Tuning the Flat Band in Bi2O2Se by Pressure to Induce Superconductivity.

The discovery of superconductivity in twisted bilayer graphene has reignited enthusiasm in the field of flat-band superconductivity. However, important challenges remain, such as constructing a flat-band structure and inducing a superconducting state in materials. Here, we successfully achieved superconductivity in Bi2O2Se by pressure-tuning the flat-band electronic structure. Experimental measurements combined with theoretical calculations reveal that the occurrence of pressure-induced superconductivity at 30 GPa is associated with a flat-band electronic structure near the Fermi level. Moreover, in Bi2O2Se, a van Hove singularity is observed at the Fermi level alongside pronounced Fermi surface nesting. These remarkable features play a crucial role in promoting strong electron-phonon interactions, thus potentially enhancing the superconducting properties of the material. These findings demonstrate that pressure offers a potential experimental strategy for precisely tuning the flat band and achieving superconductivity.

Chinese visceral adiposity index and its transition patterns: impact on cardiovascular and cerebrovascular diseases in a national cohort study.

BACKGROUND: Obesity affects approximately 800 million people worldwide and may contribute to various diseases, especially cardiovascular and cerebrovascular conditions. Fat distribution and content represent two related yet distinct axes determining the impact of adipose tissue on health. Unlike traditional fat measurement indices, which often overlook fat distribution, the Chinese visceral adiposity index (CVAI) is a novel metric used to assess visceral fat accumulation and associated health risks. Our objective is to evaluate its association with the risk of cardiovascular and cerebrovascular diseases. METHODS: A nationwide longitudinal study spanning 9 years was conducted to investigate both the effects of baseline CVAI levels (classified as low and high) and dynamic changes in CVAI over time, including maintenance of low CVAI, transition from low to high, transition from high to low, and maintenance of high CVAI. Continuous scales (restricted cubic spline curves) and categorical scales (Kaplan-Meier curves and multivariable Cox regression analyses) were utilized to evaluate the relationship between CVAI and cardiovascular and cerebrovascular diseases. Furthermore, subgroup analyses were conducted to investigate potential variations. RESULTS: Totally 1761 individuals (22.82%) experienced primary outcomes among 7717 participants. In the fully adjusted model, for each standard deviation increase in CVAI, there was a significant increase in the risk of primary outcomes [1.20 (95%CI: 1.14-1.27)], particularly pronounced in the high CVAI group [1.38 (95%CI: 1.25-1.54)] compared to low CVAI group. Regarding transition patterns, individuals who consistently maintained high CVAI demonstrated the highest risk ratio compared to those who consistently maintained low CVAI [1.51 (95%CI: 1.31-1.74)], followed by individuals transitioning from low to high CVAI [1.22 (95% CI: 1.01-1.47)]. Analysis of restricted cubic spline curves indicated a positive dose-response relationship between CVAI and risk of primary outcomes (p for non-linear = 0.596). Subgroup analyses results suggest that middle-aged individuals with high CVAI face a notably greater risk of cardiovascular and cerebrovascular diseases in contrast to elderly individuals [1.75 (95% CI: 1.53-1.99)]. CONCLUSION: This study validates a significant association between baseline levels of CVAI and its dynamic changes with the risk of cardiovascular and cerebrovascular diseases. Vigilant monitoring and effective management of CVAI significantly contribute to early prevention and risk stratification of cardiovascular and cerebrovascular diseases.

Abnormal Metal-Semiconductor-Like Transition and Exceptional Enhanced Superconducting State in Pressurized Restacked TaS2.

Interlayer coupling and stacking order play essential roles in shaping the exotic electronic properties of two-dimensional materials. Here, we employ restacked TaS2─a novel transition metal dichalcogenide (TMD) with weak vdW bonding and twisted angles─to investigate the strain effects of interlayer modulation on the electronic properties. Under pressure, an unexpected transition from metallic to semiconducting-like states occurs. Superconductivity coexists with the semiconducting-like state over a wide pressure range, which has never before been observed in TMDs. Upon further compression, a new superconducting SC-II state emerges without structural evolution and gradually replaces the initial SC-I state. The emerging SC-II state exhibits robust zero-resistance superconductivity and an ultrahigh upper critical field. The abundant electronic state changes in RS-TaS2 are strongly related to band-structure engineering resulting from pressure-induced interlayer stacking angle modulation. Our results reveal the remarkable effect of interlayer rearrangement on electronic properties and provide a special way to explore the unique properties of 2D materials.

