties of soil, as well as nitrogen (N) uptake and utilization in N-fertilized crops. However, few studies have characterized the effects of urea and biochar application on soil biochemical traits and its effect on paddy rice. Therefore, a field trial was conducted in the early and late seasons of 2020 in a randomized complete block design with two N levels (135 and 180 kg ha-1) and four levels of biochar (0, 10, 20, and 30 t ha-1). The treatment combinations were as follows: 135 kg N ha-1 + 0 t B ha-1 (T1), 135 kg N ha-1 + 10 t B ha-1 (T2), 135 kg N ha-1 + 20 t B ha-1 (T3), 135 kg N ha-1 + 30 t B ha-1 (T4), 180 kg N ha-1 + 0 t B ha-1 (T5), 180 kg N ha-1 + 10 t B ha-1 (T6), 180 kg N ha-1 + 20 t B ha-1 (T7) and 180 kg N ha-1 + 30 t B ha-1 (T8). The results showed that soil amended with biochar had higher soil pH, soil organic carbon content, total nitrogen content, and mineral nitrogen (NH4+-N and NO3--N) than soil that had not been amended with biochar. In both seasons, the 20 t ha-1 and 30 t ha-1 biochar treatments had the highest an average concentrations of NO3--N (10.54 mg kg-1 and 10.25 mg kg-1, respectively). In comparison to soil that had not been treated with biochar, the average activity of the enzymes urease, polyphenol oxidase, dehydrogenase, and chitinase was, respectively, 25.28%, 14.13%, 67.76%, and 22.26% greater; however, the activity of the enzyme catalase was 15.06% lower in both seasons. Application of biochar considerably increased the abundance of ammonia-oxidizing bacteria (AOB), which was 48% greater on average in biochar-amended soil than in unamended soil. However, there were no significant variations in the abundances of ammonia-oxidizing archaea (AOA) or nitrite-oxidizing bacteria (NOB) across treatments. In comparison to soil that had not been treated with biochar, the average N content was 24.46%, 20.47%, and 19.08% higher in the stem, leaves, and panicles, respectively. In general, adding biochar at a rate of 20 to 30 t ha-1 with low-dose urea (135 kg N ha-1) is a beneficial technique for improving the nutrient balance and biological processes of soil, as well as the N uptake and grain yield of rice plants.

Reintervention after Thoracic Endovascular Aortic Repair of Uncomplicated Type B Aortic Dissection.

BACKGROUND: Data are scarce regarding the incidence, reasons, potential risk factors, and long-term outcomes of reintervention after thoracic endovascular aortic repair (TEVAR) in patients with uncomplicated type B aortic dissection (TBAD). METHODS: Between January 2010 and December 2020, 238 patients with uncomplicated TBAD who received TEVAR were analyzed retrospectively. The clinical baseline data, aorta anatomy, dissection characteristics, and details of the TEVAR procedure were evaluated and compared. A competing-risk regression model was used to estimate the cumulative incidences of reintervention. The multivariate Cox model was used to identify the independent risk factors. RESULTS: The mean follow-up time was 68.6 months. A total of 27 (11.3%) cases of reintervention were observed. The competing-risk analyses showed that the 1-, 3-, and 5-year cumulative incidences of reintervention were 5.07%, 7.08%, and 14.0%, respectively. Reasons for reintervention included endoleak (25.9%), aneurysmal dilation (22.2%), retrograde type A aortic dissection (18.5%), distal stent-graft-induced new entry and false lumen expansion (18.5%), and dissection progression and/or malperfusion (14.8%). Multivariable Cox analysis demonstrated that a larger initial maximal aortic diameter (Hazard ratio [HR], 1.75; 95% Confidence interval [CI], 1.13-2.69, p = 0.011) and increased proximal landing zone oversizing (HR, 1.07; 95% CI, 1.01-1.47, p = 0.033) were the significant risk factors for reintervention. Long-term survival rates were comparable between patients with or without reintervention (p = 0.915). CONCLUSIONS: Reintervention after TEVAR in patients with uncomplicated TBAD is not uncommon. A larger initial maximal aortic diameter and excessive proximal landing zone oversizing are associated with the second intervention. Reintervention does not significantly affect long-term survival.

