Category Technology

A group from School of Life Sciences, Nanjing University, Nanjing, China, etc. has reported four miRNAs (miR-7-5p, miR-24-3p, miR-145-5p and miR-223-3p) that are remarkably decreased in the elderly and diabetic individuals can inhibit SARS-CoV-2 replication.
https://www.nature.com/articles/s41392-021-00716-y

To comprehensively investigate the differences in circulating miRNA expression patterns in the serum between young and elderly people, age-related non-coding RNA expression profiles obtained by high-throughput sequencing from the NCBI Gene Expression Omnibus database were downloaded. A total of 13 samples (3 young, age <30 and 10 old, age >60) were analyzed, and differentially expressed miRNAs were screened and identified.

Quite interestingly, it was found that four miRNAs (miR-7-5p, miR-24-3p, miR-145-5p and miR-223-3p) through high-throughput sequencing and quantitative real-time PCR analysis, that are remarkably decreased in the elderly and diabetic groups.

Then, it was demonstrated that these miRNAs, either in the exosome or in the free form, can directly inhibit S protein expression and SARS-CoV-2 replication. A figure below shows the case of exosome.

A group from University of Oxford, UK, etc. has reported on mapping of SARS-CoV-2 spike glycoprotein-derived antigens presented by HLA class II on dendritic cells.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116342/

It is very curious for blog admin whether HLA-II bound glycopeptides presented as SARS-CoV-2-specific antigens on dendritic cells have the same glycosylation as phagocytized SARS-CoV-2 by dendritic cells.

HLA-II-bound glycopeptides were identified from 14 N-linked glycosylation sites in Spike from total 22 glycosylation sites. HLA-II-bound peptides carried predominantly short paucimannosidic-type N-glycans while original Spike carried oligomannosidic- and GlcNAc-capped complex-type N-glycan structures at these sites. The paucimannosylation of the HLA-II-bound peptides comprised both core-fucosylated and fucosylated species. This reveals there is substantial trimming of glycan residues on the glycopeptides during antigen processing in dendritic cells.

The heatmap colors in a figure above indicate the relative frequency of each glycan composition present, and the total number of peptide spectral matches (PSM) is also shown (blue bars).

A group from Chinese Academy of Agricultural Sciences, Shenzhen, China, etc. has reported that high Zn wheat recruit more bacteria relevant to Zn mobilization in the rhizosphere.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261137/

Around 20% of the world population are suffering from zinc (Zn) deficiency, and the situation will become worse with the increase of atmosphere carbon dioxide. An effective solution to address human Zn deficiency is to increase the grain Zn concentration of staple food crops like wheat, namely, Zn biofortification. The target of wheat Zn biofortification is to increase the current grain Zn concentration of 20 ~ 30 mg/kg to above 40 mg/kg that is sufficient for human Zn nutrition.

Due to the poor mobility of Zn in soil, the absorption of Zn by plant roots mainly occurs in the rhizosphere, where the activities of roots and microorganisms can somewhat increase the amount of available Zn. In the calcareous soils distributed worldwide, Zn availability is restricted by alkaline environment and high carbonate content; and various root exudates like carboxylic acids, amino acids, and low-molecular-weight polypeptides can acidify the rhizosphere and solubilize the Zn immobilized in minerals. Besides, the microbes living on root exudates can also produce organic acids, siderophores, and exopolysaccharides that can mobilize micronutrients in rhizosphere soil.

Comparisons of the relative abundances of rhizosphere-enriched species between High Zn (HZn) and Low Zn (LZn) wheat found that 30 species were significantly enriched in HZn with the abundance ratio of HZn to LZn >1.5 and two species were enriched in LZn with the abundance ratio of HZn to LZn <0.5. Of the 32 species, three HZn-enriched species belong to the reported soil Zn-mobilizing genus Pseudomonas, which is one of the 38 previously published Zn-mobilizing microbial species or genera. Nearly half of the previously reported Zn-mobilizing microbes were enriched in wheat rhizosphere, but most of them showed no significant difference between HZn and LZn. Differently, the 32 HZn- or LZn-enriched species were also enriched in wheat rhizosphere, and they exhibited significant differences between HZn and LZn, such as much higher abundances of Pseudomonas and Massilia species in HZn than those in LZn. Besides, genome functional annotation of the 32 species showed that 28 HZn-enriched and two LZn-enriched species possess the functional genes involved in soil Zn mobilization. Therefore, the previously reported Zn-mobilizing microbes can promote the Zn uptake of all wheat plants, while the identified 30 HZn- or LZn-enriched species may be the potential soil Zn-mobilizing microbes contributing to the variations of shoot Zn uptake and grain Zn concentration among cultivars.

