Dye-doped cellulose nanocrystals as novel dusting powders for visualizing latent fingerprints.

Powder-dusting method based on the visual contrast between the background surface and powder-covered ridges of a fingerprint is widely used to develop the invisible latent fingerprints (LFPs) left at crime scenes. Recently, the development of nano-sized powders with excellent optical performances has been extensively explored. In this work, we employed environmentally friendly and low-toxicity cellulose nanocrystals as the novel support. Using dye-doped cellulose nanocrystals as novel dusting powders, two dyes (phenylfluorone and curcumin) were adsorbed on the cellulose nanocrystals by a simple batch adsorption method. The dye-doped cellulose nanocrystals (namely, phenylfluorone-doped cellulose nanocrystals (PDCN) and curcumin-doped cellulose nanocrystals (CDCN)) containing 2% of the loaded mass of both the dyes with bright green fluorescence were developed to visualize LFPs on the surfaces of various substrates (such as glass slide, printing paper, orange plastic card, tile, stainless steel, compact disc, red plastic packing, copper foil and aluminum foil). Images of the LFPs can been obtained by both the dye-doped cellulose nanocrystals with sufficient affinity to the ridges of LFPs. High-quality ridge details with features at the second and third level can be detected by CDCN, whereas PDCN only display the secondary-level features of ridge details. Compared with PDCN, CDCN illustrate higher sensitivity, higher selectivity, and better contrast, especially for detecting fresh and non-fresh LFPs on porous and non-porous substrates, and has the potential for practical use in forensic science.

Immunotherapy for small cell lung cancer: the current state and future trajectories.

Small cell lung cancer (SCLC) constitutes approximately 10% to 15% of all lung cancer diagnoses and represents a pressing global public health challenge due to its high mortality rates. The efficacy of conventional treatments for SCLC is suboptimal, characterized by limited anti-tumoral effects and frequent relapses. In this context, emerging research has pivoted towards immunotherapy combined with chemotherapy, a rapidly advancing field that has shown promise in ameliorating the clinical outcomes of SCLC patients. Through originally developed for non-small cell lung cancer (NSCLC), these therapies have extended new treatment avenues for SCLC. Currently, a nexus of emerging hot-spot treatments has demonstrated significant therapeutic efficacy. Based on the amalgamation of chemotherapy and immunotherapy, and the development of new immunotherapy agents, the treatment of SCLC has seen the hoping future. Progress has been achieved in enhancing the tumor immune microenvironment through the concomitant use of chemotherapy, immunotherapy, and tyrosine kinase inhibitors (TKI), as evinced by emerging clinical trial data. Moreover, a tripartite approach involving immunotherapy, targeted therapy, and chemotherapy appears auspicious for future clinical applications. Overcoming resistance to post-immunotherapy regimens remains an urgent area of exploration. Finally, bispecific antibodies, adoptive cell transfer (ACT), oncolytic virus, monotherapy, including Delta-like ligand 3 (DLL3) and T cell immunoreceptor with Ig and ITIM domains (TIGIT), as well as precision medicine, may present a prospective route towards achieving curative outcomes in SCLC. This review aims to synthesize extant literature and highlight future directions in SCLC treatment, acknowledging the persistent challenges in the field. Furthermore, the continual development of novel therapeutic agents and technologies renders the future of SCLC treatment increasingly optimistic.

Synthesis and Characterization of Copper-Crosslinked Carbon Dot Nanoassemblies for Efficient Macrophage Manipulation.

