Spontaneous Regression of a Large Vestibular Schwannoma: Is Nonoperative Management Reasonable?

Vestibular schwannomas (VSs) are the most common cerebellopontine tumors. The natural history of smaller-sized VSs (<30 mm) has been well-studied, leading to the recommendation of a "watch and wait" approach. However, large VSs (>30 mm) have not been extensively studied, mainly because of their rarity. As such, most patients are conventionally offered surgery which carries a significant risk of neurological morbidity. Here, we report a case of a giant VS (>40 mm) in a 30-year-old man who regressed spontaneously. He was lost to follow-up for 18 years and, upon re-presentation, the symptomatology drastically improved and repeat imaging demonstrated a marked reduction in tumor size. Referring to similar cases in other studies, we postulate that most large and giant VSs undergo a phase of growth and stasis, followed by regression due to shifts in the balance between tumorigenic and regressive factors. Taken together with emerging molecular data, further studies are required to better understand the history of large and giant VSs to shape more personalized treatment options. This potentially includes non-operative management as a tenable option.

Single-tube protocol for culture-independent spoligotyping of Mycobacterium tuberculosis based on MeltArray.

IMPORTANCE: Spacer oligonucleotide typing (spoligotyping), the first-line genotyping assay for Mycobacterium tuberculosis (MTB), plays a fundamental role in the investigation of its epidemiology and evolution. In this study, we established a single-tube spoligotyping assay using MeltArray, a highly multiplex polymerase chain reaction (PCR) approach that runs on a real-time PCR thermocycler. The MeltArray protocol included an internal positive control, gyrB, to indicate the abundance of MTB via the quantification cycle and 43 spacers to identify the spoligotype via melting curve analysis. The entire protocol was completed in a single step within 2.5 hours. The lowest detectable copy number for the tested strains was 20 copies/reaction and thus sufficient for analyzing both culture and sputum samples. We conclude that MeltArray-based spoligotyping could be used immediately in low- and middle-income countries with a high tuberculosis burden, given its easy access, improved throughput, and potential applicability to clinical samples.

Epidemiological Insights into the Omicron Outbreak via MeltArray-Assisted Real-Time Tracking of SARS-CoV-2 Variants.

The prolonged course of the COVID-19 pandemic necessitates sustained surveillance of emerging variants. This study aimed to develop a multiplex real-time polymerase chain reaction (rt-PCR) suitable for the real-time tracking of Omicron subvariants in clinical and wastewater samples. Plasmids containing variant-specific mutations were used to develop a MeltArray assay. After a comprehensive evaluation of both analytical and clinical performance, the established assay was used to detect Omicron variants in clinical and wastewater samples, and the results were compared with those of next-generation sequencing (NGS) and droplet digital PCR (ddPCR). The MeltArray assay identified 14 variant-specific mutations, enabling the detection of five Omicron sublineages (BA.2*, BA.5.2*, BA.2.75*, BQ.1*, and XBB.1*) and eight subvariants (BF.7, BN.1, BR.2, BQ.1.1, XBB.1.5, XBB.1.16, XBB.1.9, and BA.4.6). The limit of detection (LOD) of the assay was 50 copies/reaction, and no cross-reactivity was observed with 15 other respiratory viruses. Using NGS as the reference method, the clinical evaluation of 232 swab samples exhibited a clinical sensitivity of > 95.12% (95% CI 89.77-97.75%) and a specificity of > 95.21% (95% CI, 91.15-97.46%). When used to evaluate the Omicron outbreak from late 2022 to early 2023, the MeltArray assay performed on 1408 samples revealed that the epidemic was driven by BA.5.2* (883, 62.71%) and BF.7 (525, 37.29%). Additionally, the MeltArray assay demonstrated potential for estimating variant abundance in wastewater samples. The MeltArray assay is a rapid and scalable method for identifying SARS-CoV-2 variants. Integrating this approach with NGS and ddPCR will improve variant surveillance capabilities and ensure preparedness for future variants.

Ameliorative effects of the Coptis inflorescence extract against lung injury in diabetic mice by regulating AMPK/NEU1 signaling.

