ABA-induced phosphorylation of basic leucine zipper 29, ABSCISIC ACID INSENSITIVE 19, and Opaque2 by SnRK2.2 enhances gene transactivation for endosperm filling in maize.

Opaque2 (O2) functions as a central regulator of the synthesis of starch and storage proteins and the O2 gene is transcriptionally regulated by a hub coordinator of seed development and grain filling, ABSCISIC ACID INSENSITIVE 19 (ZmABI19), in maize (Zea mays). Here, we identified a second hub coordinator, basic Leucine Zipper 29 (ZmbZIP29) that interacts with ZmABI19 to regulate O2 expression. Like zmabi19, zmbzip29 mutations resulted in a dramatic decrease of transcript and protein levels of O2 and thus a significant reduction of starch and storage proteins. zmbzip29 seeds developed slower and had a smaller size at maturity than those of the wild type. The zmbzip29;zmabi19 double mutant displayed more severe seed phenotypes and a greater reduction of storage reserves compared to the single mutants, whereas overexpression of the two transcription factors enhanced O2 expression, storage-reserve accumulation, and kernel weight. ZmbZIP29, ZmABI19, and O2 expression was induced by abscisic acid (ABA). With ABA treatment, ZmbZIP29 and ZmABI19 synergistically transactivated the O2 promoter. Through liquid chromatography tandem-mass spectrometry analysis, we established that the residues threonine(T) 57 in ZmABI19, T75 in ZmbZIP29, and T387 in O2 were phosphorylated, and that SnRK2.2 was responsible for the phosphorylation. The ABA-induced phosphorylation at these sites was essential for maximum transactivation of downstream target genes for endosperm filling in maize.

Cuproptosis associated cytoskeletal destruction contributes to podocyte injury in chronic kidney disease.

The podocyte cytoskeleton determines the stability of podocyte structure and function, and their imbalance plays a pathogenic role in podocyte diseases. However, the underlying mechanism of podocyte cytoskeleton damage is not fully understood. Here, we investigate the specific role of cuproptosis in inducing podocyte cytoskeleton injury. In vitro and in vivo studies, exposure to high levels of copper and adriamycin (ADR) caused significant increases in copper concentration in intracellular and renal tissue. Moreover, excessive accumulation of copper induced cuproptosis, resulting in the destruction of the podocyte cytoskeleton. However, inhibition of copper accumulation to reduce cuproptosis also significantly alleviated the damage of podocyte cytoskeleton. In addition, inhibition of cuproptosis mitigated ADR-induced mitochondrial damage as well as the production of reactive oxygen species and depolarization of mitochondrial membrane potential, and restored ATP synthesis. Among the transcriptome sequencing data, the difference of CXCL5 was the most significant. Both high copper and ADR exposure can cause up-regulation of CXCL5, and CXCL5 deletion inhibits the occurrence of cuproptosis, thereby alleviating the podocyte cytoskeleton damage. This suggests that CXCL5 may act upstream of cuproptosis that mediates podocyte cytoskeleton damage. In conclusion, cuproptosis induced by excessive copper accumulation may induce podocyte cytoskeleton damage by promoting mitochondrial dysfunction, thereby causing podocyte injury. This indicates that cuproptosis plays an important role in the pathogenesis of podocyte injury and provides a basis for seeking potential targets for the treatment of chronic kidney disease.

Nanobodies as negative allosteric modulators for human calcium sensing receptor.

Human calcium sensing receptor (CaSR) senses calcium ion concentrations in vivo and is an important class of drug targets. Mutations in the receptor can lead to disorders of calcium homeostasis, including hypercalcemia and hypocalcemia. Here, 127 CaSR-targeted nanobodies were generated from camels, and four nanobodies with inhibitory function were further identified. Among these nanobodies, NB32 can effectively inhibit the mobilization of intracellular calcium ions (Ca2+i) and suppress the G12/13 and ERK1/2 signaling pathways downstream of CaSR. Moreover, it enhanced the inhibitory effect of the calcilytics as a negative allosteric modulator (NAM). We determined the structure of complex and found NB32 bound to LB2 (Ligand-binding 2) domain of CaSR to prevent the interaction of LB2 domains of two protomers to stabilize the inactive state of CaSR.

