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Introduction: Hyperuricemia may be involved in the phenotypic transformation of vascular smooth muscle cells, thus promoting the occurrence of atherosclerosis, and autophagy may be one of the important links, but little is known about the specific molecular mechanism. Methods: We established a mouse model of hyperuricemia and studied the relationship between changes in autophagy levels and the phenotypic transformation of muscle cells. Results: Our study found that high uric acid levels promote the phenotypic transformation of muscle cells by inhibiting autophagy, thus enhancing their proliferation and migration abilities. If autophagy is restored, phenotypic transformation can be reversed by reducing the levels of the transcription factor Kruppel-like factor 4. Conclusion: Uric acid may induce the phenotypic transformation of muscle cells and promote the occurrence of atherosclerosis by disrupting normal autophagy. [ABSTRACT FROM AUTHOR]

Problem: Pemphigus vulgaris may worsen during pregnancy, leading to both maternal and fetal complications. The relationship between pemphigus vulgaris and pregnancy remains unclear, and the outcomes and treatments of pemphigus vulgaris during pregnancy have not been extensively discussed. Method of Study: This article systematically reviews the literature, focusing on the relationship between pemphigus vulgaris and pregnancy. We conducted comprehensive searches in PubMed, Embase, Cochrane Library, and Web of Science databases, identifying 42 studies reporting the disease course, pregnancy outcomes, and management of both pregnancy and pemphigus vulgaris. Results: A total of 57 cases were included in the analysis, categorized into three distinct forms: pemphigus vulgaris onset before pregnancy (n = 33), onset during pregnancy (n = 20), and onset during the postpartum period (n = 4). Fifty four cases reported treatment strategies, among them, 44 cases (81.5%) initially received systemic corticosteroid therapy during pregnancy. Out of these cases, 7 (15.9%) did not achieve successful remission and required alternative treatment approaches. In terms of pregnancy outcomes, 23 out of 62 neonates (37.1%) exhibited skin lesions or tested positive for anti‐dsg IgG in their serum, while 16 neonates (25.8%) experienced other complications. Conclusions: These findings highlight the importance of effectively managing pemphigus vulgaris during pregnancy to ensure optimal outcomes. [ABSTRACT FROM AUTHOR]

A multifunctional silicon carbide (6H–SiC) material with efficient wicking and evaporative cooling performances in a temperature range of 23–180 °C is created through hierarchical surface nano/microstructuring by a femtosecond laser. The elaborated hierarchical surface structure is an array of nanotextured microgrooves that includes structural features in a range between about 15 nm and 140 μm, integrating benefits from micro- and nanoscale physics of capillarity and thermodynamics. The spatiotemporal dynamics of both water spreading and temperature field obtained by optical and infrared imaging show the excellent wicking and evaporative cooling functionalities of the created material. The range of applications of the developed multifunctional 6H–SiC material includes the technologies for enhancing power generation efficiency, waste heat recovery, and cooling high-heat-flux Si- and SiC-based electronic devices. The application of the created material in cooling technologies for power generation can result in substantial fuel savings and global reduction in greenhouse gas emissions. [ABSTRACT FROM AUTHOR]

Summary: Characterization and genetic engineering of plant transporters involved in the pesticide uptake and translocation facilitate pesticide relocation to the tissue where the pests feed, thus improving the bioavailability of the agrichemicals. We aimed to identify thiamethoxam (THX) transporters in rice and modify their expression for better brown planthopper (BPH) control with less pesticide application. A yeast library expressing 1385 rice transporters was screened, leading to the identification of an amino acid transporter‐like (ATL) gene, namely OsATL15, which facilitates THX uptake in both yeast cells and rice seedlings. In contrast to a decrease in THX content in osatl15 knockout mutants, ectopic expression of OsATL15 under the control of the CaMV 35S promoter or a vascular‐bundle‐specific promoter gdcsPpro significantly increased THX accumulation in rice plants, thus further enhancing the THX efficacy against BPH. OsATL15 was localized in rice cell membrane and abundant in the root transverse sections, vascular bundles of leaf blade, and stem longitudinal sections, but not in hull and brown rice at filling stages. Our study shows that OsATL15 plays an essential role in THX uptake and its systemic distribution in rice. OsATL15 could be valuable in achieving precise pest control by biotechnology approaches. [ABSTRACT FROM AUTHOR]

• Propose an ensemble model-based method for estimating failure probability function. • Different surrogate models and PDF approximation methods are studied and used. • A novel convergence criterion as well as a learning function is presented to assist the ensemble model. • A real-world RBO problem of a hydraulic pipeline system is effectively solved by the proposed method. The failure probability function (FPF) is a function of failure probability that varies with distribution parameters of random inputs, and is required in reliability-based optimization. To estimate the failure probability at each possible value of distribution parameters, it is necessary to conduct a great quantity of model evaluations. This results in a huge computational burden especially in practical engineering applications. The introduction of surrogate models effectively improves the computational efficiency by constructing a cheap-to-evaluate metamodel to approximate the true performance function. However, it is tough to determine which surrogate model is a prior when the performance function is extremely complex or even implicit. Based on the Bayes' rule and augmented theory, this paper proposes an ensemble model method for estimating the FPF. Since the ensemble model utilizes each individual surrogate's capacity to predict outcomes by using a weighted form to combine numerous surrogate models and eliminates the trouble of seeking a proper individual model, it possesses better estimation accuracy and generalization ability than the individual surrogate model. Several examples have proved that the proposed ensemble model method for estimating the FPF not only further improves the computational efficiency but also gets sufficiently accurate estimation. Finally, the reliability-based optimization of a hydraulic pipeline system under random excitation is solved effectively by the proposed method. [ABSTRACT FROM AUTHOR]

Background: Rosacea is a chronic inflammatory disease mainly with skin or ocular manifestations. Topical calcineurin inhibitors, pimecrolimus and tacrolimus, can be used to treat rosacea. However, they can also induce rosacea‐like eruptions. Aims: This study systematically reviewed the double‐edged sword effects of pimecrolimus and tacrolimus on rosacea. Methods: Four databases were retrieved to search for articles on the effects of pimecrolimus and tacrolimus on rosacea, including Cochrane Library, Embase, PubMed, and Web of Science. Only English articles were included in the systematic review. Relevant data were collected, and the levels of evidence were evaluated. Results: 28 articles published between 2001 and 2016 were included. 11 articles were about pimecrolimus as the treatment of rosacea, 4 articles were about the pimecrolimus‐induced rosacea, 9 articles were about tacrolimus as the treatment of rosacea, and 4 articles were about tacrolimus‐induced rosacea. Participants for each study ranged from 1 to 200. Several types of outcome measurements were used for these publications. Conclusions: Both pimecrolimus and tacrolimus might have double‐edged sword effects on rosacea. Pimecrolimus and tacrolimus could be effective for rosacea. However, both of them could also induce rosacea. Larger, randomized, controlled studies on pimecrolimus and tacrolimus as the treatment of rosacea and studies on the mechanisms of pimecrolimus and tacrolimus in treating or inducing rosacea are needed. This systematic review emphasized the double‐edged sword role of topical calcineurin inhibitors in rosacea, which may pave the way for future research. [ABSTRACT FROM AUTHOR]