Nanomedicines loaded in macrophages (MAs) can actively target tumors without dominantly relying on the enhanced permeability and retention (EPR) effect, making them effective for treating EPR-deficient malignancies. Herein, copper-crosslinked carbon dot clusters (CDCs) are synthesized with both photodynamic and chemodynamic functions to manipulate MAs, aiming to direct the MA-mediated tumor targeting. First, green fluorescent CDs (g-CDs) are prepared by a one-step hydrothermal method. Subsequently, the g-CDs are complexed with divalent copper ions to form copper-crosslinked CDCs (g-CDCs/Cu), which are incubated with MAs for their manipulation. Experimental results revealed that the prepared g-CDCs/Cu displayed good aqueous dispersibility and fluorescent emission properties. The nanoassemblies can be activated to deplete the overexpressed glutathione (GSH) and generate reactive oxygen species (ROS) in the presence of laser irradiation through the combined Cu-mediated chemodynamic therapy and CD-mediated photodynamic therapy. Furthermore, the ROS produced in MAs enabled polarization of MAs to antitumor M1 phenotype, suggesting the future potential use to reverse the immunosuppressive tumor microenvironment. These results obtained from the current study suggest a significant potential to develop g-CDCs/Cu for GSH depletion, ROS generation, and MA M1 polarization as a theransotic agent to tackle cancer.

A new long-acting analgesic formulation for postoperative pain management.

Local anesthetics (LA), as part of multimodal analgesia, have garnered significant interest for their role in delaying the initiation of opioid therapy, reducing postoperative opioid usage, and mitigating both hospitalization duration and related expenses. Despite numerous endeavors to extend the duration of local anesthetic effects, achieving truly satisfactory long-acting analgesia remains elusive. Drawing upon prior investigations, vesicular phospholipid gels (VPGs) emerge as promising candidates for extended-release modalities in small-molecule drug delivery systems. Therefore, we tried to use the amphiphilicity of phospholipids to co-encapsulate levobupivacaine hydrochloride and meloxicam, two drugs with different hydrophilicity, to obtain a long-term synergistic analgesic effect. Initially, the physicochemical attributes of the formulation were characterized, followed by an examination of its in vitro release kinetics, substantiating the viability of extending the release duration of the dual drugs. Sequentially, in vivo investigations encompassing pharmacokinetic profiling and assessment of analgesic efficacy were undertaken, revealing a prolonged release duration of up to 120 h and attainment of optimal postoperative analgesia. Subsequently, inquiries into the mechanism underlying synergistic analgesic effects and safety evaluations pertinent to the delivery strategy were pursued. In summation, we successfully developed a promising formulation to achieve long-acting analgesia.

[Relationship between dietary risk factors and sedentary recreational screen time among school-age children in grades 4-6 in Baise City from 2018 to 2019].

OBJECTIVE: To explore the relationship between dietary risk factors and sedentary recreational screen time of adolescents. METHODS: A total of 6363 pupils of Grades 4-6 from 6 primary schools in Baise were recruited with cluster-sampling method from Sep.2018 to Nov.2019. Participants were asked to report the average duration of watching television, digital devices use, intakes of sugar-sweetened beverage(SSB), snacks, fast-food, soymilk/milk product, skipping breakfast, and frequency of fruit/vegetable. We performed multivariable logistic regression to estimate OR and 95%CI for the relations between duration of sedentary recreational screen time and dietary risk factors, accounting for complex survey sampling and adjusting for potential confounders. RESULTS: (1)Both prolonged watching television and leisure-time digital devices use were associated with high intakes of SSBs, snacks, and low intakes of fruits and vegetables. And compared with <2 h/d, two kinds of screen-time(>4 h/d) was associated with significantly higher odds for intakes of fast food(watching television: OR=2.551;leisure-time digital devices use: OR=3.024), and frequent breakfast skipping(watching television: OR=1.646;leisure-time digital devices use: OR=1.674). (2)Compared with the reference groups(<2 h/d), participants spending more time per day on sedentary recreational screen time were more likely to drink sugar-sweetened beverages(OR=1.717-3.272), consume snacks(OR=1.626-3.154)and less likely to consume fruit/vegetable(OR=1.526-2.251). Compared to ≤2 h/d, estimated ORs of high intakes of fast food were 2.118 for>3 h/d of screen time, and 2.357 for >4 h/d. CONCLUSION: Increased television viewing and digital devices use in adolescence of Grades 4-6 is associated with higher odds of consumption of sweetened beverages, snacks and lower odds of fruit consumption in Baise.

