Evaluating complementaries among urban water, energy, infrastructure, and social Sustainable Development Goals in China.

Urban areas' performance in water, energy, infrastructure, and socio-economic sectors is intertwined and measurable through Sustainable Development Goals (SDGs) 6-13. Effective synergy among these is critical for sustainability. This study constructs an indicator framework that reflects progress towards these urban SDGs in China. Findings indicate underperformance in SDGs 8-11, suggesting the need for transformative actions. Through network analysis, the research reveals complementarities among these SDGs. Notably, the SDG space divides into socio-economic and ecological clusters, with SDG 6 (Clean Water and Sanitation) central to both. Additionally, SDG 8 (Decent Work and Economic Growth) and SDG 9 (Industry, Innovation, and Infrastructure) act as bridges, while greater synergies exist between SDG 12 (Responsible Consumption and Production) and SDG 13 (Climate Action). An in-depth view at the indicator-level shows a core-periphery structure, emphasizing indicators like SDG 6.2 (Wastewater Treatment Rate) and SDG 6.6 (Recycled Water Production Capacity per capita) as pivotal. This study confirms the urban SDG space's stability and predictiveness, underscoring its value in steering well-aligned policy decisions for sustainable growth.

Genome-wide CRISPR-Cas9 knockout screens identify DNMT1 as a druggable dependency in sonic hedgehog medulloblastoma.

Sonic hedgehog subgroup of medulloblastoma (SHH-MB) is characterized by aberrant activation of the SHH signaling pathway. An inhibition of the positive SHH regulator Smoothened (SMO) has demonstrated promising clinical efficacy. Yet, primary and acquired resistance to SMO inhibitors limit their efficacy. An understanding of underlying molecular mechanisms of resistance to therapy is warranted to bridge this unmet need. Here, we make use of genome-wide CRISPR-Cas9 knockout screens in murine SMB21 and human DAOY cells, in order to unravel genetic dependencies and drug-related genetic interactors that could serve as alternative therapeutic targets for SHH-MB. Our screens reinforce SMB21 cells as a faithful model system for SHH-MB, as opposed to DAOY cells, and identify members of the epigenetic machinery including DNA methyltransferase 1 (DNMT1) as druggable targets in SHH-dependent tumors. We show that Dnmt1 plays a crucial role in normal murine cerebellar development and is required for SHH-MB growth in vivo. Additionally, DNMT1 pharmacological inhibition alone and in combination with SMO inhibition effectively inhibits tumor growth in murine and human SHH-MB cell models and prolongs survival of SHH-MB mouse models by inhibiting SHH signaling output downstream of SMO. In conclusion, our data highlight the potential of inhibiting epigenetic regulators as a novel therapeutic avenue in SMO-inhibitor sensitive as well as resistant SHH-MBs.

Janus structural TaON/Graphene-like carbon dual-supported Pt electrocatalyst enables efficient oxygen reduction reaction.

Developing carbon-supported Pt-based electrocatalysts with high activity and long-durability for the oxygen reduction reaction (ORR) is an enormous challenge for their commercial applications due to the corrosion of carbon supports in acid/alkaline solution at high potential. In this work, a Janus structural TaON/graphene-like carbon (GLC) was synthesized via an in-situ molecular selfassembly strategy, which was used as a dual-carrier for platinum (Pt). The as-obtained Pt/TaON/GLC presents high half-wave potential (0.94 V vs. RHE), excellent mass (1.48 A mgPt-1) and specific (1.75 mA cmPt-2) activities at 0.9 V, and superior long-term durability with a minimal loss (8.0 %) of mass activity after 10,000 cycles in alkaline solution, outperforming those of Pt/C and other catalysts. The structural characterizations and density functional theory (DFT) calculations indicate that the Pt/TaON/GLC catalyst exhibits the maximum synergies, including enhanced interfacial electron density, improved charge transfer, enhanced O2 adsorption, andsuperimposed OO cleavage. This work shows a potential strategy for preparing the high-active and long-durable Pt-based electrocatalyst by synergism-promoted interface engineering.

Human movement strategies in uncertain environments: A synergy-based approach to the stability-agility tradeoff.

