Histamine H1 receptors in dentate gyrus-projecting cholinergic neurons of the medial septum suppress contextual fear retrieval in mice.

Fear memory is essential for survival and adaptation, yet excessive fear memories can lead to emotional disabilities and mental disorders. Despite previous researches have indicated that histamine H1 receptor (H1R) exerts critical and intricate effects on fear memory, the role of H1R is still not clarified. Here, we show that deletion of H1R gene in medial septum (MS) but not other cholinergic neurons selectively enhances contextual fear memory without affecting cued memory by differentially activating the dentate gyrus (DG) neurons in mice. H1R in cholinergic neurons mediates the contextual fear retrieval rather than consolidation by decreasing acetylcholine release pattern in DG. Furthermore, selective knockdown of H1R in the MS is sufficient to enhance contextual fear memory by manipulating the retrieval-induced neurons in DG. Our results suggest that H1R in MS cholinergic neurons is critical for contextual fear retrieval, and could be a potential therapeutic target for individuals with fear-related disorders.

Vat Photopolymerization of Ceramic Parts: Effects of Carbon Fiber Additives on Microstructure and Mechanical Performance.

Vat photopolymerization (VPP), as an additive manufacturing (AM) technology, can conveniently produce ceramic parts with high resolution and excellent surface quality. However, due to the inherent brittleness and low toughness of ceramic materials, manufacturing defect-free ceramic parts remains a challenge. Many researchers have attempted to use carbon fibers as additives to enhance the performance of ceramic parts, but these methods are mostly applied in processes like fused deposition modeling and hot pressing. To date, no one has applied them to VPP-based AM technology. This is mainly because the black carbon fibers reduce laser penetration, making it difficult to cure the ceramic slurry and thus challenging to produce qualified ceramic parts. To address this issue, our study has strictly controlled the amount of carbon fibers by incorporating trace amounts of carbon fiber powder into the original ceramic slurry with the aim to investigate the impact of these additions on the performance of ceramic parts. In this study, ceramic slurries with three different carbon fiber contents (0 wt.%, 0.1 wt.%, 0.2 wt.%, and 0.3 wt.%) were used for additive manufacturing. A detailed comparative analysis of the microstructure, physical properties, and mechanical performance of the parts was conducted. The experimental results indicate that the 3D-printed alumina parts with added carbon fibers show varying degrees of improvement in multiple performance parameters. Notably, the samples prepared with 0.2 wt.% carbon fiber content exhibited the most significant performance enhancements.

Evaluation of fragility fracture risk using deep learning based on ultrasound radio frequency signal.

BACKGROUND: It was essential to identify individuals at high risk of fragility fracture and prevented them due to the significant morbidity, mortality, and economic burden associated with fragility fracture. The quantitative ultrasound (QUS) showed promise in assessing bone structure characteristics and determining the risk of fragility fracture. AIMS: To evaluate the performance of a multi-channel residual network (MResNet) based on ultrasonic radiofrequency (RF) signal to discriminate fragility fractures retrospectively in postmenopausal women, and compared it with the traditional parameter of QUS, speed of sound (SOS), and bone mineral density (BMD) acquired with dual X-ray absorptiometry (DXA). METHODS: Using QUS, RF signal and SOS were acquired for 246 postmenopausal women. An MResNet was utilized, based on the RF signal, to categorize individuals with an elevated risk of fragility fracture. DXA was employed to obtain BMD at the lumbar, hip, and femoral neck. The fracture history of all adult subjects was gathered. Analyzing the odds ratios (OR) and the area under the receiver operator characteristic curves (AUC) was done to evaluate the effectiveness of various methods in discriminating fragility fracture. RESULTS: Among the 246 postmenopausal women, 170 belonged to the non-fracture group, 50 to the vertebral group, and 26 to the non-vertebral fracture group. MResNet was competent to discriminate any fragility fracture (OR = 2.64; AUC = 0.74), Vertebral fracture (OR = 3.02; AUC = 0.77), and non-vertebral fracture (OR = 2.01; AUC = 0.69). After being modified by clinical covariates, the efficiency of MResNet was further improved to OR = 3.31-4.08, AUC = 0.81-0.83 among all fracture groups, which significantly surpassed QUS-SOS (OR = 1.32-1.36; AUC = 0.60) and DXA-BMD (OR = 1.23-2.94; AUC = 0.63-0.76). CONCLUSIONS: This pilot cross-sectional study demonstrates that the MResNet model based on the ultrasonic RF signal shows promising performance in discriminating fragility fractures in postmenopausal women. When incorporating clinical covariates, the efficiency of the modified MResNet is further enhanced, surpassing the performance of QUS-SOS and DXA-BMD in terms of OR and AUC. These findings highlight the potential of the MResNet as a promising approach for fracture risk assessment. Future research should focus on larger and more diverse populations to validate these results and explore its clinical applications.