Oral secretions from striped stem borer (Chilo suppressalis) induce defenses in rice.

BACKGROUND: The striped stem borer (SSB, Chilo suppressalis) is one of the most destructive insect pests on rice. As a chewing insect, SSB larval feeding causes a dramatic increase in rice defense responses. However, the effects of oral secretions (OSs) during SSB feeding on rice defense remain largely unexplored. RESULTS: In this study, based on transcriptome analysis results, treatment with SSB OSs regulated the expression of genes involved in the plant defense-related pathways of calcium, mitogen-activated protein kinases, reactive oxygen species, jasmonic acid (JA), herbivore-induced plant volatiles (HIPVs), and protease inhibitors. Unsurprisingly, treatment with SSB OSs elicited the accumulation of JA and JA-isoleucine in rice. The defense mechanisms activated by the cascade not only induced the expression of trypsin inhibitors, inhibiting the normal growth of SSB larvae but also induced HIPVs emission, rendering rice attractive to a common larval parasitoid. High-throughput proteome sequencing of SSB OSs led to 534 proteins being identified and 343 proteins with two or more unique peptides being detected. CONCLUSION: The study demonstrates that SSB OSs trigger both direct and indirect defense mechanisms in rice, akin to the effects of SSB feeding. It identifies specific proteins in SSB OSs that may influence the interactions between SSB and rice during feeding, providing valuable insights for effectors research. © 2024 Society of Chemical Industry.

A radiogenomic clinical decision support system to inform individualized treatment in advanced nasopharyngeal carcinoma.

Both concurrent chemoradiotherapy (CCRT) and induction chemotherapy (ICT) followed by CCRT are standard care of advanced nasopharyngeal carcinoma (NPC). However, tailoring personalized treatment is lacking. Herein, we established a radiogenomic clinical decision support system to classify patients into three subgroups according to their predicted disease-free survival (DFS) with CCRT and ICT response. The CCRT-preferred group was suitable for CCRT since they achieved good survival with CCRT, which could not be improved by ICT. The ICT-preferred group was suitable for ICT plus CCRT since they had poor survival with CCRT; additional ICT could afford an improved DFS. The clinical trial-preferred group was suitable for clinical trials since they exhibited poor survival regardless of receiving CCRT or ICT plus CCRT. These findings suggest that our radiogenomic clinical decision support system could identify optimal candidates for CCRT, ICT plus CCRT, and clinical trials, and may thus aid in personalized management of advanced NPC.

Antibody-drug conjugates for breast cancer: a bibliometric study and clinical trial analysis.

