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This study explored the pathogenesis of human immunodeficiency virus (HIV) and monkeypox co-infection, identifying candidate hub genes and potential drugs using bioinformatics and machine learning. Datasets for HIV (GSE 37250) and monkeypox (GSE 24125) were obtained from the GEO database. Common differentially expressed genes (DEGs) in co-infection were identified by intersecting DEGs from monkeypox datasets with genes from key HIV modules screened using Weighted Gene Co-Expression Network Analysis (WGCNA). After gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and construction of protein-protein interaction (PPI) network, candidate hub genes were further screened based on machine learning algorithms. Transcriptional factors (TFs) and miRNA-candidate hub gene networks were constructed to understand regulatory mechanisms and protein-drug interactions to identify potential therapeutic drugs. Seven candidate hub genes—MX2, ADAR, POLR2H, RPL5, IFI16, IFIT2, and RPS5—were identified. TFs and miRNAs associated with these hub genes, playing a key role in regulating viral infection and inflammation due to the activation of antiviral innate immunity, were also identified through network analysis. Potential therapeutic drugs were screened based on these hub genes: AZT, a nucleotide reverse transcriptase inhibitor, suppressed viral replication in HIV and monkeypox co-infection, while mefloquine inhibited inflammation due to the activation of antiviral innate immunity. In conclusion, the study identified candidate hub genes, their transcriptional regulation, signaling pathways, and small-molecule drugs in HIV and monkeypox co-infection, contributing to understanding the pathogenesis of HIV and monkeypox co-infection and informing precise therapeutic strategies. [ABSTRACT FROM AUTHOR]

Objective: To compare efficacy of proximal and distal laparoscopic ureteroureterostomy (UU) for complete duplex kidneys in children. Methods: Patients who underwent laparoscopic UU for complete duplex kidneys between December 2016 and July 2022 were reviewed retrospectively. 71 patients who had normal lower pole moiety without vesicoureteral reflux (VUR) were recruited. All of them underwent ultrasound, voiding cystourethrography (VCUG), renal scintigraphy, and magnetic resonance urography preoperatively. Proximal laparoscopic UU was performed in 35 patients and distal laparoscopic UU in 36 patients. Double J stents were placed in normal lower pole moieties. Clinical data, including general information, diagnosis, surgical management, imaging characteristics, clinical symptoms and postoperative complications (classified according to the modified Clavien–Dindo classification), and length of stay were recorded. Measurement date comparisons between groups were performed by t test, counting date were analyzed by chi-square test. Results: The study consisted of 71 patients (56 females and 15 males) with complete duplex kidneys (41 in left kidney and 30 in right kidney). The patients' mean age was 34 m (range 3–161 m) and follow-up ranged from 25 to 81 m. No significant difference was found in age and follow-up time between the two groups. Laparoscopic UU was performed in all patients successfully. The operation time of the two groups was 108.42 ± 26.95 min for distal UU vs 121.46 ± 35.15 min for proximal UU(p = 0.14). No significant difference in postoperative complications was seen between the two groups (22.2% vs 31.4%, p = 0.345). However, in terms of the grading of postoperative complications, the proximal UU group had a higher grade (3 of them had a grade of IV) and more serious complications. Conclusions: There was no significant difference in the overall incidence of complications between distal and proximal UU. Compared with proximal laparoscopic UU, distal laparoscopic UU is easier to perform with less injury to the peripheral tissues. Postoperative complications of proximal UU are more serious and more difficult to manage. We recommend complete duplex kidney ureteral reconstruction with distal UU. [ABSTRACT FROM AUTHOR]

Soil amendments play a pivotal role in regulating rhizosphere microbial communities, which is essential for maintaining robust plant growth under adverse environmental conditions. However, the microbial mechanisms that underlie the impact of biochar on phytoremediation performance remain incompletely understood in the context of different application rates. Here, we compared the phytoremediation performance, rhizosphere microbial community characteristics, and microbial interactions in Salix psammophila across different biochar application rates (1%, 3%, 5%, and 7%) in Cd-contaminated soil. Applying 5% biochar increased plant biomass by 10.02%, root activity by 183.82%, and Cd accumulation by 13.65%. Lower biochar rates (1% and 3%) decreased Cd accumulation in plants by 21.89% and 42.05%, respectively, compared to the control. Rhizosphere soil properties and Cd content, except for nitrogen, showed a gradient change with increasing biochar application rates. This was accompanied by an elevation in the Chao1 index for the bacterial community, although the fungal community remained unaffected in terms of diversity and structure. Null-model analyses indicated that fungal community assembly was mainly driven by ecological drift, explaining its unresponsiveness to biochar application. Applying 1% biochar enhanced microbial network stability while reducing bacterial network complexity. Conversely, 3% biochar application resulted in the lowest microbial network stability. Biochar application, except 3%, reduced the proportion of bacteria-fungi associations, suggesting increased independence between two microbial kingdoms. Random forest and piecewise structural equation models revealed that phytoremediation performance is influenced by microbial network stability, complexity, and bacteria-fungi associations. Fungal complexity and stability, along with bacterial stability, were identified as key predictors of phytoremediation performance. Our findings reveal potential mechanisms by which biochar influences phytoremediation through altering microbial interactions. For long-term microbial stability and cost-effectiveness, a 1% biochar application is recommended for phytoremediation. Conversely, for rapid Cd accumulation in plants, a 5% biochar application is optimal. Highlights: • Bacterial rather than fungal communities were regulated by biochar application rate in soil. • Drift and homogeneous dispersal respectively dominated assembly of fungi and bacteria. • Biochar affects phytoremediation by regulating rhizosphere microbial interactions. • 1% of biochar is more appropriate considering the cost and the sustainability. [ABSTRACT FROM AUTHOR]