BACKGROUND: In diabetic patients, complications are the leading cause of death and disability, while diabetic lung damage has received little research. The Coptis inflorescence extract (CE) has hypoglycemic properties, but the mechanism of its protective role on diabetic lung injury is understood. PURPOSE: This study aims to explore the protective actions and molecular mechanism of CE and its active ingredients in diabetic lung disease. METHOD: Twenty-nine metabolites were identified in the metabolomic profile of CE using HPLC-ESI/MS, and high-content substances of berberine (BBR) and linarin (LIN) were isolated from CE using column chromatography. The potential targets and molecular mechanisms of CE against diabetic lung damage were systematically investigated by network pharmacology and in vitro experimental validation. RESULTS: CE significantly improved lung function and pathology. CE (360 mg/kg) or metformin treatment significantly improved lipid metabolism disorders, including decreased HDL-C and elevated serum TG, TC, and LDL-C levels. Furthermore, CE's chemical composition was determined using the HPLC-QTOF-MS method. CE identified five compounds as candidate active compounds (Berberine, Linarin, Palmatine, Worenine, and Coptisine). Network pharmacology analysis predicted CE contained five active compounds and target proteins, that AMPK, TGFß1, and Smad might be the key targets in treating diabetic lung injury. Then we investigated the therapeutic effect of bioactive compounds of CE on diabetic lung damage through in vivo and in vitro experiments. Intragastric administration with BBR (50 mg/kg) or LIN (20 mg/kg) suppressed weight loss, hyperglycemia, and dyslipidemia, significantly alleviating lung inflammation in diabetic mice. Further mechanism research revealed that LIN or BBR inhibited alveolar epithelial-mesenchymal transition induced by high glucose by regulating AMPK/NEU-mediated signaling pathway. CONCLUSION: In conclusion, the administration of CE can effectively alleviate diabetic lung damage, providing a scientific basis for lowering blood sugar to moisturize lung function. BBR and LIN, the main components of CE, can effectively alleviate diabetic lung damage by regulating AMPK/NEU1 Signaling and inhibiting the TGF-ß1 level, which may be a critical mechanism of its effects.

Polypropylene microplastics aging under natural conditions in winter and summer and its effects on the sorption and desorption of nonylphenol.

Plastics in the environment undergo various aging effects. Due to the changes in physical and chemical properties, the sorption behavior of aged microplastics (MPs) for pollutants differs from that of pristine MPs. In this paper, the most common disposable polypropylene (PP) rice box was used as the source of MPs to study the sorption and desorption behavior of nonylphenol (NP) on pristine and naturally aged PPs in summer and winter. The results show that summer-aged PP has more obvious property changes than winter-aged PP. The equilibrium sorption amount of NP on PP is summer-aged PP (477.08 µg/g) > winter-aged PP (407.14 µg/g) > pristine PP (389.29 µg/g). The sorption mechanism includes the partition effect, van der Waals forces, hydrogen bonds and hydrophobic interaction, among which chemical sorption (hydrogen bonding) dominates the sorption; moreover, partition also plays an important role in this process. Aged MPs' more robust sorption capacity is attributed to the larger specific surface area, stronger polarity and more oxygen-containing functional groups on the surface that are conducive to forming hydrogen bonds with NP. Desorption of NP in the simulated intestinal fluid is significant owning to intestinal micelles' presence: summer-aged PP (300.52 µg/g) > winter-aged PP (291.08 µg/g) > pristine PP (287.12 µg/g). Hence, aged PP presents a more vital ecological risk.

Damage law and mechanism of coal-rock joint structure induced by liquid nitrogen at low temperature.

The width and degree of connectivity of coal-rock joints directly affect the seepage capacity of flow energy such as gas. To study the damage law and mechanism of the coal-rock joint structure under the action of liquid nitrogen, two methods of liquid nitrogen unloaded and liquid nitrogen freeze-thaw were used to carry out damage modification experiments on coal-rock with different water saturation. Using OLS4000 laser confocal microscope and MH-25 universal testing machine to conduct electron microscope scanning and uniaxial compression test, measure the joint width expansions and Young's modulus of the coal-rock surface before and after the test, establish a physical and mechanical model of freeze-thaw damage to analyze the ice-wedge expansion stress influence on the damage of coal-rock joint structure and establish damage criterion. The research results show that the ice-wedge expansion stress, confining pressure, and temperature stress in the joint jointly affect the structural damage of coal-rock joints, and the ice-wedge expansion stress contributes the most. With the increase of water saturation, the damage to the coal-rock joint structure intensifies, and the ice-wedge expansion stress under the water saturation state has the most obvious influence on the damage to the coal-rock joint structure. The damage criterion constructed by the freeze-thaw damage physical-mechanical model can reveal the damage mechanism of the effect of ice-wedge expansion stress on the coal-rock joint structure. This paper has certain practical significance for the safety and stability evaluation of rock engineering in cold and arid regions and provides new ideas for effectively extracting clean energy such as coalbed methane and preventing rock bursts.