Dual-Interface Solar Evaporator with Highly-Efficient Thermal Regulation via Suspended Multilayer Design.

Facing the increasing global shortage of freshwater resources, this study presents a suspended multilayer evaporator (SMLE), designed to tackle the principal issues plaguing current solar-driven interfacial evaporation technologies, specifically, substantial thermal losses and limited water production. This approach, through the implementation of a multilayer structural design, enables superior thermal regulation throughout the evaporation process. This evaporator consists of a radiation damping layer, a photothermal conversion layer, and a bottom layer that leverages radiation, wherein the bottom layer exhibits a notable infrared emissivity. The distinctive feature of the design effectively reduces radiative heat loss and facilitates dual-interface evaporation by heating the water surface through mid-infrared radiation. The refined design leads to a notable evaporation rate of 2.83 kg m-2 h-1. Numerical simulations and practical performance evaluations validate the effectiveness of the multilayer evaporator in actual use scenarios. This energy-recycling and dual-interface evaporation multilayered approach propels the design of high-efficiency solar-driven interfacial evaporators forward, presenting new insights into developing effective water-energy transformation systems.

Spatial Information Lasing Enabled by Full-k-Space Bound States in the Continuum.

Optical amplification and massive information transfer in modern physics depend on stimulated radiation. However, regardless of traditional macroscopic lasers or emerging micro- and nanolasers, the information modulations are generally outside the lasing cavities. On the other hand, bound states in the continuum (BICs) with inherently enormous Q factors are limited to zero-dimensional singularities in momentum space. Here, we propose the concept of spatial information lasing, whose lasing information entropy can be correspondingly controlled by near-field Bragg coupling of guided modes. This concept is verified in gain-loss metamaterials supporting full-k-space BICs with both flexible manipulations and strong confinement of light fields. The counterintuitive high-dimensional BICs exist in a continuous energy band, which provide a versatile platform to precisely control each lasing Fourier component and, thus, can directly convey rich spatial information on the compact size. Single-mode operation achieved in our scheme ensures consistent and stable lasing information. Our findings can be expanded to different wave systems and open new scenarios in informational coherent amplification and high-Q physical frameworks for both classical and quantum applications.

Revealing the material basis and mechanism for the inhibition of intestinal peristalsis by Zingiber officinale Roscoe through integrated metabolomics, serum pharmacochemistry, and network pharmacology.

Abnormal relaxation and contraction of intestinal smooth muscle can cause various intestinal diseases. Diarrhea is a common and important public health problem worldwide in epidemiology. Zingiber officinale Roscoe (fresh ginger) has been found to treat diarrhea, but the material basis and mechanism of action that inhibits intestinal peristalsis remain unclear. Metabolomics and serum pharmacology were used to identify differential metabolites, metabolic pathways, and pharmacodynamic substances, and were then combined with network pharmacology to explore the potential targets of ginger that inhibit intestinal peristalsis during diarrhea treatment, and the targets identified were verified using molecular docking and molecular dynamic simulation. We found that 25 active components of ginger (the six most relevant components), 35 potential key targets (three core targets), 40 differential metabolites (four key metabolites), and four major metabolic pathways were involved in the process by which ginger inhibits intestinal peristalsis during diarrhea treatment. This study reveals the complex mechanism of action and pharmacodynamic material basis of ginger in the inhibition of intestinal peristalsis, and this information helps in the development of new Chinese medicine to treat diarrhea and lays the foundation for the clinical application of ginger.

An atypical Phytophthora sojae RxLR effector manipulates host vesicle trafficking to promote infection.