Information industry is one of the major drivers of the world economy. Its rapid growth, however, leads to severe heat problem which strongly hinders further development. This calls for a non-charge-based technology. Magnon, capable of transmitting spin information without electron movement, holds tremendous potential in post-Moore era. Given the cornerstone role of the field effect transistor in modern electronics, creating its magnonic equivalent is highly desired but remains a challenge. Here, we demonstrate a nonvolatile three-terminal lateral magnon field effect transistor operating at room temperature. The device consists of a ferrimagnetic insulator (Y3Fe5O12) deposited on a ferroelectric material [Pb(Mg1/3Nb2/3)0.7Ti0.3O3 or Pb(Zr0.52Ti0.48)O3], with three Pt stripes patterned on Y3Fe5O12 as the injector, gate, and detector, respectively. The magnon transport in Y3Fe5O12 can be regulated by the gate voltage pulses in a nonvolatile manner with a high on/off ratio. Our findings provide a solid foundation for designing energy-efficient magnon-based devices. Searching non-charge-based devices is crucial for sustainable information processing. Here, the authors make a nonvolatile magnon field effect transistor at room temperature, enabling efficient magnon transport control via the gate voltage pulses. [ABSTRACT FROM AUTHOR]

Physical neural networks are artificial neural networks that mimic synapses and neurons using physical systems or materials. These networks harness the distinctive characteristics of physical systems to carry out computations effectively, potentially surpassing the constraints of conventional digital neural networks. A recent advancement known as “physical self-learning” aims to achieve learning through intrinsic physical processes rather than relying on external computations. This article offers a comprehensive review of the progress made in implementing physical self-learning across various physical systems. Prevailing learning strategies that contribute to the realization of physical self-learning are discussed. Despite challenges in understanding the fundamental mechanism of learning, this work highlights the progress towards constructing intelligent hardware from the ground up, incorporating embedded self-organizing and self-adaptive dynamics in physical systems. [ABSTRACT FROM AUTHOR]

Nuclear factor erythroid 2-related factor 2 (Nrf2) functions as a central regulator in modulating the activities of diverse antioxidant enzymes, maintaining cellular redox balance, and responding to oxidative stress (OS). Kelch-like ECH-associated protein 1 (Keap1) serves as a principal negative modulator in controlling the expression of detoxification and antioxidant genes. It is widely accepted that OS plays a pivotal role in the pathogenesis of various diseases. When OS occurs, leading to inflammatory infiltration of neutrophils, increased secretion of proteases, and the generation of large quantities of reactive oxygen radicals (ROS). These ROS can oxidize or disrupt DNA, lipids, and proteins either directly or indirectly. They also cause gene mutations, lipid peroxidation, and protein denaturation, all of which can result in disease. The Keap1-Nrf2 signaling pathway regulates the balance between oxidants and antioxidants in vivo, maintains the stability of the intracellular environment, and promotes cell growth and repair. However, the antioxidant properties of the Keap1-Nrf2 signaling pathway are reduced in disease. This review overviews the mechanisms of OS generation, the biological properties of Keap1-Nrf2, and the regulatory role of its pathway in health and disease, to explore therapeutic strategies for the Keap1-Nrf2 signaling pathway in different diseases. [ABSTRACT FROM AUTHOR]

Abstract Single‐cell technologies allow measuring chromatin accessibility and gene expression in each cell, but jointly utilizing both layers to map bona fide gene regulatory networks and enhancers remains challenging. Here, we generate independent single‐cell RNA‐seq and single‐cell ATAC‐seq atlases of the Drosophila eye‐antennal disc and spatially integrate the data into a virtual latent space that mimics the organization of the 2D tissue using ScoMAP (Single‐Cell Omics Mapping into spatial Axes using Pseudotime ordering). To validate spatially predicted enhancers, we use a large collection of enhancer–reporter lines and identify ~ 85% of enhancers in which chromatin accessibility and enhancer activity are coupled. Next, we infer enhancer‐to‐gene relationships in the virtual space, finding that genes are mostly regulated by multiple, often redundant, enhancers. Exploiting cell type‐specific enhancers, we deconvolute cell type‐specific effects of bulk‐derived chromatin accessibility QTLs. Finally, we discover that Prospero drives neuronal differentiation through the binding of a GGG motif. In summary, we provide a comprehensive spatial characterization of gene regulation in a 2D tissue.

Minimal research exists on polychlorinated biphenyl (PCB) exposure from traditional Chinese medicines (TCMs), despite their significant contributions to domestic and international health protection. This study is the first to investigate the levels, profiles, and health risks of PCB residue in Pheretima, a typical TCM produced from earthworm. Seventy-seven Pheretima samples from different regions of China were analyzed for 45 PCB congeners. PCBs were found in all samples exhibiting species-dependent discrepancies. ∑45PCBs was ranging from 0.532 to 25.2 µg/kg (mean 4.46 µg/kg), with CB-11 being the most abundant congener contributing 71.8% ± 10.8% to ∑45PCBs, followed by CB-47, which were all non-Aroclor congeners called unintentionally produced PCBs (UP-PCBs). The average estimated daily intake of ∑45PCBs, ∑7ID-PCBs (indicative polychlorinated biphenyls), and CB-11 were 0.71, 0.04, and 0.51 ng/kg bw/d, respectively. The ∑HQ of PCBs in Pheretima samples was 2.97 × 10−4–2.46 × 10−2 (mean 2.77 × 10−3, 95th 4.21 × 10−3), while the ∑RQ ranged from 1.19 × 10−8 to 2.88 × 10−6 (mean 4.87 × 10−7, 95th 2.31 × 10−6). These findings indicate that Pheretima ingestion does not pose significant non-carcinogenic risks. However, certain individual samples exhibit an acceptable level of potential risks, particularly when considering that PCBs are recognized as endocrine disruptors and classified as probable carcinogens. These results contribute to the safety evaluation of traditional medicines and suggest the potential use of Pheretima as a bioindicator for PCB pollution. It is advisable to monitor UP-PCBs as indicator congeners and gather additional toxicological data. [ABSTRACT FROM AUTHOR]