BACKGROUND: Breast cancer (BC) remains the most commonly malignancy among women worldwide. Although early-stage BC typically presents with curative possibilities, advanced-stage disease, especially with metastasis, is significantly limited in terms of effective therapeutic interventions, thereby establishing it as the second leading cause of cancer-related deaths in women. Antibody-Drug Conjugates (ADCs) establish a groundbreaking class of anti-neoplastic agents characterized by high specificity and targeting precision. These agents have been significant in reshaping the therapeutic approach to breast cancer, especially those subtypes with overexpression of the Human Epidermal Growth Factor Receptor 2 (HER2). Comprising monoclonal antibodies, cytotoxic payloads, and conjugative linkers, ADCs function by specifically targeting antigens on cancer cells, thereby facilitating the intracellular delivery of the toxic payload. The present investigation endeavors to synthesize existing primary research outcomes through rigorous bibliometric and data analytical approaches, thereby elucidating the current research landscape, delineating research foci, and identifying potential avenues for future innovation. METHODS: For bibliometric analysis, a comprehensive data set comprising 2181 entries related to ADCs in breast cancer was retrieved from the Web of Science Core Collection (WoSCC) spanning the years 1999 to 2023. This data was further filtered from the Science Citation Index Expanded (SCI-Expanded). Analysis software tools such as CiteSpace and VOSviewer were employed for multifaceted analyses such as trends of publications, contributions of countries, and burst analytics. In the dimension of clinical trials, we interrogated databases including ClinicalTrials.gov ( https://www. CLINICALTRIALS: gov ) and the WHO International Clinical Trials Registry Platform (ICTRP) ( https://trialsearch.who.int ). A total of 239 clinical trials were initially sourced, among which, 175 were from ClinicalTrials.gov and 64 from ICTRP. After repetitive and correlation-based screening, 119 trials specifically addressing ADC therapeutic strategies in breast cancer were included. Analytical algorithms were executed using Microsoft-based software to evaluate treatment paradigms, emergent research themes, and progress. RESULTS: Our investigations signify a growing trend of research on ADCs, with consistent advancements in scientific achievements. The analysis revealed that variables such as economic stratification of nations, healthcare investment paradigms, and disease incidence rates serve as significant determinants in shaping research output. Geographically, the United States emerged as the predominant contributor to the research corpus (36.56%), closely followed by China (21.33%). The underpinning of research accomplishments was found to be significantly bolstered by advancements in molecular biology, immunology, and genetic research. Moreover, the advent of nuclear magnetic resonance diagnostic modalities has contributed saliently to the diagnostic and therapeutic management of breast cancer. CONCLUSION: Our study provides a comprehensive overview of the ADC research landscape through rigorous bibliometric and clinical trial evaluations. At present, the ADC arena has witnessed the successful development and FDA approval of 14 distinct agents, substantially improving the clinical outcomes for a broad spectrum of oncological patients. Future research imperatives may include the exploration of ADCs targeting mutated oncoproteins, dual-specificity ADCs, combination payload strategies, peptide-drug conjugates (PDCs), and non-internalizing ADC modalities. With sustained academic and clinical focus, the ADC domain is poised for transformative advancements in targeted therapeutics across a variety of malignancies.

Homotypic cell-in-cell structure as a novel prognostic predictor in non-small cell lung cancer and frequently localized at the invasive front.

Homotypic cell-in-cell structures (hoCICs) are associated with tumor proliferation, invasion, and metastasis and is considered a promising prognostic marker in various cancers. However, the role of hoCICs in non-small cell lung cancer (NSCLC) remains unclear. Tumor tissue sections were obtained from 411 NSCLC patients. We analyzed the relationship between clinicopathological variables and the number of hoCICs. LASSO and multivariate Cox regression analysis were employed to identify prognostic factors for NSCLC. The impact of hoCICs on overall survival (OS) and disease-free survival (DFS) was assessed using the Kaplan-Meier curves and log-rank test. Prognostic models for OS and DFS were developed and validated using the C-index, time-dependent area under the curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), calibration curves and decision curve analysis (DCA). Among the cohort, 56% of patients had hoCICs while 44% did not. Notably, hoCICs were primarily found at the tumor invasion front. Male gender, smoking, squamous cell carcinoma, low differentiation, tumor size ≥ 3 cm, advanced TNM stage, lymph node metastasis, pleural invasion, vascular invasion, necrosis, P53 mutation, and high expression of Ki-67 were identified as relative risk factors for hoCICs. Furthermore, hoCICs was found to be a significant prognostic factor for both OS and DFS, with higher frequencies of hoCICs correlating with poorer outcomes. We constructed nomograms for predicting 1-, 3-, and 5-year OS and DFS based on hoCICs, and the calibration curves showed good agreement between the predicted and actual outcomes. The results of the C-index, time-dependent AUC, NRI, IDI, and DCA analyses demonstrated that incorporating hoCICs into the prognostic model significantly enhanced its predictive power and clinical applicability. HoCICs indicated independent perdictive value for OS and DFS in patients with NSCLC. Furthermore, the frequent localization of hoCICs at the tumor invasion front suggested a strong association between hoCICs and tumor invasion as well as metastasis.

