MEIKIN expression and its C-terminal phosphorylation by PLK1 is closely related the metaphase-anaphase transition by affecting cyclin B1 and Securin stabilization in meiotic oocyte.

Oocyte meiotic maturation failure and chromosome abnormality is one of the main causes of infertility, abortion, and diseases. The mono-orientation of sister chromatids during the first meiosis is important for ensuring accurate chromosome segregation in oocytes. MEIKIN is a germ cell-specific protein that can regulate the mono-orientation of sister chromatids and the protection of the centromeric cohesin complex during meiosis I. Here we found that MEIKIN is a maternal protein that was highly expressed in mouse oocytes before the metaphase I (MI) stage, but became degraded by the MII stage and dramatically reduced after fertilization. Strikingly, MEIKIN underwent phosphorylation modification after germinal vesicle breakdown (GVBD), indicating its possible function in subsequent cellular event regulation. We further showed that MEIKIN phosphorylation was mediated by PLK1 at its carboxyl terminal region and its C-terminus was its key functional domain. To clarify the biological significance of meikin degradation during later stages of oocyte maturation, exogenous expression of MEIKIN was employed, which showed that suppression of MEIKIN degradation resulted in chromosome misalignment, cyclin B1 and Securin degradation failure, and MI arrest through a spindle assembly checkpoint (SAC)-independent mechanism. Exogenous expression of MEIKIN also inhibited metaphase II (MII) exit and early embryo development. These results indicate that proper MEIKIN expression level and its C-terminal phosphorylation by PLK1 are critical for regulating the metaphase-anaphase transition in meiotic oocyte. The findings of this study are important for understanding the regulation of chromosome segregation and the prevention meiotic abnormality.

A new isocoumarin derivative from endophytic fungus Pezicula neosporulosa VDB39 from Vaccinium dunalianum.

Four isocoumarin derivatives (1-4) and five phenols (5-9) were obtained from the endophytic fungus Pezicula neosporulosa VDB39, which was isolated from the branches of Vaccinium dunalianum Wight (Ericaceae). Compound 1 is a new derivative of isocoumarin. The structures were elucidated by spectroscopic methods. Single X-ray crystallography confirmed the absolute configuration of compound 1. Additionally, the antiphytopathogenic fungi activity of isocoumarin derivatives (1-4) was evaluated.

Quasi-Planar Core based Spiro-Type Hole-Transporting Material for Dopant-Free Perovskite Solar Cells.

Hole-transporting materials (HTMs) are crucial for obtaining the stability and high efficiency of perovskite solar cells (PSCs). However, the current state-of-the-art n-i-p PSCs relied on the use of 2,2',7,7'-tetrakis(N,N-di-p-methoxyphenylamine)-9,9'-spirobifluorene (spiro-OMeTAD) exhibit inferior intrinsic and ambient stability due to the p-dopant and hydrophilic Li-TFSI additive. In this study, a new spiro-type HTM with a critical quasi-planar core (Z-W-03) is developed to improve both the thermal and ambient stability of PSCs. The results suggest that the planar carbazole structure effectively passivates the trap states compared to the triphenylamine with a propeller-like conformation in spiro-OMeTAD. This passivation effect leads to the shallower trap states when the quasi-planar HTMs interact with the Pb-dimer. Consequently, the device using Z-W-03 achieves a higher Voc of 1.178 V compared to the spiro-OMeTAD's 1.155 V, resulting in an enhanced efficiency of 24.02%. In addition, the double-column π-π stacking of Z-W-03 results in high hole mobility (~10-4 cm2 V-1 s-1) even without p-dopant. Moreover, when the surface interface is modified, the undoped Z-W-03 device can achieve an efficiency of nearly 23%. Compared to the PSCs using spiro-OMeTAD, those with Z-W-03 exhibit enhanced stability under N2 and ambient conditions.

Efficient Charge Transfer in Graphene/CrOCl Heterostructures by van der Waals Interfacial Coupling.

