In the traditional view, riverine organic matter typically has a higher C:N ratio than marine phytoplankton 6.7:1 and has therefore been thought to be a carbon source in estuaries and coastal waters. ...Thus, a decrease in the riverine organic C:N ratio to <6.7:1 would potentially switch riverine organic matter from a coastal carbon source to sink. However, few studies have paid an attention to such a change. Our field investigation showed that organic C:N ratio was 11.8:1 in the pristine upstream section of a natural reserve, but decreased after the river passed through several urban cities, reaching 5.0:1 in near the Pearl River estuary. Along the river, dissolved inorganic nitrogen, total organic carbon and nitrogen all increased and they were highly negatively correlated with organic C:N ratios. The observation has a great implication that organic matter with a decreased C:N ratio from the Pearl River would potentially switch from a coastal carbon source of 2.8 × 1011 g C/year to a sink of 2.2 × 1011 g C/year. This carbon sink (2.2 × 1011 g C/year) contributes to 56% of the previous estimate of the Pearl River estuarine-coastal net carbon sink. Such a decrease in organic C:N ratio also occurs in some other large rivers, which should be considered in the assessment of global coastal carbon budgets and metabolic balance.
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•Organic C:N decreases downstream from 11.8:1 to 5.0:1 along the Pearl River.•The Pearl River organic matter switches from a coastal carbon source to sink.•River organic C:N decrease affects global coastal metabolic balance and carbon budgets.
Various vaccine strategies have been proposed in response to the global COVID-19 pandemic, each with unique strategies for eliciting immune responses. Here, we developed nanoparticle vaccines by ...covalently conjugating the self-assembled 24-mer ferritin to the receptor binding domain (RBD) and/or heptad repeat (HR) subunits of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) spike (S) protein. Compared to monomer vaccines, nanoparticle vaccines elicited more robust neutralizing antibodies and cellular immune responses. RBD and RBD-HR nanoparticle vaccinated hACE2 transgenic mice vaccinated with RBD and/or RBD-HR nanoparticles exhibited reduced viral load in the lungs after SARS-CoV-2 challenge. RBD-HR nanoparticle vaccines also promoted neutralizing antibodies and cellular immune responses against other coronaviruses. The nanoparticle vaccination of rhesus macaques induced neutralizing antibodies, and T and B cell responses prior to boost immunization; these responses persisted for more than three months. RBD- and HR-based nanoparticles thus present a promising vaccination approach against SARS-CoV-2 and other coronaviruses.
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•RBD and HR nanoparticle vaccines induce potent neutralizing antibody responses•Nanoparticle vaccines protect against SARS-CoV-2 infection in mice•HR antigens elicit both humoral and cellular immune responses•HR antigens within nanoparticles contribute to cross-protective immunity
Ma et al. construct two Ferritin-based nanoparticle vaccines that conjugate RBD and HR antigens in SARS-CoV-2 Spike protein utilizing the SpyTag/SpyCatcher system. RBD and RBD-HR nanoparticles vaccines elicit more potent neutralizing antibody responses and stronger T cell immune responses than monomers. HR-containing nanoparticles induce cross-reactive immune responses against other coronaviruses.
To perform air missions with an unmanned aerial vehicle (UAV) swarm is a significant trend in warfare. The task assignment among the UAV swarm is one of the key issues in such missions. This paper ...proposes PSO-GA-DWPA (discrete wolf pack algorithm with the principles of particle swarm optimization and genetic algorithm) to solve the task assignment of a UAV swarm with fast convergence speed. The PSO-GA-DWPA is confirmed with three different ground-attack scenarios by experiments. The comparative results show that the improved algorithm not only converges faster than the original WPA and PSO, but it also exhibits excellent search quality in high-dimensional space.
Purpose
Accurate preoperative diagnosis of lymph node metastasis (LNM) in papillary thyroid carcinoma (PTC) remains an unsolved problem. This study aimed to construct a nomogram and scoring system ...for predicting LNM based on the clinical characteristics of patients with PTC.
Methods
1400 patients with PTC who underwent thyroidectomy and lymph node dissection at the First Affiliated Hospital of Sun Yat-sen University were retrospectively enrolled and randomly divided into training and internal testing sets. Furthermore, 692 patients with PTC from three other medical centers were collected as external testing sets. Least absolute shrinkage and selection operator (LASSO) was used to screen the predictors, and a nomogram was constructed. In addition, a scoring system was constructed using 10-fold cross-validation. The performances of the two models were verified among datasets and compared with preoperative ultrasound (US).