In plants, the apoplast is a critical battlefield for plant-microbe interactions. Plants secrete defense-related proteins into the apoplast to ward off the invasion of pathogens. How microbial pathogens overcome plant apoplastic immunity remains largely unknown. In this study, we reported that an atypical RxLR effector PsAvh181 secreted by Phytophthora sojae, inhibits the secretion of plant defense-related apoplastic proteins. PsAvh181 localizes to plant plasma membrane and essential for P. sojae infection. By co-immunoprecipitation assay followed by liquid chromatography-tandem mass spectrometry analyses, we identified the soybean GmSNAP-1 as a candidate host target of PsAvh181. GmSNAP-1 encodes a soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein, which associates with GmNSF of the SNARE complex functioning in vesicle trafficking. PsAvh181 binds to GmSNAP-1 in vivo and in vitro. PsAvh181 interferes with the interaction between GmSNAP-1 and GmNSF, and blocks the secretion of apoplastic defense-related proteins, such as pathogenesis-related protein PR-1 and apoplastic proteases. Taken together, these data show that an atypical P. sojae RxLR effector suppresses host apoplastic immunity by manipulating the host SNARE complex to interfere with host vesicle trafficking pathway.

A Plasmon Resonance Enhanced Photo-Electrode to Promote NH3 Yield in Sustainable N2 Conversion.

A key challenge for electrochemical nitrogen reduction reactions (NRR) is the difficulty for conventional catalysts to achieve high currents at low H* coverage to produce appreciable NH3 . Herein, we specially designed an Au nanoparticle-embedded ZnSe photo-electrode to solve the problem. As-designed photo-electrode achieves excellent NRR performance with a high NH3 yield (12.2 µg cm-2 h-1 ) and Faradaic efficiency (27.3 %). Our work reveals that the unique plasmon resonance effect of embedded Au nanoparticles plays a key role in increasing catalytic current when the H* coverage is decreased. Moreover, we successfully established a correlation between H* coverage and NRR performance based on theoretical calculations and experimental observations. This work paves the path for the future design of catalytic materials to overcome the selectivity and yield challenge of sustainable NH3 production.

Gibberellic acid overproduction in Fusarium fujikuroi using regulatory modification and transcription analysis.

Gibberellic acid (GA3), one of the natural diterpenoids produced by Fusarium fujikuroi, serves as an important phytohormone in agriculture for promoting plant growth. Presently, the metabolic engineering strategies for increasing the production of GA3 are progressing slowly, which seriously restricted the advancing of the cost-effective industrial production of GA3. In this study, an industrial strain with high-yield GA3 of F. fujikuroi was constructed by metabolic modification, coupling with transcriptome analysis and promoter engineering. The over-expression of AreA and Lae1, two positive factors in the regulatory network, generated an initial producing strain with GA3 production of 2.78 g L-1. Compared with a large abundance of transcript enrichments in the GA3 synthetic gene cluster discovered by the comparative transcriptome analysis, geranylgeranyl pyrophosphate synthase 2 (Ggs2), and cytochrome P450-3 genes, two key genes that respectively participated in the initial and final step of biosynthesis, were identified to be downregulated when the highest GA3 productivity was obtained. Employing with a nitrogen-responsive bidirectional promoter, the two rate-limiting genes were dynamically upregulated, and therefore, the production of GA3 was increased to 3.02 g L-1. Furthermore, the top 20 upregulated genes were characterized in GA3 over-production, and their distributions in chromosomes suggested potential genomic regions with a high transcriptional level for further strain development. The construction of a GA3 high-yield-producing strain was successfully achieved, and insights into the enriched functional transcripts provided novel strain development targets of F. fujikuroi, offering an efficient microbial development platform for industrial GA3 production. KEY POINTS: • Global regulatory modification was achieved in F. fujikuroi for GA3 overproduction. • Comparative transcriptome analysis revealed bottlenecks in GA specific-pathway. • A dynamically nitrogen-regulated bidirectional promoter was cloned and employed.