Rosacea is a chronic inflammatory disease characterized by facial flushing, erythema, telangiectasia, papules, and pustules. Its pathogenesis has not been fully understood. In 2017, the global ROSacea COnsensus (ROSCO) panel updated the diagnosis, classification, and assessment of rosacea. Phenotype‐based treatments and long‐term managements have also been recommended. Murine models are a powerful tool in unveiling and dissecting the mechanisms of human diseases. Here, we summarized murine models of rosacea developed or used in previous research, including LL‐37 intradermal injection model, KLK‐5‐induced inflammation model, croton oil inflammation model, 12‐O‐Tetradecanoylphorbol‐13‐acetate inflammation model, arachidonic acid inflammation model, RTX‐induced vasodilation model, and UVB‐induced model. LL‐37 injection model has become the most intensively used model in rosacea research. Each model could show the pathophysiological and clinical features of rosacea to some extent. However, no model can show the full picture of the characteristics of rosacea. Improving existed murine models, developing new murine models, and applying them to pathogenesis and treatment research on rosacea are highly warranted in the future. [ABSTRACT FROM AUTHOR]

The body donation program of Peking Union Medical College was established in May 1999. From May 1999 to December 2017, a total of 5,576 registrants registered and 1,459 donors donated their bodies. Demographic and medical characteristics of the donors were analyzed. The top four causes of death were neoplasms, heart diseases, respiratory diseases, and cerebrovascular diseases. Age at death among donors who died of neoplasms were significantly lower than other causes of death (all p <.05), and the interval between registration and donation among donors who died of neoplasms was significantly shorter than that among donors with other causes (all p <.001). The age of donors when they registered (p <.001) and donated (p <.001) was significantly older than that of general Beijing population. This study may provide a guide for medical colleges or research institutions to establish or enhance their own body donation programs. [ABSTRACT FROM AUTHOR]

When dealing with complex reliability problems, the classical ensemble of surrogate models (CESM) has better ability of prediction and generalization than the individual surrogate model. However, since the CESM only considers the global errors of the sample set, the prediction results of the sample points far away from the region where most of the samples gather might not be so accurate, and the fitting accuracy of the limit state function will also be affected when the sample points are sparse. In view of the above situation, this paper proposes an adaptive ensemble of surrogate models based on hybrid measure (AESMHM), which comprehensively considers the global errors and local errors. The global weight matrix is modified by the local weight matrix of representative sample points to obtain the hybrid weight of each surrogate model. Through the discussion of four examples, it can be proved that AESMHM can not only improve the prediction accuracy of the whole sample points, but also have higher computational efficiency. Finally, the reliability problem of a radome structure in composite material is solved efficiently by the proposed method. [ABSTRACT FROM AUTHOR]

Polarized photodetectors have been widely used in military and civilian applications. The investigation of promising two-dimensional materials with low symmetry structures will be of great significance for the development of polarized integrated nanodevices. In this work, chromium thiophosphate (CrPS4), a ternary layered semiconductor with low symmetry puckered structures and unique linear dichroism (LD) conversion behavior is introduced to act as a polarization-sensitive photodetector. Angle-resolved polarized Raman spectra (ARPRS), polarization-resolved photoluminescence (PL) spectra, polarization-resolved absorption spectroscopy (PRAS), and electrical transport measurement systematically indicate intriguing anisotropic optical and electrical properties in 2D (two-dimensional) CrPS4. The photodetector of CrPS4 shows a linear anisotropy ratio of ≈1.33 with 405 nm illumination. This pioneering research not only stimulates interest in the development of novel anisotropic 2D materials but also enriches the family of polarization-sensitive photodetectors. [ABSTRACT FROM AUTHOR]

Introduction: Dermatologists play essential roles in providing dermatology consultations to inpatients admitted to hospital for care in another speciality ward. Data on dermatology consultations provided to inpatients admitted to general surgery wards are limited. The aim of this study was to analyze the reasons for and diagnoses of consultations provided by dermatologists to hospitalized patients in a general surgery ward and compare the provisional diagnoses by surgical residents and the final diagnoses by dermatologists. Methods: Electronic health records were retrieved for patients admitted to a general surgery ward who received dermatology consultations while inpatients in Peking Union Medical College Hospital between 1 September 2015 and 31 August 2020. Sex, age, surgical diagnosis, reason for dermatology consultation, provisional diagnosis by surgical residents, and final diagnosis by dermatologists were reviewed. Results: A total of 262 dermatology consultations for 251 patients (n = 251, 123 women and 128 men) were identified, of whom 240 (95.6%) required only one consultation and 11 (4.4%) required two. Dermatology consultations were classified into three categories: preoperative consultation (n = 45, 17.9%), postoperative consultation (n = 65, 25.9%), and consultation unrelated to general surgery diseases or treatments (including surgery) (n = 141, 56.2%). For consultations falling in the category preoperative consultation, common reasons for the consultation were: to evaluate whether the current treatment plan for previously diagnosed skin diseases needed to be changed; to evaluate and manage skin problems that emerged after admission; to evaluate syphilis; and to evaluate whether previously diagnosed skin diseases would affect surgical incision or wound healing. Drug eruption, dermatitis/eczema, infectious skin disorders, and urticaria were the most common skin diseases in the hospitalized general surgery patients. Only 32 (12.7%) provisional diagnoses were made, of which 25 (78.1%) were correct and seven (21.9%) were incorrect. Surgical residents mainly had difficulty distinguishing herpes zoster, drug eruption, and infectious skin disorders from dermatitis/eczema. Conclusion: Our results facilitate the understanding of inpatient dermatology consultations in general surgery wards and may help in the design of future educational materials and/or management guidelines. [ABSTRACT FROM AUTHOR]

In order to overcome the issues of thrust saturation, uneven energy consumption and suboptimal control associated with the traditional hierarchical control strategy employed in ship dynamic positioning (DP) systems, an integrative control allocation strategy is proposed by combining the low-level thrust allocation into the high-level motion controller. The proposed scheme is implemented via the neural network-based nonlinear predictive control (NNPC) and solved via an improved particle swarm optimization (PSO) algorithm. A data-driven recurrent neural network (RNN) ship motion and thrust allocation model is off-line identified based only on the current and historical measured output and thrust input data. Utilizing the established RNN model to predict the future multi-step outputs, and combining the motion control, the thruster energy consumption and the thruster wear and tear as an integrative control objective, the integrated NNPC online optimization problem with thruster constraints is established and solved by an improved evolution algorithm of PSO. Simulations are respectively carried out for setpoint regulation and trajectory tracking. Simulation results well demonstrate the feasibility and superiority of the proposed control strategy. • The thrust allocation and motion controller are combined as an integrative NMPC problem. • A data-driven RNN integrative model for ship motion and thrust allocation is built. • The integrative control strategy of neural network predictive control (NNPC) is proposed. • The integrated NNPC constrained optimization problem is solved by improved PSO. • The feasibility and effectiveness of the proposed method are verified. [ABSTRACT FROM AUTHOR]

