Safety, immunogenicity and protective effectiveness of heterologous boost with a recombinant COVID-19 vaccine (Sf9 cells) in adult recipients of inactivated vaccines.

Vaccines have proven effective in protecting populations against COVID-19, including the recombinant COVID-19 vaccine (Sf9 cells), the first approved recombinant protein vaccine in China. In this positive-controlled trial with 85 adult participants (Sf9 cells group: n = 44; CoronaVac group: n = 41), we evaluated the safety, immunogenicity, and protective effectiveness of a heterologous boost with the Sf9 cells vaccine in adults who had been vaccinated with the inactivated vaccine, and found a post-booster adverse events rate of 20.45% in the Sf9 cells group and 31.71% in the CoronaVac group (p = 0.279), within 28 days after booster injection. Neither group reported any severe adverse events. Following the Sf9 cells vaccine booster, the geometric mean titer (GMT) of binding antibodies to the receptor-binding domain of prototype SARS-CoV-2 on day 28 post-booster was significantly higher than that induced by the CoronaVac vaccine booster (100,683.37 vs. 9,451.69, p < 0.001). In the Sf9 cells group, GMTs of neutralizing antibodies against pseudo SARS-CoV-2 viruses (prototype and diverse variants of concern [VOCs]) increased by 22.23-75.93 folds from baseline to day 28 post-booster, while the CoronaVac group showed increases of only 3.29-10.70 folds. Similarly, neutralizing antibodies against live SARS-CoV-2 viruses (prototype and diverse VOCs) increased by 68.18-192.67 folds on day 14 post-booster compared with the baseline level, significantly greater than the CoronaVac group (19.67-37.67 folds). A more robust Th1 cellular response was observed with the Sf9 cells booster on day 14 post-booster (mean IFN-γ+ spot-forming cells per 2 × 105 peripheral blood mononuclear cells: 26.66 vs. 13.59). Protective effectiveness against symptomatic COVID-19 was approximately twice as high in the Sf9 cells group compared to the CoronaVac group (68.18% vs. 36.59%, p = 0.004). Our study findings support the high protective effectiveness of heterologous boosting with the recombinant COVID-19 vaccine (Sf9 cells) against symptomatic COVID-19 of diverse SARS-CoV-2 variants of concern, while causing no apparent safety concerns.

Insulin-like growth factor binding protein 5 accelerate the senescence of periodontal ligament stem cells.

Evidences have showed stem cell mediated tissue regeneration is a promising method for the treatment of periodontitis. Insulin-like growth factor binding proteins-5 (IGFBP5) is a member of the insulin growth factor (IGFs) family and plays a regulatory role in cell proliferation and differentiation. Our previous study showed that IGFBP5 can promote osteogenic differentiation of periodontal ligament stem cells (PDLSCs) and enhance periodontal tissue regeneration mediated by PDLSCs. However, the function of IGFBP5 in the process of PDLSCs senescence remains unclear. The present study showed IGFBP5 mRNA level was highly expressed in passage-induced aged PDLSCs cells. IGFBP5 knockdown decreased the ratio of senescence associated ß-galactosidase (SA-ß-Gal) positive cells, enhanced the activity of TERT, and down-regulated the expression levels of P16, P21, P53 mRNA and protein. Overexpression of IGFBP5 increased the ratio of SA-ß-Gal positive staining PDLSCs, decreased the activity of telomerase TERT, and up-regulated the expression levels of P16, P21, P53 mRNA and protein related to PDLSCs senescence. In conclusion, IGFBP5 can accelerate the senescence of PDLSCs, indicating the potential target for maintaining the "young state" of stem cells.

Tuning the Roundabout of Four-Point-Star Tiles with the Core Arm Length of Three Half-Turns for 2D DNA Arrays.

