Placing steroid hormones within the human ABCC3 transporter reveals a compatible amphiphilic substrate-binding pocket.

The human ABC transporter ABCC3 (also known as MRP3) transports a wide spectrum of substrates, including endogenous metabolites and exogenous drugs. Accordingly, it participates in multiple physiological processes and is involved in diverse human diseases such as intrahepatic cholestasis of pregnancy, which is caused by the intracellular accumulation of bile acids and estrogens. Here, we report three cryogenic electron microscopy structures of ABCC3: in the apo-form and in complexed forms bound to either the conjugated sex hormones ß-estradiol 17-(ß-D-glucuronide) and dehydroepiandrosterone sulfate. For both hormones, the steroid nuclei that superimpose against each other occupy the hydrophobic center of the transport cavity, whereas the two conjugation groups are separated and fixed by the hydrophilic patches in two transmembrane domains. Structural analysis combined with site-directed mutagenesis and ATPase activity assays revealed that ABCC3 possesses an amphiphilic substrate-binding pocket able to hold either conjugated hormone in an asymmetric pattern. These data build on consensus features of the substrate-binding pocket of MRPs and provide a structural platform for the rational design of inhibitors.

Structures and organizations of PSI-AcpPCI supercomplexes from red tidal and coral symbiotic photosynthetic dinoflagellates.

Marine photosynthetic dinoflagellates are a group of successful phytoplankton that can form red tides in the ocean and also symbiosis with corals. These features are closely related to the photosynthetic properties of dinoflagellates. We report here three structures of photosystem I (PSI)-chlorophylls (Chls) a/c-peridinin protein complex (PSI-AcpPCI) from two species of dinoflagellates by single-particle cryoelectron microscopy. The crucial PsaA/B subunits of a red tidal dinoflagellate Amphidinium carterae are remarkably smaller and hence losing over 20 pigment-binding sites, whereas its PsaD/F/I/J/L/M/R subunits are larger and coordinate some additional pigment sites compared to other eukaryotic photosynthetic organisms, which may compensate for the smaller PsaA/B subunits. Similar modifications are observed in a coral symbiotic dinoflagellate Symbiodinium species, where two additional core proteins and fewer AcpPCIs are identified in the PSI-AcpPCI supercomplex. The antenna proteins AcpPCIs in dinoflagellates developed some loops and pigment sites as a result to accommodate the changed PSI core, therefore the structures of PSI-AcpPCI supercomplex of dinoflagellates reveal an unusual protein assembly pattern. A huge pigment network comprising Chls a and c and various carotenoids is revealed from the structural analysis, which provides the basis for our deeper understanding of the energy transfer and dissipation within the PSI-AcpPCI supercomplex, as well as the evolution of photosynthetic organisms.

Newcastle disease virus activates diverse signaling pathways via Src to facilitate virus entry into host macrophages.

As an intrinsic cellular mechanism responsible for the internalization of extracellular ligands and membrane components, caveolae-mediated endocytosis (CavME) is also exploited by certain pathogens for endocytic entry [e.g., Newcastle disease virus (NDV) of paramyxovirus]. However, the molecular mechanisms of NDV-induced CavME remain poorly understood. Herein, we demonstrate that sialic acid-containing gangliosides, rather than glycoproteins, were utilized by NDV as receptors to initiate the endocytic entry of NDV into HD11 cells. The binding of NDV to gangliosides induced the activation of a non-receptor tyrosine kinase, Src, leading to the phosphorylation of caveolin-1 (Cav1) and dynamin-2 (Dyn2), which contributed to the endocytic entry of NDV. Moreover, an inoculation of cells with NDV-induced actin cytoskeletal rearrangement through Src to facilitate NDV entry via endocytosis and direct fusion with the plasma membrane. Subsequently, unique members of the Rho GTPases family, RhoA and Cdc42, were activated by NDV in a Src-dependent manner. Further analyses revealed that RhoA and Cdc42 regulated the activities of specific effectors, cofilin and myosin regulatory light chain 2, responsible for actin cytoskeleton rearrangement, through diverse intracellular signaling cascades. Taken together, our results suggest that an inoculation of NDV-induced Src-mediated cellular activation by binding to ganglioside receptors. This process orchestrated NDV endocytic entry by modulating the activities of caveolae-associated Cav1 and Dyn2, as well as specific Rho GTPases and downstream effectors. IMPORTANCE: In general, it is known that the paramyxovirus gains access to host cells through direct penetration at the plasma membrane; however, emerging evidence suggests more complex entry mechanisms for paramyxoviruses. The endocytic entry of Newcastle disease virus (NDV), a representative member of the paramyxovirus family, into multiple types of cells has been recently reported. Herein, we demonstrate the binding of NDV to induce ganglioside-activated Src signaling, which is responsible for the endocytic entry of NDV through caveolae-mediated endocytosis. This process involved Src-dependent activation of the caveolae-associated Cav1 and Dyn2, as well as specific Rho GTPase and downstream effectors, thereby orchestrating the endocytic entry process of NDV. Our findings uncover a novel molecular mechanism of endocytic entry of NDV into host cells and provide novel insight into paramyxovirus mechanisms of entry.

