Surface-enhanced Raman scattering spectroscopy monitoring and degradation of organic pollutants using a novel nanowire.

A multifunctional Ag/AlOOH nanowires (ANW) composite substrate was constructed, which not only accomplishes highly sensitive detection of organic dye molecules, but also has excellent performance in the degradation of pollutants. The ANW in the Ag/ANW substrate possesses a high aspect ratio, which extends the distribution area of Ag and enables a large number of hot spots on the active substrate. Additionally, due to the abundant OH groups on the ANW, there is an increased number of anchor sites for adsorbed metal ions in the Ag/ANW compound, thus contributing to the enhancement and degradation of molecules. Moreover, the constructed multifunctional Ag/ANW nanocomplexes also show great promise for practical applications, providing a reference for the detection and degradation of contaminants.

Mechanism of lncRNA SNHG16 on kidney clear cell carcinoma cells by targeting miR-506-3p/ETS1/RAS/ERK molecular axis.

Objective: This study aimed to investigate the mechanism of long noncoding ribonucleic acid (lncRNA) SNHG16 on kidney clear cell carcinoma (KIRC) cells by targeting miR-506-3p/ETS proto-oncogene 1, transcription factor (ETS1)/RAS/Extracellular regulated protein kinases (ERK) molecular axis, thus to provide reference for clinical diagnosis and treatment of KIRC in the future. Methods: Thirty-six patients with KIRC were enrolled in this study, and their carcinoma tissues and adjacent tissues were obtained for the detection of SNHG16/miR-506-3p/ETS1/RAS/ERK expression. Then, over-expressed SNHG16 plasmid and silenced plasmid were transfected into KIRC cells to observe the changes of their biological behavior. Results: SNHG16 and ETS1 were highly expressed while miR-506- 3p was low expressed in KIRC tissues; the RAS/ERK signaling pathway was significantly activated in KIRC tissues (P < 0.05). After SNHG16 silence, KIRC cells showed decreased proliferation, invasion and migration capabilities and increased apoptosis rate; correspondingly, increase in SNHG16 expression achieved opposite results (P < 0.05). Finally, in the rescue experiment, the effects of elevated SNHG16 on KIRC cells were reversed by simultaneous increase in miR-506-3p, and the effects of miR-506-3p were reversed by ETS1. Activation of the RAS/ERK pathway had the same effect as increase in ETS1, which further worsened the malignancy of KIRC. After miR-506-3p increase and ETS1 silence, the RAS/ERK signaling pathway was inhibited (P < 0.05). At last, the rescue experiment (co-transfection) confirmed that the effect of SNHG16 on KIRC cells is achieved via the miR-506-3p/ETS1/RAS/ERK molecular axis. Conclusion: SNHG16 regulates the biological behavior of KIRC cells by targeting the miR-506-3p/ETS1/RAS/ERK molecular axis.

Recent developments in photocatalytic production of hydrogen peroxide.

Hydrogen peroxide (H2O2), an environmentally friendly strong oxidant and energy carrier, has attracted widespread attention in photocatalysis. Artificial photosynthesis of H2O2 using water and oxygen as raw materials, solar energy as an energy source, and semiconductor materials as catalysts is considered a promising technology. In the past few decades, encouraging progress has been made in the photocatalytic production of H2O2. Therefore, we summarize the research achievements in this field in recent years. This review first briefly introduces the reaction pathway, detection techniques and evaluation metrics. Then, the recent advances in photocatalysts are highlighted. Furthermore, the existing challenges and possible solutions in this field are presented. At last, we look forward to the future development direction of this field. This review provides valuable insights and guidance for efficient photocatalytic H2O2 production.

The microbial metabolite agmatine acts as an FXR agonist to promote polycystic ovary syndrome in female mice.