By rationally adjusting the weaving modes of point-star tiles, the curvature inherent in the tiles can be changed, and various DNA nanostructures can be assembled, such as planar wireframe meshes, perforated wireframe tubes, and curved wireframe polyhedra. Based on the weaving and tiling architectures for traditional point-star tiles with the core arm length at two DNA half-turns, we improved the weaving modes of our newly reported four-point-star tiles with the core arm length at three half-turns to adjust their curvature and rigidity for assembling 2D arrays of DNA grids and tubes. Following our previous terms and methods to analyze the structural details of E-tiling tubes, we used the chiral indices (n,m) to describe the most abundant tube of typical assemblies; especially, we applied both one-locus and/or dual-locus biotin/streptavidin (SA) labelling strategies to define the configurations of two specific tubes, along with the absolute conformations of their component tiles. Such structural details of the DNA tubes composed of tiles with addressable concave and convex faces and packing directions should help us understand their physio-chemical and biological properties, and therefore promote their applications in drug delivery, biocatalysis, biomedicine, etc.

Distinguish the Value of the Benign Nevus and Melanomas Using Machine Learning: A Meta-Analysis and Systematic Review.

Background: Melanomas, the most common human malignancy, are primarily diagnosed visually, beginning with an initial clinical screening and followed potentially by dermoscopic analysis, a biopsy, and histopathological examination. We aimed to systematically review the performance and quality of machine learning-based methods in distinguishing melanoma and benign nevus in the relevant literature. Method: Four databases (Web of Science, PubMed, Embase, and the Cochrane library) were searched to retrieve the relevant studies published until March 26, 2022. The Predictive model Deviation Risk Assessment tool (PROBAST) was used to assess the deviation risk of opposing law. Result: This systematic review included thirty researches with 114007 subjects and 71 machine learning models. The convolutional neural network was the main machine learning method. The pooled sensitivity was 85% (95% CI 82-87%), the specificity was 86% (82-88%), and the C-index was 0.87 (0.84-0.90). Conclusion: The findings of our study showed that ML algorithms had high sensitivity and specificity for distinguishing between melanoma and benign nevi. This suggests that state-of-the-art ML-based algorithms for distinguishing melanoma from benign nevi may be ready for clinical use. However, a large proportion of the earlier published studies had methodological flaws, such as lack of external validation and lack of clinician comparisons. The results of these studies should be interpreted with caution.

MicroRNA-196a-5p overexpression in Wharton's jelly umbilical cord stem cells promotes their osteogenic differentiation and new bone formation in bone defects in the rat calvarium.

The peri-tooth root alveolar loss often does not have sufficient space for repair material transplantation and plasticity. Mesenchymal stem cell (MSC) sheets have an advantage in providing more extracellular matrix (ECM) and may prove to be a new therapeutic consideration for this bone defect repair. The identification of key regulators that stimulate MSCs' osteogenic potential and sheet-derived ECM deposition is the key to promoting its application. In this study, we found that inhibition or overexpression of miR-196a-5p led to a decline or enhancement, respectively, in the alkaline phosphatase (ALP) activity, mineralization, and the levels of osteogenic markers, Osteocalcin (OCN), Dentin Matrix Protein 1 (DMP1), Bone Sialoprotein (BSP), and Dentin Sialophosphoprotein (DSPP) of Wharton's jelly of umbilical cord stem cells (WJCMSCs) in vitro. Moreover, the 5,6-Carboxyfluorescein Diacetate Succinimidyl Ester (CFSE) analysis revealed inhibition of the WJCMSCs' proliferative ability upon miR-196a-5p overexpression. Characterization of the sheet formation by picrosirius red and Masson staining indicated that miR-196a-5p overexpression significantly promoted the collagen content in whole WJCMSC sheet-derived ECM. Furthermore, micro-CT and histopathology results indicated that the miR-196a-5p-overexpressed WJCMSC sheets significantly promoted new bone regeneration and rat calvarial bone defect closure 12 weeks following transplantation. The mRNA microarray analysis of miR-196a-5p-overexpressed WJCMSCs revealed 959 differentially expressed genes (DEGs) (34 upregulated and 925 downregulated). Moreover, 241 genes targeted by miR-196a-5p were predicted by using miRNA function websites of which only 19 predicted genes were consistent with the microarray revealed DEGs. Hence, one unrevealed downregulated DEG Serpin Family B Member 2 (SERPINB2) was investigated. And the deletion of SERPINB2 enhanced the ALP activity and mineralization of WJCMSCs in vitro. In conclusion, our study found that miR-196a-5p, as a key regulator, could repress the proliferation tendency, while stimulating osteogenic ability and WJCMSC sheet-derived ECM deposition, thus promoting new bone formation and rat calvarial bone defect closure. Furthermore, SERPINB2 is a key downstream gene involved in the miR-196a-5p-promoted WJCMSC osteogenesis.