New insights on the photocomplex of Roseiflexus castenholzii revealed from comparisons of native and carotenoid-depleted complexes.

In wild-type phototrophic organisms, carotenoids (Crts) are primarily packed into specific pigment-protein complexes along with (Bacterio)chlorophylls and play important roles in the photosynthesis. Diphenylamine (DPA) inhibits carotenogenesis but not phototrophic growth of anoxygenic phototrophs and eliminates virtually all Crts from photocomplexes. To investigate the effect of Crts on assembly of the reaction center-light-harvesting (RC-LH) complex from the filamentous anoxygenic phototroph Roseiflexus (Rfl.) castenholzii, we generated carotenoidless (Crt-less) RC-LH complexes by growing cells in the presence of DPA. Here, we present cryo-EM structures of the Rfl. castenholzii native and Crt-less RC-LH complexes with resolutions of 2.86 Å and 2.85 Å, respectively. From the high-quality map obtained, several important but previously unresolved details in the Rfl. castenholzii RC-LH structure were determined unambiguously including the assignment and likely function of three small polypeptides, and the content and spatial arrangement of Crts with bacteriochlorophyll molecules. The overall structures of Crt-containing and Crt-less complexes are similar. However, structural comparisons showed that only five Crts remain in complexes from DPA-treated cells and that the subunit X (TMx) flanked on the N-terminal helix of the Cyt-subunit is missing. Based on these results, the function of Crts in the assembly of the Rfl. castenholzii RC-LH complex and the molecular mechanism of quinone exchange is discussed. These structural details provide a fresh look at the photosynthetic apparatus of an evolutionary ancient phototroph as well as new insights into the importance of Crts for proper assembly and functioning of the RC-LH complex.

The immunomodulatory of interleukin-33 in rheumatoid arthritis: A systematic review.

