Surface segregation of rigid polyarylene ether amidoxime on polyurethane nanofiber into hierarchical membranes as substrate of flexible SERS nanosensor for sulfamethoxazole detection.

Electrospun polymeric nanofibrous membranes are emerging as the promising substrates for preparation of flexible SERS nanosensors due to their intrinsic nanoscale surface roughness, easy scalability as well as rich surface reactivity. Although the nanofiber membranes prepared from high performance thermoplastics exhibit good mechanical stability, the SERS nanosensors based on these substrates normally have lower signal-to-noise ratio because of the interference from background Raman signals of aromatic moieties. Herein, we synthesized an optically transparent polyurethane (PU) and rigid polyarylene ether amidoxime (PEA), which were electrospun into core-shell nanofibers membranes with a "beads-on-web" morphology. Furthermore, the PU-PEA membranes were coated with ultra-thin silver layer and thermally annealed to prepare the flexible SERS nanosensor without any background noises. In addition, the Raman enhancement of SERS nanosensor can be readily improved by tuning of PU-PEA composition, silver thickness as well as thermal annealing temperature. Finally, the optimized SERS nanosensor enables label-free detection of sulfamethoxazole as low as 0.1 nM with a good reproducibility and detection performance in real water sample. Meanwhile, the optimized SERS nanosensor shows long term anti-biofouling capacity. Thanks to its facile fabrication, competitive analytical performance and resistance to biofouling, the current work basically open new way for design of flexible SERS nanosensors for biomedical applications.

Chloroflexus aurantiacus acetyl-CoA carboxylase evolves fused biotin carboxylase and biotin carboxyl carrier protein to complete carboxylation activity.

Acetyl-CoA carboxylases (ACCs) convert acetyl-CoA to malonyl-CoA, a key step in fatty acid biosynthesis and autotrophic carbon fixation pathways. Three functionally distinct components, biotin carboxylase (BC), biotin carboxyl carrier protein (BCCP), and carboxyltransferase (CT), are either separated or partially fused in different combinations, forming heteromeric ACCs. However, an ACC with fused BC-BCCP and separate CT has not been identified, leaving its catalytic mechanism unclear. Here, we identify two BC isoforms (BC1 and BC2) from Chloroflexus aurantiacus, a filamentous anoxygenic phototroph that employs 3-hydroxypropionate (3-HP) bi-cycle rather than Calvin cycle for autotrophic carbon fixation. We reveal that BC1 possesses fused BC and BCCP domains, where BCCP could be biotinylated by E. coli or C. aurantiacus BirA on Lys553 residue. Crystal structures of BC1 and BC2 at 3.2 Å and 3.0 Å resolutions, respectively, further reveal a tetramer of two BC1-BC homodimers, and a BC2 homodimer, all exhibiting similar BC architectures. The two BC1-BC homodimers are connected by an eight-stranded ß-barrel of the partially resolved BCCP domain. Disruption of ß-barrel results in dissociation of the tetramer into dimers in solution and decreased biotin carboxylase activity. Biotinylation of the BCCP domain further promotes BC1 and CTß-CTα interactions to form an enzymatically active ACC, which converts acetyl-CoA to malonyl-CoA in vitro and produces 3-HP via co-expression with a recombinant malonyl-CoA reductase in E. coli cells. This study revealed a heteromeric ACC that evolves fused BC-BCCP but separate CTα and CTß to complete ACC activity.IMPORTANCEAcetyl-CoA carboxylase (ACC) catalyzes the rate-limiting step in fatty acid biosynthesis and autotrophic carbon fixation pathways across a wide range of organisms, making them attractive targets for drug discovery against various infections and diseases. Although structural studies on homomeric ACCs, which consist of a single protein with three subunits, have revealed the "swing domain model" where the biotin carboxyl carrier protein (BCCP) domain translocates between biotin carboxylase (BC) and carboxyltransferase (CT) active sites to facilitate the reaction, our understanding of the subunit composition and catalytic mechanism in heteromeric ACCs remains limited. Here, we identify a novel ACC from an ancient anoxygenic photosynthetic bacterium Chloroflexus aurantiacus, it evolves fused BC and BCCP domain, but separate CT components to form an enzymatically active ACC, which converts acetyl-CoA to malonyl-CoA in vitro and produces 3-hydroxypropionate (3-HP) via co-expression with recombinant malonyl-CoA reductase in E. coli cells. These findings expand the diversity and molecular evolution of heteromeric ACCs and provide a structural basis for potential applications in 3-HP biosynthesis.