Oryza sativa PECTIN DEFECTIVE TAPETUM1 affects anther development through a pectin-mediated signaling pathway in rice.

Galacturonosyltransferase (GalAT) is required for the synthesis of pectin, an important component of plant cell walls that is also involved in signal transduction. Here, we describe the rice (Oryza sativa) male-sterile mutant O. sativa pectin-defective tapetum1 (ospdt1), in which GalAT is mutated. The ospdt1 mutant exhibited premature programmed cell death (PCD) of the tapetum and disordered pollen walls, resulting in aborted pollen grains. Pectin distribution in the anther sac was comparable between the mutant and the wild-type, suggesting that the structural pectin was not dramatically affected in ospdt1. Wall-associated kinases are necessary for the signal transduction of pectin, and the intracellular distribution of O. sativa indica WALL-ASSOCIATED KINASE1 (OsiWAK1), which binds pectic polysaccharides to its extracellular domain, was affected in ospdt1. OsiWAK1 RNA interference lines exhibited earlier tapetal PCD, similar to ospdt1. Furthermore, overexpression of OsiWAK1 in ospdt1 lines partially rescued the defects observed in ospdt1, suggesting that OsiWAK1 plays pivotal roles in the function of OsPDT1. These results suggest that the mutation of OsPDT1 does not dramatically affect structural pectin but affects components of the pectin-mediated signaling pathway, such as OsiWAK1, and causes male sterility.

Precise Delivery of Nanomedicines to M2 Macrophages by Combining "Eat Me/Don't Eat Me" Signals and Its Anticancer Application.

Targeted delivery of nanomedicines to M2 tumor-associated macrophages (TAMs) has been proposed to reduce tumor promotion and enhance the efficacy of anticancer therapy. However, upregulated receptors on M2 TAMs are also expressed on M1 TAMs and other macrophages in normal tissues. Therefore, improving targeting specificity remains a key challenge. Here, we developed a precise M2 TAM-targeted delivery system using "eat-me" and "don't-eat-me" signals. A CD47-derived self-peptide ligand (don't-eat-me signal) and galactose ligand (eat-me signal) were introduced on liposomes. Cleavable phospholipid-polyethylene glycol was covered on the surface and could combine with the self-peptide to inhibit macrophage recognition even after immunoglobulin M adsorption and protect galactose from hepatic clearance to prolong the circulation time and promote the accumulation of liposomes in tumors. This detachable polymer can be removed by the redox microenvironment upon transcytosis through the tumor endothelium and re-expose the self-peptide and galactose. The self-peptide highly reduced M1 macrophage phagocytosis, and the galactose ligand enhanced the interaction between the liposomes and M2 macrophages. Thus, the modified liposomes enabled specific recognition of M1/M2 TAMs. In vitro evidence revealed reduced endocytosis of the liposomes by M1 macrophages. Moreover, in vivo studies demonstrated that doxorubicin-loaded liposomes efficiently eliminated M2 TAMs but did not affect M1 TAMs, enhancing the potency of the antitumor therapy. Collectively, our results demonstrate the potential of combining active escape and active targeting for precisely delivering a drug of interest to M2 macrophages and suggest its application in anticancer therapy.

Contamination of SARS-CoV-2 in patient surroundings and on personal protective equipment in a non-ICU isolation ward for COVID-19 patients with prolonged PCR positive status.

