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The ongoing coronavirus disease 2019 (COVID-19) pandemic caused more than 96 million infections and over 2 million deaths worldwide so far. However, there is no approved vaccine available for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the disease causative agent. Vaccine is the most effective approach to eradicate a pathogen. The tests of safety and efficacy in animals are pivotal for developing a vaccine and before the vaccine is applied to human populations. Here we evaluated the safety, immunogenicity, and efficacy of an inactivated vaccine based on the whole viral particles in human ACE2 transgenic mouse and in non-human primates. Our data showed that the inactivated vaccine successfully induced SARS-CoV-2-specific neutralizing antibodies in mice and non-human primates, and subsequently provided partial (in low dose) or full (in high dose) protection of challenge in the tested animals. In addition, passive serum transferred from vaccine-immunized mice could also provide full protection from SARS-CoV-2 infection in mice. These results warranted positive outcomes in future clinical trials in humans. Supplementary Information The online version contains supplementary material available at 10.1007/s12250-021-00376-w.

The ongoing COVID-19 pandemic is causing huge impact on health, life, and global economy, which is characterized by rapid spreading of SARS-CoV-2, high number of confirmed cases and a fatality/case rate worldwide reported by WHO. The most effective intervention measure will be to develop safe and effective vaccines to protect the population from the disease and limit the spread of the virus. An inactivated, whole virus vaccine candidate of SARS-CoV-2 has been developed by Wuhan Institute of Biological Products and Wuhan Institute of Virology. The low toxicity, immunogenicity, and immune persistence were investigated in preclinical studies using seven different species of animals. The results showed that the vaccine candidate was well tolerated and stimulated high levels of specific IgG and neutralizing antibodies. Low or no toxicity in three species of animals was also demonstrated in preclinical study of the vaccine candidate. Biochemical analysis of structural proteins and purity analysis were performed. The inactivated, whole virion vaccine was characterized with safe double-inactivation, no use of DNases and high purity. Dosages, boosting times, adjuvants, and immunization schedules were shown to be important for stimulating a strong humoral immune response in animals tested. Preliminary observation in ongoing phase I and II clinical trials of the vaccine candidate in Wuzhi County, Henan Province, showed that the vaccine is well tolerant. The results were characterized by very low proportion and low degree of side effects, high levels of neutralizing antibodies, and seroconversion. These results consistent with the results obtained from preclinical data on the safety.

Optimal air feed control of PEM fuel cell system is a very important issue to prevent stack degradation and maximize the net power output of the fuel cell stack. The control objective is to adjust ...

Full-scan gas chromatography-mass spectrometry (GC-MS) provides rapid untargeted screening and detection for trace and coeluting components. Even though modern mass spectrometers have sufficient sensitivity to detect signals of trace components, this does not translate to the ability of the data-processing approach to isolate interference signals and extract pure component spectra. The raw band-target entropy minimization (rBTEM) approach based on band-target entropy minimization was previously reported to enable accurate spectra reconstruction from severely coeluting and trace GC-MS components. In this study, we evaluate the limit of detection for the approach. This study is systematically compared to classical spectral deconvolution for measurements of chlorpyrifos pesticide standards sampled with solid-phase microextraction at various concentration levels in both distilled and seawater media. The rBTEM approach was able to detect chlorpyrifos at 0.5 ppb in distilled water and 1.0 ppb in seawater while the classical approach provided numerous false negative results. In addition, rBTEM consistently provided higher match scores for chlorpyrifos. Attaining accurate identification of trace and coeluting components from full-scan GC-MS analysis has immense potential impact in biomedical, agricultural, and environmental work.

Multi-layer multi-pass (MLMP) welding of medium thickness plate is always the focus and difficulty of research and application. It is widely used in shipbuilding and pressure vessel manufacturing. This paper summarizes the research developments of MLMP in recent years, including welding technologies, advances and future prospects. In welding technology, some modified welding techniques are included, such as ASDAW. The welding simulation process is also discussed in detail. In automation part, the novel feature extraction methods based on different sensing techniques are summarized. Then, the emphasis is laid on the researches of recent years on path planning model and seam tracking techniques. At the end of this paper, summary is made and future prospects of application of advanced technology in intelligent robotic MLMP welding are given. And the promising development directions of MLMP are prospected in intelligent robotic welding of medium thickness plate.