Characterization of individual spores of two biological insecticides, Bacillus thuringiensis and Lysinibacillus sphaericus, in response to glutaraldehyde using single-cell optical approaches.

Bacillus thuringiensis (Bt) and Lysinibacillus sphaericus (Ls) are the most widely used microbial insecticides. Both encounter unfavorable environmental factors and pesticides in the field. Here, the responses of Bt and Ls spores to glutaraldehyde were characterized using Raman spectroscopy and differential interference contrast imaging at the single-cell level. Bt spores were more sensitive to glutaraldehyde than Ls spores under prolonged exposure: <1.0% of Bt spores were viable after 10 min of 0.5% (v/v) glutaraldehyde treatment, compared to ~ 20% of Ls spores. The Raman spectra of glutaraldehyde-treated Bt and Ls spores were almost identical to those of untreated spores; however, the germination process of individual spores was significantly altered. The time to onset of germination, the period of rapid Ca2+-2,6-pyridinedicarboxylic acid (CaDPA) release, and the period of cortex hydrolysis of treated Bt spores were significantly longer than those of untreated spores, with dodecylamine germination being particularly affected. Similarly, the germination of treated Ls spores was significantly prolonged, although the prolongation was less than that of Bt spores. Although the interiors of Bt and Ls spores were undamaged and CaDPA did not leak, proteins and structures involved in spore germination could be severely damaged, resulting in slower and significantly prolonged germination. This study provides insights into the impact of glutaraldehyde on bacterial spores at the single cell level and the variability in spore response to glutaraldehyde across species and populations.

Regulating molecular brush structure on cotton textiles for efficient antibacterial properties.

The molecular brush structures have been developed on cotton textiles for long-term and efficient broad-spectrum antimicrobial performances through the cooperation of alkyl-chain and quaternary ammonium sites. Results show that efficient antibacterial performances can be achieved by the regulation of the alkyl chain length and quaternary ammonium sites. The antibacterial efficiency of the optimized molecular brush structure of [3-(N,N-Dimethylamino)propyl]trimethoxysilane with cetyl modification on cotton textiles (CT-DM-16) can reach more than 99 % against both E. coli and S. aureus. Alkyl-chain grafting displayed significantly improvement in the antibacterial activity against S. aureus with (N,N-Diethyl-3-aminopropyl)trimethoxysilane modification on cotton textiles (CT-DE) based materials. The positive N sites and alkyl chains played important roles in the antibacterial process. Proteomic analysis reveals that the contributions of cytoskeleton and membrane-enclosed lumen in differentially expressed proteins have been increased for the S. aureus antibacterial process, confirming the promoted puncture capacity with alkyl-chain grafting. Theoretical calculations indicate that the positive charge of N sites can be enhanced through alkyl-chain grafting, and the possible distortion of the brush structure in application can further increase the positive charge of N sites. Uncovering the regulation mechanism is considered to be important guidance to develop novel and practical antibacterial materials.

MolProphet: A One-Stop, General Purpose, and AI-Based Platform for the Early Stages of Drug Discovery.

Artificial intelligence (AI) is an effective tool to accelerate drug discovery and cut costs in discovery processes. Many successful AI applications are reported in the early stages of small molecule drug discovery. However, most of those applications require a deep understanding of software and hardware, and focus on a single field that implies data normalization and transfer between those applications is still a challenge for normal users. It usually limits the application of AI in drug discovery. Here, based on a series of robust models, we formed a one-stop, general purpose, and AI-based drug discovery platform, MolProphet, to provide complete functionalities in the early stages of small molecule drug discovery, including AI-based target pocket prediction, hit discovery and lead optimization, and compound targeting, as well as abundant analyzing tools to check the results. MolProphet is an accessible and user-friendly web-based platform that is fully designed according to the practices in the drug discovery industry. The molecule screened, generated, or optimized by the MolProphet is purchasable and synthesizable at low cost but with good drug-likeness. More than 400 users from industry and academia have used MolProphet in their work. We hope this platform can provide a powerful solution to assist each normal researcher in drug design and related research areas. It is available for everyone at https://www.molprophet.com/.

Identification of Hub Genes in Liver Hepatocellular Carcinoma Based on Weighted Gene Co-expression Network Analysis.

