Structural insight into H4K20 methylation on H2A.Z-nucleosome by SUV420H1.

DNA replication ensures the accurate transmission of genetic information during the cell cycle. Histone variant H2A.Z is crucial for early replication origins licensing and activation in which SUV420H1 preferentially recognizes H2A.Z-nucleosome and deposits H4 lysine 20 dimethylation (H4K20me2) on replication origins. Here, we report the cryo-EM structures of SUV420H1 bound to H2A.Z-nucleosome or H2A-nucleosome and demonstrate that SUV420H1 directly interacts with H4 N-terminal tail, the DNA, and the acidic patch in the nucleosome. The H4 (1-24) forms a lasso-shaped structure that stabilizes the SUV420H1-nucleosome complex and precisely projects the H4K20 residue into the SUV420H1 catalytic center. In vitro and in vivo analyses reveal a crucial role of the SUV420H1 KR loop (residues 214-223), which lies close to the H2A.Z-specific residues D97/S98, in H2A.Z-nucleosome preferential recognition. Together, our findings elucidate how SUV420H1 recognizes nucleosomes to ensure site-specific H4K20me2 modification and provide insights into how SUV420H1 preferentially recognizes H2A.Z nucleosome.

Structural insight into BRCA1-BARD1 complex recruitment to damaged chromatin.

The BRCA1-BARD1 complex directs the DNA double-strand break (DSB) repair pathway choice to error-free homologous recombination (HR) during the S-G2 stages. Targeting BRCA1-BARD1 to DSB-proximal sites requires BARD1-mediated nucleosome interaction and histone mark recognition. Here, we report the cryo-EM structure of BARD1 bound to a ubiquitinated nucleosome core particle (NCPUb) at 3.1 Å resolution and illustrate how BARD1 simultaneously recognizes the DNA damage-induced mark H2AK15ub and DNA replication-associated mark H4K20me0 on the nucleosome. In vitro and in vivo analyses reveal that the BARD1-NCPUb complex is stabilized by BARD1-nucleosome interaction, BARD1-ubiquitin interaction, and BARD1 ARD domain-BARD1 BRCT domain interaction, and abrogating these interactions is detrimental to HR activity. We further identify multiple disease-causing BARD1 mutations that disrupt BARD1-NCPUb interactions and hence impair HR. Together, this study elucidates the mechanism of BRCA1-BARD1 complex recruitment and retention by DSB-flanking nucleosomes and sheds important light on cancer therapeutic avenues.

The zinc finger protein DHHC09 S-acylates the kinase STRK1 to regulate H2O2 homeostasis and promote salt tolerance in rice.

Soil salinity results in oxidative stress and heavy losses to crop production. The S-acylated protein SALT TOLERANCE RECEPTOR-LIKE CYTOPLASMIC KINASE 1 (STRK1) phosphorylates and activates CATALASE C (CatC) to improve rice (Oryza sativa L.) salt tolerance, but the molecular mechanism underlying its S-acylation involved in salt signal transduction awaits elucidation. Here, we show that the DHHC-type zinc finger protein DHHC09 S-acylates STRK1 at Cys5, Cys10, and Cys14 and promotes salt and oxidative stress tolerance by enhancing rice H2O2-scavenging capacity. This modification determines STRK1 targeting to the plasma membrane or lipid nanodomains and is required for its function. DHHC09 promotes salt signaling from STRK1 to CatC via transphosphorylation, and its deficiency impairs salt signal transduction. Our findings demonstrate that DHHC09 S-acylates and anchors STRK1 to the plasma membrane to promote salt signaling from STRK1 to CatC, thereby regulating H2O2 homeostasis and improving salt stress tolerance in rice. Moreover, overexpression of DHHC09 in rice mitigates grain yield loss under salt stress. Together, these results shed light on the mechanism underlying the role of S-acylation in RLK/RLCK-mediated salt signal transduction and provide a strategy for breeding highly salt-tolerant rice.

Genome evolution of the ancient hexaploid Platanus × acerifolia (London planetree).