Rheumatoid arthritis (RA) is a systemic chronic autoimmune disease that primarily affects the joints and surrounding soft tissues, characterized by chronic inflammation and proliferation of the synovium. Various immune cells are involved in the pathophysiology of RA. The complex interplay of factors such as chronic inflammation, genetic susceptibility, dysregulation of serum antibody levels, among others, contribute to the complexity of the disease mechanism, disease activity, and treatment of RA. Recently, the cytokine storm leading to increased disease activity in RA has gained significant attention. Interleukin-33 (IL-33), a member of the IL-1 family, plays a crucial role in inflammation and immune regulation. ST2 (suppression of tumorigenicity 2 receptor), the receptor for IL-33, is widely expressed on the surface of various immune cells. When IL-33 binds to its receptor ST2, it activates downstream signaling pathways to exert immunoregulatory effects. In RA, IL-33 regulates the progression of the disease by modulating immune cells such as circulating monocytes, tissue-resident macrophages, synovial fibroblasts, mast cells, dendritic cells, neutrophils, T cells, B cells, endothelial cells, and others. We have summarized and analyzed these findings to elucidate the pathways through which IL-33 regulates RA. Furthermore, IL-33 has been detected in the synovium, serum, and synovial fluid of RA patients. Due to inconsistent research results, we conducted a meta-analysis on the association between serum IL-33, synovial fluid IL-33, and the risk of developing RA in patients. The pooled SMD was 1.29 (95% CI: 1.15-1.44), indicating that IL-33 promotes the onset and pathophysiological progression of RA. Therefore, IL-33 may serve as a biomarker for predicting the risk of developing RA and treatment outcomes. As existing drugs for RA still cannot address drug resistance in some patients, new therapeutic approaches are needed to alleviate the significant burden on RA patients and healthcare systems. In light of this, we analyzed the potential of targeting the IL-33/ST2-related signaling pathway to modulate immune cells associated with RA and alleviate inflammation. We also reviewed IL-33 and RA susceptibility-related single nucleotide polymorphisms, suggesting potential involvement of IL-33 and macrophage-related drug-resistant genes in RA resistance therapy. Our review elucidates the role of IL-33 in the pathophysiology of RA, offering new insights for the treatment of RA.

Decreased RNA-binding protein heterogeneous nuclear ribonucleoprotein U improves multiple myeloma sensitivity to lenalidomide.

Multiple myeloma (MM) is an incurable plasma cell cancer in the bone marrow. Immunomodulatory drugs, such as lenalidomide (LEN) and pomalidomide, are backbone agents in MM treatment, and LEN resistance is commonly seen in the MM clinic. In this study, we presented that heterogeneous nuclear ribonucleoprotein U (hnRNPU) affected MM resistance to LEN via the regulation of target mRNA translation. hnRNPULow MM cells exhibited upregulated CRBN and IKZF1 proteins, stringent IKZF1/3 protein degradation upon LEN addition and increased sensitivity to LEN. RNA pulldown assays and RNA electrophoretic mobility shift assays revealed that hnRNPU bound to the 3'-untranslated region of CRBN and IKZF1 mRNA. A sucrose gradient assay suggested that hnRNPU specifically regulated CRBN and IKZF1 mRNA translation. The competition of hnRNPU binding to its target mRNAs by small RNAs with hnRNPU-binding sites restored MM sensitivity to LEN. hnRNPU function in vivo was confirmed in an immunocompetent MM mouse model constructed by the inoculation of Crbn-humanized murine 5TGM1 cells into CrbnI391V/+ mice. Overall, this study suggests a novel mechanism of LEN sensitivity in which hnRNPU represses CRBN and IKZF1 mRNA translation.

Single-cell sequencing reveals the correlation of aggrephagy signaling and multiple myeloma immune microenvironment composition.

Aggrephagy, a type of autophagy, degrades the aggregation of misfolded protein in cells. However, the role of aggrephagy in multiple myeloma (MM) has not been fully demonstrated. In this study, we first investigated the correlation between aggrephagy signaling, MM immune microenvironment composition and disease prognosis. Single-cell RNA-seq data, including the expression profiles of 12,187 single cells from seven MM bone marrow (BM) and seven healthy BM samples, were analyzed by non-negative matrix factorization for 44 aggrephagy-related genes. Bulk RNA-seq cohorts from the Gene Expression Omnibus database were used to evaluate the prognostic value of aggrephagy-related immune cell subtypes and predict immune checkpoint blockade immunotherapeutic response in MM. Compared with healthy BM, MM BM exhibited different patterns of aggrephagy-related gene expression. In MM BM, macrophages, CD8+ T cells, B cells and natural killer cells could be grouped into four to nine aggrephagy-related subclusters. The signature of aggrephagy signaling molecule expression in the immune cells correlates with the patient's prognosis. Our investigation provides a novel view of aggrephagy signaling in MM tumor microenvironment cells, which might be a prognostic indicator and potential target for MM treatment.