Biosensor-assisted titratable CRISPRi high-throughput (BATCH) screening for over-production phenotypes.

With rapid advances in the development of metabolic pathways and synthetic biology toolkits, a persisting challenge in microbial bioproduction is how to optimally rewire metabolic fluxes and accelerate the concomitant high-throughput phenotype screening. Here we developed a biosensor-assisted titratable CRISPRi high-throughput (BATCH) screening approach that combines a titratable mismatch CRISPR interference and a biosensor mediated screening for high-production phenotypes in Escherichia coli. We first developed a programmable mismatch CRISPRi that could afford multiple levels of interference efficacy with a one-pot sgRNA pool (a total of 16 variants for each target gene) harboring two consecutive random mismatches in the seed region of sgRNA spacers. The mismatch CRISPRi was demonstrated to enable almost a full range of gene knockdown when targeting different positions on genes. As a proof-of-principle demonstration of the BATCH screening system, we designed doubly mismatched sgRNA pools targeting 20 relevant genes in E. coli and optimized a PadR-based p-coumaric acid biosensor with broad dynamic range for the eGFP fluorescence guided high-production screening. Using sgRNA variants for the combinatorial knockdown of pfkA and ptsI, the p-coumaric acid titer was increased by 40.6% to o 1308.6 mg/l from glycerol in shake flasks. To further demonstrate the general applicability of the BATCH screening system, we recruited a HpdR-based butyrate biosensor that facilitated the screening of E. coli strains achieving 19.0% and 25.2% increase of butyrate titer in shake flasks with sgRNA variants targeting sucA and ldhA, respectively. This work reported the establishment of a plug-and-play approach that enables multilevel modulation of metabolic fluxes and high-throughput screening of high-production phenotypes.

A 2-oxoglutarate-dependent dioxygenase converts dihydrofuran to furan in Salvia diterpenoids.

Tanshinone ⅡA (TⅡA), a diterpene quinone with a furan ring, is a bioactive compound found in the medicinal herb redroot sage (Salvia miltiorrhiza Bunge), in which both furan and dihydrofuran analogs are present in abundance. Progress has been made recently in elucidating the tanshinone biosynthetic pathway, including heterocyclization of the dihydrofuran D-ring by cytochrome P450s; however, dehydrogenation of dihydrofuran to furan, a key step of furan ring formation, remains uncharacterized. Here, by differential transcriptome mining, we identified six 2-oxoglutarate-dependent dioxygenase (2-ODD) genes whose expressions corresponded to tanshinone biosynthesis. We showed that Sm2-ODD14 acts as a dehydrogenase catalyzing the furan ring aromatization. In vitro Sm2-ODD14 converted cryptotanshinone to TⅡA and thus was designated TⅡA synthase (SmTⅡAS). Furthermore, SmTⅡAS showed a strict substrate specificity, and repression of SmTⅡAS expression in hairy root by RNAi led to increased accumulation of total dihydrofuran-tanshinones and decreased production of furan-tanshinones. We conclude that SmTⅡAS controls the metabolite flux from dihydrofuran- to furan-tanshinones, which influences medicinal properties of S. miltiorrhiza.

Bacterial synthesis of C3-C5 diols via extending amino acid catabolism.

Amino acids are naturally occurring and structurally diverse metabolites in biological system, whose potentials for chemical expansion, however, have not been fully explored. Here, we devise a metabolic platform capable of producing industrially important C3-C5 diols from amino acids. The presented platform combines the natural catabolism of charged amino acids with a catalytically efficient and thermodynamically favorable diol formation pathway, created by expanding the substrate scope of the carboxylic acid reductase toward noncognate ω-hydroxylic acids. Using the established platform as gateways, seven different diol-convertible amino acids are converted to diols including 1,3-propanediol, 1,4-butanediol, and 1,5-pentanediol. Particularly, we afford to optimize the production of 1,4-butanediol and demonstrate the de novo production of 1,5-pentanediol from glucose, with titers reaching 1.41 and 0.97 g l-1, respectively. Our work presents a metabolic platform that enriches the pathway repertoire for nonnatural diols with feedstock flexibility to both sugar and protein hydrolysates.