Humans frequently prepare for agile movements by decreasing stability. This facilitates transitions between movements but increases vulnerability to external disruptions. Therefore, humans might weigh the risk of disruption against the gain in agility and scale their stability to the likelihood of having to perform an agility-demanding action. We used the theory of motor synergies to investigate how humans manage this stability-agility tradeoff under uncertainty. This theory has long quantified stability using the synergy index, and reduction in stability before movement transitions using anticipatory synergy adjustment (ASA). However, the impact of uncertainty - whether a quick action should be executed or inhibited - on ASA is unknown. Furthermore, the impact of ASA on execution and inhibition of the action is unclear. We combined multi-finger, isometric force production with the go/no-go paradigm. Thirty participants performed constant force (no-go task), rapid force pulse (go task), and randomized go and no-go trials (go/no-go task) in response to visual cues. We measured the pre-cue finger forces and computed ASA using the uncontrolled manifold method and quantified the spatio-temporal features of the force after the visual cue. We expected ASA in both go/no-go and go tasks, but larger ASA for the latter. Surprisingly, we observed ASA only for the go task. For the go/no-go task, 53% of participants increased stability before the cue. The high stability hindered performance, leading to increased errors in no-go trials and lower peak forces in go trials. These results align with the stability-agility tradeoff. It is puzzling why some participants increased stability even though 80% of the trials demanded agility. This study indicates that individual differences in the effect of task uncertainty and motor inhibition on ASA is unexplored in motor synergy theory and presents a method for further development.

Environment-responsive dopamine nanoplatform for tumor synergistic therapy.

Nanoparticle-based photothermal therapy (PTT) has emerged as a promising approach in tumor treatment due to its high selectivity and low invasiveness. However, the penetration of near-infrared light (NIR) is limited, leading it fails to induce damage to the deep-seated tumor cells within the tumor tissue. Additionally, inefficient uptake of photothermal nanoparticles by tumor cells results in suboptimal outcomes for PTT. In this study, we utilized the adhesive properties of photothermal material, polydopamine (PDA), which can successfully load the photosensitizer indocyanine green (ICG) and chemotherapeutic drug doxorubicin (DOX) to achieve photothermal and chemotherapy synergy treatment (PDA/DOX&ICG), aiming to compensate the defects of single tumor treatment. To extending the blood circulation time of PDA/DOX&ICG nanoparticles, evading clearance by the body immune system and achieving targeted delivery to tumor tissues, a protective envelopment was created using erythrocyte membranes modified with folate acid (FA-EM). After reaching the tumor tissue, the obtained FA-EM@PDA/DOX&ICG nanoparticles can specific bind with folate acid receptors on the surface of tumor cells, which can improve the uptake behavior of FA-EM@PDA/DOX&ICG nanoparticles by tumor cells, and leading to the release of loaded DOX and ICG in response to the unique tumor microenvironment. ICG, as a typical photosensitizer, significantly enhances the photothermal conversion performance of FA-EM@PDA/DOX&ICG nanoparticles, thus inducing tumor cells damage. In vitro and in vivo experimental results demonstrated that the coordinated NIR treatment with FA-EM@PDA/DOX&ICG not only effectively inhibits tumor growth, but also exhibits superior biocompatibility, effectively mitigating DOX-induced tissue damage.

Dynamic measurement for the impact of project portfolio synergy.

Measuring the impact of project portfolio synergy (PPSI) is crucial for making informed decisions to improve the strategic realization of a project portfolio. However, the literature has failed to measure PPSI effectively from the perspective of project element flow and to explore the differences in synergy relationships between homogeneous and heterogeneous projects. Consequently, this study proposes a framework for measuring PPSI from the perspective of project element flow. First, based on analyzing the synergistic relationship between projects, the corresponding project element datum quantity is determined according to the different types of element flow forms. Second, the synergy degree between homogeneous and heterogeneous projects is quantified through project similarity and correlation. Third, a dynamic measurement model is constructed using System Dynamics to solve the complex interactive feedback and dynamics in the PPSI measurement system. Finally, the framework is demonstrated and validated by a numerical example of project management in Xi'an, Shaanxi Province. The results indicate that the model can effectively measure PPSI and identify the key factors generating it. In implementing the portfolio, managers must focus on sharing and integrating newly developed technologies and information, thus facilitating the generation of PPSI. This study extends the boundary of project portfolio synergy theory and contributes to the literature on measuring PPSI by focusing on the elements flow within portfolios. Additionally, the model provides an effective tool for managers to forecast PPSI and determine appropriate optimization strategies.