Polycystic ovary syndrome (PCOS), an endocrine disorder afflicting 6-20% of women of reproductive age globally, has been linked to alterations in the gut microbiome. We previously showed that in PCOS, elevation of Bacteroides vulgatus in the gut microbiome was associated with altered bile acid metabolism. Here we show that B. vulgatus also induces a PCOS-like phenotype in female mice via an alternate mechanism independent of bile acids. We find that B. vulgatus contributes to PCOS-like symptoms through its metabolite agmatine, which is derived from arginine by arginine decarboxylase. Mechanistically, agmatine activates the farnesoid X receptor (FXR) pathway to subsequently inhibit glucagon-like peptide-1 (GLP-1) secretion by L cells, which leads to insulin resistance and ovarian dysfunction. Critically, the GLP-1 receptor agonist liraglutide and the arginine decarboxylase inhibitor difluoromethylarginine ameliorate ovarian dysfunction in a PCOS-like mouse model. These findings reveal that agmatine-FXR-GLP-1 signalling contributes to ovarian dysfunction, presenting a potential therapeutic target for PCOS management.

Lightweight, Strong, and Transparent Wood Films Produced by Capillary Driven Self-Densification.

Wood delignification and densification enable the production of high strength and/or transparent wood materials with exceptional properties. However, processing needs to be more sustainable and besides the chemical delignification treatments, energy intense hot-pressing calls for alternative approaches. Here, this study shows that additional softening of delignified wood via a mild swelling process using an ionic liquid-water mixture enables the densification of tube-line wood cells into layer-by-layer sheet structures without hot-pressing. The natural capillary force induces self-densification in a simple drying process resulting in a transparent wood film. The as-prepared films with ≈150 µm thickness possess an optical transmittance ≈70%, while maintaining optical haze >95%. Due to the densely packed sheet structure with a large interfacial area, the reassembled wood film is fivefold stronger and stiffer than the delignified wood in fiber direction. Owing to a low density, the specific tensile strength and elastic modulus are as high as 282 MPa cm3 g-1 and 31 GPa cm3 g-1. A facile and highly energy efficient wood nanotechnology approach are demonstrated toward more sustainable materials and processes by directly converting delignified wood into transparent wood omitting polymeric matrix infiltration or mechanical pressing.

Fluorescent response mechanism based on ESIPT and TICT of novel probe H2QJI: A TD-DFT investigation.

Recently, synthesized N-linked-disalicylaldehyde H2QJI probes have been used to detect heavy metal ions in the experiment conveniently. Nevertheless, there needs to be a more in-depth examination of the excited state intramolecular proton transfer (ESIPT) mechanism and photophysical properties of the probe. This work remedied it based on quantum chemistry calculations. We contained due hydrogen bond (O1-H2 ⋯ N3 and O4-H5 ⋯ O6) and then analyzed bond parameters, IR vibration spectra, and non-covalent interaction. The bond strength is enhanced under photoexcitation, and the former is significantly stronger. The calculated electron spectra are in agreement with the experimental values. The results of the S0 and S1 potential energy curves and IRC calculations also confirm the unique ESIPT behavior, which isan excited stated stepwise double proton transfer. The fluorescence, internal conversion, and intersystem crossing rate of KD molecules (twisted-, double proton transfer) were calculated respectively to reveal the radiative and non-radiative pathways. It proved that the corresponding spectra are not obtained since the electrons are mainly deactivated by the ISC (S1->T1). Furthermore, the interfragment charge transfer (IFCT) approach indicates that the molecule possesses twisted intramolecular charge transfer (TICT) characteristics, which lead to the quenching of fluorescence introduction.

3D Conjugated Hole Transporting Materials for Efficient and Stable Perovskite Solar Cells and Modules.

