Motif-Aware miRNA-Disease Association Prediction Via Hierarchical Attention Network.

As post-transcriptional regulators of gene expression, micro-ribonucleic acids (miRNAs) are regarded as potential biomarkers for a variety of diseases. Hence, the prediction of miRNA-disease associations (MDAs) is of great significance for an in-depth understanding of disease pathogenesis and progression. Existing prediction models are mainly concentrated on incorporating different sources of biological information to perform the MDA prediction task while failing to consider the fully potential utility of MDA network information at the motif-level. To overcome this problem, we propose a novel motif-aware MDA prediction model, namely MotifMDA, by fusing a variety of high- and low-order structural information. In particular, we first design several motifs of interest considering their ability to characterize how miRNAs are associated with diseases through different network structural patterns. Then, MotifMDA adopts a two-layer hierarchical attention to identify novel MDAs. Specifically, the first attention layer learns high-order motif preferences based on their occurrences in the given MDA network, while the second one learns the final embeddings of miRNAs and diseases through coupling high- and low-order preferences. Experimental results on two benchmark datasets have demonstrated the superior performance of MotifMDA over several state-of-the-art prediction models. This strongly indicates that accurate MDA prediction can be achieved by relying solely on MDA network information. Furthermore, our case studies indicate that the incorporation of motif-level structure information allows MotifMDA to discover novel MDAs from different perspectives. The data and codes are available at https://github.com/stevejobws/MotifMDA.

Escape sites from the endo-lysosomal trafficking route manipulate exocytosis of nanoparticles in polar epithelium.

The endo-lysosomal pathway is a major barrier for the trans-epithelial transport of nanoparticles (NPs), but escape strategies could facilitate trans-epithelial delivery. Based on the polarization properties of the epithelium, different escape compartments may result in different exocytosis fates of NPs and further affect the delivery efficiency. Therefore, optimizing the escape sites is critical for trans-epithelial delivery. Here, commonly used PEG-coated-poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles were fabricated as model nanoparticles (MNPs) and the intestinal epithelium was chosen as the polarized epithelium. The MNPs were incubated with different endosomolytic agents for early endosomal escape, late endosomal escape and lysosomal escape, respectively. According to in vitro and in vivo studies, MNPs escaping from early endosomes and late endosomes exhibited stronger capacity for trans-epithelial transport than those escaping from lysosomes. By further probing into the mechanism, we surprisingly found that although MNPs escaping from early endosomes quickly egressed from the apical side of epithelia, they were subsequently followed by "reuptake" via caveolae and trafficked through the endoplasmic reticulum-Golgi apparatus (ER/GA) secretory pathway, achieving efficient trans-epithelial transport; MNPs escaping from late endosomes, which were located near the nucleus, were prone to enter the ER/GA for efficient basolateral exocytosis. However, MNPs escaping from lysosomes were detained within cells by autophagosomes. Collectively, our research suggested that early endosomes and late endosomes were ideal escape sites for trans-epithelial delivery.

The Construction of a Lattice Image and Dislocation Analysis in High-Resolution Characterizations Based on Diffraction Extinctions.

This paper introduces a method for high-resolution lattice image reconstruction and dislocation analysis based on diffraction extinction. The approach primarily involves locating extinction spots in the Fourier transform spectrum (reciprocal space) and constructing corresponding diffraction wave functions. By the coherent combination of diffraction and transmission waves, the lattice image of the extinction planes is reconstructed. This lattice image is then used for dislocation localization, enabling the observation and analysis of crystal planes that exhibit electron diffraction extinction effects and atomic jump arrangements during high-resolution transmission electron microscopy (HRTEM) characterization. Furthermore, due to the method's effectiveness in localizing dislocations, it offers a unique advantage when analyzing high-resolution images with relatively poor quality. The feasibility of this method is theoretically demonstrated in this paper. Additionally, the method was successfully applied to observed edge dislocations, such as 1/6[211-], 1/6[2-11-], and 1/2[01-1], which are not easily observable in conventional HRTEM characterization processes, in electro-deposited Cu thin films. The Burgers vectors were determined. Moreover, this paper also attempted to observe screw dislocations that are challenging to observe in high-resolution transmission electron microscopy. By shifting a pair of diffraction extinction spots and superimposing the reconstructed images before and after the shift, screw dislocations with a Burgers vector of 1/2[011-] were successfully observed in electro-deposited Cu thin films.