Limited endoscopic sphincterotomy (EST) combined with endoscopic papillary balloon dilation (EPBD) is widely used. However, the optimal duration of small balloon dilation in choledocholithiasis remains controversial. We aimed to determine the optimal duration for 10 mm diameter balloon dilation after limited EST in choledocholithiasis. In this randomized controlled clinical trial, 320 patients were randomly assigned to receive small balloon dilation (10 mm in diameter) for 1 min (n = 160) or 3 min (n = 160) after deep bile duct cannulation. No significant difference in success rate of stone extraction between the two groups was observed. The incidence of post-ERCP pancreatitis (PEP) was higher in the 1 min group (10.6%) than in the 3 min group (4.4%) (P = 0.034). The logistic regression analysis showed that guidewire into the pancreatic duct, cannulation time > 5 min and 1 min balloon dilation were independent risk factors for PEP. There were no significant differences in other post-ERCP adverse events such as acute cholangitis, bleeding, perforation, etc. between the two groups. In conclusion, 3 min in duration was determined to be the optimal dilation condition for the removal of common bile duct stones. [ABSTRACT FROM AUTHOR]

The nuclear loss and cytoplasmic accumulation of TDP-43 (TAR DNA/RNA binding protein 43) are pathological hallmarks of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Previously, we reported that the primate-specific cleavage of TDP-43 accounts for its cytoplasmic mislocalization in patients’ brains. This prompted us to investigate further whether and how the loss of nuclear TDP-43 mediates neuropathology in primate brain. In this study, we report that TDP-43 knockdown at the similar effectiveness, induces more damage to neuronal cells in the monkey brain than rodent mouse. Importantly, the loss of TDP-43 suppresses the E3 ubiquitin ligase PJA1 expression in the monkey brain at transcriptional level, but yields an opposite upregulation of PJA1 in the mouse brain. This distinct effect is due to the species-dependent binding of nuclear TDP-43 to the unique promoter sequences of the PJA1 genes. Further analyses reveal that the reduction of PJA1 accelerates neurotoxicity, whereas overexpressing PJA1 diminishes neuronal cell death by the TDP-43 knockdown in vivo. Our findings not only uncover a novel primate-specific neurotoxic contribution to the loss of function theory of TDP-43 proteinopathy, but also underscore a potential therapeutic approach of PJA1 to the loss of nuclear TDP-43. [ABSTRACT FROM AUTHOR]

This article, published in the Chemistry of Natural Compounds journal, explores the chemical composition of the roots of Cynanchum atratum, a plant used in traditional Chinese medicine. The study identifies sixteen compounds in the plant, including steroidal saponins, acetophenones, alkaloids, and volatile oils. The researchers used NMR data and ESI-MS to determine the structures of these compounds. The article provides detailed information about the chemical constituents of Cynanchum atratum and their potential medicinal properties. The research was supported by grants from the National Natural Science Foundation of China and Guizhou Science and Technology Innovation Talent Team. [Extracted from the article]

The south of Hunan is rich in low temperature geothermal water resources, yet their formation mechanism has not been well investigated. This study focused on the occurrence conditions of geothermal water and estimation the thermal reservoir temperature and the circulation depth of geothermal water in this area. The hydrogeochemical analyses of 23 geothermal water samples are proceeded with the help of Origin, PHREEQC and Aquachem software. The results show that the main hydrochemical type of geothermal water in the study area is HCO3·SO4–Ca·Mg and HCO3–Na. The δD and δ18O of the geothermal water samples show a linear right-up trend, indicating the geothermal waters were recharged by meteoric water. The mineral saturation index was calculated by PHREEQC, which indicated that the quartz and chalcedony minerals were close to the saturation state. The reservoir temperature range of geothermal water is estimated to be 38–122°C by using a silica (quartz) geothermometer, with an average of 73°C. The geothermal water circulation depth range calculated by the geothermal gradient is 1–4 km, with an average of 2.13 km. [ABSTRACT FROM AUTHOR]

The thermal effect of electrokinetic remediation (EKR) is a kind of energy dissipation, which is an important part of the useless work in the process of EKR. Therefore, this study aims to reveal the phenomenon and mechanism of thermal effect and the energy distribution mechanism in the process of EKR. To explore the distribution mechanism of soil temperature during the EKR process, nine groups of orthogonal EKR experiments lasting 120 h were carried out. The experimental results show that the phenomenon of thermal effect is common in the process of electric remediation of uranium pollution, and it is positively correlated with the current of the system. At the same time, soil pH, moisture, and conductivity are all related to soil temperature. According to the range analysis, the voltage gradient has the greatest impact on the current utilization rate. Under the conditions of 0.5 V/cm and 0.5 mol/L citric acid (CA), the maximum removal efficiency of U(VI) in the soil is 36.58%, and the maximum current utilization rate η is 3.85%. In general, the study of the general law of thermal effect in the process of EKR will provide theoretical support for weakening the effect of thermal effect, avoiding wasting more energy, improving the utilization efficiency of energy, and transforming the EKR process. Therefore, this study has a positive significance for the law of thermal effect in the process of EK and the engineering application of EKR technology. Highlights: • Current utilization efficiency and energy distribution mechanisms were discovered during the EKR process. • The distribution mechanism of temperature in soil cell was revealed in the EKR process. • Optimizing experimental combination, providing a theoretical basis for engineering practical application. [ABSTRACT FROM AUTHOR]