Liver hepatocellular carcinoma (LIHC) is a malignant cancer with high incidence and poor prognosis. To investigate the correlation between hub genes and progression of LIHC and to provided potential prognostic markers and therapy targets for LIHC. Our study mainly used The Cancer Genome Atlas (TCGA) LIHC database and the gene expression profiles of GSE54236 from the Gene Expression Omnibus (GEO) to explore the differential co-expression genes between LIHC and normal tissues. The differential co-expression genes were extracted by Weighted Gene Co-expression Network Analysis (WGCNA) and differential gene expression analysis methods. The Genetic Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were carried out to annotate the function of differential genes. Then the hub genes were validated using protein-protein interaction (PPI) network. And the expression level and prognostic analysis were performed. The probable associations between the expression of hub genes and both tumor purity and infiltration of immune cells were explored by TIMER. A total of 68 differential co-expression genes were extracted. These genes were mainly enriched in complement activation (biological process), collagen trimer (cellular component), carbohydrate binding and receptor ligand activity (molecular function) and cytokine - cytokine receptor interaction. Then we demonstrated that the 10 hub genes (CFP, CLEC1B, CLEC4G, CLEC4M, FCN2, FCN3, PAMR1 and TIMD4) were weakly expressed in LIHC tissues, the qRT-PCR results of clinical samples showed that six genes were significantly downregulated in LIHC patients compared with adjacent tissues. Worse overall survival (OS) and disease-free survival (DFS) in LIHC patients were associated with the lower expression of CFP, CLEC1B, FCN3 and TIMD4. Ten hub genes had positive association with tumor purity. CFP, CLEC1B, FCN3 and TIMD4 could serve as novel potential molecular targets for prognosis prediction in LIHC.

Preparation and brain targeting effects study of recombinant human ferritin nanoparticles.

Human heavy-chain ferritin is a naturally occurring protein with high stability and multifunctionality in biological systems. This study aims to utilize a prokaryotic expression system to produce recombinant human heavy-chain ferritin nanoparticles and investigate their targeting ability in brain tissue. The human heavy-chain ferritin gene was cloned into the prokaryotic expression vector pET28a and transformed into Escherichia coli BL21 (DE3) competent cells to explore optimal expression conditions. The recombinant protein was then purified to evaluate its immunoreactivity and characteristics. Additionally, the distribution of the administered protein in normal mice and its permeability in an in vitro blood-brain barrier (BBB) model were measured. The results demonstrate that the purified protein can self-assemble extracellularly into nano-cage structures of approximately 10 nm and is recognized by corresponding antibodies. The protein effectively penetrates the blood-brain barrier and exhibits slow clearance in mouse brain tissue, showing excellent permeability in the in vitro BBB model. This study highlights the stable expression of recombinant human heavy-chain ferritin using the Escherichia coli prokaryotic expression system, characterized by favorable nano-cage structures and biological activity. Its exceptional brain tissue targeting and slow metabolism lay an experimental foundation for its application in neuropharmaceutical delivery and vaccine development fields.

An Hsp70 promoter-based mouse for heat shock-induced gene modulation.

Physical therapy is extensively employed in clinical settings. Nevertheless, the absence of suitable animal models has resulted in an incomplete understanding of the in vivo mechanisms and cellular distribution that respond to physical stimuli. The objective of this research was to create a mouse model capable of indicating the cells affected by physical stimuli. In this study, we successfully established a mouse line based on the heat shock protein 70 (Hsp70) promoter, wherein the expression of CreERT2 can be induced by physical stimuli. Following stimulation of the mouse tail, ear, or cultured calvarias with heat shock (generated by heating, ultrasound, or laser), a distinct Cre-mediated excision was observed in cells stimulated by these physical factors with minimal occurrence of leaky reporter expression. The application of heat shock to Hsp70-CreERT2; FGFR2-P253R double transgenic mice or Hsp70-CreERT2 mice infected with AAV-BMP4 at calvarias induced the activation of Cre-dependent mutant FGFR2-P253R or BMP4 respectively, thereby facilitating the premature closure of cranial sutures or the repair of calvarial defects. This novel mouse line holds significant potential for investigating the underlying mechanisms of physical therapy, tissue repair and regeneration, lineage tracing, and targeted modulation of gene expression of cells in local tissue stimulated by physical factor at the interested time points. KEY MESSAGES: In the study, an Hsp70-CreERT2 transgenic mouse was generated for heat shock-induced gene modulation. Heat shock, ultrasound, and laser stimulation effectively activated Cre expression in Hsp70-CreERT2; reporter mice, which leads to deletion of floxed DNA sequence in the tail, ear, and cultured calvaria tissues of mice. Local laser stimuli on cultured calvarias effectively induce Fgfr2-P253R expression in Hsp70-mTmG-Fgfr2-P253R mice and result in accelerated premature closure of cranial suture. Heat shock activated AAV9-FLEX-BMP4 expression and subsequently promoted the repair of calvarial defect of Hsp70-CreERT2; Rosa26-mTmG mice.