Identification and initial validation of neuroendocrine differentiation as a novel prognostic factor in stage II colorectal cancer patients.

Neuroendocrine differentiation is often found in colorectal cancer but its impact on prognosis remains controversial. This study explored the association between neuroendocrine differentiation and prognosis in stage II/III colorectal cancer patients. METHODS: Between 2012 and 2018, a total of 3,441 stage II/III colorectal cancer patients were included for analysis. To verify neuroendocrine differentiation, immunohistochemistry was performed to explore the expression of chromogranin A and synaptophysin in colorectal cancer. In addition, the difference in overall survival between groups was analyzed. A Kaplan-Meier analysis was used to determine the clinicopathological characteristics significantly correlated with survival, and a Cox proportional hazards analysis was used to identify factors independently affecting overall survival prognosis. Furthermore, the findings were validated by the Gene Expression Omnibus database. RESULTS: Among the 3441 stage II/III colorectal cancer patients, in comparison to patients with neuroendocrine differentiation (+), patients with neuroendocrine differentiation (+) had a poorer prognosis (P = 0.001). Furthermore, multivariate survival analysis of stage II cases revealed that tumor differentiation (P = 0.018), nerve invasion (P < 0.001) and neuroendocrine differentiation (+) (P = 0.002) were independent prognostic factors. Moreover, the prognosis of patients with neuroendocrine differentiation (+) was similar to that of patients with high-risk factors in stage II cases (P = 0.639). High chromogranin A expression was correlated with poor prognosis in stage II colorectal cancer patients in the Gene Expression Omnibus database (P < 0.001). CONCLUSION: The prognosis of colorectal cancer with neuroendocrine differentiation (+) was poor, especially in stage II colorectal cancer patients. neuroendocrine differentiation might be another high-risk factor for the prognosis of stage II colorectal cancer patients.

Host-microbe interactions rewire metabolism in a C. elegans model of leucine breakdown deficiency.

In humans, defects in leucine catabolism cause a variety of inborn errors in metabolism. Here, we use Caenorhabditis elegans to investigate the impact of mutations in mccc-1, an enzyme that functions in leucine breakdown. Through untargeted metabolomic and transcriptomic analyses we find extensive metabolic rewiring that helps to detoxify leucine breakdown intermediates via conversion into previously undescribed metabolites and to synthesize mevalonate, an essential metabolite. We also find that the leucine breakdown product 3,3-hydroxymethylbutyrate (HMB), commonly used as a human muscle-building supplement, is toxic to C. elegans and that bacteria modulate this toxicity. Unbiased genetic screens revealed interactions between the host and microbe, where components of bacterial pyrimidine biosynthesis mitigate HMB toxicity. Finally, upregulated ketone body metabolism genes in mccc-1 mutants provide an alternative route for biosynthesis of the mevalonate precursor 3-hydroxy-3-methylglutaryl-CoA. Our work demonstrates that a complex host-bacteria interplay rewires metabolism to allow host survival when leucine catabolism is perturbed.

Free-breathing three-dimensional simultaneous myocardial T1 and T2 mapping based on multi-parametric SAturation-recovery and Variable-flip-Angle.