PI3K/AKT/mTOR signaling pathway: an important driver and therapeutic target in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a highly heterogeneous tumor lacking estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. It has higher aggressiveness and metastasis than other subtypes, with limited effective therapeutic strategies, leading to a poor prognosis. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling pathway is prevalently over-activated in human cancers and contributes to breast cancer (BC) growth, survival, proliferation, and angiogenesis, which could be an interesting therapeutic target. This review summarizes the PI3K/AKT/mTOR signaling pathway activation mechanism in TNBC and discusses the relationship between its activation and various TNBC subtypes. We also report the latest clinical studies on kinase inhibitors related to this pathway for treating TNBC. Our review discusses the issues that need to be addressed in the clinical application of these inhibitors.

Gold-Template-Assisted Mechanical Exfoliation of Large-Area 2D Layers Enables Efficient and Precise Construction of Moiré Superlattices.

Moiré superlattices, consisting of rotationally aligned 2D atomically thin layers, provide a highly novel platform for the study of correlated quantum phenomena. However, reliable and efficient construction of moiré superlattices is challenging because of difficulties to accurately angle-align small exfoliated 2D layers and the need to shun wet-transfer processes. Here, efficient and precise construction of various moiré superlattices is demonstrated by picking up and stacking large-area 2D mono- or few-layer crystals with predetermined crystal axes, made possible by a gold-template-assisted mechanical exfoliation method. The exfoliated 2D layers are semiconductors, superconductors, or magnets and their high quality is confirmed by photoluminescence and Raman spectra and by electrical transport measurements of fabricated field-effect transistors and Hall devices. Twisted homobilayers with angle-twisting accuracy of ≈0.3°, twisted heterobilayers with sub-degree angle-alignment accuracy, and multilayer superlattices are precisely constructed and characterized by their moiré patterns, interlayer excitons, and second harmonic generation. The present study paves the way for exploring emergent phenomena in moiré superlattices.

Surgical Outcomes and Predictive Factors in Patients With Detrusor Underactivity Undergoing Bladder Outlet Obstruction Surgery.

PURPOSE: This study was conducted to evaluate the efficacy of bladder outlet surgery in patients with detrusor underactivity (DU) and to identify factors associated with successful outcomes. METHODS: We conducted a retrospective review of men diagnosed with DU in urodynamic studies who underwent bladder outlet surgery for lower urinary tract symptoms between May 2018 and April 2023. The International Prostate Symptom Score (IPSS) questionnaire, uroflowmetry (UFM), and multichannel urodynamic studies were administered. Successful treatment outcomes were defined as either an IPSS improvement of at least 50% or the regaining of spontaneous voiding in patients urethral catheterization prior to surgery. RESULTS: The study included 93 male patients. Men diagnosed with significant or equivocal bladder outlet obstruction (BOO) experienced significant postoperative improvements in IPSS (from 20.6 to 6.0 and from 17.4 to 6.5, respectively), maximum urine flow rate (from 5.0 mL/sec to 14.4 mL/sec and from 8.8 mL/sec to 12.2 mL/sec, respectively) and voiding efficiency (from 48.8% to 86.0% and from 61.2% to 85.1%, respectively). However, in the group without obstruction, the improvements in IPSS and UFM results were not significant. The presence of detrusor overactivity (odds ratio [OR], 3.152; P=0.025) and preoperative urinary catheterization (OR, 2.756; P=0.040) were associated with favorable treatment outcomes. Conversely, an unobstructed bladder outlet was identified as a negative prognostic factor. CONCLUSION: In men with DU accompanied by equivocal or significant BOO, surgical intervention to alleviate the obstruction may enhance the IPSS, quality of life, and UFM results. However, those with DU and an unobstructed bladder outlet face a comparatively high risk of treatment failure. Preoperative detrusor overactivity and urinary catheterization are associated with more favorable surgical outcomes. Consequently, active deobstructive surgery should be considered for patients with DU who are experiencing urinary retention.

