biosynthesis of 4,6-dihydroxycoumarin in .

Coumarins and their derivatives possess crucial biochemical and pharmaceutical properties. However, the exploration of the coumarin biosynthesis pathways remains limited, restricting their microbial biosynthesis, especially for hydroxycoumarins. In this work, we designed and verified novel artificial pathways to produce a valuable compound 4,6-dihydroxycoumarin (4,6-DHC) in .

Structure of the WIPI3/ATG16L1 Complex Reveals the Molecular Basis for the Recruitment of the ATG12~ATG5-ATG16L1 Complex by WIPI3.

Macroautophagy deploys a wealth of autophagy-related proteins to synthesize the double-membrane autophagosome, in order to engulf cytosolic components for lysosome-dependent degradation. The recruitment of the ATG12~ATG5-ATG16L1 complex by WIPI family proteins is a crucial step in autophagosome formation. Nevertheless, the molecular mechanism by which WIPI3 facilitates the recruitment of the ATG12~ATG5-ATG16L1 complex remains largely unknown.

Molecular Basis of the Recognition of the Active Rab8a by Optineurin.

Optineurin (OPTN), a multifunctional adaptor protein in mammals, plays critical roles in many cellular processes, such as vesicular trafficking and autophagy. Notably, mutations in optineurin are directly associated with many human diseases, such as amyotrophic lateral sclerosis (ALS). OPTN can specifically recognize Rab8a and the GTPase-activating protein TBC1D17, and facilitate the inactivation of Rab8a mediated by TBC1D17, but with poorly understood mechanism.

Architecting a transcriptional repressor-based genetic inverter for tryptophan derived pathway regulation in Escherichia coli.

Efficient microbial cell factories require intricate and precise metabolic regulations for optimized production, which can be significantly aided by implementing regulatory genetic circuits with versatile functions. However, constructing functionally diverse genetic circuits in host strains is challenging. Especially, functional diversification based on transcriptional repressors has been rarely explored due to the difficulty in inverting their repression properties.

Investigating and Engineering an 1,2-Propanediol-Responsive Transcription Factor-Based Biosensor.

Transcription factor (TF)-based biosensors have arisen as powerful tools in the advancement of metabolic engineering. However, with the emergence of numerous bioproduction targets, the variety of applicable TF-based biosensors remains severely limited. In this study, we investigated and engineered an 1,2-propanediol (1,2-PD)-responsive transcription activator, PocR, from to enrich the current biosensor repertoire.

Advancing microbial production through artificial intelligence-aided biology.

Microbial cell factories (MCFs) have been leveraged to construct sustainable platforms for value-added compound production. To optimize metabolism and reach optimal productivity, synthetic biology has developed various genetic devices to engineer microbial systems by gene editing, high-throughput protein engineering, and dynamic regulation. However, current synthetic biology methodologies still rely heavily on manual design, laborious testing, and exhaustive analysis.

Neural basis of reward expectancy inducing proactive aggression.

Proactive aggression refers to deliberate and unprovoked behavior, typically motivated by personal gain or expected reward. Reward expectancy is generally recognized as a critical factor that may influence proactive aggression, but its neural mechanisms remain unknown. We conducted a task-based functional magnetic resonance imaging (fMRI) experiment to investigate the relationship between reward expectancy and proactive aggression.

Inhibition of Nogo-B reduces the progression of pancreatic cancer by regulation NF-κB/GLUT1 and SREBP1 pathways.

Pancreatic cancer (PC) is a lethal disease and associated with metabolism dysregulation. Nogo-B is related to multiple metabolic related diseases and types of cancers. However, the role of Nogo-B in PC remains unknown.

Recent progresses in analytical method development for Pb in environmental and biological samples.

As a decay product of uranium series, Pb spreads widely in the nature and imposes strong radiological and chemical toxicity. It is vital to establish reliable and efficient radioanalytical methods for Pb determination to support environment and food radioactivity monitoring programs. This article critically reviews analytical methods developed for determining Pb in environmental and biological samples, especially new development in recent years.

Neural correlates of aggression outcome expectation and their association with aggression: A voxel-based morphometry study.

Background: Aggression outcome expectation is an important cognitive factor of aggression. Discovering the neural mechanism of aggression outcome expectation is conducive to developing aggression research. However, the neural correlates underlying aggression outcome expectation and its effect remain elusive.

Determination and human health risk assessment of TFWT, OBT and carbon-14 in seafood around Qinshan Nuclear Power Plant.

This work aims to evaluate the effects of the operation of Qinshan nuclear Power Plant (QNPP) on tritium (H) and carbon-14 (C) levels in seafood and assess the health risks caused by seafood consumption. Five kinds of seafood, including marine fish, prawn, razor clam, crabs, and seaweed, were collected from QNPP and the sea around Hangzhou Bay. The activity concentrations of tissue free water tritium (TFWT), organically bound tritium (OBT) and C were determined, respectively, and the annual intake and annual effective dose (AED) were calculated.