Results
Six independent predictors were included in the multivariate logistic model: age, sex, US diagnosis of LNM, tumor diameter, location, and thyroid peroxidase antibody level. The areas under the receiver operating characteristic curve (AUROC) (95% confidence interval) of this nomogram in the training, internal testing, and three external testing sets were 0.816 (0.791–0.840), 0.782 (0.727–0.837), 0.759 (0.699–0.819), 0.749 (0.667–0.831), and 0.777 (0.726–0.828), respectively. The AUROC of the scoring system were 0.810 (0.785–0.835), 0.772 (0.718–0.826), 0.736 (0.675–0.798), 0.717 (0.635–0.799) and 0.756 (0.704–0.808), respectively. The prediction performances were both significantly superior to those of preoperative US (
P
< 0.001).
Conclusion
The nomogram and scoring system performed well in different datasets and significantly improved the preoperative prediction of LNM than US alone.
Carrier based dry powder inhalers (DPIs) have become a hotspot in recent years. Lactose is the most commonly used carrier in DPI, while its further application was hindered by its hygroscopicity. ...Agglomeration induced by hygroscopicity would cause the deterioration of aerosolization performance. In this study, cyclodextrin-lactose binary carriers (CLBCs) were produced by spray-drying so as to surmount the hygroscopicity. Physicochemical attributes of CLBCs were explored in detail. Hygroscopicity of CLBCs was elucidated by dynamic vapor sorption study. Aerosolization performance of its corresponding DPIs was evaluated by the next generation impactor (NGI). In addition, the preliminary reserach on the formation mechanism of CLBCs was carried out. The optimal formulation of CLBC (L3) was proven to possess anti-hygroscopicity and aerosolization performance enhancement properties. To be concise, the moisture uptake of L3 was ca. 2.8% which was far lower than spray-driedlactose (L0, ca. 50.1%). L3 exhibited a high fine particle fraction value of 59.16 ± 1.41 and it was 3.7-fold against L0. After 10-day storage in high humidity, L3 maintained its physicochemical properties and the superior aerosolization performance. It was proved that CLBC with anti-hygroscopicity and aerosolization performance enhancement properties was a promising approach for pulmonary drug delivery, which could provide new possibilities to the application of hygroscopic carriers for DPI.
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•Hygroscopicity of carriers was overcome by addition of hydroxypropyl-β-cyclodextrin.•Novel carriers with anti-hygroscopicity and better aerosolization performance.•The formation mechanism of hydroxypropyl-β-cyclodextrin aggregate was explored.
Since the outbreak of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), public health worldwide has been greatly threatened. The ...development of an effective treatment for this infection is crucial and urgent but is hampered by the incomplete understanding of the viral infection mechanisms and the lack of specific antiviral agents. We previously reported that teicoplanin, a glycopeptide antibiotic that has been commonly used in the clinic to treat bacterial infection, significantly restrained the cell entry of Ebola virus, SARS-CoV, and MERS-CoV by specifically inhibiting the activity of cathepsin L (CTSL). Here, we found that the cleavage sites of CTSL on the spike proteins of SARS-CoV-2 were highly conserved among all the variants. The treatment with teicoplanin suppressed the proteolytic activity of CTSL on spike and prevented the cellular infection of different pseudotyped SARS-CoV-2 viruses. Teicoplanin potently prevented the entry of SARS-CoV-2 into the cellular cytoplasm with an IC
of 2.038 μM for the Wuhan-Hu-1 reference strain and an IC
of 2.116 μM for the SARS-CoV-2 (D614G) variant. The pre-treatment of teicoplanin also prevented SARS-CoV-2 infection in hACE2 mice. In summary, our data reveal that CTSL is required for both SARS-CoV-2 and SARS-CoV infection and demonstrate the therapeutic potential of teicoplanin for universal anti-CoVs intervention.