How does physical activity improve adolescent resilience? Serial indirect effects via self-efficacy and basic psychological needs.

Background: Resilience is vital for improving mental health and well-being during adolescence, which is an important yet vulnerable period. Previous research has indicated that physical activity enhances individual resilience. However, limited studies have examined underlying psychological mechanisms between them. The current study aimed to investigate the effect of physical activity on adolescent resilience via self-efficacy and basic psychological needs. Methods: A cross-sectional survey was conducted with 1,732 high school students aged 16 to 20 years old (mean age: 16.51 ± 0.77 years), with nearly equal number of boys (47.63%) and girls (52.37%). They each completed the Physical Exercise Questionnaire, Basic Psychological Needs in Exercise Scale, General Self-Efficacy Scale, and Resilience Scale, respectively. A serial indirect model was constructed to examine how physical activity influences resilience. Results: Structural equation model analysis revealed that physical activity significantly and directly predicted resilience. When self-efficacy and basic psychological needs were included in the model, both direct and indirect effects were observed. Specifically, the positive relationship between physical activity and resilience was partially mediated by self-efficacy and basic psychological needs. In addition, basic psychological needs and self-efficacy were found to serially mediate the direct relathonship between physical activity and resilience. Conclusions: The present study provides novel theoretical insights into sports psychology by establishing a link between basic psychological needs and self-efficacy. The findings have implications for school administrators and physical education instructors in designing targeted interventions to promote adolescent resilience. These interventions may involve creating supportive environment conductive to fulfilling students' basic psychological needs, implementing strategies to enhance self-efficacy beliefs, and providing opportunities for skill development and mastery experiences in sports and physical activities.

Evaluating the efficacy and safety of oral triple sequential combination therapy for treating patients with pulmonary arterial hypertension: A multicenter retrospective study.

This study aimed to evaluate the effectiveness and safety of an oral sequential triple combination therapy with selexipag after dual combination therapy with endothelin receptor antagonist (ERA) and phosphodiesterase-5 inhibitor (PDE5I)/riociguat in pulmonary arterial hypertension (PAH) patients. A total of 192 PAH patients from 10 centers had received oral sequential selexipag therapy after being on dual-combination therapy with ERA and PDE5i/riociguat for a minimum of 3 months. Clinical data were collected at baseline and after 6 months of treatment. The study analyzed the event-free survival at 6 months and all-cause death over 2 years. At baseline, the distribution of patients among the risk groups was as follows: 22 in the low-risk group, 35 in the intermediate-low-risk group, 91 in the intermediate-high-risk group, and 44 in the high-risk group. After 6 months of treatment, the oral sequential triple combination therapy resulted in reduced NT-proBNP levels (media from 1604 to 678 pg/mL), a decline in the percentage of WHO-FC III/IV (from 79.2% to 60.4%), an increased in the 6MWD (from 325 ± 147 to 378 ± 143 m) and a rise in the percentage of patients with three low-risk criteria (from 5.7% to 13.5%). Among the low-risk group, there was an improvement in the right heart remodeling, marked by a decrease in right atrium area and eccentricity index. The intermediate-low-risk group exhibited significant enhancements in WHO-FC and tricuspid annular plane systolic excursion. For those in the intermediate-high and high-risk groups, there were marked improvements in activity tolerance, as reflected by WHO-FC and 6MWD. The event-free survival rate at 6 months stood at 88%. Over the long-term follow-up, the survival rates at 1 and 2 years were 86.5% and 86.0%, respectively. In conclusion, the oral sequential triple combination therapy enhanced both exercise capacity and cardiac remodeling across PAH patients of different risk stratifications.

An injectable thermosensitive hyaluronic acid/pluronic F-127 hydrogel for deep penetration and combination therapy of frozen shoulder.