Enhanced degradation mechanism of tetracycline by MnO2 with the presence of organic acids.

In this study, we constructed MnO2/organic acid (OA) systems using MnO2 colloid, the most reactive phase of Mn(IV), and two kinds of OA (oxalic acid and l-tartaric acid). We investigated the effect of OA on tetracycline (TC) degradation by MnO2. The results show that both OA obviously accelerate TC degradation by MnO2. Mn(III) formed during the reaction lead to the acceleration. Mn(III)-oxalate complex formed in oxalic acid system resulted in the lower degradation efficiency than that in l-tartaric acid system. The acceleration of oxalic acid was decreased when the concentration was more than 75 µM, and even completely disappeared with the concentration of 500 µM, owning to the fact that excess oxalic acid decreased the pH and some MnO2 was fast reduced to Mn2+ by oxalic acid and unable to react with TC. The impact of pH on TC degradation resulted from the influences of H+ on MnO2 redox potentials and TC deprotonation. And acidic conditions accelerated TC degradation. The addition of Mg2+, Ca2+, Fe3+ and Zn2+ exhibited an inhibitory effect in both systems for their occupying reactive sites on MnO2 surface and blocking the access of TC to MnO2. Similar intermediates in the two systems were detected, indicating a similar TC degradation mechanism including a series of reactions like dehydration, hydroxylation and oxidation. The MnO2/OA system provides an efficient treatment of TC in wastewater. And it is also noticeable that MnO2/OA system should also have an important effect on the fate of pollutants in environment, from our results.

Alignment-free sequence comparison for virus genomes based on location correlation coefficient.

Coronaviruses (especially SARS-CoV-2) are characterized by rapid mutation and wide spread. As these characteristics easily lead to global pandemics, studying the evolutionary relationship between viruses is essential for clinical diagnosis. DNA sequencing has played an important role in evolutionary analysis. Recent alignment-free methods can overcome the problems of traditional alignment-based methods, which consume both time and space. This paper proposes a novel alignment-free method called the correlation coefficient feature vector (CCFV), which defines a correlation measure of the L-step delay of a nucleotide location from its location in the original DNA sequence. The numerical feature is a 16×L-dimensional numerical vector describing the distribution characteristics of the nucleotide positions in a DNA sequence. The proposed L-step delay correlation measure is interestingly related to some types of L+1 spaced mers. Unlike traditional gene comparison, our method avoids the computational complexity of multiple sequence alignment, and hence improves the speed of sequence comparison. Our method is applied to evolutionary analysis of the common human viruses including SARS-CoV-2, Dengue virus, Hepatitis B virus, and human rhinovirus and achieves the same or even better results than alignment-based methods. Especially for SARS-CoV-2, our method also confirms that bats are potential intermediate hosts of SARS-CoV-2.

Photodegradation of dissolved organic matter of chicken manure: Property changes and effects on Zn2+/Cu2+ binding property.

Untreated livestock manure contains high concentrations of dissolved organic matter (DOM), which can enter the environment through leaching and eluviation, showing an important impact on the environment. In this research, fresh chicken manure from a large-scale chicken farm was collected as the source of DOM. The infrared spectrum of the original DOM was characterized. TOC analysis, UV spectrum and 3D fluorescence spectrum were used to measure the properties of DOM before and after photodegradation. Infrared spectroscopy results show that chicken manure DOM may contain aliphatic and aromatic compounds, alcohols, phenols, polysaccharides and some protein substances; In three systems, the order of TOC removal rates of DOM was water + UV system (85%) > > water + simulated sunlight system (7.2%) > ice + simulated sunlight system (4.5%); Changes of UV spectra, fluorescence spectra, molecular weight distribution and pH value show that, in three systems, as the illumination time increased, photodegradation reduced pH value of the systems, aromaticity and humus contents of DOM, while increased the proportion of medium and/or small molecular weight components of DOM. The amounts of all these changes were proportional to DOM photodegradation rates in the system. The binding ability of DOM with Cu2+ and Zn2+ in water solution decreased significantly after the photodegradation.