The orthogonal structure of the widely used hole transporting material (HTM) 2,2',7,7'-tetrakis(N, N-di-p-methoxyphenylamino)-9,9'-spirobifluorene (Spiro-OMeTAD) imparts isotropic conductivity and excellent film-forming capability. However, inherently weak intra- and inter-molecular π-π interactions result in low intrinsic hole mobility. Herein, a novel HTM, termed FTPE-ST, with a twist conjugated dibenzo(g,p)chrysene core and coplanar 3,4-ethylenedioxythiophene (EDOT) as extended donor units, is designed to enhance π-π interactions, without compromising on solubility. The three-dimensional (3D) configuration provides the material multi-direction charge transport as well as excellent solubility even in 2-methylanisole, and its large conjugated backbone endows the HTM with a high hole mobility. Moreover, the sulfur donors in EDOT units coordinate with lead ions on the perovskite surface, leading to stronger interfacial interactions and the suppression of defects at the perovskite/HTM interface. As a result, perovskite solar cells (PSCs) employing FTPE-ST achieve a champion power conversion efficiency (PCE) of 25.21% with excellent long-time stability, one of the highest PCEs for non-spiro HTMs in n-i-p PSCs. In addition, the excellent film-forming capacity of the HTM enables the fabrication of FTPE-ST-based large-scale PSCs (1.0 cm2) and modules (29.0 cm2), which achieve PCEs of 24.21% (certificated 24.17%) and 21.27%, respectively.

Kaempferol attenuates inflammation in lipopolysaccharide-induced gallbladder epithelial cells by inhibiting the MAPK/NF-κB signaling pathway.

Kaempferol (KPR), a flavonoid compound found in various plants and foods, has garnered attention for its anti-inflammatory, antioxidant, and anticancer properties. In preliminary studies, KPR can modulate several signaling pathways involved in inflammation, making it a candidate for treating cholecystitis. This study aimed to explore the effects and mechanisms of KPR on lipopolysaccharide (LPS)-induced human gallbladder epithelial cells (HGBECs). To assess the impact of KPR on HGBECs, the HGBECs were divided into control, KPR, LPS, LPS + KPR, and LPS + UDCA groups. Cell viability and cytotoxicity were evaluated by MTT assay and lactate dehydrogenase (LDH) assay, respectively, and concentrations of KPR (10-200 µM) were tested. LPS-induced inflammatory responses in HGBECs were to create an in vitro model of cholecystitis. The key inflammatory markers (IL-1ß, IL-6, and TNF-α) levels were quantified using ELISA, The modulation of the MAPK/NF-κB signaling pathway was measured by western blot using specific antibodies against pathway components (p-IκBα, IκBα, p-p65, p65, p-JNK, JNK, p-ERK, ERK, p-p38, and p38). The cell viability and LDH levels in HGBECs were not significantly affected by 50 µM KPR, thus it was selected as the optimal KPR intervention concentration. KPR increased the viability of LPS-induced HGBECs. Additionally, KPR inhibited the inflammatory factors level (IL-1ß, IL-6, and TNF-α) and protein expression (iNOS and COX-2) in LPS-induced HGBECs. Furthermore, KPR reversed LPS-induced elevation of p-IκBα/IκBα, p-p65/p65, p-JNK/JNK, p-ERK/ERK, and p-p38/p38 ratios. KPR attenuates the LPS-induced inflammatory response in HGBECs, possibly by inhibiting MAPK/NF-κB signaling.

Mechanochemically Enabled Metastable Niobium Tungsten Oxides.

Metastable compounds have greatly expanded the synthesizable compositions of solid-state materials and have attracted enormous amounts of attention in recent years. Especially, mechanochemically enabled metastable materials synthesis has been very successful in realizing cation-disordered materials with highly simple crystal structures, such as rock salts. Application of the same strategy for other structural types, especially for non-close-packed structures, is peculiarly underexplored. Niobium tungsten oxides (NbWOs), a class of materials that have been under the spotlight because of their diverse structural varieties and promising electrochemical and thermoelectric properties, are ideally suited to fill such a knowledge gap. In this work, we develop a new series of metastable NbWOs and realize one with a fully cation-disordered structure. Furthermore, we find that metastable NbWOs transform to a cation-disordered cubic structure when applied as a Li-ion battery anode, highlighting an intriguing non-close-packed-close-packed conversion process, as evidenced in various physicochemical characterizations, in terms of diffraction, electronic, and vibrational structures. Finally, by comparing the cation-disordered NbWO with other trending cation-disordered oxides, we raise a few key structural features for cation disorder and suggest a few possible research opportunities for this field.