Whole-genome duplication (WGD; i.e., polyploidy) and chromosomal rearrangement (i.e., genome shuffling) significantly influence genome structure and organization. Many polyploids show extensive genome shuffling relative to their pre-WGD ancestors. No reference genome is currently available for Platanaceae (Proteales), one of the sister groups to the core eudicots. Moreover, Platanus × acerifolia (London planetree; Platanaceae) is a widely used street tree. Given the pivotal phylogenetic position of Platanus and its 2-y flowering transition, understanding its flowering-time regulatory mechanism has significant evolutionary implications; however, the impact of Platanus genome evolution on flowering-time genes remains unknown. Here, we assembled a high-quality, chromosome-level reference genome for P. × acerifolia using a phylogeny-based subgenome phasing method. Comparative genomic analyses revealed that P. × acerifolia (2n = 42) is an ancient hexaploid with three subgenomes resulting from two sequential WGD events; Platanus does not seem to share any WGD with other Proteales or with core eudicots. Each P. × acerifolia subgenome is highly similar in structure and content to the reconstructed pre-WGD ancestral eudicot genome without chromosomal rearrangements. The P. × acerifolia genome exhibits karyotypic stasis and gene sub-/neo-functionalization and lacks subgenome dominance. The copy number of flowering-time genes in P. × acerifolia has undergone an expansion compared to other noncore eudicots, mainly via the WGD events. Sub-/neo-functionalization of duplicated genes provided the genetic basis underlying the unique flowering-time regulation in P. × acerifolia. The P. × acerifolia reference genome will greatly expand understanding of the evolution of genome organization, genetic diversity, and flowering-time regulation in angiosperms.

Characterization of a CXCR4 antagonist TIQ-15 with dual tropic HIV entry inhibition properties.

The chemokine co-receptors CXCR4 and CCR5 mediate HIV entry and signal transduction necessary for viral infection. However, to date only the CCR5 antagonist maraviroc is approved for treating HIV-1 infection. Given that approximately 50% of late-stage HIV patients also develop CXCR4-tropic virus, clinical anti-HIV CXCR4 antagonists are needed. Here, we describe a novel allosteric CXCR4 antagonist TIQ-15 which inhibits CXCR4-tropic HIV-1 infection of primary and transformed CD4 T cells. TIQ-15 blocks HIV entry with an IC50 of 13 nM. TIQ-15 also inhibits SDF-1α/CXCR4-mediated cAMP production, cofilin activation, and chemotactic signaling. In addition, TIQ-15 induces CXCR4 receptor internalization without affecting the levels of the CD4 receptor, suggesting that TIQ-15 may act through a novel allosteric site on CXCR4 for blocking HIV entry. Furthermore, TIQ-15 did not inhibit VSV-G pseudotyped HIV-1 infection, demonstrating its specificity in blocking CXCR4-tropic virus entry, but not CXCR4-independent endocytosis or post-entry steps. When tested against a panel of clinical isolates, TIQ-15 showed potent inhibition against CXCR4-tropic and dual-tropic viruses, and moderate inhibition against CCR5-tropic isolates. This observation was followed by a co-dosing study with maraviroc, and TIQ-15 demonstrated synergistic activity. In summary, here we describe a novel HIV-1 entry inhibitor, TIQ-15, which potently inhibits CXCR4-tropic viruses while possessing low-level synergistic activities against CCR5-tropic viruses. TIQ-15 could potentially be co-dosed with the CCR5 inhibitor maraviroc to block viruses of mixed tropisms.

The protein phosphatase PC1 dephosphorylates and deactivates CatC to negatively regulate H2O2 homeostasis and salt tolerance in rice.

Catalase (CAT) is often phosphorylated and activated by protein kinases to maintain hydrogen peroxide (H2O2) homeostasis and protect cells against stresses, but whether and how CAT is switched off by protein phosphatases remains inconclusive. Here, we identified a manganese (Mn2+)-dependent protein phosphatase, which we named PHOSPHATASE OF CATALASE 1 (PC1), from rice (Oryza sativa L.) that negatively regulates salt and oxidative stress tolerance. PC1 specifically dephosphorylates CatC at Ser-9 to inhibit its tetramerization and thus activity in the peroxisome. PC1 overexpressing lines exhibited hypersensitivity to salt and oxidative stresses with a lower phospho-serine level of CATs. Phosphatase activity and seminal root growth assays indicated that PC1 promotes growth and plays a vital role during the transition from salt stress to normal growth conditions. Our findings demonstrate that PC1 acts as a molecular switch to dephosphorylate and deactivate CatC and negatively regulate H2O2 homeostasis and salt tolerance in rice. Moreover, knockout of PC1 not only improved H2O2-scavenging capacity and salt tolerance but also limited rice grain yield loss under salt stress conditions. Together, these results shed light on the mechanisms that switch off CAT and provide a strategy for breeding highly salt-tolerant rice.