Removal of tetracyclines from aqueous solutions by electrocoagulation/pecan nutshell coupling processes: synergistic effect and mechanism.

The present work compared electrocoagulation (EC)/pecan shell (PS) coupling process with a simple electrocoagulation (EC) process for the removal of tetracyclines (TCs). The results indicated that the addition of appropriate PS could lead to the enhancement of the removal efficiency and decrease of operating time via synergistic influence, including conventional EC process, biomass materials adsorption, charge neutralization and coordination adsorption. The ideal condition for the coupling process was 2.5 mA/cm2 for current density and 3 cm for plate spacing. Based on the optimum condition, when the dosage of PS was 5 g/L, the initial concentration of tetracycline hydrochloride (TC), oxytetracycline hydrochloride (OTC) and chlortetracycline hydrochloride (CTC) was 250 mg/L, the removal rate of PS was 55.90%, 45.10% and 14.98% higher than those of EC process after 40 min treatment. In addition, compared to conventional EC process, the unit energy demand (UED) decreased by 49.62%, 53.2 4% and 26.35% and the unit electrode material demand (UEMD) decreased by 49.80%, 85.65% and 44.37%, respectively, which means more energy conservation and environmental protection.

Ecological environment assessment based on land use simulation: A case study in the Heihe River Basin.

Ecological environment assessment can not only provide significant references for effective solutions to regional ecological problems, but also promote the benign interaction of socio-economic-ecological development. This study selected the Heihe River Basin (HRB) as the typical area to comprehensively evaluate the ecological environment from 2010 to 2030 based on the dynamics of land system (DLS) model, which is coupled with the biological abundance index (BAI), vegetation coverage index (VCI), water density index (WDI), land degradation index (LDI), and eco-environment quality index (EQI). The results indicate that the BAI and VCI will be high in the south and east, low in the north and west in general. Under the future baseline scenario, the changes of biological abundance, vegetation coverage, and deteriorating land in the midstream and downstream regions will may seriously hinder restoration of the ecological environment. In particular, the BAI in the midstream and downstream regions will decline more rapidly, with a rate of 10.30% and 18.59%, respectively. The water area will be scattered and less abundant overall, but the WDI in the midstream, that is up to 3.86 in 2030, will be higher than that in other regions. Results also show that the regions with high EQI are mainly located in the northeast and south region. It is predicted that the ecological fragile zones in the future will mainly distribute in the midstream and downstream regions, especially in Jiayuguan City and Jinta County. The EQI will drop by 44.28% and 11.40% during 2010-2030 without external conditions intervened. In addition, Qilian Mountain, Jiuquan City, Gaotai County, Linze County, and Shandan County will also have relatively strong recovery capacities under the influence of ecological policies. All above could provide the basis for the development of future watershed ecological environment management and protection planning.

Robust Landmark Detection and Position Measurement Based on Monocular Vision for Autonomous Aerial Refueling of UAVs.

In this paper, a position measurement system, including drogue's landmark detection and position computation for autonomous aerial refueling of unmanned aerial vehicles, is proposed. A multitask parallel deep convolution neural network (MPDCNN) is designed to detect the landmarks of the drogue target. In MPDCNN, two parallel convolution networks are used, and a fusion mechanism is proposed to accomplish the effective fusion of the drogue's two salient parts' landmark detection. Considering the drogue target's geometric constraints, a position measurement method based on monocular vision is proposed. An effective fusion strategy, which fuses the measurement results of drogue's different parts, is proposed to achieve robust position measurement. The error of landmark detection with the proposed method is 3.9%, and it is obviously lower than the errors of other methods. Experimental results on the two KUKA robots platform verify the effectiveness and robustness of the proposed position measurement system for aerial refueling.

