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Lithium dendrite (filaments) propagation in solid electrolytes (SEs) leading to short circuits is one of the biggest obstacles to the application of all-solid-state lithium metal batteries. Due to the lack of operando techniques that can provide high resolution, the insufficient knowledge of the lithium dendrite growth inside SEs makes it difficult to suppress the dendrite growth. To reveal the mechanism of the Li filament growth in SEs, we achieved real-time monitoring of the nanoscale Li filament growth by operando small-angle neutron scattering (SANS) in representative Li6.5La3Zr1.5Nb0.5O12 SEs. On continuous plating, the Li filament growth is not simply an accumulation of Li, but there is a dynamic evolution due to the competition between the Li filament growth and self-healing. With the aid of simulations and experiments, this dynamic competition was demonstrated to be highly dependent on temperature variation. The enhanced self-healing ability of Li at elevated temperatures plays a positive role in suppressing the Li filament growth. The heat therapy improved the cell's cycle life, which provided insight into suppressing the Li filament growth. Operando SANS with high Li sensitivity provides a platform for investigating Li filaments in SEs. [ABSTRACT FROM AUTHOR]

• A stereolithography-based 3D printing method for BTO was proposed. The curing ability of BTO slurry was greatly improved by using a high refractive index monomer. • A method for selecting printing parameters based on curing ability, printing stability and forming efficiency was established for BTO slurries with different formulations. • Piezoelectric composites with octet-truss and gyroid structures were prepared and further made into hydrophones, which verified the feasibility of DLP 3D printing in the manufacture of complex-structured ceramics and functional devices. A digital light processing (DLP) technology has been developed for 3D printing lead-free barium titanate (BTO) piezoelectric ceramics. By comparing the curing and rheological properties of slurries with different photosensitive monomer, a high refractive index monomer acryloyl morpholine (ACMO) was chosen, and a design and preparation method of BTO slurry with high solid content, low viscosity and high curing ability was proposed. By further selecting the printing parameters, the single-layer exposure time was reduced and the forming efficiency has been greatly improved. Sintered specimens were obtained after a nitrogen-air double-step debinding and furnace sintering process, and the BTO ceramics fabricated with 80 wt% slurry shows the highest relative density (95.32 %) and piezoelectric constant (168.1 pC/N). Furthermore, complex-structured BTO ceramics were prepared, impregnated by epoxy resin and finally assembly made into hydrophones, which has significance for the future design and manufacture of piezoelectric ceramic-based composites that used in functional devices. [ABSTRACT FROM AUTHOR]

Summary In the primate visual system, direction-selective (DS) neurons are critical for visual motion perception. While DS neurons in the dorsal visual pathway have been well characterized, the response properties of DS neurons in other major visual areas are largely unexplored. Recent optical imaging studies in monkey visual cortex area 2 (V2) revealed clusters of DS neurons. This imaging method facilitates targeted recordings from these neurons. Using optical imaging and single-cell recording, we characterized detailed response properties of DS neurons in macaque V2. Compared with DS neurons in the dorsal areas (e.g., middle temporal area [MT]), V2 DS neurons have a smaller receptive field and a stronger antagonistic surround. They do not code speed or plaid motion but are sensitive to motion contrast. Our results suggest that V2 DS neurons play an important role in figure-ground segregation. The clusters of V2 DS neurons are likely specialized functional systems for detecting motion contrast. Graphical Abstract Highlights • DS neurons in a non-dorsal visual area (V2) were studied with map-guided recordings • V2 DS neurons exhibit features distinct from the DS neurons in the dorsal area MT • Clusters of V2 DS neurons form functional architectures sensitive to motion contrast • Response properties of V2 DS neurons are suitable for figure-ground segregation Direction-selective (DS) neurons are widely distributed in the primate visual system. Hu et al. examined visual responses of DS neurons in the second largest visual area (V2) in macaque monkeys and demonstrate distinctive response properties of these neurons compared with DS neurons in the well-studied traditional motion area MT. [ABSTRACT FROM AUTHOR]

The effects of self-impinging injection and unlike-impinging injection on the performance of powdered magnesium-liquid carbon dioxide rocket engine have been investigated via numerical simulation and experimentation. The results indicate that the unlike-impinging injection achieves a combustion efficiency of 88.7%, which is 23% higher than that of self-impinging injection. Moreover, significant deposition of unburned magnesium particles is observed at the head of the combustor when using self-impinging injection, whereas unlike-impinging injection exhibits much less deposition. Self-impinging injection leads to an uneven temperature field distribution at the head of the combustion chamber, while high temperature areas under the unlike-impinging injection scheme are relatively concentrated. The mutual collision between carbon dioxide droplets also reduces the degree of mixing between carbon dioxide droplets and magnesium particles under self-impinging injection which is less likely to occur in the unlike-impinging injection scheme. [ABSTRACT FROM AUTHOR]

• Continual evolution of SARS-CoV-2 warrants adaptive therapeutic approaches. • 3CLpro is a well-characterized and important protein for viral replication. • 3CLpro inhibitor co-crystal structures guide potential degrader development. • Degrader design requires synergy of computational and synthetic chemistry expertise. • Targeted protein degradation is the next frontier for antiviral therapies. COVID-19 remains a severe public health threat despite the WHO declaring an end to the public health emergency in May 2023. Continual development of SARS-CoV-2 variants with resistance to vaccine-induced or natural immunity necessitates constant vigilance as well as new vaccines and therapeutics. Targeted protein degradation (TPD) remains relatively untapped in antiviral drug discovery and holds the promise of attenuating viral resistance development. From a unique structural design perspective, this review covers antiviral degrader merits and challenges by highlighting key coronavirus protein targets and their co-crystal structures, specifically illustrating how TPD strategies can refine existing SARS-CoV-2 3CL protease inhibitors to potentially produce superior protease-degrading agents. [ABSTRACT FROM AUTHOR]

Background: Exosomes are nanoscale extracellular vesicles (30–160 nm) with endosome origin secreted by almost all types of cells, which are considered to be messengers of intercellular communication. Cancerous exosomes serve as a rich source of biomarkers for monitoring changes in cancer-related physiological status, because they carry a large number of biological macromolecules derived from parental tumors. The ultrasensitive quantification of trace amounts of cancerous exosomes is highly valuable for non-invasive early cancer diagnosis, yet it remains challenging. Herein, we developed an aptamer-carrying tetrahedral DNA (Apt-TDNA) microelectrode sensor, assisted by a polydopamine (PDA) coating with semiconducting properties, for the ultrasensitive electrochemical detection of cancer-derived exosomes. Results: The stable rigid structure and orientation of Apt-TDNA ensured efficient capture of suspended exosomes. Without PDA coating signal amplification strategy, the sensor has a linear working range of 102–107 particles mL−1, with LOD of ~ 69 exosomes and ~ 42 exosomes for EIS and DPV, respectively. With PDA coating, the electrochemical signal of the microelectrode is further amplified, achieving single particle level sensitivity (~ 14 exosomes by EIS and ~ 6 exosomes by DPV). Conclusions: The proposed PDA-assisted Apt-TDNA microelectrode sensor, which integrates efficient exosome capture, sensitive electrochemical signal feedback with PDA coating signal amplification, provides a new avenue for the development of simple and sensitive electrochemical sensing techniques in non-invasive cancer diagnosis and monitoring treatment response. [ABSTRACT FROM AUTHOR]

Micro‐sized silicon (mSi) anodes offer advantages in cost and tap density over nanosized counterparts. However, its practical application still suffers from poor cyclability and low initial and later‐cycle coulombic efficiency (CE), caused by the unstable solid electrolyte interphase (SEI) and irreversible lithiation of the surface oxide layer. Herein, a bifunctional fluorine (F)‐free electrolyte was designed for the mSi anode to stabilize the interphase and improve the CE. A combined analysis revealed that this electrolyte can chemically pre‐lithiate the native oxide layer by the reductive LiBH4, and relieve SEI formation and accumulation to preserve the internal conductive network. The significance of this F‐free electrolyte brings unprecedented F‐free interphase that also enables the high‐performance mSi electrode (80 wt % mSi), including high specific capacity of 2900 mAh/g, high initial CE of 94.7 % and excellent cyclability capacity retention of 94.3 % after 100 cycles at 0.2 C. This work confirms the feasibility of F‐free interphase, thus opening up a new avenue toward cost‐advantaged and environmentally friendly electrolytes for more emerging battery systems. [ABSTRACT FROM AUTHOR]