Cu-phen Coordination Enabled Selective Electrocatalytic Reduction of CO2 to Methane.

Manipulation of selectivity in the catalytic electrochemical carbon dioxide reduction reaction (eCO2RR) poses significant challenges due to inevitable structure reconstruction. One approach is to develop effective strategies for controlling reaction pathways to gain a deeper understanding of mechanisms in robust CO2RR systems. In this work, by precise introduction of 1,10-phenanthroline as a bidentate ligand modulator, the electronic property of the copper site was effectively regulated, thereby directing selectivity switch. By modification of [Cu3(btec)(OH)2]n, the use of [Cu2(btec)(phen)2]n·(H2O)n achieved the selectivity switch from ethylene (faradaic efficiency (FE) = 41%, FEC2+ = 67%) to methane (FECH4 = 69%). Various in situ spectroscopic characterizations revealed that [Cu2(btec)(phen)2]n·(H2O)n promoted the hydrogenation of *CO intermediates, leading to methane generation instead of dimerization to form C2+ products. Acting as a delocalized π-conjugation scaffold, 1,10-phenanthroline in [Cu2(btec)(phen)2]n·(H2O)n helps stabilize Cuδ+. This work presents a novel approach to regulate the coordination environment of active sites with the aim of selectively modulating the CO2RR.

Enhancement of NiTiO3 piezocatalytic hydrogen evolution by doping with large radius elements.

Piezocatalysis is a direct method for converting mechanical vibration into chemical energy. Herein, NiTiO3 is used in the piezocatalytic hydrogen evolution field for the first time. The noncentral symmetry of NiTiO3 is enhanced by doping with large radius elements. It is demonstrated that when a metal element replaces the sites of nickel, it results in lattice distortion and a higher piezoelectric response. In particular, Cd-doped NiTiO3 exhibits the highest H2 generation rate (1.52 mmol g-1 h-1), which is 13 times that of original NiTiO3.

Gut symbionts alleviate MASH through a secondary bile acid biosynthetic pathway.

The gut microbiota has been found to play an important role in the progression of metabolic dysfunction-associated steatohepatitis (MASH), but the mechanisms have not been established. Here, by developing a click-chemistry-based enrichment strategy, we identified several microbial-derived bile acids, including the previously uncharacterized 3-succinylated cholic acid (3-sucCA), which is negatively correlated with liver damage in patients with liver-tissue-biopsy-proven metabolic dysfunction-associated fatty liver disease (MAFLD). By screening human bacterial isolates, we identified Bacteroides uniformis strains as effective producers of 3-sucCA both in vitro and in vivo. By activity-based protein purification and identification, we identified an enzyme annotated as ß-lactamase in B. uniformis responsible for 3-sucCA biosynthesis. Furthermore, we found that 3-sucCA is a lumen-restricted metabolite and alleviates MASH by promoting the growth of Akkermansia muciniphila. Together, our data offer new insights into the gut microbiota-liver axis that may be leveraged to augment the management of MASH.

Nanoarchitectonics of Bimetallic Cu-/Co-Doped Nitrogen-Carbon Nanozyme-Functionalized Hydrogel with NIR-Responsive Phototherapy for Synergistic Mitigation of Drug-Resistant Bacterial Infections.

