Human ACE2‑Functionalized Gold “Virus‑Trap” Nanostructures for Accurate Capture of SARS‑CoV‑2 and Single‑Virus SERS Detection

The current COVID-19 pandemic urges the extremely sensitive and prompt detection of SARS-CoV-2 virus. Here, we present a Human Angiotensin-converting-enzyme 2 (ACE2)-functionalized gold “virus traps” nanostructure as an extremely sensitive SERS biosensor, to selectively capture and rapidly detect S-protein expressed coronavirus, such as the current SARS-CoV-2 in the contaminated water, down to the single-virus level. Such a SERS sensor features extraordinary 106- fold virus enrichment originating from high-affinity of ACE2 with S protein as well as “virus-traps” composed of oblique gold nanoneedles, and 109- fold enhancement of Raman signals originating from multicomponent SERS effects. Furthermore, the identification standard of virus signals is established by machine-learning and identification techniques, resulting in an especially low detection limit of 80 copies mL− 1 for the simulated contaminated water by SARS-CoV-2 virus with complex circumstance as short as 5 min, which is of great significance for achieving real-time monitoring and early warning of coronavirus. Moreover, here-developed method can be used to establish the identification standard for future unknown coronavirus, and immediately enable extremely sensitive and rapid detection of novel virus

Finding branched pathways in metabolic network via atom group tracking.

Finding non-standard or new metabolic pathways has important applications in metabolic engineering, synthetic biology and the analysis and reconstruction of metabolic networks. Branched metabolic pathways dominate in metabolic networks and depict a more comprehensive picture of metabolism compared to linear pathways. Although progress has been developed to find branched metabolic pathways, few efforts have been made in identifying branched metabolic pathways via atom group tracking. In this paper, we present a pathfinding method called BPFinder for finding branched metabolic pathways by atom group tracking, which aims to guide the synthetic design of metabolic pathways. BPFinder enumerates linear metabolic pathways by tracking the movements of atom groups in metabolic network and merges the linear atom group conserving pathways into branched pathways. Two merging rules based on the structure of conserved atom groups are proposed to accurately merge the branched compounds of linear pathways to identify branched pathways. Furthermore, the integrated information of compound similarity, thermodynamic feasibility and conserved atom groups is also used to rank the pathfinding results for feasible branched pathways. Experimental results show that BPFinder is more capable of recovering known branched metabolic pathways as compared to other existing methods, and is able to return biologically relevant branched pathways and discover alternative branched pathways of biochemical interest. The online server of BPFinder is available at http://114.215.129.245:8080/atomic/. The program, source code and data can be downloaded from https://github.com/hyr0771/BPFinder

Trace Element Contents in Sphalerite from the Nayongzhi Zn-Pb Deposit, Northwestern Guizhou, China: Insights into Incorporation Mechanisms, Metallogenic Temperature and Ore Genesis