Due to the large volume of exposed atoms and electrons at the surface of two-dimensional materials, interfacial charge coupling has been proven as an efficient strategy to engineer the electronic structures of two-dimensional materials assembled in van der Waals heterostructures. Recently, heterostructures formed by graphene stacked with CrOCl have demonstrated intriguing quantum states, including a distorted quantum Hall phase in the monolayer graphene and the unconventional correlated insulator in the bilayer graphene. Yet, the understanding of the interlayer charge coupling in the heterostructure remains challenging. Here, we demonstrate clear evidences of efficient hole doping in the interfacial-coupled graphene/CrOCl heterostructure by detailed Raman spectroscopy and electrical transport measurements. The observation of significant blue shifts and stiffness of graphene Raman modes quantitatively determines the concentration of hole injection of about 1.2 × 1013 cm-2 from CrOCl to graphene, which is highly consistent with the enhanced conductivity of graphene. First-principles calculations based on density functional theory reveal that due to the large work function difference and the electronegativity of Cl atoms in CrOCl, the electrons are efficiently transferred from graphene to CrOCl, leading to hole doping in graphene. Our findings provide clues for understanding the exotic physical properties of graphene/CrOCl heterostructures, paving the way for further engineering of quantum electronic states by efficient interfacial charge coupling in van der Waals heterostructures.

Antibiotic-induced severe cutaneous adverse reactions: a single-center retrospective study over ten years.

Objective: Severe cutaneous adverse reactions (SCARs) are rare but life-threatening, with antibiotics being the main cause. This retrospective study from a single center was designed to analyze the culprit drugs, clinical features and treatment outcomes of antibiotic-induced SCARs. Methods: We analyzed cases of antibiotic-induced SCARs in a tertiary hospital in China between January 2013 and January 2024, including Steven-Johnson syndrome (SJS) or Stevens-Johnson syndrome-toxic epidermal necrolysis (SJS-TEN) overlap, toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP). Descriptive analysis of the demographic characteristics, clinical manifestations, treatment and prognosis were carried out. Results: Among 354 cases of SCARs, 63 validated antibiotic-related cases were included. Cephalosporins (31.7%), penicillins (25.4%), and quinolones (19.0%) were the most common triggers for SCARs. Overall, liver (50.8%), lungs (31.7%), and kidneys (23.8%) were the most frequently affected organ in SCARs cases. Eight patients (28.6%) in the SJS/SJS-TEN overlap group and 8 patients (80.0%) in the TEN group received combination therapy of corticosteroids and IVIG. Patients with SCARs caused by penicillins or cephalosporins could receive alternative treatments such as lincomamides, quinolones, and tetracyclines. The mortality rate in the TEN group was the highest at 20.0%, followed by the SJS/SJS-TEN overlap group (7.1%), and no deaths were observed in the DRESS and AGEP groups. Conclusion: The identification of the culprit antibiotics and the application of alternative antibiotic therapies are crucial for the management of antibiotic-induced SCARs. If complicated underlying conditions and complications like advanced age, cancer and pneumonia coexist with SCARs, patients might be more at risk for mortality.

Advances in diffuse glioma assessment: preoperative and postoperative applications of chemical exchange saturation transfer.

Chemical Exchange Saturation Transfer (CEST) is a technique that uses specific off-resonance saturation pulses to pre-saturate targeted substances. This process influences the signal intensity of free water, thereby indirectly providing information about the pre-saturated substance. Among the clinical applications of CEST, Amide Proton Transfer (APT) is currently the most well-established. APT can be utilized for the preoperative grading of gliomas. Tumors with higher APTw signals generally indicate a higher likelihood of malignancy. In predicting preoperative molecular typing, APTw values are typically lower in tumors with favorable molecular phenotypes, such as isocitrate dehydrogenase (IDH) mutations, compared to IDH wild-type tumors. For differential diagnosis, the average APTw values of meningiomas are significantly lower than those of high-grade gliomas. Various APTw measurement indices assist in distinguishing central nervous system lesions with similar imaging features, such as progressive multifocal leukoencephalopathy, central nervous system lymphoma, solitary brain metastases, and glioblastoma. Regarding prognosis, APT effectively differentiates between tumor recurrence and treatment effects, and also possesses predictive capabilities for overall survival (OS) and progression-free survival (PFS).

