LDLa containing C-type lectin mediates phagocytosis of V.anguillarum and regulates immune effector genes in shrimp.

C-type lectins (CTLs) function as pattern recognition receptors (PRRs) by recognizing invading microorganisms, thereby triggering downstream immune events against infected pathogens. In this study, a novel CTL containing a low-density lipoprotein receptor class A (LDLa) domain was obtained from Litopenaeus vannamei, designed as LvLDLalec. Stimulation by the bacterial pathogen Vibrio anguillarum (V. anguillarum) resulted in remarkable up-regulation of LvLDLalec, as well as release of LvLDLalec into hemolymph. The rLvLDLalec protein possessed broad-spectrum bacterial binding and agglutinating activities, as well as hemocyte attachment ability. Importantly, LvLDLalec facilitated the bacterial clearance in shrimp hemolymph and protected shrimp from bacterial infection. Further studies revealed that LvLDLalec promoted hemocytes phagocytosis against V. anguillarum and lysosomes were involved in the process. Meanwhile, LvLDLalec participated in humoral immunity through activating and inducing nuclear translocation of Dorsal to regulate phagocytosis-related genes and antimicrobial peptides (AMPs) genes, thereby accelerated the removal of invading pathogens in vivo and improved the survival rate of L. vannamei. These results unveil that LvLDLalec serves as a PRR participate in cellular and humoral immunity exerting opsonin activity to play vital roles in the immune regulatory system of L. vannamei.

Antimicrobial resistance crisis: could artificial intelligence be the solution?

Antimicrobial resistance is a global public health threat, and the World Health Organization (WHO) has announced a priority list of the most threatening pathogens against which novel antibiotics need to be developed. The discovery and introduction of novel antibiotics are time-consuming and expensive. According to WHO's report of antibacterial agents in clinical development, only 18 novel antibiotics have been approved since 2014. Therefore, novel antibiotics are critically needed. Artificial intelligence (AI) has been rapidly applied to drug development since its recent technical breakthrough and has dramatically improved the efficiency of the discovery of novel antibiotics. Here, we first summarized recently marketed novel antibiotics, and antibiotic candidates in clinical development. In addition, we systematically reviewed the involvement of AI in antibacterial drug development and utilization, including small molecules, antimicrobial peptides, phage therapy, essential oils, as well as resistance mechanism prediction, and antibiotic stewardship.

All-Solid-State Mg-Air Battery Enhanced with Free-Standing N-Doped 3D Nanoporous Graphene.

Nitrogen (N) doping of graphene with a three-dimensional (3D) porous structure, high flexibility, and low cost exhibits potential for developing metal-air batteries to power electric/electronic devices. The optimization of N-doping into graphene and the design of interconnected and monolithic graphene-based 3D porous structures are crucial for mass/ion diffusion and the final oxygen reduction reaction (ORR)/battery performance. Aqueous-type and all-solid-state primary Mg-air batteries using N-doped nanoporous graphene as air cathodes are assembled. N-doped nanoporous graphene with 50-150 nm pores and ≈99% porosity is found to exhibit a Pt-comparable ORR performance, along with satisfactory durability in both neutral and alkaline media. Remarkably, the all-solid-state battery exhibits a peak power density of 72.1 mW cm-2 ; this value is higher than that of a battery using Pt/carbon cathodes (54.3 mW cm-2 ) owing to the enhanced catalytic activity induced by N-doping and rapid air breathing in the 3D porous structure. Additionally, the all-solid-state battery demonstrates better performances than the aqueous-type battery owing to slow corrosion of the Mg anode by solid electrolytes. This study sheds light on the design of free-standing and catalytically active 3D nanoporous graphene that enhances the performance of both Mg-air batteries and various carbon-neutral-technologies using neutral electrolytes.

The complex dynamics of the 2023 Kahramanmaras, Turkey, Mw 7.8-7.7 earthquake doublet.

The destructive 2023 moment magnitude (Mw) 7.8-7.7 earthquake doublet ruptured multiple segments of the East Anatolian Fault system in Turkey. We integrated multiscale seismic and space-geodetic observations with multifault kinematic inversions and dynamic rupture modeling to unravel the events' complex rupture history and stress-mediated fault interactions. Our analysis reveals three subshear slip episodes during the initial Mw 7.8 earthquake with a delayed rupture initiation to the southwest. The Mw 7.7 event occurred 9 hours later with a larger slip and supershear rupture on its western branch. Mechanically consistent dynamic models accounting for fault interactions can explain the unexpected rupture paths and require a heterogeneous background stress. Our results highlight the importance of combining near- and far-field observations with data-driven and physics-based models for seismic hazard assessment.