Effect of quadriceps training at different levels of blood flow restriction on quadriceps strength and thickness in the mid-term postoperative period after anterior cruciate ligament reconstruction: a randomized controlled external pilot study.

BACKGROUND: More than 2 million anterior cruciate ligament (ACL) injuries occur worldwide each year. Most surgeons suggest that athletes and active persons with significant knee functional demands, including cutting motions, require and should be offered ligament reconstruction surgery. Despite concentrated rehabilitation efforts, deficits in quadriceps size and strength can persist for years after surgery. Blood flow restriction (BFR) training can help overcome disuse muscular atrophy in the mid-term postoperative period after anterior cruciate ligament reconstruction (ACLR) surgery. The purpose of this study was to evaluate the effects of quadriceps training with different levels of blood flow restriction on quadriceps strength and thickness of participants after ACLR. METHODS: In this study, 30 post-ACL reconstruction participants were randomly divided into three groups (control, 40% Arterial Occlusion Pressure [AOP] and 80% AOP groups). All patients were subjected to different levels of BFR, combined with conventional quadriceps rehabilitation, for 8 weeks. Assessments included scaled maximal isokinetic knee extension strength at 60°/s and 180°/s, the sum of the thickness of the affected femoris rectus and vastus intermedius, Y-balance test performance, and International Knee Documentation Committee questionnaire responses before and after the intervention. RESULTS: In total, 23 participants completed the entire study. The 80% AOP compression group showed an increase in quadriceps femoris muscle strength and muscle thickness (p < 0.01). As compared with the control group, outcome indicators in the 40% AOP and 80% AOP group were improved (p < 0.05). After 8 weeks of experimental BFR intervention, the results were better for the 80% AOP compression group than for the 40% AOP compression group in quadriceps peak torque to body weight at 60°/s and 180°/s angular velocity, as well as the sum of the thickness of the rectus femoris and vastus intermedius. CONCLUSION: The combination of BFR and low-intensity quadriceps femoris training can effectively improve the muscle strength and thickness of knee extensors in participants with ACLR and help reduce the difference between the healthy and surgical sides of the knee joint while improving knee-joint function. Choosing quadriceps training with 80% AOP compression intensity could provide the most benefits. Meanwhile, BFR can accelerate the rehabilitation process of patients and allow early entry into the next rehabilitation cycle. REGISTRATION: Trial registration Chinese Clinical Trial Registry, registration number ChiCTR2100050011, date of registration: 15/08/2021.

Home-based exercise program and Health education in patients with patellofemoral pain: a randomized controlled trial.

BACKGROUND: Patellofemoral pain (PFP) is one of the most common disorders of the knee joint. Home-based exercise is an effective intervention to achieve self-management for chronic diseases. This study evaluated the effects of home-based exercise and health education in patients with PFP. METHODS: Patients who had PFP were randomly allocated to an intervention group (IG) or control group (CG). Patients in the IG received a 6-week tailored home-based exercise program with health education via remote support, while patients in the CG group only received health education. Clinical outcomes were compared using the Anterior Knee Pain Scale (AKPS) to measure function and the Visual Analog Scale (VAS) to measure "worst pain" and "pain with daily activity". Muscle strength was measured according to the peak torque of the knee muscles using an isokinetic system. RESULTS: Among a total of 112 participants screened for eligibility, 38 were randomized and analyzed, including 19 participants in the intervention group and 19 participants in the control group. There were no significant differences in baseline characteristics between the groups. At 6-week follow-up, the intervention group showed a greater worst pain reduction (between-group difference, -19.3 [95%CI, -23.2 to -15.5]; P < 0.01) and pain with daily activity (between-group difference, -22.9 [95%CI, -28.3 to -17.4]; P < 0.01) than the control group. Similarly, the intervention group had better improvements in AKPS (between-group difference, 9.0 [95%CI, 4.1 to 13.9]; P < 0.01) and knee extensor strength (between-group difference, 20.1 [95%CI, 14.5 to 25.8]; P < 0.01), compared to the control group. No adverse events were reported. CONCLUSION: Home-based exercise and health education resulted in less pain, better function, and higher knee muscle strength compared with no exercise in patients with PFP. A large randomized controlled trial with long-term follow-up is required to confirm these findings. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2200056224 ( https://www.chictr.org.cn/showproj.aspx?proj=135506 ). Registered on February 1, 2022.