Long-Term Sodium Deficiency Reduces Sodium Excretion but Impairs Renal Function and Increases Stone Formation in Hyperoxaluric Calcium Oxalate Rats.

Excessive sodium intake is associated with nephrolithiasis, but the impact of sodium-deficient (SD) diets is unknown. Hence, we investigated the effects of short- and long-term SD diets on the expression of renal aquaporins and sodium transporters, and thus calcium oxalate (CaOx) crystal formation in hyperoxaluria rats. In a short-term sodium balance study, six male rats received drinking water and six received 0.75% ethylene glycol (EG) to induce hyperoxaluria. After a 30-day period of feeding on normal chow, both groups were treated with a normal-sodium diet for 5 days, followed by a sodium-free diet for the next 5 days. In a long-term SD study (42 days), four groups, induced with EG or not, were treated with normal-sodium water and sodium-free drinking water, alternately. Short-term sodium restriction in EG rats reversed the daily positive sodium balance, but progressively caused a negative cumulative water balance. In the long-term study, the abundant levels of of Na/H exchanger, thiazide-sensitive Na-Cl cotransporter, Na-K-ATPase, and aquaporins-1 from SD + EG rats were markedly reduced, corresponding to a decrease in Uosm, as compared to SD rats. Increased urine calcium, AP(CaOx)index, and renal CaOx deposition were also noted in SD + EG rats. Although the SD treatment reduced sodium excretion, it also increased urinary calcium and impaired renal function, ultimately causing the formation of more CaOx crystals.

Lipoic acid-mediated oral drug delivery system utilizing changes on cell surface thiol expression for the treatment of diabetes and inflammatory diseases.

Lipoic acid (LA), which has good safety and oral absorption, is obtained from various plant-based food sources and needs to be supplemented through human diet. Moreover, substances with a disulfide structure can enter cells through dynamic covalent disulfide exchange with thiol groups on the cell membrane surface. Based on these factors, we constructed LA-modified nanoparticles (LA NPs). Our results showed that LA NPs can be internalized into intestinal epithelial cells through surface thiols, followed by intracellular transcytosis via the endoplasmic reticulum-Golgi pathway. Further mechanistic studies indicated that disulfide bonds within the structure of LA play a critical role in this transport process. In a type I diabetes rat model, the oral administration of insulin-loaded LA NPs exhibited a more potent hypoglycemic effect, with a pharmacokinetic bioavailability of 5.42 ± 0.53%, representing a 1.6 fold enhancement compared to unmodified PEG NPs. Furthermore, a significant upregulation of surface thiols in inflammatory macrophages was reported. Thus, we turned our direction to investigate the uptake behavior of inflammatory macrophages with increased surface thiols towards LA NPs. Inflammatory macrophages showed a 2.6 fold increased uptake of LA NPs compared to non-inflammatory macrophages. Surprisingly, we also discovered that the antioxidant resveratrol facilitates the uptake of LA NPs in a concentration-dependent manner. This is mainly attributed to an increase in glutathione, which is involved in thiol uptake. Consequently, we employed LA NPs loaded with resveratrol for the treatment of colitis and observed a significant alleviation of colitis symptoms. These results suggest that leveraging the variations of thiol expression levels on cell surfaces under both healthy and diseased states through an oral drug delivery system mediated by the small-molecule nutrient LA can be employed for the treatment of diabetes and certain inflammatory diseases.

Household income and health-related quality of life in children receiving treatment for acute myeloid leukemia: Potential impact of selection bias in health equity research.