Antibacterial and immunoregulatory activity of an antimicrobial peptide hepcidin in loach (Misgurnus anguillicaudatus).

Antimicrobial peptides (AMPs) are members of humoral immunity and particpate in resisting microbial invasion. In this study, an AMP gene hepcidin was obtained from the oriental loach Misgurnus anguillicaudatus and named Ma-Hep. This Ma-Hep encodes a peptide of 90 amino acids, with a predicted active peptide segment (Ma-sHep) of 25 amino acids at C terminus. Stimulation by a bacterial pathogen Aeromonas hydrophila resulted in significant up-regulation of Ma-Hep transcripts in loach midgut, head kidney, and gill. Ma-Hep and Ma-sHep proteins were expressed in Pichia pastoris and their antibacterial activity was examined. Results showed that Ma-sHep possessed stronger antibacterial activity against various Gram-positive and Gram-negative bacteria, compared to Ma-Hep. Scanning electron microscopy showed that Ma-sHep might kill bacteria by destroying bacterial cell membranes. Moreover, we found that Ma-sHep had an inhibitory effect on blood cell apoptosis induced by A. hydrophila and facilitated the bacterial phagocytosis and clearance in loach. Histopathological analysis indicated Ma-sHep could protect liver and gut of loach from bacterial infection. Ma-sHep has high thermal stability and PH stability, which is conducive to further feed addition. Feed supplemented with Ma-sHep expressing yeast improved the intestinal flora of loach by increasing the dominant bacteria and decreasing the harmful bacteria. Feed supplemented with Ma-sHep expressing yeast also regulated the expression of inflammatory related factors in various tissues of loach and reduced the mortality of loach upon bacterial infection. These findings show that the antibacterial peptide Ma-sHep is involved in the antibacterial defense of loach and can be used as a candidate for new antimicrobial agents in aquaculture.

Revealing Atomic Configuration and Synergistic Interaction of Single-Atom-Based Zn-Co-Fe Trimetallic Sites for Enhancing Oxygen Reduction and Evolution Reactions.

Anchoring single metal atom to carbon supports represents an exceptionally effective strategy to maximize the efficiency of catalysts. Recently, dual-atom catalysts (DACs) emerge as an intriguing candidate for atomic catalysts, which perform better than single-atom catalysts (SACs). However, the clarification of the polynary single-atom structures and their beneficial effects remains a daunting challenge. Here, atomically dispersed triple Zn-Co-Fe sites anchored to nitrogen-doped carbon (ZnCoFe-N-C) prepared by one-step pyrolysis of a designed metal-organic framework precursor are reported. The atomically isolated trimetallic configuration in ZnCoFe-N-C is identified by annular dark-field scanning transmission electron microscopy and spectroscopic techniques. Benefiting from the synergistic effect of trimetallic single atoms, nitrogen, and carbon, ZnCoFe-N-C exhibits excellent catalytic performance in bifunctional oxygen reduction/evolution reactions in an alkaline medium, outperforming other SACs and DACs. The ZnCoFe-N-C-based Zn-air battery exhibits a high specific capacity (liquid state: 931.8 Wh kgZn -1 ), power density (liquid state: 137.8 mW cm-2 ; all-solid-state: 107.9 mW cm-2 ), and good cycling stability. Furthermore, density-functional theory calculations rationalize the excellent performance by demonstrating that the ZnCoFe-N-C catalyst has upshifted d-band center that enhances the adsorption of the reaction intermediates.

Designing strategies and enhancing mechanism for multicomponent high-entropy catalysts.

High-entropy materials (HEMs) are new-fashioned functional materials in the field of catalysis owing to their large designing space, tunable electronic structure, interesting "cocktail effect", and entropy stabilization effect. Many effective strategies have been developed to design advanced catalysts for various important reactions. Herein, we firstly review effective strategies developed so far for optimizing HEM-based catalysts and the underlying mechanism revealed by both theoretical simulations and experimental aspects. In light of this overview, we subsequently present some perspectives about the development of HEM-based catalysts and provide some serviceable guidelines and/or inspiration for further studying multicomponent catalysts.

Curvature effects on the bifunctional oxygen catalytic performance of single atom metal-N-C.