Structural basis of nucleosome dynamics modulation by histone variants H2A.B and H2A.Z.2.2.

Nucleosomes are dynamic entities with wide-ranging compositional variations. Human histone variants H2A.B and H2A.Z.2.2 play critical roles in multiple biological processes by forming unstable nucleosomes and open chromatin structures, but how H2A.B and H2A.Z.2.2 confer these dynamic features to nucleosomes remains unclear. Here, we report cryo-EM structures of nucleosome core particles containing human H2A.B (H2A.B-NCP) at atomic resolution, identifying large-scale structural rearrangements in the histone octamer in H2A.B-NCP. H2A.B-NCP compacts approximately 103 bp of DNA wrapping around the core histones in approximately 1.2 left-handed superhelical turns, in sharp contrast to canonical nucleosome encompassing approximately 1.7 turns of DNA. Micrococcal nuclease digestion assay reveals that nineteen H2A.B-specific residues, including a ROF ("regulating-octamer-folding") sequence of six consecutive residues, are responsible for loosening of H2A.B-NCPs. Unlike H2A.B-NCP, the H2A.Z.2.2-containing nucleosome (Z.2.2-NCP) adopts a less-extended structure and compacts around 125 bp of DNA. Further investigation uncovers a crucial role for the H2A.Z.2.2-specific ROF in both H2A.Z.2.2-NCP opening and SWR1-dependent histone replacement. Taken together, these first high-resolution structure of unstable nucleosomes induced by histone H2A variants elucidate specific functions of H2A.B and H2A.Z.2.2 in enhancing chromatin dynamics.

Deubiquitinase UCHL1 promotes angiogenesis and blood-spinal cord barrier function recovery after spinal cord injury by stabilizing Sox17.

Improving the function of the blood-spinal cord barrier (BSCB) benefits the functional recovery of mice following spinal cord injury (SCI). The death of endothelial cells and disruption of the BSCB at the injury site contribute to secondary damage, and the ubiquitin-proteasome system is involved in regulating protein function. However, little is known about the regulation of deubiquitinated enzymes in endothelial cells and their effect on BSCB function after SCI. We observed that Sox17 is predominantly localized in endothelial cells and is significantly upregulated after SCI and in LPS-treated brain microvascular endothelial cells. In vitro Sox17 knockdown attenuated endothelial cell proliferation, migration, and tube formation, while in vivo Sox17 knockdown inhibited endothelial regeneration and barrier recovery, leading to poor functional recovery after SCI. Conversely, in vivo overexpression of Sox17 promoted angiogenesis and functional recovery after injury. Additionally, immunoprecipitation-mass spectrometry revealed the interaction between the deubiquitinase UCHL1 and Sox17, which stabilized Sox17 and influenced angiogenesis and BSCB repair following injury. By generating UCHL1 conditional knockout mice and conducting rescue experiments, we further validated that the deubiquitinase UCHL1 promotes angiogenesis and restoration of BSCB function after injury by stabilizing Sox17. Collectively, our findings present a novel therapeutic target for treating SCI by revealing a potential mechanism for endothelial cell regeneration and BSCB repair after SCI.

Epstein-Barr virus protein BKRF4 restricts nucleosome assembly to suppress host antiviral responses.