In this study, by using coconut shell and chitosan (CS) as raw materials, mesoporous chitosan@coconut shell-derived biochar composites (CS@BC) were prepared and were used for Cd2+ removal from aqueous solutions. The tests of SEM, BET, XRD, FTIR, and XPS were used to identify the adsorbent structure and adsorption mechanisms. Batch adsorption experiments shown that the Cd2+ adsorption by biochar was strongly dependent on the initial pH of the solution. The pseudo-second-order kinetic model and Langmuir isotherm model can describe the process of Cd2+ adsorption by biochars more accurately, which indicated that the adsorption process was a chemical reaction and single-layer adsorption. Under the conditions of initial pH 5.0, dosage 10 mg, contact time 360 min, and temperature 25 °C, the maximum Cd2+ adsorption capacity of BC and CS@BC was 48.84 mg/g and 63.88 mg/g, respectively. Notably, the Cd2+ removal efficiency of CS@BC in three different water bodies was almost 100%. In addition, after 5 times of adsorption-desorption experiments, the Cd2+ removal efficiency of CS@BC remained above 90%, which indicated that CS@BC had excellent regenerative properties. The adsorption mechanisms of Cd2+ by BC and CS@BC were mainly attributed to ion exchange (Qex), co-precipitation (Qpre), complexation with O-containing functional groups (Qco), and Cd2+-π interaction (Qπ). Hence, inexpensive, readily available and simply prepared CS@BC composites were highly efficient adsorbent materials that can be applied for the removal of Cd2+ from aqueous solutions. [ABSTRACT FROM AUTHOR]

Background: Although the incidence of adenocarcinoma of the esophagogastric junction (AEG) has been increasing since the past decade, the proportion of AEG cases in two previous clinical trials (ACTS-GC and CLASSIC) that investigated the efficacy of adjuvant chemotherapy was relatively small. Therefore, whether AEG patients can benefit from adjuvant chemotherapy remains unclear. Methods: Patients who were diagnosed with pathological stage II/III, Siewert II/III AEG, and underwent curative surgery at three high-volume institutions were assessed. Clinical outcomes were analyzed by using Kaplan-Meier curves, log-rank test, and Cox regression model. Propensity score matching (PSM) was used to reduce the selection bias. Results: A total of 927 patients were included (the chemotherapy group: 696 patients; the surgery-only group: 231 patients). The median follow-up was 39.0 months. The 5-year overall survival was 63.1% (95% confidence interval [CI]: 59.0-67.6%) for the chemotherapy group and 50.2% in the surgery-only group (hazard ratio [HR] = 0.69, 95% CI: 0.54-0.88; p = 0.003). The 5-year, disease-free survival was 35.4% for the chemotherapy group and 16.6% for the surgery-only group (HR = 0.66, 95% CI: 0.53-0.83; p < 0.001). After PSM, the survival benefit of adjuvant chemotherapy for AEG was maintained. Multivariate analysis for overall survival and disease-free survival further demonstrated the survival benefit of adjuvant chemotherapy, with HRs of 0.63 (p < 0.001) and 0.52 (p < 0.001), respectively. Conclusions: Postoperative adjuvant chemotherapy was associated with improved overall survival and disease-free survival in patients with operable stage II or III AEG after D2 gastrectomy. [ABSTRACT FROM AUTHOR]

Artificial spin ice (ASI) consisting patterned array of nano-magnets with frustrated dipolar interactions offers an excellent platform to study frustrated physics using direct imaging methods. Moreover, ASI often hosts a large number of nearly degenerated and non-volatile spin states that can be used for multi-bit data storage and neuromorphic computing. The realization of the device potential of ASI, however, critically relies on the capability of transport characterization of ASI, which has not been demonstrated so far. Using a tri-axial ASI system as the model system, we demonstrate that transport measurements can be used to distinguish the different spin states of the ASI system. Specifically, by fabricating a tri-layer structure consisting a permalloy base layer, a Cu spacer layer and the tri-axial ASI layer, we clearly resolve different spin states in the tri-axial ASI system using lateral transport measurements. We have further demonstrated that the tri-axial ASI system has all necessary required properties for reservoir computing, including rich spin configurations to store input signals, nonlinear response to input signals, and fading memory effect. The successful transport characterization of ASI opens up the prospect for novel device applications of ASI in multi-bit data storage and neuromorphic computing.Artificial spin ices consist of small magnets arranged in a lattice. Their simplicity belies their rich behaviour; they allowed for the investigation of effective magnetic monopoles, and more recently have been suggested as promising platforms for neuromorphic computing. For this latter function, efficient readout of the artificial spin ice state is critical. In this manuscript, Hu et al succeed in distinguishing artificial spin ice states using simple transport measurements. [ABSTRACT FROM AUTHOR]

Anisotropy is a manifestation of lowered symmetry in material systems that have profound fundamental and technological implications. For van der Waals magnets, the two-dimensional (2D) nature greatly enhances the effect of in-plane anisotropy. However, electrical manipulation of such anisotropy as well as demonstration of possible applications remains elusive. In particular, in-situ electrical modulation of anisotropy in spin transport, vital for spintronics applications, has yet to be achieved. Here, we realized giant electrically tunable anisotropy in the transport of second harmonic thermal magnons (SHM) in van der Waals anti-ferromagnetic insulator CrPS4 with the application of modest gate current. Theoretical modeling found that 2D anisotropic spin Seebeck effect is the key to the electrical tunability. Making use of such large and tunable anisotropy, we demonstrated multi-bit read-only memories (ROMs) where information is inscribed by the anisotropy of magnon transport in CrPS4. Our result unveils the potential of anisotropic van der Waals magnons for information storage and processing. The anisotropic electrical and optical response of materials has allowed for the development of variety of sensors, memories and other interesting devices. Here, Qi et al turn their attention to the van der Waals antiferromagnetic insulator CrPS4, and demonstrate a very large, electrically tunable anisotropy in magnon transport, and present a multibit read-only memory based on this anisotropy. [ABSTRACT FROM AUTHOR]

