Decoding the role of the arginine dihydrolase pathway in shaping human gut community assembly and health-relevant metabolites.

The arginine dihydrolase pathway (arc operon) provides a metabolic niche by transforming arginine into metabolic byproducts. We investigate the role of the arc operon in probiotic Escherichia coli Nissle 1917 on human gut community assembly and health-relevant metabolite profiles. By stabilizing environmental pH, the arc operon reduces variability in community composition in response to pH perturbations and frequently enhances butyrate production in synthetic communities.

Covalent Modification of Protein by Chemical Probe in Living Cells for Structural and Interaction Studies.

Cellular activities are predominantly carried out by proteins that can dynamically adopt different structural conformations and differentially interact with other biomolecules according to cellular needs. Chemical probes are small molecules used to selectively interact and modulate the activities of specific proteins to study their functions such as the validation of potential drug targets. The remarkable performance of AlphaFold algorithms in the prediction of protein structures has pivoted interest toward elucidating the intracellular dynamics of protein structural conformation where covalent modification of proteins by chemical probes could be used to shed light upon.

Shaping human gut community assembly and butyrate production by controlling the arginine dihydrolase pathway.

The arginine dihydrolase pathway ( operon) present in a subset of diverse human gut species enables arginine catabolism. This specialized metabolic pathway can alter environmental pH and nitrogen availability, which in turn could shape gut microbiota inter-species interactions. By exploiting synthetic control of gene expression, we investigated the role of the operon in probiotic Nissle 1917 on human gut community assembly and health-relevant metabolite profiles and in the murine gut.

Inferring delays in partially observed gene regulation processes.

Motivation: Cell function is regulated by gene regulatory networks (GRNs) defined by protein-mediated interaction between constituent genes. Despite advances in experimental techniques, we can still measure only a fraction of the processes that govern GRN dynamics. To infer the properties of GRNs using partial observation, unobserved sequential processes can be replaced with distributed time delays, yielding non-Markovian models.

Transcriptomic Analysis of the Response of Susceptible and Resistant Bitter Melon ( L.) to Powdery Mildew Infection Revealing Complex Resistance via Multiple Signaling Pathways.

The challenge of mitigating the decline in both yield and fruit quality due to the intrusion of powdery mildew (PM) fungus looms as a pivotal concern in the domain of bitter melon cultivation. Yet, the intricate mechanisms that underlie resistance against this pathogen remain inscrutable for the vast majority of bitter melon variants. In this inquiry, we delve deeply into the intricate spectrum of physiological variations and transcriptomic fluctuations intrinsic to the PM-resistant strain identified as '04-17-4' (R), drawing a sharp contrast with the PM-susceptible counterpart, designated as '25-15' (S), throughout the encounter with the pathogenic agent .

Programming bacteria for multiplexed DNA detection.

DNA is a universal and programmable signal of living organisms. Here we develop cell-based DNA sensors by engineering the naturally competent bacterium Bacillus subtilis (B. subtilis) to detect specific DNA sequences in the environment.

Efficient plasmid transfer via natural competence in a microbial co-culture.

The molecular and ecological factors shaping horizontal gene transfer (HGT) via natural transformation in microbial communities are largely unknown, which is critical for understanding the emergence of antibiotic-resistant pathogens. We investigate key factors shaping HGT in a microbial co-culture by quantifying extracellular DNA release, species growth, and HGT efficiency over time. In the co-culture, plasmid release and HGT efficiency are significantly enhanced than in the respective monocultures.

Organocatalytic Enantioselective 1,10-Addition of Alkynyl Indole Imine Methides with Thiazolones: An Access to Axially Chiral Tetrasubstituted Allenes.

An asymmetric organocatalytic remote 1,10-addition of alkynyl indole imine methides generated from α-(6-indolyl) propargylic alcohols with thiazolones has been developed for the first time, affording axially chiral tetrasubstituted allenes featuring vicinal sulfur-containing quaternary carbon stereocenters in high yields with excellent stereoselectivities. The representative scale-up reaction and transformations of the 1,10-adduct were examined. The reaction mechanism was expounded by control experiments and DFT calculations.