Background Diabetes mellitus (DM) is an important risk factor in the long-term outcomes of surgical revascularization. However, few studies have focused on patients with left ventricular dysfunction (LVD) and DM, and the results are controversial. This study aimed to evaluate the effect of DM on the long-term outcomes of patients with ischemic heart disease (IHD) and LVD undergoing coronary artery bypass grafting(CABG). Methods In this propensity-matched study, patients with IHD and LVD who underwent CABG in our hospital from January 2007 to December 2017 were enrolled. The patients were divided into two groups according to whether they had DM. The primary endpoint was all-cause death, and the secondary endpoint was a composite of all-cause death, stroke, recurrent myocardial infarction, and re-revascularization. Results There was no significant difference in all-cause mortality between the two groups(5.78%vs.4.05%,P=0.216). The incidence of main adverse cardiovascular and cerebrovascular events(MACCE) in the secondary endpoint was significantly higher in the DM group than in the non-DM group (10.40% vs. 8.09%, P=0.023).Conclusions DM can negatively affect the long-term outcome of patients with IHD and LVD undergoing CABG by significantly increasing the overall incidence of MACCE, though the long-term survival doesn’t show significant difference between the DM and non-DM patients.

Summary COVID-19 has spread worldwide since 2019 and is now a severe threat to public health. We previously identified the causative agent as a novel SARS-related coronavirus (SARS-CoV-2) that uses human angiotensin-converting enzyme 2 (hACE2) as the entry receptor. Here, we successfully developed a SARS-CoV-2 hACE2 transgenic mouse (HFH4-hACE2 in C3B6 mice) infection model. The infected mice generated typical interstitial pneumonia and pathology that were similar to those of COVID-19 patients. Viral quantification revealed the lungs as the major site of infection, although viral RNA could also be found in the eye, heart, and brain in some mice. Virus identical to SARS-CoV-2 in full-genome sequences was isolated from the infected lung and brain tissues. Lastly, we showed that pre-exposure to SARS-CoV-2 could protect mice from severe pneumonia. Our results show that the hACE2 mouse would be a valuable tool for testing potential vaccines and therapeutics., Highlights • SARS-CoV-2 could infect HFH4-hACE2 mice and cause death. • SARS-CoV-2 infection localizes to lungs of mice and causes typical interstitial pneumonia. • Pre-exposure to SARS-CoV-2 protects mice from lethal challenge., A SARS-CoV-2 hACE2 transgenic mouse infection model recapitulates a number of infection symptoms and pathology in COVID-19 patients. Pre-exposure to SARS-CoV-2 was able to protect mice from severe pneumonia.

Gas chromatography-mass spectrometry (GC-MS) is a versatile analytical method but its data is usually complicated by the presence of severely co-eluting and trace-level components. In this work, we introduce an optimized band-target entropy minimization approach for the analysis of complex mass spectral data. This new approach enables an automated mass spectral analysis which does not require any user-dependent inputs. Moreover, the approach provides improved sensitivity and accuracy for mass spectral reconstruction of severely co-eluting and trace-level components. The accuracy of our approach is compared to the automatic mass spectral deconvolution and identification system (AMDIS) with two controlled mixtures and a sample of Eucalyptus essential oil. Our approach was able to putatively identify 130 compounds in Eucalyptus essential oil, which was 46% in excess of that identified by AMDIS. This new approach is expected to benefit GC-MS analysis of complex mixtures such as biological samples and essential oils, in which the data are often complicated by co-eluting and trace-level components. Graphical abstract ᅟ.

Gas chromatography-mass spectrometry (GC-MS) is an important analytical technique for the analysis of organophosphorus pesticides in food products. Because of the complex matrices of food products, multiple preprocessing steps are required prior to performing the GC-MS analysis. Despite that, it is difficult to totally eliminate the interference of complex matrix background. In this work, we introduce an entropy minimization technique that can eliminate the need for comprehensive preprocessing steps to detect organophosphorus pesticides in a fortified orange juice sample. The pure mass spectra and extracted-ion chromatograms of the pesticides were extracted and reconstructed. The results achieved higher National Institute of Standard and Technology (NIST) match scores in comparison to the conventional background subtraction technique. Taken together, the entropy minimization technique is capable of providing rapid qualitative and quantitative analyses of complex GC-MS data. This technique is expected to have great potential for natural products and food analysis applications.