Abiotic synthesis of graphitic carbons in the Eoarchean Saglek-Hebron metasedimentary rocks.

Graphite in metasedimentary rocks of the Eoarchean Saglek-Hebron Gneiss Complex (Canada) is depleted in 13C and has been interpreted as one of the oldest traces of life on Earth. The variation in crystallinity of this oldest graphitic carbon could possibly confirm the effect of metamorphism on original biomass, but this is still unexplored. Here, we report specific mineral associations with graphitic carbons that also have a range of crystallinity in the Saglek-Hebron metasedimentary rocks. Petrographic, geochemical and spectroscopic analyses in the Saglek-Hebron banded iron formations suggest that poorly crystalline graphite is likely deposited from C-H-O fluids derived from thermal decomposition of syngenetic organic matter, which is preserved as crystalline graphite during prograde metamorphism. In comparison, in the Saglek-Hebron marble, disseminations of graphite co-occur with carbonate and magnetite disseminations, pointing to abiotic synthesis of graphitic carbons via decarbonation. Our results thus highlight that variably crystalline graphitic carbons in the Saglek-Hebron metasedimentary rocks are potential abiotic products on early Earth, which lay the groundwork for identifying the preservation of prebiotic organic matter through metamorphism on Earth and beyond.

In-Sensor Tactile Fusion and Logic for Accurate Intention Recognition.

Touch control intention recognition is an important direction for the future development of human-machine interactions (HMIs). However, the implementation of parallel-sensing functional modules generally requires a combination of different logical blocks and control circuits, which results in regional redundancy, redundant data, and low efficiency. Here, a location-and-pressure intelligent tactile sensor (LPI tactile sensor) unprecedentedly combined with sensing, computing, and logic is proposed, enabling efficient and ultrahigh-resolution action-intention interaction. The LPI tactile sensor eliminates the need for data transfer among the functional units through the core integration design of the layered structure. It actuates in-sensor perception through feature transmission, fusion, and differentiation, thereby revolutionizing the traditional von Neumann architecture. While greatly simplifying the data dimensionality, the LPI tactile sensor achieves outstanding resolution sensing in both location (<400 µm) and pressure (75 Pa). Synchronous feature fusion and decoding support the high-fidelity recognition of action and combinatorial logic intentions. Benefiting from location and pressure synergy, the LPI tactile sensor demonstrates robust privacy as an encrypted password device and interaction intelligence through pressure enhancement. It can recognize continuous touch actions in real time, map real intentions to target events, and promote accurate and efficient intention-driven HMIs.

Prognostic significance of postoperative serological incomplete conversion of AFP and PIVKA-II after hepatic resection for hepatocellular carcinoma: a multicenter analysis of 1755 patients.