Superbug infections and transmission have become major challenges in the contemporary medical field. The development of novel antibacterial strategies to efficiently treat bacterial infections and conquer the problem of antimicrobial resistance (AMR) is extremely important. In this paper, a bimetallic CuCo-doped nitrogen-carbon nanozyme-functionalized hydrogel (CuCo/NC-HG) has been successfully constructed. It exhibits photoresponsive-enhanced enzymatic effects under near-infrared (NIR) irradiation (808 nm) with strong peroxidase (POD)-like and oxidase (OXD)-like activities. Upon NIR irradiation, CuCo/NC-HG possesses photodynamic activity for producing singlet oxygen(1O2), and it also has a high photothermal conversion effect, which not only facilitates the elimination of bacteria but also improves the efficiency of reactive oxygen species (ROS) production and accelerates the consumption of GSH. CuCo/NC-HG shows a lower hemolytic rate and better cytocompatibility than CuCo/NC and possesses a positive charge and macroporous skeleton for restricting negatively charged bacteria in the range of ROS destruction, strengthening the antibacterial efficiency. Comparatively, CuCo/NC and CuCo/NC-HG have stronger bactericidal ability against methicillin-resistant Staphylococcus aureus (MRSA) and ampicillin-resistant Escherichia coli (AmprE. coli) through destroying the cell membranes with a negligible occurrence of AMR. More importantly, CuCo/NC-HG plus NIR irradiation can exhibit satisfactory bactericidal performance in the absence of H2O2, avoiding the toxicity from high-concentration H2O2. In vivo evaluation has been conducted using a mouse wound infection model and histological analyses, and the results show that CuCo/NC-HG upon NIR irradiation can efficiently suppress bacterial infections and promote wound healing, without causing inflammation and tissue adhesions.

Sequential surgery for the treatment of type I knee ankylosis: a series of 62 cases.

BACKGROUNDS: The lack of systematic classification and standard treatment principles for knee ankylosis prevents optimal treatments. This study explored treatments for type I (mild) knee joint ankylosis. METHOD: This retrospective study analysed patients with knee joint ankylosis admitted from March 2013 to January 2018 who underwent sequential arthroscopic release. RESULT: The 62 patients had 12-36 (average, 18) months of follow-up. Thirty-eight patients were released; of these, 18 were assisted by limited incision with partial quadriceps femoris expansion myotomy and released according to arthroscopy. Six patients underwent lengthening and release of the quadriceps femoris. All surgeries combined with full-course rehabilitation resulted in improved joint mobility. The range of motion (ROM) of the knee joint recovered to a range of 0° to 85°-140° (mean: 118.32 ± 9.42°) from the preoperative range of 30°-70° (mean: 45° ± 15.50°). The clinical effect was evaluated according to the Judet criteria at the final follow-up. The outcomes at the last follow-up (at least for 1 year) were excellent in 55 cases, good in six cases, and fair in one case. CONCLUSION: Sequential arthroscopic release, minimal selective invasion of limited incision of partial quadriceps femoris expansion myotomy, assisted by pie-crusting technique to release, or quadriceps femoris lengthening, and release surgery for type I knee joint ankylosis, accompanied by early rehabilitation training provided satisfactory results without significant complications.

Dopant-Free Pyrene-Based Hole Transporting Material Enables Efficient and Stable Perovskite Solar Cells.

Dopant-free hole transporting materials (HTMs) is significant to the stability of perovskite solar cells (PSCs). Here, we developed a novel star-shape arylamine HTM, termed Py-DB, with a pyrene core and carbon-carbon double bonds as the bridge units. Compared to the reference HTM (termed Py-C), the extension of the planar conjugation backbone endows Py-DB with typical intermolecular π-π stacking interactions and excellent solubility, resulting in improved hole mobility and film morphology. In addition, the lower HOMO energy level of the Py-DB HTM provides efficient hole extraction with reduced energy loss at the perovskite/HTM interface. Consequently, an impressive power conversion efficiency (PCE) of 24.33 % was achieved for dopant-free Py-DB-based PSCs, which is the highest PCE for dopant-free small molecular HTMs in n-i-p configured PSCs. The dopant-free Py-DB-based device also exhibits improved long-term stability, retaining over 90 % of its initial efficiency after 1000 h exposure to 25 % humidity at 60 °C. These findings provide valuable insights and approaches for the further development of dopant-free HTMs for efficient and reliable PSCs.

Dopant-additive synergism enhances perovskite solar modules.