BACKGROUND: Quantitative myocardial tissue characterization with T1 and T2 parametric mapping can provide an accurate and complete assessment of tissue abnormalities across a broad range of cardiomyopathies. However, current clinical T1 and T2 mapping tools rely predominantly on two-dimensional (2D) breath-hold sequences. Clinical adoption of three-dimensional (3D) techniques is limited by long scan duration. The aim of this study is to develop and validate a time-efficient 3D free-breathing simultaneous T1 and T2 mapping sequence using multi-parametric SAturation-recovery and Variable-flip-Angle (mSAVA). METHODS: mSAVA acquires four volumes for simultaneous whole-heart T1 and T2 mapping. We validated mSAVA using simulations, phantoms, and in-vivo experiments at 3T in 11 healthy subjects and 11 patients with diverse cardiomyopathies. T1 and T2 values by mSAVA were compared with modified Look-Locker inversion recovery (MOLLI) and gradient and spin echo (GraSE), respectively. The clinical performance of mSAVA was evaluated against late gadolinium enhancement (LGE) imaging in patients. RESULTS: Phantom T1 and T2 by mSAVA showed a strong correlation to reference sequences (R2 = 0.98 and 0.99). In-vivo imaging with an imaging resolution of 1.5 × 1.5 × 8 mm3 could be achieved. Myocardial T1 and T2 of healthy subjects by mSAVA were 1310 ± 46 and 44.6 ± 2.0 ms, respectively, with T1 standard deviation higher than MOLLI (105 ± 12 vs 60 ± 16 ms) and T2 standard deviation lower than GraSE (4.5 ± 0.8 vs 5.5 ± 1.0 ms). mSAVA T1 and T2 maps presented consistent findings in patients undergoing LGE. Myocardial T1 and T2 of all patients by mSAVA were 1421 ± 79 and 47.2 ± 3.3 ms, respectively. CONCLUSION: mSAVA is a fast 3D technique promising for clinical whole-heart T1 and T2 mapping.

A novel OsGST gene encoding 9glutathione reductase negatively regulates cadmium accumulation in rice.

Cadmium (Cd) accumulates in rice and then moves up the food chain, causing serious health problems for humans. Glutathione S-transferase (GST) binds exogenous hazardous compounds to glutathione (GSH), which performs a variety of roles in plant responses to Cd stress. Here, Cd stimulated the transcripts of a novel OsGST gene, and the OsGST protein, which was localized in the nucleus and cytoplasm, was also induced by Cd. In OsGST deletion mutant lines generated by CRISPR/Cas9, more Cd was accumulated, and Cd hypersensitive phenotypes were observed, while transgenic lines overexpressing OsGST exhibited enhanced Cd tolerance and less Cd accumulation. Further analysis indicated that the osgst mutants exhibited considerably greater reactive oxygen species (ROS) and higher GSH level, and the antioxidant activity associated genes' expression were down-regulated, imply that OsGST controlled rice Cd accumulation and resistance through preserving the equilibrium of the GSH and redox in rice.

Unraveling the modulatory manner and function of circRNAs in the Asian honey bee larval guts.

Circular RNAs (circRNAs) are a class of non-coding RNAs (ncRNAs) that can participate in biological processes such as gene expression, growth, and development. However, little has been explored about the function of circRNAs in the development of Apis cerana larval guts. By using our previously gained deep sequencing data from the guts of A. cerana worker larvae at 4-, 5-, and 6-day-old (Ac4, Ac5, and Ac6 groups), the expression pattern and regulatory role of circular RNAs (circRNAs) during the development process was comprehensively investigated, with a focus on differentially expressed circRNAs (DEcircRNAs) relevant to immunity pathways and developmental signaling pathways, followed by validation of the binding relationships among a key competing endogenous RNA (ceRNA) axis. Here, 224 (158) DEcircRNAs were detected in the Ac4 vs. Ac5 (Ac5 vs. Ac6) comparison group. It's suggested that 172 (123) parental genes of DEcircRNAs were involved in 26 (20) GO terms such as developmental process and metabolic process and 138 (136) KEGG pathways like Hippo and Wnt signaling pathways. Additionally, ceRNA network analysis indicated that 21 (11) DEcircRNAs could target seven (three) DEmiRNAs, further targeting 324 (198) DEmRNAs. These DEmRNAs can be annotated to 33 (26) GO terms and 168 (200) KEGG pathways, including 12 (16) cellular and humoral immune pathways (endocytosis, lysosome, Jak-STAT, etc.) and 10 (nine) developmental signaling pathways (Hippo, mTOR, Hedgehog, etc.). Interestingly, DEcircRNAs in these two comparison groups could target the same ace-miR-6001-y, forming complex sub-networks. The results of PCR and Sanger sequencing confirmed the back-splicing sites within four randomly selected DEcircRNAs. RT-qPCR detection of these four DEcircRNAs verified the reliability of the used transcriptome data. The results of dual-luciferase reporter assay verified the binding relationships between novel_circ_001627 and ace-miR-6001-y and between ace-miR-6001-y and apterous-like. Our data demonstrated that DEcircRNAs were likely to modulate the developmental process of the A. cerana worker larval guts via regulation of parental gene transcription and ceRNA network, and novel_circ_001627/ace-miR-6001-y/apterous-like was a potential regulatory axis in the larval gut development. Findings from this work offer a basis and a candidate ceRNA axis for illustrating the circRNA-modulated mechanisms underlying the A. cerana larval guts.