Organocatalytic enantioselective [2 + 4]-annulation of γ-substituted allenoates with -acyldiazenes for the synthesis of optically active 1,3,4-oxadiazines.

An enantioselective [2 + 4]-annulation of γ-substituted allenoates with N-acyldiazenes has been developed for the first time. In the presence of an l-proline-derived DMAP analogue, the annulation proceeded smoothly to afford a broad range of 1,3,4-oxadiazine derivatives in good to excellent yields with high stereoselectivities.

Enantioselective construction of 3-substituted 3-amino-2-oxindoles containing an N,N-ketal skeleton via organocatalyzed aza-addition of isatin imines.

The first example of organocatalytic chemo-, regio- and enantioselective aza-Mannich reactions of triazoles and arylamines, respectively, with isatin-derived imines has been achieved in the presence of double hydrogen bonding organocatalysts, affording the valuable optically active 3-substituted 3-amino-2-oxindoles featuring N,N-ketal structural motifs in high yields. This strategy was featured by low catalyst loading, mild conditions, broad substrate scope, and high efficiency and selectivity.

Organocatalytic enantioselective conjugate addition of 2-naphthols to -hydroxyphenyl substituted -quinone methides: access to unsymmetrical triarylmethanes.

The enantioselective conjugate addition of 2-naphthols to -hydroxyphenyl substituted -quinone methides has been achieved with the aid of a chiral phosphoric acid. Importantly, the reaction took place with excellent chemo- and regioselectivities. In addition, the protocol features a low catalyst loading, mild reaction conditions, and enables the formation of unsymmetrical triarylmethanes in good to high yields with generally high enantioselectivities.

Bayesian inference of distributed time delay in transcriptional and translational regulation.

Motivation: Advances in experimental and imaging techniques have allowed for unprecedented insights into the dynamical processes within individual cells. However, many facets of intracellular dynamics remain hidden, or can be measured only indirectly. This makes it challenging to reconstruct the regulatory networks that govern the biochemical processes underlying various cell functions.

ETV4 promotes proliferation and invasion of lung adenocarcinoma by transcriptionally upregulating MSI2.

The oncogenic roles of ETV4 have been revealed in multiple cancers. However, its expression and functions in lung cancer are rarely explored. Here, we firstly detected the expression of ETV4 in lung adenocarcinoma (LUAD) via online data and local experiment validation.

Remote Stereocontrolled Construction of Vicinal Axially Chiral Tetrasubstituted Allenes and Heteroatom-Functionalized Quaternary Carbon Stereocenters.

The direct diastereo- and enantioselective 1,8-conjugate additions of thiazolones and azlactones, respectively, to para-quinone methides generated in situ from propargylic alcohols have been achieved in the presence of chiral phosphoric acids. The remote stereocontrolled activation protocol provides an efficient and facile approach for the construction of vicinal axially chiral tetrasubstituted allenes and heteroatom-functionalized quaternary carbon stereocenters, which expands the synthetic potential of chiral phosphoric acids.

Regioselective [3 + 2]-annulation of hydrazonyl chlorides with 1,3-dicarbonyl compounds for assembling of polysubstituted pyrazoles.

A facile approach to polysubstituted pyrazoles from hydrazonyl chlorides and 1,3-dicarbonyl compounds has been developed. In the presence of DMAP combined with Et3N, hydrazonyl chlorides reacted with N-phenyl-3-oxobutanamides smoothly to afford a series of polysubstituted pyrazoles in 67-98% yields via the [3 + 2]-cycloaddition.

Catalyst-Controlled Diastereodivergent Construction of Vicinal Sulfur-Functionalized Quaternary and Tertiary Stereocenters.