A self-regulated network for dynamically balancing multiple precursors in complex biosynthetic pathways.

Microbial synthesis has emerged as a promising and sustainable alternative to traditional chemical synthesis and plant extraction. However, the competition between synthetic pathways and central metabolic pathways for cellular resources may impair final production efficiency. Moreover, when the synthesis of target product requires multiple precursors from the same node, the conflicts of carbon flux have further negative impacts on yields.

Structure-based development of potent and selective type-II kinase inhibitors of RIPK1.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge.

Effects of LED Light Colors on the Growth Performance, Intestinal Morphology, Cecal Short-Chain Fatty Acid Concentrations and Microbiota in Broilers.

This study aimed to explore the effects of light-emitting diode (LED) light colors on growth, intestinal morphology, and cecal microbiota in broilers. A total of 360 healthy male Arbor Acres (AA) broilers with similar weights were selected and divided into four groups with six replicates in each group and 15 broilers in each replicate: LED white light (W), LED green light (G), LED blue light (B), and LED blue-green composite light (BG). The experimental period was 42 d, the light cycle of each treatment group was 23L:1D (23 h of light, one hour of darkness) from 1 to 3 d, and the light cycle from 4 to 42 d was 16L:8D; light intensity was 20 Lux.

Mechanistic insights into the enzymatic activity of E3 ligase HOIL-1L and its regulation by the linear ubiquitin chain binding.

Heme-oxidized IRP2 ubiquitin ligase 1 (HOIL-1L) serves as a unique E3 ligase to catalyze the mono-ubiquitination of relevant protein or sugar substrates and plays vital roles in numerous cellular processes in mammals. However, the molecular mechanism underpinning the E3 activity of HOIL-1L and the related regulatory mechanism remain elusive. Here, we report the crystal structure of the catalytic core region of HOIL-1L and unveil the key catalytic triad residues of HOIL-1L.

Mechanistic Insights into the Interactions of Arl8b with the RUN Domains of PLEKHM1 and SKIP.

Arl8b, a specific Arf-like family GTPase present on lysosome, and plays critical roles in many lysosome-related cellular processes such as autophagy. The active Arl8b can be specifically recognized by the RUN domains of two Arl8b-effectors PLEKHM1 and SKIP, thereby regulating the autophagosome/lysosome membrane fusion and the intracellular lysosome positioning, respectively. However, the mechanistic bases underlying the interactions of Arl8b with the RUN domains of PLEKHM1 and SKIP remain elusive.

Identifying, Characterizing, and Engineering a Phenolic Acid-Responsive Transcriptional Factor from .

Transcriptional factors-based biosensors are commonly used in metabolic engineering for inducible control of gene expression and related applications such as high-throughput screening and dynamic pathway regulations. Mining for novel transcriptional factors is essential for expanding the usability of these toolsets. Here, we report the identification, characterization, and engineering of a phenolic acid responsive regulator PadR from (BaPadR).

Application of Metabolite-Responsive Biosensors for Plant Natural Products Biosynthesis.

Plant natural products (PNPs) have shown various pharmaceutical activities, possessing great potential in global markets. Microbial cell factories (MCFs) provide an economical and sustainable alternative for the synthesis of valuable PNPs compared with traditional approaches. However, the heterologous synthetic pathways always lack native regulatory systems, bringing extra burden to PNPs production.

ATG16L1 is equipped with two distinct WIPI2-binding sites to drive autophagy.

The recruitment of ATG12-ATG5-ATG16L1 complex to phagophore mediated by the specific interaction between ATG16L1 and WIPI2, is pivotal to the formation of autophagosomes during macroautophagy. Recently, we reported that ATG16L1 contains two distinct WIPI2-binding sites, the previously reported WIPI2-binding site (WBS1), and the newly identified site (WBS2). By determining the crystal structures of WIPI2 with ATG16L1 WBS1 and WBS2 respectively, we uncovered that, unlike ATG16L1 WBS1, ATG16L1 WBS2 and its binding mechanism to WIPI2 are conserved from yeast to mammals.

ATG16L1 adopts a dual-binding site mode to interact with WIPI2b in autophagy.

Macroautophagy plays crucial roles in the regulation of cellular physiology and requires de novo synthesis of double-membrane autophagosomes, which relies on a specific interaction between autophagy-related 16L1 (ATG16L1) and WD repeat domain phosphoinositide-interacting protein 2b (WIPI2b). However, the molecular mechanism governing the interaction of ATG16L1 with WIPI2b remains elusive. Here, we find that ATG16L1 has two distinct binding sites for interacting with WIPI2b, the previously reported WIPI2b-binding site (WBS1) and the previously unidentified site (WBS2).

Governance of China's Potatso National Park Influenced by Local Community Participation.

Conservationists recognize that protected areas (PAs) have limited prospects without the involvement and support of local people. As a governance strategy, community participation is to implement the coordinated development of communities and PAs. However, the effects of community participation on national park governance have rarely been tested.