Boosting the ultralow temperature (below −30 °C) performance of Na‐ion hybrid capacitors (SIHCs), which integrate the high energy density of batteries with the high output power and long life of supercapacitors, is critical for the application of advanced electronics in extreme environments. However, their low‐temperature performance, especially fast charging capability, is hindered by difficult desolvation and slow pass solid electrolyte interphase (SEI) together with sluggish diffusion within the electrode. Herein, a "single‐solute–single‐solvent" electrolyte is developed and a through‐hole hollow carbon sphere (TH‐HCS) is constructed, and it is demonstrated through theoretical calculations and experimental investigations that the weakly solvated structure and high ionic conductivity facilitate the Na+ transportation at low temperatures, the highly fluorinated SEI facilitates the Na+ migration, and the through‐hole hollow structure alleviates the volume expansion during sodiation, thus ensuring fast kinetics and structural stability. As expected, TH‐HCS using this electrolyte exhibits a high specific capacity of 87.5 mAh g−1 after 11 000 cycles at 1.0 A g−1 and −40 °C. Coupled with activated carbon, the assembled SIHC displays an energy density of 106.1 and 52.0 Wh kg−1 at 25 and −40 °C, respectively, far exceeding the performance of commercial energy storage systems at low temperature. [ABSTRACT FROM AUTHOR]

In this work, a novel amplification-free CRISPR/Cas13a-powered dry chemistry-based electrochemiluminescence (ECL) gene sensor was developed for ultrasensitive RNA detection, where the self-enhanced probe dried on the cloth-based closed bipolar electrode-ECL (C-BPE-ECL) lateral flow chip captured the trans-cleavage products of CRISPR/Cas13a. The poly-(L-lysine) (PLL) having the ability to covalently bind abundant Ru(II) luminescent substances was utilized to construct the intra-molecular self-enhanced ECL probes (S1 and S2), and as a result the ECL signals were greatly amplified and meanwhile no additional co-reactants were applied onto the lateral flow chip. In addition, the trans-cleavage of Cas13a served to amplify the signals, while CRISPR/Cas13a's two-part recognition mechanism enhanced the detection specificity. Therefore, the proposed ECL method realized the amplification-free detection of RNA. With the optimized conditions, the proposed gene sensor had a wide linear range (10–105 fM) for RNA detection of Escherichia coli O157:H7, with a limit detection of 0.65 fM. Moreover, the sensor exhibited acceptable selectivity, reproducibility and storage stability, and had been successfully applied to detect Escherichia coli O157:H7 RNA in clinical human urine and blood samples. Importantly, the proposed method possessed good versatility for detection of different RNA targets, and provided the potential for rapid and sensitive detection in 20 min. These results revealed that the ECL method possessed great prospects for RNA detection with wide applications. [Display omitted] • An amplification-free, CRISPR/Cas13a-powered dry chemistry-based ECL (DC-ECL-CRISPR) gene sensor has firstly been developed. • The Ru(II)-PLL complex, together with the CRISPR/Cas13a system, achieves the effect of two-stage signal amplification. • The DC-ECL-CRISPR gene sensor can detect E. coli RNA as low as 0.65 fM. • The whole RNA detection is achieved in 20 min. • The sensor has the potential application in gene detection of different diseases. [ABSTRACT FROM AUTHOR]

[Display omitted] • Developed a novel hydrogel-supported electrocatalyst, HFc-NG@PVA, for OER. • Achieved low overpotential (η 10 = 310 mV) and small Tafel slope (49 mV dec−1). • Enhanced OER performance due to synergy between redox-active HFc and PVA. • HFc-NG@PVA shows excellent mechanical strength, stability, and durability. • Mechanistic insights via DFT and COMSOL simulations reveal reduced activation energy. The oxygen evolution reaction (OER) is a crucial process in renewable energy technologies, yet it remains hindered by sluggish reaction kinetics, high overpotentials, and poor electron and ion transfer. This study introduces a novel hydrogel-supported electrocatalyst, HFc-NG@PVA, which combines hydrazinocarbonylferrocene-modified nitrogen-doped graphene (HFc-NG) with polyvinyl alcohol (PVA) to enhance OER performance. HFc-NG@PVA exhibited a low overpotential (η 10 = 310 mV) and a small Tafel slope (49 mV dec−1), outperforming conventional carbon-based electrodes and approaching the performance of IrO 2. Additionally, the hydrogels exhibit excellent mechanical strength, elasticity, and durability, maintaining stable OER performance over 24 h. Mechanistic studies, including density functional theory (DFT) and COMSOL simulation, reveal that the HFc-NG facilitates electron transfer through redox-active HFc, while PVA, a hydrogel, improves ion conduction, hydration, and mechanical support. The integration of HFc-NG into the PVA matrix not only boosts the mechanical and electrochemical properties of the hydrogel but also enhances the stability of the active sites, enabling more efficient OER. The unique hydrogen-bonding network between HFc-NG and PVA further lowers the activation energy for OER, contributing to its superior catalytic efficiency. This work highlights the potential of hydrogel-supported catalysts as promising candidates for efficient, stable, and cost-effective electrocatalysis in energy conversion systems. [ABSTRACT FROM AUTHOR]

The novel 3D hollow Sb 2 S 3 /S@S-doped carbon composite were prepared based on coupling reaction and superior electrochemical performance was achieved. [Display omitted] • Sb 2 S 3 /S@S-doped carbon composite with a hollow core–shell structure is synthesized. • The structure is prepared based on template method and coupling reaction. • S/S-doped carbon can interact with Sb 2 S 3 to improve the reactivity with Na+. • The as-prepared composite electrode displays superior sodium storage performance. Although the high-capacity Sb 2 S 3 -based anode materials for sodium-ion batteries can combine the advantages of multi-step conversion of Sb 2 S 3 to Sb and alloying reaction between Sb and Na for improving the performance, the slow reaction kinetics, low electronic conductivity, and poor reversibility of the sodium storage process have limited their practical application. To effectively improve the electrochemical performance, a three-dimensional Sb 2 S 3 /S@S-doped carbon composite with a hollow core–shell structure based on the combination of template method and coupling reaction is successfully synthesized. By combining the finite element simulation, dynamic analysis, and density functional theory calculation, the respective roles of S-composite and hollow core–shell structure in boosting performance are revealed. The internal S and external S-doped carbon can interact with Sb 2 S 3 to improve its reactivity with Na+, and effectively release the stress of Sb 2 S 3 in the sodiation process. The S-doped carbon can accelerate Na+ diffusion and further stabilize the structure of Sb 2 S 3. Benefited from the special structure, the as-prepared anode displays high reversible capacity, superior cycle performance and high rate capability. The assembled full battery also exhibits an excellent energy density under high power, and can still maintain a high reversible capacity of 310 mAh/g at 1 A/g over 500 cycles. [ABSTRACT FROM AUTHOR]

Steppe bison are a typical representative of the Mid-Late Pleistocene steppes of the northern hemisphere. Despite the abundance of fossil remains, many questions related to their genetic diversity, population structure and dispersal route are still elusive. Here, we present both near-complete and partial mitochondrial genomes, as well as a partial nuclear genome from fossil bison samples excavated from Late Pleistocene strata in northeastern China. Maximum-likelihood and Bayesian trees both suggest the bison clade are divided into three maternal haplogroups (A, B and C), and Chinese individuals fall in two of them. Bayesian analysis shows that the split between haplogroup C and the ancestor of haplogroups A and B dates at 326 ky BP (95% HPD: 397-264 ky BP). In addition, our nuclear phylogenomic tree also supports a basal position for the individual carrying haplogroup C. Admixture analyses suggest that CADG467 (haplogroup C) has a similar genetic structure to steppe bison from Siberia (haplogroup B). Our new findings indicate that the genetic diversity of Pleistocene bison was probably even higher than previously thought and that northeastern Chinese populations of several mammalian species, including Pleistocene bison, were genetically distinct. [ABSTRACT FROM AUTHOR]

In order to mitigate the increasing severity of electromagnetic interference (EMI), it is imperative to develop advanced rubber composites. Despite recent advancements in structural design and filler hybridization for enhancing their EMI shielding performance, challenges persist in terms of suboptimal mechanical properties and intricate processing techniques. To overcome these limitations, bio-based Eucommia ulmoides gum (EUG) composites with segregated network structures were fabricated by simple mechanical blending, capitalizing on the characteristics of highly cross-linked rubbers with restricted molecular chains. Highly cross-linked EUG (HCE) effectively segregated the conductive fillers into the EUG phase, while the crystallization of EUG promoted the dispersion of fillers within the amorphous region of the EUG. Therefore, a highly efficient 3D conductive network was formed due to the segregated structure and crystallization, enabling the EUG/HCE/CNT composite to achieve an exceptional shielding effectiveness (SE) value of 83.0 dB with a high absorption loss ranging from 8.2 GHz to 12.4 GHz. [Display omitted] • Achieving efficient electromagnetic shielding using simple mechanical technology. • Enhanced electromagnetic shielding performance through volume exclusion effect. • Highly cross-linked rubber facilitated the formation of segregated structure. • The synergistic effect of segregated structure and rubber crystallization. • Reinforcement effect for composites due to interfacial cross-linking. [ABSTRACT FROM AUTHOR]