Social navigation modulates the anterior and posterior hippocampal circuits in the resting brain.

Social navigation is a dynamic and complex process that requires the collaboration of multiple brain regions. However, the neural networks for navigation in a social space remain largely unknown. This study aimed to investigate the role of hippocampal circuit in social navigation from a resting-state fMRI data. Here, resting-state fMRI data were acquired before and after participants performed a social navigation task. By taking the anterior and posterior hippocampus (HPC) as the seeds, we calculated their connectivity with the whole brain using the seed-based static functional connectivity (sFC) and dynamic FC (dFC) approaches. We found that the sFC and dFC between the anterior HPC and supramarginal gyrus, sFC or dFC between posterior HPC and middle cingulate cortex, inferior parietal gyrus, angular gyrus, posterior cerebellum, medial superior frontal gyrus were increased after the social navigation task. These alterations were related to social cognition of tracking location in the social navigation. Moreover, participants who had more social support or less neuroticism showed a greater increase in hippocampal connectivity. These findings may highlight a more important role of the posterior hippocampal circuit in the social navigation, which is crucial for social cognition.

Photo-activated autophagy-associated tumour cell death by lysosome impairment based on manganese-doped graphene quantum dots.

Autophagy is indispensable in normal cellular processes, yet detrimental to cancer treatment because it severely lowers the therapeutic efficiency. One of the keys to solve this problem may lie in lysosomes, which requires the rational design of nanomedicine that is capable of localizing and maintaining its efficacy in lysosomes. In this work, a facile and versatile nanoplatform based on manganese-doped graphene quantum dots (Mn-FGQDs) is developed for effective and precise photodynamic impairment of lysosomes. Specifically, the incorporation of Mn not only strengthens the generation capability of reactive oxygen species (ROS), but also facilitates its accumulation in lysosomes. Moreover, Mn-FGQDs are structurally robust and retain their high photodynamic efficiency in the lysosomal environment. On this basis, the light-triggered generation of ROS would primarily influence the function of lysosomes, leading to lysosome impairment and thereby effectively blocking the protective autophagy recycling. More impressively, a continuous increase in the oxidative stress level in lysosomes causes severe autophagy dysfunction, as revealed from an abnormal increase in autophagosomes and autolysosomes. This eventually results in autophagy-associated cancer cell death accompanied by the characteristics of apoptosis and ferroptosis. Overall, the present work paves a new way for cancer therapy via precise lysosome impairment induced autophagy dysfunction.

High efficiency electrochemical separation of uranium(VI) from uranium-containing wastewater by microbial fuel cells with different cathodes.

As an emerging versatile technology for separating uranium from uranium-containing wastewater (UCW), microbial fuel cell (MFC) offers a novel approach to UCW treatment. Its cathode is essential for the treatment of UCW. To thoroughly investigate the efficacy of MFC in treating UCW, investigations were conducted using MFCs with five materials (containing iron sheet (IP), stainless steel mesh (SSM), carbon cloth (CC), carbon brush (CB), and nickel foam (NF)) as cathodes. The results revealed that each MFC system performed differently in terms of carbon source degradation, uranium removal, and electricity production. In terms of carbon source degradation, CB-MFC showed the best performance. The best uranium removal method was NF-MFC, and the best electricity production method was carbon-based cathode MFC. Five MFC systems demonstrated stable performance and consistent difference over five cycles, with CC-MFC outperforming the others. Furthermore, SEM and XPS characterization of the cathode materials before and after the experiment revealed that a significant amount of U(IV) was generated during the uranium removal process, indicating that uranium ions were primarily removed by electrochemical reduction precipitation. This study confirmed that abiotic cathode MFC had a high UCW removal potential and served as a good guideline for obtaining the best cathode for MFC.