OBJECTIVE: Examine the influence of household income on health-related quality of life (HRQOL) among children with newly diagnosed acute myeloid leukemia (AML). DESIGN: Secondary analysis of data prospectively collected from pediatric patients receiving treatment for AML at 14 hospitals across the United States. EXPOSURE: Household income was self-reported on a demographic survey. The examined mediators included the acuity of presentation and treatment toxicity. OUTCOME: Caregiver proxy reported assessment of patient HRQOL from the Peds QL 4.0 survey. RESULT: Children with AML (n = 131) and caregivers were prospectively enrolled to complete PedsQL assessments. HRQOL scores were better for patients in the lowest versus highest income category (mean ± SD: 76.0 ± 14 household income <$25,000 vs. 59.9 ± 17 income ≥$75,000; adjusted mean difference: 11.2, 95% CI: 2.2-20.2). Seven percent of enrolled patients presented with high acuity (ICU-level care in the first 72 h), and 16% had high toxicity (any ICU-level care); there were no identifiable differences by income, refuting mediating roles in the association between income and HRQOL. Enrolled patients were less likely to be Black/African American (9.9% vs. 22.2%), more likely to be privately insured (50.4% vs. 40.7%), and more likely to have been treated on a clinical trial (26.7% vs. 18.5%) compared to eligible unenrolled patients not enrolled. Evaluations of potential selection bias on the association between income and HRQOL suggested differences in HRQOL may be smaller than observed or even in the opposing direction. CONCLUSIONS: While primary analyses suggested lower household income was associated with superior HRQOL, differential participation may have biased these results. Future studies should partner with patients/families to identify strategies for equitable participation in clinical research.

Multi-level bioinformatics resources support drug target discovery of protein-protein interactions.

Drug discovery often begins with a new target. Protein-protein interactions (PPIs) are crucial to multitudinous cellular processes and offer a promising avenue for drug-target discovery. PPIs are characterized by multi-level complexity: at the protein level, interaction networks can be used to identify potential targets, whereas at the residue level, the details of the interactions of individual PPIs can be used to examine a target's druggability. Much great progress has been made in target discovery through multi-level PPI-related computational approaches, but these resources have not been fully discussed. Here, we systematically survey bioinformatics tools for identifying and assessing potential drug targets, examining their characteristics, limitations and applications. This work will aid the integration of the broader protein-to-network context with the analysis of detailed binding mechanisms to support the discovery of drug targets.

Effects of building envelope features on airflow and pollutant dispersion within a symmetric street canyon.

Building envelope features (BEFs) have attracted more and more attention as they have a significant impact on flow structure and pollutant dispersion within street canyons. This paper conducted CFD numerical models validated by wind-tunnel experiments, to explore the effects of the BEFs on characteristics of the airflow and pollutant distribution inside a symmetric street canyon under perpendicular incoming flow. Three different BEFs (balconies, overhangs, and wing walls) and their locations and continuity/discontinuity structures were considered. For each canyon with various BEFs, the air exchange rate (ACH), airflow patterns, and pollutant distributions were evaluated and compared in detail. The results show that compared to the regular canyon, the BEFs will reduce the ACH of the canyon, but increase the disturbances (the proportion of ACH') inside the canyon. The BEFs on the leeward wall have the least influence on the in-canyon airflow and pollutant distributions, followed by that on the windward wall. Then when the BEFs are on both walls, the ventilation capacity of the canyon is weakened greatly, and the pollutant concentration in the ground center is increased significantly, especially near the windward side. Moreover, the discontinuity BEFs will weaken the effect of the continuity BEFs on the in-canyon flow and dispersion, specifically, the discontinuity BEFs reduced the region of high pollutant concentration distributions. These findings can help optimize the BEFs design to enhance ventilation and mitigate traffic pollution.

Enhanced oral and pulmonary delivery of biomacromolecules via amplified transporter targeting.