Copper and zinc, but not other priority toxic metals, pose risks to native aquatic species in a large urban lake in Eastern China.

Over the past 20 years, global production of copper (Cu) and zinc (Zn) rank in the top three compared to other metals such as Pb, Cd, Cr, Ni, As and Hg. However, due to the potential for exposure and toxicity to humans, more attention of environmental pollution was paid to other metals such as Cd and Hg. Aquatic organisms are sensitive to Cu and Zn. Even though internal concentrations of these required elements are homeostatically controlled, toxic effects can occur at the fish gill surface. In this work, concentrations in surface waters and toxic effects of Cu, Zn, Ni, Cr, Pb, Cd, As, Hg were determined and risk of various metals in Tai Lake, China were evaluated using both risk quotients and joint probability distributions. Two transition metals, Cu and Zn posed the greatest risks to aquatic organisms while measured concentrations of other metals were less than thresholds for adverse effects. Approximately 99.9% and 50.7% of the aquatic organisms were predicted to be affected by Cu and Zn in surface water of Tai Lake respectively. Our results highlight ecological risks of Cu and Zn in water of a typical, large, urban lake in Eastern China, which was ignored in the past.

Cryo-EM structure of the bacteriophage T4 portal protein assembly at near-atomic resolution.

The structure and assembly of bacteriophage T4 has been extensively studied. However, the detailed structure of the portal protein remained unknown. Here we report the structure of the bacteriophage T4 portal assembly, gene product 20 (gp20), determined by cryo-electron microscopy (cryo-EM) to 3.6 Å resolution. In addition, analysis of a 10 Å resolution cryo-EM map of an empty prolate T4 head shows how the dodecameric portal assembly interacts with the capsid protein gp23 at the special pentameric vertex. The gp20 structure also verifies that the portal assembly is required for initiating head assembly, for attachment of the packaging motor, and for participation in DNA packaging. Comparison of the Myoviridae T4 portal structure with the known portal structures of φ29, SPP1 and P22, representing Podo- and Siphoviridae, shows that the portal structure probably dates back to a time when self-replicating microorganisms were being established on Earth.

Rubella virus capsid protein structure and its role in virus assembly and infection.

Rubella virus (RV) is a leading cause of birth defects due to infectious agents. When contracted during pregnancy, RV infection leads to severe damage in fetuses. Despite its medical importance, compared with the related alphaviruses, very little is known about the structure of RV. The RV capsid protein is an essential structural component of virions as well as a key factor in virus-host interactions. Here we describe three crystal structures of the structural domain of the RV capsid protein. The polypeptide fold of the RV capsid protomer has not been observed previously. Combining the atomic structure of the RV capsid protein with the cryoelectron tomograms of RV particles established a low-resolution structure of the virion. Mutational studies based on this structure confirmed the role of amino acid residues in the capsid that function in the assembly of infectious virions.

[Nitrogen non-point source pollution identification based on ArcSWAT in Changle River].

The ArcSWAT (Soil and Water Assessment Tool) model was adopted for Non-point source (NPS) nitrogen pollution modeling and nitrogen source apportionment for the Changle River watershed, a typical agricultural watershed in Southeast China. Water quality and hydrological parameters were monitored, and the watershed natural conditions (including soil, climate, land use, etc) and pollution sources information were also investigated and collected for SWAT database. The ArcSWAT model was established in the Changle River after the calibrating and validating procedures of the model parameters. Based on the validated SWAT model, the contributions of different nitrogen sources to river TN loading were quantified, and spatial-temporal distributions of NPS nitrogen export to rivers were addressed. The results showed that in the Changle River watershed, Nitrogen fertilizer, nitrogen air deposition and nitrogen soil pool were the prominent pollution sources, which contributed 35%, 32% and 25% to the river TN loading, respectively. There were spatial-temporal variations in the critical sources for NPS TN export to the river. Natural sources, such as soil nitrogen pool and atmospheric nitrogen deposition, should be targeted as the critical sources for river TN pollution during the rainy seasons. Chemical nitrogen fertilizer application should be targeted as the critical sources for river TN pollution during the crop growing season. Chemical nitrogen fertilizer application, soil nitrogen pool and atmospheric nitrogen deposition were the main sources for TN exported from the garden plot, forest and residential land, respectively. However, they were the main sources for TN exported both from the upland and paddy field. These results revealed that NPS pollution controlling rules should focus on the spatio-temporal distribution of NPS pollution sources.