A major challenge for accurate GC-MS analysis is to achieve excellent chromatographic separation and a high signal-to-noise ratio. In fact, real-world samples are often contaminated with impurities that manifest as intense background noise in GC-MS data. Herein, a dynamic background noise removal system is developed based on an entropy minimization algorithm to extract pure mass spectra of straight-chain n-alkane components in a sample of hydrogenated jet fuel. This system is capable of extracting pure component spectra from overlapping peaks that are heavily superimposed by background noise without a priori information. The performance of the system surpasses that of the background subtraction method applied in Agilent ChemStation software. The robustness of the system to accurately analyse real-world samples is expected to simplify and revolutionise the application of GC-MS for chemical analysis.

Liquid chromatography-mass spectrometry (LC/MS) is a major technique for the analysis of complex samples. Data processing for LC/MS untargeted analysis is very challenging due to the presence of asymmetric, co-eluted at trace-level peaks. We report a multivariate curve resolution approach based on entropy minimization to resolve LC/MS data. Our liquid chromatography band-target entropy minimization (lc-BTEM) approach enables automated resolution of complex LC/MS peaks without the requirement of any parameter inputs. We demonstrated the performance of our approach on a co-eluted and trace-level peaks in an American ginseng extract. Consequently, we were able to putatively annotate the presence of more than 50 ginsenosides. The extracted pure mass spectra and in-source fragments information further enabled the annotation of [M+H]+, [M+H-Neu]+ and [M-H]- ions. This approach is expected to benefit LC/MS untargeted analysis and data independent analysis of complex samples.

Chemical profiling with gas chromatography/mass spectrometry (GC/MS) full-spectrum acquisition mode often leads to the discovery of known-unknown components. These are non-identified components which arise from the limitation of the data processing method or limited breadth of mass spectral libraries. The recent introduction of the NIST Hybrid Search sought to relieve the latter limitation by providing an improved class annotation technique. Herein, we demonstrate the importance of using a precise mass spectral reconstruction technique to increase the confidence of detecting the presence of known-unknowns and subsequently identifying them successfully with NIST Hybrid Search function. We compared the AMDIS algorithm against the rBTEM algorithm and found that the latter could more accurately reconstruct the mass spectra of co-eluting known-unknown components. This has a far-reaching implication to increase the number of identified compounds in GC/MS scan data.

In this paper, the chemical composition of vehicle damage brake drum occurred in the heavy traffic accident on the highway is analyzed, and analyzed the influence on the braking performance of vehicles, pointed out that the direct cause of the accident is due to the friction surface of the drum brake has a penetrating crack.

OBJECTIVE: To investigate the long-term outcomes of off-pump coronary artery bypass grafting (OPCAB) in patients aged over 75 years and analyze the risk factors affecting the outcomes of the procedure. METHODS: Clinical data were reviewed for 97 consecutive patients aged 75 years or above receiving OPCAB at our center between November, 2000 and November, 2013. The perioperative data including length of ICU stay, duration of mechanical ventilation, incidence of postoperative complications and mortality rate of the patients were analyzed. The follow-up data of the patients were also analyzed including all-cause mortality rate and major adverse cardiac and cerebral events (MACCE, including myocardial infarction, cerebrovascular event, and repeated revascularization). RESULTS: The perioperative mortality rate was 3.09% (3/97) in these patients. Of the 97 patients analyzed, 91 (93%) were available for follow-up for 29-192 months (with a median of 95.61±34.07 months). The 10-year survival rate of the patients was 62% with a 10-year MACCE-free survival rate of 47.4%. During the follow-up, 6 (6.8%) patients underwent repeated revascularization procedures, 12 (12.37%) had cerebrovascular accidents and 5 (5.15%) had myocardial infarction. Logistic regression analysis showed that hypertension (OR=1.388, P=0.043) and diabetes (OR=1.692, P=0.017) were independent predictors of MACCE, and incomplete revascularization did not increase the risk of postoperative MACCE. CONCLUSION: OPCAB is safe and effective in elderly patients with good long-term outcomes. Hypertension and diabetes are independent risk factors of MACCE, and adequate control of blood pressure and blood glucose can reduce the incidence of postoperative MACCE. Incomplete revascularization is not detrimental to the long-term outcomes of OPCAB in elderly patients.

For a graph G and an integer r ≥ 1, G is r-EKR if no intersecting family of independent r-sets of G is larger than the largest star (a family of independent r-sets containing some fixed vertex in G), and G is strictly r-EKR if every extremal intersecting family of independent r-sets is a star. Recently, Hurlbert and Kamat gave a preliminary result about EKR property of ladder graphs. They showed that a ladder graph with n rungs is 3-EKR for all n ≥ 3. The present paper proves that this graph is r-EKR for all 1 ≤ r ≤ n, and strictly r-EKR except for r = n − 1.