The surface flat pristine biochar provides limited adsorption sites for Cd(II) adsorption. To address this issue, a novel sludge-derived biochar (MNBC) was prepared by NaHCO3 activation and KMnO4 modification. The batch adsorption experiments illustrated that the maximum adsorption capacity of MNBC was twice that of pristine biochar and reached equilibrium more quickly. The pseudo-second order and Langmuir model were more suitable for analyzing the Cd(II) adsorption process on MNBC. Na+, K+, Mg2+, Ca2+, Cl− and NO−3 had no effect on the Cd(II) removal. Cu2+ and Pb2+ inhibited the Cd(II) removal, while PO3−4 and humic acid (HA) promoted it. After 5 repeated experiments, the Cd(II) removal efficiency on MNBC was 90.24%. The Cd(II) removal efficiency of MNBC in different actual water bodies was over 98%. Furthermore, MNBC owned excellent Cd(II) adsorption performance in fixed bed experiments, and the effective treatment capacity was 450 BV. The co-precipitation, complexation, ion exchange and Cd(II)-π interaction were involved in Cd(II) removal mechanism. XPS analysis showed that NaHCO3 activation and KMnO4 modification enhanced the complexation ability of MNBC to Cd(II). The results suggested that MNBC can be used as an effective adsorbent for treating of Cd-contaminated wastewater. [ABSTRACT FROM AUTHOR]

Abstract Despite extensive study of individual enzymes and their organization into pathways, the means by which enzyme networks control metabolite concentrations and fluxes in cells remains incompletely understood. Here, we examine the integrated regulation of central nitrogen metabolism in Escherichia coli through metabolomics and ordinary‐differential‐equation‐based modeling. Metabolome changes triggered by modulating extracellular ammonium centered around two key intermediates in nitrogen assimilation, α‐ketoglutarate and glutamine. Many other compounds retained concentration homeostasis, indicating isolation of concentration changes within a subset of the metabolome closely linked to the nutrient perturbation. In contrast to the view that saturated enzymes are insensitive to substrate concentration, competition for the active sites of saturated enzymes was found to be a key determinant of enzyme fluxes. Combined with covalent modification reactions controlling glutamine synthetase activity, such active‐site competition was sufficient to explain and predict the complex dynamic response patterns of central nitrogen metabolites.

The stochastic resonance (SR) phenomenon for an underdamped bistable system with two kinds of velocity time-delays driven by multiplicative and additive noise is investigated. Applying small time-delay approximation, under detailed balance condition, the stationary probability for the system is obtained. The expression for the transition rates out of the two stable states and that for the output signal-to-noise ratio (SNR) of the system are deduced by virtue of two-state theory. Single-peak phenomenon appears when the SNR changes with the velocity time-delays. Traditional SR occurs on the curves of the SNR versus the strengths of the multiplicative and additive noise. A resonance peak takes place when the SNR varies with the damping coefficient. Moreover, it is found that the effects of the two kinds of time-delays and those of the two noises on the SNR are different. The non-monotonous effect of system parameters on the SNR is also investigated. [ABSTRACT FROM AUTHOR]

Objective: To assess the efficacy and safety of Guanxin Danshen Dripping Pills (GXDS) in the treatment of depression or anxiety in patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI). Methods: From September 2017 to June 2019, 200 CHD patients after PCI with depression and anxiety were included and randomly divided into GXDS (100 cases) and placebo control groups (100 cases) by block randomization and a random number table. Patients in the GXDS and control groups were given GXDS and placebo, respectively, 0.4 g each time, 3 times daily for 12 weeks. The primary outcomes were scores of Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Scale (GAD-7) and the Seattle Angina Pectoris Scale (SAQ). The secondary outcomes included 12 Health Survey Summary Form (SF-12) scores and the first onset time and incidence of major adverse cardiovascular events (MACEs). Other indices including blood pressure, blood lipids, microcirculation and inflammatory-related indices, etc. were monitored at baseline, week 4, and week 12. Results: In the full analysis set (200 cases), after treatment, the PHQ-9 and GAD-7 scores in the GXDS group were considerably lower than those in the control group (P<0.05). Compared with the baseline, the total PHQ-9 scores of the experimental and control groups decreased by 3.97 and 1.18, respectively. The corrected mean difference between the two groups was −2.78 (95% CI: −3.47, −2.10; P<0.001). The total GAD-7 score in the GXDS group decreased by 3.48% compared with the baseline level, while that of the placebo group decreased by 1.13%. The corrected mean difference between the two groups was −2.35 (95% CI: −2.95, −1.76; P<0.001). The degree of improvement in SAQ score, SF-12 score, endothelin and high-sensitive C-reactive protein levels in the GXDS group were substantially superior than those in the placebo group, and the differences between the two groups were statistically significant (P<0.05). Similar results were obtained in the per protocol population analysis of 177 patients. Three cases of MACES were reported in this study (1 in the GXDS group and 2 in the placebo group), and no serious adverse events occurred. Conclusions: GXDS can significantly alleviate depression and anxiety, relieve symptoms of angina, and improve quality of life in patients with CHD after PCI. (Registration No. ChiCTR1800014291) [ABSTRACT FROM AUTHOR]

The paper investigates the event-triggered sub-optimal control problem for two-time-scale systems with unknown slow dynamics. Specifically, a composite event-triggered optimal controller design is proposed for the decoupled slow and fast subsystems with different triggering conditions. To handle the unknown dynamics, the actor and critic networks are utilized to approximate the optimal controller employing tuning laws applied to the weights. The results indicate that a system employing the proposed event-triggered mechanism can achieve asymptotic stability and afford a sub-optimal controller. Furthermore, Zeno behavior is excluded with rigorous proof, and several simulation examples and comparative studies demonstrate the method's effectiveness. [ABSTRACT FROM AUTHOR]

Huntington's disease (HD) is an autosomal dominantly-inherited neurodegenerative disease, which is caused by CAG trinucleotide expansion in exon 1 of the Huntingtin (HTT) gene. Although HD is a rare disease, its monogenic nature makes it an ideal model in which to understand pathogenic mechanisms and to develop therapeutic strategies for neurodegenerative diseases. Clustered regularly-interspaced short palindromic repeats (CRISPR) is the latest technology for genome editing. Being simple to use and highly efficient, CRISPR-based genome-editing tools are rapidly gaining popularity in biomedical research and opening up new avenues for disease treatment. Here, we review the development of CRISPR-based genome-editing tools and their applications in HD research to offer a translational perspective on advancing the genome-editing technology to HD treatment. [ABSTRACT FROM AUTHOR]

