Elevated acetyl‐CoA by amino acid recycling fuels microalgal neutral lipid accumulation in exponential growth phase for biofuel production

Microalgal neutral lipids [mainly in the form of triacylglycerols (TAGs)], feasible substrates for biofuel, are typically accumulated during the stationary growth phase. To make microalgal biofuels economically competitive with fossil fuels, generating strains that trigger TAG accumulation from the exponential growth phase is a promising biological approach. The regulatory mechanisms to trigger TAG accumulation from the exponential growth phase (TAEP) are important to be uncovered for advancing economic feasibility. Through the inhibition of pyruvate dehydrogenase kinase by sodium dichloroacetate, acetyl‐CoA level increased, resulting in TAEP in microalga Dunaliella tertiolecta. We further reported refilling of acetyl‐CoA pool through branched‐chain amino acid catabolism contributed to an overall sixfold TAEP with marginal compromise (4%) on growth in a TAG‐rich D. tertiolecta mutant from targeted screening. Herein, a three‐step α loop‐integrated metabolic model is introduced to shed lights on the neutral lipid regulatory mechanism. This article provides novel approaches to compress lipid production phase and heightens lipid productivity and photosynthetic carbon capture via enhancing acetyl‐CoA level, which would optimize renewable microalgal biofuel to fulfil the demanding fuel market.     

The ubiquitin-interacting motif-type ubiquitin receptor HDR3 interacts with and stabilizes the histone acetyltransferase GW6a to control the grain size in rice

For grain crops such as rice (Oryza sativa), grain size substantially affects yield. The histone acetyltransferase GRAIN WEIGHT 6a (GW6a) determines grain size and yield in rice. However, the gene regulatory network underlying GW6a-mediated regulation of grain size has remained elusive. In this study, we show that GW6a interacts with HOMOLOG OF DA1 ON RICE CHROMOSOME 3 (HDR3), a ubiquitin-interacting motif-containing ubiquitin receptor. Transgenic rice plants overexpressing HDR3 produced larger grains, whereas HDR3 knockout lines produce smaller grains compared to the control. Cytological data suggest that HDR3 modulates grain size in a similar manner to GW6a, by altering cell proliferation in spikelet hulls. Mechanistically, HDR3 physically interacts with and stabilizes GW6a in an ubiquitin-dependent manner, delaying protein degradation by the 26S proteasome. The delay in GW6a degradation results in dramatic enhancement of the local acetylation of H3 and H4 histones. Furthermore, RNA sequencing analysis and chromatin immunoprecipitation assays reveal that HDR3 and GW6a bind to the promoters of and modulate a common set of downstream genes. In addition, genetic analysis demonstrates that HDR3 functions in the same genetic pathway as GW6a to regulate the grain size. Therefore, we identified the grain size regulatory module HDR3–GW6a as a potential target for crop yield improvement.

A ubiquitin receptor ubiquitylates and stabilizes a histone acetyltransferase; this module regulates downstream gene expression, altering rice grain size by modulating cell proliferation.     

Elementary Flux Mode Analysis Revealed Cyclization Pathway as a Powerful Way for NADPH Regeneration of Central Carbon Metabolism

NADPH regeneration capacity is attracting growing research attention due to its important role in resisting oxidative stress. Besides, NADPH availability has been regarded as a limiting factor in production of industrially valuable compounds. The central carbon metabolism carries the carbon skeleton flux supporting the operation of NADPH-regenerating enzyme and offers flexibility in coping with NADPH demand for varied intracellular environment. To acquire an insightful understanding of its NADPH regeneration capacity, the elementary mode method was employed to compute all elementary flux modes (EFMs) of a network representative of central carbon metabolism. Based on the metabolic flux distributions of these modes, a cluster analysis of EFMs with high NADPH regeneration rate was conducted using the self-organizing map clustering algorithm. The clustering results were used to study the relationship between the flux of total NADPH regeneration and the flux in each NADPH producing enzyme. The results identified several reaction combinations supporting high NADPH regeneration, which are proven to be feasible in cells via thermodynamic analysis and coincident with a great deal of previous experimental report. Meanwhile, the reaction combinations showed some common characteristics: there were one or two decarboxylation oxidation reactions in the combinations that produced NADPH and the combination constitution included certain gluconeogenesis pathways. These findings suggested cyclization pathways as a powerful way for NADPH regeneration capacity of bacterial central carbon metabolism.     

Cutaneous and Mucosal Phaeohyphomycosis Caused by Exophiala spinifera in a Pregnant Patient: Case Report and Literature Review

We report a case of mucocutaneous phaeohyphomycosis caused by Exophiala spinifera. Crusty plaques and nodules were major clinical features. Histological examination revealed brown yeast-like cells and hyphae. Mycological and molecular data identified E. spinifera as etiologic agent. Oral itraconazole was effective, which was in accordance with the results of in vitro susceptibility testing. We speculated that her pregnancy may play a role of risk factor in the infection by E. spinifera.     