BACKGROUND: The value of serum biomarkers, particularly alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II), gains increasing attention in prognostic evaluation and recurrence monitoring for patients with hepatocellular carcinoma (HCC). This study investigated the implications of serological incomplete conversion (SIC) of these 2 biomarkers as prognostic indicators for long-term outcomes after HCC resection. METHODS: A multicenter observational study was conducted on a cohort of HCC patients presenting with AFP (>20 ng/mL) or PIVKA-II (>40 mAU/mL) positivity who underwent curative-intent resection. Based on their postoperative AFP and PIVKA-II levels at first postoperative follow-up (4~8 weeks after surgery), these patients were stratified into the serological incomplete conversion (SIC) and serological complete conversion (SCC) groups. The study endpoints were recurrence and overall survival (OS). RESULTS: Among 1755 patients, 379 and 1376 were categorized as having SIC and SCC, respectively. The SIC group exhibited 1- and 5-year OS rates of 67.5% and 26.3%, with the corresponding recurrence rates of 53.2% and 79.0%, respectively; while the SCC group displayed 1- and 5-year OS rates of 95.8% and 62.5%, with the corresponding recurrence rates of 16.8% and 48.8%, respectively (both P < .001). Multivariate Cox regression analysis demonstrated that postoperative SIC was an independent risk factor for both increased recurrence (HR: 2.40, 95% CI, 2.04-2.81, P < .001) and decreased OS (HR: 2.69, 95% CI, 2.24-3.24, P < .001). CONCLUSION: The results emphasize that postoperative incomplete conversion of either AFP or PIVKA-II is a significant prognostic marker, indicating a higher risk for adverse oncologic outcomes following HCC resection. This revelation has crucial implications for refining postoperative adjuvant therapy and surveillance strategies for HCC patients.

Hydroxyl Group as the 'Bridge' to Enhance the Single-Molecule Conductance by Hyperconjugation.

For designing single-molecule devices that have both conjugation systems and structural flexibility, a hyperconjugated molecule with a σ-π bond interaction is considered an ideal candidate. In the investigation of conductance at the single-molecule level, since few hyperconjugation systems have been involved, the strategy of building hyperconjugation systems and the mechanism of electron transport within this system remain unexplored. Based on the skipped-conjugated structure, we present a rational approach to construct a hyperconjugation molecule using a hydroxyl group, which serves as a bridge to interact with the conjugated fragments. The measurement of single-molecule conductance reveals a two-fold conductance enhancement of the hyperconjugation system having the 'bridging' hydroxyl group compared to hydroxyl-free derivatives. Theoretical studies demonstrate that the hydroxyl group in the hyperconjugation system connects the LUMO of the two conjugated fragments and opens a through-space channel for electron transport to enhance the conductance.

Ultrafast T2 and T2* mapping using single-shot spatiotemporally encoded MRI with reduced field of view and spiral out-in-out-in trajectory.

BACKGROUND: T2 and T2* mapping are crucial components of quantitative magnetic resonance imaging, offering valuable insights into tissue characteristics and pathology. Single-shot methods can achieve ultrafast T2 or T2* mapping by acquiring multiple readout echo trains. However, the extended echo trains pose challenges, such as compromised image quality and diminished quantification accuracy. PURPOSE: In this study, we develop a single-shot method for ultrafast T2 and T2* mapping with reduced echo train length. METHODS: The proposed method is based on ultrafast single-shot spatiotemporally encoded (SPEN) MRI combined with reduced field of view (FOV) and spiral out-in-out-in (OIOI) trajectory. Specifically, a biaxial SPEN excitation scheme was employed to excite the spin signal into the spatiotemporal encoding domain. The OIOI trajectory with high acquisition efficiency was employed to acquire signals within targeted reduced FOV. Through non-Cartesian super-resolved (SR) reconstruction, 12 aliasing-free images with different echo times were obtained within 150 ms. These images were subsequently fitted to generate T2 or T2* mapping simultaneously using a derived model. RESULTS: Accurate and co-registered T2 and T2* maps were generated, closely resembling the reference maps. Numerical simulations demonstrated substantial consistency (R2 > 0.99) with the ground truth values. A mean difference of 0.6% and 1.7% was observed in T2 and T2*, respectively, in in vivo rat brain experiments compared to the reference. Moreover, the proposed method successfully obtained T2 and T2* mappings of rat kidney in free-breathing mode, demonstrating its superiority over multishot methods lacking respiratory navigation. CONCLUSIONS: The results suggest that the proposed method can achieve ultrafast and accurate T2 and T2* mapping, potentially facilitating the application of T2 and T2* mapping in scenarios requiring high temporal resolution.