Vesicular neurotransmitters exocytosis monitored by amperometry: theoretical quantitative links between experimental current spikes shapes and intravesicular structures.

Single cell amperometry has proven to be a powerful and well-established method for characterizing single vesicular exocytotic events elicited at the level of excitable cells under various experimental conditions. Nevertheless, most of the reported characteristics are descriptive, being mostly concerned with the morphological characteristics of the recorded current spikes (maximum current intensities, released charge, rise and fall times, etc.) which are certainly important but do not provide sufficient kinetic information on exocytotic mechanisms due to lack of quantitative models. Here, continuing our previous efforts to provide rigorous models rationalizing the kinetic structures of frequently encountered spike types (spikes with unique exponential decay tails and kiss-and-run events), we describe a new theoretical approach enabling a quantitative kinetic modeling of all types of exocytotic events giving rise to current spikes exhibiting exponential decay tails. This model follows directly from the fact that the condensation of long intravesicular polyelectrolytic strands by high concentrations of monocationic neurotransmitter molecules leads to a matrix structure involving two compartments in constant kinetic exchanges during release. This kinetic model has been validated theoretically (direct and inverse problems) and its experimental interest established by the analysis of the amperometric spikes relative to chromaffin and PC12 cells previously published by some of us.

Nocardamine mitigates cellular dysfunction induced by oxidative stress in periodontal ligament stem cells.

BACKGROUND: The role of periodontal ligament stem cells (PDLSCs) in repairing periodontal destruction is crucial, but their functions can be impaired by excessive oxidative stress (OS). Nocardamine (NOCA), a cyclic siderophore, has been shown to possess anti-cancer and anti-bacterial properties. This study aimed to investigate the protective mechanisms of NOCA against OS-induced cellular dysfunction in PDLSCs. METHODS: The cytotoxicity of NOCA on PDLSCs was assessed using a CCK-8 assay. PDLSCs were then treated with hydrogen peroxide (H2O2) to induce OS. ROS levels, cell viability, and antioxidant factor expression were analyzed using relevant kits after treatment. Small molecule inhibitors U0126 and XAV-939 were employed to block ERK signaling and Wnt pathways respectively. Osteogenic differentiation was assessed using alkaline phosphatase (ALP) activity staining and Alizarin Red S (ARS) staining of mineralized nodules. Expression levels of osteogenic gene markers and ERK pathway were determined via real-time quantitative polymerase chain reaction (RT-qPCR) or western blot (WB) analysis. ß-catenin nuclear localization was examined by western blotting and confocal microscopy. RESULTS: NOCA exhibited no significant cytotoxicity at concentrations below 20 µM and effectively inhibited H2O2-induced OS in PDLSCs. NOCA also restored ALP activity, mineralized nodule formation, and the expression of osteogenic markers in H2O2-stimulated PDLSCs. Mechanistically, NOCA increased p-ERK level and promoted ß-catenin translocation into the nucleus; however, blocking ERK pathway disrupted the osteogenic protection provided by NOCA and impaired its ability to induce ß-catenin nuclear translocation under OS conditions in PDLSCs. CONCLUSIONS: NOCA protected PDLSCs against H2O2-induced OS and effectively restored impaired osteogenic differentiation in PDLSCs by modulating the ERK/Wnt signaling pathway.

A universal oral microbiome-based signature for periodontitis.

We analyzed eight oral microbiota shotgun metagenomic sequencing cohorts from five countries and three continents, identifying 54 species biomarkers and 26 metabolic biomarkers consistently altered in health and disease states across three or more cohorts. Additionally, machine learning models based on taxonomic profiles achieved high accuracy in distinguishing periodontitis patients from controls (internal and external areas under the receiver operating characteristic curves of 0.86 and 0.85, respectively). These results support metagenome-based diagnosis of periodontitis and provide a foundation for further research and effective treatment strategies.

Controlled Synthesis of 2D Ferromagnetic/Antiferromagnetic Cr7Te8/MnTe Vertical Heterostructures for High-Tunable Coercivity.