Raynaud's phenomenon is a common disorder affecting body extremities and other vascular beds. As infodemiological methods have developed, online search tools could be used to explore the public interest of the disease. The study aimed to determine the annual trend, seasonal pattern, and associated topics of Raynaud's phenomenon. Google Trends was used to collect the data. "Raynaud syndrome" was selected as the search term. Data on monthly relative search volume (RSV) were collected from four selected countries (United States, United Kingdom, Australia, and New Zealand) and globally. Related topics were obtained, and annual‐related topics were also collected for analysis. The maximum RSV appeared in January 2019, and the minimum value was observed in August 2011. The peak for RSV occurred in winter, and the bottom appeared in summer. In top related topics, "Maurice Raynaud" was the most related. In rising related topics, disease manifestations and autoimmune connective diseases were highly concerned. For annual‐related topics, associated diseases were attracting more attention over time. The population is interested in related diseases, pathogenesis, and treatment. There was a peak in winter for searching and supported the importance of season variation on the impact of Raynaud's phenomenon. [ABSTRACT FROM AUTHOR]

Background: Alopecia is a common disease influencing the quality of life of the patients. Botulinum toxin has been widely employed in cosmetic dermatology and was applied in some clinical trials to treat alopecia. Aims: Hence, We conducted a systematic review to examine the safety and efficacy of using botulinum toxin in treating alopecia. Methods: Cochrane Library, Embase, PubMed, and Web of Science databases were used to search for articles. A PICOS question was formed and the author, year of publication, number of participants, study design, product, dilution and dosing, outcome measurement, findings, side effects, and follow‐up were retrieved. The Oxford Centre for Evidence‐Based Medicine 2011 Levels of Evidence was used as a qualitative indicator to evaluate the levels of evidence. Results: Eleven articles published between 2005 and 2019 were included. 9 of which were about treatment effects and 2 were concerning adverse effects. The total number of the participants was 106, and the number for each article was ranged from 1 to 50. Varying type of outcome measurements was used for the publications. 8 articles were evaluated as Level 4 and 1 was evaluated as Level 5 during the 9 articles with treatment effects. Conclusions: The results showed that botulinum toxin may function as a double‐edged sword and have a low degree of efficacy and safety in treating alopecia. The study may be useful to remind the physicians of adverse effects in clinical practice and pave the way for further research. A larger, randomized, placebo‐controlled study is warranted. [ABSTRACT FROM AUTHOR]

• A 2D Bi 2 MoO 6 /CQDs photocatalyst was prepared by hydrothermal method. • 2D Bi 2 MoO 6 /CQDs showed good visible and near-infrared light Hg0 removal performance. • The introduction of CQDs reduced the carrier recombination rate of 2D Bi 2 MoO 6. • 2D Bi 2 MoO 6 /CQDs owned UPCL characteristics. Carbon quantum dots (CQDs) was prepared and supported on 2D Bi 2 MoO 6 by hydrothermal method to prepare 2D Bi 2 MoO 6 /CQDs composite photocatalyst with up-conversion luminescence (UPCL) characteristics. The properties of 2D Bi 2 MoO 6 /CQDs were characterized by a series of characterization tools. Then, 2D Bi 2 MoO 6 and 2D Bi 2 MoO 6 /CQDs catalysts were applied to photocatalytic Hg0 removal. The experimental results show that Hg0 removal efficiency of 2D Bi 2 MoO 6 /CQDs increased from 30.5% to 80.1% under visible light and from 7.2% to 26.4% under near-infrared light compared with 2D Bi 2 MoO 6. The photostability test shows that 2D Bi 2 MoO 6 /CQDs nanocomposites could maintain high photostability after five photoreaction cycles. UPCL test proved that CQDs had the ability to absorb infrared light and emit visible light, thus expanding the light utilization range of composite catalyst. Moreover, in N 2 +6%O 2 +12%CO 2 +NO atmosphere, Hg0 removal efficiency of 2D Bi 2 MoO 6 /CQDs first dropped and then raised with the increase of NO concentration due to the simultaneous reduction and oxidation of NO in the system. Finally, the ESR test shows that the modification of CQDs could not only enhance light absorption rang of photocatalyst, but also promote the transfer of photogenerated carriers on the catalyst surface, thereby enhancing the photocatalytic Hg0 removal capability of the 2D Bi 2 MoO 6 /CQDs catalyst. [ABSTRACT FROM AUTHOR]

The performance, microbial enzymatic activity and microbial community of a sequencing batch reactor (SBR) were explored under instantaneous Cd(II) shock loading. After a 24-h Cd(II) shock loading of 100 mg/L, the chemical oxygen demand and NH 4 +-N removal efficiencies decreased significantly from 92.73% and 99.56% on day 22 to 32.73% and 43% on day 24, respectively, and then recovered to the normal values gradually. The specific oxygen utilization rate (SOUR), specific ammonia oxidation rate (SAOR), specific nitrite oxidation rate (SNOR), specific nitrite reduction rate (SNIRR) and specific nitrate reduction rate (SNRR) decreased by 64.81%, 73.28%, 77.77%, 56.84% and 52.46% on day 23 in comparison with the absence of Cd(II) shock loading, respectively, and they gradually returned to the normal levels. The changing trends of their associated microbial enzymatic activities including dehydrogenase, ammonia monooxygenase, nitrite oxidoreductase, nitrite reductase and nitrate reductase were in accordance with SOUR, SAOR, SNOR, SNIRR and SNRR, respectively. Cd(II) shock loading promoted the microbial reactive oxygen species production and lactate dehydrogenase release, indicating that instantaneous shock caused oxidative stress and damaged to cell membranes of the activated sludge. The microbial richness and diversity, and the relative abundance of Nitrosomonas and Thauera obviously decreased under the stress of Cd(II) shock loading. PICRUSt prediction showed that Cd (II) shock loading significantly affected Amino acid biosynthesis, Nucleoside and nucleotide biosynthesis. The present results are conducive to take adequate precautions to reduce the adverse effect on bioreactor performance in wastewater treatment systems. [Display omitted] • The COD and NH 4 +-N removal sharply decreased under the Cd(II) shock loading. • The Cd(II) shock inhibited nitrogen removal rates and microbial enzymatic activities. • The Cd(II) shock induced the ROS production and LDH release of activated sludge. • The Cd(II) shock reduced the microbial richness and diversity obviously. • The SBR performance gradually recovered after the instantaneous Cd(II) shock. [ABSTRACT FROM AUTHOR]

Abstract To determine the effects of organic amendment on communities of ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA) in rice-wheat rotation ecosystem, a long-term plot experiment with 5 treatments was conducted, and the temporal dynamics (10 growth stages) and spatial distribution (0–100 cm) of AOB and AOA abundance were determined using qPCR. The five treatments were as follows: no fertilizer control (CK), regular fertilization (RT), straw returning (SR), straw biochar returning (SB) and organic-chemical mixed fertilization (MF). The results showed the following. 1) Organic addition did not affect the temporal dynamics of AOB abundance but altered those of AOA abundance. Relative to RT, SR and MF significantly lowered AOB population sizes across the 10 sampling time points by 34.49% and 16.42%, respectively, whereas no significant differences in total AOA population size were observed among the 4 fertilization regimes. 2) Compared with the other treatments, treatments involving organic addition had higher total AOB abundance in the 0–100 cm soil layer. However, SB was the only treatment with organic addition that had a significantly higher total AOA abundance than RT (by 24.91%). 3) Under organic addition, the potential nitrification rate (PNR) was still highly correlated with AOB abundance (P < 0.01) but not AOA abundance. [ABSTRACT FROM AUTHOR]

The Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS/PUMC) Human Brain Bank was established in December 2012 and had accomplished 197 brain donations by November 2017. The brain bank was based on a large-scale willed body donation program in CAMS/PUMC starting from 1999. Demographic and medical characteristic analysis of brain donors was conducted to facilitate the construction of the brain bank. The average postmortem delay of brain donors was 17.7 h and 77.7% of these donors died less than 15 km away from the brain bank. Donors were predominantly with higher-level education (p < 0.001) and at an older age when registration (p < 0.001) and donation (p < 0.001) occurred. Our results elucidated the characteristics of donors in the CAMS/PUMC Human Brain Bank, which may provide useful information to target potential donors and improve the quality and quantity of brain specimens. The current study may pave the way for the construction of a nationwide network of standardized human brain banks in China. [ABSTRACT FROM AUTHOR]

Background: Previous observational studies reported altered melanoma risks in relation to many potential factors, such as coffee intake, smoking habits and photodamage‐related conditions. Considering the susceptibility of epidemiological studies to residual confounders, there remains uncertainty about the actual causal roles of these reported factors in melanoma aetiology. Objectives: This study aims to investigate the causal association between cutaneous melanoma (CM) and previously reported factors: coffee intake, alcohol consumption, lifetime smoking, socioeconomic status (SES), ease of skin tanning, childhood sunburn and facial ageing, providing insight into its underlying aetiology and preventative strategies. Methods: We utilized a two‐sample MR analysis on data from the largest meta‐analysis summary statistics of confirmed cutaneous melanoma including 30,134 patients. Genetic instrumental variables were constructed by identifying single nucleotide polymorphisms (SNPs) that associate with corresponding factors. Inverse variance weighted (IVW) was the primary MR method. For sensitivity and heterogeneity, MR Egger, weighted median, simple mode, weighted mode and MR Egger intercept tests were examined. Results: Cutaneous melanoma risks were found to be elevated in association with a predisposition towards ease of skin tanning (IVW: OR = 2.842, 95% CI 2.468–3.274, p < 0.001) and with childhood sunburn history (IVW: OR = 6.317, 95% CI 4.479–8.909, p < 0.001). Repeated MR after removing potential confounders and outliers demonstrated resolved horizontal pleiotropy and statistically significant results that closely mirrored the initial findings. Other potential factors, such as coffee intake, alcohol consumption, smoking and socioeconomic status (SES), indicated insignificant effects on melanoma risk in the analysis, and therefore, our Mendelian randomization study does not support their roles in modifying melanoma risks. Conclusions: Our extensive MR analysis provides strong evidence of the causative role of ease of skin tanning and childhood sunburn history in elevating melanoma risk. Curtailing ultraviolet radiation (UVR) exposure may be the single best preventative strategy to reduce melanoma risk. [ABSTRACT FROM AUTHOR]

With extension of the average lifespan, aging has become a heavy burden in society. Immune senescence is a key risk factor for many age-related diseases such as cancer and increased infections in the elderly, and hence has elicited much attention in recent years. As our body's guardian, the immune system maintains systemic health through removal of pathogens and damage. Autophagy is an important cellular ‘clearance’ process by which a cell internally delivers damaged organelles and macromolecules to lysosomes for degradation. Here, we discuss the most current knowledge of how impaired autophagy can lead to cellular and immune senescence. We also provide an overview, with examples, of the clinical potential of exploiting autophagy to delay immune senescence and/or rejuvenate immunity to treat various age-related diseases. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX) is a potent anthracycline antineoplastic drug. However, its dose-dependent cardiotoxicity limits its clinical application. Ononin is a natural isoflavone glycoside that is crucial in modulating apoptosis-related signaling pathways. In this study, we assessed the possible cardioprotective effects of ononin in DOX-induced cardiotoxicity and elucidated the underlying molecular mechanisms. In vitro and in vivo assessments were performed using DOX-treated H9C2 cells and rats, respectively. First, DOX was injected into the tail veins of Wistar rats to induce cardiomyopathy. Next, rats in the DOX + Ononin30 and DOX + Ononin60 groups were intragastrically administered ononin two weeks before DOX treatment. H9C2 cells were treated with vehicle or DOX with or without ononin. Next, 3-TYP was used to determine the relationship between endoplasmic reticulum (ER) stress and sirtuin 3 (SIRT3) expression. Ononin treatment ameliorated DOX-induced myocardial injury as determined by echocardiography. Furthermore, ononin partially restored DOX-induced cardiac dysfunction; the left ventricular ejection fraction (LVEF) and left ventricular systolic fractional shortening (LVFS) increased after pre-treatment with ononin. Further, ononin suppressed DOX-induced ER stress and apoptosis in rat cardiomyocytes and H9C2 cells. The Bax/Bcl-2 ratio and 78-kD glucose-regulated protein (GRP78) and CCAAT enhancer-binding protein (CHOP) expression levels were higher in the DOX-treated group than in the control group but ononin treatment improved these parameters. These effects are associated with SIRT3 activity. Moreover, 3-TYP blocked the ononin-mediated protective effects. Hence, ononin positively affected DOX-induced cardiotoxicity by inhibiting ER stress and apoptosis, possibly mediated by stimulation of the SIRT3 pathway. [Display omitted] • Ononin prevented DOX-induced cardiac tissue damage in vivo. • Ononin inhibited DOX-induced apoptosis in vivo and in vitro. • Ononin inhibited DOX-induced ER stress in vivo and in vitro. • Ononin adjusted SIRT3 level in vivo and in vitro. • 3-TYP(a selective SIRT3 inhibitor) reversed the effect of Ononin in vivo and in vitro. [ABSTRACT FROM AUTHOR]

• Hydraulic resistance of supercritical H 2 O/CO 2 mixtures is experimentally studied. • Friction factor of H 2 O/CO 2 mixtures features a deeper and wider pit than H 2 O. • A new correlation is developed with a root mean square error as low as 7.9%. Hydraulic resistance of H 2 O/CO 2 mixtures for supercritical conditions, typical for a promising power generation system, has been a knowledge gap. In this work, it was experimentally investigated in a high-temperature, high-pressure, and multi-function apparatus and was further correlated. For the experimental conditions, the CO 2 mass fractions were 10, 15, and 18.5%, the pressure was 24 MPa, the temperatures were 300–430℃, and the mass fluxes were 900–1500 kg m −2 s −1. Results show that the friction factor curve for supercritical H 2 O/CO 2 mixtures features a pit near the pseudo-critical point, which is more significant and wider compared to supercritical pure water. This is caused by crossing two-phase region and distinct thermophysical property variation with the temperature. Based on these understandings, a new friction factor correlation with a root mean square error as low as 7.9% was developed for supercritical H 2 O/CO 2 mixtures. The friction factor of the supercritical pure water was used as the basis and two correction factors were used to interpret the two-phase effect and the thermophysical property variations. [ABSTRACT FROM AUTHOR]