The production of return propellant through Martian in-situ resources has been proposed in the assumptions of Mars exploration missions. The Mg/CO 2 scheme is one of these approaches in which powdered magnesium comes from the Earth as fuel and CO 2 is collected on the surface of Mars as the oxidant. The propellant of Mg/CO 2 engines has a good storage stability, has no chemical reactions in the in-situ resource utilization process, and contains a simple structure; thus, it is regarded as one of the technologically less complex choices for missions on Mars. However, the low specific impulse of Mg/CO 2 engines requires evaluating their applications and performance. Three Mg/CO 2 application scenarios (Ascent Vehicle, Hopper, and Two-stage Returnable Aircraft) are reviewed here, and two of them are estimated in detail from the established motion models. It is found that when a Mg/CO 2 engine is used as an Ascent Vehicle, a two-stage rocket is more suitable. The propellant carried from Earth for Mg/CO 2 engines could be reduced by 27.7% compared with the conventional storable UDMH/N 2 O 4 (specific impulse is 330 s) two-stage rocket. The saved propellant is largest when the total velocity pulse is approximately 3430 m/s. When Mg/CO 2 engines are used as a jump vehicle "Hopper", the increased maximum thrust, engine working time, and total jump times decrease the marginal benefit, which means that these parameters cannot be too large. Based on the Ascent Vehicle and Hopper schemes, a Two-stage Returnable Aircraft is proposed for material and personnel circulation between different Mars bases. • Detailed motion models of Mars aircrafts with Mg/CO 2 engine are firstly established. • The advantages of Mg/CO 2 engine as Mars Ascent vehicle are analyzed in detail. • The influence of key parameters on the performance of Mars jump vehicle "Hopper" with Mg/CO 2 engine is obtained. • A new Mars two-stage returnable aircraft is conceived. [ABSTRACT FROM AUTHOR]

To solve the problem of thermal protection posed by the long working time of Mg/CO 2 powder rocket engines, an experimental system is designed to study the heat-transfer characteristics of liquid CO 2 in the regenerative cooling channel. How the heat flux, coolant temperature, mass flux, and back pressure influence the heat-transfer coefficient, the thermodynamic quality, and the gas-phase formation point of nearly saturated CO 2 is studied. The heat-transfer coefficient is found to increase with increasing mass flux or decreasing inlet temperature. Higher heat flux increases the rate of bubble formation and promotes nucleate-boiling heat transfer, but it also intensifies the film boiling, thereby degrading the heat-transfer performance. Lower back pressure does not affect the heat-transfer performance in the nucleate-boiling region, but it worsens it in the film-boiling region. It is also found that the classical boiling-heat-transfer models do not predict the experimental heat-transfer coefficient well. Combined with experimental data, how reduced pressure affects heat transfer is considered, and a new empirical correlation formula is proposed for the heat-transfer coefficient of CO 2 near saturation. The optimized model can successfully predict 90.23% of the experimental data, and the prediction accuracy is improved greatly. The present research provides a theoretical basis for designing a regenerative cooling scheme for an Mg/CO 2 powder rocket engine. • Liquid CO 2 is used as coolant for the first time to conduct heat transfer experiments in a regenerative cooling channel. • A method for calculating the heat transfer coefficient along the microchannel is established. • The effects of different heat fluxes, coolant temperatures, mass fluxes and back pressures on the heat transfer performance of CO 2 are obtained. • An empirical correlation for heat transfer of CO 2 boiling flow in a regenerative cooling channel at near saturation state is obtained. [ABSTRACT FROM AUTHOR]

Powder supply system is the key component of powder engines with multiple ignition capability, and thrust modulation function. Similar to the pure gas phase, the gas-solid two-phase flow in powder engines also has a choking phenomenon. The powder pneumatic conveying experiments at choked mode and non-choked mode were carried out to compare their conveying characteristics. In the choked mode (mode A and mode B), when the initial pressure of the fluidization chamber is higher than the pressure in the stable stage, the powder supply system is prone to flow peaks. In the choked mode A where the amount of fluidization gas is determined by the area of the throttle channel, the powder supply system is prone to fluctuations, and the frequency and amplitude of the fluctuation are related to the throttle channel area. The choked mode A has good repeatability and flow regulation performance when the throttle channel area is large. Employing pressure simulator and wavelet analysis, the transition from choked flow to non-choked flow was achieved and the effective frequency (<20 Hz) of the powder supply system is obtained. Experimental results and theoretical analysis show that powder flow has an upper limit in the non-choked mode. • A semi-empirical model of powder mass flow rate at non-choked mode is established. • Reveals the mechanism of powder flow peak at choked mode. • The effective frequency of the powder supply system is obtained. • A new method to study the critical pressure ratio of gas-solid two-phase flow. • Propose two methods to adjustment powder mass flow rate. [ABSTRACT FROM AUTHOR]

• The role of intratumoural microbiome in the progression of malignant ascites secondary to HCC is still unknown. • Ascitis Gustave Roussy Immune (aGRIm) score shows superior prognostic significance to serum GRIm (sGRIm) score. • Significant bacterium in malignant ascites associated with the level of aGRIm score. • Significant immune cells in malignant ascites correlated with the level of aGRIm score. The Gustave Roussy Immune (GRIm) score predicts survival outcomes in several cancers. However, the prognostic significance of the GRIm score in patients with malignant ascites has not yet been investigated. Clinical samples were collected from a cohort of patients with malignant ascites secondary to hepatocellular carcinoma (HCC). We calculated serum GRIm (sGRIm) and ascites GRIm (aGRIm) scores and divided the samples into low and high GRIm score groups. Survival analysis was used to compare the prognostic significance of the sGRIm and aGRIm scores. 16S rRNA sequencing was performed to determine the profiles of the intratumoral microbiota in the groups. A fluorescent multiplex immunohistochemistry (mIHC) assay was used to detect the expression of different immune cells by labeling seven markers of malignant ascites. 155 patients with HCC and malignant ascites were enrolled in this study. Survival analysis revealed that the aGRIm score showed a superior prognostic significance compared to the sGRIm score. Microbial analysis demonstrated that the bacterial richness and diversity were higher in the low aGRIm score group than in the high aGRIm score group. LefSe analysis revealed that certain bacteria were correlated with high aGRIm scores. Fluorescent mIHC displayed the tumor microenvironment of malignant ascites and found that the density of CD8 + T cells was significantly higher in the low aGRIm score group than in the high aGRIm score group. Our present study identified a novel scoring system (aGRIm score) that can predict the survival outcome of patients with malignant ascites secondary to HCC. [ABSTRACT FROM AUTHOR]

The implantation of bioresorbable compositions has emerged as a promising therapeutic strategy to treat damaged bone tissues. To develop versatile bone scaffolds, polycaprolactone (PCL) is known as a dominant polymeric material regarding its unique biocompatibility and biodegradability. However, using PCL in a single structure reveals insufficient mechanical properties, in tandem with poor biological activity. To modulate these features, the combination of PCL and chitosan has been broadly proposed due to the proper bioactivity behavior of the chitosan component. It is also declared that the presence of MXene elements in the bone scaffolds could enhance the osteogenic impact and modify the mechanical behavior to match the surrounding bone tissue. To explore the synergetic effect of chitosan and MXene in enhancing the features of PCL structure, the PCL/chitosan/MXene ternary system was designed in this study. Accordingly, MXene nanosheets were synthesized and incorporated with various filler contents of 1, 3, and 5 % into PCL/chitosan to boost the overall characteristics. The obtained data exhibited a rise in porosity ratio from 22 to 30 % and a decrease in contact angle from 95.45 to 79.86⁰ by embedding MXene up to 3 %. Young's modulus was enhanced from 0.4 to 1.2 MPa, corroborating the generation of scaffolds with superior mechanical strength and rigidity. The compositions containing MXene up to 3 % revealed no cytotoxicity and human osteoblast cell assay approved the cell adhesion affinity of the designed architectures. Furthermore, the presence of MXene nanosheets resulted in the promoting of antimicrobial features in the membranes as a bifunctional behavior. Correspondingly, embedding an optimized ratio of MXene nanoparticles into the PCL/chitosan scaffold could create a suitable scaffolding architecture toward the generation of new bone tissues, benefiting appropriate cell attachment, proliferation, and differentiation. [Display omitted] • PCL/chitosan bifunctional compositions loaded with MXene (Ti 3 C 2 T x) nanoflakes were developed for bone tissue regeneration. • The addition of Ti 3 C 2 T x filler into the PCL/chitosan caused the formation of tiny pores in a highly porous structure. • Inherent features of Ti 3 C 2 T x and chitosan components enhanced hydrophilicity in the designed tissues. • PCL and Ti 3 C 2 T x provided proper mechanical characteristics in the developed ternary architecture. • Cell adhesion and antimicrobial properties were inclined as a result of MXene presence in the deployed scaffolds. [ABSTRACT FROM AUTHOR]