Constructing MXene-based mixed-dimensional structure with multiple interfaces to optimize dielectric-magnetic synergistic effect for effective electromagnetic wave absorption.

Exploring efficient microwave absorbing materials (MAMs) which could convert electromagnetic (EM) energy into thermal energy represents an approbatory vision to reducing EM radiation and interference. Designing of mixed-dimensional structure with multiple interfaces represents the available target to investigate an ideal MAMs, which maximizes the superiority of mixed-dimensional structure in electromagnetic wave absorption (EMWA). Herein, we take full advantage of multiple interfaces engineering of MXene for optimizing the impedance matching to improve EMWA, MXene-based mixed-dimensional structure was designed by incorporating three-dimensional Fe3C@Carbon layers coated zero-dimensional Fe3O4 nanoparticles (NPs) supported two-dimensional MXene nanosheets (MXene/Fe3O4@Fe3C@Carbon, MFC). The Fe3O4@Fe3C@C with Core@shell structure arrests the essentially self-restacked of MXene and provides various attenuation mechanisms for the incident electromagnetic waves (EMWs). By regulating the carbonization temperature, the MFC exhibits enhanced EMWA property which is attributed to the characteristic structure and optimized dielectric-magnetic synergy effect. The minimum reflection loss (RLmin) value of MFC can reach to -64.3 dB with a matching thickness of 1.73 mm. Otherwise, the maximum effective absorption bandwidth (EAB) (RLmin < -10 dB) reaches 6.42 GHz at only 1.5 mm. Thus, our study refers a novel-fire enlighten to develop excellent mixed-dimensional microwave absorbent based on MXene.

Physicochemical, structural and functional properties of pomelo peel pectin extracted by combination of pulsed electric field and cellulase hydrolysis.

In this study, pectin extracted from pomelo peel was investigated using three different combination methods of pulsed electric field (PEF) and cellulase. Three action sequences were performed, including PEF treatment followed by enzymatic hydrolysis, enzymatic hydrolysis followed by PEF treatment, and enzymatic hydrolysis simultaneously treated by PEF. The three corresponding pectins were namely PEP, EPP and SP. The physiochemical, molecular structural and functional properties of the three pectins were determined. The results showed that PEP had excellent physiochemical properties, with the highest yield (12.08 %), total sugar (80.17 %) and total phenol content (38.20 %). The monosaccharide composition and FT-IR analysis indicated that the three pectins were similar. The molecular weights of PEP, EPP and SP were 51.13, 88.51 and 40.00 kDa, respectively. PEP showed the best gel properties, emulsification stability and antioxidant capacity among the three products, due to its high galacturonic acid and total phenol content, appropriate protein and low molecular weight. The mechanism of PEF-assisted cellulase hydrolysis of pomelo peel was also revealed by SEM analysis. These results suggested that PEF pretreatment was the best method, which not only improved the efficiency of enzymatic extraction, but also reduced resource waste and increased financial benefits.

Synergistic Efficacy of CDK4/6 Inhibitor Abemaciclib and HDAC Inhibitor Panobinostat in Pancreatic Cancer Cells.

The current 5-year survival rate of pancreatic cancer is about 12%, making it one of the deadliest malignancies. The rapid metastasis, acquired drug resistance, and poor patient prognosis necessitate better therapeutic strategies for pancreatic ductal adenocarcinoma (PDAC). Multiple studies show that combining chemotherapeutics for solid tumors has been successful. Targeting two distinct emerging hallmarks, such as non-mutational epigenetic changes by panobinostat (Pan) and delayed cell cycle progression by abemaciclib (Abe), inhibits pancreatic cancer growth. HDAC and CDK4/6 inhibitors are effective but are prone to drug resistance and failure as single agents. Therefore, we hypothesized that combining Abe and Pan could synergistically and lethally affect PDAC survival and proliferation. Multiple cell-based assays, enzymatic activity experiments, and flow cytometry experiments were performed to determine the effects of Abe, Pan, and their combination on PDAC cells and human dermal fibroblasts. Western blotting was used to determine the expression of cell cycle, epigenetic, and apoptosis markers. The Abe-Pan combination exhibited excellent efficacy and produced synergistic effects, altering the expression of cell cycle proteins and epigenetic markers. Pan, alone and in combination with Abe, caused apoptosis in pancreatic cancer cells. Abe-Pan co-treatment showed relative safety in normal human dermal fibroblasts. Our novel combination treatment of Abe and Pan shows synergistic effects on PDAC cells. The combination induces apoptosis, shows relative safety, and merits further investigation due to its therapeutic potential in the treatment of PDAC.