Proper phosphorylation of septin 12 regulates septin 4 and soluble adenylyl cyclase expression to induce sperm capacitation

Septin-based ring complexes maintain the sperm annulus. Defective annular structures are observed in the sperm of Sept12- and Sept4-null mice. In addition, sperm capacitation, a process required for proper fertilization, is inhibited in Sept4-null mice, implying that the sperm annulus might play a role in controlling sperm capacitation. Hence, we analyzed sperm capacitation of sperm obtained from SEPT12 Ser196 phosphomimetic (S196E), phosphorylation-deficient (S196A), and SEPT4-depleted mutant mice. Capacitation was reduced in the sperm of both the Sept12 S196E- and Sept12 S196A-knock-in mice. The protein levels of septins, namely, SEPT4 and SEPT12, were upregulated, and these proteins were concentrated in the sperm annulus during capacitation. Importantly, the expression of soluble adenylyl cyclase (sAC), a key enzyme that initiates capacitation, was upregulated, and sAC was recruited to the sperm annulus following capacitation stimulation. We further found that SEPT12, SEPT4, and sAC formed a complex and colocalized to the sperm annulus. Additionally, sAC expression was reduced and disappeared in the annulus of the SEPT12 S196E- and S196A-mutant mouse sperm. In the sperm of the SEPT4-knockout mice, sAC did not localize to the annulus. Thus, our data demonstrate that SEPT12 phosphorylation status and SEPT4 activity jointly regulate sAC protein levels and annular localization to induce sperm capacitation.     

Efficient polymer-mediated delivery system for thiocyclam: Nanometerization remarkably improves the bioactivity toward green peach aphids

The unscientific application of synthetic pesticides has brought various negative effects on the environment, hindering the sustainable development of agriculture. Nanoparticles can be applied as carriers to improve pesticide delivery, showing great potential in the development of pesticide formulation in recent years. Herein, a star polymer (SPc) was constructed as an efficient pesticide nanocarrier/adjuvant that could spontaneously assemble with thiocyclam or monosultap into a complex, through hydrophobic association and hydrogen bonding, respectively, with the pesticide-loading contents of 42.54% and 19.3%. This complexation reduced the particle sizes of thiocyclam from 543.54 to 52.74 nm for pure thiocyclam, and 3 814.16 to 1 185.89 nm for commercial preparation (cp) of thiocyclam. Interestingly, the introduction of SPc decreased the contact angles of both pure and cp thiocyclam on plant leaves, and increased the plant uptake of cp thiocyclam to 2.4–1.9 times of that without SPc. Meanwhile, the SPc could promote the bioactivity of pure/cp thiocyclam against green peach aphids through leaf dipping method and root application. For leaf dipping method, the 50% lethal concentration decreased from 0.532 to 0.221 g/L after the complexation of pure thiocyclam with SPc, and that decreased from 0.390 to 0.251 g/L for cp thiocyclam. SPc seems a promising adjuvant for nanometerization of both pure and cp insecticides, which is beneficial for improving the delivery efficiency and utilization rate of pesticides.     

MALDI-TOF mass spectrometry rapid pathogen identification and outcomes of patients with bloodstream infection: A systematic review and meta-analysis

There was inconsistent evidence regarding the use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for microorganism identification with/without antibiotic stewardship team (AST) and the clinical outcome of patients with bloodstream infections (BSI). In a systematic review and meta-analysis, we evaluated the effectiveness of rapid microbial identification by MALDI-TOF MS with and without AST on clinical outcomes. We searched PubMed and EMBASE databases from inception to 1 February 2022 to identify pre–post and parallel comparative studies that evaluated the use of MALDI-TOF MS for microorganism identification. Pooled effect estimates were derived using the random-effects model. Twenty-one studies with 14,515 patients were meta-analysed. Compared with conventional phenotypic methods, MALDI-TOF MS was associated with a 23% reduction in mortality (RR = 0.77; 95% CI: 0.66; 0.90; I² = 35.9%; 13 studies); 5.07-h reduction in time to effective antibiotic therapy (95% CI: −5.83; −4.31; I² = 95.7%); 22.86-h reduction in time to identify microorganisms (95% CI: −23.99; −21.74; I² = 91.6%); 0.73-day reduction in hospital stay (95% CI: −1.30; −0.16; I² = 53.1%); and US$4140 saving in direct hospitalization cost (95% CI: $-8166.75; $-113.60; I² = 66.1%). No significant heterogeneity sources were found, and no statistical evidence for publication bias was found. Rapid pathogen identification by MALDI-TOF MS with or without AST was associated with reduced mortality and improved outcomes of BSI, and may be cost-effective among patients with BSI.