Preparation of Carbon Dots@r-GO Nanocomposite with an Enhanced Pseudo-Capacitance.

Carbon materials with pseudocapacitive performance have attracted emerging interest in the energy storage and conversion field. Reduced graphene oxide (r-GO) with superior conductivity and electrochemical stability has been extensively investigated as an efficient capacitive electrode material. In this study, three-dimensional carbon dots (CDs)@r-GO hydrogel electrode was successfully in situ prepared by the one-pot method, where the CDs play a critical role in serving as both reduction agent and electrochemical active sites. With prolonged reaction time, the oxygen content of the CDs@r-GO nanocomposite material could be effectively reduced to ensure better electric conductivity, and the nitrogen content, which provides pseudocapacitance, was gradually increased. The representative two pairs of fast and reversible current peaks appeared in cyclic voltammetry curves, with around three times higher specific capacitance of CDs@r-GO hydrogel electrode (290 F g-1 at the current density of 1 A g-1 in 1 M H2SO4 electrolyte). This simple and mild approach is promising and it is believed it will shed more light on the preparation of high-efficiency and high-performance energy storage materials based on functional reductive CDs.

A review: strategies to reduce infection in tantalum and its derivative applied to implants.

Implant-associated infection is the main reasons for implant failure. Titanium and titanium alloy are currently the most widely used implant materials. However, they have limited antibacterial performance. Therefore, enhancing the antibacterial ability of implants by surface modification technology has become a trend of research. Tantalum is a potential implant coating material with good biological properties. With the development of surface modification technology, tantalum coating becomes more functional through improvement. In addition to improving osseointegration, its antibacterial performance has also become the focus of attention. In this review, we provide an overview of the latest strategies to improve tantalum antibacterial properties. We demonstrate the potential of the clinical application of tantalum in reducing implant infections by stressing its advantageous properties.

Immunomodulatory effect of IL-2 induced bone marrow mononuclear cell therapy on control of allergic asthma.

Asthma is a chronic airway disease. Allergic reactions and T helper (h)2 immune response play a key role in asthma occurrence. Cell therapy can control inflammation and remodeling responses in allergic asthma, and cytokines can change this effect. Therefore, in this study, the effect of treated cell therapy with IL-2 to control allergic asthma was studied. Bone marrow cells were extracted and co-cultured with IL-2 and the cells were used via intra-tracheal administration in allergic asthma mice. Levels of IL-4, IL-5, IL-13, Leukotriene B4 and C4, and remodeling factors were measured. At least, a histopathology test of lung tissue was done. Type2 cytokines, leukotrienes, remodeling factors, mucus secretion, goblet cell hyperplasia, peri-bronchial and peri-vascular inflammation were significantly (p˂0.05) decreased by treating with bone marrow-derived mononuclear cells (BMDMCs) and IL-2-BMDMCs. Treatment with IL-2-BMDMCs could significantly decrease IL-13, transforming growth factor (TGF)-ß, HP levels, and mucus secretion (p˂0.05) compared to BMDMCs treatment. In this study, BMDMCs and IL-2-BMDMCs therapy could decrease inflammation, allergic, and remodeling factors in allergic asthma. Cell therapy with BMDMCs had a strong and notable effect on the control of allergic asthma pathophysiology when co-cultured and used with IL-2.

Immunomodulatory effect of IL-2 induced bone marrow mononuclear cell therapy on control of allergic asthma