Based on second-order cone programming, we present a new superdirective beamforming method with interferences and noise suppression for small aperture HF receive arrays. In the novel method, low side lobe level (SLL) and nulls are not only used to suppress interferences and noise, but also play an important part in overcoming the low array e-ciency brought by superdirective beamforming. According to the actual condition, the new method can present a good tradeofi between directive gain, array e-ciency, SLL, nulls and robustness against array uncertainty. Compared with the existing methods, it is more efiective in suppressing interference and noise. The superiority and validity of the proposed method can be illustrated by numerical results.

Fin widely used in industrial practice, and the surface heat transfer coefficient is not constant value. In this paper, through appropriate simplification, the mathematical model in Longitudinal Fin of Rectangular Profile has been established, When the surface heat transfer coefficient along the fin in the exponential changes. The exact solution of fin conduction has been get, and derived efficiency and the corresponding fin heat flux formula. And an example has been given to verify. The solution can be applied to engineering practice, and guided theoretical the heat transfer enhancement in the design of fin.

In order to reduce the error of the phase lock-loop (PLL) and compensate the delay of the low pass filter on harmonics detection, In the paper, a detecting-method without PLL in single-phase circuit is researched. In this method, the PLL and LPF are omitted, the feedback and average theory are used, so that the problem of detecting accuracy induced by PLL and real-time induced by LPF is solved. It is testified through comparison, analysis and simulation, that both methods can reduce the latency, improve dynamic response speed, the feedback method can reduce the delay in a dynamic, continuous process, while the average theoretical method can reduce the delay quantitatively.

Let Circ(r, n) be a circular graph. It is well known that its independence number α(Circ(r, n)) = r. In this paper we prove that $$\alpha (Circ(r,n) \times H) = \max \{ r|H|,n\alpha (H)\} $$ for every vertex transitive graph H, and describe the structure of maximum independent sets in Circ(r, n) × H. As consequences, we prove $$\alpha (G \times H) = \max \{ \alpha (G)|V(H)|,\alpha (H)|V(G)|\} $$ for G being Kneser graphs, and the graphs defined by permutations and partial permutations, respectively. The structure of maximum independent sets in these direct products is also described.

This study is aimed to evaluate the brain distribution of transforming growth factor-beta1 (TGF-beta1) following intranasal administration and the subsequent biological effects of TGF-beta1. Adult rats were given recombinant human TGF-beta1 (rhTGF-beta1) or vehicle solution intranasally. TGF-beta1 concentrations were significantly raised in several brain regions and the trigeminal nerve following intranasal delivery. The elevation appeared within 30 min and was sustained for at least 6 h, reaching its greatest level at 60 min. A concentration gradient in the central nervous system (CNS) regions was produced during the first 2 h after intranasal administration, with the OB presenting a significantly higher concentration than any other CNS regions. The nasally administered TGF-beta1 subsequently regulated gene expressions of its two receptors (TGF-beta receptor types I and II) in vivo, but did not affect mRNA level of TGF-beta1 itself. Our results suggest that TGF-beta1 can be transported into the CNS via the olfactory and trigeminal pathways, and may consequently exert its biological effects by regulating gene expressions of its receptors. Intranasal administration of neurotrophic factors may offer a potential strategy for treating some CNS disorders.

T-joint is widely used in box girder structure of lifting machinery and bridges. The welding of T-joint by use of manual arc welding has many problems, such as large deformation, operational difficulties inside the box, low productivity and so on. To solve these problems, the technical feasibility of welding for T-joint by use laser hybrid welding has been study. The results show that the single face welding-double face forming of T-joint for box girder structure can be achieved by use laser hybrid welding, and the weld quality and productivity is greatly improved.

To understand the present status of the heavy metal (Cr, Cu, Zn, Cd, Pb and Hg) pollution of the sediments in water supply reservoirs in Huizhou, sediment cores were sampled from three representative reservoirs. The heavy metal concentrations were analyzed by ICP-MS, and the pollution status was assessed by geo-accumulation index (Igeo) and potential ecological risk index (RI). In the meantime, the possible sources of the heavy metals were analyzed by the principal component analysis (PCA). In the sediments of the three reservoirs, the test heavy metals had different vertical distribution, some had less change, the others decreased or increased with depth, and the distribution patterns differed with the reservoirs. According to the Igeo, the sediments in the reservoirs were seriously polluted by Zn and Pb (Zn: 49.98-640.29 mg x kg(-1); Pb: 21.94-300.66 mg x kg(-1)), reaching slight to high pollution, and the middle or bottom part of the sediments was slightly polluted by Cu (16.85-45.46 mg x kg(-1)). On the whole, the sediments were not polluted by Cr, Cd and Hg. According to the RI and the potential ecological risk coefficient [Er(i)], the sediments in the three reservoirs were under low potential ecological risk. Based on the PCA and relevant information, the human activities such as mining and smelting, urbanization, and agriculture and forestry had great contribution to the heavy metal pollution. The Zn and Pb pollution mainly originated from mining and smelting, Pb pollution also came from motor vehicle exhaust emission and domestic wastes, and Cu pollution mainly derived from agriculture and forestry.