Advances in Drug Delivery Systems for the Treatment of Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a common and catastrophic hematological neoplasm with high mortality rates. Conventional therapies, including chemotherapy, hematopoietic stem cell transplantation (HSCT), immune therapy, and targeted agents, have unsatisfactory outcomes for AML patients due to drug toxicity, off-target effects, drug resistance, drug side effects, and AML relapse and refractoriness. These intrinsic limitations of current treatments have promoted the development and application of nanomedicine for more effective and safer leukemia therapy. In this review, the classification of nanoparticles applied in AML therapy, including liposomes, polymersomes, micelles, dendrimers, and inorganic nanoparticles, is reviewed. In addition, various strategies for enhancing therapeutic targetability in nanomedicine, including the use of conjugating ligands, biomimetic-nanotechnology, and bone marrow targeting, which indicates the potential to reverse drug resistance, are discussed. The application of nanomedicine for assisting immunotherapy is also involved. Finally, the advantages and possible challenges of nanomedicine for the transition from the preclinical phase to the clinical phase are discussed.

Exploring shared decision-making needs in lung cancer screening among high-risk groups and health care providers in China: a qualitative study.

BACKGROUND: The intricate balance between the advantages and risks of low-dose computed tomography (LDCT) impedes the utilization of lung cancer screening (LCS). Guiding shared decision-making (SDM) for well-informed choices regarding LCS is pivotal. There has been a notable increase in research related to SDM. However, these studies possess limitations. For example, they may ignore the identification of decision support and needs from the perspective of health care providers and high-risk groups. Additionally, these studies have not adequately addressed the complete SDM process, including pre-decisional needs, the decision-making process, and post-decision experiences. Furthermore, the East-West divide of SDM has been largely ignored. This study aimed to explore the decisional needs and support for shared decision-making for LCS among health care providers and high-risk groups in China. METHODS: Informed by the Ottawa Decision-Support Framework, we conducted qualitative, face-to-face in-depth interviews to explore shared decision-making among 30 lung cancer high-risk individuals and 9 health care providers. Content analysis was used for data analysis. RESULTS: We identified 4 decisional needs that impair shared decision-making: (1) LCS knowledge deficit; (2) inadequate supportive resources; (3) shared decision-making conceptual bias; and (4) delicate doctor-patient bonds. We identified 3 decision supports: (1) providing information throughout the LCS process; (2) providing shared decision-making decision coaching; and (3) providing decision tools. CONCLUSIONS: This study offers valuable insights into the decisional needs and support required to undergo LCS among high-risk individuals and perspectives from health care providers. Future studies should aim to design interventions that enhance the quality of shared decision-making by offering LCS information, decision tools for LCS, and decision coaching for shared decision-making (e.g., through community nurses). Simultaneously, it is crucial to assess individuals' needs for effective deliberation to prevent conflicts and regrets after arriving at a decision.

Physiology and pharmacological targeting of phase separation.

Liquid-liquid phase separation (LLPS) in biology describes a process by which proteins form membraneless condensates within a cellular compartment when conditions are met, including the concentration and posttranslational modifications of the protein components, the condition of the aqueous solution (pH, ionic strength, pressure, and temperature), and the existence of assisting factors (such as RNAs or other proteins). In these supramolecular liquid droplet-like inclusion bodies, molecules are held together through weak intermolecular and/or intramolecular interactions. With the aid of LLPS, cells can assemble functional sub-units within a given cellular compartment by enriching or excluding specific factors, modulating cellular function, and rapidly responding to environmental or physiological cues. Hence, LLPS is emerging as an important means to regulate biology and physiology. Yet, excessive inclusion body formation by, for instance, higher-than-normal concentrations or mutant forms of the protein components could result in the conversion from dynamic liquid condensates into more rigid gel- or solid-like aggregates, leading to the disruption of the organelle's function followed by the development of human disorders like neurodegenerative diseases. In summary, well-controlled formation and de-formation of LLPS is critical for normal biology and physiology from single cells to individual organisms, whereas abnormal LLPS is involved in the pathophysiology of human diseases. In turn, targeting these aggregates or their formation represents a promising approach in treating diseases driven by abnormal LLPS including those neurodegenerative diseases that lack effective therapies.