Inhibition of host DNA damage response (DDR) is a common mechanism used by viruses to manipulate host cellular machinery and orchestrate viral life cycles. Epstein-Barr virus tegument protein BKRF4 associates with cellular chromatin to suppress host DDR signaling, but the underlying mechanism remains elusive. Here, we identify a BKRF4 histone binding domain (residues 15-102, termed BKRF4-HBD) that can accumulate at the DNA damage sites to disrupt 53BP1 foci formation. The high-resolution structure of the BKRF4-HBD in complex with a human H2A-H2B dimer shows that BKRF4-HBD interacts with the H2A-H2B dimer via the N-terminal region (NTR), the DWP motif (residues 80-86 containing D81, W84, P86), and the C-terminal region (CTR). The "triple-anchor" binding mode confers BKRF4-HBD the ability to associate with the partially unfolded nucleosomes, promoting the nucleosome disassembly. Importantly, disrupting the BKRF4-H2A-H2B interaction impairs the binding between BKRF4-HBD and nucleosome in vitro and inhibits the recruitment of BKRF4-HBD to DNA breaks in vivo. Together, our study reveals the structural basis of BKRF4 bindings to the partially unfolded nucleosome and elucidates an unconventional mechanism of host DDR signal attenuation.

FLASH X-ray spares intestinal crypts from pyroptosis initiated by cGAS-STING activation upon radioimmunotherapy.

DNA-damaging treatments such as radiotherapy (RT) have become promising to improve the efficacy of immune checkpoint inhibitors by enhancing tumor immunogenicity. However, accompanying treatment-related detrimental events in normal tissues have posed a major obstacle to radioimmunotherapy and present new challenges to the dose delivery mode of clinical RT. In the present study, ultrahigh dose rate FLASH X-ray irradiation was applied to counteract the intestinal toxicity in the radioimmunotherapy. In the context of programmed cell death ligand-1 (PD-L1) blockade, FLASH X-ray minimized mouse enteritis by alleviating CD8+ T cell-mediated deleterious immune response compared with conventional dose rate (CONV) irradiation. Mechanistically, FLASH irradiation was less efficient than CONV X-ray in eliciting cytoplasmic double-stranded DNA (dsDNA) and in activating cyclic GMP-AMP synthase (cGAS) in the intestinal crypts, resulting in the suppression of the cascade feedback consisting of CD8+ T cell chemotaxis and gasdermin E-mediated intestinal pyroptosis in the case of PD-L1 blocking. Meanwhile, FLASH X-ray was as competent as CONV RT in boosting the antitumor immune response initiated by cGAS activation and achieved equal tumor control in metastasis burdens when combined with anti-PD-L1 administration. Together, the present study revealed an encouraging protective effect of FLASH X-ray upon the normal tissue without compromising the systemic antitumor response when combined with immunological checkpoint inhibitors, providing the rationale for testing this combination as a clinical application in radioimmunotherapy.

Chiral Separation of Copper Sulfide [S-Cu36] Nanocluster Using a Chiral Adaptive Counterion.

This work presents a new strategy to achieve the growth of copper sulfide nanoclusters with high nuclearity. Through a phosphine-assisted C-S reductive cleavage approach, an intrinsically chiral [Cu4] cluster passes through a [S-Cu9] cluster and transforms into a higher-nuclearity [S-Cu36] cluster, which features a core-shell structure with a [Cu4]4+ core encapsulated by a chiral [Cu20S12] shell. Interestingly, the spiral arrangement of the bidental ligands on the surface of the [S-Cu36] cluster leads to the L-/R-enantiomeric configurations. Moreover, by utilization of [Na(THF)6]+ as a chiral adaptive counterion, [S-Cu36] can be interlocked separately, thus enabling the isolation of homochiral clusters. Theoretical calculation suggests that the configuration transition between two enantiomeric [Na(THF)6]+ species is favorable at room temperature, thereby promoting the cocrystallization of resulting chiral products. This study introduces a novel perspective on the synthesis of chiral copper sulfide nanoclusters and presents an innovative approach to achieving the chiral separation of nanoclusters.

Stratifying ICIs-responsive tumor microenvironment in HCC: from parsing out immune-hypoxic crosstalk to clinically applicable MRI-radiomics models.

