Epstein-Barr virus envelope glycoprotein 110 inhibits NF-κB activation by interacting with NF-κB subunit p65.

Epstein-Barr virus (EBV) is a member of the lymphotropic virus family and is highly correlated with some human malignant tumors. It has been reported that envelope glycoprotein 110 (gp110) plays an essential role in viral fusion, DNA replication, and nucleocapsid assembly of EBV. However, it has not been established whether gp110 is involved in regulating the host's innate immunity. In this study, we found that gp110 inhibits tumor necrosis factor α-mediated NF- κB promoter activity and the downstream production of NF- κB-regulated cytokines under physiological conditions. Using dual-luciferase reporter assays, we showed that gp110 might impede the NF-κB promoter activation downstream of NF-κB transactivational subunit p65. Subsequently, we used coimmunoprecipitation assays to demonstrate that gp110 interacts with p65 during EBV lytic infection, and that the C-terminal cytoplasmic region of gp110 is the key interaction domain with p65. Furthermore, we determined that gp110 can bind to the N-terminal Rel homologous and C-terminal domains of p65. Alternatively, gp110 might not disturb the association of p65 with nontransactivational subunit p50, but we showed it restrains activational phosphorylation (at Ser536) and nuclear translocation of p65, which we also found to be executed by the C-terminal cytoplasmic region of gp110. Altogether, these data suggest that the surface protein gp110 may be a vital component for EBV to antagonize the host's innate immune response, which is also helpful for revealing the infectivity and pathogenesis of EBV.

Acute hospitalizations after proton therapy versus intensity-modulated radiotherapy for locally advanced non-small cell lung cancer in the durvalumab era.

INTRODUCTION: It was hypothesized that use of proton beam therapy (PBT) in patients with locally advanced non-small cell lung cancer treated with concurrent chemoradiation and consolidative immune checkpoint inhibition is associated with fewer unplanned hospitalizations compared with intensity-modulated radiotherapy (IMRT). METHODS: Patients with locally advanced non-small cell lung cancer treated between October 2017 and December 2021 with concurrent chemoradiation with either IMRT or PBT ± consolidative immune checkpoint inhibition were retrospectively identified. Logistic regression was used to assess the association of radiation therapy technique with 90-day hospitalization and grade 3 (G3+) lymphopenia. Competing risk regression was used to compare G3+ pneumonitis, G3+ esophagitis, and G3+ cardiac events. Kaplan-Meier method was used for progression-free survival and overall survival. Inverse probability treatment weighting was applied to adjust for differences in PBT and IMRT groups. RESULTS: Of 316 patients, 117 (37%) received PBT and 199 (63%) received IMRT. The PBT group was older (p < .001) and had higher Charlson Comorbidity Index scores (p = .02). The PBT group received a lower mean heart dose (p < .0001), left anterior descending artery V15 Gy (p = .001), mean lung dose (p = .008), and effective dose to immune circulating cells (p < .001). On inverse probability treatment weighting analysis, PBT was associated with fewer unplanned hospitalizations (adjusted odds ratio, 0.55; 95% CI, 0.38-0.81; p = .002) and less G3+ lymphopenia (adjusted odds ratio, 0.55; 95% CI, 0.37-0.81; p = .003). There was no difference in other G3+ toxicities, progression-free survival, or overall survival. CONCLUSIONS: PBT is associated with fewer unplanned hospitalizations, lower effective dose to immune circulating cells and less G3+ lymphopenia compared with IMRT. Minimizing dose to lymphocytes may be warranted, but prospective data are needed.

Facilely Modified Nickel-Based Hole Transporting Layers for Organic Solar Cells with 19.12% Efficiency and Enhanced Stability.