Significant Differences in Intestinal Bacterial Communities of Sympatric Bean Goose, Hooded Crane, and Domestic Goose.

The host's physiological well-being is intricately associated with the gut microbiota. However, previous studies regarding the intestinal microbiota have focused on domesticated or captive birds. This study used high-throughput sequencing technology to identify the gut bacterial communities of sympatric bean geese, hooded cranes, and domestic geese. The results indicated that the gut bacterial diversity in domestic geese and hooded cranes showed considerably higher diversity than bean geese. The gut bacterial community compositions varied significantly among the three hosts (p < 0.05). Compared to the hooded crane, the bean goose and domestic goose were more similar in their genotype and evolutionary history, with less difference in the bacterial community composition and assembly processes between the two species. Thus, the results might support the crucial role of host genotypes on their gut microbiota. The gut bacteria of wild hooded cranes and bean geese had a greater capacity for energy metabolism compared to domestic geese, suggesting that wild birds may rely more on their gut microbiota to survive in cold conditions. Moreover, the intestines of the three hosts were identified as harboring potential pathogens. The relative abundance of pathogens was higher in the hooded crane compared to the other two species. The hooded crane gut bacterial community assemblage revealed the least deterministic process with the lowest filtering/selection on the gut microbiota, which might have been a reason for the highest number of pathogens result. Compared to the hooded crane, the sympatric bean goose showed the least diversity and relative abundance of pathogens. The intestinal bacterial co-occurrence network showed the highest stability in the bean goose, potentially enhancing host resistance to adverse environments and reducing the susceptibility to pathogen invasion. In this study, the pathogens were also discovered to overlap among the three hosts, reminding us to monitor the potential for pathogen transmission between poultry and wild birds. Overall, the current findings have the potential to enhance the understanding of gut bacterial and pathogenic community structures in poultry and wild birds.

Comparative physiological, biochemical and transcriptomic analyses to reveal potential regulatory mechanisms in response to starvation stress in Cipangopaludina chinensis.

Cipangopaludina chinensis, as a financially significant species in China, represents a gastropod in nature which frequently encounters starvation stress owing to its limited prey options. However, the underlying response mechanisms to combat starvation have not been investigated in depth. We collected C. chinensis under several times of starvation stress (0, 7, 30, and 60 days) for nutrient, biochemical characteristics and transcriptome analyses. The results showed that prolonged starvation stress (> 30 days) caused obvious fluctuations in the nutrient composition of snails, with dramatic reductions in body weight, survival and digestive enzyme activity (amylase, protease, and lipase), and markedly enhanced the antioxidant enzyme activities of the snails. Comparative transcriptome analyses revealed 3538 differentially expressed genes (DEGs), which were significantly associated with specific starvation stress-responsive pathways, including oxidative phosphorylation and alanine, aspartate, and glutamate metabolism. Then, we identified 40 candidate genes (e.g., HACD2, Cp1, CYP1A2, and GPX1) response to starvation stress through STEM and WGCNA analyses. RT-qPCR verified the accuracy and reliability of the high-throughput sequencing results. This study provides insights into snail overwintering survival and the potential regulatory mechanisms of snail adaptation to starvation stress.

Revealing the Electro-oxidation Mechanism of 5-Aminotetrazole on Nickel-Based Oxides and Synthesizing 5,5'-Azotetrazolate Salts.