Melatonin Increases Root Cell Wall Phosphorus Reutilization via an NO Dependent Pathway in Rice (Oryza sativa).

Melatonin (MT) has been implicated in the plant response to phosphorus (P) stress; however, the precise molecular mechanisms involved remain unclear. This study investigated whether MT controls internal P distribution and root cell wall P remobilization in rice. Rice was treated with varying MT and P levels and analyzed using biochemical and molecular techniques to study phosphorus utilization. The results demonstrated that low P levels lead to a rapid increase in endogenous MT levels in rice roots. Furthermore, the exogenous application of MT significantly improved rice tolerance to P deficiency, as evidenced by the increased biomass and reduced proportion of roots to shoots under P-deficient conditions. MT application also mitigated the decrease in P content regardless in both the roots and shoots. Mechanistically, MT accelerated the reutilization of P, particularly in the root pectin fraction, leading to increased soluble P liberation. In addition, MT enhanced the expression of OsPT8, a gene involved in root-to-shoot P translocation. Furthermore, we observed that MT induced the production of nitric oxide (NO) in P-deficient rice roots and that the mitigating effect of MT on P deficiency was compromised in the presence of the NO inhibitor, c-PTIO, implying that NO is involved in the MT-facilitated mitigation of P deficiency in rice. Overall, our findings highlight the potential of MT as a promising strategy for enhancing rice tolerance to P deficiency and improving P use efficiency in agricultural practices.

Tailoring Highly Branched Poly(ß-amino ester)s for Efficient and Organ-Selective mRNA Delivery.

Development of mRNA therapeutics necessitates targeted delivery technology, while the clinically advanced lipid nanoparticles face difficulty for extrahepatic delivery. Herein, we design highly branched poly(ß-amino ester)s (HPAEs) for efficacious organ-selective mRNA delivery through tailoring their chemical compositions and topological structures. Using an "A2+B3+C2" Michael addition platform, a combinatorial library of 219 HPAEs with varied backbone structures, terminal groups, and branching degrees are synthesized. The branched topological structures of HPAEs provide enhanced serum resistance and significantly higher mRNA expression in vivo. The terminal amine structures of HPAEs determine the organ-selectivity of mRNA delivery following systemic administration: morpholine facilitates liver targeting, ethylenediamine favors spleen delivery, while methylpentane enables mRNA delivery to the liver, spleen, and lungs simultaneously. This study represents a comprehensive exploration of the structure-activity relationship governing both the efficiency and organ-selectivity of mRNA delivery by HPAEs, suggesting promising candidates for treating various organ-related diseases.

Rapid and Amplification-free Nucleic Acid Detection with DNA Substrate-Mediated Autocatalysis of CRISPR/Cas12a.