Asthma is a chronic airway disease. Allergic reactions and T helper (h)2 immune response play a key role in asthma occurrence. Cell therapy can control inflammation and remodeling responses in allergic asthma, and cytokines can change this effect. Therefore, in this study, the effect of treated cell therapy with IL-2 to control allergic asthma was studied. Bone marrow cells were extracted and co-cultured with IL-2 and the cells were used via intra-tracheal administration in allergic asthma mice. Levels of IL-4, IL-5, IL-13, Leukotriene B4 and C4, and remodeling factors were measured. At least, a histopathology test of lung tissue was done. Type2 cytokines, leukotrienes, remodeling factors, mucus secretion, goblet cell hyperplasia, peri-bronchial and peri-vascular inflammation were significantly (p˂0.05) decreased by treating with bone marrow-derived mononuclear cells (BMDMCs) and IL-2-BMDMCs. Treatment with IL-2-BMDMCs could significantly decrease IL-13, transforming growth factor (TGF)-β, HP levels, and mucus secretion (p˂0.05) compared to BMDMCs treatment. In this study, BMDMCs and IL-2-BMDMCs therapy could decrease inflammation, allergic, and remodeling factors in allergic asthma. Cell therapy with BMDMCs had a strong and notable effect on the control of allergic asthma pathophysiology when co-cultured and used with IL-2 (AU)

Heterotrophic anodic denitrification coupled with cathodic metals recovery from on-site smelting wastewater with a bioelectrochemical system inoculated with mixed Castellaniella species.

Although Castellaniella species are crucial for denitrification, there is no report on their capacity to carry out denitrification and anode respiration simultaneously in a bioelectrochemical system (BES). Herein, the ability of a mixed inoculum of electricigenic Castellaniella species to perform simultaneous denitrification and anode respiration coupled with cathodic metals recovery was investigated in a BES. Results showed that 500 mg/L NO3--N significantly decreased power generation, whereas 100 and 250 mg/L NO3--N had a lesser impact. The single-chamber MFCs (SCMFCs) fed with 100 and 250 mg/L NO3--N concentrations achieved a removal efficiency higher than 90% in all cycles. In contrast, the removal efficiency in the SCMFCs declined dramatically at 500 mg/L NO3--N, which might be attributable to decreased microbial viability as revealed by SEM and CLSM. EPS protein content and enzymatic activities of the biofilms decreased significantly at this concentration. Cyclic voltammetry results revealed that the 500 mg/L NO3--N concentration decreased the redox activities of anodic biofilms, while electrochemical impedance spectroscopy showed that the internal resistance of the SCMFCs at this concentration increased significantly. In addition, BES inoculated with the Castellaniella species was able to simultaneously perform heterotrophic anodic denitrification and cathodic metals recovery from real wastewater. The BES attained Cu2+, Hg2+, Pb2+, and Zn2+ removal efficiencies of 99.86 ± 0.10%, 99.98 ± 0.014%, 99.98 ± 0.01%, and 99.17 ± 0.30%, respectively, from the real wastewater. Cu2+ was bio-electrochemically reduced to Cu0 and Cu2O, whereas Hg0 and HgO constituted the Hg species recovered via bioelectrochemical reduction and chemical deposition, respectively. Furthermore, Pb2+ and Zn2+ were bio-electrochemically reduced to Pb0 and Zn0, respectively. Over 89% of NO3--N was removed from the BES anolyte during the recovery of the metals. This research reveals promising denitrifying exoelectrogens for enhanced power generation, NO3--N removal, and heavy metals recovery in BES.

Deep Learning-Based System for Disease Screening and Pathologic Region Detection From Optical Coherence Tomography Images.

Purpose: This study was designed to apply deep learning models in retinal disease screening and lesion detection based on optical coherence tomography (OCT) images. Methods: We collected 37,138 OCT images from 775 patients and labelled by ophthalmologists. Multiple deep learning models including ResNet50 and YOLOv3 were developed to identify the types and locations of diseases or lesions based on the images. Results: The model were evaluated using patient-based independent holdout set. For binary classification of OCT images with or without lesions, the performance accuracy was 98.5%, sensitivity was 98.7%, specificity was 98.4%, and the F1 score was 97.7%. For multiclass multilabel disease classification, the models was able to detect vitreomacular traction syndrome and age-related macular degeneration both with an accuracy of more than 99%, sensitivity of more than 98%, specificity of more than 98%, and an F1 score of more than 97%. For lesion location detection, the recalls for different lesion types ranged from 87.0% (epiretinal membrane) to 98.2% (macular pucker). Conclusions: Deep learning-based models have potentials to aid retinal disease screening, classification and diagnosis with excellent performance, which may serve as useful references for ophthalmologists. Translational Relevance: The deep learning-based models are capable of identifying and predicting different eye diseases and lesions from OCT images and may have potential clinical application to assist the ophthalmologists for fast and accuracy retinal disease screening.