Highlights • KAMPC takes the kinematics and trajectory tracking control as a combined problem. • KAMPC is the exploration process of intrinsic characteristics for autonomous systems. • We verified the algorithm from both theoretical analysis and real experiment. • KAMPC can reduce the average tracking residuals and has good statistical performance. Abstract Although accurate trajectory tracking of autonomous vehicles strongly depends on a precise model, it is difficult to establish a precise model for high-speed tracked vehicles under off-road conditions, due to the complicated interactions between the tracks and the terrain. This paper presents a novel trajectory tracking methodology, called kinematics-aware model predictive control (KAMPC), by combining the slip kinematic model with a trajectory tracking control strategy for skid-steered tracked vehicles. For the slip kinematic model, an online identification methodology called six-parameter slip parameter estimation (SSPE) algorithm is proposed based on the instantaneous centers of rotation. For the trajectory tracking control strategy, optimized algorithm model predictive control is used to obtain the optimal control inputs. Finally, our method is validated through extensive experiments based on a distributed electric-drive high-speed tracked vehicle test platform over different types of terrain and varied off-road surface conditions. Experiment results show that the tracked vehicle kinematic characteristics are distinctive in off-road conditions, and the slipping and skidding that occur when turning are critical to this work. Compared with the other three widely used types of methodologies, the present KAMPC approach can reduce the average tracking residuals and has the best statistical performance. [ABSTRACT FROM AUTHOR]

Efficient extracellular vesicle (EV) enrichment and timely internal RNA detection for cancer diagnostics are highly desirable and remain a challenge. Here, we report a rapid EV aggregation induced in-situ microRNA detection technology based on cationic lipid-polymer hybrid nanoparticles encapsulating cascade system of catalytic hairpin assembly and CRISPR-Cas12a (CLHN-CCC), allowing for EV enrichment in three-dimensional space and in-situ detection of internal microRNAs in one step within 30 min. The enrichment efficiency (>90%) of CLHN-CCC is demonstrated in artificial EVs, cell-secreted EVs and serum EVs, which is 5-fold higher than that of traditional ultracentrifugation. The sensitive detection of artificial EVs and internal miR-1290 was achieved with the limit of detection of 10 particles/μL and 0.07 amol, respectively. After lyophilization, CLHN-CCC shows no obvious loss of performance within 6 months, making it much more robust and user friendly. This technique could sensitively (sensitivity = 92.9%) and selectively (selectivity = 85.7%) identify low amount miR-1290 in serum EVs, distinguishing early-stage pancreatic cancer patients from healthy subjects, showing high potential for clinical applications. [ABSTRACT FROM AUTHOR]

• A CRISPR-powered single-reaction multiple detection technology was developed. • RCA and HCR are integrated with CRISPR/Cas12a system for signal amplification and discrimination. • Its high performance is confirmed by identifying breast cancer patients. • Its application can be extended to construction of DNA logic gates. Recently, CRISPR/Cas system has garnered considerable attention owing to its high cleavage efficiency. However, it lacks the ability to differentiate between signal sources. To address this, we have developed a multiplex detection system called Cas-Rainbow. This system combines CRISPR/Cas with rolling circle amplification (RCA) and hybridization chain reaction (HCR) to enable the detection of multiple miRNAs using reporter probes labeled with different fluorescent groups. The RCA product can trigger the formation of HCR and activate the Cas12a/crRNA complex, achieving the simultaneous detection of multiple miRNAs. Detection limits of three miRNAs (miR-155, miR-10b, and miR-21) were 33 fM, 41 fM, and 79 fM, respectively. Cas-Rainbow system could effectively identify these three miRNAs in serum, distinguishing breast cancer patients from healthy donors with accuracy of 100 %. Moreover, this system exhibited exceptional performance in logic gate circuits, showcasing its remarkable versatility and robustness. In summary, our proposed method offers a new approach for multiplex detection based on the CRISPR/Cas system. [ABSTRACT FROM AUTHOR]

Abstract Mechanisms of powder magnesium and carbon dioxide combustion are required for the concept of Mars propulsion based on the perspective of in-situ resource utilization. Most current characterizations are based on laboratory experiments conducted in stationary or simple flow configuration. However, the chamber condition in most applications of engine is very complicated with high pressure and multi-phase flow environment, and the combustion process in engine-scale has not been established. The burning efficiency, combustion stability and excessive deposition are the mainly primary issues that limit the combustion performance in rocket environment, the experimental study aims at combustion characteristics and the affection mechanism of powder magnesium and carbon dioxide in rocket engine. A new configuration of powder rocket system is established. Meanwhile, a multiple-inlet configuration of CO 2 injection is designated to control the CO 2 injection positions and parameters, such as global and local oxidant-fuel ratio. Ignition process is studied and an empirical model for ignition judgment is established according to the result of ignition tests. Mechanism for combustion deposition is studied by the analysis of morphology, composition and distribution, characteristics of combustion efficiency are estimated based on test pressure and thermodynamic calculation, and oscillation mechanism of combustion pressure is obtained by frequency domain analysis. The higher concentration of magnesium particle, the cool CO 2 injection and the increasing of CO concentration is supposed to be the main reasons for the deposition in different areas along the axis of the combustion chamber. The allocation of gas injection is an important factor that affects the combustion sufficiency associated to the heterogeneous reaction. Raising the O/F ratio in chamber head is an effective way to improve combustion efficiency for rocket engine, and the efficiency is improved firstly and then is decreased with increasing flow rate of fluidization gas. The low frequency oscillation is supposed to be related to flame instability induced by the gas injection in chamber head. The influence caused by primary and secondary gas injection are further analyzed in the frequency domain, the related characteristic bands are classified and the fluctuation tendency is obtained. Graphical abstract Image 1 Highlights Highlights of Experimental Study on Combustion Characteristics of Magnesium and Carbon Dioxide in Powder Rocket Environment: • Combustion investigation of magnesium and carbon dioxide in engine-scale • Powder combustion based on in-situ resource utilization for Mars exploration • Multiple gas injection configuration for combustion chamber of prototype rocket • Analysis of combustion efficiency and stability by fire experiment • Deposition characteristics and mechanism in combustion chamber [ABSTRACT FROM AUTHOR]

Powdered Mg and CO 2 bipropellant engine providing a practical demonstration of in situ resource utilization (ISRU) for Mars Sample Return (MSR) mission seems to be feasible by current investigations. However, essential functions of the engine to satisfy the complicated ballistics requirements such as thrust modulation and multiple pulse have not been established yet. The aim of this experimental study is to evaluate the engine's thrust modulation feasibility and to investigate its thrust modulation characteristics. A powdered Mg and CO 2 bipropellant engine construction aiming to achieve thrust modulation ability was proposed. A mass flow rate calibration experiment to evaluate the gas-solid mass flow rate regulating performance was conducted before fire tests. Fire test result shows that the engine achieved successful ignition as well as self-sustaining combustion; Thrust modulation of the engine is feasible, detail thrust estimating result of the test shows that maximum thrust is 135.91 N and the minimum is 5.65 N with a 22.11 thrust modulation ratio, moreover, the transportation period is quick and the thrust modulation ratio is adjustable. At the same time, the powder feed system reaches a two-step flow rate regulating with a modulation ratio of 4.5–5. What’ more, caused by the uneven engine working conditions, there is an obvious difference in combustion efficiency value, maximum combustion efficiency of the powdered Mg and CO 2 bipropellant engine is 80.20%. [ABSTRACT FROM AUTHOR]

MicroRNA (miRNA) has gained significant attention as a potential biomarker for cancer clinics, and there is an urgent need for developing sensing strategies with high selectivity, sensitivity, and low background. In vitro diagnosis based on Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-Associated protein (CRISPR/Cas) technology could simplify the detection procedure, improve sensitivity and selectivity, and has broad application prospects as the next-generation molecular diagnosis technology. We propose a novel dual signal amplification strategy, called CENTER, which integrates the CRISPR/Cas12a system, an entropy-driven DNA signaling network, and strand displacement amplification to achieve ultrasensitive detection of miR-141, a potential marker for prostate cancer. The experimental results demonstrate that CENTER can distinguish single nucleotide mutations, and the strategy exhibits a good linear calibration curve ranging from 100 aM to 1 pM. Due to dual signal amplification, the detection limit is as low as 34 aM. We proposed a method for identifying miR-141 expressed in human serum and successfully distinguished between prostate cancer patients (n = 20) and healthy individuals (n = 15) with an impressive accuracy of 94%. Overall, CENTER shows great promise for the detection of miRNA. [Display omitted] • Proposal of a novel dual signal amplification strategy based on CRISPR/Cas12a. • Abundant CRISPR/Cas12a enzymes enable highly sensitive detection of miR-141. • The proposed strategy show excellent practical performance in human serum samples. [ABSTRACT FROM AUTHOR]