Two-dimensional ferromagnetic/antiferromagnetic (2D-FM/AFM) heterostructures are of great significance to realize the application of spintronic devices such as miniaturization, low power consumption, and high-density information storage. However, traditional mechanical stacking can easily damage the crystal quality or cause chemical contamination residues for 2D materials, which can result in weak interface coupling and difficulty in device regulation. Chemical vapor deposition (CVD) is an effective way to achieve a high-quality heterostructure interface. Herein, high-quality interface 2D-FM/AFM Cr7Te8/MnTe vertical heterostructures were successfully synthesized via a one-pot CVD method. Moreover, the atomic-scale structural scanning transmission electron microscope (STEM) characterization shows that the interface of the vertical heterostructure is clear and flat without an excess interface layer. Compared to the parent Cr7Te8, the coercivity (HC) of the high-quality interface Cr7Te8/MnTe heterostructure is significantly reduced as the thickness of MnTe increases, with a maximum decrease of 74.5% when the thickness of the MnTe nanosheet is around 30 nm. Additionally, the HC of the Cr7Te8/MnTe heterostructure can also be regulated by applying a gate voltage, and the HC increases or decreases with increasing positive or negative gate voltages. Thus, the effective regulation of HC is essential to improving the performance of advanced spintronic devices (e.g., MRAM and magnetic sensors). Our work will provide ideas for spin controlling and device application of 2D-FM/AFM heterostructures.

Intratumoral microbiome promotes liver metastasis and dampens adjuvant imatinib treatment in gastrointestinal stromal tumor.

Understanding the determinants of long-term liver metastasis (LM) outcomes in gastrointestinal stromal tumor (GIST) patients is crucial. We established the feature selection model of intratumoral microbiome at the surgery, achieving robust predictive accuracies of 0.953 and 0.897 AUCs in discovery (n = 74) and validation (n = 34) cohorts, respectively. Notably, despite the significant reduction in LM occurrence with adjuvant imatinib (AI) treatment, intratumoral microbiome exerted independently stronger effects on post-operative LM. Employing both 16S and full-length rRNA sequencing, we pinpoint intracellular Shewanella algae as a foremost LM risk factor in both AI- and non-AI-treated patients. Experimental validation confirmed S. algae's intratumoral presence in GIST, along with migration/invasion-promoting effects on GIST cells. Furthermore, S. algae promoted LM and impeded AI treatment in metastatic mouse models. Our findings advocate for incorporating intratumoral microbiome evaluation at surgery, and propose S. algae as a therapeutic target for LM suppression in GIST.

Indium Phosphide Single Crystal Furnace Cooling Crystallization Temperature Control Model Research.

Indium phosphide (InP) single crystals, as key III-V compound semiconductor materials, play an irreplaceable role in various fields, such as optical communication and microwave millimeter-wave communication. Vertical gradient freeze (VGF) has become one of the main methods for industrial production of InP single crystals due to its advantages in temperature gradient control. However, defects such as twins and dislocations are easily generated during the production of InP single crystals by the VGF method. Through an in-depth study of the thermal field during the growth of InP single crystals, it is found that the cooling rate of the thermal field during single crystal growth is crucial and is closely related to the generation of twins, dislocations, and polycrystallization defects. Therefore, constructing a cooling model based on temperature control and the quality of InP single crystals has a positive driving effect on improving the yield of single crystal products. In this paper, by establishing a thermal field model of an InP single crystal furnace produced by the VGF method, the characteristics of temperature variation are analyzed in depth. Subsequently, numerical analysis of discrete cooling data during the cooling crystallization process is conducted, considering the quality of the InP single crystal growth. Combined with the spline regression algorithm, the optimal cooling model is fitted. Through positive and reverse experiment verification, the model shows significant effects in controlling internal stress in the crystal and reducing defect generation. Based on this model, we have successfully achieved effective suppression of defects, such as twins and dislocations, thereby significantly improving the quality of InP single crystals. This research not only provides a solid theoretical basis for the production of InP single crystals but also provides strong support for experimental applications.

Long-read sequencing reveals extensive gut phageome structural variations driven by genetic exchange with bacterial hosts.