Frozen shoulder (FS) is a common and progressive shoulder disorder that causes glenohumeral joint stiffness, characterized by inflammation and fibrosis. The treatment options are quite limited, and the therapeutic response is hindered by the fibrous membrane formed by excessive collagen and the rapid removal by synovial fluid. To address these challenges, we designed a hyaluronic acid/Pluronic F-127 (HP)-based injectable thermosensitive hydrogel as a drug carrier loaded with dexamethasone and collagenase (HPDC). We screened for an optimal HP hydrogel that can sustain drug release for approximately 10 days both in vitro and in vivo. In the meanwhile, we found that HP hydrogel could inhibit the proliferation and diminish the adhesion capacity of rat synovial cells induced by transforming growth factor-ß1. Furthermore, using an established immobilization rat model of FS, intra-articular injection of HPDC significantly improved joint range of motion compared to medication alone. Relying on sustained drug release, the accumulated collagen fibers were degraded by collagenase to promote the deep delivery of dexamethasone. These findings showed a positive combined treatment effect of HPDC, providing a novel idea for the comprehensive treatment of FS.

NIPBL-mediated RAD21 facilitates tumorigenicity by the PI3K pathway in non-small-cell lung cancer.

It is urgent to identify novel early diagnostic markers and therapeutic targets for non-small-cell lung cancer (NSCLC), which accounts for 85% of lung cancer cases and has a 5-year survival rate of 4-17%. Here, chromatin immunoprecipitation (ChIP) was used to identify DNA‒protein interactions, RNA methylation was determined by methylated RNA immunoprecipitation (MeRIP), RNA stability was tested by an RNA decay assay. We showed that RAD21, a member of the cohesin complex, is upregulated in NSCLC tissues and cell lines and found to be an independent prognostic factor for overall survival (OS) of NSCLC patients. Mechanistically, the cohesin loading factor Nipped-B-Like Protein (NIPBL) promoted RAD21 gene transcription by enhancing histone H3 lysine 27 (H3K27) demethylation via recruiting lysine demethylase 6B (KDM6B) to the RAD21 gene promoter. RAD21 enhanced phosphatidylinositol 3-kinase (PI3K) gene transcription, and NIPBL reversed the effect of enhancer of zeste 2; catalytic subunit of polycomb repressive complex 2 (EZH2) on RAD21-mediated PI3K gene transcription by disrupting the association between EZH2 and RAD21. Moreover, NIPBL level was increased by stabilization of its transcripts through mRNA methylation. These findings highlight the oncogenic role of RAD21 in NSCLC and suggest its use as a potential diagnostic marker and therapeutic target for NSCLC.

Impact of different sequential triple oral combination therapies based selexipag on outcomes in pulmonary arterial hypertension.

BACKGROUND: While the GRIPHON study and others have confirmed the efficacy and safety of selexipag with single, dual, and initial triple combination therapy for patients with pulmonary arterial hypertension (PAH), multicenters studies concerning diverse triple oral combination therapies based on selexipag are limited. HYPOTHESIS: This study was conducted to evaluate the effects of various sequential triple oral combination therapies on PAH outcomes. METHODS: A retrospective study was carried out involving 192 patients from 10 centers, who were receiving sequential triple oral combination therapy consisting of an endothelin receptor antagonist (ERA), a phosphodiesterase 5 inhibitor (PDE5i)/riociguat and selexipag. Clinical parameters, event-free survival, and all-cause survival were assessed and analyzed at baseline and posttreatment. RESULTS: Among the 192 patients, 37 were treated with ERA + riociguat + selexipag, and 155 patients received ERA + PDE5i + selexipag. Both sequential triple oral combination therapies improved the World Health Organization functional class and raised the count of low-risk parameters. As a result of the larger patients' population in the ERA + PDE5i + selexipag group, these individuals exhibited significant increases in 6-minute walking distance (6MWD), pulmonary arterial systolic pressure, pulmonary arterial pressure, right ventricle, and eccentricity index, and significant decreases in N-terminal probrain natriuretic peptide after 6 months of treatment. Nevertheless, both sequential triple oral combination therapy groups demonstrated similar shifts in these clinical parameters between baseline and 6 months. Baseline 6MWD and mean pulmonary arterial pressure were independent predictors of survival in patients undergoing ERA + PDE5i + selexipag therapy. Importantly, no significant differences were found in 6-month event-free survival and all-cause survival between two groups. CONCLUSIONS: Different oral sequential triple combination therapies based on selexipag could comparably improve outcomes in patients with PAH.