Understanding the fundamental relationship between the structural information of electrocatalysts and their catalytic activities plays a key role in controlling many important electrochemical processes. Recently, single-atom catalysts (SACs) with the so-called MN4 structure, consisting of a central transition metal quadruply bound to four pyridine nitrogen atoms all situated in an extended carbon-based matrix, have attracted intensive scientific attention owing to their exceptional catalytic performance. In this work, we perform the first-principles density functional theory (DFT) calculations to explore the curvature effects of the carbon matrix surfaces on the catalytic activities for two fundamental electrochemical processes, namely, the oxygen reduction reaction (ORR) and the oxygen evolution reaction (OER). Our DFT results suggest that the curved surface structure can weaken the interaction between the metal atom and the N-doped carbon matrix, modify the electronic structure of the metal atom, and thus increase the adsorption strength of the reaction intermediates, resulting in enhanced OER and ORR catalytic activities of MN4 catalysts. More importantly, a prediction model is developed to evaluate the bifunctional catalytic activities of such catalysts based on their directly obtained parameters including the surface curvature of the catalysts, the number of d electrons of the metal element, and the electronegativity of the metal atom and its coordination atoms in MN4 catalysts. This prediction model not only provides some candidates, for example, FeN4, CoN4 and OsN4 for the ORR; CoN4, NiN4, RuN4, RhN4 and IrN4 for the OER; and CoN4, RuN4, IrN4 and OsN4 for the bifunctional ORR and OER, but also reasonably links the structure of catalysts with their catalytic performance, providing new possibilities for the quick design of high-performance catalysts.

Impact of aluminum exposure on oxidative stress, intestinal changes and immune responses in red swamp crayfish (Procambarus clarkii).

Aluminum (Al) is an abundant metal that has been classified as a threatening pollutant due to indiscriminate use and anthropogenic activities. This study aimed to evaluate the impacts of Al on crayfish (Procambarus clarkii), including biochemical change, histological alteration, gut microbial community diversification, and immune changes. The bioaccumulation of Al was detected in the hemolymph and intestine of crayfish after Al exposure at different time points. Results showed that Al exposure significantly induced oxidative stress and caused pathohistological changes on intestinal barrier structures in crayfish. It was found that the intestinal microbiota was affected by retained Al and the intestinal community diversity was changed after Al treated in the crayfish. Furthermore, Al exposure affected the immunity in crayfish, by altering the expression of a set of immune-related genes, as well as reducing the phenoloxidase and lysozyme activities. Moreover, Al exposure promoted hemocytes apoptosis and impaired hemophagocytic capacity against Vibro parahamolyticus, resulting in higher mortality of crayfish upon bacterial infection. Taken these results together, we conclude that excessive Al exposure caused adverse effects on multiple biological processes of crayfish and Al pollution is a potential threat to crayfish culture.

Structure of a TOC-TIC supercomplex spanning two chloroplast envelope membranes.

The TOC and TIC complexes are essential translocons that facilitate the import of the nuclear genome-encoded preproteins across the two envelope membranes of chloroplast, but their exact molecular identities and assembly remain unclear. Here, we report a cryoelectron microscopy structure of TOC-TIC supercomplex from Chlamydomonas, containing a total of 14 identified components. The preprotein-conducting pore of TOC is a hybrid ß-barrel co-assembled by Toc120 and Toc75, while the potential translocation path of TIC is formed by transmembrane helices from Tic20 and YlmG, rather than a classic model of Tic110. A rigid intermembrane space (IMS) scaffold bridges two chloroplast membranes, and a large hydrophilic cleft on the IMS scaffold connects TOC and TIC, forming a pathway for preprotein translocation. Our study provides structural insights into the TOC-TIC supercomplex composition, assembly, and preprotein translocation mechanism, and lays a foundation to interpret the evolutionary conservation and diversity of this fundamental translocon machinery.

A fourteen-component high-entropy alloy@oxide bifunctional electrocatalyst with a record-low ΔE of 0.61 V for highly reversible Zn-air batteries.