• Propose a general hierarchical ensemble-learning framework for reliability analysis. • Two-layer models cooperate with each other to fit the limit state function. • The entire training process is divided into three different phases. • A method called CESM-ELF is proposed to check the framework's effectiveness. • The proposed framework can improve the prediction accuracy of ensemble-learning. Existing ensemble-learning methods for reliability analysis are usually developed by combining ensemble-learning with a learning function. A commonly used strategy is to construct the initial training set and the test set in advance. The training set is used to train the initial ensemble model, while the test set is adopted to allocate weight factors and check the convergence criterion. Reliability analysis focuses more on the local prediction accuracy near the limit state surface than the global prediction accuracy in the entire space. However, samples in the initial training set and the test set are generally randomly generated, which will result in the learning function failing to find the real "best" update samples and the allocation of weight factors may be suboptimal or even unreasonable. These two points have a detrimental impact on the overall performance of the ensemble model. Thus, we propose a general hierarchical ensemble-learning framework (ELF) for reliability analysis, which consists of two-layer models and three different phases. A novel method called CESM-ELF is proposed by embedding the classical ensemble of surrogate models (CESM) in the proposed ELF. Four examples are investigated to show that CESM-ELF outperforms CESM in prediction accuracy and is more efficient in some cases. [ABSTRACT FROM AUTHOR]

Coal gasification is one of the most promising clean coal technologies. However, gasification process also produces a huge amount of solid waste of high carbon content, named coal gasification fine slag. The coal gasification fine slag is mainly handled by landfilling, which is not only a hazardous pollution, but also wasting the energy from residual carbon. Developing a technology to utilize coal gasification fine slag and recover the residual carbon is becoming essential for an eco-friendly coal chemical industry. In this paper, the enrichment behavior of residual carbon in coal gasification fine slag by a spiral separator is studied. The raw coal gasification fine slag sample and separator products are characterized on particle size distribution, size-depending ash content, reactivity, micromorphology and porous structure. The experimental results show that the spiral separator is efficient to remove ash and enriched carbonaceous components in coal gasification fine slag by separating feed (100%) into concentrate (81.2%), middlings (8.8%), and tailings (10.08%), where the ash content in tailings is up to 90%, accounting for 18.5% of total ash in feeding. The beneficial product "concentrate" has a good distribution of size-depending ash content, that most combustibles are enriched in these particles of diameter >100 μm. After spiral separator, the concentrate products have a more pure and developed porous structure with the surface area increasing from 199.8 m2/g (feeding) to 231.8 m2/g, as well as a better combustion reactivity of lower ignition temperature compared with feedings. Accordingly, an economic and feasible combination process of spiral separator connecting sieve can produce an enriched-carbon product of ∼45% yield and ∼80% carbonaceous content. The Iodine adsorption ability of sieved products increases by 47.6% compared with feed, and reaches up to about half of industry activated carbon. The finally sieved concentrate products have a good market prospect as fuel and adsorbent. • High-carbon products are obtained from waste coal gasification fine slag. • The ash content of spiral tailings product is up to 90%. • The spiral concentrate has a high surface area 232 m2/g and a high porosity. • The carbon content of concentrate can be enhanced into 80% by screening. [ABSTRACT FROM AUTHOR]

Moisture content of corn directly affects its quality and storage time, and the rapid on-line detection of the moisture content of corn ears not threshed or in vivo in the fields is required. Because of the special shape of corn ear, the rapid, low cost and non-destructive bioelectrical impedance measurement is more suitable for its moisture content detection. Using the four-electrode method with the Agilent E4980A precision LCR meter, the electrical impedance spectroscopies of the sweet corn ears and waxy corn ears at different moisture contents were acquired. The frequency range of the detection was from 20 Hz to 2 MHz and to enhance the contact, the attached-type electrodes were wrapped in cotton soaked with 0.1% NaCl solution. The impedance data over the frequency range from 300 Hz to 5 kHz were used to obtain the parameters of the bio-impedance Cole-Cole model. The results showed a good linear correlation (coefficient of determination R2=0.960) between the equivalent parallel resistance R∞ of sweet corn ear and the moisture content value determined by standard chemical method. The research proved that the bioelectrical impedance spectroscopy can be used for detecting the moisture content of corn ear. [ABSTRACT FROM AUTHOR]

The efficient recycling of agricultural chestnut shell waste is of considerable interest due to its large availability and economic feasibility. Herein, an alkaline-activated biochar was thermally prepared using chestnut shell by finely regulating main conditions; its morphological, structural and physic-chemical properties were well characterized. Fenton-like capacity to trigger peroxymonosulfate activation for superior pollutant degradation with high efficiency and good selectivity was validated in different water matrix. Both radical formation and electron transfer were identified as reaction pathways, while the selective non-radical mechanism played the major role in pollutant degradation. Surface ketonic groups were identified as the main reactive sites for non-selective radical production, while crystal edges and structural defects on sp2/sp3 carbon network could smoothly mediate the selective electron transfer from pollutant to oxidant in the non-radical Fenton-like catalysis. The two-mixed radical/non-radical pathways exhibited important advantages for environmental decontamination, in comparison with the one-single radical or non-radical mechanism. Our study provided a promising recycling strategy for agricultural chestnut shell, as well as an environment-friendly catalyst for heterogeneous Fenton-like catalysis in green water purification rendered by the synergistic radical/non-radical reaction pathways. [Display omitted] • A two-step pyrolytic strategy was proposed to recycle chestnut shell. • Biochar-based Fenton system was designed and estimated using phenols. • KOH-activated biochar exhibited good reactivity and selectivity in Fenton-like catalysis. • Radical/non-radical synergistic catalytic mechanisms were elucidated. [ABSTRACT FROM AUTHOR]

Nitrogen (N) contamination from rice paddy cultivation has threatened the quality of water resources in the upper reaches of the Huangpu River. In this study, a 3-year experiment (2009–2011) was conducted at a typical rice field in the Huangpu River watershed. The rates of N loading via surface runoff and subsurface leaching from the field were measured with a permanently installed lysimeter system. In the experiment, four treatments were tested, including applications of only chemical fertilizer (CT), only organic manure (OT), a mixture of the two types of fertilizers (MT) and a control (CK). The field data indicated that the average rates of the seasonal N loading induced by both runoff and leaching for CK, CT, MT and OT were 3.38, 16.79, 15.07 and 7.14 kg N/ha, respectively. However, OT decreased the rice yields to 5482 kg/ha, whereas MT maintained the optimal yields of 6818 kg/ha. A process-based model, denitrification–decomposition or DNDC, was adopted to assist with interpreting and integrating the experimental results. DNDC has been calibrated and validated against the field data and accurately simulated the N losses via surface runoff and subsurface leaching from the paddy field. The modeled seasonal N loading rates for CK, CT, MT and OT were 3.25, 18.84, 15.54 and 6.46 kg N/ha, respectively, which were in accordance with field observations. The modeled rice yields (4126–7365 kg/ha) across the treatments were also in agreement with the observations (3788–6818 kg/ha), though approximately 8% higher than observations. The results of sensitivity analysis indicated that increases in precipitation or fertilization or decreases in soil clay fraction increased the N loading rate. In addition, the scenario simulation tests indicated that the application of urea at a rate of 170 kg N/ha was the optimal fertilization method for the rice field, which maintained the optimal rice yields with a relatively low rate of N loading of 11.55 kg N/ha. The revised DNDC model proved to be an effective tool for assessing best management practices that reduce N loading in rice paddy field in China. [ABSTRACT FROM AUTHOR]