The Antioxidant Salidroside Ameliorates the Quality of Postovulatory Aged Oocyte and Embryo Development in Mice.

Postovulatory aging is known to impair the oocyte quality and embryo development due to oxidative stress in many different animal models, which reduces the success rate or pregnancy rate in human assisted reproductive technology (ART) and livestock timed artificial insemination (TAI), respectively. Salidroside (SAL), a phenylpropanoid glycoside, has been shown to exert antioxidant and antitumor effects. This study aimed to investigate whether SAL supplementation could delay the postovulatory oocyte aging process by alleviating oxidative stress. Here, we show that SAL supplementation decreases the malformation rate and recovers mitochondrial dysfunction including mitochondrial distribution, mitochondrial membrane potential (ΔΨ) and ATP content in aged oocytes. In addition, SAL treatment alleviates postovulatory aging-caused oxidative stress such as higher reactive oxygen species (ROS) level, lower glutathione (GSH) content and a reduced expression of antioxidant-related genes. Moreover, the cytoplasmic calcium ([Ca2+]c) and mitochondrial calcium ([Ca2+]mt) of SAL-treated oocytes return to normal levels. Notably, SAL suppresses the aging-induced DNA damage, early apoptosis and improves spindle assembly in aged oocytes, ultimately elevating the embryo developmental rates and embryo quality. Finally, the RNA-seq and confirmatory experience showed that SAL promotes protective autophagy in aged oocytes by activating the MAPK pathway. Taken together, our research suggests that supplementing SAL is an effective and feasible method for preventing postovulatory aging and preserving the oocyte quality, which potentially contributes to improving the successful rate of ART or TAI.

Sirt6 ablation in the liver causes fatty liver that increases cancer risky by upregulating Serpina12.

Non-alcoholic fatty liver disease is a chronic liver abnormality that exhibits high variability and can lead to liver cancer in advanced stages. Hepatic ablation of SIRT6 results in fatty liver disease, yet the potential mechanism of SIRT6 deficiency, particularly in relation to downstream mediators for NAFLD, remains elusive. Here we identify Serpina12 as a key gene regulated by Sirt6 that plays a crucial function in energy homeostasis. Specifically, Sirt6 suppresses Serpina12 expression through histone deacetylation at its promoter region, after which the transcription factor, Cebpα, binds to and regulates its expression. Sirt6 deficiency results in an increased expression of Serpina12 in hepatocytes, which enhances insulin signaling and promotes lipid accumulation. Importantly, CRISPR-Cas9 mediated Serpina12 knockout in the liver ameliorated fatty liver disease caused by Sirt6 ablation. Finally, we demonstrate that Sirt6 functions as a tumor suppressor in the liver, and consequently, deletion of Sirt6 in the liver leads to not only the spontaneous development of tumors but also enhanced tumorigenesis in response to DEN treatment or under conditions of obesity.

Cryo-EM structure of HQNO-bound Alternative Complex III from the anoxygenic phototrophic bacterium Chloroflexus aurantiacus.

Alternative complex III (ACIII) couples quinol oxidation and electron acceptor reduction with potential transmembrane proton translocation. It is compositionally and structurally different from the cytochrome bc1/b6f complexes, but functionally replaces these enzymes in the photosynthetic and/or respiratory electron transport chains (ETCs) of many bacteria. However, the true compositions and architectures of ACIIIs remain unclear, as do their structural and functional relevance in mediating the ETCs. We here determined cryogenic electron microscopy structures of photosynthetic ACIII isolated from Chloroflexus aurantiacus (CaACIIIp), in apo-form and in complexed form bound to a menadiol analog 2-heptyl-4-hydroxyquinoline-N-oxide (HQNO). Besides six canonical subunits (ActABCDEF), the structures revealed conformations of two previously unresolved subunits, ActG and I, which contributed to the complex stability. We also elucidated the structural basis of menaquinol oxidation and subsequent electron transfer along the [3Fe-4S]-6 hemes wire to its periplasmic electron acceptors, using electron paramagnetic resonance (EPR), spectroelectrochemistry, enzymatic analyses and molecular dynamics (MD) simulations. A unique insertion loop in ActE was shown to function in determining the binding specificity of CaACIIIp for downstream electron acceptors. This study broadens our understanding of the structural diversity and molecular evolution of ACIIIs, enabling further investigation of the (mena)quinol oxidoreductases evolved coupling mechanism in bacterial energy conservation.