A catalyst-controlled diastereodivergence is described for the enantioselective conjugate addition of o-hydroxyphenyl-substituted p-QMs with 5 H-thiazol-4-ones. The reactions were enabled by two chiral complementary, nonenantiomeric catalysts to furnish a series of adducts possessing vicinal sulfur-functionalized quaternary and tertiary stereocenters in high yields with excellent asymmetric induction. Moreover, o-QMs generated in situ from o-hydroxybenzyl alcohols were also compatible.

Enantioselective Organocatalytic 1,6-Addition of Azlactones to para-Quinone Methides: An Access to α,α-Disubstituted and β,β-Diaryl-α-amino acid Esters.

This work describes the first enantioselective 1,6-additions of azlactones to para-quinone methides. In the presence of a chiral phosphoric acid, 1,6-adducts were obtained in high yields (up to 96%) with excellent diastereoselectivities and enantioselectivities (all >20:1 diastereoselectivity ratio (dr), up to 99% enantiomeric excess (ee)). Importantly, the method offers a facile synthetic approach, not only to enantiopure α,α-disubstituted α-amino acid esters, but also to unnatural enantioenriched β,β-diaryl-α-amino acid esters bearing adjacent tertiary and quaternary stereogenic centers.

Organocatalytic Enantioselective [1 + 4] Annulation of Morita-Baylis-Hillman Carbonates with Electron-Deficient Olefins: Access to Chiral 2,3-Dihydrofuran Derivatives.

A reaction has been developed for the chiral phosphine-catalyzed enantioselective [1 + 4] annulation of Morita-Baylis-Hillman carbonates with electron-deficient olefins via a Michael alkylation process. Morita-Baylis-Hillman carbonates reacted smoothly with β,γ-unsaturated α-keto ester and α,β-unsaturated ketone substrates under 1,2-bis[(2R,5R)-2,5-dimethylphospholano]benzene monoxide catalysis to furnish a wide range of optically active 2,3-dihydrofurans in high yields (up to 95%) with excellent asymmetric induction (up to >99% ee, >20:1 dr). This protocol represents an efficient strategy for the synthesis of optically active multifunctional 2,3-dihydrofurans via an asymmetric Michael alkylation domino reaction.

The Timing of Transcriptional Regulation in Synthetic Gene Circuits.

Transcription factors and their target promoters are central to synthetic biology. By arranging these components into novel gene regulatory circuits, synthetic biologists have been able to create a wide variety of phenotypes, including bistable switches, oscillators, and logic gates. However, transcription factors (TFs) do not instantaneously regulate downstream targets.

Organocatalytic condensation-ring opening-annulation cascade reactions between N-Bocindolin-2-ones/benzofuran-2(3H)-ones and salicylaldehydes for synthesis of 3-arylcoumarins.

An organocatalytic cascade synthesis of 3-arylcoumarins has been developed. Mediated by 1,8-diazabicyclo[5,4,0]-undec-7-ene or tetramethylguanidine, a number of 3-arylcoumarins were obtained in good to excellent yields via condensation-ring opening-annulation between N-Bocindolin-2-ones/benzofuran-2(3H)-ones and salicylaldehydes. This method was featured by a broad scope of reactants, mild conditions, and simple operation.

Organocatalytic Asymmetric Benzylation and Aldol-Hemiacetalization of α,β-Unsaturated Trifluoromethyl Ketones: Efficient Enantioselective Construction of 3,4-Dihydroisocoumarins.

A new method has been developed for the organocatalytic enantioselective benzylation and aldol-hemiacetalization of α,β-unsaturated trifluoromethyl ketones with toluene derivatives in the presence of a tertiary amine-thiourea catalyst. This method represents a facile and efficient strategy for the asymmetric synthesis of optically active 3,4-dihydroisocoumarins bearing a trifluoromethylated tetrasubstituted carbon stereocenter with high enantioselectivity. Notably, this strategy was used to synthesize several chiral trifluoromethylated analogues of typharin with high efficiency.