Hole transporting layers (HTLs), strategically positioned between electrode and light absorber, play a pivotal role in shaping charge extraction and transport in organic solar cells (OSCs). However, the commonly used poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) HTL, with its hygroscopic and acidic nature, undermines the operational durability of OSC devices. Herein, an environmentally friendly approach is developed utilizing nickel acetate tetrahydrate (NiAc·4H2O) and [2-(9H-carbazol-9-yl)ethyl] phosphonic acid (2PACz) as the NiAc·4H2O/2PACz HTL, aiming at overcoming the limitations posed by the conventional PEDOT:PSS one. Encouragingly, a remarkable power conversion efficiency (PCE) of 19.12% is obtained for the OSCs employing NiAc·4H2O/2PACz as the HTL, surpassing that of devices with the PEDOT:PSS HTL (17.59%), which is ranked among the highest ones of OSCs. This improvement is attributed to the appropriate work function, enhanced hole mobility, facilitated exciton dissociation efficiency, and lower recombination loss of NiAc·4H2O/2PACz-based devices. Furthermore, the NiAc·4H2O/2PACz-based OSCs exhibit superior operational stability compared to their PEDOT:PSS-based counterparts. Of significant note, the NiAc·4H2O/2PACz HTL demonstrates a broad generality, boosting the PCE of the PM6:PY-IT and PM6:Y6-based OSCs from 16.47% and 16.79% (with PEDOT:PSS-based analogs as HTLs) to 17.36% and 17.57%, respectively. These findings underscore the substantial potential of the NiAc·4H2O/2PACz HTL in advancing OSCs, offering improved performance and stability, thereby opening avenue for highly efficient and reliable solar energy harvesting technologies.

MiR-22 inhibits myocardial fibrosis in rats with myocardial infarction by targeting PTEN/Akt/mTOR signaling pathway.

This study aimed to evaluate the effects of miR-22 on myocardial fibrosis in rats with myocardial infarction (MI) and to further explore the possible underlying mechanism. A total of 80 rats were randomly divided into Sham group, miR-22 overexpression group, MI group or MI + miR-22 overexpression group. Reverse transcription-polymerase chain reaction (RT-PCR) results showed that compared with Sham group, miR-22 expression level in myocardial tissues of rats decreased significantly in MI group. Overexpression of miR-22 could remarkably relieve cardiac insufficiency in MI rats, increase EF% and FS%, and reduce collagen deposition and the mRNA expression level of fibrosis-promoting genes in myocardial tissues of MI rats. The cross-sectional area of myocardial cells in MI + miR-22 mimic group was smaller than that in MI group. According to the results of immunohistochemical staining, overexpression of miR-22 notably reduced the level of oxidative stress marker 4-HNE in myocardial tissues of MI rats. Meanwhile, myocardial cells in MI + miR-22 mimic group exhibited a prominently lower apoptosis rate than those in MI group. Furthermore, Western blotting results demonstrated that overexpression of miR-22 inhibited the activation of the phosphatase and tensin homolog deleted on chromosome ten (PTEN)/Akt/mTOR signaling pathway in myocardial tissues of MI rats. The inhibitory effects of miR-22 on myocardial fibrosis and hypertrophy after MI in rats may be related to its inhibition on the PTEN/Akt/mTOR signaling pathway. All our findings suggested that miR-22 is expected to become a targeted drug for the clinical treatment of MI.

Unsaturation effects on lipid transmembrane asymmetry.

Within cell plasma membranes, unsaturated lipids are asymmetrically distributed over the inner and outer leaflets, offering an attractive local structural feature. However, the mechanism to keep lipid transmembrane asymmetry and the closely related transmembrane movement (flip-flop) for unsaturated lipids remain poorly understood. Here, we applied sum frequency generation vibrational spectroscopy to investigate this lipid transmembrane asymmetry upon mimicking the cell membrane homeostatic processes. On the one hand, unsaturated lipids were found to hinder the flip-flop process and preserve lipid transmembrane asymmetry in model cell membranes, owing to the steric hindrance caused by their bent tails. On the other hand, local unsaturated lipids in the mixed unsaturated/saturated lipid bilayer were conducive to the formation of the local asymmetry. Therefore, lipid unsaturation can be recognized as an intrinsic key factor to form and maintain lipid transmembrane asymmetry in cell membranes.