To increase the surface hardness of titanium (Ti), the boride layers composed of TiB 2 and TiB, were prepared on the CP-Ti substrate by spark plasma sintering (SPS) technique with micro-TiB 2 powders as boride source. Effects of sintering temperature and holding time on the microstructure, thickness, growth kinetic and hardness of boride layers were investigated. Experimental results showed that the boride layers were composed of a continuous TiB 2 top-layer and a TiB nano-whisker sub-layer. The maximum thickness of boride layers of TiB 2 and TiB were 2.24 ± 0.49 μm and 15.63 ± 6.97 μm, respectively. The activation energy of boron atom for the SPS boride process was calculated to be 386.49 kJmol−1 for the TiB 2 layer and 343.57 kJmol−1 for the TiB layer, which indicates that the SPS can provide enough energy that required in the surface treatment. Boride layers can grow well at a vacuum level of 6 Pa in the SPS. The borided Ti is about six times the hardness of the pure Ti. Boron atoms in the TiB 2 powders were activated by the high temperature and plasma, then reacted with Ti to form TiB nano-whiskers. The holding time of the present method was significantly shorter than other boriding processes. This SPS process provides a new approach for boriding of Ti and its alloys. [Display omitted] • Ti boride layer by SPS was composed of TiB 2 and TiB nano-whisker. • The growth of titanium boride layers was enhanced significantly by SPS. • Six times increased hardness of Ti was achieved with short holding time in SPS. • The growth kinetic of boride layers is a diffusion-controlled model. [ABSTRACT FROM AUTHOR]

We read with interest the review by Searle and colleagues published online on July 3.1 This review summarized the association of rosacea and cardiovascular system, emphasizing the need to evaluate the underlying cardiovascular risk factors for rosacea patients. A simple health examination and noninvasive screening could be recommended to rosacea patients even without signs or symptoms of systemic disorders if budget permits. [Extracted from the article]

Dear Editor, The health care of lesbian, gay, bisexual, and transgender (LGBT) has been widely concerned in recent years. Thus, we strongly advise administrators in government and medical association to develop rules and regulations on LGBT health care, to construct and perfect the LGBT health care training system for clinicians, especially dermatologists, and, if possible, to include courses on LGBT health care in medical curricula. [Extracted from the article]

Obeticholic acid (OCA) is exemplified as a potent drug for treating primary biliary cirrhosis and nonalcoholic fatty liver disease by inhibiting bile acid synthesis. However, it remains unclear whether the effect of OCA is mediated by the function of brown adipose tissue (BAT). In the present study, brown adipogenesis differentiation in vitro and db/db mouse model treated with OCA were used to assess the anti-obesity function by body weight tracking, O2 consumption, food intake, physical activity, glucose tolerance tests. In addition, uncoupling protein 1 (Ucp1) protein expression in brown adipose tissue was measured by western blotting, morphometry of brown adipose tissue was analyzed by hematoxylin and eosin staining. Hepatic steatosis was detected by Oil-Red O staining and serological analysis was performed to assess the effect of OCA on hyperlipidemia. OCA treatment enhanced brown adipocyte cell differentiation and upregulated the expression of the BAT-specific gene Ucp1) in C3H10T1/2 cells in vitro. Consistent with these findings, OCA increased whole-body energy metabolism and glucose homeostasis by enhancing BAT activity in vivo, and ultimately decreased body weight gain in db/db mice. In addition, the results demonstrated that spontaneous hepatic steatosis in db/db mice was ameliorated following OCA treatment. In summary, OCA functioned as a BAT activator to help ameliorate obesity and maintain glucose homeostasis in db/db mice. The present results may provide a novel potential therapeutic approach to activate brown fat in patients with obesity and other metabolic disorders. [ABSTRACT FROM AUTHOR]

Zinc finger in the cerebellum 1 ( Zic1) is known to regulate neurogenesis and myogenesis in the developmental stage and widely used as one of the brown adipocyte-specific markers. In this study, we examined the effect of Zic1 on brown adipogenesis. Overexpression of Zic1 attenuated the lipid accumulation and the expressions of PPARγ2 and C/EBPα in CHT mesenchymal stem cells. The mRNA levels of BAT-specific thermogenic genes ( PRDM16, PGC-1α and UCP1) and fatty acid oxidation regulatory genes ( PPARα, CPT1α, CPT1β and COX7α1) were suppressed in Zic1-overexpressed cells. Moreover, overexpression of Zic1 reduced the mitochondrial oxidative phosphorylation (OXPHOS) regulatory proteins including ATP5α, UQCRC2, SDHB and NDUFB5. These results indicate a potential role of Zic1 in the regulation of brown adipogenesis via inhibiting adipogenesis, fatty acid oxidation and mitochondrial OXPHOS. [ABSTRACT FROM AUTHOR]

Rosacea is a chronic and inflammatory skin disease characterized by flushing, nontransient erythema, papules/pustules, telangiectasia, and phymatous changes. Secondary manifestations, such as itching, burning, or stinging, are often observed in patients with rosacea. In 2017, a phenotype-based approach for diagnosis and classification was recommended. With the update of the diagnosis and classification of rosacea, treatment options for patients with rosacea have attracted the attention of dermatologists. Here, we summarize the latest advances in rosacea treatment, including skin care and cosmetic treatments, topical therapies, oral therapies, laser- and light-based therapies, injection therapies, treatments for specific types of rosacea, treatments for systemic comorbidities, and combination therapies. The impact of the phenotype-based approach on rosacea treatment and future directions are also discussed. [ABSTRACT FROM AUTHOR]

Objectives: HIV‐associated kidney disease is common but data on the pathology spectrum of kidney biopsy in China is lacking. This study aimed to illustrate the clinical presentation, laboratory findings and pathological spectrum of different subtypes of HIV‐associated kidney disease in China. Methods: Eighteen HIV patients with renal biopsy indications at the Peking Union Medical College Hospital from January 2002 to October 2021 were retrospectively enrolled. All had CD4 counts and HIV viral load measurements. Renal biopsies were examined with light microscopy, immunofluorescence, and electron microscopy. Shapiro‐Wilk test was used to test whether the data was normally distributed. The data is presented as medians (interquartile range), number (%), or means (±SD) according to their distribution. Results: Seventeen patients had glomerular disease, and one patient had interstitial nephritis. Membranous nephropathy was present in eight patients (47.1%), and IgA nephropathy in four patients (23.5%). The difference in urine protein and serum albumin before and after treatment was statistically significant and no deaths or dialysis were observed to the end of follow‐up. Conclusion: This study found that classic HIV‐associated nephropathy (HIVAN) was uncommon in Chinese HIV patients. HIV immune complex kidney (HIVICK) disease, such as membranous or IgA nephropathy, was more common, and associated with better prognosis. Antiretroviral therapy, ACE inhibitors, and angiotensin II receptor blockers were effective in decreasing proteinuria and preserving renal function. The use of corticosteroids and immunosuppressive agents seems safe. However, the nephrotoxic effect of antiretroviral agents and other medications should be carefully monitored. [ABSTRACT FROM AUTHOR]