Huntingtin-associated protein 1 (HAP1) is the first identified protein whose function is affected by its abnormal interaction with mutant huntingtin (mHTT), which causes Huntington disease. However, the expression patterns of Hap1 and Htt in the rodent brain are not correlated. Here we found that the primate HAP1, unlike the rodent Hap1, is correlatively expressed with HTT in the primate brains. CRISPR/Cas9 targeting revealed that HAP1 deficiency in the developing human neurons did not affect neuronal differentiation and gene expression as seen in the mouse neurons. However, deletion of HAP1 exacerbated neurotoxicity of mutant HTT in the organotypic brain slices of adult monkeys. These findings demonstrate differential HAP1 expression and function in the mouse and primate brains, and suggest that interaction of HAP1 with mutant HTT may be involved in mutant HTT-mediated neurotoxicity in adult primate neurons. [ABSTRACT FROM AUTHOR]

Blockchain platform Ethereum has involved millions of accounts due to its strong potential for providing numerous services based on smart contracts. These massive accounts can be divided into diverse categories, such as miners, tokens, and exchanges, which is termed as account diversity in this paper. The benefit of investigating diversity are multi-fold, including understanding the Ethereum ecosystem deeper and opening the possibility of tracking certain abnormal activities. Unfortunately, the exploration of blockchain account diversity remains scarce. Even the most relevant studies, which focus on the deanonymization of the accounts on Bitcoin, can hardly be applied on Ethereum since their underlying protocols and user idioms are different. To this end, we present the first attempt to demystify the account diversity on Ethereum. The key observation is that different accounts exhibit diverse behavior patterns, leading us to propose the heuristics for classification as the premise. We then raise the coverage rate of classification by the statistical learning model Maximum Likelihood Estimation (MLE). We collect real-world data through extensive efforts to evaluate our proposed method and show its effectiveness. Furthermore, we make an in-depth analysis of the dynamic evolution of the Ethereum ecosystem and uncover the abnormal arbitrage actions. As for the former, we validate two sweeping statements reliably: (1) standalone miners are gradually replaced by the mining pools and cooperative miners; (2) transactions related to the mining pool and exchanges take up a large share of the total transactions. The latter analysis shows that there are a large number of arbitrage transactions transferring the coins from one exchange to another to make a price difference. [ABSTRACT FROM AUTHOR]

A new C21-steroidal cynansteroid O (1), together with one new natural product 20-hydroxylateqingyangshengenin (2), and three known compounds (3–5) were isolated from the roots of Cynanchum auriculatum. The chemical structures were elucidated by analyses of physio-chemical properties and spectral data and compared with the published data with given references. Compounds 1–3 were isolated for the first time from the roots of C. auriculatum. [ABSTRACT FROM AUTHOR]

Since the advent of cryptocurrencies such as Bitcoin, blockchain, as their underlying technologies, has drawn a massive amount of attention from both academia and the industry. This ever-evolving technology inherits the “genes” of distributed systems, offering significant advantages of immutability, transparency, auditability, and tamper-resistance. These benefits help blockchain re-establish public confidence, and hold the significant promise of reliable information sharing and value transfer. Therefore, blockchain has become the foundation of crucial strategic deployments in countries across the world, and the fundamental basis for building the next generation Web 3.0 — “Internet of value”. In this article, we will start with unraveling the essential ingredients of blockchain technology, and showing the characteristics of each of these ingredients in the context of distributed systems. We will then present the core technical challenges that need to be addressed prior to unleashing its full potential, including its performance, scalability, and cross-chain interoperability. Finally, we will introduce the recent developments of blockchain systems, and discuss the future trends of the blockchain ecosystem. [ABSTRACT FROM AUTHOR]

Deception attacks aim to destroy the integrity of data and will further lead to instability of dynamical systems. How to develop an effective analysis and synthesis approach based on system intrinsic characteristics is constantly being explored and faces great challenges. In this paper, we investigate the stabilization problem for singularly perturbed switched systems subject to unmodeled dynamics and deception attacks. Unlike most existing control schemes specialized for SPSSs, in which neither cyber attacks nor unmodeled dynamics are considered and the full system information is required, an observer equipped with a robust term is designed to estimate the system states and deception attacks bound, and an ε -dependent integral sliding mode surface is then constructed to introduce multiple time scales feature to the sliding mode dynamics. By using ε -dependent multiple Lyapunov functions and average dwell time technique, some well-conditioned stability conditions are given to ensure the stability of the state estimation error systems and the sliding mode dynamics. Moreover, an adaptive sliding mode control law is synthesized to ensure the reachability of the prescribed sliding surface, which further leads to the stability of the closed-loop system. Finally, a numerical simulation is given to show the validity of the obtained results. [ABSTRACT FROM AUTHOR]

