RBM8A, a new target of TEAD4, promotes breast cancer progression by regulating IGF1R and IRS-2.

BACKGROUND: Breast cancer (BC) is the most common malignant tumor in women worldwide, and further elucidation of the molecular mechanisms involved in BC pathogenesis is essential to improve the prognosis of BC patients. RNA Binding Motif Protein 8 A (RBM8A), with high affinity to a myriad of RNA transcripts, has been shown to play a crucial role in genesis and progression of multiple cancers. We attempted to explore its functional significance and molecular mechanisms in BC. METHODS: Bioinformatics analysis was performed on publicly available BC datasets. qRT-PCR was used to determine the expression of RBM8A in BC tissues. MTT assay, clone formation assay and flow cytometry were employed to examine BC cell proliferation and apoptosis in vitro. RNA immunoprecipitation (RIP) and RIP-seq were used to investigate the binding of RBM8A/EIF4A3 to the mRNA of IGF1R/IRS-2. RBM8A and EIF4A3 interactions were determined by co-immunoprecipitation (Co-IP) and immunofluorescence. Chromatin immunoprecipitation (Ch-IP) and dual-luciferase reporter assay were carried out to investigate the transcriptional regulation of RBM8A by TEAD4. Xenograft model was used to explore the effects of RBM8A and TEAD4 on BC cell growth in vivo. RESULTS: In this study, we showed that RBM8A is abnormally highly expressed in BC and knockdown of RBM8A inhibits BC cell proliferation and induces apoptosis in vitro. EIF4A3, which phenocopy RBM8A in BC, forms a complex with RBM8A in BC. Moreover, EIF4A3 and RBM8A complex regulate the expression of IGF1R and IRS-2 to activate the PI3K/AKT signaling pathway, thereby promoting BC progression. In addition, we identified TEAD4 as a transcriptional activator of RBM8A by Ch-IP, dual luciferase reporter gene and a series of functional rescue assays. Furthermore, we demonstrated the in vivo pro-carcinogenic effects of TEAD4 and RBM8A by xenograft tumor experiments in nude mice. CONCLUSION: Collectively, these findings suggest that TEAD4 novel transcriptional target RBM8A interacts with EIF4A3 to increase IGF1R and IRS-2 expression and activate PI3K/AKT signaling pathway, thereby further promoting the malignant phenotype of BC cells.

Phylogenomic analyses sheds new light on the phylogeny and diversification of Corydalis DC. in Himalaya-Hengduan Mountains and adjacent regions.

The Himalaya-Hengduan Mountains (HHM), a renowned biodiversity hotspot of the world, harbors the most extensive habitats for alpine plants with extraordinary high levels of endemism. Although the general evolution pattern has been elucidated, the underlying processes driving spectacular radiations in many species-rich groups remain elusive. Corydalis DC. is widely distributed throughout the Northern Hemisphere containing more than 500 species, with high diversity in HHM and adjacent regions. Using 95 plastid genes, 3,258,640 nuclear single nucleotide polymorphisms (SNPs) and eight single-copy nuclear genes (SCNs) generated from genome skimming data, we reconstructed a robust time-calibrated phylogeny of Corydalis comprising more than 100 species that represented all subgenera and most sections. Molecular dating indicated that all main clades of Corydalis began to diverge in the Eocene, with the majority of extant species in HHM emerged from a diversification burst after the middle Miocene. Global pattern of mean divergence times indicated that species distributed in HHM were considerably younger than those in other regions, particularly for the two most species-rich clades (V and VI) of Corydalis. The early divergence and the recent diversification of Corydalis were most likely promoted by the continuous orogenesis and climate change associated with the uplift of the Qinghai-Tibetan Plateau (QTP). Our study demonstrates the effectivity of phylogenomic analyses with genome skimming data on the phylogeny of species-rich taxa, and sheds lights on how the uplift of QTP has triggered the evolutionary radiations of large plant genera in HHM and adjacent regions.

Remarkable Enhancement of Piezoelectric Performance by Heavy Halogen Substitution in Hybrid Perovskite Ferroelectrics.