• A CRISPR-powered multifunctional detection biosensor was developed. • Three DNA nanodumbbell lock structures were used for multiple molecular detection. • Early-stage prostate cancer patients could be distinguished from healthy people. • The DNA nanodumbbell locks were able to assembled in advance, allowing its application even in resource limited settings. Detection of multiple biomarkers for accurate diagnosis of disease is highly desirable but remains challenging. Here, we developed a versatile diagnostic biosensor (SMARTLOCK) through the unique combination of DNA tetrahedron, nonlinear HCR and CRISPR-Cas12a system for simultaneous detection of multiple nucleic acids, small molecules, proteins and different types of combinations. Two DNA tetrahedrons are assembled into a functional dumbbell lock, which was unlocked by the target molecules, thereby triggering a two-stage signal amplification of nonlinear HCR and CRISPR-Cas12a to generate powerful fluorescence signals. The capability of multi-target simultaneous detection of SMARTLOCK is demonstrated in the detection of miR-141, miR-375, miR-21, ATP, cortisol, insulin and their combinations. SMARTLOCK could selectively (specificity = 93.3%) and sensitively (sensitivity = 90%) distinguish early-stage prostate cancer (PCa) patients (n = 10) from healthy donors (n = 30). Measurement of two PCa-related RNAs (miR-141 and miR-375) shows the potential of SMARTLOCK to be a highly accurate and low-cost tool for the screening, diagnosis and prognosis of various diseases. [ABSTRACT FROM AUTHOR]

[Display omitted] • A MEA-DMF based S free solution for preparing CZTSe was successfully developed. • Phase evolution of CZTSe thin film during selenization was studied. • A device efficiency of 7.53% was obtained by using the MEA-DMF solution method. Most precursor solutions for preparing Cu 2 ZnSn(S,Se) 4 thin films use sulfur containing groups to complex metal ions. However, solutions with sulfur containing groups are always toxic and harmful gases, such as H 2 S and SO x , will be released when drying precursor films. Based on the excellent chelating ability of ethanolamine, a stable molecular precursor solution without using sulfur based complexing agent was successfully developed. Cu-Sn alloy phase is formed in the precursor film, which makes the phase evolution of the absorber during selenization similar to that of Cu 2 ZnSnSe 4 film grown from metallic precursor. Impacts of selenization time on compositional, morphological and photovoltaic properties of the Cu 2 ZnSnSe 4 film were studied. Finally, a Cu 2 ZnSnSe 4 solar cell with conversion efficiency of 7.53% was obtained by using the ethanolamine-dimethyl formamide based solution. [ABSTRACT FROM AUTHOR]

Most reported solution processed Cu 2 ZnSn(S,Se) 4 thin film solar cells are fabricated from precursor solution with sulfur source. However, the use of sulfur-containing solution is undesirable from the viewpoint of environment and security due to the release of sulfur-containing harmful gases when drying precursors. Here, a novel sulfur/selenium-free solution method using ethanolamine-dimethyl formamide as solvent was developed for the preparation of Cu 2 ZnSnSe 4 thin films. It was found that Cu-Sn alloy phases were formed in precursor during drying process. The formation and phase transition mechanisms of the Cu-Sn phases were illustrated. The aggregation level of the alloy phases and their distribution in the precursor depend on the drying time. Effects of different drying time on structural, morphological and photoelectric properties of the resulted Cu 2 ZnSnSe 4 films were systematically investigated. The Cu 2 ZnSnSe 4 absorbers exhibit a sandwiched structure or a four-layer structure, which is determined by the drying time of precursor, implying two different grain growth mechanisms. The devices with drying time of 6 min show larger grain size, longer carrier life time, higher external quantum efficiency and better average photovoltaic performance. [Display omitted] • A S/Se free pure solution method was developed for growing CZTSe thin films. • Formation and phase transition mechanisms of Cu-Sn alloys in precursor were investigated. • Short drying time of precursor leads to carbon-rich surface of CZTSe thin film. • Aggregation level of Cu-Sn phase affects absorber morphology and device performance. [ABSTRACT FROM AUTHOR]

An experimental system is established to study the behavior of burning aluminum droplets impacting a wall in a solid-rocket-motor environment. First, the rebound process of droplets impinging on the wall is observed using shadow shooting; the size range of the burning aluminum droplets is 150–500 μm, and their range of impact speed is 1–5 m/s. Second, a formula is developed for predicting the droplet–wall contact time, and combined with energy conservation, a model for predicting the behavior of aluminum droplets impacting the wall is established. Furthermore, analyzing the droplet velocity reveals that the total restitution coefficient decreases gradually with increasing Weber number, whereupon a model for calculating the restitution coefficient is proposed. Compared with experimental results, the errors of the prediction model are within 15%. Finally, a new phenomenon involving the oscillatory motion of burning aluminum droplets is discovered; analyzing this oscillatory behavior gives an equation for the attenuation of the oscillation of droplets moving in a gas flow, and the results of this equation agree well with experimental data. The present experimental system and measurement method are suitable for fine measurements of the rebound process of burning aluminum droplets, and the present results lay a foundation for (i) studying the law governing the motion of aluminum droplets in a solid rocket motor and (ii) revealing the mechanism for interaction between them and the inner surface of the combustion chamber. [ABSTRACT FROM AUTHOR]

Red deer (Cervus elaphus/hanglu/canadensis) are a group of closely-related species that survived through the Last Glacial period in Eurasia and expanded into North America. The evolutionary modes of red deer in Europe through glacial and interglacial cycles have been established relatively well based on both modern and ancient genomes, while the evolutionary and migratory history of red deer in Asia are not so clear. Northern China, as the southern border of their current distribution, is a significant area for exploring the evolution of wapitoids (Cervus canadensis). Here, we constructed six mitochondrial genomes (lengths of 13,282–16,306 bp) from Late Pleistocene fossil cervid materials in Northeastern China, and four modern complete mitochondrial DNA sequences (16,798–16943 bp) from Northern China. Phylogenetic analyses suggest four clades in wapitoids, with our new individuals clustered into three out of the four clades. BEAST analysis indicates that the divergence between elaphoids (including Cervus elaphus and Cervus hanglu) and the complex of 'wapitoids + sika deer (Cervus nippon)' occurred at approximately 1.37 million years ago (Ma, 95%Cl: 1.64–1.15 Ma). Bayesian skyline plots (BSPs) show that the effective maternal population size of wapitoids had a slight and stable expansion between Marine isotope stages (MIS) 7–3, and then shrank from the beginning of the Last Glacial Maximum (LGM). Combined with the divergence dates, population dynamics, and fossil findings in Northern China, we infer that after wapitoids migrated eastward from Central Asia to Northeastern Asia, they had multiple migrations southward into Northern China. The current distribution of wapitoids in Northern China was likely shaped by these migrations as well as habitat fragmentation. Meanwhile, the radiocarbon dates of ancient individuals indicate that the Northeast China Plain, located at the same latitude as European refugia, may have provided a refugium for megafaunal species such as red deer to survive the LGM. • First combined sampling of both ancient and extant mitogenomes of wapitoids in China. • Demonstrating habitat fragmentation or multiple migratory events of wapitoids in Northern China. • Indicating a possible refuge for megafauna species in Northeastern China in LGM. [ABSTRACT FROM AUTHOR]

Rapid and specific quantitation of a variety of RNAs with low expression levels in early-stage cancer is highly desirable but remains a challenge. Here, we present a dual signal amplification strategy consisting of the CRISPR/Cas13a system and a catalytic hairpin DNA circuit (CHDC), integrated on a reusable electrochemical biosensor for rapid and accurate detection of RNAs. Signal amplification is accomplished through the unique combination of the CRISPR/Cas13a system with CHDC, achieving a limit of detection of 50 aM within a readout time of 6 min and an overall process time of 36 min, using a measuring volume of 10 μL. Enzymatic regeneration of the sensor surface and ratiometric correction of background signal allow up to 37 sequential RNA quantifications by square-wave voltammetry on a single biosensor chip without loss of sensitivity. The reusable biosensor platform could selectively (specificity = 0.952) and sensitively (sensitivity = 0.900) identify low expression RNA targets in human serum, distinguishing early-stage patients (n = 20) suffering from non-small-cell lung carcinoma (NSCLC) from healthy subjects (n = 30) and patients with benign lung disease (n = 12). Measurement of six NSCLC-related RNAs (miR-17, miR-155, TTF-1 mRNA, miR-19b, miR-210 and EGFR mRNA) shows the ability of the electrochemical CRISPR/CHDC system to be a fast, low-cost and highly accurate tool for early cancer diagnostics. Image 1 • An electrochemical biosensor based on dual isothermal amplification is developed. • Program the CRISPR/Cas13a system with catalytic hairpin DNA circuit to detect RNAs. • Enzymatic surface regeneration and ratiometric background correction are achieved. • Early-stage lung cancer patients are distinguished from healthy ones. [ABSTRACT FROM AUTHOR]

Graphene oxide was found to be a highly efficient and cost-effective heterogeneous catalyst for the direct metal-free transformation of quinoline and isoquinoline N -oxides into the corresponding nitriles under mild conditions. This method is simple, economic and environmentally benign, representing a useful strategy for the convenient synthesis of α-cyano N -oxides that are difficult to prepare by transition-metal-free catalyzed methods. In vitro , compound 2s exhibited good activities against T-24 cell lines with IC 50 values in 10.23 ± 1.05 μM. Further studies investigated the mechanism of the effective inhibition of cell growth, including apoptosis ratio dection, cell cycle analysis, measurement of Ca2+ generation, ROS, and mitochondrial dysfunction. [Display omitted] • The GO-catalyzed cyanation of N -oxides under metal-free and base-free reaction conditions. • This protocol is green and practical due to the use of inexpensive GO as the catalyst. • 4-Bromo-1-cyanoisoquinoline 2-oxide exhibited good activities against T-24 cell lines. • This protocol is not accompanied by the N-O bond cleavage. [ABSTRACT FROM AUTHOR]