Ligand-modified nanocarriers can promote oral or inhalative administration of macromolecular drugs across the intestinal or pulmonary mucosa. However, enhancing the unidirectional transport of the nanocarriers through "apical uptake→intracellular transport→basolateral exocytosis" route remains a hot topic and challenge in current research. Forskolin is a naturally occurring diterpenoid compound extracted from the roots of C. forskohlii. In our studies, we found that forskolin could increase the transcellular transport of butyrate-modified nanoparticles by 1.67-fold and 1.20-fold in Caco-2 intestinal epithelial cell models and Calu-3 lung epithelial cell models, respectively. Further mechanistic studies revealed that forskolin, on the one hand, promoted the cellular uptake of butyrate-modified nanoparticles by upregulating the expression of monocarboxylic acid transporter-1 (MCT-1) on the apical membrane. On the other hand, forskolin facilitated the binding of MCT-1 to caveolae, thereby mediating butyrate-modified nanoparticles hijacking caveolae to promote the basolateral exocytosis of butyrate-modified nanoparticles. Studies in normal mice model showed that forskolin could promote the transmucosal absorption of butyrate-modified nanoparticles by >2-fold, regardless of oral or inhalative administration. Using semaglutide as the model drug, both oral and inhalation delivery approaches demonstrated significant hypoglycemic effects in type 2 diabetes mice model, in which inhalative administration was more effective than oral administration. This study optimized the strategies aimed at enhancing the transmucosal absorption of ligand-modified nanocarriers in the intestinal or pulmonary mucosa.

Genome-wide identification and expression analysis of the cryptochromes reveal the CsCRY1 role under low-light-stress in cucumber.

Introduction: Low-light-stress is a common meteorological disaster that can result in slender seedlings. The photoreceptors play a crucial role in perceiving and regulating plants' tolerance to low-light-stress. However, the low-light-stress tolerance of cucumber has not been effectively evaluated, and the functions of these photoreceptor genes in cucumber, particularly under low-light-stress conditions, are not clear. Methods: Herein, we evaluated the growth characteristics of cucumber seedlings under various LED light treatment. The low-light-stress tolerant cucumber CR and intolerant cucumber CR were used as plant materials for gene expression analysis, and then the function of CsCRY1 was analyzed. Results: The results revealed that light treatment below 40 µmol m-2 s-1 can quickly and effectively induce low-light-stress response. Then, cucumber CR exhibited remarkable tolerance to low-light-stress was screened. Moreover, a total of 11 photoreceptor genes were identified and evaluated. Among them, the cryptochrome 1 (CRY1) had the highest expression level and was only induced in the low-light sensitive cucumber CS. The transcript CsaV3_3G047490.1 is predicted to encode a previously unknown CsCRY1 protein, which lacks 70 amino acids at its C-terminus due to alternative 5' splice sites within the final intron of the CsCRY1 gene. Discussion: CRY1 is a crucial photoreceptor that plays pivotal roles in regulating plants' tolerance to low-light stress. In this study, we discovered that alternative splicing of CsCRY1 generates multiple transcripts encoding distinct CsCRY1 protein variants, providing valuable insights for future exploration and utilization of CsCRY1 in cucumber.

The characteristics and risk factors of fatal falls among adults aged 60 and above in Southwest China.

Falls constitute a leading cause of unintentional injury deaths among older adults. This study aimed to examine the comprehensive characteristics of fatal falls among older individuals in Yunnan Province, China, to highlight the challenges faced in elderly care. A total of 22,798 accidental fall-related deaths were extracted from China's National Disease Surveillance Points System aged 60 and above between 2015 and 2019. Quantitative and textual data were analyzed to assess the incidence rates of initiating factors, locations, symptoms, and overall survival (OS) outcomes after falling. Hypertension emerged as the most significant intrinsic factor, especially among individuals aged between 70 and 79, female older adults, and urban residents (P < 0.001). Home was identified as the most common location where fatal falls occurred (61.19%). The head was the most commonly injured body region (58.75%). The median of OS for all fatal falls was 2 days (0.13, 30), of which deaths occurred within 24 h [9287 (49.36%)]. There were instances where timely discovery after falling did not occur in 625 cases; their median of OS was significantly shorter compared to those discovered promptly after falling (P < 0.001). Targeted interventions focusing on fall prevention and post-fall care are equally crucial for the well-being of older adults.

Characterizing the Efficacy and Safety of Chemotherapy Plus Everolimus in HER2-Negative Metastatic Breast Cancer Harboring Altered PI3K/AKT/mTOR.