Piezoelectric materials that enable electromechanical conversion have great application value in actuators, transducers, sensors, and energy harvesters. Large piezoelectric (d33) and piezoelectric voltage (g33) coefficients are highly desired and critical to their practical applications. However, obtaining a material with simultaneously large d33 and g33 has long been a huge challenge. Here, we reported a hybrid perovskite ferroelectric [Me3NCH2Cl]CdBrCl2 to mitigate and roughly address this issue by heavy halogen substitution. The introduction of a large-size halide element softens the metal-halide bonds and reduces the polarization switching barrier, resulting in excellent piezoelectric response with a large d33 (∼440 pC/N), which realizes a significant optimization compared with that of previously reported [Me3NCH2Cl]CdCl3 (You et al. Science2017, 357, 306-309). More strikingly, [Me3NCH2Cl]CdBrCl2 simultaneously shows a giant g33 of 6215 × 10-3 V m/N, far exceeding those of polymers and conventional piezoelectric ceramics. Combined with simple solution preparation, easy processing of thin films, and a high Curie temperature of 373 K, these attributes make [Me3NCH2Cl]CdBrCl2 promising for high-performance piezoelectric sensors in flexible, wearable, and biomechanical devices.

The First Enantiomeric Stereogenic Sulfur-Chiral Organic Ferroelectric Crystals.

Chiral ferroelectric crystals with intriguing features have attracted great interest and many with point or axial chirality based on the stereocarbon have been successively developed in recent years. However, ferroelectric crystals with stereogenic heteroatomic chirality have never been documented so far. Here, we discover and report a pair of enantiomeric stereogenic sulfur-chiral single-component organic ferroelectric crystals, Rs -tert-butanesulfinamide (Rs -tBuSA) and Ss -tert-butanesulfinamide (Ss -tBuSA) through the deep understanding of the chemical design of molecular ferroelectric crystals. Both enantiomers adopt chiral-polar point group 2 (C2 ) and exhibit mirror-image relationships. They undergo high-temperature 432F2-type plastic ferroelectric phase transition around 348 K. The ferroelectricity has been well confirmed by ferroelectric hysteresis loops and domains. Polarized light microscopy records the evolution of the ferroelastic domains, according with the fact that the 432F2-type phase transition is both ferroelectric and ferroelastic. The very soft characteristics with low elastic modulus and hardness reveals their excellent mechanical flexibility. This finding indicates the first stereosulfur chiral molecular ferroelectric crystals, opening up new fertile ground for exploring molecular ferroelectric crystals with great application prospects.

PFM (piezoresponse force microscopy)-aided design for molecular ferroelectrics.

With prosperity, decay, and another spring, molecular ferroelectrics have passed a hundred years since Valasek first discovered ferroelectricity in the molecular compound Rochelle salt. Recently, the proposal of ferroelectrochemistry has injected new vigor into this century-old research field. It should be highlighted that piezoresponse force microscopy (PFM) technique, as a non-destructive imaging and manipulation method for ferroelectric domains at the nanoscale, can significantly speed up the design rate of molecular ferroelectrics as well as enhance the ferroelectric and piezoelectric performances relying on domain engineering. Herein, we provide a brief review of the contribution of the PFM technique toward assisting the design and performance optimization of molecular ferroelectrics. Relying on the relationship between ferroelectric domains and crystallography, together with other physical characteristics such as domain switching and piezoelectricity, we believe that the PFM technique can be effectively applied to assist the design of high-performance molecular ferroelectrics equipped with multifunctionality, and thereby facilitate their practical utilization in optics, electronics, magnetics, thermotics, and mechanics among others.

A 1-µm-Band Injection-Locked Semiconductor Laser with a High Side-Mode Suppression Ratio and Narrow Linewidth.

We demonstrate a narrow-linewidth, high side-mode suppression ratio (SMSR) semiconductor laser based on the external optical feedback injection locking technology of a femtosecond-apodized (Fs-apodized) fiber Bragg grating (FBG). A single frequency output is achieved by coupling and integrating a wide-gain quantum dot (QD) gain chip with a Fs-apodized FBG in a 1-µm band. We propose this low-cost and high-integration scheme for the preparation of a series of single-frequency seed sources in this wavelength range by characterizing the performance of 1030 nm and 1080 nm lasers. The lasers have a maximum SMSR of 66.3 dB and maximum output power of 134.6 mW. Additionally, the lasers have minimum Lorentzian linewidths that are measured to be 260.5 kHz; however, a minimum integral linewidth less than 180.4 kHz is observed by testing and analyzing the power spectra of the frequency noise values of the lasers.