Adsorptive-Photocatalytic Composites of α-Ferrous Oxalate Supported on Activated Carbon for the Removal of Phenol under Visible Irradiation.

Adsorptive-photocatalytic composites based on activated carbon (AC) and α-ferrous oxalate dihydrate (α-FOD) were synthesized by an original two-step method and subsequently used for the removal of phenol from aqueous solutions. To obtain the composites, ferrotitaniferous black mineral sands (0.6FeTiO3·0.4Fe2O3) were first dissolved in an oxalic acid solution at ambient pressure, and further treated under hydrothermal conditions to precipitate α-FOD on the AC surface. The ratio of oxalic acid to the mineral sand precursor was tuned to obtain composites with 8.3 and 42.7 wt.% of α-FOD on the AC surface. These materials were characterized by X-ray powder diffraction, scanning electron microscopy, and the nitrogen adsorption-desorption method. The phenol removal efficiency of the composites was determined during 24 h of adsorption under dark conditions, followed by 24 h of adsorption-photocatalysis under visible light irradiation. AC/α-FOD composites with 8.3 and 42.7 wt.% of α-FOD adsorbed 60% and 51% of phenol in 24 h and reached a 90% and 96% removal efficiency after 12 h of irradiation, respectively. Given its higher photocatalytic response, the 42.7 wt.% α-FOD composite was also tested during successive cycles of adsorption and adsorption-photocatalysis. This composite exhibited a reasonable level of cyclability (~99% removal after four alternated dark/irradiated cycles of 24 h and ~68% removal after three simultaneous adsorption-photocatalysis cycles of 24 h). The promising performance of the as-prepared composites opens several opportunities for their application in the effective removal of organic micropollutants from water.

Targeted Polymeric Micelles System, Designed to Carry a Combined Cargo of L-Asparaginase and Doxorubicin, Shows Vast Improvement in Cytotoxic Efficacy.

L-asparaginases (ASP) and Doxorubicin (Dox) are both used in the treatment of leukemia, including in combination. We have attempted to investigate if their combination within the same targeted delivery vehicle can make such therapy more efficacious. We assembled a micellar system, where the inner hydrophobic core was loaded with Dox, while ASP would absorb at the surface due to electrostatic interactions. To make such absorption stronger, we conjugated the ASP with oligoamines, such as spermine, and the lipid components of the micelle-lipoic and oleic acids-with heparin. When loaded with Dox alone, the system yielded about a 10-fold improvement in cytotoxicity, as compared to free Dox. ASP alone showed about a 2.5-fold increase in cytotoxicity, so, assuming additivity of the effect, one could expect a 25-fold improvement when the two agents are applied in combination. But in reality, a combination of ASP + Dox loaded into the delivery system produced a synergy, with a whopping 50× improvement vs. free individual component. Pharmacokinetic studies have shown prolonged circulation of micellar formulations in the bloodstream as well as an increase in the effective concentration of Dox in micellar form and a reduction in Dox accumulation to the liver and heart (which reduces hepatotoxicity and cardiotoxicity). For the same reason, Dox's liposomal formulation has been in use in the treatment of multiple types of cancer, almost replacing the free drug. We believe that an opportunity to deliver a combination of two types of drugs to the same target cell may represent a further step towards improvement in the risk-benefit ratio in cancer treatment.

The Antioxidant and HDAC-Inhibitor α-Lipoic Acid Is Synergistic with Exemestane in Estrogen Receptor-Positive Breast Cancer Cells.