Butyrate attenuates sympathetic activation in rats with chronic heart failure by inhibiting microglial inflammation in the paraventricular nucleus.

Sympathetic activation is a hallmark of heart failure and the underlying mechanism remains elusive. Butyrate is generated by gut microbiota and influences numerous physiological and pathological processes in the host. The present study aims to investigate whether the intestinal metabolite butyrate reduces sympathetic activation in rats with heart failure (HF) and the underlying mechanisms involved. Sprague-Dawley rats (220‒250 g) are anaesthetized with isoflurane, and the left anterior descending artery is ligated to model HF. Then, the rats are treated with or without butyrate sodium (NaB, a donor of butyrate, 10 g/L in water) for 8 weeks. Blood pressure and renal sympathetic nerve activity (RSNA) are recorded to assess sympathetic outflow. Cardiac function is improved (mean ejection fraction, 22.6%±4.8% vs 38.3%±5.3%; P<0.05), and sympathetic activation is decreased (RSNA, 36.3%±7.9% vs 23.9%±7.6%; P<0.05) in HF rats treated with NaB compared with untreated HF rats. The plasma and cerebrospinal fluid levels of norepinephrine are decreased in HF rats treated with NaB. The infusion of N-methyl-D-aspartic acid (NMDA) into the paraventricular nucleus (PVN) of the hypothalamus of HF model rats increases sympathetic nervous activity by upregulating the NMDA receptor. Microglia polarized to the M2 phenotype and inflammation are markedly attenuated in the PVN of HF model rats after NaB administration. In addition, HF model rats treated with NaB exhibit enhanced intestinal barrier function and increased levels of GPR109A, zona occludens-1 and occludin, but decreased levels of lipopolysaccharide-binding protein and zonulin. In conclusion, butyrate attenuates sympathetic activation and improves cardiac function in rats with HF. The improvements in intestinal barrier function, reductions in microglia-mediated inflammation and decreases in NMDA receptor 1 expression in the PVN are all due to the protective effects of NaB.

Meta-Analysis on the Recovery Effect of Acupuncture Combined With Rehabilitation Therapy in Spinal Cord Injury Patients.

Objective: To explore the recovery effect of acupuncture combined with rehabilitation therapy on muscle spasms in patients with spinal cord injury through a systematic review of meta-analysis methods. Methods: Use "acupuncture," "electronic-acupuncture," "spinal cord," "spasm," and "paraplegia" as keywords, CNKI, Google, Wanfang, VIP, sci-hub, Web of Science, PubMed, and other Chinese or English databases were searched. To collect the domestic and foreign research on acupuncture combined with rehabilitation for muscle spasms in patients with spinal cord injury. Preliminary screening was conducted, and data extraction and quality evaluation were carried out on the included literature, including publication time, sample size, treatment methods, recovery effects, etc. According to the literature, the influence of acupuncture combined with rehabilitation therapy on muscle spasms in patients with spinal cord injury and related indices was analyzed. The search period was from January 2018 to June 2023, and the selected research results were tested by RevMan5.3 software and data consolidation for consistency. The methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS). Results: A preliminary literature search yielded 172 papers. 53 papers from sci-hub, 71 papers from HowNet, 36 papers from Wanfang, and 12 papers from VIP. Finally, 10 articles that met the criteria were included, including 594 patients. According to different treatment methods, the literature about acupuncture combined with rehabilitation therapy for muscle spasms in patients with spinal cord injury was analyzed for consistency, and data were merged. It was concluded that acupuncture combined with rehabilitation The clinical curative effect of the experimental group of patients is higher than that of the control group MD=5.31, 95%CI (2.94, 7.81), Z=5.64, P < .001; the clinical effective rate of the experimental group is higher than that of the control group. The improvement of the clinical spasticity index (CSI) score index of the patients in the experimental group was better than that of the control group MD = -3.09, 95%CI (-4.51, -1.67), Z =4.28, P < .001; the MAS score of the patients in the experimental group The improvement was better than that of the control group MD =-0.76, 95%CI (-1.16, -0.38), Z=8.13, P < .001; the improvement of Barthel index (BI) in the experimental group was better than that of the control group MD=9.81, 95%CI (7.84,11.71), Z=12.71, P < .001; no adverse events were reported in the experimental group and the control group. Conclusion: This study shows that acupuncture and rehabilitation are more effective than other therapeutic methods in the treatment of muscle spasms after spinal cord injury, and more randomized controlled trials are needed to verify this in the future.