Harnessing plasmid replication mechanism to enable dynamic control of gene copy in bacteria.

Dynamic regulation has been proved efficient in controlling gene expression at transcriptional, translational, and post-translational level. However, the dynamic regulation at gene replication level has been rarely explored so far. In this study, we established dynamic regulation at gene copy level through engineering controllable plasmid replication to dynamically control the gene expression. Prototypic genetic circuits with different control logic were applied to enable diversified dynamic behaviors of gene copy. To explore the applicability of this strategy, the dynamic gene copy control was employed in regulating the biosynthesis of p-coumaric acid, which resulted in an up to 78% increase in p-coumaric acid titer to 1.69 g/L in shake flasks. These results indicated the great potential of applying dynamic gene copy control for engineering biosynthesis of valuable compounds in metabolic engineering.

Establishing an Autonomous Cascaded Artificial Dynamic (AutoCAD) regulation system for improved pathway performance.

Endogenous metabolic pathways in microbial cells are usually precisely controlled by sophisticated regulation networks. However, the lack of such regulations when introducing heterologous pathways in microbial hosts often causes unbalanced enzyme expression and carbon flux distribution, hindering the construction of highly efficient microbial biosynthesis systems. Here, using naringenin as the target compound, we developed an Autonomous Cascaded Artificial Dynamic (AutoCAD) regulation system to automatically coordinate the pathway expression and redirect carbon fluxes for enhanced naringenin production. The AutoCAD regulation system, consisting of both intermediate-based feedforward and product-based feedback control genetic circuits, resulted in a 16.5-fold increase in naringenin titer compared with the static control. Fed-batch fermentation using the strain with AutoCAD regulation further enhanced the naringenin titer to 277.2 mg/L. The AutoCAD regulation system, with intermediate-based feedforward control and product-triggered feedback control, provides a new paradigm of developing complicated cascade dynamic control to engineer heterologous pathways.

Comparative Genomics and Functional Studies of Putative m6A Methyltransferase (METTL) Genes in Cotton.

N6-methyladenosine (m6A) RNA modification plays important regulatory roles in plant development and adapting to the environment, which requires methyltransferases to achieve the methylation process. However, there has been no research regarding m6A RNA methyltransferases in cotton. Here, a systematic analysis of the m6A methyltransferase (METTL) gene family was performed on twelve cotton species, resulting in six METTLs identified in five allotetraploid cottons, respectively, and three to four METTLs in the seven diploid species. Phylogenetic analysis of protein-coding sequences revealed that METTL genes from cottons, Arabidopsis thaliana, and Homo sapiens could be classified into three clades (METTL3, METTL14, and METTL-like clades). Cis-element analysis predicated the possible functions of METTL genes in G. hirsutum. RNA-seq data revealed that GhMETTL14 (GH_A07G0817/GH_D07G0819) and GhMETTL3 (GH_A12G2586/GH_D12G2605) had high expressions in root, stem, leaf, torus, petal, stamen, pistil, and calycle tissues. GhMETTL14 also had the highest expression in 20 and 25 dpa fiber cells, implying a potential role at the cell wall thickening stage. Suppressing GhMETTL3 and GhMETTL14 by VIGS caused growth arrest and even death in G. hirsutum, along with decreased m6A abundance from the leaf tissues of VIGS plants. Overexpression of GhMETTL3 and GhMETTL14 produced distinct differentially expressed genes (DEGs) in A. thaliana, indicating their possible divergent functions after gene duplication. Overall, GhMETTLs play indispensable but divergent roles during the growth of cotton plants, which provides the basis for the systematic investigation of m6A in subsequent studies to improve the agronomic traits in cotton.

Engineering high coenzyme Q10 tomato.