Anti-estrogenic therapy is established in the management of estrogen receptor (ER)-positive breast cancer. However, to overcome resistance and improve therapeutic outcome, novel strategies are needed such as targeting widely recognized aberrant epigenetics. The study aims to investigate the combination of the aromatase inhibitor exemestane and the histone deacetylase (HDAC) inhibitor and antioxidant α-lipoic acid in ER-positive breast cancer cells. First, the enantiomers and the racemic mixture of α-lipoic acid, and rac-dihydro-lipoic acid were investigated for HDAC inhibition. We found HDAC inhibitory activity in the 1-3-digit micromolar range with a preference for HDAC6. Rac-dihydro-lipoic acid is slightly more potent than rac-α-lipoic acid. The antiproliferative IC50 value of α-lipoic acid is in the 3-digit micromolar range. Notably, the combination of exemestane and α-lipoic acid resulted in synergistic behavior under various incubation times (24 h to 10 d) and readouts (MTT, live-cell fluorescence microscopy, caspase activation) analyzed by the Chou-Talalay method. α-lipoic acid increases mitochondrial fusion and the expression of apoptosis-related proteins p21, APAF-1, BIM, FOXO1, and decreases expression of anti-apoptotic proteins survivin, BCL-2, and c-myc. In conclusion, combining exemestane with α-lipoic acid is a promising novel treatment option for ER-positive breast cancer.

Synergistic removal of Staphylococcus aureus biofilms by using a combination of phage Kayvirus rodi with the exopolysaccharide depolymerase Dpo7.

Introduction: Bacteriophages have been shown to penetrate biofilms and replicate if they find suitable host cells. Therefore, these viruses appear to be a good option to tackle the biofilm problem and complement or even substitute more conventional antimicrobials. However, in order to successfully remove biofilms, in particular mature biofilms, phages may need to be administered along with other compounds. Phage-derived proteins, such as endolysins or depolymerases, offer a safer alternative to other compounds in the era of antibiotic resistance. Methods: This study examined the interactions between phage Kayvirus rodi with a polysaccharide depolymerase (Dpo7) from another phage (Rockefellervirus IPLA7) against biofilms formed by different Staphylococcus aureus strains, as determined by crystal violet staining, viable cell counts and microscopy analysis. Results and discussion: Our results demonstrated that there was synergy between the two antimicrobials, with a more significant decreased in biomass and viable cell number with the combination treatment compared to the phage and enzyme alone. This observation was confirmed by microscopy analysis, which also showed that polysaccharide depolymerase treatment reduced, but did not eliminate extracellular matrix polysaccharides. Activity assays on mutant strains did not identify teichoic acids or PNAG/PIA as the exclusive target of Dpo7, suggesting that may be both are degraded by this enzyme. Phage adsorption to S. aureus cells was not significantly altered by incubation with Dpo7, indicating that the mechanism of the observed synergistic interaction is likely through loosening of the biofilm structure. This would allow easier access of the phage particles to their host cells and facilitate infection progression within the bacterial population.

Exploring antimicrobial interactions between metal ions and quaternary ammonium compounds toward synergistic metallo-antimicrobial formulations.

Multi-target antimicrobial agents are considered a viable alternative to target-specific antibiotics, resistance to which emerged as a global threat. Used centuries before the discovery of conventional antibiotics, metal(loid)-based antimicrobials (MBAs), which target multiple biomolecules within the bacterial cell, are regaining research interest. However, there is a significant limiting factor-the balance between cost and efficiency. In this article, we utilize a checkerboard assay approach to explore antimicrobial combinations of MBAs with commonly used quaternary ammonium compound (QAC) antiseptics in order to discover novel combinations with more pronounced antimicrobial properties than would be expected from a simple sum of antimicrobial effects of initial components. This phenomenon, called synergy, was herein demonstrated for several mixtures of Al3+with cetyltrimethylammonium bromide (CTAB) and TeO32- with benzalkonium chloride (BAC) and didecyldimethylammonium bromide (DDAB) against planktonic and biofilm growth of Pseudomonas aeruginosa ATCC27853. Biofilm growth of Escherichia coli ATCC25922 was synergistically inhibited by the Cu2 +and benzalkonium chloride (BAC) mixture. Multiple additive mixtures were identified for both organisms. The current study observed unexpected species and growth state specificities for the synergistic combinations. The benefit of synergistic mixtures will be captured in economy/efficiency optimization for antimicrobial applications in which MBAs and QACs are presently used. IMPORTANCE: We are entering the antimicrobial resistance era (AMR), where resistance to antibiotics is becoming more and more prevalent. In order to address this issue, various approaches are being explored. In this article, we explore for synergy between two very different antimicrobials, the antiseptic class of quaternary ammonium compounds and antimicrobial metals. These two antimicrobials have very different actions. Considering a OneHealth approach to the problem, finding synergistic mixtures allows for greater efficacy at lower concentrations, which would also address antimicrobial pollution issues.