Nanostructured high-entropy materials such as alloys, oxides, etc., are attracting extensive attention because of their widely tunable surface electronic structure/catalytic activity through mixing different elements in one system. To further tune the catalytic performance and multifunctionality, the designed fabrication of multicomponent high-entropy nanocomposites such as high-entropy alloy@high-entropy oxides (HEA@HEO) should be very promising. In this work, we design a two-step alloying-dealloying strategy to synthesize ultra-small HEA nanoclusters (∼2 nm) loaded on nanoporous HEO nanowires, and the compositions of both the HEA and HEO can be adjusted separately. To demonstrate this concept, a seven-component HEA (PtPdAuAgCuIrRu) clusters@seven-component HEO (AlNiCoFeCrMoTi)3O4 was prepared, which is highly active for both oxygen evolution and reduction reactions. Our comprehensive experimental results and first-principles density functional theory (DFT) calculations clearly show that better oxygen evolution reaction (OER) performance is obtained by optimizing the composition of the HEO support, and the seven-component HEA nanocluster is much more active for the ORR when compared with pure Pt due to the modified surface electronic structure. Specifically, the high-entropy composite exhibits an OER activity comparable to the best reported value, and the ORR activity exceeded the performance of commercial Pt/C in alkaline solutions with a record-low bifunctional ΔE of 0.61 V in 0.1 M KOH solution. This work shows an important route to prepare complex HEA@HEO nanocomposites with tuned catalytic performance for multifunctional catalysis and energy conversion.

Overexpression of PBK/TOPK relates to poor prognosis of patients with breast cancer: a retrospective analysis.

BACKGROUND: PDZ-binding kinase/T-lymphokine-activated killer cell-derived protein kinase (PBK/TOPK) is a potential prognostic indicator for patients with breast cancer. The objective of the present study was to explore the relationship between PBK/TOPK expression and clinicopathological indicators as well as the survival of patients with breast cancer. METHODS: Immunohistochemical staining was used to detect the expression of PBK/TOPK in 202 cases of breast cancer tissues. The relationship between PBK/TOPK and clinicopathological parameters was evaluated using Spearman's rank-order correlation. The difference in PBK/TOPK expression among different molecular types was analyzed with the chi-square test. Kaplan-Meier analysis was used to create a survival curve and the log rank test was used to analyze the overall survival (OS) and disease-free survival (DFS). Prognostic correlation was assessed using univariate and multivariate Cox regression analyses. RESULTS: Among 202 breast cancer samples, PBK/TOPK was expressed ("+" and "++") in 182 samples (90.1%). In addition, the histological grade, TNM stages, lymph node metastasis, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), and Ki-67 were positively associated with PBK/TOPK expression. With regard to the molecular type, the expression of PBK/TOPK is different. The expression level of PBK/TOPK was negatively correlated with both the OS and DFS of breast cancer patients. The difference in the above results is meaningful (P < 0.05). CONCLUSIONS: PBK/TOPK is overexpressed in breast cancer, and the expression is closely related to the clinicopathological characteristics of the disease. Breast cancer patients with high expression of PBK/TOPK have a poor prognosis. Therefore, healthcare providers can optimize breast cancer management using this indicator.

RuO2 electronic structure and lattice strain dual engineering for enhanced acidic oxygen evolution reaction performance.

Developing highly active and durable electrocatalysts for acidic oxygen evolution reaction remains a great challenge due to the sluggish kinetics of the four-electron transfer reaction and severe catalyst dissolution. Here we report an electrochemical lithium intercalation method to improve both the activity and stability of RuO2 for acidic oxygen evolution reaction. The lithium intercalates into the lattice interstices of RuO2, donates electrons and distorts the local structure. Therefore, the Ru valence state is lowered with formation of stable Li-O-Ru local structure, and the Ru-O covalency is weakened, which suppresses the dissolution of Ru, resulting in greatly enhanced durability. Meanwhile, the inherent lattice strain results in the surface structural distortion of LixRuO2 and activates the dangling O atom near the Ru active site as a proton acceptor, which stabilizes the OOH* and dramatically enhances the activity. This work provides an effective strategy to develop highly efficient catalyst towards water splitting.

Structural insights into the HBV receptor and bile acid transporter NTCP.

Around 250 million people are infected with hepatitis B virus (HBV) worldwide1, and 15 million may also carry the satellite virus hepatitis D virus (HDV), which confers even greater risk of severe liver disease2. The HBV receptor has been identified as sodium taurocholate co-transporting polypeptide (NTCP), which interacts directly with the first 48 amino acid residues of the N-myristoylated N-terminal preS1 domain of the viral large protein3. Despite the pressing need for therapeutic agents to counter HBV, the structure of NTCP remains unsolved. This 349-residue protein is closely related to human apical sodium-dependent bile acid transporter (ASBT), another member of the solute carrier family SLC10. Crystal structures have been reported of similar bile acid transporters from bacteria4,5, and these models are believed to resemble closely both NTCP and ASBT. Here we have used cryo-electron microscopy to solve the structure of NTCP bound to an antibody, clearly showing that the transporter has no equivalent of the first transmembrane helix found in other SLC10 proteins, and that the N terminus is exposed on the extracellular face. Comparison of our structure with those of related proteins indicates a common mechanism of bile acid transport, but the NTCP structure displays an additional pocket formed by residues that are known to interact with preS1, presenting new opportunities for structure-based drug design.