Hybrid 2D/3D-quantitative structure-activity relationship studies on the bioactivities and molecular mechanism of antibacterial peptides.

Antimicrobial peptide (AMP) is the polypeptide, which protects the organism avoiding attack from pathogenic bacteria. Studies have shown that there were some antimicrobial peptides with molecular action mechanism involved in crossing the cell membrane without inducing severe membrane collapse, then interacting with cytoplasmic target-nucleic acid, and exerting antibacterial activity by interfacing the transmission of genetic information of pathogenic microorganisms. However, the relationship between the antibacterial activities and peptide structures was still unclear. Therefore, in the present work, a series of AMPs with a sequence of 20 amino acids was extracted from DBAASP database, then, quantitative structure-activity relationship (QSAR) methods were conducted on these peptides. In addition, novel antimicrobial peptides with  stronger antimicrobial activities were designed according to the information originated from the constructed models. Hence, the outcome of this study would lay a solid foundation for the in-silico design and exploration of novel antibacterial peptides with improved activity activities.

Precise Control Light Emission of PVDF-CH3NH3PbBr3-xClx Nanocrystalline Films Using a Cl-(CH3OH)n System.

Methylammonium lead halide perovskites with highly efficient pure-color or white-light generation have gained increasing scientific interest and promote the development of a great commercial opportunity in displays, lighting, and other applications. However, the poor stabilities, lead toxicity, and unfriendly solvents and ligands in the growth process severely restrict their commercial application. Here, we proposed a green method for preparing uniform and stable polymer-encapsulated photoluminescence (PL) tunable CH3NH3PbBr3-xClx NC thin films at room temperature. Utilizing the swelling effect between alcohol compounds and organic polymers and the ionization of NaCl in methanol solution, the anion exchange process can be achieved rapidly within 7 min. Moreover, the PL wavelengths of the CH3NH3PbBr3-xClx NCs films were precisely tuned with steps as fine as 2 nm. Experimental results showed that NaCl dissolved in methanol solution can form Cl-(CH3OH)n, which brings ionized Cl into the polymer-encapsulated CH3NH3PbBr3 NCs film for CH3NH3PbBr3-xClx NCs film growth. Based on the swelling and anion exchange dynamics, a modified NaCl-CH3OH-MABr solution system was developed to trigger CH3NH3PbBr3-xClx NCs film PL emission tuning from 528 to 463 nm with several-fold intensity enhancement. The realization of precisely controlled photoluminescence from the perovskite nanocrystal film would have wide applications in the optical and imaging fields.

Pipette-tip solid-phase extraction coupled with matrix-assisted laser desorption/ionization mass spectrometry enables rapid and high-throughput analysis of antidepressants in rat serum.

Therapeutic drug monitoring is essential for ensuring the efficacy and safety of medications. This study introduces a streamlined approach that combines pipette-tip solid-phase extraction (PT-SPE) with matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), facilitating rapid and high-throughput monitoring of drug concentrations. As a demonstration, this method was applied to the extraction and quantification of antidepressants in serum. Utilizing Zip-Tip C18, the method enabled the extraction of antidepressants from complex biological matrices in less than 2 min, with the subsequent MALDI-MS analysis yielding results in just 1 min. Optimal extraction recoveries were achieved using a sampling solution at pH 9.0 and a 10 µL ethanol desorption solution containing 0.1% phosphoric acid. For MALDI analysis, 2,5-dihydroxybenzoic acid was identified as the most effective matrix for producing the highest signal intensity. The quantification strategy exhibited robust linearities (R2 ≥ 0.997) and satisfactory limits of quantification, ranging from 0.05 to 0.5 µg/mL for a suite of antidepressants. The application for monitoring dynamic concentration changes of antidepressants in rat serum emphasized the method's efficacy. This strategy offers the advantages of high throughput, minimal sample usage, environmental sustainability, and simplicity, providing ideas and a reference basis for the subsequent development of methods for therapeutic drug monitoring.