Coenzyme Q (CoQ) is vital for energy metabolism in living organisms. In humans, CoQ10 deficiency causes diseases and must be replenished via diet; however, CoQ content in plant foods is primarily low. Here, we report the breeding of high CoQ10 tomato lines by expressing four enzymes with a fruit-specific promoter, which modifies the chloroplast chorismate pathway, enhances cytosolic isoprenoid biosynthesis, and up-regulates the first two reactions in mitochondrion that construct the CoQ10 polyisoprenoid tail. We show that, while the level of the aromatic precursor could be markedly elevated, head group prenylation is the key to increasing the final CoQ10 yield. In the HUCD lines expressing all four transgenes, the highest CoQ10 content (0.15 mg/g dry weight) shows a seven-fold increase from the wild-type level and reaches an extraordinarily rich CoQ10 food grade. Overviewing the changes in other terpenoids by transcriptome and metabolic analyses reveals variable contents of carotenoids and α-tocopherol in the HUCD lines. In addition to the enigmatic relations among different terpenoid pathways, high CoQ10 plants maintaining substantial levels of either vitamin can be selected. Our investigation paves the way for the development of CoQ10-enriched crops as dietary supplements.

Spiro Scaffold Chiral Organocatalyst of 3,2'-Pyrrolidinyl Spiro-oxindole Amine and Its Catalytic Evaluation in the Enantioselective Aldol Condensation between 3-(3-Hydroxy-1H-pyrazol-1-yl)-Oxindole and Paraformaldehyde.

The spiro scaffold chiral organocatalyst of 3,2'-pyrrolidinyl spiro-oxindole amine was successfully prepared from racemic spiro-oxindole amine using l-menthol as a chiral pool in 4 steps in 28%-40% overall yields with at least 99% ee in scale-up preparation, and its catalytic activity was evaluated in the enantioselective aldol condensation between 3-(3-hydroxy-1H-pyrazol-1-yl)-oxindole and paraformaldehyde. The spiro organocatalyst showed superior catalytic activity and selectivity compared with its counterparts, and most substrates offered good to excellent results with up to 96% yield in 96% ee.

Organocatalytic enantioselective aza-Friedel-Crafts reaction between benzothiazolimines and 2-naphthols for the preparation of chiral 2'-aminobenzothiazolomethyl naphthols.

A bifunctional cinchona squaramide catalyzed enantioselective aza-Friedel-Crafts reaction between 2-naphthols and benzothiazolimines has been developed, and a series of chiral 2'-aminobenzothiazolomethyl naphthols with potential antiproliferative and anthelmintic activities have been successfully and effectively prepared in good to excellent yields (up to 98%) with excellent enantioselectivities (up to >99% ee) even in a scale-up preparation under mild conditions.

Entomomonas moraniae gen. nov., sp. nov., a member of the family Pseudomonadaceae isolated from Asian honey bee gut, possesses a highly reduced genome.

The honey bee gut microbiota contains many bacterial lineages that are specific to this ecosystem. Apis cerana, raised across the Asian continent, is of great significance to the maintenance and development of ecology and agriculture in Asia. Here, we report the isolation and characterization of strain QZS01T from the gut of Apis cerana from Pingwu County, Sichuan Province, PR China. The results of phylogenetic analysis based on 16S rRNA sequences showed that strain QZS01T forms a monophyletic group together with clone sequences derived from variable insect hosts, and it shows 92% sequence similarity to its closest relative, Pseudomonas knackmussii. Strain QZS01T possesses a reduced genome (3.3 Mbp; G+C content, 38.05 mol%) compared to all other Pseudomonas species, and the whole-genome based phylogenetic reconstruction showed that strain QZS01T represents a novel genus within the family Pseudomonadaceae. Strain QZS01T is a Gram-stain-negative facultative anaerobe. It grows on brain heart infusion agar and the energy sources utilized for growth are very limited. Based on the results of genotypic and phenotypic analyses, we propose a novel genus and species, Entomomonas moraniae gen. nov., sp. nov., with the type strain QZS01T (=CGMCC 1.13498T=KCTC 62495T).