Mechanisms of cadmium release from manganese-rich sediments driven by exogenous DOM and the role of microorganisms.

Dissolved organic matter (DOM) is a crucial component of natural sediments that alters Cd sequestration. Nevertheless, how different types of DOM fuel Cd mobilization in Mn-rich sediments has not been elucidated. In the present study, four typical DOM, fluvic acid (FA), bovine serum albumin (BSA), sodium alginate (SA), and sodium dodecyl benzene sulfonate (SDBS), were used to amend Cd-contaminated sediment to study their effects on Cd/Mn biotransformation and microbial community response. The results demonstrated that different DOM drive microbial community shifts and enhance microbially mediated Mn oxide (MnO) reduction and Cd release. The amendment of terrestrial- and anthropogenic-derived DOM (FA and SDBS) mainly contributed to enriching Mn-reducing bacteria phylum Proteobacteria, and its abundance increased by 38.16-74.47 % and 56.41-73.98 %, respectively. Meanwhile, microbial-derived DOM (BSA and SA) mainly stimulated the abundances of metal(loid)-resistant bacteria phylum Firmicutes. Accompanied by microbial community structure, diversity, and co-occurrence network shifts, the DOM concentration and oxidation-reduction potential changed, resulting in enhanced Cd mobilization. Importantly, FA stimulated Cd release most remarkably, probably because of the decreased cooperative interactions between bacterial populations, stronger reduction of MnOs, and higher aromaticity and hydrophobicity of the sediment DOM after amendment. This study linked DOM types to functional microbial communities, and explored the potential roles of different DOM types in Cd biotransformation in lake sediments.

Revealing the Mechanism of NLRP3 Inflammatory Pathway Activation through K+ Efflux Induced by PLO via Signal Point Mutations.

Trueperella pyogenes is an important opportunistic pathogenic bacterium widely distributed in the environment. Pyolysin (PLO) is a primary virulence factor of T. pyogenes and capable of lysing many different cells. PLO is a member of the cholesterol-dependent cytolysin (CDC) family of which the primary structure only presents a low level of homology with other members from 31% to 45%. By deeply studying PLO, we can understand the overall pathogenic mechanism of CDC family proteins. This study established a mouse muscle tissue model infected with recombinant PLO (rPLO) and its single-point mutations, rPLO N139K and rPLO F240A, and explored its mechanism of causing inflammatory damage. The inflammatory injury abilities of rPLO N139K and rPLO F240A are significantly reduced compared to rPLO. This study elaborated on the inflammatory mechanism of PLO by examining its unit point mutations in detail. Our data also provide a theoretical basis and practical significance for future research on toxins and bacteria.

Thermodynamic Entropy-Based Fatigue Life Assessment Method for Nickel-Based Superalloy GH4169 at Elevated Temperature Considering Cyclic Viscoplasticity.

This paper develops a thermodynamic entropy-based life prediction model to estimate the low-cycle fatigue (LCF) life of the nickel-based superalloy GH4169 at elevated temperature (650 °C). The gauge section of the specimen was chosen as the thermodynamic system for modeling entropy generation within the framework of the Chaboche viscoplasticity constitutive theory. Furthermore, an explicitly numerical integration algorithm was compiled to calculate the cyclic stress-strain responses and thermodynamic entropy generation for establishing the framework for fatigue life assessment. A thermodynamic entropy-based life prediction model is proposed with a damage parameter based on entropy generation considering the influence of loading ratio. Fatigue lives for GH4169 at 650 °C under various loading conditions were estimated utilizing the proposed model, and the results showed good consistency with the experimental results. Finally, compared to the existing classical models, such as Manson-Coffin, Ostergren, Walker strain, and SWT, the thermodynamic entropy-based life prediction model provided significantly better life prediction results.