Structural analyses at pseudo atomic resolution of Chikungunya virus and antibodies show mechanisms of neutralization.

A 5.3 Å resolution, cryo-electron microscopy (cryoEM) map of Chikungunya virus-like particles (VLPs) has been interpreted using the previously published crystal structure of the Chikungunya E1-E2 glycoprotein heterodimer. The heterodimer structure was divided into domains to obtain a good fit to the cryoEM density. Differences in the T = 4 quasi-equivalent heterodimer components show their adaptation to different environments. The spikes on the icosahedral 3-fold axes and those in general positions are significantly different, possibly representing different phases during initial generation of fusogenic E1 trimers. CryoEM maps of neutralizing Fab fragments complexed with VLPs have been interpreted using the crystal structures of the Fab fragments and the VLP structure. Based on these analyses the CHK-152 antibody was shown to stabilize the viral surface, hindering the exposure of the fusion-loop, likely neutralizing infection by blocking fusion. The CHK-9, m10 and m242 antibodies surround the receptor-attachment site, probably inhibiting infection by blocking cell attachment. DOI:http://dx.doi.org/10.7554/eLife.00435.001.

[Bivariate statistical model for calculating phosphorus input loads to the river from point and nonpoint sources].

Based on the hydrological difference between the point source (PS) and nonpoint source (NPS) pollution processes and the major influencing mechanism of in-stream retention processes, a bivariate statistical model was developed for relating river phosphorus load to river water flow rate and temperature. Using the calibrated and validated four model coefficients from in-stream monitoring data, monthly phosphorus input loads to the river from PS and NPS can be easily determined by the model. Compared to current hydrologica methods, this model takes the in-stream retention process and the upstream inflow term into consideration; thus it improves the knowledge on phosphorus pollution processes and can meet the requirements of both the district-based and watershed-based wate quality management patterns. Using this model, total phosphorus (TP) input load to the Changle River in Zhejiang Province was calculated. Results indicated that annual total TP input load was (54.6 +/- 11.9) t x a(-1) in 2004-2009, with upstream water inflow, PS and NPS contributing to 5% +/- 1%, 12% +/- 3% and 83% +/- 3%, respectively. The cumulative NPS TP input load during the high flow periods (i. e. , June, July, August and September) in summer accounted for 50% +/- 9% of the annual amount, increasing the alga blooming risk in downstream water bodies. Annual in-stream TP retention load was (4.5 +/- 0.1) t x a(-1) and occupied 9% +/- 2% of the total input load. The cumulative in-stream TP retention load during the summer periods (i. e. , June-September) accounted for 55% +/- 2% of the annual amount, indicating that in-stream retention function plays an important role in seasonal TP transport and transformation processes. This bivariate statistical model only requires commonly available in-stream monitoring data (i. e. , river phosphorus load, water flow rate and temperature) with no requirement of special software knowledge; thus it offers researchers an managers with a cost-effective tool for quantifying TP pollution processes in both district and watershed scales.

Structure of Sputnik, a virophage, at 3.5-Å resolution.

"Sputnik" is a dsDNA virus, referred to as a virophage, that is coassembled with Mimivirus in the host amoeba. We have used cryo-EM to produce an electron density map of the icosahedral Sputnik virus at 3.5-Å resolution, sufficient to verify the identity of most amino acids in the capsid proteins and to establish the identity of the pentameric protein forming the fivefold vertices. It was also shown that the virus lacks an internal membrane. The capsid is organized into a T = 27 lattice in which there are 260 trimeric capsomers and 12 pentameric capsomers. The trimeric capsomers consist of three double "jelly-roll" major capsid proteins creating pseudohexameric capsomer symmetry. The pentameric capsomers consist of five single jelly-roll proteins. The release of the genome by displacing one or more of the pentameric capsomers may be the result of a low-pH environment. These results suggest a mechanism of Sputnik DNA ejection that probably also occurs in other big icosahedral double jelly-roll viruses such as Adenovirus. In this study, the near-atomic resolution structure of a virus has been established where crystallization for X-ray crystallography was not feasible.