It would be true that the HZn wheat recruit more bacteria relevant to soil Zn mobilization in the rhizosphere, suggesting that the difference between Hzn wheat and LZn wheat cultivars comes from the difference in microbiome of the rhizosphere. However, how HZn wheat recruit Zn mobilization bacteria is still unknown.

A group from National Cancer Institute, Frederick, USA, etc. has reported good Serum cytokine and chemokine markers associated with effective immune response to SARS-CoV-2 in mRNA vaccination.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299183/

A cohort of 63 health-care workers received the BNT162b2 mRNA vaccine and was monitored for the development of neutralizing antibodies. There were two types of recipients in this cohort. One is individuals without any SARS-CoV-2 infection before the vaccination (58 recipients), and the other was individuals with pre-existing SARS-CoV-2 infection (6 recipients). The 58 recipients showed immune responses first detected 3 weeks after the 1st dose (day 22), which was followed by a significant increase after the 2nd dose by day 36. The neutralizing ability was measured using a surrogate virus neutralization test, and an assay that reached a median of 96% inhibition after the 2nd dose, In contrast, the 5 recipients with pre-existing SARS-CoV-2 immunity showed antibody responses to SARS-CoV-2 at the day of vaccination, followed by an immediate strong anamnestic response after the 1st dose (day 8). The antibody responses did not further increase upon the 2nd vaccination and remained significantly higher than those in the SARS-CoV-2-naive vaccine recipients.

This study highlights important associations of several immunoregulatory molecules induced by vaccination with innate and adaptive immune responses elicited by an mRNA-based vaccine. The early cytokine/chemokine signature featuring IL-15, IFN-γ, and IP-10/CXCL10 may be used to monitor effective vaccination and as a guide to optimize the efficacy of mRNA vaccination strategies.

A group from Lehigh University, Bethlehem, USA has reported on pulling force between RBD of various SARS-CoV-2 variants and ACE2 taking into consideration of glycans.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8328061/

Pulling force analysis using molecular dynamics simulations was performed on RBD-ACE2 complexes as a function of distance between the centers of mass of RBD and ACE2 proteins. Fully-glycosylated S RBD-ACE2 complex model was employed for the pulling simulation, and the following variants were covered.

Alpha variant (first identified in United Kingdom, B.1.1.7: N501Y),
Beta variant (first identified in South Africa, B.1.351: K417N, E484K, N501Y),
Gamma variant (first identified in Japan/Brazil, P.1: K417T, E484K, N501Y),
Delta variant (first identified in India, B.1.617.2: L452R, T478K)),
Epsilon variant (first identified in US-California, B.1.427: L452R) ,
Kappa variant (first identified in India, B.1.617.1: L452R, E484Q)),

Alpha variant requires the highest force for initial separation from ACE2, followed by Beta and Gamma variants or Delta variant. K417N/T mutations of Beta and Gamma appear to make the RBD-ACE2 interactions less strong compared to Alpha variant. In addition, Epsilon variant is likely to be relatively easily dissociated from ACE2 than others due to its destabilized RBD structure upon the L452R mutation. In addition, Delta variant specifically shows stronger interactions with ACE2 than other variants at a relatively far distance between RBD and ACE2.

The Delta variant, interestingly, shows distinct features that are not found in other variants. Upon the T478K mutation, it requires the highest force for the RBD-ACE2 complex to be completely dissociated at D = 78 Å. In order to see what makes the difference, the number of contacts between RBD residue 478 and heavy atoms of selected key interacting residues of ACE2 was calculated. RBD Delta exclusively makes more contacts with ACE2 than other variants. Delta K478 retains contacts with ACE2 P84 and M82 at D = 78 Å, but Epsilon T478 already lost such interactions. It is possible that residue 478 located in the flexible loop could first have a chance to contact with ACE2, and the stronger interactions of Delta K478 with ACE2 could explain the reason why the proportion of Delta variant is recently dramatically being increased with high infectivity.