There were several species of Equus in northern China during the Late Pleistocene, including Equus przewalskii and Equus dalianensis. A number of morphological studies have been carried out on E. przewalskii and E. dalianensis , but their evolutionary history is still unresolved. In this study, we retrieved near-complete mitochondrial genomes from E. dalianensis and E. przewalskii specimens excavated from Late Pleistocene strata in northeastern China. Phylogenetic analyses revealed that caballoid horses were divided into two subclades: the New World and the Old World caballine horse subclades. The Old World caballine horses comprise of two deep phylogenetic lineages, with modern and ancient Equus caballus and modern E. przewalskii forming lineage Ⅰ, and the individuals in this study together with one Yakut specimen forming lineage Ⅱ. Our results indicate that Chinese Late Pleistocene caballoid horses showed a closer relationship to other Eurasian caballine horses than that to Pleistocene horses from North America. In addition, phylogenetic analyses suggested a close relationship between E. dalianensis and the Chinese fossil E. przewalskii , in agreement with previous researches based on morphological analyses. Interestingly, E. dalianensis and the fossil E. przewalskii were intermixed rather than split into distinct lineages, suggesting either that gene flow existed between these two species or that morphology-based species assignment of palaeontological specimens is not always correct. Moreover, Bayesian analysis showed that the divergence time between the New World and the Old World caballoid horses was at 1.02 Ma (95% CI: 0.86–1.24 Ma), and the two Old World lineages (Ⅰ & Ⅱ) split at 0.88 Ma (95% CI: 0.69–1.13 Ma), which indicates that caballoid horses seem to have evolved into different populations in the Old World soon after they migrated from North America via the Bering Land Bridge. Finally, the TMRCA of E. dalianensis was estimated at 0.20 Ma (95% CI: 0.15–0.28 Ma), and it showed a relative low genetic diversity compared with other Equus species. • The Late Pleistocene Equus dalianensis and Equus przewalskii from China belong to a separate clade. • Chinese Late Pleistocene caballoid horses were closer to other Eurasian counterparts than to Pleistocene horses from Yukon. • The New World and the Old World caballoid horses split at 1.02 Ma, and the two Old World lineages split at 0.88 Ma. • Equus dalianensis showed a relative low genetic diversity compared with other Equus species. [ABSTRACT FROM AUTHOR]

Carbon deposition can significantly reduce the working stability and specific impulse performance of magnesium/carbon dioxide (Mg/CO 2) powder rocket engines; however, few studies have quantitatively analyzed carbon generation characteristics during the Mg/CO 2 combustion process. Therefore, this study presents a quantitative analysis of the carbon generation characteristics and degree of heterogeneous reaction during Mg/CO 2 combustion in a closed high-temperature furnace. The analytical methods used include elemental analysis (EA) and inductively coupled plasma-optical emission spectrometry (ICP-OES). Experimental results showed that increasing the ambient temperature and decreasing the particle size both effectively suppressed carbon generation through a heterogeneous reaction, which is discussed from a thermodynamic perspective. When the particle size was 5 μm, the degree of heterogeneous reaction increased from 16.2% to 26.6% as the ambient temperature decreased from 1573 K to 1173 K; and when the ambient temperature was 1573 K, the degree of heterogeneous reaction increased from 16.2% to 23.2% as the particle size increased from 5 μm to 160 μm. Excessive CO concentration on the surface of Mg particles resulted in a large amount of carbon deposition, along with an insufficient Mg burnout rate. The proportion of Mg in the two pretreated powder samples participating in the heterogeneous reaction is reduced by 41% and 52%, respectively, compared with that in the source powder. Moreover, the combustion performance of pretreated Mg powder is typically excellent in CO 2 due to the micro-explosion phenomenon. These findings are expected to contribute to improved working stability and specific impulse performance of Mg/CO 2 powder rocket engines intended for Mars exploration. [ABSTRACT FROM AUTHOR]

High salinity in wastewater often hampers the performance of traditional adsorbents by disrupting electrostatic interactions and ion exchange processes, limiting their efficiency. This study addresses these challenges by investigating the salt-promoted adsorption of Cu ions onto amino-functionalized chloromethylated polystyrene (EDA@CMPS) millispheres. The adsorbent was synthesized by grafting ethylenediamine (EDA) onto CMPS, which significantly improved Cu adsorption, achieving nearly three times the capacity in saline solutions (1.65 mmol g -1 ) compared to non-saline solutions (0.66 mmol g -1 ). Mechanistic analysis showed that the presence of salts, such as NaCl, promoted the protonation of amino groups on EDA@CMPS, increasing their positive charge and enhancing their affinity for Cu ions. The solution's ionic strength further amplified this protonation, reducing electrostatic repulsion between the adsorbent and the Cu ions, thus improving binding efficiency. Additionally, the increased ionic strength altered Cu speciation, favoring the formation of Cu(NH 3 ) 4 2+ complexes, which were more easily adsorbed. These synergistic effects resulted in faster adsorption kinetics, higher capacity, and improved Cu ion removal, particularly in saline environments. Overall, these findings bridge the gap between material design and functional performance in high-salinity wastewater, offering a promising strategy for efficient heavy metal removal and environmental remediation.

The links between Thyroid dysfunction diseases (TDFDs) and osteoporosis (OP) has received widespread attention, but the causal relationships and mediating factors have not been systematically studied. We used two-sample Mendelian randomization (MR) analysis to elucidate the causal relationship between TDFDs and OP. Moreover, we performed mediation MR analyses to explore the role of thyroid-related hormones and OP risk factors in the association between TDFDs and OP. Two sample MR analyses showed that hyperthyroidism increased OP (OR = 1.080, 95% CI 1.026 to 1.137; P = 0.0032) risk. Hypothyroidism increases OP (OR = 1.183, 95% CI 1.125 to 1.244; P < 0.0001) risk. Furthermore, mediation analysis revealed that TSH mediated 5.314% of the relationship between hypothyroidism and OP. In contrast, FT4 mediated 9.670% of the relationship between hyperthyroidism and OP. In European populations, TDFDs may increase OP risk. TSH mediates in the causal association between hypothyroidism and OP, and similarly, FT4 mediates in the causal link between hyperthyroidism and OP. Our findings underscore the significance of improving integrative care for individuals with TDFDs to mitigate the risk of OP. It is essential to maintain stable levels of thyroid hormones and closely monitor bone health to effectively mitigate and prevent OP., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Cancer is a group of complex diseases, with tumor heterogeneity, durable drug efficacy, emerging resistance, and host toxicity presenting major challenges to the development of effective cancer therapeutics. While traditionally used methods have remained limited in their capacity to overcome these challenges in cancer drug development, efforts have been made in recent years toward applying "big data" to cancer research and precision oncology. By curating, standardizing, and integrating data from various databases, we developed deep learning architectures that use perturbation and baseline transcriptional signatures to predict efficacious small molecule compounds and genetic dependencies in cancer. A series of internal validations followed by prospective validation in prostate cancer cell lines were performed to ensure consistent performance and model applicability. We report SensitivitySeq , a novel bioinformatics tool for prioritizing small molecule compounds and gene dependencies in silico to drive the development of targeted therapies for cancer. To the best of our knowledge, this is the first supervised deep learning approach, validated in vitro , to predict drug sensitivity using baseline cancer cell line gene expression alongside cell line-independent perturbation-response consensus signatures., Competing Interests: Declaration of interests The authors declare no competing interests.