Very high-frequency, gate-tunable CrPS4 nanomechanical resonator with single mode.

Two-dimensional (2D) antiferromagnetic semiconductor chromium thiophosphate (CrPS4) has gradually become a major candidate material for low-dimensional nanoelectromechanical devices due to its remarkable structural, photoelectric characteristics and potentially magnetic properties. Here, we report the experimental study of a new few-layer CrPS4 nanomechanical resonator demonstrating excellent vibration characteristics through the laser interferometry system, including the uniqueness of resonant mode, the ability to work at the very high frequency, and gate tuning. In addition, we demonstrate that the magnetic phase transition of CrPS4 strips can be effectively detected by temperature-regulated resonant frequencies, which proves the coupling between magnetic phase and mechanical vibration. We believe that our findings will promote the further research and applications of the resonator for 2D magnetic materials in the field of optical/mechanical signal sensing and precision measurement.

Gate-tunable bolometer based on strongly coupled graphene mechanical resonators.

Bolometers based on graphene have demonstrated outstanding performance with high sensitivity and short response time. In situ adjustment of bolometers is very important in various applications, but it is still difficult to implement in many systems. Here we propose a gate-tunable bolometer based on two strongly coupled graphene nanomechanical resonators. Both resonators are exposed to the same light field, and we can measure the properties of one bolometer by directly tracking the resonance frequency shifts, and indirectly measure the other bolometer through mechanical coupling. We find that the sensitivity and the response bandwidth of both bolometers can be independently adjusted by tuning the corresponding gate voltages. Moreover, the properties of the indirectly measured bolometer show a dependence on the coupling between the two resonators, with other parameters being fixed. Our method has the potential to optimize the design of large-scale bolometer arrays, and open new horizons in infrared/terahertz astronomy and communication systems.

Enhanced Sum Frequency Generation for Monolayers on Au Relative to Silica: Local Field Factors and SPR Effect.

Using metals as signal magnified substrates, surface plasmon-enhanced sum frequency generation (SFG) vibrational spectroscopy is a promising technique to probe weak molecular-level signals at surfaces and interfaces. In this study, the vibrational signals of the n-alkane monolayer on the gold (Au) and silica substrates are investigated using the broadband femtosecond SFG. The enhancement factors are discovered to be up to ∼1076 and ∼31 for the methyl symmetric and asymmetric stretching (ss and as) modes of the monolayer, respectively. By systematically analyzing the second-order nonlinear susceptibility tensor components (χijks), the Fresnel coefficients (Fijks), and the surface plasmon resonance (SPR) effect, we find that the interplay between Fijk and χijk terms and the SPR effect dominate the SFG signal enhancement. Our study reveals that the relative contributions of different influencing factors (i.e., Fresnel coefficients and SPR) to the SFG signal enhancement provide an approach to interpreting enhanced SFG vibrational signals detected from probe molecules on distinct substrates and may finally guide the design of the experimental methodology to improve the detection sensitivity and signal-to-noise ratio.

Antibiotics and antibiotic resistance genes in the water sources of the Wuhan stretch of the Yangtze River: Occurrence, distribution, and ecological risks.