Systemic meta-analysis: apigenin's effects on lung inflammation and oxidative stress.

OBJECTIVE: This study aimed to investigate the potential anti-inflammatory and antioxidant effects of apigenin in rats with acute lung injury (ALI). We also examined changes in levels of inflammatory and antioxidant factors after apigenin treatment in a rat model of ALI.Methods: We searched several databases, including PubMed, Scopus, EMBASE, Web of Science, ProQuest, and GoogleScholar, to retrieve relevant articles for our systematic review and meta-analysis.Five studies with 226 rat models of ALI were included in this study. We investigated inflammatory factors and oxidative stress with the corresponding 95% confidence interval in three groups: 1. Group1 (control vs. ALI), 2. Group2 (ALI vs. apigenin10), and 3. Group3 (ALI vs. apigenin20). RESULTS: Estimating the correlation and 95% confidence intervals for the inflammatory agents and oxidative stress in the intervention group (ALI), compared with that in the control group, respectively (correlation: 0.194; 95% confidence intervals, 0.101-0.282, p value = .001, z-value= 4.08) and (correlation: 0.099; 95% confidence intervals, 0.016-0.182, p value = .020, z value= 2.325). Estimating the correlation and 95% confidence intervals for the inflammatory agents and oxidative stress in the intervention group (apigenin 10 mg/kg), compared with that in the control group (ALI), respectively (correlation: 0.476; 95% confidence intervals, 0.391-0.553, p value = .001, z-value= 9.678) and (correlation: 0.415; 95% confidence intervals, 0.313-0.508, p value= .001, z-value= 7.349). CONCLUSION: Apigenin may have potential anti-inflammatory and antioxidant effects in rat models of ALI. However, the efficacy of apigenin as a therapeutic strategy requires further investigation through prospective controlled randomized trials.

A specialized spinal circuit for command amplification and directionality during escape behavior.

In vertebrates, action selection often involves higher cognition entailing an evaluative process. However, urgent tasks, such as defensive escape, require an immediate implementation of the directionality of escape trajectory, necessitating local circuits. Here we reveal a specialized spinal circuit for the execution of escape direction in adult zebrafish. A central component of this circuit is a unique class of segmentally repeating cholinergic V2a interneurons expressing the transcription factor Chx10. These interneurons amplify brainstem-initiated escape commands and rapidly deliver the excitation via a feedforward circuit to all fast motor neurons and commissural interneurons to direct the escape maneuver. The information transfer within this circuit relies on fast and reliable axo-axonic synaptic connections, bypassing soma and dendrites. Unilateral ablation of cholinergic V2a interneurons eliminated escape command propagation. Thus, in vertebrates, local spinal circuits can implement directionality of urgent motor actions vital for survival.

Relationship between phthalates exposure, risk of decreased ovarian reserve, and oxidative stress levels.

Phthalates (PAEs), a group of environmental endocrine disruptors, are associated with oxidative stress and have adverse effects on female ovarian reserves. However, this association has been poorly investigated, particularly with respect to clinical evidence. In this study, we provided clinical evidence of a relationship between exposure levels of PAEs, oxidative stress and decreased ovarian reserve (DOR). Firstly, the urinary concentrations of metabolites of PAEs were measured by high performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). The serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and anti-Mullerian hormone (AMH), and the biomarkers of oxidative stress, malondialdehyde (MDA), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC), were determined. Finally, statistical analyses were conducted to describe the relationship between the PAEs exposure, oxidative stress and DOR. We found that the levels of monomethyl phthalate (MMP), monoisobutyl phthalate (MiBP), mono-(2-ethylhexyl) phthalate (MEHP), and mono-(2-ethyl-5-hydroxypentyl) phthalate (MECPP) in the DOR group were significantly higher than those in the control group. There was a significant negative association between AMH and MMP, MiBP levels. and a significant positive association between FSH and MMP levels. PAEs exposure was also associated with a significant increase in MDA levels and decrease in SOD levels. In conclusion, the exposure of PAEs was closely associated with DOR, potentially mediated by oxidative stress pathways; however, small sample size was a limitation in this study.