Protection efficacy and the safety of the synergy between modified Bazhen powder and PRRSV modified-live virus vaccine against HP-PRRSV in piglets.

The highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) poses a significant threat to the global swine industry. Vaccination is a preventive measure against viral infections. However, the use of vaccines in livestock healthcare programs faces the challenge of safety and delayed immune responses. Earlier studies have shown the potential of modified Bazhen powder as an immunomodulator with significant biological properties, but its effect on vaccines against HP-PRRSV is yet to be studied. This study elucidated how modified Bazhen powder could improve the safety and efficacy of the conventional PRRSV vaccine by evaluating T-cell responses, antibody levels, clinical symptoms, levels of viremia, organ health, and cytokine production. The results revealed that the oral application of modified Bazhen powder in combination with PRRS vaccination improved both cellular and humoral immunity, accelerated viremia clearance, improved lung injury scores, and reduced viral load in the tonsils. The modified Bazhen powder also effectively reduced inflammatory responses following a PRRSV challenge. These findings further highlight the pharmacological properties of modified Bazhen powder as a potential oral immunomodulatory agent that could enhance vaccine efficacy and ensure broad-spectrum protection against HP-PRRSV in pigs.

Synergistic interaction between Chlorella vulgaris extract and Origanum elongatum essential oil against methicillin-resistant Staphylococcus aureus.

The massive emergence of antimicrobial resistance in recent decades has rendered the use of a single-agent strategy ineffective. Consequently, the combination of different therapeutic agents has emerged as a promising new approach. The aim of the present study was to investigate the combined effect of Chlorella vulgaris methanol extract (CVME) and Origanum elongatum essential oil (OEEO) on methicillin-resistant Staphylococcus aureus (MRSA). Thus, the antibacterial activity of OEEO and CVME on Escherichia coli, Staphylococcus aureus, and MRSA was evaluated using the agar well diffusion and broth microdilution methods. The killing activity of CVME and OEEO, individually and in combination, on MRSA ATCC 43300 was tested using the time-kill assay. The synergistic effect was examined by determining the fractional inhibitory concentration index (FICI) using the checkerboard test. The results showed very significant antibacterial activity against all the bacteria tested, for both OEEO and CVME, with minimum inhibitory concentrations (MICs) ranging from 0.125 to 0.25% (v/v) for OEEO and from 3.12 to 6.25 mg mL-1 for CVME. Minimum bactericidal concentration (MBC) values for OEEO and CVME were in the range 0.125-0.5% (v/v) and 6.25-12.5 mg mL-1, respectively. The inhibition zones associated with OEEO were distinctly greater than those associated with CVME for all the bacteria examined. When used individually, the time-kill curves of OEEO and CVME revealed a dose-dependent effect on MRSA proliferation. Compared with controls, both agents were able to prolong the latent phase of growth curves and decelerate bacterial growth. The killing effect of OEEO on MRSA was considerably higher than that observed with CVME. OEEO prevented MRSA proliferation at only 1/2 of its MIC, while the CVME did so at 2 times its MIC. The combination of OEEO with CVME demonstrated a synergistic effect against MRSA, with a FIC index value of 0.49. The findings therefore suggest that the combination of C. vulgaris methanol extract and O. elongatum essential oil at very low doses may be promising anti-MRSA candidates. A search of the published literature revealed that, to our knowledge, no studies have yet been carried out on the antibacterial potential of combining essential oils and microalgae extracts in the fight against MRSA.

Robust fatigue markers obtained from muscle synergy analysis.

This study aimed to utilize the nonnegative matrix factorization (NNMF) algorithm for muscle synergy analysis, extracting synergy structures and muscle weightings and mining biomarkers reflecting changes in muscle fatigue from these synergy structures. A leg press exercise to induce fatigue was performed by 11 participants. Surface electromyography (sEMG) data from seven muscles, electrocardiography (ECG) data, Borg CR-10 scale scores, and the z-axis acceleration of the weight block were simultaneously collected. Three indices were derived from the synergy structures: activation phase difference, coactivation area, and coactivation time. The indicators were further validated for single-leg landing. Differences in heart rate (HR) and heart rate variability (HRV) were observed across different fatigue levels, with varying degrees of disparity. The median frequency (MDF) exhibited a consistent decline in the primary working muscle groups. Significant differences were noted in activation phase difference, coactivation area, and coactivation time before and after fatigue onset. Moreover, a significant correlation was found between the activation phase difference and the coactivation area with fatigue intensity. The further application of single-leg landing demonstrated the effectiveness of the coactivation area. These indices can serve as biomarkers reflecting simultaneous alterations in the central nervous system and muscle activity post-exertion.