The Nayongzhi Zn-Pb deposit, located in the southeastern margin of the Sichuan-Yunnan-Guizhou (S-Y-G) Zn-Pb metallogenic province, China, has been recently discovered in this region and has an estimated resource of 1.52 Mt of metal at average grades of 4.82 wt % Zn and 0.57 wt % Pb. The ore bodies are hosted in the Lower Cambrian Qingxudong Formation dolostone and occur as stratiform, stratoid and steeply dipping veins. The predominant minerals are sphalerite, galena, dolomite, calcite with minor pyrite, and barite. In this paper, the inductively coupled plasma mass spectrometry (ICP-MS) technique has been used to investigate the concentrations of Fe, Cd, Ge, Ga, Cu, Pb, Ag, In, Sn, Sb, Co and Mn in bulk grain sphalerite from the Nayongzhi deposit, in an effort to provide significant insights into the element substitution mechanisms, ore-forming temperature and genesis of the deposit. This study shows that those trace elements (i.e., Cd, In, Sn, Sb, Fe, Mn, Cu, Ga, Ge, Ag, and Co) are present in the form of isomorphism in sphalerite, and strong binary correlation among some elements suggests direct substitution as Zn2+Fe2+ and coupled substitutions as Zn2+Ga3+ + (Cu, Ag)(+) and Zn2+In3+ + Sn3+ + (vacancy), despite there being no clear evidence for the presence of Sn3+. Sphalerite from the Nayongzhi deposit is enriched in Cd, Ge and Ga and depleted in Fe, Mn, In and Co, which is similar to that of the Mississippi Valley-type (MVT) deposit and significantly different from that of the Volcanogenic Massive Sulfide (VMS) deposit, Sedimentary-exhalative (Sedex) deposit, skarn, and epithermal hydrothermal deposit. Moreover, the ore-forming temperature is relatively low, ranging from 100.5 to 164.4 degrees C, as calculated by the GGIMFis geothermometer. Geological characteristics, mineralogy and trace element contents of sphalerite suggest that the Nayongzhi deposit is a MVT deposit. In addition, according to the geological characteristics, Ag content in sphalerite, and Pb isotope evidence, the Nayongzhi deposit is distinct from the deposits associated with the Indosinian Orogeny in S-Y-G Zn-Pb metallogenic province (e.g., Huize, Daliangzi, Tianbaoshan and Tianqiao deposits), thus, suggesting that multi-stage Zn-Pb mineralization may have occurred in this region

Combination of folic acid with nifedipine is completely effective in attenuating aortic aneurysm formation as a novel oral medication

Aortic aneurysms are prevalent and severe vascular diseases with high mortality from unpredicted ruptures, while the only treatment option is surgical correction of large aneurysms with considerable risk. We have shown that folic acid (FA) is highly effective in alleviating development of aneurysms although not sufficient to completely attenuate aneurysm formation. Here, we examined therapeutic effects on aneurysms of combining FA with Nifedipine as novel and potentially more effective oral medication. Oral administration with FA (15 mg/kg/day) significantly reduced incidence of AAA from 85.71% to 18.75% in Ang II-infused apolipoprotein E (apoE) null mice, while combination of FA with Nifedipine (1.5, 5.0 or 20 mg/kg/day) substantially and completely further reduced incidence of AAA to 12.5%, 11.76% and 0.00% respectively in a dose-dependent manner. The combinatory therapy substantially and completely further alleviated enlargement of abdominal aortas defined by ultrasound, vascular remodeling characterized by elastin degradation and adventitial hypertrophy, as well as aortic superoxide production and eNOS uncoupling activity also in a dose-dependent manner, with combination of FA with 20 mg/kg/day Nifedipine attenuating all of these features by 100% to control levels. Aortic NO and H4B bioavailabilities were also dose-dependently further improved by combining FA with Nifedipine. These data establish entirely innovative and robust therapeutic regime of FA combined with Nifedipine for the treatment of aortic aneurysms. The comminatory therapy can serve as a first-in-class and most effective oral medication for aortic aneurysms, which can be rapidly translated into clinical practice to revolutionize management of the devastating vascular diseases of aortic aneurysms known as silent killers

Modified anterior approach versus traditional posterior approach for ultrasound-guided superior laryngeal nerve block in awake endotracheal intubation: a randomized non-inferiority clinical trial