Effect of river-lake connectivity on ecological stoichiometry of lake and carbon storage status in Eastern Plain, China.

C, N, and P in lake sediment are the basis of material and energy cycle, reflecting the economic development, ecological function, and environmental effect. Current research on the effect of lake eutrophication on carbon storage and the river-lake connectivity on nutrient diffusion is lack. This work investigated the accumulation, distribution, correlations, and stoichiometric ratios of C, N, and P of 82 lakes (≥ 10 km2) in Eastern China, analyzed the nutrient limitation, sediment carbon sink, and effect of river-lake connectivity, and discussed the relationships between eutrophication and sediment carbon storage. The average concentrations and ranges of total C, N, and P in lake sediments were (23.26 mg/g, 0.08-153.45 mg/g), (2.32 mg/g, 0.29-14.17 mg/g), and (0.86 mg/g, 0.23-2.64 mg/g), respectively. The ecological stoichiometry of C: N: P in lake sediments was 32: 3.2: 1. P can be easily accumulated in lakes connected from the Yangtze River, while C and N can be easily accumulated in disconnected lakes. The soil-water erosion in runoff is an important factor for P diffusion. The C/N and C/N/P weren't affected by the river-lake connectivity but depended on the plant type. The Eastern Plain Lake Region of China is C and N co-depletion, and P enrichment. The lake eutrophication leading to algal bloom is unfavorable to the goal of carbon storage and carbon neutrality. Outcome of this study will provide a significant reference and strategies for carbon sequestration research, eco-environmental protection, and watershed nutrient management.

Toxin-Enabled "On-Demand" Liposomes for Enhanced Phototherapy to Treat and Protect against Methicillin-Resistant Staphylococcus aureus Infection.

An effective therapeutic strategy against methicillin-resistant Staphylococcus aureus (MRSA) that does not promote further drug resistance is highly desirable. While phototherapies have demonstrated considerable promise, their application toward bacterial infections can be limited by negative off-target effects to healthy cells. Here, a smart targeted nanoformulation consisting of a liquid perfluorocarbon core stabilized by a lipid membrane coating is developed. Using vancomycin as a targeting agent, the platform is capable of specifically delivering an encapsulated photosensitizer along with oxygen to sites of MRSA infection, where high concentrations of pore-forming toxins trigger on-demand payload release. Upon subsequent near-infrared irradiation, local increases in temperature and reactive oxygen species effectively kill the bacteria. Additionally, the secreted toxins that are captured by the nanoformulation can be processed by resident immune cells to promote multiantigenic immunity that protects against secondary MRSA infections. Overall, the reported approach for the on-demand release of phototherapeutic agents into sites of infection could be applied against a wide range of high-priority pathogens.

Phytophthora sojae apoplastic effector AEP1 mediates sugar uptake by mutarotation of extracellular aldose and is recognized as a MAMP.