Biocatalytic Depletion of Tumorigenic Energy Sources Driven by Cascade Reactions for Efficient Antitumor Therapy.

Glucose and lactate play important roles for tumor growth. How to simultaneously deprive tumors of glucose and lactate is a big challenge. We have developed a cascade catalytic system (denoted as FPGLC) based on fluorinated polymer (FP) with co-loading of glucose oxidase (GOx), lactate oxidase (LOx), and catalase (CAT). GOx and LOx deprive glucose and lactate, respectively, resulting in abundant hydrogen peroxide (H2 O2 ) generation. Meanwhile, CAT catalyzes H2 O2 into O2 , which not only promotes catalytic reactions of GOx and LOx for consuming more glucose and lactate, but also alleviates tumor hypoxia. Benefiting from the excellent cross-membrane and transmucosal penetration capacities of FP, FPGLC rapidly accumulated in tumors and subsequently mediated enhanced cascade catalytic therapy under the guidance of photoacoustic imaging. These results demonstrate that the dual depletion of glucose and lactate with O2 supply is a promising strategy for efficient antitumor starvation therapy.

Multichannel Control of Multiferroicity in Single-Component Homochiral Organic Crystals.

A ferroelectric/ferroelastic is a material whose spontaneous polarization/strain can be switched by applying an external electric field/mechanical stress. However, the optical control of spontaneous polarization/strain remains relatively unexplored in crystalline materials, although photoirradiation stands out as a nondestructive, noncontact, and remote-controlled stimulus beyond stress or electric field. Here, we present two new organic single-component homochiral photochromic multiferroics, (R)- and (S)-N-3,5-di-tert-butylsalicylidene-1-4-bromophenylethylamine (SA-Ph-Br(R) and SA-Ph-Br(S)), which show a full ferroelectric/ferroelastic phase transition of 222F2 type at 336 K. Under photoirradiation, their spontaneous polarization/strain can be switched quickly within seconds and reversibly between two ferroelectric/ferroelastic phases with the respective enol and trans-keto forms triggered by structural photoisomerizations. In addition, they possess a superior acoustic impedance characteristic with a value of ∼2.42 × 106 kg·s-1·m-2, lower than that of polyvinylidene fluoride (PVDF, (3.69-4.25) × 106 kg·s-1·m-2), which can better match human tissues. This work realizes for the first time that multiple ferroic orders in single-component organic crystals with ultralow acoustic impedance can be simultaneously controlled and coupled by three physical channels (electric, stress, light fields), suggesting their great potential in multichannel data storage, optoelectronics, and related applications compatible with all-organic electronics and human tissues.

Optical Control of Polarization Switching in a Single-Component Organic Ferroelectric Crystal.

The optical control of polarization switching is attracting tremendous interest because photoirradiation stands out as a nondestructive, noncontact, and remote-control means beyond an electric or strain field. The current research mainly uses various photoexcited electronic effects to achieve the photocontrol polarization, such as a light-driven flexoelectric effect and a photovoltaic effect. However, since photochromism was discovered in 1867, the structural phase transition caused by photoisomerization has never been associated with ferroelectricity. Here, we successfully synthesized an organic photochromic ferroelectric with polar space group Pna21, 3,4,5-trifluoro-N-(3,5-di-tert-butylsalicylidene)aniline, whose color can change between yellow and orange via laser illumination. Its dielectric permittivity and spontaneous polarization can be switched reversibly with a photoinduced phase transition triggered by structural photoisomerization between the enol form and the trans-keto form. To our knowledge, this is the first photoswitchable ferroelectric crystal to achieve polarization switching through a structural phase transition triggered by photoisomerization. This finding paves the way toward photocontrol of smart materials and biomechanical applications in the future.

Human osteoarthritis cartilage-derived stromal cells activate joint degeneration through TGF-beta lateral signaling.