Objective: To investigate the prevalence and risk factors of psychological symptoms and quality of life (QoL) in early patients with inflammatory bowel disease (IBD)., Methods: From September 2021 to May 2022, a unified questionnaire was developed to collect clinical data from early patients with IBD from 42 tertiary care hospitals. The influencing factors of psychological symptoms and poor QoL are screened by logistic regression analysis for constructing model in predicting poor QoL. The consistency index, receiver operating characteristic (ROC) curve, area under the ROC curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), calibration curve, and decision curve analysis (DCA) were used to evaluate the performance of the model., Results: A total of 939 early patients with IBD were surveyed, Among them, 20.3% exhibited anxiety, 21.7% had depression, 57.3% experienced sleep disturbance, and 41.9% reported poor QoL. The factors influencing psychological symptoms varied between ulcerative colitis (UC) and Crohn's disease (CD) patients. The QoL was primarily affected by disease activity, income level and depression. The AUC value of the model in the training group was 0.781 (95% CI: 0.748-0.814). The calibration diagram of the model closely matched the ideal curve. Compared to other prediction models, our model showed superior predictive capability, with NRI and IDI values of 0.324 (95%CI:0.196-0.4513) and 0.026 (95%CI:0.014-0.038), respectively. DCA indicated that the nomogram model could provide clinical benefits., Conclusion: Early patients with IBD exhibit a high prevalence of psychological symptoms and poor QoL. The nomogram prediction model we constructed demonstrates high accuracy and performance in predicting QoL in early patients with IBD., Competing Interests: Declarations Ethics approval and consent to participate The study complies with the Declaration of Helsinki. The study was approved by the Institutional Review Board of Renmin Hospital of Wuhan University, and informed consent was obtained from all patients. The clinical research Ethics Review approval number of Renmin Hospital of Wuhan University was WDRY2022-K150. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Smart memristors with innovative properties are crucial for the advancement of next-generation information storage and bioinspired neuromorphic computing. However, the presence of significant sneak currents in large-scale memristor arrays results in operational errors and heat accumulation, hindering their practical utility. This study successfully synthesizes a quasi-free-standing Bi 2 O 2 Se single-crystalline film and achieves layer-controlled oxidation by developing large-scale UV-assisted intercalative oxidation, resulting β-Bi 2 SeO 5 /Bi 2 O 2 Se heterostructures. The resulting β-Bi 2 SeO 5 /Bi 2 O 2 Se memristor demonstrates remarkable self-rectifying resistive switching performance (over 10 5 for ON/OFF and rectification ratios, as well as nonlinearity) in both nanoscale (through conductive atomic force microscopy) and microscale (through memristor array) regimes. Furthermore, the potential for scalable production of self-rectifying β-Bi 2 SeO 5 /Bi 2 O 2 Se memristor, achieving sub-pA sneak currents to minimize cross-talk effects in high-density memristor arrays is demonstrated. The memristors also exhibit ultrafast resistive switching (sub-100 ns) and low power consumption (1.2 pJ) as characterized by pulse-mode testing. The findings suggest a synergetic effect of interfacial Schottky barriers and oxygen vacancy migration as the self-rectifying switching mechanism, elucidated through controllable β-Bi 2 SeO 5 thickness modulation and theoretical ab initio calculations., (© 2024 Wiley‐VCH GmbH.)

As an effective formula of traditional Chinese medicine, Yang-Gan-Jiang-Mei (YGJM) formula exhibited a unique advantage in ameliorating liver injury and hepatic steatosis of non-alcoholic steatohepatitis (NASH). Nevertheless, the related pharmacological mechanism needs to be elucidated. This study aimed to explore the molecular mechanism of YGJM formula on mitophagy mediated by PINK1/parkin signaling pathway and NOD-like receptor protein 3 (NLRP3) inflammasome in NASH. High-fat-diet rats and HepG2 cells induced by free fatty acid were used as NASH models in vivo and in vitro . Liver pathology and serum indicator embodying liver function (aspartate transferase, alanine transferase, triglyceride, and total cholesterol) were applied to evaluate the extent of hepatic damage and lipid accumulation. Besides, transmission electron microscopy, JC-1 and 2',7'-dichlorofluorescein diacetate were utilized to observe hepatic mitochondrial morphology, as well as cellular mitochondrial membrane potential and reactive oxygen species level. Additionally, expression of PINK1/parkin-mediated mitophagy and NLRP3 inflammasome was detected to elucidate the underlying mechanism of YGJM formula by immunohistochemistry, immunofluorescence, RT-PCR (reverse transcription-polymerase chain reaction) and Western blot. The manifestations of pathology and biochemical detection confirmed the efficacy of YGJM formula in relieving hepatic damage and lipid deposition. Simultaneously, YGJM formula could obviously improve mitochondrial function. In addition, YGJM formula exhibited the promotion of PINK1/parkin-mediated mitophagy, which could perturb NLRP3 inflammasome activation, and as a result, the hepatocyte inflammation was also suppressed both in vitro and in vivo . Our preliminary results indicate that YGJM formula can ameliorate NASH mechanistically by interfering with PINK1/parkin-mediated mitophagy and NLRP3 inflammasome to exert anti-inflammation ability and promote mitochondrial function restoration.

The goal of this study was to assess the impacts or benefits of sludge in situ reduction (SIR) within wastewater treatment processes with relation to global warming potential in wastewater treatment plants, with a comprehensive consideration of wastewater and sludge treatment. The anaerobic side-stream reactor (ASSR) and the sludge process reduction activated sludge (SPRAS), two typical SIR technologies, were used to compare the carbon footprint analysis results with the conventional anaerobic - anoxic - oxic (AAO) process. Compared to the AAO, the ASSR with a typical sludge reduction efficiency (SRE) of 30 % increased greenhouse gas (GHG) emissions by 1.1 - 1.7 %, while the SPRAS with a SRE of 74 % reduced GHG emissions by 12.3 - 17.6 %. Electricity consumption (0.025 - 0.027 kg CO 2-eq /m 3 ), CO 2 emissions (0.016 - 0.059 kg CO 2-eq /m 3 ), and N 2 O emissions (0.009 - 0.023 kg CO 2-eq /m 3 ) for the removal of secondary substrates released from sludge decay in the SIR processes were the major contributor to the increased GHG emissions from the wastewater treatment system. By lowering sludge production and the organic matter content in the sludge, the SIR processes significantly decreased the carbon footprints associated with sludge treatment and disposal. The threshold SREs of the ASSR for GHG reduction were 27.7 % and 34.6 % for the advanced dewatering - sanitary landfill and conventional dewatering - drying-incinerating routes, respectively. Overall, the SPRAS process could be considered as a cost-effective and sustainable low-carbon SIR technology for wastewater treatment., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Objective: The correlation between cholangiocarcinoma (CCA) progression and bile is rarely studied. Here, we aimed to identify differential metabolites in benign and malignant bile ducts and elucidate the generation, function and degradation of bile metabolites., Design: Differential metabolites in the bile from CCA and benign biliary stenosis were identified by metabonomics. Biliary molecules able to induce mast cell (MC) degranulation were revealed by in vitro and in vivo experiments, including liquid chromatography-mass spectrometry (MS)/MS and bioluminescence resonance energy transfer assays. Histamine (HA) receptor expression in CCA was mapped using a single-cell mRNA sequence. HA receptor functions were elucidated by patient-derived xenografts (PDX) in humanised mice and orthotopic models in MC-deficient mice. Genes involved in HA-induced proliferation were screened by CRISPR/Cas9., Results: Bile HA was elevated in CCA and indicated poorer prognoses. Cancer-associated fibroblasts (CAFs)-derived stem cell factor (SCF) recruited MCs, and bile N,N-dimethyl-1,4-phenylenediamine (DMPD) stimulated MCs to release HA through G protein-coupled receptor subtype 2 (MRGPRX2)-Gαq signalling. Bile-induced MCs released platelet-derived growth factor subunit B (PDGF-B) and angiopoietin 1/2 (ANGPT1/2), which enhanced CCA angiogenesis and lymphangiogenesis. Histamine receptor H1 (HRH1) and HRH2 were predominantly expressed in CCA cells and CAFs, respectively. HA promoted CCA cell proliferation by activating HRH1-Gαq signalling and hastened CAFs to secrete hepatocyte growth factor by stimulating HRH2-Gαs signalling. Solute carrier family 22 member 3 (SLC22A3) inhibited HA-induced CCA proliferation by importing bile HA into cells for degradation, and SLC22A3 deletion resulted in HA accumulation., Conclusion: Bile HA is released from MCs through DMPD stimulation and degraded via SLC22A3 import. Different HA receptors exhibit a distinct expression profile in CCA and produce different oncogenic effects. MCs promote CCA progression in a CCA-bile interplay pattern., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Colorectal cancer (CRC) is a prevalent global health issue, with 5-fluorouracil (5-FU) being a commonly used chemotherapeutic agent for its treatment. However, the efficacy of 5-FU is often hindered by drug tolerance. Sodium butyrate (NaB), a derivative of intestinal flora, has demonstrated anti-cancer properties both in vitro and in vivo through pro-apoptotic effects and has shown promise in improving outcomes when used in conjunction with traditional chemotherapy agents. This study seeks to evaluate the impact and potential mechanisms of NaB in combination with 5-FU on CRC. We employed a comprehensive set of assays, including CCK-8, EdU staining, Hoechst 33258 staining, flow cytometry, ROS assay, MMP assay, immunofluorescence, and mitophagy assay, to detect the effect of NaB on the biological function of CRC cells in vitro. Western blotting and immunohistochemistry were used to verify the above experimental results. The xenograft tumor model was established to evaluate the in vivo anti-CRC activity of NaB. Subsequently, 16S rRNA gene sequencing was used to analyze the intestinal flora. The findings of our study demonstrate that sodium butyrate (NaB) exerts inhibitory effects on tumor cell proliferation and promotes tumor cell apoptosis in vitro, while also impeding tumor progression in vivo through the enhancement of the mitophagy pathway. Furthermore, the combined treatment of NaB and 5-fluorouracil (5-FU) yielded superior therapeutic outcomes compared to monotherapy with either agent. Moreover, this combination therapy resulted in the specific enrichment of Bacteroides, LigiLactobacillus, butyric acid-producing bacteria, and acetic acid-producing bacteria in the intestinal microbiota. The improvement in the intestinal microbiota contributed to enhanced therapeutic outcomes and reduced the adverse effects of 5-FU. Taken together, these findings indicate that NaB, a histone acetylation inhibitor synthesized through intestinal flora fermentation, has the potential to significantly enhance the therapeutic efficacy of 5-FU in CRC treatment and improve the prognosis of CRC patients., (© 2024. The Author(s).)