Given the ubiquitous detection of antibiotics and antibiotic resistance genes (ARGs) in waterbodies worldwide and increasing public attention to water resource safety, this study investigated the presence of antibiotics and ARGs in the water sources of the Wuhan stretch of the Yangtze River (YR) as well as potential ecological risks. In this study, 15 antibiotics and 10 ARGs in a source of drinking water were analyzed using solid-phase extraction-ultra performance liquid chromatography-mass spectrometry technology (SPE-UPLC-MS/MS) and real-time fluorescence quantitative polymerase chain reaction (qPCR). Fourteen antibiotics were detected in the samples from 18 water sources, with the highest concentration detected for tetracycline, reaching up to 1708.33 ng/L. The detection rates of norfloxacin, enrofloxacin, ofloxacin, tetracycline, and roxithromycin were 100%. The concentrations of antibiotics were highest in She Shui, followed by the Wuhan stretch of the lower reaches of the YR, whereas the lowest concentrations were found in the Wuhan stretch of the upper reaches of the YR which were approximately equal to those in the Han River (HR). Ofloxacin and roxithromycin presented a substantial threat to aquatic organisms with high sensitivity at the majority of the sampling sites. The overall abundance of ARGs was notably greater in the lower reaches of the YR compared with the upper reaches and the HR. The highest absolute abundance was observed for sulfa ARGs. Integron intl1 strongly correlated with sul1, sul2, ermB, and qnrS, and antibiotics, strongly correlated with multiple ARGs, suggesting that antibiotics and ARGs are present in water sources in Wuhan and may present a plausible hazard to both human and ecological well-being. Hence, regulating the spread and dissemination of antibiotics and ARGs in the environment is imperative. The findings of this research offer significant insights into the stewardship and safeguarding of aquatic reserves in the Wuhan stretch of the YR.

Tetanus toxin and botulinum neurotoxin-derived fusion molecules are effective bivalent vaccines.

Tetanus toxin (TeNT) and botulinum neurotoxins (BoNTs) are neuroprotein toxins, with the latter being the most toxic known protein. They are structurally similar and contain three functional domains: an N-terminal catalytic domain (light chain), an internal heavy-chain translocation domain (HN domain), and a C-terminal heavy chain receptor binding domain (Hc domain or RBD). In this study, fusion functional domain molecules consisting of the TeNT RBD (THc) and the BoNT/A RBD (AHc) (i.e., THc-Linker-AHc and AHc-Linker-THc) were designed, prepared, and identified. The interaction of each Hc domain and the ganglioside receptor (GT1b) or the receptor synaptic vesicle glycoprotein 2 (SV2) was explored in vitro. Their immune response characteristics and protective efficacy were investigated in animal models. The recombinant THc-linker-AHc and AHc-linker-THc proteins with the binding activity had the correct size and structure, thus representing novel subunit vaccines. THc-linker-AHc and AHc-linker-THc induced high levels of specific neutralizing antibodies, and showed strong immune protective efficacy against both toxins. The high antibody titers against the two novel fusion domain molecules and against individual THc and AHc suggested that the THc and AHc domains, as antigens in the fusion functional domain molecules, do not interact with each other and retain their full key epitopes responsible for inducing neutralizing antibodies. Thus, the recombinant THc-linker-AHc and AHc-linker-THc molecules are strong and effective bivalent biotoxin vaccines, protecting against two biotoxins simultaneously. Our experimental design will be valuable to develop recombinant double-RBD fusion molecules as potent bivalent subunit vaccines against bio-toxins. KEY POINTS: • Double-RBD fusion molecules from two toxins had the correct structure and activity. • THc-linker-AHc and AHc-linker-THc efficiently protected against both biotoxins. • Such bivalent biotoxin vaccines based on the RBD are a valuable experimental design.

Manganese oxides mediated dissolve organic matter compositional changes in lake sediment and cadmium binding characteristics.