Perovskite solar cells (PSCs) are among the most promising photovoltaic technologies owing to their exceptional optoelectronic properties1,2. However, the lower efficiency, poor stability and reproducibility issues of large-area PSCs compared with laboratory-scale PSCs are notable drawbacks that hinder their commercialization3. Here we report a synergistic dopant-additive combination strategy using methylammonium chloride (MACl) as the dopant and a Lewis-basic ionic-liquid additive, 1,3-bis(cyanomethyl)imidazolium chloride ([Bcmim]Cl). This strategy effectively inhibits the degradation of the perovskite precursor solution (PPS), suppresses the aggregation of MACl and results in phase-homogeneous and stable perovskite films with high crystallinity and fewer defects. This approach enabled the fabrication of perovskite solar modules (PSMs) that achieved a certified efficiency of 23.30% and ultimately stabilized at 22.97% over a 27.22-cm2 aperture area, marking the highest certified PSM performance. Furthermore, the PSMs showed long-term operational stability, maintaining 94.66% of the initial efficiency after 1,000 h under continuous one-sun illumination at room temperature. The interaction between [Bcmim]Cl and MACl was extensively studied to unravel the mechanism leading to an enhancement of device properties. Our approach holds substantial promise for bridging the benchtop-to-rooftop gap and advancing the production and commercialization of large-area perovskite photovoltaics.

Elucidating the Role of Reduction Kinetics in the Phase-Controlled Growth on Preformed Nanocrystal Seeds: A Case Study of Ru.

This study demonstrates the crucial role of reduction kinetics in phase-controlled synthesis of noble-metal nanocrystals using Ru nanocrystals as a case study. We found that the reduction kinetics played a more important role than the templating effect from the preformed seed in dictating the crystal structure of the deposited overlayers despite their intertwined effects on successful epitaxial growth. By employing two different polyols, a series of Ru nanocrystals with tunable sizes of 3-7 nm and distinct patterns of crystal phase were synthesized by incorporating different types of Ru seeds. Notably, the use of ethylene glycol and triethylene glycol consistently resulted in the formation of Ru shell in natural hexagonal close-packed (hcp) and metastable face-centered cubic (fcc) phases, respectively, regardless of the size and phase of the seed. Quantitative measurements and theoretical calculations suggested that this trend was a manifestation of the different reduction kinetics associated with the precursor and the chosen polyol, which, in turn, affected the reduction pathway (solution versus surface) and packing sequence of the deposited Ru atoms. This work not only underscores the essential role of reduction kinetics in controlling the packing of atoms and thus the phase taken by Ru nanocrystals but also suggests a potential extension to other noble-metal systems.

Baicalin administration could rescue high glucose-induced craniofacial skeleton malformation by regulating neural crest development.

Hyperglycemia in pregnancy can increase the risk of congenital disorders, but little is known about craniofacial skeleton malformation and its corresponding medication. Our study first used meta-analysis to review the previous findings. Second, baicalin, an antioxidant, was chosen to counteract high glucose-induced craniofacial skeleton malformation. Its effectiveness was then tested by exposing chicken embryos to a combination of high glucose (HG, 50 mM) and 6 µM baicalin. Third, whole-mount immunofluorescence staining and in situ hybridization revealed that baicalin administration could reverse HG-inhibited neural crest cells (NCC) delamination and migration through upregulating the expression of Pax7 and Foxd3, and mitigate the disordered epithelial-mesenchymal transition (EMT) process by regulating corresponding adhesion molecules and transcription factors (i.e., E-cadherin, N-cadherin, Cadherin 6B, Slug and Msx1). Finally, through bioinformatic analysis and cellular thermal shift assay, we identified the AKR1B1 gene as a potential target. In summary, these findings suggest that baicalin could be used as a therapeutic agent for high glucose-induced craniofacial skeleton malformation.

The clinical and hemodynamic characteristics of pulmonary hypertension in patients with OSA-COPD overlap syndrome.