OBJECTIVES: We performed an environmental sampling study to investigate the environmental contamination of SARS-CoV-2 by COVID-19 patients with prolonged PCR positive status of clinical samples. METHODS: We sampled the air from rooms for nine COVID-19 patients with illness or positive PCR > 30 days, before and after nasopharyngeal/oropharyngeal swabbing and before and after nebulization treatment. We also sampled patients' surroundings and healthcare workers' personal protection equipment (PPE) in a non-ICU ward. SARS-CoV-2 was detected by PCR. RESULTS: Eighty-eight samples were collected from high-touch surfaces and floors in patient rooms and toilets, with only the bedsheets of two patients and one toilet positive for SARS-CoV-2. All air samples (n = 34) were negative for SARS-CoV-2. Fifty-five samples collected from PPE were all negative. CONCLUSION: Contamination of near-patient surroundings was uncommon for COVID-19 patients with prolonged PCR positive status if environmental cleaning/disinfection were performed rigorously. Airborne transmission of SARS-CoV-2 was unlikely in these non-ICU settings.

Using sodium D-gluconate to suppress hydrogen production in wet aluminium waste dust collection systems.

The reaction of aluminium dust and water generated in the production of aluminium products generates hydrogen, which poses a risk to wet collection systems for hydrogen explosions. In this paper, non-toxic and environmentally friendly sodium D-gluconate is used to suppress the hydrogen production reaction of aluminium waste dust and water. The results of the hydrogen evolution curves and chemical kinetics of 7 different concentrations of sodium D-gluconate showed that when the sodium D-gluconate concentration reached 0.25 g L-1, there was almost no hydrogen generation, and the rate constant was almost zero. The scanning electron microscopy (SEM) results showed that the surface of the reaction product became smoother with increasing solution concentration. The energy dispersive spectroscopy (EDS) results showed that increasing the solution concentration slowed the formation of aluminium oxide in the product, confirming the effectiveness of sodium D-gluconate in inhibiting the reaction of aluminium waste dust particles with water. The Fourier transform infrared (FTIR) results showed that sodium D-gluconate formed a chemical adsorption film on the surface of aluminium waste dust particles to prevent the dust from contacting water, thus suppressing hydrogen production. This method provides a new approach to design safe wet collection systems by suppressing hydrogen production.

Study of hydrogen explosion control measures by using l-phenylalanine for aluminum wet dust removal systems.

Wet dust removal systems are an effective design for preventing aluminum dust explosion in the process of metal polishing. However, wet dust removal systems pose hydrogen fire and explosion risks because aluminum dust can react with water to produce hydrogen gas. According to previous studies, l-phenylalanine can be used to solve the corrosion problem of metal slabs. In this work, a hydrogen inhibition method was proposed to inhibit hydrogen production in wet dust removal systems by using l-phenylalanine. The hydrogen evolution curves of aluminum particles reacting with different concentrations of l-phenylalanine solutions obtained via hydrogen inhibition experiments revealed that when the concentration of l-phenylalanine solutions reached 20 g L-1, essentially no hydrogen gas was produced. Scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) were used to characterize the aluminum particles before and after the reaction. This work shows that l-phenylalanine is a good inhibitor. The adsorption of l-phenylalanine on the aluminum particle surface obeys the Langmuir adsorption isotherm. Additionally, Fourier transform infrared (FTIR) analysis was conducted to explain the physicochemical mechanism of the l-phenylalanine inhibition of hydrogen production. l-Phenylalanine is an environmentally friendly inhibitor and hence can be used in wet dust removal systems for the treatment of aluminum dust, which can reduce the hydrogen fire and explosion risk.

LATERAL FLORET 1 induced the three-florets spikelet in rice.