Interface Synergy of Exposed Oxygen Vacancy and Pd Lewis Acid Sites Enabling Superior Cooperative Photoredox Synthesis.

Photo-driven cross-coupling of o-arylenediamines and alcohols has emerged as an alternative for the synthesis of bio-active benzimidazoles. However, tackling the key problem related to efficient adsorption and activation of both coupling partners over photocatalysts towards activity enhancement remains a challenge. Here, we demonstrate an efficient interface synergy strategy by coupling exposed oxygen vacancies (VO) and Pd Lewis acid sites for benzimidazole and hydrogen (H2) coproduction over Pd-loaded TiO2 nanospheres with the highest photoredox activity compared to previous works so far. The results show that the introduction of VO optimizes the energy band structure and supplies coordinatively unsaturated sites for adsorbing and activating ethanol molecules, affording acetaldehyde active intermediates. Pd acts as a Lewis acid site, enhancing the adsorption of alkaline amine moleculesvia Lewis acid-base pair interactions and driving the condensation process. Furthermore, VO and Pd synergistically promote interfacial charge transfer and separation. This work offers new insightful guidance for the rational design of semiconductor-based photocatalysts with interface synergy at the molecular level towards the high-performance coproduction of renewable fuels and value-added feedstocks.

BCL6 confers resistance to HDAC inhibitors in DLBCL.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin lymphoma with limited response to chemotherapy. Histone acetylation is reduced in DLBCL. Chidamide, a histone deacetylase inhibitor, shows promise in lymphomas but needs further investigation for DLBCL. Our study indicated that chidamide effectively suppresses DLBCL both in vitro and in vivo. High-throughput RNA sequencing analysis provided comprehensive evidence that chidamide markedly influences crucial signaling pathways in DLBCL, including the MAPK, MYC and p53 pathway. Additionally, we observed substantial variability in the sensitivity of DLBCL cells to chidamide, and identified that elevated expression of BCL6 might confer resistance to chidamide in DLBCL. Moreover, our investigations revealed that BCL6 inhibited chidamide-induced histone acetylation by recruiting histone deacetylase (HDACs), leading to drug resistance in DLBCL cells. Furthermore, we found that lenalidomide targeted BCL6 degradation through the ubiquitination pathway and restore the sensitivity of drug-resistant DLBCL to chidamide. Collectively, these findings provided valuable insights into the global impact of chidamide on DLBCL and highlight the potential of targeting HDACs as a therapeutic strategy for DLBCL. Identifying BCL6 as a biomarker for predicting the response to chidamide and the combination therapy with BCL6 inhibition has the potential to lead to more personalized and effective treatments for DLBCL patients.

Integrated Benefits of Synergistically Reducing Air Pollutants and Carbon Dioxide in China.

China's advancements in addressing air pollution and reducing CO2 emissions offer valuable lessons for collaborative strategies to achieve diverse environmental objectives. Previous studies have assessed the mutual benefits of climate policies and air pollution control measures on one another, lacking an integrated assessment of the benefits of synergistic control attributed to refined measures. Here, we comprehensively used coupled emission inventory and response models to evaluate the integrated benefits and synergy degrees of various measures in reducing air pollutants and CO2 in China during 2013-2021. Results indicated that the implemented measures yielded integrated benefits value at 6.7 (2.4-12.6) trillion Chinese Yuan. The top five contributors, accounting for 55%, included promoting non-thermal power, implementing end-of-pipe control technologies in power plants and iron and steel industry, replacing residential scattered coal, and saving building energy. Measures demonstrating high synergies and integrated benefits per unit of reduction (e.g., green traffic promotion) yielded low benefits mainly due to their low application, which are expected to gain greater implementation and prioritization in the future. Our findings provide insights into the effectiveness and limitations of strategies aimed at joint control. By ranking these measures based on their benefits and synergy, we offer valuable guidance for policy development in China and other nations with similar needs.