Intelligent microbial cell factory with genetic pH shooting (GPS) for cell self-responsive base/acid regulation.

BACKGROUND: In industrial fermentation, pH fluctuation resulted from microbial metabolism influences the strain performance and the final production. The common way to control pH is adding acid or alkali after probe detection, which is not a fine-tuned method and often leads to increased costs and complex downstream processing. Here, we constructed an intelligent pH-sensing and controlling genetic circuits called "Genetic pH Shooting (GPS)" to realize microbial self-regulation of pH. RESULTS: In order to achieve the self-regulation of pH, GPS circuits consisting of pH-sensing promoters and acid-/alkali-producing genes were designed and constructed. Designed pH-sensing promoters in the GPS can respond to high or low pHs and generate acidic or alkaline substances, achieving endogenously self-responsive pH adjustments. Base shooting circuit (BSC) and acid shooting circuit (ASC) were constructed and enabled better cell growth under alkaline or acidic conditions, respectively. Furthermore, the genetic circuits including GPS, BSC and ASC were applied to lycopene production with a higher yield without an artificial pH regulation compared with the control under pH values ranging from 5.0 to 9.0. In scale-up fermentations, the lycopene titer in the engineered strain harboring GPS was increased by 137.3% and ammonia usage decreased by 35.6%. CONCLUSIONS: The pH self-regulation achieved through the GPS circuits is helpful to construct intelligent microbial cell factories and reduce the production costs, which would be much useful in industrial applications.

Base Catalyzed Abnormal [3 + 2]-Cycloaddition between Isatin N,N'-Cyclic Azomethine Imine 1,3-Dipole and 3-Methyleneoxindole for the One-Step Construction of Tetracyclic Bispirooxindoles.

An abnormal [3 + 2]-cycloaddition and highly effective and convenient one-step preparation of tetracyclic bispirooxindoles containing two all-carbon quaternary spirocenters from isatin N,N'-cyclic azomethine imine 1,3-dipole and 3-methyleneoxindole in the presence of catalytic organic base has been disclosed. A variety of bispirooxindoles bearing a dinitrogen heterocycle with four adjacent cycles have been obtained in excellent yields (up to 95%) and diastereoselectivities (>99:1) under mild conditions.

Organocatalytic Enantioselective Michael Addition between 3-(3-hydroxy-1H-pyrazol-1-yl)Oxindole and ß-Nitrostyrene for the Preparation of Chiral Disubstituted Oxindoles.

A new enantioselective Michael addition between 3-(3-hydroxy-1H-pyrazol-1-yl)oxindole, a new synthon generated from isatin N,N'-cyclic azomethine imine 1,3-dipole, and ß-nitrostyrene has been disclosed. A series of chiral 3-(3-oxo-2,3-dihydro-1H-pyrazol-1-yl) disubstituted oxindoles were obtained in excellent results (up to 97% yield, up to 94% ee) with moderate to good diastereoselectivities (up to 4.3:1 dr).

A base-catalyzed domino reaction between isoindigos and α-alkylidene succinimides-convenient preparation of highly steric bispirooxindoles.

A new base promoted Michael-Michael domino cycloaddition between isoindigos and α-alkylidene succinimides has been developed for highly efficient and one-step convenient preparation of highly steric bispiroxindoles with two adjacent quaternary carbon centers and four consecutive cycles in excellent yields (up to 96%) and diastereoselectivities (up to >20 : 1) under mild conditions within a few minutes. A series of bisprooxindoles were obtained and the synthetic potential of the protocol was evaluated in a scale-up preparation.

Efficient photocatalytic inactivation of E. coli by Mn-CdS/ZnCuInSe/CuInS2 quantum dots-sensitized TiO2 nanowires.