BACKGROUND: Our study aimed to assess the clinical and hemodynamic characteristics of pulmonary hypertension (PH) in patients with overlapping obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD), referred to OSA-COPD overlap syndrome (OS). METHODS: We enrolled a total of 116 patients with OS, COPD, or OSA who underwent right heart catheterization (RHC) due to suspected PH. We conducted a retrospective analysis of the clinical and hemodynamic characteristics of these patients. RESULTS: Among the three groups (OS group, n = 26; COPD group, n = 36; OSA group, n = 54), the prevalence of PH was higher in the OS group (n = 17, 65.4%)compared to OSA group (n = 26,48.1%) and COPD group (n = 20,55.6 %). Among three groups with PH, the superior vena cava pressure (CVP) and right ventricular pressure (RAP) were higher in the OS group than in the OSA group (P < 0.05). Patients in the OS and COPD groups had higher pulmonary artery wedge pressure (PAWP) than in the OSA group (14.88 ± 4.79 mmHg, 13.45 ± 3.68 mmHg vs. 11.00 ± 3.51 mmHg, respectively, P < 0.05). OS patients with PH exhibited higher respiratory event index (REI), time spent with SpO2 <90%, oxygen desaturation index (ODI), minimal SpO2 (MinSpO2) and mean SpO2 (MSpO2) compared to OS patients without PH. After adjusting for potential covariates, we found that MinSpO2 (OR 0.937, 95 % CI 0.882-0.994, P = 0.032), MSpO2 (OR 0.805, 95% CI 0.682-0.949, P = 0.010), time spent with SpO2 <90% (OR 1.422, 95% CI 1.137-1.780, P = 0.002), and FEV1 % pred (OR 0.977, 95 % CI 0.962-0.993, P = 0.005) were related to the development of PH. CONCLUSIONS: Patients with OS showed higher prevalence of PH, along with higher PAWP, CVP and RAP. Worse nocturnal hypoxemia was found in OS patients with PH.

ATX1 and HUB1/2 promote recruitment of the transcription elongation factor VIP2 to modulate the floral transition in Arabidopsis.

Histone 2B ubiquitination (H2Bub) and trimethylation of H3 at lysine 4 (H3K4me3) are associated with transcription activation. However, the function of these modifications in transcription in plants remains largely unknown. Here, we report that coordination of H2Bub and H3K4me3 deposition with the binding of the RNA polymerase-associated factor VERNALIZATION INDEPENDENCE2 (VIP2) to FLOWERING LOCUS C (FLC) modulates flowering time in Arabidopsis. We found that RING domain protein HISTONE MONOUBIQUITINATION1 (HUB1) and HUB2 (we refer as HUB1/2), which are responsible for H2Bub, interact with ARABIDOPSIS TRITHORAX1 (ATX1), which is required for H3K4me3 deposition, to promote the transcription of FLC and repress the flowering time. The atx1-2 hub1-10 hub2-2 triple mutant in FRIGIDIA (FRI) background displayed early flowering like FRI hub1-10 hub2-2 and overexpression of ATX1 failed to rescue the early flowering phenotype of hub1-10 hub2-2. Mutations in HUB1 and HUB2 reduced the ATX1 enrichment at FLC, indicating that HUB1 and HUB2 are required for ATX1 recruitment and H3K4me3 deposition at FLC. We also found that the VIP2 directly binds to HUB1, HUB2, and ATX1 and that loss of VIP2 in FRI hub1-10 hub2-2 and FRI atx1-2 plants resulted in early flowering like that observed in FRI vip2-10. Loss of function of HUB2 and ATX1 impaired VIP2 enrichment at FLC, and reduced the transcription initiation and elongation of FLC. In addition, mutations in VIP2 reduced HUB1 and ATX1 enrichment and H2Bub and H3K4me3 levels at FLC. Together, our findings revealed that HUB1/2, ATX1, and VIP2 coordinately modulate H2Bub and H3K4me3 deposition, FLC transcription, and flowering time.