Core sediments were collected from the riverine, transition and lacustrine zones of Hedi Reservoir in southern China to investigate the spatial distributions of nutrients and heavy metals and assess the potential ecological risk of heavy metals. The total nitrogen (TN) contents of the sediments at three sampling sites are between 2.314-2.427 mg x g(-1), while total phosphorus (TP) contents range from 0.591 mg x g(-1) to 0.760 mg x g(-1), TN contents of the surface sediments increase from the riverine zone to the lacustrine zone, but the TP content in the transition zone is higher than that in the other two sites (riverine zone and lacustrine zone). The mean contents of heavy metals are: 31.094, 46.85, 75.615, 385.739, 0.624 and 0.171 mg x kg(-1) respectively, except Cr, the contents of heavy metals in sediment of lacustrine zone are higher than the sediment of transition zone. In all core sediments, the contents of nutrients and heavy metals decrease from the surface to the bottom of core sediments. Inorganic phosphorus (IP) is the dominant fraction of phosphorus in the sediment and the NaOH-P is the main forms of inorganic phosphorus. The potential ecological risk assessed by using of the highest environmental background values before industrialization as the reference indicates that each single heavy metal only causes slightly pollution, but two heavy metals (Cd and Hg) cause heavy pollution based on the soil environmental background values of Guangdong province. In spite of the slight difference between two kinds of risk assessment, all demonstrated that Cd and Hg resulted in more serious pollution than the other metals and these two metals contributed most to the RI values.

To investigate the phenotype, pathogenesis and molecular biological features of 46, XX testicular disorder of sex development.We obtained the history of 2 patients with 46, XX testicular disorder of sex development, examined the cavitas pelvis by type-B ultrasonography, analyzed the karyotype of the chromosome, and detected the genes SRY, YRRM1, DYS240 and DAZ by PCR amplification.Microrchidia, azoospermia and maldevelopment of secondary sex characteristics were observed in both of the patients, but ultrasonography revealed no female internal genitals. Their chromosome gender was karyotyped as 46, XX, with the SRY gene positive in both, but the YRRM1 gene positive in only one of the cases.Chromosome karyotyping and detection of the SRY gene for patients with abnormal sex development can give us an insight into the genetic pathogenesis and provide us with scientific evidence for the diagnosis and treatment of the condition.

Azoospermia factor (AZF) microdeletions of the Y chromosome, which occur in 1 - 55% of infertile men, are closely associated with severe spermatogenic failure and represent the most frequent molecular genetic causes of azoospermia and severe oligozoospermia. Researches on AZF and its related genes, approaching the mechanisms of spermatogenic failure at the molecular level, are of great significance for the diagnosis, treatment and prognosis of male infertility. The detection of AZF microdeletions can provide scientific basis for correct diagnosis and reasonable therapy. This article outlines the structure and functional characteristics of AZF, as well as its relationship with male infertility, cryptorchidism, varicocele, Klinefelter syndrome, seminoma, and recurrent abortion.

To investigate the efficacy and possible action mechanism of Qianlie Beixi Capsule in the treatment of unliquefiable semen.A total of 240 patients with unliquefiable semen were randomly divided into a treatment group (n = 180), treated with Qianlie Beixi Capsule, and a control group (n = 60), given compound tablets of zinc and protein. The treatment lasted two courses of 45 days each, and the seminal changes were observed and recorded.Of the patients in the treatment group, 144 were cured, 12 responded and 24 failed to respond to the medication after the first course; and 158 were cured, 7 responded and 15 failed to after the second course, with the effectiveness rate of 91.67%. Meanwhile, sperm motility was obviously improved, with statistically significant difference from that of the controls (P0.01).Qianlie Beixi Capsule is effective for unliquefiable semen by improving the function of the prostate and shortening the time of seminal liquefaction.