With the gradual expansion of the application of organic electromechanical synthesis in the field of energetic materials, it is necessary to explore deeply the mechanisms behind the organic electromechanical oxidation of energetic materials in order to develop efficient electrocatalysts. Electrochemical synthesis of 5,5'-azotetrazolate (ZT) salts is not only environmentally friendly and efficient but also can replace oxygen evolution reaction (OER) combined with hydrogen production, significantly reducing the battery voltage of overall water splitting (OWS) and achieving low energy consumption hydrogen production. Here, we prepared the Co-modified nickel-based oxide electrodes (Ni3-xCoO4/carbon cloth (CC), x = 1, 2) as a medium to reveal the oxidative coupling mechanism of 5-aminotetrazole (5-AT). Experimental and theoretical calculations verified that Ni-catalyzed oxidative coupling of 5-AT is a proton-coupled electron transfer (PCET) process, including electron transfer of electrocatalytic intermediates (Ni2+-O + OH- = Ni3+-O(OH) + e-) and spontaneous dehydrogenation process (Ni3+-O(OH) + X-H = Ni2+-O + X•). The Ni3+-O(OH) is an extremely fast nonreducing electron transfer center that serves as a chemical oxidant to directly abstract hydrogen atoms from the 5-AT. Simultaneously, the synergistic effect of Co doping on the electric cloud around Ni causes the upshift of the d-band centers, which is conducive to the easier adsorption of OH*, forming the generation of active intermediate Ni3+-O(OH). Thus, Ni2CoO4/CC has higher Faraday efficiency (FE) and yield for the oxidation reaction of 5-AT, with a yield of approximately 72.3% after electrolysis at 1.7 V vs reversible hydrogen electrode (RHE).

Antibacterial activity and mechanisms of D-3263 against Staphylococcus aureus.

Multi-drug-resistant Staphylococcus aureus infections necessitate novel antibiotic development. D-3263, a transient receptor potential melastatin member 8 (TRPM8) agonist, has potential antineoplastic properties. Here, we reported the antibacterial and antibiofilm activities of D-3263. Minimum inhibitory concentrations (MICs) against S. aureus, Enterococcus faecalis and E. faecium were ≤ 50 µM. D-3263 exhibited bactericidal effects against clinical methicillin-resistant S. aureus (MRSA) and E. faecalis strains at 4× MIC. Subinhibitory D-3263 concentrations effectively inhibited S. aureus and E. faecalis biofilms, with higher concentrations also clearing mature biofilms. Proteomic analysis revealed differential expression of 29 proteins under 1/2 × MIC D-3263, influencing amino acid biosynthesis and carbohydrate metabolism. Additionally, D-3263 enhanced membrane permeability of S. aureus and E. faecalis. Bacterial membrane phospholipids phosphatidylethanolamine (PE), phosphatidylglycerol (PG), and cardiolipin (CL) dose-dependently increased D-3263 MICs. Overall, our data suggested that D-3263 exhibited potent antibacterial and antibiofilm activities against S. aureus by targeting the cell membrane.

Design and simulation investigations on charge transport layers-free in lead-free three absorber layer all-perovskite solar cells.

The multiple absorber layer perovskite solar cells (PSCs) with charge transport layers-free (CTLs-free) have drawn widespread research interest due to their simplified architecture and promising photoelectric characteristics. Under the circumstances, the novel design of CTLs-free inversion PSCs with stable and nontoxic three absorber layers (triple Cs3Bi2I9, single MASnI3, double Cs2TiBr6) as optical-harvester has been numerically simulated by utilizing wxAMPS simulation software and achieved high power conversion efficiency (PCE) of 14.8834%. This is owing to the innovative architecture of PSCs favors efficient transport and extraction of more holes and the slender band gap MASnI3 extends the absorption spectrum to the near-infrared periphery compared with the two absorber layers architecture of PSCs. Moreover, the performance of the device with p-type-Cs3Bi2I9/p-type-MASnI3/n-type-Cs2TiBr6 architecture is superior to the one with the p-type-Cs3Bi2I9/n-type-MASnI3/n-type-Cs2TiBr6 architecture due to less carrier recombination and higher carrier life time inside the absorber layers. The simulation results reveal that Cs2TiF6 double perovskite material stands out as the best alternative. Additionally, an excellent PCE of 21.4530% can be obtained with the thicker MASnI3 absorber layer thickness (0.4 µm). Lastly, the highest-performance photovoltaic devices (28.6193%) can be created with the optimized perovskite doping density of around E15 cm3 (Cs3Bi2I9), E18 cm3 (MASnI3), and 1.5E19 cm3 (Cs2TiBr6). This work manifests that the proposed CTLs-free PSCs with multi-absorber layers shall be a relevant reference for forward applications in electro-optical and optoelectronic devices.