AbstractStudy objective This study was undertaken to compare the effect of the modified ultrasound-guided anterior superior laryngeal nerve block (SLNB) with the traditional ultrasound-guided posterior SLNB in providing intubation conditions during awake tracheal intubation (ATI) in patients without difficult airway.Design Randomized, assessor-blind. Registration number: ChiCTR2200058086.Setting West China Hospital of Sichuan University, Chengdu, China.Patients 104 patients aged 18–65 years, of American Society of Anesthesiologists status I-III, posted for elective general surgery with general endotracheal anesthesia.Interventions The patients were randomized into two groups (modified group, n = 52; traditional group, n = 52). Modified anterior SLNB or traditional posterior SLNB was performed under ultrasound guidance.Measurements The primary outcome was the proportion of acceptable intubation condition (AIC), which was analyzed in both per-protocol (PP) and intention-to-treat (ITT) populations. The prespecified non-inferiority margin was −4.8%. Secondary outcomes included intubation success rate on the first attempt, hemodynamic parameters during ATI, time taken for airway anesthesia and intubation, recall of intubation, patient perception of comfort, and incidence and severity of postoperative complications.Main results In the PP population, the proportion of AIC in the modified group was 49/49 (100%) and that in the traditional group was 49/49 (100%), absolute difference 0, lower limit of 1-sided 95% CI, −0.3%. In the ITT population, the primary outcomes in the modified and traditional group were 52/52 (100%) and 51/52 (98.1%), respectively, with an absolute difference of 1.9% and a lower limit of 1-sided 95% CI of −1.2%. The non-inferiority of modified ultrasound-guided anterior SLNB was confirmed in both populations.Conclusions Among adults without difficult airways during videolaryngoscope-assisted ATI, the modified ultrasound-guided anterior SLNB, compared to the traditional posterior approach, showed a statistically non-inferior effect in terms of providing AIC

Combination of folic acid with nifedipine is completely effective in attenuating aortic aneurysm formation as a novel oral medication

Aortic aneurysms are prevalent and severe vascular diseases with high mortality from unpredicted ruptures, while the only treatment option is surgical correction of large aneurysms with considerable risk. We have shown that folic acid (FA) is highly effective in alleviating development of aneurysms although not sufficient to completely attenuate aneurysm formation. Here, we examined therapeutic effects on aneurysms of combining FA with Nifedipine as novel and potentially more effective oral medication. Oral administration with FA (15 mg/kg/day) significantly reduced incidence of AAA from 85.71% to 18.75% in Ang II-infused apolipoprotein E (apoE) null mice, while combination of FA with Nifedipine (1.5, 5.0 or 20 mg/kg/day) substantially and completely further reduced incidence of AAA to 12.5%, 11.76% and 0.00% respectively in a dose-dependent manner. The combinatory therapy substantially and completely further alleviated enlargement of abdominal aortas defined by ultrasound, vascular remodeling characterized by elastin degradation and adventitial hypertrophy, as well as aortic superoxide production and eNOS uncoupling activity also in a dose-dependent manner, with combination of FA with 20 mg/kg/day Nifedipine attenuating all of these features by 100% to control levels. Aortic NO and H4B bioavailabilities were also dose-dependently further improved by combining FA with Nifedipine. These data establish entirely innovative and robust therapeutic regime of FA combined with Nifedipine for the treatment of aortic aneurysms. The comminatory therapy can serve as a first-in-class and most effective oral medication for aortic aneurysms, which can be rapidly translated into clinical practice to revolutionize management of the devastating vascular diseases of aortic aneurysms known as silent killers

Identification of Di/Tripeptide(s) With Osteoblasts Proliferation Stimulation Abilities of Yak Bone Collagen by in silico Screening and Molecular Docking

Endothelial protein C receptor (EPCR), cannabinoid receptor 2 (CBR2), and estrogen receptor α (ERα) play vital roles in osteoblasts proliferation. Also, collagen peptides have osteoblasts proliferation stimulation abilities, and di/tri-peptides could be absorbed by the intestine more easily. This study obtained three di/tripeptides with potential osteoblasts proliferation stimulation abilities of yak bone collagen, namely, MGF, CF, and MF, by in silico screening. Results suggested that these three peptides exhibited good absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. They also had strong affinities with EPCR, CBR2, and ERα, and the total -CDOCKER energy (-CE) values were 150.9469, 113.1835, and 115.3714 kcal/mol, respectively. However, further Cell Counting Kit-8 (CCK-8) assays indicated that only MGF could significantly (P < 0.05) stimulate osteoblasts proliferation at 0.3 mg/ml. At the same time, the proliferating index (PI) of the osteoblasts treated with MGF increased significantly (P < 0.05), and the alkaline phosphatase (ALP) activity decreased highly significantly (P < 0.01). In summary, MGF exhibited the potential to be an effective treatment for osteoporosis