Multi-objective ecological restoration priority in China: Cost-benefit optimization in different ecological performance regimes based on planetary boundaries.

In the context of the "United Nations Decade on Ecosystem Restoration", optimizing spatiotemporal arrangements for ecological restoration is an important approach to enhancing overall socioecological benefits for sustainable development. However, against the background of ecological degradation caused by the human use of most natural resources at levels that have approached or exceeded the safe and sustainable boundaries of ecosystems, it is key to explain how to optimize ecological restoration by classified management and optimal total benefits. In response to these issues, we combined spatial heterogeneity and temporal dynamics at the national scale in China to construct five ecological performance regimes defined by indicators that use planetary boundaries and ecological pressures which served as the basis for prioritizing ecological restoration areas and implementing zoning control. By integrating habitat conservation, biodiversity, water supply, and restoration cost constraints, seven ecological restoration scenarios were simulated to optimize the spatial layout of ecological restoration projects (ERPs). The results indicated that the provinces with unsustainable freshwater use, climate change, and land use accounted for more than 25%, 66.7%, and 25%, respectively, of the total area. Only 30% of the provinces experienced a decrease in environmental pressure. Based on the ecological performance regimes, ERP sites spanning the past 20 years were identified, and more than 50% of the priority areas were clustered in regime areas with increased ecological stress. As the restoration area targets doubled (40%) from the baseline (20%), a multi-objective scenario presents a trade-off between expanded ERPs in areas with highly beneficial effects and minimal restoration costs. In conclusion, a reasonable classification and management regime is the basis for targeted restoration. Coordinating multiple objectives and costs in ecological restoration is the key to maximizing socio-ecological benefits. Our study offered new perspectives on systematic and sustainable planning for ecological restoration.

Structural insights into the unusual core photocomplex from a triply extremophilic purple bacterium, Halorhodospira halochloris.

Halorhodospira (Hlr.) halochloris is a triply extremophilic phototrophic purple sulfur bacterium, as it is thermophilic, alkaliphilic, and extremely halophilic. The light-harvesting-reaction center (LH1-RC) core complex of this bacterium displays an LH1-Qy transition at 1,016 nm, which is the lowest-energy wavelength absorption among all known phototrophs. Here we report the cryo-EM structure of the LH1-RC at 2.42 Å resolution. The LH1 complex forms a tricyclic ring structure composed of 16 αßγ-polypeptides and one αß-heterodimer around the RC. From the cryo-EM density map, two previously unrecognized integral membrane proteins, referred to as protein G and protein Q, were identified. Both of these proteins are single transmembrane-spanning helices located between the LH1 ring and the RC L-subunit and are absent from the LH1-RC complexes of all other purple bacteria of which the structures have been determined so far. Besides bacteriochlorophyll b molecules (B1020) located on the periplasmic side of the Hlr. halochloris membrane, there are also two arrays of bacteriochlorophyll b molecules (B800 and B820) located on the cytoplasmic side. Only a single copy of a carotenoid (lycopene) was resolved in the Hlr. halochloris LH1-α3ß3 and this was positioned within the complex. The potential quinone channel should be the space between the LH1-α3ß3 that accommodates the single lycopene but does not contain a γ-polypeptide, B800 and B820. Our results provide a structural explanation for the unusual Qy red shift and carotenoid absorption in the Hlr. halochloris spectrum and reveal new insights into photosynthetic mechanisms employed by a species that thrives under the harshest conditions of any phototrophic microorganism known.

[Index of microcirculatory resistance is associated with left ventricular remodeling in patients with acute anterior ST-segment elevation myocardial infarction undergoing emergency primary percutaneous coronary intervention].