Accumulation of polyethylene microplastics induces oxidative stress, microbiome dysbiosis and immunoregulation in crayfish.

Microplastics have become a worldwide pollutant, widely discovered in soil, air and aquatic environment. Microplastics have been found in habitats where crayfish (Procambarus clarkii) cultivated, but the impact of microplastics on crayfish remains unclear. In this study, after 21-day dietary exposure, polyethylene (PE) particles were found to accumulate in intestine, hepatopancreas, gills and hemolymph of crayfish. Furthermore, PE particles can still be detected in these tissues after a 7-day depuration in clean water. PE retained in these tissues caused oxidative stress responses, as indicated by the change of oxidative-stress-related index, such as the increase of H2O2 level and SOD activity. PE exposure also caused hemocytic encapsulation in crayfish hepatopancreas and increase of mucus secretion in intestine. Moreover, PE exposure affected the microbiota balance in crayfish, by reducing the total microbiota abundance and altering the proportions of many bacterial families. Interestingly, results showed that PE exposure led to of lower numbers of hemocytes and declination of phenoloxidase activity. Finally, PE exposure induced the expression of immune-related genes, including transcription factors and antimicrobial peptides. Taken these together, we conclude that PE microplastics exert considerable toxic effects on crayfish and are a potential threat to crayfish aquaculture and consumption. This study provides basic toxicological data toward quantifying and illuminating the impact of PE microplastics on freshwater animals.

Fecal Microbiota Transplantation Ameliorates Active Ulcerative Colitis by Downregulating Pro-inflammatory Cytokines in Mucosa and Serum.

Background: Ulcerative colitis (UC) is a multi-factor disease characterized by alternating remission periods and repeated occurrence. It has been shown that fecal microbiota transplantation (FMT) is an emerging and effective approach for UC treatment. Since most existing studies chose adults as donors for fecal microbiota, we conducted this study to determine the long-term efficacy and safety of the microbiota from young UC patient donors and illustrate its specific physiological effects. Methods: Thirty active UC patients were enrolled and FMT were administered with the first colonoscopy and two subsequent enema/transendoscopic enteral tubing (TET) practical regimens in The First Affiliated Hospital of Anhui Medical University in China. Disease activity and inflammatory biomarkers were assessed 6 weeks/over 1 year after treatment. The occurrence of adverse events was also recorded. The samples from blood and mucosa were collected to detect the changes of inflammatory biomarkers and cytokines. The composition of gut and oral microbiota were also sampled and sequenced to confirm the alteration of microbial composition. Results: Twenty-seven patients completed the treatment, among which 16 (59.3%) achieved efficacious clinical response and 11 (40.7%) clinical remission. Full Mayo score and calprotectin dropped significantly and remained stable over 1 year. FMT also significantly reduced the levels of C-reactive protein (CRP), interleukin-1 beta (IL-1ß), and interleukin-6 (IL-6). The gut microbiota altered significantly with increased bacterial diversity and decreased metabolic diversity in responsive patients. The pro-inflammatory enterobacteria decreased after FMT and the abundance of Collinsella increased. Accordingly, the altered metabolic functions, including antigen synthesis, amino acids metabolism, short chain fatty acid production, and vitamin K synthesis of microbiota, were also corrected by FMT. Conclusion: Fecal microbiota transplantation seems to be safe and effective for active UC patients who are nonresponsive to mesalazine or prednisone in the long-term. FMT could efficiently downregulate pro-inflammatory cytokines to ameliorate the inflammation.

Theoretically Revealed and Experimentally Demonstrated Synergistic Electronic Interaction of CoFe Dual-Metal Sites on N-doped Carbon for Boosting Both Oxygen Reduction and Evolution Reactions.

Heteronuclear double-atom catalysts, unlike single atom catalysts, may change the charge density of active metal sites by introducing another metal single atom, thereby modifying the adsorption energies of reaction intermediates and increasing the catalytic activities. First, density functional theory calculations are used to figure out the best combination by modeling two transition-metal atoms from Fe, Co, and Ni onto N-doped graphene. Generally, Fe and Co sites are highly active for the oxygen reduction reaction (ORR) and the oxygen evolution reaction (OER), respectively. The combination of Co and Fe to form CoFe-N-C not only further improves the Fe's ORR and Co's OER activities but also greatly enhances the Co site's ORR and Fe site's OER activities. Then, we synthesize the CoFe-N-C by a two-step pyrolysis process and find that the CoFe-N-C exhibits exceptional ORR and OER electrocatalytic activities in alkaline media, significantly superior to Fe-N-C and Co-N-C and even commercial catalysts.