To enable rapid and accurate point-of-care DNA detection, we have developed a single-step, amplification-free nucleic acid detection platform, a DNA substrate-mediated autocatalysis of CRISPR/Cas12a (DSAC). DSAC makes use of the trans-cleavage activity of Cas12a and target template-activated DNA substrate for dual signal amplifications. DSAC employs two distinct DNA substrate types: one that enhances signal amplification and the other that negatively modulates fluorescent signals. The positive inducer utilizes nicked- or loop-based DNA substrates to activate CRISPR/Cas12a, initiating trans-cleavage activity in a positive feedback loop, ultimately amplifying the fluorescent signals. The negative modulator, which involves competitor-based DNA substrates, competes with the probes for trans-cleaving, resulting in a signal decline in the presence of target DNA. These DNA substrate-based DSAC systems were adapted to fluorescence-based and paper-based lateral flow strip detection platforms. Our DSAC system accurately detected African swine fever virus (ASFV) in swine's blood samples at femtomolar sensitivity within 20 min. In contrast to the existing amplification-free CRISPR/Dx platforms, DSAC offers a cost-effective and straightforward detection method, requiring only the addition of a rationally designed DNA oligonucleotide. Notably, a common ASFV sequence-encoded DNA substrate can be directly applied to detect human nucleic acids through a dual crRNA targeting system. Consequently, our single-step DSAC system presents an alternative point-of-care diagnostic tool for the sensitive, accurate, and timely diagnosis of viral infections with potential applicability to human disease detection.

Rotational inertia-induced glassy transition in chiral particle systems.

The dense active matter exhibits characteristics reminiscent of traditional glassy phenomena, yet the role of rotational inertia in glass dynamics remains elusive. In this study, we investigate the glass dynamics of chiral active particles influenced by rotational inertia. Rotational inertia endows exponential memory to particle orientation, restricting its alteration and amplifying the effective persistence time. At lower spinning frequencies, the diffusion coefficient exhibits a peak function relative to rotational inertia for shorter persistence times, while it steadily increases with rotational inertia for longer persistence times. In the realm of high-frequency spinning, the impact of rotational inertia on diffusion behavior becomes more pronounced, resulting in a nonmonotonic and intricate relationship between the diffusion coefficient and rotational inertia. Consequently, the introduction of rotational inertia significantly alters the glassy dynamics of chiral active particles, allowing for the control over transitions between fluid and glassy states by modulating rotational inertia. Moreover, our findings indicate that at a specific spinning temperature, there exists an optimal spinning frequency at which the diffusion coefficient attains its maximum value.

Genome-wide analysis of MYB transcription factor family and AsMYB1R subfamily contribution to ROS homeostasis regulation in Avena sativa under PEG-induced drought stress.

BACKGROUND: The myeloblastosis (MYB) transcription factor (TF) family is one of the largest and most important TF families in plants, playing an important role in a life cycle and abiotic stress. RESULTS: In this study, 268 Avena sativa MYB (AsMYB) TFs from Avena sativa were identified and named according to their order of location on the chromosomes, respectively. Phylogenetic analysis of the AsMYB and Arabidopsis MYB proteins were performed to determine their homology, the AsMYB1R proteins were classified into 5 subgroups, and the AsMYB2R proteins were classified into 34 subgroups. The conserved domains and gene structure were highly conserved among the subgroups. Eight differentially expressed AsMYB genes were screened in the transcriptome of transcriptional data and validated through RT-qPCR. Three genes in AsMYB2R subgroup, which are related to the shortened growth period, stomatal closure, and nutrient and water transport by PEG-induced drought stress, were investigated in more details. The AsMYB1R subgroup genes LHY and REV 1, together with GST, regulate ROS homeostasis to ensure ROS signal transduction and scavenge excess ROS to avoid oxidative damage. CONCLUSION: The results of this study confirmed that the AsMYB TFs family is involved in the homeostatic regulation of ROS under drought stress. This lays the foundation for further investigating the involvement of the AsMYB TFs family in regulating A. sativa drought response mechanisms.