BACKGROUND: We aimed to redefine Immune checkpoint inhibitors (ICIs)-responsive "hot" TME and develop a corresponding stratification model to maximize ICIs-efficacy in Hepatocellular Carcinoma (HCC). METHODS: Hypoxic scores were designed, and the relevance to immunotherapy responses were validated in pan-cancers through single cell analysis. Multi-omics analysis using the hypoxic scores and immune infiltrate abundance was performed to redefine the ICIs-responsive TME subtype in HCC patients from TCGA (n = 363) and HCCDB database (n = 228). The immune hypoxic stress index (IHSI) was constructed to stratify the ICIs-responsive TME subtype, with exploring biological mechanism in vitro and in vivo. MRI-radiomics models were built for clinical applicability. RESULTS: The hypoxic scores were lower in the dominant cell-subclusters of responders in pan-cancers. The higher immune infiltrate-normoxic (HIN) subtype was redefined as the ICIs-responsive TME. Stratification of the HIN subtype using IHSI effectively identified ICIs-responders in Melanoma (n = 122) and urological cancer (n = 22). TRAF3IP3, the constituent gene of IHSI, was implicated in ICIs-relevant "immune-hypoxic" crosstalk by stimulating MAVS/IFN-I pathway under normoxic condition. MRI-radiomics models assessing TRAF3IP3 with HIF1A expression (AUC > 0.80) screened ICIs-Responders in HCC cohort (n = 75). CONCLUSION: The hypoxic-immune stratification redefined ICIs-responsive TME and provided MRI-Radiomics models for initial ICIs-responders screening, with IHSI facilitating further identification.

Linking homocysteine and ferroptosis in cardiovascular disease: insights and implications.

Homocysteine (Hcy) is a metabolic intermediate product derived from methionine. Hyperhomocysteinemia is a condition associated with various diseases. Hcy is recognized as a risk factor for cardiovascular disease (CVD). Ferroptosis, a novel form of cell death, is primarily characterized by substantial iron accumulation and lipid peroxidation. Recent research indicates a close association between ferroptosis and the pathophysiological processes of tumors, neurological diseases, CVD, and other ailments. However, limited research has been conducted on the impact of Hcy on ferroptosis. Therefore, this paper aimed to investigate the potential roles and mechanisms of homocysteine and ferroptosis in the context of cardiovascular disease. By conducting comprehensive literature research and analysis, we aimed to summarize recent advancements in understanding the effects of homocysteine on ferroptosis in cardiovascular diseases. This research contributes to a profound understanding of this critical domain.

Th17 Cell-Derived Amphiregulin Promotes Colitis-Associated Intestinal Fibrosis Through Activation of mTOR and MEK in Intestinal Myofibroblasts.

BACKGROUND & AIMS: Intestinal fibrosis is a significant complication of Crohn's disease (CD). Gut microbiota reactive Th17 cells are crucial in the pathogenesis of CD; however, how Th17 cells induce intestinal fibrosis is still not completely understood. METHODS: In this study, T-cell transfer model with wild-type (WT) and Areg-/- Th17 cells and dextran sulfate sodium (DSS)-induced chronic colitis model in WT and Areg-/- mice were used. CD4+ T-cell expression of AREG was determined by quantitative reverse-transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay. The effect of AREG on proliferation/migration/collagen expression in human intestinal myofibroblasts was determined. AREG expression was assessed in healthy controls and patients with CD with or without intestinal fibrosis. RESULTS: Although Th1 and Th17 cells induced intestinal inflammation at similar levels when transferred into Tcrßxδ-/- mice, Th17 cells induced more severe intestinal fibrosis. Th17 cells expressed higher levels of AREG than Th1 cells. Areg-/- mice developed less severe intestinal fibrosis compared with WT mice on DSS insults. Transfer of Areg-/- Th17 cells induced less severe fibrosis in Tcrßxδ-/- mice compared with WT Th17 cells. Interleukin (IL)6 and IL21 promoted AREG expression in Th17 cells by activating Stat3. Stat3 inhibitor suppressed Th17-induced intestinal fibrosis. AREG promoted human intestinal myofibroblast proliferation, motility, and collagen I expression, which was mediated by activating mammalian target of rapamycin and MEK. AREG expression was increased in intestinal CD4+ T cells in fibrotic sites compared with nonfibrotic sites from patients with CD. CONCLUSIONS: These findings reveal that Th17-derived AREG promotes intestinal fibrotic responses in experimental colitis and human patients with CD. Thereby, AREG might serve as a potential therapeutic target for fibrosis in CD.