OBJECTIVE: To evaluate whether index of microcirculatory resistance (IMR) is associated with left ventricular (LV) remodeling in acute anterior ST elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI). METHODS: This was a single-center retrospective cohort study. The patients with first anterior STEMI who received PPCI from January 2014 to August 2017 in Peking University Third Hospital was enrolled. After PPCI, IMR was measured immediately by using pressure/temperature guidewire. The success rate of IMR measurement was 100%. Also we collected some related clinical data from the medical records and laboratory results. Infarct size [assessed as creatine kinase (CK) peak], echocardiography at baseline and 1 year follow-up were assessed. LV adverse remodeling (LVAR) was defined as ≥20% increase in LV end-diastolic volume (LVEDV). RESULTS: A total of forty-three patients were enrolled, with an average age of (58.7±12.4) years.The patients were divided into two groups as IMR ≤25 and IMR>25 by normal values recommended by previous literature. Compared with IMR ≤25 group, IMR>25 group had a higher percentage of initial thrombolysis in myocardial infraction (TIMI) grade 0 (95.7% vs. 65.0%, P=0.029), higher serum CK peak value [4 090 (383, 15 833)vs. 1 580 (396, 5 583), P=0.004]. The IMR>25 group suffered higher rates of ventricular aneurysm (30.4% vs. 5.0%, P=0.021). There was no difference in LVEDV [(111.0±18.8) mL vs. (115.0±23.6) mL, P=0.503] between the two groups 1 day after MI, but after 1 year, LVEDV in IMR>25 group was significantly higher than in IMR≤25 group [(141.5±33.7) mL vs. (115.9±27.9) mL, P=0.018]. The incidence of LVAR was more significant in IMR>25 group (47.4% vs. 11.8%, P=0.024). Binary Logistics regression showed that IMR [B=0.079, exp(B) (95%CI)=1.082 (1.018－1.149), P=0.011] and serum triglyceride level [B=1.610, exp(B) (95%CI)=5.005 (1.380－18.152), P=0.014] were the predictors of LVAR 1 year after MI. IMR had a good predictive value for LVAR 1 year after MI [area under the curve (AUC)=0.749, P=0.019], IMR>29 was a good cutoff value with sensitivity 81.8% and specificity 68.0%. CONCLUSION: Our study elaborates that immediate measurement of IMR after PPCI in patients with STEMI can reflect the microvascular function.And IMR could be used as a quantitative biomarker to predict LVAR after STEMI.

The distribution of marginal excess cement of implant-supported vented and non-vented zirconia crowns with and without cleaning procedures.

PURPOSE: To investigate the distribution of marginal excess cement in vented and non-vented crowns and evaluate the effect of clinical cleaning procedures on the reduction of excess cement. MATERIALS AND METHODS: Forty models with implant analogs in the position of the right maxillary first molar were divided into four groups (n = 10/group, vented/non-vented crowns with or without cleaning procedures). The abutment finish lines were placed 1 mm below the artificial gingiva buccally, mesially, and distally and at the gingival level palatally. A standardized amount (20 mg) of resin cement was applied in a thin layer to the intaglio surface of zirconia vented and non-vented crowns. The excess cement was removed by a dental explorer in groups with cleaning procedures. The distribution (area and depth) of the marginal excess cement was measured at each quadrant (buccal, mesial, palatal, and distal) for all study samples. The data were analyzed using descriptive and analytical statistics (ɑ = 0.05). RESULTS: The area and depth values of the excess cement in each quadrant in the vented group were significantly smaller than that in the non-vented group, both with and without cleaning (p < 0.001). Cleaning procedures significantly reduced the area of excess cement in both vented and non-vented groups (all, p < 0.001 except for p < 0.05 at the buccal aspect of the vented group). The depth of excess cement in the vented group was significantly decreased with cleaning in the buccal quadrant compared with that without cleaning (p < 0.01). However, the depth of excess cement of the non-vented group was significantly increased with cleaning in all quadrants compared with that without cleaning (all, p < 0.001 except for p < 0.05 at the distal aspect). CONCLUSIONS: Crown venting significantly reduced the area and depth of the marginal excess cement in vitro. Cleaning procedure with a dental explorer significantly reduced the area of marginal excess cement in vitro; however, the excess cement can be pushed deeper in the non-vented group.