Extant Old World camels (genus Camelus) contributed to the economic and cultural exchanges between the East and West for thousands of years. 1 , 2 Although many remains have been unearthed, 3 , 4 , 5 we know neither whether the prevalent hybridization observed between extant Camelus species 2 , 6 , 7 also occurred between extinct lineages and the ancestors of extant Camelus species nor why some populations became extinct while others survived. To investigate these questions, we generated paleogenomic and stable isotope data from an extinct two-humped camel species, Camelus knoblochi. We find that in the mitochondrial phylogeny, all C. knoblochi form a paraphyletic group that nests within the diversity of modern, wild two-humped camels (Camelus ferus). In contrast, they are clearly distinguished from both wild and domesticated (Camelus bactrianus) two-humped camels on the nuclear level. Moreover, the divergence pattern of the three camel species approximates a trifurcation, because the most common topology is only slightly more frequent than the two other possible topologies. This mito-nuclear phylogenetic discordance likely arose due to interspecific gene flow between all three species, suggesting that interspecific hybridization is not exclusive to modern camels but a recurrent phenomenon throughout the evolutionary history of the genus Camelus. These results suggest that the genomic complexity of Old World camels' evolutionary history is underestimated when considering data from only modern species. Finally, we find that C. knoblochi populations began declining prior to the last glacial maximum and, by integrating palaeoecological evidence and stable isotope data, suggest that this was likely due to failure to adapt to a changing environment., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Gastric cancer (GC) represents a significant health burden with dire prognostic implications upon metastasis and recurrence. Pterostilbene (PTE) has been proven to have a strong ability to inhibit proliferation and metastasis in other cancers, while whether PTE exhibits anti-GC activity and its potential mechanism remain unclear., Purpose: To explore the efficacy and potential mechanism of PTE in treating GC., Methods: We employed a comprehensive set of assays, including CCK-8, EdU staining, colony formation, flow cytometry, cell migration, and invasion assays, to detect the effect of PTE on the biological function of GC cells in vitro. The xenograft tumor model was established to evaluate the in vivo anti-GC activity of PTE. Network pharmacology was employed to predict PTE's potential targets and pathways within GC. Subsequently, Western blotting, immunofluorescence, and immunohistochemistry were utilized to analyze protein levels related to the cell cycle, EMT, and the JAK2/STAT3 pathway., Results: Our study demonstrated strong inhibitory effects of PTE on GC cells both in vitro and in vivo. In vitro, PTE significantly induced cell cycle arrest at G0/G1 and S phases and suppressed proliferation, migration, and invasion of GC cells. In vivo, PTE led to a dose-dependent reduction in tumor volume and weight. Importantly, PTE exhibited notable safety, leaving mouse weight, liver function, and kidney function unaffected. The involvement of the JAK2/STAT3 pathway in PTE's anti-GC effect was predicted utilizing network pharmacology. PTE suppressed JAK2 kinase activity by binding to the JH1 kinase structural domain and inhibited the downstream STAT3 signaling pathway. Western blotting confirmed PTE's inhibition of the JAK2/STAT3 pathway and EMT-associated protein levels. The anti-GC effect was partially reversed upon STAT3 activation, validating the pivotal role of the JAK2/STAT3 signaling pathway in PTE's activity., Conclusion: Our investigation validates the potent inhibitory effects of PTE on the proliferation and metastasis of GC cells. Importantly, we present novel evidence implicating the JAK2/STAT3 pathway as the key mechanism through which PTE exerts its anti-GC activity. These findings not only establish the basis for considering PTE as a promising lead compound for GC therapeutics but also contribute significantly to our comprehension of the intricate molecular mechanisms underlying its exceptional anti-cancer properties., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Portal vein tumor thrombosis (PVTT) frequently leads to malignant ascites (MA) in individuals with hepatocellular carcinoma (HCC), remaining a bottleneck in the treatment. This study aimed to explore the differences in microbes in paired groups and provide novel insights into PVTT and MA-related treatments. Formalin-fixed paraffin embedding ascite samples were collected from MA secondary to HCC and benign ascites (BA) secondary to liver cirrhosis (LC). Ascitic microbiota profiles were determined in the HCC and LC groups by 16S rRNA sequencing. Prognostic risk factors were screened using survival analysis. The correlation between the significantly different microbial signatures in the groups with PVTT (WVT) and non-PVTT (NVT) and clinical characteristics was explored. The expression of different immune cells was determined by labeling four markers in the MA tissue chips using multiplex immunohistochemistry. A total of 240 patients (196 with HCC with MA and 44 with LC with BA) were included in this study. Microbial profiles differed between the HCC and LC groups. PVTT and Barcelona Clinic Liver Cancer stage were shown to be prognostic risk factors. Significant differences in the alpha and beta diversities were observed between the WVT and NVT groups. Gammaproteobacteria and Acinetobacter were the most abundant in the HCC MA. Differences in microbial signatures between the WVT and NVT groups were correlated with the level of C-reactive protein and apolipoprotein A1. This study revealed the microbial differences in the tumor microenvironment of MA secondary to HCC and BA secondary to LC.IMPORTANCEFirst, we explored the alteration of the ascites ecosystem through the microbiota in patients with hepatocellular carcinoma (HCC) and liver cirrhosis. Second, this is the first clinical study to investigate the differences between patients with HCC with and without portal vein tumor thrombosis via 16S rRNA sequencing. These results revealed a decreased microbial diversity and metabolic dysregulation in individuals with HCC and portal vein tumor thrombosis. Gammaproteobacteria and Acinetobacter were the most abundant in the HCC malignant ascitic fluid. Our study provides a new perspective on treating malignant ascites secondary to HCC., Competing Interests: The authors declare no conflict of interest.

Simultaneous multi-target detection and multi-site gene editing are two key factors restricting the development of disease diagnostic and treatment technologies. Despite numerous explorations on the source, classification, functional features, crystal structure, applications and engineering of CRISPR-Cas13a, all reports use the contiguous target RNA activation paradigm that only enables single-target detection in vitro and one-site gene editing in vivo. Here we propose a noncontiguous target RNA activation paradigm of Cas13a and establish a CRISPR-Cas13a Gemini System composed of two Cas13a:crRNA binary complexes, which can provide rapid, simultaneous, highly specific and sensitive detection of two RNAs in a single readout, as well as parallel dual transgene knockdown. CRISPR-Cas13a Gemini System are demonstrated in the detection of two miRNAs (miR-155 and miR-375) for breast cancer diagnosis and two small RNAs (EBER-1 and EBER-2) for Epstein-Barr virus diagnosis using multiple diagnostic platforms, including fluorescence and colorimetric-based lateral flow systems. We also show that CRISPR-Cas13a Gemini System can knockdown two foreign genes (EGFP and mCherry transcripts) in mammalian cells simultaneously. These findings suggest the potential of highly effective and simultaneous detection of multiple biomarkers and gene editing of multiple sites., (© 2024. The Author(s).)

Background: Preeclampsia (PE) is one of the most severe pregnancy-related diseases; however, there is still a lack of reliable biomarkers. In this study, we aimed to develop models for predicting early-onset PE, severe PE, and the gestation duration of patients with PE., Methods: Eligible patients with PE were enrolled and divided into a training ( n = 253) and a validation ( n = 108) cohort. Multivariate logistic and Cox models were used to identify factors associated with early-onset PE, severe PE, and the gestation duration of patients with PE. Based on significant factors, nomograms were developed and evaluated using the area under the curve (AUC) and a calibration curve., Results: In the training cohort, multiple gravidity experience ( p = 0.005), lower albumin (ALB; p < 0.001), and higher lactate dehydrogenase (LDH; p < 0.001) were significantly associated with early-onset PE. Abortion history ( p = 0.017), prolonged thrombin time (TT; p < 0.001), and higher aspartate aminotransferase ( p = 0.002) and LDH ( p = 0.003) were significantly associated with severe PE. Abortion history ( p < 0.001), gemellary pregnancy ( p < 0.001), prolonged TT ( p < 0.001), higher mean platelet volume ( p = 0.014) and LDH ( p < 0.001), and lower ALB ( p < 0.001) were significantly associated with shorter gestation duration. Three nomograms were developed and validated to predict the probability of early-onset PE, severe PE, and delivery time for each patient with PE. The AUC showed good predictive performance, and the calibration curve and decision curve analysis demonstrated clinical practicability., Conclusion: Based on the clinical features and peripheral blood laboratory indicators, we identified significant factors and developed models to predict early-onset PE, severe PE, and the gestation duration of pregnant women with PE, which could help clinicians assess the clinical outcomes early and design appropriate strategies for patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xia, Wang, Yuan, Hu, Zhang, Xie, Zhao, Hao, Ren and Wu.)