The spikelet is a unique inflorescence structure in grass. The molecular mechanisms behind the development and evolution of the spikelet are far from clear. In this study, a dominant rice mutant, lateral florets 1 (lf1), was characterized. In the lf1 spikelet, lateral floral meristems were promoted unexpectedly and could generally blossom into relatively normal florets. LF1 encoded a class III homeodomain-leucine zipper (HD-ZIP III) protein, and the site of mutation in lf1 was located in a putative miRNA165/166 target sequence. Ectopic expression of both LF1 and the meristem maintenance gene OSH1 was detected in the axil of the sterile lemma primordia of the lf1 spikelet. Furthermore, the promoter of OSH1 could be bound directly by LF1 protein. Collectively, these results indicate that the mutation of LF1 induces ectopic expression of OSH1, which results in the initiation of lateral meristems to generate lateral florets in the axil of the sterile lemma. This study thus offers strong evidence in support of the "three-florets spikelet" hypothesis in rice.

Structural Insight into Nucleoprotein Conformation Change Chaperoned by VP35 Peptide in Marburg Virus.

Marburg virus (MARV) encodes a nucleoprotein (NP) to encapsidate its genome by oligomerization and form a ribonucleoprotein complex (RNP). According to previous investigation on nonsegmented negative-sense RNA viruses (nsNSV), the newly synthesized NPs must be prevented from indiscriminately binding to noncognate RNAs. During the viral RNA synthesis process, the RNPs undergo a transition from an RNA-bound form to a template-free form, to open access for the interaction between the viral polymerase and the RNA template. In filoviruses, this transition is regulated by VP35 peptide and other viral components. To further understand the dynamic process of filovirus RNP formation, we report here the structure of MARV NPcore, both in the apo form and in the VP35 peptide-chaperoned form. These structures reveal a typical bilobed structure, with a positive-charged RNA binding groove between two lobes. In the apo form, the MARV NP exists in an interesting hexameric state formed by the hydrophobic interaction within the long helix of the NPcore C-terminal region, which shows high structural flexibility among filoviruses and may imply critical function during RNP formation. Moreover, the VP35 peptide-chaperoned NPcore remains in a monomeric state and completely loses its affinity for single-stranded RNA (ssRNA). The structural comparison reveals that the RNA binding groove undergoes a transition from closed state to open state, chaperoned by VP35 peptide, thus preventing the interaction for viral RNA. Our investigation provides considerable structural insight into the filovirus RNP working mechanism and may support the development of antiviral therapies targeting the RNP formation of filovirus.IMPORTANCE Marburg virus is one of the most dangerous viruses, with high morbidity and mortality. A recent outbreak in Angola in 2005 caused the deaths of 272 persons. NP is one of the most essential proteins, as it encapsidates and protects the whole virus genome simultaneously with self-assembly oligomerization. Here we report the structures of MARV NPcore in two different forms. In the MARV NP apo form, we identify an interesting hexamer formed by hydrophobic interaction within a long helix, which is highly conserved and flexible among filoviruses and may indicate its critical function during the virus RNP formation. Moreover, the structural comparison with the NP-VP35 peptide complex reveals a structural transition chaperoned by VP35, in which the RNA binding groove undergoes a transition from closed state to open state. Finally, we discussed the high conservation and critical role of the VP35 binding pocket and its potential use for therapeutic development.

ABNORMAL VASCULAR BUNDLES regulates cell proliferation and procambium cell establishment during aerial organ development in rice.

To understand the molecular mechanisms of rice aerial organ development, we identified a mutant gene that caused a significant decrease in the width of aerial organs, termed ABNORMAL VASCULAR BUNDLES (AVB). Histological analysis showed that the slender aerial organs were caused by cell number reduction. In avb, the number of vascular bundles in aerial organs was reduced, whereas the area of the vascular bundles was increased. Ploidy analysis and the in situ expression patterns of histone H4 confirmed that cell proliferation was impaired during lateral primordia development, whereas procambium cells showed a greater ability to undergo cell division in avb. RNA sequencing (RNA-seq) showed that the development process was affected in avb. Map-based cloning and genetic complementation demonstrated that AVB encodes a land plant conserved protein with unknown functions. Our research shows that AVB is involved in the maintenance of the normal cell division pattern in lateral primordia development and that the AVB gene is required for procambium establishment following auxin signaling.