Diseases caused by Phytophthora pathogens devastate many crops worldwide. During infection, Phytophthora pathogens secrete effectors, which are central molecules for understanding the complex plant-Phytophthora interactions. In this study, we profiled the effector repertoire secreted by Phytophthora sojae into the soybean (Glycine max) apoplast during infection using liquid chromatography-mass spectrometry. A secreted aldose 1-epimerase (AEP1) was shown to induce cell death in Nicotiana benthamiana, as did the other two AEP1s from different Phytophthora species. AEP1 could also trigger immune responses in N. benthamiana, other Solanaceae plants, and Arabidopsis (Arabidopsis thaliana). A glucose dehydrogenase assay revealed AEP1 encodes an active AEP1. The enzyme activity of AEP1 is dispensable for AEP1-triggered cell death and immune responses, while AEP-triggered immune signaling in N. benthamiana requires the central immune regulator BRASSINOSTEROID INSENSITIVE 1-associated receptor kinase 1. In addition, AEP1 acts as a virulence factor that mediates P. sojae extracellular sugar uptake by mutarotation of extracellular aldose from the α-anomer to the ß-anomer. Taken together, these results revealed the function of a microbial apoplastic effector, highlighting the importance of extracellular sugar uptake for Phytophthora infection. To counteract, the key effector for sugar conversion can be recognized by the plant membrane receptor complex to activate plant immunity.

Updated design strategies for oral delivery systems: maximized bioefficacy of dietary bioactive compounds achieved by inducing proper digestive fate and sensory attributes.

Interest in the application of dietary bioactive compounds (DBC) in healthcare and pharmaceutical industries has motivated researchers to develop functional delivery systems (FDS) aiming to maximize their bioefficacy. As the direct and indirect health benefiting effects of DBC are acknowledged, traditional design principle of FDS aiming at improving the bioavailability of intact DBC is challenged by the updated one, where the maximized bioefficacy of DBC delivered by FDS will be achieved via rationally absorbed at target sites with proper metabolism pathways. This article briefly summarized the absorption and metabolic fates of orally digested DBC along with their direct and indirect mechanisms to perform health benefiting effects. Current strategies in designing the next generation FDS with an emphasis on their modulation effects on the distribution portion between the upper and lower digestive tract, portal vein and lymphatic absorption, human digestive and gut microbiota enzymatic mediated metabolism were highlighted. Updated research progresses of FDS in adjusting sensory attributes of food end products and inducing synergistic effects rooting from matrix materials and co-delivered cargos were also discussed. Challenges as well as future perspectives concerning the precise nutrition and the critical role of delivery systems in dietary intervention were proposed.

Metallic-semiconducting transition and spin polarized-unpolarized transition in a single molecule with a negative Poisson's ratio.

Different from conventional materials, structures with a negative Poisson's ratio (NPR) contract/expand laterally under a longitudinal compressive/tensile strain, usually exhibiting peculiar features. Through first-principles calculations, we investigate the electronic and transport properties of Pd9B16 molecules. Its Poisson's ratio is found to be negative under uniaxial strain along a specific direction. By contacting with Au nanowires, atomic Au chains and atomic C chain electrodes, two kinds of transitions for transmission states could be realized by the modulation of the strain and the contacting site, i.e., metallic-semiconducting transition and spin polarized-unpolarized transition. Further analysis shows that it is the suppression and shifting of density of states, caused by the strain or contacting electrodes, that trigger the transitions. Those findings combine NPR and spintronics at the single-molecule level, which may throw light on the development of nanoelectronic devices.

Development of stable agar/carrageenan-Fe3O4-Klebsiella pneumoniae composite beads for efficient phenol degradation.

It's of practical importance but highly challenging for cell immobilization supports to maintain mechanical strength and reduce microbial leakage in environmental and industrial applications. Herein, we developed an agar/κ-carrageenan composite hydrogel to entrap Klebsiella pneumoniae with the combination of nano-Fe3O4 for processing phenol wastes. The agar/carrageenan-K. pneumoniae composite bead showed good pelletizing properties, superior material strength and high cell loading. Introduction of nano-Fe3O4 to the composite gel further enhanced phenol degradation rate by >10% owing to strengthened phenol oxidation by Fe3O4-induced hydroxyl radicals (·OH) and improved mass and electron transfers. 50 successive cycles of degradation and recycling using the agar/carrageenan-K. pneumoniae composite bead showed that 1500 mg/L phenol was fully degraded for all cycles with the highest rate of 55.12 mg L-1·h-1 obtained at the 15th cycles. The improved stability and recyclability render the as-prepared immobilized phenol-degrading bacteria with great potential for industrial applications.