In sediment environments, manganese (Mn) minerals have high dissolved organic matter (DOM) affinities, and could regulate the changes of DOM constituents and reactivity by fractionation. However, the effects of DOM fractionation by Mn minerals on the contaminant behaviors remain unclear. Herein, the transformations of mineral phases, DOM properties, and Cd(II) binding characteristics to sediment DOM before and after adsorption by four Mn oxides (δ-MnO2, ß-MnO2, γ-MnOOH, and Mn3O4) were investigated using multi-spectroscopic tools. Results showed a subtle structural variation of Mn oxides in response to DOM reduction, and no phase transformations were observed. Two-dimensional correlation spectroscopy based on synchronous fluorescence spectra and Fourier transform infrared spectroscopy indicated that tryptophan-like substances and the amide (II) N-H groups could preferentially interact with Cd(II) for the original DOM. Nevertheless, preferential bonding of Cd(II) to tyrosine-like substances and phenolic OH groups was exhibited after fractionations by Mn oxides. Furthermore, the binding stability and capacity of each DOM fraction to Cd(II) were decreased after fractionation based on the modified Stern-Volmer equation. These differences may be attributed to DOM molecules with high aromaticity, hydrophobicity, molecular weight, and amounts of O/N-containing group were preferentially removed by Mn oxides. Overall, the environmental hazard of Cd will be more severe after DOM fractionation on Mn minerals. This study facilitates a better understanding of the Cd geochemical cycle in lake sediments under the DOM-mineral interactions, and recommends being careful with outbreaks of aquatic Cd pollution when sediments are rich in dissolved protein-like components and Mn minerals.

Biology activity and characterization of the functional L-HN fragment derivative of botulinum neurotoxin serotype E.

OBJECTIVES: The mature botulinum neurotoxin (BoNT) is a long peptide chain consisting of a light chain (L) and a heavy chain (H) linked by a disulfide bond, where the heavy chain is divided into a translocation domain and an acceptor binding domain (Hc). In this study, we further explored the biology activity and characteristics of recombinant L-HN fragment (EL-HN) composed of the L and HN domains of BoNT/E in vivo and in vitro. METHODS: Neurotoxicity of L-HN fragments from botulinum neurotoxins was assessed in mice. Cleavage of dichain EL-HN in vitro and in neuro-2a cells was assessed and compared with that of single chain EL-HN. Interaction of HN domain and the receptor synaptic vesicle glycoprotein 2C (SV2C) was explored in vitro and in neuro-2a cells only expressing SV2C. RESULTS: We found that the 50% mouse lethal dose of the nicked dichain EL-HN fragment (EL-HN-DC) was 0.5 µg and its neurotoxicity was the highest among the L-HN's of the four serotypes of BoNT (A/B/E/F). The cleavage efficiency of EL-HN-DC toward synaptosome associated protein 25 (SNAP25) in vitro was 3-fold higher than that of the single chain at the cellular level, and showed 200-fold higher animal toxicity. The EL-HN-DC fragment might enter neuro-2a cells via binding to SV2C to efficiently cleave SNAP25. CONCLUSIONS: The EL-HN fragment showed good biological activities in vivo and in vitro, and could be used as a drug screening model and to further explore the molecular mechanism of its transmembrane transport.

A Robot-Operation-System-Based Smart Machine Box and Its Application on Predictive Maintenance.

Predictive maintenance is a proactive approach to maintenance in which equipment and machinery are monitored and analyzed to predict when maintenance is needed. Instead of relying on fixed schedules or reacting to breakdowns, predictive maintenance uses data and analytics to determine the appropriate time to perform maintenance activities. In industrial applications, machine boxes can be used to collect and transmit the feature information of manufacturing machines. The collected data are essential to identify the status of working machines. This paper investigates the design and implementation of a machine box based on the ROS framework. Several types of communication interfaces are included that can be adopted to different sensor modules for data sensing. The collected data are used for the application on predictive maintenance. The key concepts of predictive maintenance include data collection, a feature analysis, and predictive models. A correlation analysis is crucial in a feature analysis, where the dominant features can be determined. In this work, linear regression, a neural network, and a decision tree are adopted for model learning. Experimental results illustrate the feasibility of the proposed smart machine box. Also, the remaining useful life can be effectively predicted according to the trained models.

Efficient removal of thiamethoxam by freshwater microalgae Scenedesmus sp. TXH: Removal mechanism, metabolic degradation and application.