Genetic variations are instrumental for unraveling phage evolution and deciphering their functional implications. Here, we explore the underlying fine-scale genetic variations in the gut phageome, especially structural variations (SVs). By using virome-enriched long-read metagenomic sequencing across 91 individuals, we identified a total of 14,438 nonredundant phage SVs and revealed their prevalence within the human gut phageome. These SVs are mainly enriched in genes involved in recombination, DNA methylation, and antibiotic resistance. Notably, a substantial fraction of phage SV sequences share close homology with bacterial fragments, with most SVs enriched for horizontal gene transfer (HGT) mechanism. Further investigations showed that these SV sequences were genetic exchanged between specific phage-bacteria pairs, particularly between phages and their respective bacterial hosts. Temperate phages exhibit a higher frequency of genetic exchange with bacterial chromosomes and then virulent phages. Collectively, our findings provide insights into the genetic landscape of the human gut phageome.

The effect of fasting plasma glucose on in-hospital mortality after acute myocardial infarction in patients with and without diabetes: findings from a prospective, nationwide, and multicenter registry.

OBJECTIVES: To evaluate the predictive value of fasting plasma glucose (FPG) for in-hospital mortality in patients with acute myocardial infarction (AMI) with different glucose metabolism status. METHODS: We selected 5,308 participants with AMI from the prospective, nationwide, multicenter CAMI registry, of which 2,081 were diabetic and 3,227 were nondiabetic. Patients were divided into high FPG and low FPG groups according to the optimal cutoff values of FPG to predict in-hospital mortality for diabetic and nondiabetic cohorts, respectively. The primary endpoint was in-hospital mortality. RESULTS: Overall, 94 diabetic patients (4.5%) and 131 nondiabetic patients (4.1%) died during hospitalization, and the optimal FPG thresholds for predicting in-hospital death of the two cohorts were 13.2 mmol/L and 6.4 mmol/L, respectively. Compared with individuals who had low FPG, those with high FPG were significantly associated with higher in-hospital mortality in diabetic cohort (10.1% vs. 2.8%; odds ratio [OR] = 3.862, 95% confidence interval [CI]: 2.542-5.869) and nondiabetic cohort (7.4% vs. 1.7%; HR = 4.542, 95%CI: 3.041-6.782). After adjusting the potential confounders, this significant association was not changed. Furthermore, FPG as a continuous variable was positively associated with in-hospital mortality in single-variable and multivariable models regardless of diabetic status. Adding FPG to the original model showed a significant improvement in C-statistic and net reclassification in diabetic and nondiabetic cohorts. CONCLUSIONS: This large-scale registry indicated that there is a strong positive association between FPG and in-hospital mortality in AMI patients with and without diabetes. FPG might be useful to stratify patients with AMI.

Eikenella corrodens isolated from pleural effusion: A case report.

BACKGROUND: The bacterium Eikenella, classified as a gram-negative member of the phylum Proteobacteria, is distinguished by its rarity, corrosive nature, facultative anaerobic properties, and conditional pathogenicity. It represents the sole species within its genus-Eikenella corrodens (E. corrodens)-and can be found colonizing both human and animal oral and nasopharyngeal regions. Additionally, it occasionally inhabits the gastrointestinal or urogenital tracts. However, its slow growth rate can be attributed to its high nutritional requirements. However, there is an uneven distribution of construction and diagnostic capacity in China which poses undeniable challenges for the clinical examination and analysis of this case, especially in the basic hospitals. CASE SUMMARY: Here we presented a case of empyema associated with E. corrodens infection in a 67-year-old male patient without any previous history of infectious diseases in our primary hospital in Dongguan district of China. The patient was admitted due to recurrent worsening cough, sputum production, and dyspnea for 3 d, which had persisted for over 20 years. Moreover, the patient experienced a one-hour episode of unconsciousness. Upon admission, immediate comprehensive examinations were conducted on the patient which subsequently led to his admission to the intensive care unit. Meanwhile, the patient presented with drowsiness and profuse sweating along with bilateral conjunctival edema observed during initiation of non-invasive ventilation, suggesting empyema. A significant amount of coffee-colored malodorous pleural fluid was drained during the procedure above and sent to the laboratory department for inspection. Finally, laboratory culture results confirmed the presence of E. corrodens infection in the pleural fluid sample. The patient received antimicrobial therapy until died on day 22 in the hospital. CONCLUSION: In this report, we presented a case of empyema associated with E. corrodens infection. Multiple courses of morphological examination, viable culture analysis, and biochemical identification revealed its difficulties in detecting distinctive characteristics, as well as a detection model worth promoting. It's just that there were still certain deficiencies in terms of morphological assessment, biochemical identification, and drug susceptibility testing.