This work investigated the effects of the aging process on the performance of asphalt binder under multiple environmental conditions based on multitechnique experimental results. The aging process of matrix asphalt binder with the increase of temperature for 96 h, 192 h, and 288 h was simulated by an aging oven. Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) were used to quantify the microcosmic characteristics of asphalt after aging. The results showed that the aging process of asphalt is an oxidation process, and the oxygen-containing functional groups (C═O and S═O) increased with aging. At the macroscopic level, the changes of adhesion properties and bond strength of asphalt were studied by testing the changes in three major indexes. The penetration and ductility of asphalt decreased, and the softening point increased with aging. The changes of rheological performance were tested by dynamic shear rheometer (DSR) and Brookfield viscometer. Mutual transformation of aromatic phenol, colloid, and asphaltene led to an increase in asphalt viscosity and decrease in workability. Antifatigue performance gradually decreased under the action of load with the extension of time. The elastic properties were finally damaged by fatigue. [ABSTRACT FROM AUTHOR]

Supercritical H 2 O/CO 2 mixtures are the working fluids in a novel power generation system with coal gasified in supercritical water, but their heat transfer behaviors have received less attention compared with those of the supercritical water. Here, we experimentally investigated the heat transfer to these important mixtures. First, a stable and accurate apparatus was designed and established to measure the forced convection heat transfer coefficients (HTCs) of supercritical H 2 O/CO 2 mixtures. The measurement uncertainty of this apparatus is lower than those reported in literature attributed to the well controls of the pressure and the component mass fraction throughout the apparatus. Then HTCs were measured for the H 2 O/CO 2 mixtures that flow in a vertically upward smooth tube with the fluid pressure of 24 MPa, temperatures from 400 to 460 °C, CO 2 mass fractions up to 20.1% and mass velocities up to 1270 kg m−2 s−1. Results show that the supercritical mixtures have similar convection heat transfer behavior to supercritical pure fluids, and that the forced convection heat transfer coefficients of these mixtures can be well predicted using the correlation developed for supercritical pure fluids. These results lay the foundation for designing heat transfer devices with supercritical mixtures as heat transfer fluids. [ABSTRACT FROM AUTHOR]

• High-molecular-weight γ-PGA (over 4000 kDa) was produced by Bacillus sp. A-5. • Appropriate rate of γ-PGA increased vegetable yield and the apparent fertilizer utilization efficiencies. • Moderate and high rates of γ-PGA application offset the chemical fertilizer reduction. • γ-PGA regulated soil microbial structure in a concentration-dependent manner. In this study, we investigated the effect of high-molecular-weight γ-PGA (over 4000 kDa) produced by Bacillus sp. A-5 on Chinese cabbage (Brassica rapa L. ssp. chinensis L.) productivity, apparent fertilizer utilization efficiencies, and soil bacterial community structure. Compared to CF treatment, γ-PGA application at low rates (P0 and P1) decreased vegetable yield by 14.29% and 17.30%, respectively; however, P2, P3, and F2 (moderate and high doses of γ-PGA application) offset the chemical fertilizer reduction and thereby increased the apparent utilization efficiencies by 27.82–52.27% for N, 17.05–64.59% for P, and 32.73–41.43% for K. With reduced fertilizer application, the P2, P3, and F2 treatments increased soil bacterial community diversity, richness, and evenness; in contrast, the P0 and P1 treatments decreased these variables. In conclusion, γ-PGA can enhance the apparent fertilizer utilization efficiencies and increase the relative abundances of potential plant-growth-promoting bacteria in soil in a concentration-dependent manner, thereby improving Chinese cabbage yield. [ABSTRACT FROM AUTHOR]

Failure to make adaptive immune responses is a hallmark of aging. Reduced B cell function leads to poor vaccination efficacy and a high prevalence of infections in the elderly. Here we show that reduced autophagy is a central molecular mechanism underlying immune senescence. Autophagy levels are specifically reduced in mature lymphocytes, leading to compromised memory B cell responses in old individuals. Spermidine, an endogenous polyamine metabolite, induces autophagy in vivo and rejuvenates memory B cell responses. Mechanistically, spermidine post-translationally modifies the translation factor eIF5A, which is essential for the synthesis of the autophagy transcription factor TFEB. Spermidine is depleted in the elderly, leading to reduced TFEB expression and autophagy. Spermidine supplementation restored this pathway and improved the responses of old human B cells. Taken together, our results reveal an unexpected autophagy regulatory mechanism mediated by eIF5A at the translational level, which can be harnessed to reverse immune senescence in humans. • The endogenous polyamine spermidine maintains autophagy via hypusinating eIF5A • Hypusinated translation factor eIF5A controls TFEB expression and autophagy • Spermidine restores B cell responses in old mice and humans • TFEB levels decline with age and can be used as drug target/biomarker for human aging In this study, Zhang et al. restore B cell immunity in the elderly with spermidine, a cellular polyamine metabolite depleted with age. They find that autophagy is maintained by spermidine via promoting eIF5A function and TFEB translation. This pathway provides an explanation for the age-related decline of autophagy. [ABSTRACT FROM AUTHOR]

In recent years, Industrial Internet of Things (IIoT) has gradually attracted the attention of the industry owing to its accurate time synchronization, communication accuracy, and high adaptability. As an important data structure, graphs are widely used in IIoT applications, where entities and their relationships can be expressed in the form of graphs. With the widespread adoption of IIoT and cloud computing, an increasing number of individuals or organizations are outsourcing their IIoT graph data to cloud servers to enjoy the unlimited storage space and fast computing service. To protect the privacy of graph data, graphs are usually encrypted before being outsourced. In this article, we propose a search pattern privacy system for approximate shortest distance query of encrypted graphs in IIoT. To realize search pattern privacy, we adopt two noncolluded cloud servers to accomplish different tasks. We leverage the first server to store the encrypted data and perform query operations, and use the second one to rerandomize the contents and shuffle the locations of the queried records. Before queries, we generate the trapdoors by using different random numbers. After queries, we ask the second server to rerandomize the contents of the records that the first server touched. In addition, we shuffle the physical locations of original records by inserting some fake records. In this way, all contents and physical locations of the touched records change, so that the first server cannot distinguish whether two queries are the same or not. To enhance the efficiency on the user side, we further improve this system by moving some heavy workloads from the user to the cloud. The security analysis and the performance evaluation show that our work is secure and efficient. [ABSTRACT FROM AUTHOR]

TGFβ1 signaling pathway is associated with many diseases, which can induce the activation of hepatic stellate cells (HSCs) and induce liver fibrosis. Studies have shown that 20S-protopanaxadiol (PPD) has a therapeutic effect on liver fibrosis, but the target is unknown. In this study, we confirmed that PPD reduced the mRNA expression of downstream genes of the TGFβ1 pathway, which suggesting PPD is associated with the TGFβ1 pathway. The protein dissociation temperature and dissociation constant (Kd) of PPD on TGFβR1 and TGFβR2 were determined, which showed that PPD combined with TGFβR1 (Kd = 1.54 μM). The docking and simulation methods were used to find their binding sites. Site mutations, protein expression and in vitro binding experiments were performed to demonstrated these sites. In particular, these sites of TGFβR1 were also the active sites of TGFβR2. Therefore, we speculated that PPD blocked the combination of TGFβR1 and TGFβR2 by binding to the D57, R58, P59, and N78 of the TGFβR1 extracellular domain. Thus, PPD could block the transmission of TGFβ1 pathway and inhibit the activation of HSCs, and treating fibrosis. Our studies showed that PPD has the potential to treat diseases related to the TGFβ1 pathway and broadens its clinical application. [ABSTRACT FROM AUTHOR]