Human osteoarthritis cartilage contains chondrocytes (OAC) and mesenchymal stromal cells (OA-MSC). Here, we found that TGF-ß had different effects on OA-MSC and OAC, and revealed its lateral signaling mechanism in OA. RNAseq analysis indicated that OA-MSC expressed the same level of Bone Morphogenetic Protein (BMP) Receptor-1A as OAC but only 1/12 of Transforming Growth Factor beta (TGF-ß) Receptor-1. While TGF-ß specifically activated SMAD2 in OAC, it also activated BMP signaling-associated SMAD1 in OA-MSC. While TGF-ß stimulated chondrogenesis in OAC, it induced hypertrophy, mineralization, and MMP-13 in OA-MSC. Inhibiting TGF-ßR1 suppressed MMP-13 in OA-MSC but stimulated it in OAC. In contrast, by specifically targeting BMPR1A/ACVR1 in both cell types, LDN193189 inhibits cartilage degeneration through suppressing hypertrophy and MMP-13 in a mouse osteoarthritis model. Thus, LDN193189, a drug under development to inhibit constitutive BMP signaling during heterotopic ossification, may be re-purposed for OA treatment.

The First High-Temperature Supramolecular Radical Ferroics.

Organic radical ferroics such as TEMPO have attracted widespread interest. However, the relatively low Curie temperature of 287 K and melting point of 311 K severely hinder its application potential. Despite extensive interest, high-temperature radical ferroics have not yet been found. Here, taking advantage of chemical design and supramolecular radical chemistry, we designed two high-temperature organic supramolecular radical ferroics [(NH3 -TEMPO)([18]crown-6)](ReO4 ) (1) and [(NH3 -TEMPO)([18]crown-6)](ClO4 ) (2), which can retain ferroelectricity up to 413 K and 450 K, respectively. To our knowledge, they are both the first supramolecular radical ferroics and unprecedented high-temperature radical ferroics, where the supramolecular component is vital for the stabilization of the radical and extending the working temperature window. Both also have paramagnetism, non-interacting spin moments, and excellent piezoelectric and electrostrictive behaviors comparable to that of LiNbO3 .

Three-Dimensional Lead Bromide Hybrid Ferroelectric Realized by Lattice Expansion.

Three-dimensional (3D) organic-inorganic lead halide hybrids have become a hot academic topic because of their various functional properties. However, 3D lead halide hybrid ferroelectrics are still very rare until now. Here, we report a new 3D lead halide perovskite-related ferroelectric, (EATMP)Pb2Br6 [EATMP = (2-aminoethyl)trimethylphosphanium]. Based on nonferroelectric CH3NH3PbBr3, by replacing PbBr6 octahedra with a Pb2Br10 dimer of edge-sharing octahedra as the basic building unit, the expanded 3D lead bromide perovskite analog was formed with the large [EATMP]2+ cations occupying the voids of framework. Notably, (EATMP)Pb2Br6 displays a direct bandgap of 2.81 eV, four polarization directions, and a high Curie temperature (Tc) of 518 K (much beyond that of BaTiO3, 393 K), which is the highest among all reported 3D organic-inorganic hybrid ferroelectrics. Such a high Tc may result from the high rotational energy barrier of cations induced by a larger molecular volume and relatively low crystal symmetry. Our work provides an efficient avenue to construct new 3D organic-inorganic lead halide hybrids and would inspire the further exploration of 3D lead halide ferroelectrics.

Epigenetic regulation of chondrocyte hypertrophy and apoptosis through Sirt1/P53/P21 pathway in surgery-induced osteoarthritis.