Real-Time Estimation of Satellite-Derived PM2.5 Based on a Semi-Physical Geographically Weighted Regression Model

The real-time estimation of ambient particulate matter with diameter no greater than 2.5 μm (PM2.5) is currently quite limited in China. A semi-physical geographically weighted regression (GWR) model was adopted to estimate PM2.5 mass concentrations at national scale using the Aqua Moderate Resolution Imaging Spectroradiometer (MODIS) Aerosol Optical Depth product fused by the Dark Target (DT) and Deep Blue (DB) algorithms, combined with meteorological parameters. The fitting results could explain over 80% of the variability in the corresponding PM2.5 mass concentrations, and the estimation tends to overestimate when measurement is low and tends to underestimate when measurement is high. Based on World Health Organization standards, results indicate that most regions in China suffered severe PM2.5 pollution during winter. Seasonal average mass concentrations of PM2.5 predicted by the model indicate that residential regions, namely Jing-Jin-Ji Region and Central China, were faced with challenge from fine particles. Moreover, estimation deviation caused primarily by the spatially uneven distribution of monitoring sites and the changes of elevation in a relatively small region has been discussed. In summary, real-time PM2.5 was estimated effectively by the satellite-based semi-physical GWR model, and the results could provide reasonable references for assessing health impacts and offer guidance on air quality management in China

Impact and Suggestion of Column-to-Surface Vertical Correction Scheme on the Relationship between Satellite AOD and Ground-Level PM2.5 in China

As China is suffering from severe fine particle pollution from dense industrialization and urbanization, satellite-derived aerosol optical depth (AOD) has been widely used for estimating particulate matter with an aerodynamic diameter less than 2.5 μm (PM2.5). However, the correlation between satellite AOD and ground-level PM2.5 could be influenced by aerosol vertical distribution, as satellite AOD represents the entire column, rather than just ground-level concentration. Here, a new column-to-surface vertical correction scheme is proposed to improve separation of the near-surface and elevated aerosol layers, based on the ratio of the integrated extinction coefficient within 200–500 m above ground level (AGL), using the Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP)) aerosol profile products. There are distinct differences in climate, meteorology, terrain, and aerosol transmission throughout China, so comparisons between vertical correction via CALIOP ratio and planetary boundary layer height (PBLH) were conducted in different regions from 2014 to 2015, combined with the original Pearson coefficient between satellite AOD and ground-level PM2.5 for reference. Furthermore, the best vertical correction scheme was suggested for different regions to achieve optimal correlation with PM2.5, based on the analysis and discussion of regional and seasonal characteristics of aerosol vertical distribution. According to our results and discussions, vertical correction via PBLH is recommended in northwestern China, where the PBLH varies dramatically, stretching or compressing the surface aerosol layer; vertical correction via the CALIOP ratio is recommended in northeastern China, southwestern China, Central China (excluding summer), North China Plain (excluding Beijing), and the spring in the southeast coast, areas that are susceptible to exogenous aerosols and exhibit the elevated aerosol layer; and original AOD without vertical correction is recommended in Beijing and the southeast coast (excluding spring), where the elevated aerosol layer rarely occurs and a large proportion of aerosol is aggregated in near-surface. Moreover, validation experiments in 2016 agreed well with our discussions and conclusions drawn from the experiments of the first two years. Furthermore, suggested vertical correction scheme was applied into linear mixed effect (LME) model, and high cross validation (CV) R2 (~85%) and relatively low root mean square errors (RMSE, ~20 μg/m3) were achieved, which demonstrated that the PM2.5 estimation agreed well with the measurements. When compared to the original situation, CV R2 values and RMSE after vertical correction both presented improvement to a certain extent, proving that the suggested vertical correction schemes could further improve the estimation accuracy of PM2.5 based on sophisticated model in China. Estimating PM2.5 with better accuracy could contribute to a more precise research of ecology and epidemiology, and provide a reliable reference for environmental policy making by governments