Is the Triggering of PD-L1 Dimerization a Potential Mechanism for Food-Derived Small Molecules in Cancer Immunotherapy? A Study by Molecular Dynamics.

Using small molecules to inhibit the PD-1/PD-L1 pathway is an important approach in cancer immunotherapy. Natural compounds such as capsaicin, zucapsaicin, 6-gingerol and curcumin have been proposed to have anticancer immunologic functions by downregulating the PD-L1 expression. PD-L1 dimerization promoted by small molecules was recently reported to be a potential mechanism to inhibit the PD-1/PD-L1 pathway. To clarify the molecular mechanism of such compounds on PD-L1 dimerization, molecular docking and molecular dynamics simulations were performed. The results evidenced that these compounds could inhibit PD-1/PD-L1 interactions by directly targeting PD-L1 dimerization. Binding free energy calculations showed that capsaicin, zucapsaicin, 6-gingerol and curcumin have strong binding ability with the PD-L1 dimer, where the affinities of them follow the trend of zucapsaicin > capsaicin > 6-gingerol ≈ curcumin. Analysis by residue energy decomposition, contact numbers and nonbonded interactions revealed that these compounds have a tight interaction with the C-sheet, F-sheet and G-sheet fragments of the PD-L1 dimer, which were also involved in the interactions with PD-1. Moreover, non-polar interactions between these compounds and the key residues Ile54, Tyr56, Met115 and Ala121 play a key role in stabilizing the protein−ligand complexes in solution, in which the 4'-hydroxy-3'-methoxyphenyl group and the carbonyl group of zucapsaicin, capsaicin, 6-ginger and curcumin were significant for the complexation of small molecules with the PD-L1 dimer. The conformational variations of these complexes were further analyzed by free energy landscape (FEL) and principal component analysis (PCA) and showed that these small molecules could make the structure of dimers more stable. This work provides a mechanism insight for food-derived small molecules blocking the PD-1/PD-L1 pathway via directly targeting the PD-L1 dimerization and offers theoretical guidance to discover more effective small molecular drugs in cancer immunotherapy.

Small vessel disease burden predicts functional outcomes in patients with acute ischemic stroke using machine learning.

AIMS: Our purpose is to assess the role of cerebral small vessel disease (SVD) in prediction models in patients with different subtypes of acute ischemic stroke (AIS). METHODS: We enrolled 398 small-vessel occlusion (SVO) and 175 large artery atherosclerosis (LAA) AIS patients. Functional outcomes were assessed using the modified Rankin Scale (mRS) at 90 days. MRI was performed to assess white matter hyperintensity (WMH), perivascular space (PVS), lacune, and cerebral microbleed (CMB). Logistic regression (LR) and machine learning (ML) were used to develop predictive models to assess the influences of SVD on the prognosis. RESULTS: In the feature evaluation of SVO-AIS for different outcomes, the modified total SVD score (Gain: 0.38, 0.28) has the maximum weight, and periventricular WMH (Gain: 0.07, 0.09) was more important than deep WMH (Gain: 0.01, 0.01) in prognosis. In SVO-AIS, SVD performed better than regular clinical data, which is the opposite of LAA-AIS. Among all models, eXtreme gradient boosting (XGBoost) method with optimal index (OI) has the best performance to predict excellent outcome in SVO-AIS. [0.91 (0.84-0.97)]. CONCLUSIONS: Our results revealed that different SVD markers had distinct prognostic weights in AIS patients, and SVD burden alone may accurately predict the SVO-AIS patients' prognosis.