Sirt1 involved in cellular aging and aging-related diseases, including osteoarthritis (OA). Our previous study showed Sirt1 played a role in the pathogenesis of OA, however, the underlying mechanisms are still poorly elicited. In this study, we investigated the role of Sirt1 in epigenetically regulating P53/P21 pathway in a Sirt1 loss model. Sirt1 deletion male mice (n = 10) with destabilization of the medial meniscus (DMM) were used to observe its role on OA development. Then, the relationships between SIRT1 and P53 were detected by Coimmunoprecipitation (CoIP), and the gain-off function of P53 gene was indicated by P53 activators and inhibitors in vitro. Finally, human cartilage samples from patients with OA were collected. Sirt1 deletion mice displayed a spontaneous OA development, manifesting severe chondrocytes hypertrophy markers MMP13 and ADAMTS5, highly expressed P53 and P21. Strikingly, surgery-induced meniscus injury promoted the OA pathogenesis and apoptosis in Sirt1 deficient mice. Ultimately, our CoIP data demonstrated that Sirt1 directly interacted with P53 in vitro. However inhibition of P53 alleviated OA progression. We also observed that chondrocyte apoptosis and P53 increased in osteoarthritis (OA) progression with a declining expression of Sirt1 in human cartilage. Loss of Sirt1 in cartilage led to accelerated OA pathogenesis via aberrant activation of p53/p21 mediated senescence associated secretory phenotype, hypertrophy and apoptosis.

TGIF2 is a potential biomarker for diagnosis and prognosis of glioma.

Background: TGFB-induced factor homeobox 2 (TGIF2), a member of the Three-Amino-acid-Loop-Extension (TALE) superfamily, has been implicated in various malignant tumors. However, its prognostic significance in glioma, impact on tumor immune infiltration, and underlying mechanisms in glioma development remain elusive. Methods: The expression of TGIF2 in various human normal tissues, normal brain tissues, and gliomas was investigated using HPA, TCGA, GTEx, and GEO databases. The study employed several approaches, including Kaplan-Meier analysis, ROC analysis, logistic regression, Cox regression, GO analysis, KEGG analysis, and GSEA, to explore the relationship between TGIF2 expression and clinicopathologic features, prognostic value, and potential biological functions in glioma patients. The impact of TGIF2 on tumor immune infiltration was assessed through Estimate, ssGSEA, and Spearman analysis. Genes coexpressed with TGIF2 were identified, and the protein-protein interaction (PPI) network of these coexpressed genes were constructed using the STRING database and Cytoscape software. Hub genes were identified using CytoHubba plugin, and their clinical predictive value was explored. Furthermore, in vitro experiments were performed by knocking down and knocking out TGIF2 using siRNA and CRISPR/Cas9 gene editing, and the role of TGIF2 in glioma cell invasion and migration was analyzed using transwell assay, scratch wound-healing assay, RT-qPCR, and Western blot. Results: TGIF2 mRNA was found to be upregulated in 21 cancers, including glioma. High expression of TGIF2 was associated with malignant phenotypes and poor prognosis in glioma patients, indicating its potential as an independent prognostic factor. Furthermore, elevated TGIF2 expression positively correlated with cell cycle regulation, DNA synthesis and repair, extracellular matrix (ECM) components, immune response, and several signaling pathways that promote tumor progression. TGIF2 showed correlations with Th2 cells, macrophages, and various immunoregulatory genes. The hub genes coexpressed with TGIF2 demonstrated significant predictive value. Additionally, in vitro experiments revealed that knockdown and knockout of TGIF2 inhibited glioma cell invasion, migration and suppressed the epithelial-mesenchymal transition (EMT) phenotype. Conclusion: TGIF2 emerges as a potential biomarker for glioma, possibly linked to tumor immune infiltration and EMT.

Comprehensive analysis reveals TSPEAR as a prognostic biomarker in colorectal cancer.