Structural basis for auxiliary subunit KCTD16 regulation of the GABAB receptor.

Metabotropic GABAB receptors mediate a significant fraction of inhibitory neurotransmission in the brain. Native GABAB receptor complexes contain the principal subunits GABAB1 and GABAB2, which form an obligate heterodimer, and auxiliary subunits, known as potassium channel tetramerization domain-containing proteins (KCTDs). KCTDs interact with GABAB receptors and modify the kinetics of GABAB receptor signaling. Little is known about the molecular mechanism governing the direct association and functional coupling of GABAB receptors with these auxiliary proteins. Here, we describe the high-resolution structure of the KCTD16 oligomerization domain in complex with part of the GABAB2 receptor. A single GABAB2 C-terminal peptide is bound to the interior of an open pentamer formed by the oligomerization domain of five KCTD16 subunits. Mutation of specific amino acids identified in the structure of the GABAB2-KCTD16 interface disrupted both the biochemical association and functional modulation of GABAB receptors and G protein-activated inwardly rectifying K+ channel (GIRK) channels. These interfacial residues are conserved among KCTDs, suggesting a common mode of KCTD interaction with GABAB receptors. Defining the binding interface of GABAB receptor and KCTD reveals a potential regulatory site for modulating GABAB-receptor function in the brain.

Effect of Nanopore Geometry in the Conformation and Vibrational Dynamics of a Highly Confined Molecular Glass.

The effect of nanoporous confinement on the glass transition temperature (Tg) strongly depends on the type of porous media. Here, we study the molecular origins of this effect in a molecular glass, N,N'-bis(3-methylphenyl)-N,N'-diphenylbenzidine (TPD), highly confined in concave and convex geometries. When confined in controlled pore glass (CPG) with convex pores, TPD's vibrational spectra remained unchanged and two Tg's were observed, consistent with previous studies. In contrast, when confined in silica nanoparticle packings with concave pores, the vibrational peaks were shifted due to more planar conformations and Tg increased, as the pore size was decreased. The strong Tg increases in concave pores indicate significantly slower relaxation dynamics compared to CPG. Given TPD's weak interaction with silica, these effects are entropic in nature and are due to conformational changes at molecular level. The results highlight the role of intramolecular degrees of freedom in the glass transition, which have not been extensively explored.

Recent advances in metabolic regulation and bioengineering of gibberellic acid biosynthesis in Fusarium fujikuroi.

The plant growth hormone gibberellic acid (GA3), as one of the representative secondary metabolites, is widely used in agriculture, horticulture and brewing industry. GA3 is detected in both plants and several fungi with the ability to stimulate plant growth. Currently, the main mode of industrial production of GA3 is depended on the microbial fermentation via long-period submerged fermentation using Fusarium fujikuroi as the only producing strain, qualified for its natural productivity. However, the demand of large-sale industrialization of GA3 was still restricted by the low productivity. The biosynthetic route of GA3 in F. fujikuroi is now well-defined. Furthermore, the multi-level regulation mechanisms involved in the whole network of GA3 production have also been gradually unveiled by the past two decades based on the identification and characterization of several global regulators and their mutual functions. Combined with the quick development of genetic manipulation techniques, the rational modification of producing strain F. fujikuroi development become practical for higher productivity achievement. Herein, we review the latest advances in the molecular regulation of GA3 biosynthesis in F. fujikuroi and conclude a comprehensive network involving nitrogen depression, global regulator, histone modification and G protein signaling pathway. Correspondingly, the bioengineering strategies covering conventional random mutation, genetic manipulating platform development, metabolic edition and fermentation optimization were also systematically proposed.