X-Paste improves wound healing in diabetes via NF-E2-related factor/HO-1 signaling pathway.

BACKGROUND: Diabetic foot ulcers (DFU), as severe complications of diabetes mellitus (DM), significantly compromise patient health and carry risks of amputation and mortality. AIM: To offer new insights into the occurrence and development of DFU, focusing on the therapeutic mechanisms of X-Paste (XP) of wound healing in diabetic mice. METHODS: Employing traditional Chinese medicine ointment preparation methods, XP combines various medicinal ingredients. High-performance liquid chromatography (HPLC) identified XP's main components. Using streptozotocin (STZ)-induced diabetic, we aimed to investigate whether XP participated in the process of diabetic wound healing. RNA-sequencing analyzed gene expression differences between XP-treated and control groups. Molecular docking clarified XP's treatment mechanisms for diabetic wound healing. Human umbilical vein endothelial cells (HUVECs) were used to investigate the effects of Andrographolide (Andro) on cell viability, reactive oxygen species generation, apoptosis, proliferation, and metastasis in vitro following exposure to high glucose (HG), while NF-E2-related factor-2 (Nrf2) knockdown elucidated Andro's molecular mechanisms. RESULTS: XP notably enhanced wound healing in mice, expediting the healing process. RNA-sequencing revealed Nrf2 upregulation in DM tissues following XP treatment. HPLC identified 21 primary XP components, with Andro exhibiting strong Nrf2 binding. Andro mitigated HG-induced HUVECs proliferation, metastasis, angiogenic injury, and inflammation inhibition. Andro alleviates HG-induced HUVECs damage through Nrf2/HO-1 pathway activation, with Nrf2 knockdown reducing Andro's proliferative and endothelial protective effects. CONCLUSION: XP significantly promotes wound healing in STZ-induced diabetic models. As XP's key component, Andro activates the Nrf2/HO-1 signaling pathway, enhancing cell proliferation, tubule formation, and inflammation reduction.

Relationship between preoperative psychological stress and short-term prognosis in elderly patients with femoral neck fracture.

BACKGROUND: Older adults are at high risk of femoral neck fractures (FNFs). Elderly patients face and adapt to significant psychological burdens, resulting in different degrees of psychological stress response. Total hip replacement is the preferred treatment for FNF in elderly patients; however, some patients have poor postoperative prognoses, and the underlying mechanism is unknown. We speculated that the postoperative prognosis of elderly patients with FNF may be related to preoperative psychological stress. AIM: To explore the relationship between preoperative psychological stress and the short-term prognosis of elderly patients with FNF. METHODS: In this retrospective analysis, the baseline data, preoperative 90-item Symptom Checklist score, and Harris score within 6 months of surgery of 120 elderly patients with FNF who underwent total hip arthroplasty were collected. We analyzed the indicators of poor short-term postoperative prognosis and the ability of the indicators to predict poor prognosis and compared the correlation between the indicators and the Harris score. RESULTS: Anxiety, depression, garden classification of FNF, cause of fracture, FNF reduction quality, and length of hospital stay were independent influencing factors for poor short-term postoperative prognoses in elderly patients with FNF (P < 0.05). The areas under the curve for anxiety, depression, and length of hospital stay were 0.742, 0.854, and 0.749, respectively. The sensitivities of anxiety, depression, garden classification of FNF, and prediction of the cause of fracture were 0.857, 0.786, 0.821, and 0.821, respectively. The specificities of depression, FNF quality reduction, and length of hospital stay were the highest at 0.880, 0.783, and 0.761, respectively. Anxiety, depression, and somatization scores correlated moderately with Harris scores (r = -0.523, -0.625, and -0.554; all P < 0.001). CONCLUSION: Preoperative anxiety, depression, and somatization are correlated with poor short-term prognosis in elderly patients with FNF and warrant consideration.