A More Efficient Method for Preparing a MIP-CQDs/ZnO1-x Photodegradant with Highly Selective Adsorption and Photocatalytic Properties.

The application of semiconductor photocatalysts in wastewater treatment always has a drawback, which is the lack of selectivity for pollutants, but molecular imprinting technology (MIT) is a remarkable method for preparing highly selective adsorbents for low concentration target pollutants. Up to now, the research of molecular imprinting materials has mainly focused on organic polymers, and there has been little research on inorganic molecular imprinting materials. In the present work, we introduced carbon quantum dots (CQDs) into the flower-like hierarchical ZnO to prepare photocatalysts CQDs/ZnO. Further, with ciprofloxacin (CIP) as the template molecule, a molecular imprinting material MIP-CQDs/ZnO1-x was prepared by introducing both oxygen vacancies and imprinted cavities into CQDs/ZnO by the hydrothermal calcination method. It can not only increase the concentration of oxygen vacancies and broaden the light absorption range of zinc oxide without changing the crystal form of ZnO but also make it have the characteristics of preferential adsorption and degradation of CIP during the degradation process. Under the synergistic effect of CQDs, oxygen vacancies, and molecularly imprinted cavities, the molecularly imprinted material exhibits excellent photocatalytic and selective adsorption performance.

Sialic Acid-Functionalized Pyroptosis Nanotuner for Epigenetic Regulation and Enhanced Cancer Immunotherapy.

The efficacy of immune checkpoint blockade (ICB) in promoting an immune response against tumors still encounters challenges such as low response rates and off-target effects. Pyroptosis, an immunogenic cell death (ICD) mechanism, holds the potential to overcome the limitations of ICB by activating and recruiting immune cells. However, the expression of the pyroptosis-related protein Gasdermin-E(GSDME) in some tumors is limited due to mRNA methylation. To overcome this obstacle, sialic acid-functionalized liposomes coloaded with decitabine, a demethylation drug, and triclabendazole, a pyroptosis-inducing drug are developed. This nanosystem primarily accumulates at tumor sites via sialic acid and the Siglec receptor, elevating liposome accumulation in tumors up to 3.84-fold at 24 h and leading to the upregulation of pyroptosis-related proteins and caspase-3/GSDME-dependent pyroptosis. Consequently, it facilitates the infiltration of CD8+ T cells into the tumor microenvironment and enhances the efficacy of ICB therapy. The tumor inhibition rate of the treatment group is 89.1% at 21 days. This study highlights the potential of sialic acid-functionalized pyroptosis nanotuners as a promising approach for improving the efficacy of ICB therapy in tumors with low GSDME expression through epigenetic alteration and ICD.

A cytochrome c551 mediates the cyclic electron transport chain of the anoxygenic phototrophic bacterium Roseiflexus castenholzii.

Roseiflexus castenholzii is a gram-negative filamentous phototrophic bacterium that carries out anoxygenic photosynthesis through a cyclic electron transport chain (ETC). The ETC is composed of a reaction center (RC)-light-harvesting (LH) complex (rcRC-LH); an alternative complex III (rcACIII), which functionally replaces the cytochrome bc1/b6f complex; and the periplasmic electron acceptor auracyanin (rcAc). Although compositionally and structurally different from the bc1/b6f complex, rcACIII plays similar essential roles in oxidizing menaquinol and transferring electrons to the rcAc. However, rcACIII-mediated electron transfer (which includes both an intraprotein route and a downstream route) has not been clearly elucidated, nor have the details of cyclic ETC. Here, we identify a previously unknown monoheme cytochrome c (cyt c551) as a novel periplasmic electron acceptor of rcACIII. It reduces the light-excited rcRC-LH to complete a cyclic ETC. We also reveal the molecular mechanisms involved in the ETC using electron paramagnetic resonance (EPR), spectroelectrochemistry, and enzymatic and structural analyses. We find that electrons released from rcACIII-oxidized menaquinol are transferred to two alternative periplasmic electron acceptors (rcAc and cyt c551), which eventually reduce the rcRC to form the complete cyclic ETC. This work serves as a foundation for further studies of ACIII-mediated electron transfer in anoxygenic photosynthesis and broadens our understanding of the diversity and molecular evolution of prokaryotic ETCs.