Background: Colorectal cancer (CRC) is one of the most common malignant tumors and has high morbidity and mortality rates. Previous studies have shown that TSPEAR mutations are involved in the development and progression of gastric cancer and liver cancer. However, the role of TSPEAR in CRC is still unclear. Methods: In The Cancer Genome Atlas (TCGA) database, 590 CRC patients with complete survival information were analyzed. We assessed TSPEAR expression in a pan-cancer dataset from the TCGA database. Cox regression analysis was performed to evaluate factors associated with prognosis. Enrichment analysis via the R package "clusterProfiler" was used to explore the potential function of TSPEAR. The single-sample GSEA (ssGSEA) method from the R package "GSVA" and the TIMER database were used to investigate the association between the immune infiltration level and TSPEAR expression in CRC. The R package "maftools" was used to explore the association between tumour mutation burden (TMB) and TSPEAR expression in CRC. CCK-8 assays and cell invasion assays were used to detect the effect of TSPEAR and TGIF2 on the biological behavior of CRC cells. Results: Pan-cancer analysis revealed that TSPEAR was upregulated in CRC tissues compared to normal tissues and that high TSPEAR expression was associated with poorer overall survival (OS) (p=0.0053). The expression of TSPEAR increased with increasing TNM stage, T stage, N stage, and M stage. The nomogram constructed with TSPEAR, age, and TNM stage showed better predictive value than TSPEAR, age, or TNM stage alone. Immune cell infiltration analysis revealed that high expression of TSPEAR was associated with lower immune cell infiltration. Tumor mutation burden (TMB) analysis indicated that high expression of TSPEAR was associated with lower TMB (p=0.005), and high TMB was associated with shorter OS (p=0.02). CCK-8 assays and cell invasion assays indicated that in vitro knockdown of TSPEAR inhibited the proliferation, migration, and invasion of CRC cells. In addition, TSPEAR expression may be regulated by the upstream transcription factor TGIF2. Conclusion: TSPEAR expression was higher in CRC tissues than in normal tissues. Its upregulation was significantly associated with a poor prognosis. Additionally, TSPEAR plays a significant role in tumor immunity and the biological behavior of CRC cells. Thus, TSPEAR may become a promising prognostic biomarker and therapeutic target for CRC patients.

Discovery of molecular ferroelectric catalytic annulation for quinolines.

Ferroelectrics as emerging and attractive catalysts have shown tremendous potential for applications including wastewater treatment, hydrogen production, nitrogen fixation, and organic synthesis, etc. In this study, we demonstrate that molecular ferroelectric crystal TMCM-CdCl3 (TMCM = trimethylchloromethylammonium) with multiaxial ferroelectricity and superior piezoelectricity has an effective catalytic activity on the direct construction of the pharmacologically important substituted quinoline derivatives via one-pot [3 + 2 + 1] annulation of anilines and terminal alkynes by using N,N-dimethylformamide (DMF) as the carbon source. The recrystallized TMCM-CdCl3 crystals from DMF remain well ferroelectricity and piezoelectricity. Upon ultrasonic condition, periodic changes in polarization contribute to the release of free charges from the surface of the ferroelectric domains in nano size, which then quickly interacts with the substrates in the solution to trigger the pivotal redox process. Our work advances the molecular ferroelectric crystal as a catalytic route to organic synthesis, not only providing valuable direction for molecular ferroelectrics but also further enriching the executable range of ferroelectric catalysis.

MZT2A serves as a prognostic biomarker and promotes the progression of kidney renal clear cell carcinoma.

MZT2A is a novel core component in the γ-tubulin ring complex and aberrantly expressed in some types of tumors. However, MZT2A expression pattern across different cancers and its role in kidney renal clear cell carcinoma have not been sufficiently investigated. A thorough analysis of MZT2A expression landscape across 33 cancer types was conducted, utilizing 712 normal samples and 9807 tumor samples from TCGA (version 37.0), as well as 5112 normal samples from the GTEx databases. MZT2A's impact on KIRC cell viability and proliferation were evaluated through BrdU assays and monitored by cell imaging readers in MZT2A-expressing plasmid or siRNA-transfected cells. Additionally, the effects of MZT2A on cell apoptosis and cell cycle were detected using flow cytometry and Western blot. WGCNA analysis was employed to construct a co-expression gene network associated with MZT2A expression in KIRC, and Pearson correlation coefficient was utilized to examine the relationships between pairs of genes. MZT2A is overexpressed in 25 out of 33 types of cancer, including KIRC. In KIRC, high level of MZT2A was associated with higher clinical stage progression and poorer patients' survival. Downregulation of MZT2A decreased KIRC cell proliferation, retarded cell cycle and promoted apoptosis, while upregulation of MZT2A produced the opposite effects. WGCNA analysis and in vitro experiments revealed that MZT2A activated PI3K/AKT signaling pathway in KIRC. In all, MZT2A was overexpressed in most types of tumors. MZT2A served as an oncogene in KIRC and might be a potential target for guiding future treatments.

A Multiferroic Spin-Crossover Molecular Crystal.