VirRep: a hybrid language representation learning framework for identifying viruses from human gut metagenomes.

Identifying viruses from metagenomes is a common step to explore the virus composition in the human gut. Here, we introduce VirRep, a hybrid language representation learning framework, for identifying viruses from human gut metagenomes. VirRep combines a context-aware encoder and an evolution-aware encoder to improve sequence representation by incorporating k-mer patterns and sequence homologies. Benchmarking on both simulated and real datasets with varying viral proportions demonstrates that VirRep outperforms state-of-the-art methods. When applied to fecal metagenomes from a colorectal cancer cohort, VirRep identifies 39 high-quality viral species associated with the disease, many of which cannot be detected by existing methods.

Stabilized, ROS-sensitive ß-cyclodextrin-grafted hyaluronic supramolecular nanocontainers for CD44-targeted anticancer drug delivery.

Hyaluronic acid (HA)-based tumor microenvironment-responsive nanocontainers are attractive candidates for anticancer drug delivery due to HA's excellent biocompatibility, biodegradability, and CD44-targeting properties. Nevertheless, the consecutive synthesis of stabilized, stealthy, responsive HA-based multicomponent nanomedicines generally requires multi-step preparation and purification procedures, leading to batch-to-batch variation and scale-up difficulties. To develop a facile yet robust strategy for promoted translations, a silica monomer containing a cross-linkable diethoxysilyl unit was prepared to enable in situ crosslinking without any additives. Further combined with the host-guest inclusion complexation between ß-cyclodextrin-grafted HA (HA-CD) and ferrocene-functionalized polymers, ferrocene-terminated poly(oligo(ethylene glycol) methyl ether methacrylate (Fc-POEGMA) and Fc-terminated poly(ε-caprolactone)-b-poly(3-(diethoxymethylsilyl)propyl(2-(methacryloyloxy)ethyl) carbamate) (Fc-PCL-b-PDESPMA), a reactive oxygen species (ROS)-sensitive supramolecular polymer construct, Fc-POEGMA/Fc-PCL-b-PDESPMA@HA-CD was readily fabricated to integrate stealthy POEGMA, tumor active targeting HA, and an in situ cross-linkable PDESPMA sequence. Supramolecular amphiphilic copolymers with two different POEGMA contents of 25 wt% (P1) and 20 wt% (P2) were prepared via a simple physical mixing process, affording two core-crosslinked (CCL) micelles via an in situ sol-gel process of ethoxysilyl groups. The P1-based CCL micelles show not only desired colloidal stability against high dilution, but also an intracellular ROS-mimicking environment-induced particulate aggregation that is beneficial for promoted intracellular release of the loaded cargoes. Most importantly, P1-based nanomedicines exhibited greater cytotoxicity in CD44 receptor-positive HeLa cells than that in CD44 receptor-negative MCF-7 cells. Overall, this work developed HA-based nanomedicines with sufficient extracellular colloidal stability and efficient intracellular destabilization properties for enhanced anticancer drug delivery via smart integration of in situ crosslinking and supramolecular complexation.

A pan-TE map highlights transposable elements underlying domestication and agronomic traits in Asian rice.

Transposable elements (TEs) are ubiquitous genomic components and hard to study due to being highly repetitive. Here we assembled 232 chromosome-level genomes based on long-read sequencing data. Coupling the 232 genomes with 15 existing assemblies, we developed a pan-TE map comprising both cultivated and wild Asian rice. We detected 177 084 high-quality TE variations and inferred their derived state using outgroups. We found TEs were one source of phenotypic variation during rice domestication and differentiation. We identified 1246 genes whose expression variation was associated with TEs but not single-nucleotide polymorphisms (SNPs), such as OsRbohB, and validated OsRbohB's relative expression activity using a dual-Luciferase (LUC) reporter assays system. Our pan-TE map allowed us to detect multiple novel loci associated with agronomic traits. Collectively, our findings highlight the contributions of TEs to domestication, differentiation and agronomic traits in rice, and there is massive potential for gene cloning and molecular breeding by the high-quality Asian pan-TE map we generated.