Background: There is controversy regarding the long-term prognosis and short-term postoperative complications of different surgical strategies for proximal gastric cancer (PGC). Methods: We searched for articles published in Embase (Ovid), Medline (Ovid), PubMed, Cochrane Library, and Web of Science between January 1, 1990, and February 1, 2021. We screened out the literature comparing different surgical strategies. We then evaluated the long-term and short-term outcome of different surgical strategies using a network meta-analysis, which summarizes the hazard ratio, odds ratio, mean difference, and 95% confidence interval. Results: There were no significant differences between different surgical strategies for 5-year overall survival (OS), anastomotic leakage, or weight loss after 1 year. Compared with total gastrectomy with Roux-en-Y reconstruction (TG-RY) and proximal gastrectomy with double tract reconstruction (PG-DTR), the proximal gastrectomy with esophagogastrostomy (PG-EG) strategy significantly increased the incidence of reflux esophagitis; and the operation time and blood loss of the PG-EG strategy were significantly less than those of the other surgical strategies. The anastomotic stenosis rates of the PG-EG and proximal gastrectomy with jejunum interstitial (PG-JI) strategies were significantly higher than those of TG-RY and PG-DTR; the hemoglobin level after 1 year for the PG-DTR strategy was significantly higher than that of the TG-RY strategy. Conclusion: Our comprehensive literature research found that different surgical strategies had no significant difference in the long-term survival of PGC, but the incidence of reflux esophagitis and anastomotic stenosis after PG-DTR and TG-RY was significantly reduced. [ABSTRACT FROM AUTHOR]

The Drosophila brain is a frequently used model in neuroscience. Single-cell transcriptome analysis1–6, three-dimensional morphological classification7 and electron microscopy mapping of the connectome8,9 have revealed an immense diversity of neuronal and glial cell types that underlie an array of functional and behavioural traits in the fly. The identities of these cell types are controlled by gene regulatory networks (GRNs), involving combinations of transcription factors that bind to genomic enhancers to regulate their target genes. Here, to characterize GRNs at the cell-type level in the fly brain, we profiled the chromatin accessibility of 240,919 single cells spanning 9 developmental timepoints and integrated these data with single-cell transcriptomes. We identify more than 95,000 regulatory regions that are used in different neuronal cell types, of which 70,000 are linked to developmental trajectories involving neurogenesis, reprogramming and maturation. For 40 cell types, uniquely accessible regions were associated with their expressed transcription factors and downstream target genes through a combination of motif discovery, network inference and deep learning, creating enhancer GRNs. The enhancer architectures revealed by DeepFlyBrain lead to a better understanding of neuronal regulatory diversity and can be used to design genetic driver lines for cell types at specific timepoints, facilitating their characterization and manipulation.A chromatin accessibility atlas of 240,919 cells in the adult and developing Drosophila brain reveals 95,000 enhancers, which are integrated in cell-type specific enhancer gene regulatory networks and decoded into combinations of functional transcription factor binding sites using deep learning. [ABSTRACT FROM AUTHOR]

HIV-associated malignancies are responsible for morbidity and mortality increasingly in the era of potent antiretroviral therapy. This study aimed to investigate the distribution of HIV-associated malignancies among inpatients, the immunodeficiency and the effect of antiretroviral therapy (ART) on spectrum of HIV-associated malignancies. A total of 438 cases were enrolled from 2007 to 2020 in Beijing Ditan Hospital. Demographic, clinical and laboratory data, managements, and outcomes were collected and analyzed retrospectively. Of 438 cases, 433 were assigned to non-AIDS-defining cancers (NADCs) (n = 200, 45.7%) and AIDS-defining cancers (ADCs) (n = 233, 53.2%), 5 (1.1%) with lymphoma were not specified further. No significant change was observed in the proportion of NADCs and ADCs as time goes on. Of NADCs, lung cancer (n = 38, 19%) was the most common type, followed by thyroid cancer (n = 17, 8.5%). Patients with ADCs had lower CD4 counts(104.5/μL vs. 314/μL), less suppression of HIVRNA(OR 0.23, 95%CI 0.16–0.35) compared to those with NADCs. ART did not affect spectrum of NADCs, but affect that of ADCs (between patients with detectable and undetectable HIVRNA). ADCs remain frequent in China, and NADCs play an important role in morbidity and mortality of HIV positive population. [ABSTRACT FROM AUTHOR]

Van der Waals magnets have emerged as a fertile ground for the exploration of highly tunable spin physics and spin-related technology. Two-dimensional (2D) magnons in van der Waals magnets are collective excitation of spins under strong confinement. Although considerable progress has been made in understanding 2D magnons, a crucial magnon device called the van der Waals magnon valve, in which the magnon signal can be completely and repeatedly turned on and off electrically, has yet to be realized. Here we demonstrate such magnon valves based on van der Waals antiferromagnetic insulator MnPS3. By applying DC electric current through the gate electrode, we show that the second harmonic thermal magnon (SHM) signal can be tuned from positive to negative. The guaranteed zero crossing during this tuning demonstrates a complete blocking of SHM transmission, arising from the nonlinear gate dependence of the non-equilibrium magnon density in the 2D spin channel. Using the switchable magnon valves we demonstrate a magnon-based inverter. These results illustrate the potential of van der Waals anti-ferromagnets for studying highly tunable spin-wave physics and for application in magnon-base circuitry in future information technology. A major challenge in magnon based approaches to information processing lies in developing valves to allow or supress the magnon signal. Here, Chen et al demonstrate a van der Waals magnet based magnon valve which can be tuned electrically over an exceptionally wide range. [ABSTRACT FROM AUTHOR]

An artificial neural network consists of neurons and synapses. Neuron gives output based on its input according to non-linear activation functions such as the Sigmoid, Hyperbolic Tangent (Tanh), or Rectified Linear Unit (ReLU) functions, etc.. Synapses connect the neuron outputs to their inputs with tunable real-valued weights. The most resource-demanding operations in realizing such neural networks are the multiplication and accumulate (MAC) operations that compute the dot product between real-valued outputs from neurons and the synapses weights. The efficiency of neural networks can be drastically enhanced if the neuron outputs and/or the weights can be trained to take binary values ± 1 only, for which the MAC can be replaced by the simple XNOR operations. In this paper, we demonstrate an adiabatic training method that can binarize the fully-connected neural networks and the convolutional neural networks without modifying the network structure and size. This adiabatic training method only requires very minimal changes in training algorithms, and is tested in the following four tasks: the recognition of hand-writing numbers using a usual fully-connected network, the cat-dog recognition and the audio recognition using convolutional neural networks, the image recognition with 10 classes (CIFAR-10) using ResNet-20 and VGG-Small networks. In all tasks, the performance of the binary neural networks trained by the adiabatic method are almost identical to the networks trained using the conventional ReLU or Sigmoid activations with real-valued activations and weights. This adiabatic method can be easily applied to binarize different types of networks, and will increase the computational efficiency considerably and greatly simplify the deployment of neural networks. [ABSTRACT FROM AUTHOR]