A group from Mohammed VI Polytechnic University (UM6P), Benguerir, Morocco, etc. has reported on Phosphate solubilizing rhizobacteria stimulating wheat germination rate and seedlings growth.
https://peerj.com/articles/11583/

Recently, rhizosphere is attracting so much attention. Rhizosphere is very much like the relationship between intestine and intestinal bacteria. Intestinal endothelium corresponds to root epithelium, and intestinal bacteria correspond to soil bacteria. However, there have been few researches on rhizosphere glycome, and blog admin is watching the progress in this field with great interests as a new frontier.

Phosphorus (P) is considered one of the most important elements in plant nutrition after nitrogen. It is an essential macronutrient to all major metabolic processes in plants growth e.g., photosynthesis, energy transfer, respiration, and signal transduction. Phosphate solubilizing microorganisms including bacteria play an important role in enhancing soil fertility and plant growth. Therefore, it is paramount to explore management strategies which are considered as an environmentally friendly process and economically feasible procedure to improve crop production and maximize their yields in P-poor soils. Exploration of the biodiversity of rhizobacteria and the optimization/manipulation of microbial interactions in the rhizosphere represents an imperative step towards formulating more efficient microbial inoculants with high P-solubilizing ability. Although P is plentiful in soils in both organic and inorganic forms, it is in unavailable forms for root uptake. Numerous soil microorganisms particularly those present in plant’s rhizosphere can release the bound forms of P to a soluble form to increase its bioavailability to plants. Phosphate solubilizing bacteria belong to plant growth promoting rhizobacteria and are capable of solubilizing inorganic P from a variety of sources, such as dicalcium phosphate, tricalcium phosphate, or rock phosphate.

Bacteria screening identified nine best phosphate solubilizing strains as follows,

Indole acetic acid (IAA) stimulates plant growth,

Ammonia is a chemical compound having indirect plant health benefits, primarily by acting as metabolic inhibitor against phytopathogens. All tested strains were able to produce ammonia with various concentrations. The best one was Pseudomonas sp. J153.

As a conclusion, inoculation with P. moraviensis J12 and B. cereus J156 promote the highest rate of wheat seeds germination and seedlings growth.

A group from Jan Kochanowski University, Kielce, Poland, etc. has reported effectiveness of Tocilizumab and Dexamethasone in COVID-19 severe patients.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291861/

Comparing four groups (treated with Tocilizmab (TCZ), treated with TCZ and Dexamethason (DEX), treated with DEX, and no TCZ nor DEX), the death rate of 6.8% was significantly lower in patients receiving TCZ alone than other groups (19.6%–23.1%), particularly in patients with IL-6 concentration exceeding 100pg/mL, the death rate was significantly lower in patients receiving TCZ alone than other groups (5% vs 22.9%–51.7%, respectively).
The clinical improvements on day21 and day28 were also doubled in the case of TCZ alone (60% and 75%, respectively)comparing with that in that case of DEX alone (27.6% and 37.9%, respectively).

So, in patients with severe course of COVID-19, particularly those developing cytokine storm, administration of TCZ provides a significantly better effect than DEX regarding survival, clinical improvement, and hospital discharge rate. The combination of TCZ and DEX does not improve therapy effectiveness in patients with severe COVID-19 compared to the administration of TCZ alone.

A group from Northwestern University Feinberg School of Medicine, USA, etc. has reported on neutralizing antibody responses after one or two doses of COVID-19 mRNA vaccine in previously infected and uninfected individuals.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276631/

The following three groups were compared:
(1)COVID-19 group: previously recovered from a confirmed outpatient case of COVID-19,
(2)Seropositive group: seropositive for anti-SARS-CoV-2 receptor binding domain (RBD) IgG but no acute virus diagnostic test for COVID-19,
(3)Seronegative group: seronegative for prior SARS-CoV-2 infection prior to vaccination.

The COVID-19 group had median% neutralization (22.2 vs. 4.4, p < 0.001) in comparison with the seropositive group. The COVID-19 group had significantly higher median% neutralization (99.9 vs. 56.5, p < 0•001) in comparison with the seropositive group. Post-dose 1 responses were higher for the seropositive group in comparison with the seronegative group, but %neutralization (56.5 vs. 38.2, p = 0•12) were not significantly different. The COVID-19 group had higher post-dose 2 median% neutralization (99.9 vs. 98.5, p<0•001) in comparison with the seropositive group. The seropositive and seronegative groups did not differ significantly in post-dose 2 median% neutralization (98.5 vs. 97.9, p = 0.46). As a result, a single dose is sufficient to boost immunity to high levels among previously infected individuals.