Patterns of neurogenic lower urinary tract dysfunction management and associated factors among Chinese community-dwelling individuals with spinal cord injury.

To identify different patterns of neurogenic lower urinary tract dysfunction management among Chinese community-dwelling individuals with spinal cord injury and explore the factors associated with latent classes. This was a cross-sectional study conducted in communities throughout China Mainland. Participants were recruited through the China Association of Persons with Physical Disability and a total of 2582 participants was included in the analysis. The data were collected by a questionnaire consisting of socio-demographic factors, disease-related factors, and a list of 8 bladder management methods. Latent class analysis was used to identify different latent classes of neurogenic lower urinary tract dysfunction management. Then the multinomial logistic regression was applied to analyze the relationship between neurogenic lower urinary tract dysfunction management patterns and socio-demographic and disease-related factors. Neurogenic lower urinary tract dysfunction management pattern among community-dwelling individuals with spinal cord injury was divided into four latent classes: "urinal collecting apparatus dominated pattern" (40.3%), "bladder compression dominated pattern" (30.7%), "intermittent catheterization dominated pattern" (19.3%) and "urethral indwelling catheterization dominated pattern" (9.6%). Multinomial logistic regression analysis found that the employment status, residential region, nursing need, payment method for catheterization products, hand function, time since spinal cord injury, urinary incontinence and concerns about social interaction affected by urination problems were significantly associated with latent classes. Only 19.3% of people used the intermittent catheterization as their main neurogenic lower urinary tract dysfunction management method. More attention needs to be paid to the promotion of the standardization process of intermittent catheterization in community-dwelling individuals with spinal cord injury. The associated factors of the four classes can be used for tailored and targeted interventions to increase the use of intermittent catheterization.

Combining genome-wide association study and linkage mapping in the genetic dissection of amylose content in maize (Zea mays L.).

KEY MESSAGE: Integrated linkage and association analysis revealed genetic basis across multiple environments. The genes Zm00001d003102 and Zm00001d015905 were further verified to influence amylose content using gene-based association study. Maize kernel amylose is an important source of human food and industrial raw material. However, the genetic basis underlying maize amylose content is still obscure. Herein, we used an intermated B73 × Mo17 (IBM) Syn10 doubled haploid population composed of 222 lines and a germplasm set including 305 inbred lines to uncover the genetic control for amylose content under four environments. Linkage mapping detected 16 unique QTL, among which four were individually repeatedly identified across multiple environments. Genome-wide association study revealed 17 significant (P = 2.24E-06) single-nucleotide polymorphisms, of which two (SYN19568 and PZE-105090500) were located in the intervals of the mapped QTL (qAC2 and qAC5-3), respectively. According to the two population co-localized loci, 20 genes were confirmed as the candidate genes for amylose content. Gene-based association analysis indicated that the variants in Zm00001d003102 (Beta-16-galactosyltransferase GALT29A) and Zm00001d015905 (Sugar transporter 4a) affected amylose content across multi-environment. Tissue expression analysis showed that the two genes were specifically highly expressed in the ear and stem, respectively, suggesting that they might participate in sugar transport from source to sink organs. Our study provides valuable genetic information for breeding maize varieties with high amylose.

Compact In Situ Electrochemical NMR with Wireless and Anti-interference Strategy in Multiscenario Applications.