Selective neuronal accumulation of misfolded proteins is a key step toward neurodegeneration in a wide range of neurodegenerative diseases, including Huntington's (HD) diseases. Our recent studies suggest that Hsp70-binding protein 1 (HspBP1), an Hsp70/CHIP inhibitor that reduces protein folding, is highly expressed in neuronal cells and accounts for the accumulation of the HD protein huntingtin (HTT) in neuronal cells. To further determine the role of HspBP1 in regulation of mutant protein accumulation, we investigated whether increasing expression of HspBP1 in glial cells can also induce the accumulation of endogenous mutant HTT in glial cells and yield non-cell-autonomous toxic effects. We performed stereotaxic injection of AAV to selectively express HspBP1 in astrocytes in the brains of HD140Q knock-in (KI) mice that express mutant HTT ubiquitously but do not display obvious neurodegeneration. However, HspBP1 expression in HD140Q astrocytes led to the increased accumulation of endogenous mutant HTT and robust neuronal loss in the striatum of HD140Q KI mice. In transgenic HD mice that selectively express mutant HTT in astrocytes, increased accumulation of mutant HTT in astrocytes via HspBP1 expression did not elicit neurodegeneration but could exacerbate neurological symptoms. Consistently, suppressing the expression of endogenous HspBp1 in the striatum of HD140Q KI mice via CRISPR/Cas9 led to a significant reduction of mutant HTT accumulation. Our findings suggest that although endogenous mutant HTT in astrocytes can exacerbate neurological symptoms, it mediates neurodegeneration only when mutant HTT is also accumulated in neuronal cells. [ABSTRACT FROM AUTHOR]

As blockchain technology booms, modern electronic voting system leverages blockchain as underlying storage model to make the voting process more transparent, and guarantee immutability of data. However, the transparent characteristic may disclose sensitive information of candidate for all system users have the same right to their information. Besides that, the pseudo-anonymity of blockchain will lead to the disclosure of voters' privacy and the third-parties such as registration institutions involved in voting process also have possibility of tampering data. To overcome these difficulties, we apply authority management mechanism into blockchain-based voting systems. In this paper, we put forward AMVchain, a fully decentralized and efficient blockchain-based voting system. AMVchain has a three-layer access control architecture, and on each layer, smart contracts are responsible for validation and granting permissions. Linkable ring signature is adopted in the process of voting to protect ballot-privacy. AMVchain also makes a tradeoff between efficiency and concurrency by introducing proxy nodes. The experiments results show that our system meets the basic requirements under the high concurrent users circumstance. [ABSTRACT FROM AUTHOR]

Uranium is a relatively active and chemically toxic natural radionuclide, its enrichment in the environment poses a serious threat to human health and ecosystems. It is necessary to dispose the uranium contaminated soil safely and efficiently. In this study, the effect of coal gangue-based geopolymers on the solidification of uranium-contaminated soil was examined using a single factor experiment. The highest compressive strength of the solidified body reached 24.6 MPa, and the highest fixation efficiency of uranium reached 77.44%. The results show that lower liquid-to-solid ratio, higher alkali activator content and lower alkali activator modulus promote the solidification of uranium. [ABSTRACT FROM AUTHOR]

One of the more concerning issues in the world today is that radioactive uranium contaminates the soil and threatens the organisms. The focus of contaminated soil remediation is to immobilize the uranium in the soil and reduce its leaching. Nano-hydroxyapatite (nHAP) and nano-hydroxyapatite/nano-zero-valent iron mixture (nHAP/nZVI) are used as immobilizer to remediate uranium-contaminated soil. The leaching characteristics and morphological changes of uranium before and after immobilization were studied by using Toxicity Characteristic Leaching Procedure (TCLP) and Tessier stepwise chemical extraction method. The results show that the leaching concentration of uranium in the soil was 0.005 mg/L when nHAP was added alone, and the leaching rate was 9.14%. The leaching concentration of uranium in the soil was only 0.004 mg/L when adding nHAP/nZVI, and the leaching rate was reduced to 8.57%. U (VI) not only reacts with nHAP to form a stable complex but also is reduced by nZVI to insoluble U (IV) when nHAP/nZVI is added. As a result, both nHAP/nZVI and nHAP can effectively immobilize uranium in the soil, and nHAP/nZVI can better promote the immobilization of the uranium in the soil. [ABSTRACT FROM AUTHOR]

This study investigated the feasibility of hyperspectral imaging techniques to estimate the vigor of heat-damaged Quercus variabilis seeds. Four thermal damage grades were classified according to heat treatment duration (0, 2, 5, and 10 h). After obtaining hyperspectral images with a 370–1042 nm hyperspectral imager that included visible and near infrared light, germination was tested to confirm estimates. The Savitzky–Golay (SG) second derivative was used to preprocess the spectrum to reduce any noise impact. The successive projections algorithm (SPA), principal component analysis, and local linear embedding algorithm were used to extract the characteristic spectral bands related to seed vigor. Finally, a model for seed vigor classification of Q. variabilis based on partial least squares support vector machine (LS-SVM) with different spectral data sets was developed. The results show that the spectrum after SG second derivative preprocessing was better for developing the model, and SPA performed the best among the three feature band selection methods. The combination SG second derivative-LS-SVM provided the best classification model for Q. variabilis seed vigor, with the prediction set reaching 98.81%. This study provides an important basis for rapid and nondestructive assessment of the vigor of heat-damaged seeds using hyperspectral imaging techniques. [ABSTRACT FROM AUTHOR]