Neonicotinoids, as the most widely used pesticides in the world, help improve the production of crops. Meanwhile, it also brings potential threats to surrounding environments and other organisms because of its wide use and even abuse. In this study, Scenedesmus sp. TXH isolated from a wastewater treatment plant was used to remove the neonicotinoid pesticide thiamethoxam (THIA). The removal efficiency, degradation pathway, metabolite fate of THIA and physicochemical effects on microalgae cells were studied. Meanwhile, the feasibility of using microalgal technology to remove THIA from municipal wastewater was also explored. The results showed that 5-40 mg/L of THIA slightly promoted the growth of microalgae, while 60 mg/L THIA severely inhibited microalgal growth. It was observed that malondialdehyde content and superoxide dismutase activity in 60 mg/L THIA group increased significantly (p < 0.05) in the early stage of the experiment, indicating that THIA caused oxidative damage to microalgae. Scenedesmus sp. TXH showed high-efficient degradation ability and high resistance to THIA, with 100% removal of THIA at 5, 20 and 40 mg/L groups and 97.5% removal of THIA at 60 mg/L group on day 12. THIA was mainly removed by biodegradation, accounting for 78.18%, 93.50%, 96.81% and 91.35% under 5, 20, 40 and 60 mg/L on day 12, respectively. Six degradation products were identified, and four potential degradation pathways were proposed. In practical wastewater, the removal efficiency of total dissolved nitrogen, total dissolved phosphorus, ammonia nitrogen and THIA reached 85.68%, 90.00%, 98.43% and 100%, respectively, indicating that Scenedesmus sp. TXH was well adapted to the wastewater and effectively removed THIA and conventional pollutants.

Study on N application and N reduction potential of farmland in China.

The frequent occurrence of extreme weather in recent years poses a significant threat to food production. Ensuring food production and rationalizing the use of agricultural resources require addressing the problem of the improper application of chemical fertilizers. Several effective measures have been implemented in China to reduce agricultural non-point source pollution. Among them, the reduction of excessive nitrogen fertilizer application proves to be the most effective approach in controlling surface pollution from cultivation. Currently, it is crucial to clarify and quantify crop nutrient fertilizer requirements while evaluating the potential for reducing nitrogen fertilizer usage in China. Nitrogen requirements for major crops grown in China were assessed based on the theory of crop nutrient balance, assuming constant grain production as a guarantee. In this paper, we analyze the potential for nitrogen reduction through short-term, medium-term, and long-term scenario predictions. The results show that in the next 3 years, China has a reduction potential of 34.98%, but this potential is not sustainable. Over the next 10 years, there is a reduction potential of 15.04%, with most provinces experiencing a balanced state of soil nitrogen cycling. Hainan, Beijing, Shaanxi, and Fujian have higher reduction potential, with possible reductions of 69.95%, 64.14%, 60.72%, and 54.10%, respectively. However, there are still provinces in China where nitrogen fertilizer is insufficient, leading to soil nitrogen consumption. Specifically, Heilongjiang, Jiangxi, and Shandong Provinces need to increase their nitrogen fertilizer applications by 87.00%, 35.97%, and 8.31%, respectively. The long-term scenario analysis over the next 30 years shows a reduction potential of 40.96%. Among the regions analyzed, Hainan, Beijing, Shaanxi, Fujian, and Ningxia have higher nitrogen fertilizer reduction potentials, with values of 78.97%, 78.48%, 74.25%, 67.87%, and 67.72%, respectively. However, Heilongjiang Province still needs to increase nitrogen fertilizer application by 44.20% to address soil nitrogen depletion. Conversely, Tibet and Qinghai, with high organic fertilizer yields, lower chemical fertilizer usage, and low nitrogen loss coefficients, are well-suited for organic agriculture development. For areas with high organic fertilizers usage and a risk of fertilizer loss, we recommend implementing the organic-inorganic mixed fertilization planting mode.