Spin-crossover (SCO) ferroelectrics with dual-function switches have attracted great attention for significant magnetoelectric application prospects. However, the multiferroic crystals with SCO features have rarely been reported. Herein, a molecular multiferroic Fe(II) crystalline complex [FeII(C8-F-pbh)2] (1-F, C8-F-pbh = (1Z,N'E)-3-F-4-(octyloxy)-N'-(pyridin-2-ylmethylene)-benzo-hydrazonate) showing the coexistence of ferroelectricity, ferroelasticity, and SCO behavior is presented for the first time. By H/F substitution, the low phase transition temperature (270 K) of the non-fluorinated parent compound is significantly increased to 318 K in 1-F, which exhibits a spatial symmetry breaking 222F2 type ferroelectric phase transition with clear room-temperature ferroelectricity. Besides, 1-F also displays a spin transition between high- and low-spin states, accompanied by the d-orbital breaking within the t2g 4eg 2 and t2g 6eg° configuration change of octahedrally coordinated FeII center. Moreover, the 222F2 type ferroelectric phase transition is also a ferroelastic one, verified by the ferroelectric domains reversal and the evolution of ferroelastic domains. To the knowledge, 1-F is the first multiferroic SCO molecular crystal. This unprecedented finding sheds light on the exploration of molecular multistability materials for future smart devices.

A Versatile Cryomicroneedle Patch for Traceable Photodynamic Therapy.

Photodynamic therapy (PDT) continues to encounter multifarious hurdles, stemming from the ineffectual preservation and delivery system of photosensitizers, the dearth of imaging navigation, and the antioxidant/hypoxic tumor microenvironment. Herein, a versatile cryomicroneedle patch (denoted as CMN-CCPH) is developed for traceable PDT. The therapeutic efficacy is further amplified by catalase (CAT)-induced oxygen (O2) generation and Cu2+-mediated glutathione (GSH) depletion. The CMN-CCPH is composed of cryomicroneedle (CMN) as the vehicle and CAT-biomineralized copper phosphate nanoflowers (CCP NFs) loaded with hematoporphyrin monomethyl ether (HMME) as the payload. Importantly, the bioactive function of HMME and CAT can be optimally maintained under the protection of CCPH and CMN for a duration surpassing 60 days, leading to bolstered bioavailability and notable enhancements in PDT efficacy. The in vivo visualization of HMME and oxyhemoglobin saturation (sO2) monitored by fluorescence (FL)/photoacoustic (PA) duplex real-time imaging unveils the noteworthy implications of CMN-delivered CCPH for intratumoral enrichment of HMME and O2 with reduced systemic toxicity. This versatile CMN patch demonstrates distinct effectiveness in neoplasm elimination, underscoring its promising clinical prospects.

Genome sequence and comparative analysis of fungal antagonistic strain Bacillus velezensis LJBV19.

Bacillus species as fungal antagonistic agents have been widely used in the agriculture and considered as safe products for the management of plant pathogens. In this study, we reported the whole genome sequence of strain LJBV19 isolated from grapevine rhizosphere soil. Strain LJBV19 was identified as Bacillus velezensis through morphological, physicochemical, molecular analysis and genome comparison. Bacillus velezensis LJBV19 had a significant inhibitory effect on the growth of Magnaporthe oryzae with an inhibition ratio up to 75.55% and showed broad spectrum of activity against fungal phytopathogens. The 3,973,013-bp circular chromosome with an average GC content of 46.5% consisted of 3993 open reading frames (ORFs), and 3308 ORFs were classified into 19 cluster of orthologous groups of proteins (COG) categories. Genes related to cell wall degrading enzymes were predicted by Carbohydrate-Active enZYmes (CAZy) database and validated at the metabolic level, producing 0.53 ± 0.00 U/mL cellulose, 0.14 ± 0.01 U/mL chitinase, and 0.11 ± 0.01 U/mL chitosanase. Genome comparison confirmed the taxonomic position of LJBV19, conserved genomic structure, and genetic homogeneity. Moreover, 13 gene clusters for biosynthesis of secondary metabolites in LJBV19 genome were identified and two unique clusters (clusters 2 and 12) shown to direct an unknown compound were only present in strain LJBV19. In general, our results will provide insights into the antifungal mechanisms of Bacillus velezensis LJBV19 and further application of the strain.