The integration of electrochemistry with nuclear magnetic resonance (NMR) spectroscopy recently offers a powerful approach to understanding oxidative metabolism, detecting reactive intermediates, and predicting biological activities. This combination is particularly effective as electrochemical methods provide excellent mimics of metabolic processes, while NMR spectroscopy offers precise chemical analysis. NMR is already widely utilized in the quality control of pharmaceuticals, foods, and additives and in metabolomic studies. However, the introduction of additional and external connections into the magnet has posed challenges, leading to signal deterioration and limitations in routine measurements. Herein, we report an anti-interference compact in situ electrochemical NMR system (AICISENS). Through a wireless strategy, the compact design allows for the independent and stable operation of electrochemical NMR components with effective interference isolation. Thus, it opens an avenue toward easy integration into in situ platforms, applicable not only to laboratory settings but also to fieldwork. The operability, reliability, and versatility were validated with a series of biomimetic assessments, including measurements of microbial electrochemical systems, functional foods, and simulated drug metabolisms. The robust performance of AICISENS demonstrates its high potential as a powerful analytical tool across diverse applications.

Protein and metabolic profiles of tyrosine kinase inhibitors co-resistant liver cancer cells.

Hepatocellular Carcinoma (HCC) patients often develop resistance to tyrosine kinase inhibitors (TKIs) like sorafenib (SR) and lenvatinib (RR). We established HCC cell lines resistant to these drugs and analyzed the correlation between protein and metabolite profiles using bioinformatics. Our analysis revealed overexpression of MISP, CHMP2B, IL-18, TMSB4X, and EFEMP1, and downregulation of IFITM3, CA4, AGR2, and SLC51B in drug-resistant cells. Differential signals are mainly enriched in steroid hormone biosynthesis, cell adhesion, and immune synapses, with metabolic pathways including cytochrome P450 drug metabolism, amino acid metabolism, and glycolysis. Proteomics and metabolomics analysis showed co-enrichment signals in drug metabolism, amino acids, glucose metabolism, ferroptosis, and other biological processes. Knocking down MISP, CHMP2B, IL-18, TMSB4X, and EFEMP1 significantly reduced drug resistance, indicating their potential as therapeutic response biomarkers. This study characterizes protein and metabolic profiles of drug-resistant HCC cells, exploring metabolite-protein relationships to enhance understanding of drug resistance mechanisms and clinical treatment.

Nature's carriers: leveraging extracellular vesicles for targeted drug delivery.

With the rapid development of drug delivery systems, extracellular vesicles (EVs) have emerged as promising stars for improving targeting abilities and realizing effective delivery. Numerous studies have shown when compared to conventional strategies in targeted drug delivery (TDD), EVs-based strategies have several distinguished advantages besides targeting, such as participating in cell-to-cell communications and immune response, showing high biocompatibility and stability, penetrating through biological barriers, etc. In this review, we mainly focus on the mass production of EVs including the challenges and strategies for scaling up EVs production in a cost-effective and reproducible manner, the loading and active targeting methods, and examples of EVs as vehicles for TDD in consideration of potential safety and regulatory issues associated. We also conclude and discuss the rigor and reproducibility of EVs production, the current research status of the application of EVs-based strategies to targeted drug delivery, clinical conversion prospects, and existing chances and challenges.

Plant YABBY transcription factors: a review of gene expression, biological functions, and prospects.

Transcription factors often contain several different functional regions, including DNA-binding domains, and play an important regulatory role in plant growth, development, and the response to external stimuli. YABYY transcription factors are plant-specific and contain two special domains (N-terminal C2C2 zinc-finger and C-terminal helix-loop-helix domains) that are indispensable. Specifically, YABBY transcription factors play key roles in maintaining the polarity of the adaxial-abaxial axis of leaves, as well as in regulating: vegetative and reproductive growth, hormone response, stress resistance, and secondary metabolite synthesis in plants. Recently, the identification and functional verification of YABBY transcription factors in different plants has increased. On this basis, we summarize recent advances in the: identification, classification, expression patterns, and functions of the YABBY transcription factor family. The normal expression and function of YABBY transcription factors rely on a regulatory network that is established through the interaction of YABBY family members with other genes. We discuss the interaction network of YABBY transcription factors during leaf polarity establishment and floral organ development. This article provides a reference for research on YABBY function, plant genetic improvement, and molecular breeding.