BACKGROUND: The clinical outcomes of chemotherapy (CT) for the treatment of metastatic triple-negative (TN) and hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) have proven to be disappointing. The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway, a tumor-promoting signaling cascade frequently mutated in breast cancer (BC), has been implicated in chemoresistance. In this study, our objective is to investigate the efficacy and safety of combining everolimus with chemotherapy in mBC patients exhibiting mutations in the PI3K/AKT/mTOR pathway. METHODS: We conducted a retrospective analysis to characterize the efficacy, safety, and their association with clinical and molecular characteristics of metastatic lesions in 14 patients with HER2- mBC. These patients harbored at least one altered member of the PI3K/AKT/mTOR signaling pathway and were treated with a combination of a chemotherapy agent and the mTOR inhibitor everolimus (CT+EVE). RESULTS: The majority of patients belonged to the triple-negative (TN) subtype (9/14, 64.3%), having already undergone 2 lines of chemotherapy (CT) in the metastatic setting (11, 78.6%). These patients carried altered phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) and were administered a vinorelbine-containing regimen (10, 71.4%). The objective response rate (ORR) was 42.9%, with a disease control rate of 92.9%. The median progression-free survival (PFS) and overall survival (OS) were 5.9 (95% confidence interval (CI): 4.9-13.6) months and 14.3 (95% CI: 8.5-not reached (NR)) months, respectively. Patients with fewer prior treatment lines tended to exhibit longer PFS. OS, PFS, and ORR were comparable between hormone receptor-positive (HR+) and triple-negative breast cancer (TNBC) patients, but numerical improvements were noted in patients with a single PI3K pathway alteration compared to those with more than one alteration. Genomic alterations that surfaced upon progression on CT+EVE included cyclin dependent kinase 4 (CDK4) and epidermal growth factor receptor (EGFR) amplification, as well as neurofibromin 1 (NF1) mutation, suggesting potential mechanisms of acquired resistance. An analysis of adverse events indicated manageable toxicities. CONCLUSIONS: The findings of this study suggest both activity and safety for the combination of chemotherapy and the mTOR inhibitor everolimus (CT+EVE) in patients with HER2- mBC who have alterations in the PI3K pathway, particularly those who have received fewer prior chemotherapy. However, it is crucial to note that large-scale, randomized control studies are warranted to more comprehensively characterize the efficacy and safety of this combination therapy.

Orthoptera-TElib: a library of Orthoptera transposable elements for TE annotation.

Transposable elements (TEs) are a major component of eukaryotic genomes and are present in almost all eukaryotic organisms. TEs are highly dynamic between and within species, which significantly affects the general applicability of the TE databases. Orthoptera is the only known group in the class Insecta with a significantly enlarged genome (0.93-21.48 Gb). When analyzing the large genome using the existing TE public database, the efficiency of TE annotation is not satisfactory. To address this limitation, it becomes imperative to continually update the available TE resource library and the need for an Orthoptera-specific library as more insect genomes are publicly available. Here, we used the complete genome data of 12 Orthoptera species to de novo annotate TEs, then manually re-annotate the unclassified TEs to construct a non-redundant Orthoptera-specific TE library: Orthoptera-TElib. Orthoptera-TElib contains 24,021 TE entries including the re-annotated results of 13,964 unknown TEs. The naming of TE entries in Orthoptera-TElib adopts the same naming as RepeatMasker and Dfam and is encoded as the three-level form of "level1/level2-level3". Orthoptera-TElib can be directly used as an input reference database and is compatible with mainstream repetitive sequence analysis software such as RepeatMasker and dnaPipeTE. When analyzing TEs of Orthoptera species, Orthoptera-TElib performs better TE annotation as compared to Dfam and Repbase regardless of using low-coverage sequencing or genome assembly data. The most improved TE annotation result is Angaracris rhodopa, which has increased from 7.89% of the genome to 53.28%. Finally, Orthoptera-TElib is stored in Sqlite3 for the convenience of data updates and user access.

Cell surface patching via CXCR4-targeted nanothreads for cancer metastasis inhibition.