We investigate the problem of securely outsourcing the modular exponentiations in cryptography to an untrusted server, and analyze the security and the efficiency of three privacy-preserving outsourcing protocols for exponentiations proposed in Ding et al. (2017) [18]. Based on Coppersmith's lattice-based method, we present heuristic polynomial-time and ciphertext-only weak-key attacks on these protocols, which shows that the recommended size of the secret keys in their protocols can not assure the input privacy of the exponents. Correspondingly, we explicitly estimate the size of the secure secret keys to circumvent our attacks, and analyze the efficiency of the revised protocols with security settings. Our theoretical analysis and experimental results demonstrate that the protocol of single modular exponentiation is unavailable, the protocol of simultaneous modular exponentiations is not so efficient as claimed but still available, and the protocol of multiple modular exponentiations becomes more efficient as the number of exponentiations increases. [ABSTRACT FROM AUTHOR]

Neurosyphilis (NS) is a central nervous system (CNS) infection caused by Treponema pallidum (T. pallidum). NS can occur at any stage of syphilis and manifests as a broad spectrum of clinical symptoms. Often referred to as "the great imitator," NS can be easily overlooked or misdiagnosed due to the absence of standard diagnostic tests, potentially leading to severe and irreversible organ dysfunction. In this study, proteomic and machine learning model techniques are used to characterize 223 cerebrospinal fluid (CSF) samples to identify diagnostic markers of NS and provide insights into the underlying mechanisms of the associated inflammatory responses. Three biomarkers (SEMA7A, SERPINA3, and ITIH4) are validated as contributors to NS diagnosis through multicenter verification of an additional 115 CSF samples. We anticipate that the identified biomarkers will become effective tools for assisting in diagnosis of NS. Our insights into NS pathogenesis in brain tissue may inform therapeutic strategies and drug discoveries for NS patients. [ABSTRACT FROM AUTHOR]

The transformation between Cr(III) and Cr(VI) occurs in Cr-contaminated soil, which can be regulated by root-soil interactions, under natural conditions. In situ investigation of the effectiveness of different reductants in reducing Cr(VI) to Cr(III), and thereby the reoccurrence risk in reduced Cr-contaminated soil, can improve the understanding of Cr biogeochemistry and toxicity. Traditional and high-resolution diffusive gradients in thin films (DGT) were used to measure Cr(VI) availability and rhizosphere effect controlling the chemical behaviors of Cr(VI) in the rice rhizosphere microdomain. The Cr(VI) concentration in the soil solution (Csoln) of the rhizosphere region varied according to the reductant type and followed the order: Molasses > CaS4 >Fe(II). Rice root activity increased the Csoln in the rhizosphere region by 2.16 μg/L, 1.90 μg/L, and 1.08 μg/L for Fe(II), CaS4, and Molasses treatments, respectively. The Cr(VI) concentration measured by DGT (CDGT) in the reduced Cr-contaminated soils increased from 0.96–1.17 μg/L in the bulk region to 1.23–1.76 μg/L in rhizosphere region. The variation in the effective concentration of Cr(VI) (CE) was similar to that of Csoln in the rice rhizosphere microdomain. Csoln accounted for 14.71–19.36% of the CE, further suggesting that bioavailable Cr(VI) mainly originated from the replenishment from the solid phase. The sequence of the average Cr(VI) flux in the reduced Cr-contaminated soil was Molasses, CaS4, and Fe(II). Except for Molasses, there was no obvious Cr(III) in Fe(II) and CaS4. For Fe(II), a higher phosphate flux in the rhizosphere microdomain hindered Cr(VI) uptake. High-resolution imaging provides a theoretical basis for the bioavailability evaluation and remediation of Cr-contaminated soil. Compared with CaS4 and Molasses, Fe(II) was the most effective reductant for remediating Cr-contaminated soils. [ABSTRACT FROM AUTHOR]

Liver fibrosis is caused by the accumulation of extracellular matrix proteins on the surface of hepatocytes and results from chronic liver injury. TGFβ1 is one of the most important promoters of hepatic fibrosis, which accelerates the transformation of hepatic stellate cells to myofibroblasts and collagen expression. It is well-known that TGFβ1 binds to TGFβR2 to mediate its downstream signal cascades to regulate target gene transcription. Therefore, the TGFβR2 blocker might be a prominent drug candidate. We constructed TGFβR2 extracellular domain into living biotherapeutics Lactococcus lactis to reduce hepatic fibrosis in CCl4 treated mice in the present study. We found that the culture supernatant of the recombinant bacteria can inhibit the TGFβ1-induced collagen synthesis in the hepatic stellate cells at the cellular level. In addition, results of in vivo study showed that the recombinant bacteria significantly reduced the degree of liver fibrosis in CCl4-treated mice. Furthermore, flow cytometry results indicated that the recombinant bacteria treatment significantly reduced the CD11b+ Kupffer cells compared with the empty vector bacteria group. Consistently, fibrosis-related gene and protein expression were significantly reduced upon recombinant bacteria treatment. Finally, the subchronic toxicity test results showed that this bacteria strain did not have any significant side effects. In conclusion, our recombinant Lactococcus lactis shows tremendous therapeutic potential in liver fibrosis. Key points: • The supernatant of L. lactis expressing TGFβR2 inhibits the activation of myofibroblast. • The oral recombinant strain reduced the degree of liver fibrosis and inflammation in mice. • The recombinant strain was safe in subchronic toxicity test in mice. [ABSTRACT FROM AUTHOR]

Ammonia oxidation is the first and rate-limiting step of nitrification, driven by ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA). Straw and straw biochar retention are the popular ways to utilize the agricultural by-products in China, but their long-term effects on AOB and AOA still remain poorly understood. Based on a 7-year plot experiment, which had 4 fertilization regimes: no fertilizer (CK), regular fertilization (RT), straw retention (SR) and straw biochar retention (SB), the abundance and the composition of AOB and AOA was investigated before both the harvest of rice and wheat season by quantitative PCR and 454 high-throughput pyrosequencing, respectively. (1) Compared to RT, straw and straw biochar increased AOB abundance and diversity significantly only in wheat season (P < 0.05), and they both ranked as SB > SR > RT. Among fertilized treatments, a significant difference between SR and RT was found in AOB community composition of the winter season (R value = 0.58, P value = 0.02); (2) In contrast, AOA was almost not responsive to organic addition, except the significant enhancement of abundance by biochar in wheat season; (3) After straw and straw biochar addition, soil potential nitrification rates (PNR) was positive correlated to AOB abundance in both rice and wheat season (P < 0.01), not to AOA abundance (P = 0.211 and 0.068, respectively). This study provides scientific support for the potential of straw utilization to improve nitrification in rice-wheat rotation system with respect to soil ammonia oxidation microorganism. [ABSTRACT FROM AUTHOR]