A novel visible light-driven photocatalyst (represented as Mn-CdS/ZCISe/CIS/TiO2) for the passivation of E. coli was prepared with TiO2 nanowires as support and using CuInS2 (CIS) and ZnCuInSe (ZCISe) quantum dots (QDs), as well as Mn-doped CdS (Mn-CdS) nanoparticles (NPs) as sensitizers. The use of CIS and ZCISe QDs and Mn-CdS NPs extends the light harvest region to visible light. The photoelectric conversion efficiency was consequently improved, with a photocurrent density of 12.5 mA cm-2, about 60 times that of pure TiO2 nanowires. The germicidal efficiency of the photocatalyst was assessed by passivation of E. coli, 96% bacteria in 50 ml 105 colony forming units (CFU) ml-1 solution were killed within 50 min. Besides the high efficiency, the composite has good stability and satisfactory recycling performance. The antibiotic mechanism was also performed by using photoluminescence and a scavenging agent of different active matter, revealing that the photo-generated holes play a major role in the sterilization process.

Water-soluble ZnCuInSe quantum dots for bacterial classification, detection, and imaging.

Bacteria are everywhere and pose severe threats to human health and safety. The rapid classification and sensitive detection of bacteria are vital steps of bacterial community research and the treatment of infection. Herein, we developed optical property-superior and heavy metal-free ZnCuInSe quantum dots (QDs) for achieving rapid discrimination of Gram-positive/Gram-negative bacteria by the naked eye; driven by the structural differences of bacteria, ZnCuInSe QDs are effective in binding to Gram-positive bacteria, especially Staphylococcus aureus (S. aureus), in comparison with Gram-negative bacteria and give discernable color viewed by the naked eye. Meanwhile, based on its distinctive fluorescence response, the accurate quantification of S. aureus was investigated with a photoluminescence system in the concentration ranges of 1 × 103 to 1 × 1011 CFU/mL, with a limit of detection of 1 × 103 CFU/mL. Furthermore, we demonstrated the feasibility of ZnCuInSe QDs as a fluorescence probe for imaging S. aureus. This simple strategy based on ZnCuInSe QDs provides an unprecedented step for rapid and effective bacterial discrimination, detection, and imaging.

Melatonin ameliorates spatial memory and motor deficits via preserving the integrity of cortical and hippocampal dendritic spine morphology in mice with neurotrauma.

We aimed to elucidate the role of cortical and hippocampal dendritic spines on neurological deficits associated with hippocampal microgliosis, hippocampal neurogenesis, and neuroinflammation in mice with cortical compact impact (CCI) injury. In the present study, we found that CCI reduced spatial memory mean latency (10 s. vs 50 s) and motor dysfunction (130 s. vs 150 s.) in mice, as determined by Morris water maze and rotarod test, respectively. Golgi staining of cortical pyramidal neurons revealed that, compared to the controls, the CCI group treated with vehicle solution had significantly lower values of dendritic order (or dendritic branch number) (4.0 vs 6.2), total spine length (400 µm vs 620 µm) and spine density (40 spines/µm vs 60 spines/µm), but had significantly higher values of dendritic beading (40 beadings/mm vs 20 beadings/mm). Additionally, Sholl analysis showed that, compared to controls, the CCI + NS group mice had significantly lower values of dendritic intersections (1.0 vs 2.0). Immunofluorescence assay also revealed that, compared to controls, the CCI + NS group mice had significantly higher values of the newly formed hippocampal cells (1250/mm2 vs 1000/mm2) but significantly lower values of dendritic order (2.0 branch # vs 4.2 branch #), total spine length (180 µm vs 320 µm) and intersection (1.0 vs 3.0). The CCI + NS group mice further showed significantly higher numbers of microglia in the dentate gyrus of the hippocampus and higher concentrations of pro-inflammatory cytokines in the cerebrospinal fluids. All the CCI-induced spatial memory (40 s) and motor (150 s) dysfunction, deranged dendritic and spine morphology of cortical pyramidal neurons or hippocampal newly formed cells, hippocampal microgliosis, and central neuroinflammation were all significantly reduced by melatonin administration during post-CCI. Simultaneously, melatonin therapy caused an enhancement in the compensatory hippocampal neurogenesis and neurotrophic growth factors (e.g., doublecortin-1) and compensatory central anti-inflammatory cytokines. Our results indicate that melatonin attenuates the spatial memory and motor deficits via the modification of cortical and hippocampal dendritic spine morphology, hippocampal microgliosis and neurogenesis, and neuroinflammation in mice with traumatic brain injury.