Multiparameter Mechanical Phenotyping for Accurate Cell Identification Using High-Throughput Microfluidic Deformability Cytometry.

Mechanical phenotyping has been widely employed for single-cell analysis over recent years. However, most previous works on characterizing the cellular mechanical properties measured only a single parameter from one image. In this paper, the quasi-real-time multiparameter analysis of cell mechanical properties was realized using high-throughput adjustable deformability cytometry. We first extracted 12 deformability parameters from the cell contours. Then, the machine learning for cell identification was performed to preliminarily verify the rationality of multiparameter mechanical phenotyping. The experiments on characterizing cells after cytoskeletal modification verified that multiple parameters extracted from the cell contours contributed to an identification accuracy of over 80%. Through continuous frame analysis of the cell deformation process, we found that temporal variation and an average level of parameters were correlated with cell type. To achieve quasi-real-time and high-precision multiplex-type cell detection, we constructed a back propagation (BP) neural network model to complete the fast identification of four cell lines. The multiparameter detection method based on time series achieved cell detection with an accuracy of over 90%. To solve the challenges of cell rarity and data lacking for clinical samples, based on the developed BP neural network model, the transfer learning method was used for the identification of three different clinical samples, and finally, a high identification accuracy of approximately 95% was achieved.

In Silico-Predicted Dynamic Oxlipidomics MS/MS Library: High-Throughput Discovery and Characterization of Unknown Oxidized Lipids.

Nontargeted lipidomics using liquid chromatography-tandem mass spectrometry can detect thousands of molecules in biological samples. However, the annotation of unknown oxidized lipids is limited to the structures present in libraries, restricting the analysis and interpretation of experimental data. Here, we describe Doxlipid, a computational tool for oxidized lipid annotation that predicts a dynamic MS/MS library for every experiment. Doxlipid integrates three key simulation algorithms to predict libraries and covers 32 subclasses of oxidized lipids from the three main classes. In the evaluation, Doxlipid achieves very high prediction and characterization performance and outperforms the current oxidized lipid annotation methods. Doxlipid, combined with a molecular network, further annotates unknown chemical analogs in the same reaction or pathway. We demonstrate the broad utility of Doxlipid by analyzing oxidized lipids in ferroptosis hepatocellular carcinoma, tissue samples, and other biological samples, substantially advancing the discovery of biological pathways at the trace oxidized lipid level.

Injectable Nanocomposite Immune Hydrogel Dressings: Prevention of Tumor Recurrence and Anti-Infection after Melanoma Resection.

Complex wound repair due to tumor recurrence and infection following tumor resection presents significant clinical challenges. In this study, a bifunctional nanocomposite immune hydrogel dressing, SerMA-LJC, is developed to address the issues associated with repairing infected damaged tissues and preventing tumor recurrence. Specifically, the immune dressing is composed of methacrylic anhydride-modified sericin (SerMA) and self-assembled nanoparticles (LJC) containing lonidamine (Lon), JQ1, and chlorine e6 (Ce6). In vitro and in vivo experiments demonstrate that the nanocomposite hydrogel dressing can trigger immunogenic cell death (ICD) and has a potent anti-tumor effect. Moreover, this dressing can mitigate the acidic microenvironment of tumor cells and suppress the overexpression of PD-L1 on the tumor cell surface, thereby altering the immunosuppressive tumor microenvironment and augmenting the anti-tumor immune response. Further, the RNA sequencing analysis revealed that the hydrogel dressing significantly impacts pathways associated with positive regulation of immune response, apoptotic process, and other relevant pathways, thus triggering a potent anti-tumor immune response. More importantly, the dressing generates a substantial amount of reactive oxygen species (ROS), which can effectively kill Staphylococcus aureus and promote infectious wound healing. In conclusion, this dual-function nanocomposite immune hydrogel dressing exhibits promise in preventing tumor recurrence and promoting infectious wound healing.

Reversible Oxygen Redox With Enhanced Structural Stability Through Covalency Modulation for Layered Oxide Cathodes.