Eight-Component Nanoporous High-Entropy Oxides with Low Ru Contents as High-Performance Bifunctional Catalysts in Zn-Air Batteries.

One major challenge in heterogeneous catalysis is to reduce the usage of noble metals while maintaining the overall catalytic stability and efficiency in various chemical environments. In this work, a series of high-entropy catalysts are synthesized by a chemical dealloying method and find the increased entropy effect and non-noble metal contents would facilitate the formation of complete oxides with low crystallinity. Importantly, an optimal eight-component high-entropy oxide (HEO, Al-Ni-Co-Ru-Mo-Cr-Fe-Ti) is identified, which exhibits further enhanced catalytic activity for the oxygen evolution reaction (OER) as compared to the previously reported quinary AlNiCoRuMo and the widely-used commercial RuO2 catalysts, and at the same time similar catalytic activity for the oxygen reduction reaction (ORR) as the commercial Pt/C with a half-wave potential of 0.87 V. Such high-performance bi-functional catalysts, however, only require a half loading amount of Ru as compared to the quinary AlNiCoRuMo, due to the underlying Cr-Fe synergistic effects on tuning the electronic structures at active surface sites, as revealed by the first-principles density functional theory calculations of the authors. The eight-component HEO also demonstrates excellent stability under continuous electrochemical working conditions, suitable for a wide range of applications such as metal-air batteries.

The m6A methyltransferase METTL3 promotes the stemness and malignant progression of breast cancer by mediating m6A modification on SOX2.

PURPOSE: We aimed to uncover the role of METTL3 in stimulating the stemness and progression of breast cancer (BCa) through mediating N6-methyladenosine (m6A) modification on SOX2 mRNA. METHODS: METTL3 levels in 48 paired BCa and adjacent normal ones were examined. Kaplan-Meier method was introduced for assessing the prognostic value of METTL3 in BCa. Regulatory effects of METTL3 on invasive and migratory abilities in MCF-7 cells were evaluated by Transwell assay. Besides, the protein levels of SOX2 and tumor stem cell markers CD133 and CD44 in MCF-7 cells affected by METTL3 were determined by Western blot. In addition, the potential interaction between METTL3 and SOX2 was ascertained through RIP (RNA-Binding Protein Immunoprecipitation) assay. Moreover, the interaction between IGF2BP2 and SOX2 influenced by METTL3 was verified by RIP assay as well. RESULTS: METTL3 was upregulated in BCa tissues, especially in T3-T4 or those accompanied with lymphatic metastasis. BCa patients expressing a high level of METTL3 suffered worse prognosis. Knockdown of METTL3 downregulated protein levels of SOX2, CD133 and CD44 in MCF-7 cells. Moreover, invasive and migratory abilities were attenuated in BCa cells with METTL3 knockdown. Silencing of IGF2BP2 markedly downregulated SOX2. RIP assay confirmed the binding between METTL3 and SOX2 mRNA, and knockdown of METTL3 decreased the enrichment of SOX2 in anti-IGF2BP2. Interestingly, overexpression of SOX2 partially reversed the regulatory effects of downregulated METTL3 on MCF-7 cells. CONCLUSIONS: METTL3 is upregulated in BCa, and it promotes the stemness and malignant progression of BCa through mediating m6A modification on SOX2 mRNA.

Early-stage dynamics of chloride ion-pumping rhodopsin revealed by a femtosecond X-ray laser.

Chloride ion-pumping rhodopsin (ClR) in some marine bacteria utilizes light energy to actively transport Cl- into cells. How the ClR initiates the transport is elusive. Here, we show the dynamics of ion transport observed with time-resolved serial femtosecond (fs) crystallography using the Linac Coherent Light Source. X-ray pulses captured structural changes in ClR upon flash illumination with a 550 nm fs-pumping laser. High-resolution structures for five time points (dark to 100 ps after flashing) reveal complex and coordinated dynamics comprising retinal isomerization, water molecule rearrangement, and conformational changes of various residues. Combining data from time-resolved spectroscopy experiments and molecular dynamics simulations, this study reveals that the chloride ion close to the Schiff base undergoes a dissociation-diffusion process upon light-triggered retinal isomerization.