The binding of therapeutic antagonists to their receptors often fail to translate into adequate manipulation of downstream pathways. To fix this 'bug', here we report a strategy that stitches cell surface 'patches' to promote receptor clustering, thereby synchronizing subsequent mechano-transduction. The "patches" are sewn with two interactable nanothreads. In sequence, Nanothread-1 strings together adjacent receptors while presenting decoy receptors. Nanothread-2 then targets these decoys multivalently, intertwining with Nanothread-1 into a coiled-coil supramolecular network. This stepwise actuation clusters an extensive vicinity of receptors, integrating mechano-transduction to disrupt signal transmission. When applied to antagonize chemokine receptors CXCR4 expressed in metastatic breast cancer of female mice, this strategy elicits and consolidates multiple events, including interception of metastatic cascade, reversal of immunosuppression, and potentiation of photodynamic immunotherapy, reducing the metastatic burden. Collectively, our work provides a generalizable tool to spatially rearrange cell-surface receptors to improve therapeutic outcomes.

Investigations of the prognostic value of RUNX1 mutation in acute myeloid leukemia patients: Data from a real-world study.

RUNX1 is one of the recurrent mutated genes in newly diagnosed acute myeloid leukemia (AML). Although historically recognized as a provisional distinct entity, the AML subtype with RUNX1 mutations (AML-RUNX1mut) was eliminated from the 2022 WHO classification system. To gain more insight into the characteristics of AML-RUNX1mut, we retrospectively analyzed 1065 newly diagnosed adult AML patients from the First Affiliated Hospital of Soochow University between January 2017 and December 2021. RUNX1 mutations were identified in 112 patients (10.5%). The presence of RUNX1 mutation (RUNX1mut) conferred a lower composite complete remission (CRc) rate (40.2% vs. 58.4%, P＜0.001), but no significant difference was observed in the 5-year overall survival (OS) rate (50.2% vs. 53.9%; HR=1.293; P=0.115) and event-free survival (EFS) rate (51.5% vs. 49.4%; HR=1.487, P=0.089), even within the same risk stratification. Multivariate analysis showed that RUNX1mut was not an independent prognostic factor for OS (HR=1.352, P=0.068) or EFS (HR=1.129, P=0.513). When patients were stratified according to induction regimen, RUNX1mut was an unfavorable factor for CRc both on univariate and multivariate analysis in patients receiving conventional chemotherapy, and higher risk stratification predicted worse OS. In those who received venetoclax plus hypomethylating agents, RUNX1mut was not predictive of CRc and comparable OS and EFS were seen between intermediate-risk and adverse-risk groups. The results of this study revealed that the impact of RUNX1mut is limited. Its prognostic value depended more on treatment and co-occurrent abnormalities. VEN-HMA may abrogate the prognostic impact of RUNX1, which merits a larger prospective cohort to illustrate.

1-Selector 1-Memristor Configuration with Multifunctional a-IGZO Memristive Devices Fabricated at Room Temperature.

Serving as neuromorphic hardware accelerators, memristors play a crucial role in large-scale neuromorphic computing. Herein, two-terminal memristors utilizing amorphous indium-gallium-zinc oxide (a-IGZO) are fabricated through room-temperature sputtering. The electrical characteristics of these memristors are effectively modulated by varying the oxygen flow during the deposition process. The optimized a-IGZO memristor, fabricated under 3 sccm oxygen flow, presents a 5 × 103 ratio between its high- and low-resistance states, which can be maintained over 1 × 104 s with minimal degradation. Meanwhile, desirable properties such as electroforming-free and self-compliance, crucial for low-energy consumption, are also obtained in the a-IGZO memristor. Moreover, analog conductance switching is observed, demonstrating an interface-type behavior, as evidenced by its device-size-dependent performance. The coexistence of negative differential resistance with analog switching is attributed to the migration of oxygen vacancies and the trapping/detrapping of charges. Furthermore, the device demonstrates optical storage capabilities by exploiting the optical properties of a-IGZO, which can stably operate for up to 50 sweep cycles. Various synaptic functions have been demonstrated, including paired-pulse facilitation and spike-timing-dependent plasticity. These functionalities contribute to a simulated recognition accuracy of 90% for handwritten digits. Importantly, a one-selector one-memristor (1S1M) architecture is successfully constructed at room temperature by integrating a-IGZO memristor on a TaOx-based selector. This architecture exhibits a 107 on/off ratio, demonstrating its potential to suppress sneak currents among adjacent units in a memristor crossbar.