A fundamental element of acute lung injury (ALI) is the inflammatory response, which can affect the entire respiratory system, including the respiratory tract and alveoli. Berberine has gained ...attention because of its anti‐inflammatory effects. Nuclear factor‐erythroid 2‐related factor 2 (Nrf2) and endoplasmic reticulum (ER) stress are involved in lung injury. Nrf2 also acts as a protein kinase‐like ER kinase (PERK) substrate in heart disease. Therefore, this study investigated the effect of berberine against lipopolysaccharide (LPS)‐induced ALI and the role of the PERK‐mediated Nrf2/HO‐1 signaling axis. Berberine promoted Nrf2 nuclear translocation and phosphorylation in vitro. After LPS stimulation, this effect was further enhanced, whereas inflammatory factor (IL‐6 and IL‐8) release and reactive oxygen species generation were significantly decreased. Berberine effectively alleviated lung injury by reducing lung edema and neutrophil infiltration. Berberine also significantly reduced histopathological inflammatory changes via inhibition of ER stress and activation of Nrf2 signaling. Thapsigargin‐induced ER stress and small interference RNA (siRNA)‐mediated Nrf2 inhibition abrogated the protective effects of berberine in vitro, whereas siRNA‐mediated suppression of ER stress and sulforaphane‐induced Nrf2 activation further improved those effects. Importantly, ER stress induction led to Nrf2 activation, whereas PERK depletion partly reduced the level of Nrf2 phosphorylation and translocation in LPS‐induced cells. Therefore, berberine inhibits LPS‐induced ALI through the PERK‐mediated Nrf2/HO‐1 signaling axis.
The SARS‐CoV‐2 Delta (B.1.617.2) strain is a variant of concern (VOC) that has become the dominant strain worldwide in 2021. Its transmission capacity is approximately twice that of the original ...strain, with a shorter incubation period and higher viral load during infection. Importantly, the breakthrough infections of the Delta variant have continued to emerge in the first‐generation vaccine recipients. There is thus an urgent need to develop a novel vaccine with SARS‐CoV‐2 variants as the major target. Here, receptor binding domain (RBD)‐conjugated nanoparticle vaccines targeting the Delta variant, as well as the early and Beta/Gamma strains, are developed. Under both a single‐dose and a prime‐boost strategy, these RBD‐conjugated nanoparticle vaccines induce the abundant neutralizing antibodies (NAbs) and significantly protect hACE2 mice from infection by the authentic SARS‐CoV‐2 Delta strain, as well as the early and Beta strains. Furthermore, the elicitation of the robust production of broader cross‐protective NAbs against almost all the notable SARS‐CoV‐2 variants including the Omicron variant in rhesus macaques by the third re‐boost with trivalent vaccines is found. These results suggest that RBD‐based monovalent or multivalent nanoparticle vaccines provide a promising second‐generation vaccine strategy for SARS‐CoV‐2 variants.
Receptor binding domain (RBD)‐conjugated nanoparticle vaccines are developed with broad neutralization against SARS‐CoV‐2 Delta and other variants. There is a robust production of broader cross‐protective NAbs against almost all the notable SARS‐CoV‐2 variants including the Omicron in rhesus macaques by the third re‐boost with trivalent vaccines. These multivalent nanoparticle vaccines might be a promising second‐generation vaccine for SARS‐CoV‐2 variants.
Abstract
At present, the collection of floating garbage such as dead fish in deep and far sea cage culture waters mainly depends on manpower, which is not only difficult and inefficient, but also has ...great potential safety hazards. In order to solve the above problems, a water surface collection robot based on marine cage culture is designed and developed. The dead fish on the water surface are collected through the joint action of propeller and forearm drainage and retraction device. At the same time, the relevant performance indexes of the designed water surface collection robot are verified by making the prototype and water surface collection experiments, which meets the needs of simple and efficient collection and cleaning of dead fish in deep and open sea cage culture, so as to provide a reference basis for the practical application of the collection robot.
The development of a vaccine specific to severe acute respiratory syndrome coronavirus 2 Omicron has been hampered due to its low immunogenicity. Here, using reverse mutagenesis, we found that a ...phenylalanine-to-serine mutation at position 375 (F375S) in the spike protein of Omicron to revert it to the sequence found in Delta and other ancestral strains significantly enhanced the immunogenicity of Omicron vaccines. Sequence FAPFFAF at position 371-377 in Omicron spike had a potent inhibitory effect on macrophage uptake of receptor-binding domain (RBD) nanoparticles or spike-pseudovirus particles containing this sequence. Omicron RBD enhanced binding to Siglec-9 on macrophages to impair phagocytosis and antigen presentation and promote immune evasion, which could be abrogated by the F375S mutation. A bivalent F375S Omicron RBD and Delta-RBD nanoparticle vaccine elicited potent and broad nAbs in mice, rabbits and rhesus macaques. Our research suggested that manipulation of the Siglec-9 pathway could be a promising approach to enhance vaccine response.
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