P2-type Mn-based layered oxides have emerged as one of the most promising cathode materials for sodium-ion batteries owing to their advantages of facile preparation and high theoretical capacity. However, challenges such as phase transition and irreversible oxygen release during cycling often lead to rapid structural distortion and the formation of oxygen vacancies, ultimately resulting in rapid capacity decay. Herein, a covalency modulation strategy is adopted to address these challenges and successfully achieved a stable P2-type Mn-based layered oxide by introducing strong covalent Ni─O bonds. The robust Ni─O motif plays a crucial role in maintaining the rigidity of transition metal (TM) layered frameworks, which efficiently alleviates the structural distortion and degradation of the coordination environments of local TM sites, thereby achieving durable structural stiffness over extended cycles. In addition, the strong covalent Ni─O bonds can also stabilize the local oxygen environment, effectively suppressing the irreversible oxygen release. Benefiting from these advancements, the as-designed Na0.6Mg0.15Mn0.7Ni0.15O2 cathode displays a full solid-solution behavior with a low volume change of only 0.9% and an enhanced reversibility of lattice oxygen redox (OR) reaction. This investigation emphasizes the crucial role of covalency modulation in regulating OR chemistry and structural integrity to achieve high-energy-density Mn-based layered oxides.

Versatile CYP98A enzymes catalyse meta-hydroxylation reveals diversity of salvianolic acids biosynthesis.

Salvianolic acids (SA), such as rosmarinic acid (RA), danshensu (DSS), and their derivative salvianolic acid B (SAB), etc. widely existed in Lamiaceae and Boraginaceae families, are of interest due to medicinal properties in the pharmaceutical industries. Hundreds of studies in past decades described that 4-coumaroyl-CoA and 4-hydroxyphenyllactic acid (4-HPL) are common substrates to biosynthesize SA with participation of rosmarinic acid synthase (RAS) and cytochrome P450 98A (CYP98A) subfamily enzymes in different plants. However, in our recent study, several acyl donors and acceptors included DSS as well as their ester-forming products all were determined in SA-rich plants, which indicated that previous recognition to SA biosynthesis is insufficient. Here, we used Salvia miltiorrhiza, a representative important medicinal plant rich in SA, to elucidate the diversity of SA biosynthesis. Various acyl donors as well as acceptors are catalysed by SmRAS to form precursors of RA and two SmCYP98A family members, SmCYP98A14 and SmCYP98A75, are responsible for different positions' meta-hydroxylation of these precursors. SmCYP98A75 preferentially catalyses C-3' hydroxylation, and SmCYP98A14 preferentially catalyses C-3 hydroxylation in RA generation. In addition, relative to C-3' hydroxylation of the acyl acceptor moiety in RA biosynthesis, SmCYP98A75 has been verified as the first enzyme that participates in DSS formation. Furthermore, SmCYP98A enzymes knockout resulted in the decrease and overexpression leaded to dramatic increase of SA accumlation. Our study provides new insights into SA biosynthesis diversity in SA-abundant species and versatility of CYP98A enzymes catalytic preference in meta-hydroxylation reactions. Moreover, CYP98A enzymes are ideal metabolic engineering targets to elevate SA content.

Growth of single-crystal black phosphorus and its alloy films through sustained feedstock release.

Black phosphorus (BP), a fascinating semiconductor with high mobility and a tunable direct bandgap, has emerged as a candidate beyond traditional silicon-based devices for next-generation electronics and optoelectronics. The ability to grow large-scale, high-quality BP films is a prerequisite for scalable integrated applications but has thus far remained a challenge due to unmanageable nucleation events. Here we develop a sustained feedstock release strategy to achieve subcentimetre-size single-crystal BP films by facilitating the lateral growth mode under a low nucleation rate. The as-grown single-crystal BP films exhibit high crystal quality, which brings excellent field-effect electrical properties and observation of pronounced Shubnikov-de Haas oscillations, with high mobilities up to ~6,500 cm2 V-1 s-1 at low temperatures. We further extend this approach to the growth of single-crystal BP alloy films, which broaden the infrared emission regime of BP from 3.7 µm to 6.9 µm at room temperature. This work will greatly facilitate the development of high-performance electronics and optoelectronics based on BP family materials.