APLNR inhibited nasopharyngeal carcinoma growth and immune escape by downregulating PD-L1.

BACKGROUND: APLNR is a G protein-coupled receptor and our previous study had revealed that APLNR could inhibit nasopharyngeal carcinoma (NPC) growth and metastasis. However, the role of APLNR in regulating PD-L1 expression and immune escape in NPC is unknown. METHODS: We analyzed the expression and correlation of APLNR and PD-L1 in NPC tissues and cells. We investigated the effect of APLNR on PD-L1 expression and the underlying mechanism in vitro and in vivo. We also evaluated the therapeutic potential of targeting APLNR in combination with PD-L1 antibody in a nude mouse xenograft model. RESULTS: We found that APLNR was negatively correlated with PD-L1 in NPC tissues and cells. APLNR could inhibit PD-L1 expression by binding to the FERM domain of JAK1 and blocking the interaction between JAK1 and IFNGR1, thus suppressing IFN-γ-mediated activation of the JAK1/STAT1 pathway. APLNR could also inhibit NPC immune escape by enhancing IFN-γ secretion and CD8+ T-cell infiltration and reducing CD8+ T-cell apoptosis and dysfunction. Moreover, the best effect was achieved in inhibiting NPC growth in nude mice when APLNR combined with PD-L1 antibody. CONCLUSIONS: Our study revealed a novel mechanism of APLNR regulating PD-L1 expression and immune escape in NPC and suggested that APLNR maybe a potential therapeutic target for NPC immunotherapy.

Sex-bias of core intestinal microbiota in different stocks of Chinese mitten crabs (Eriocheir sinensis).

The differences in intestinal microbiota composition are synergistically shaped by internal and external factors of the host. The core microbiota plays a vital role in maintaining intestinal homeostasis. In this study, we conducted 16S rRNA sequencing analysis to investigate the stability of intestinal microbiota and sex-bias of six stocks of Chinese mitten crabs (105 females; and 110 males). The dominant phyla in all six stocks were Proteobacteria, Tenericutes, Bacteroidetes and Firmicutes; however, their relative abundance differed significantly. Twenty-seven core operational taxonomic units (OTUs), corresponding to 18 genera, were screened. Correlation analysis revealed that OTUs of four stocks in the Yangtze River system play important roles in maintaining the stability of intestinal microbiota. Additionally, the core intestinal microbiota was significantly sex-biased, and the top three genera in terms of relative abundance (Acinetobacter, Vibrio, and Candidatus_Hepatoplasma) were significantly dominant in female crabs. Network structure analysis also confirmed gender differences in the association pattern of intestinal microbiota. The intestinal microbiota of male crabs has a higher degree of functional enrichment. This study provided a theoretical basis for further investigating exploring the shaping effect of gender and geographical factors on the intestinal microbiota of Chinese mitten crabs.

[Cause analysis and clinical intervention of C 5 palsy after cervical surgery].

Objective: To review the research progress of C 5 palsy (C 5P) after cervical surgery, providing new clinical intervention ideas for the C 5P patients. Methods: The relevant literature domestically and abroad was extensively consulted and the latest developments in the incidence, risk factors, manifestations and diagnosis, prevention, and intervention measures of C 5P were systematically expounded. Results: C 5P is characterized by weakness in the C 5 nerve innervation area after cervical decompression surgery, manifested as limited shoulder abduction and elbow flexion, with an incidence rate more than 5%, often caused by segmental spinal cord injury or mechanical injury to the nerve roots. For patients with risk factors, careful operation and preventive measures can reduce the incidence of C 5P. Most of the patients can recover with conservative treatment such as drug therapy and physical therapy, while those without significant improvement after 6 months of treatment may require surgical intervention such as foraminal decompression and nerve displacement. Conclusion: Currently, there has been some advancement in the etiology and intervention of C 5P. Nevertheless, further research is imperative to assess the timing of intervention and surgical protocol.

Gut microbiota is necessary for pair-housing to protect against post-stroke depression in mice.

The goal of this study is to investigate the role of microbiota-gut-brain axis involved in the protective effect of pair-housing on post-stroke depression (PSD). PSD model was induced by occluding the middle cerebral artery (MCAO) plus restraint stress for four weeks. At three days after MCAO, the mice were restrained 2 h per day. For pair-housing (PH), each mouse was pair housed with a healthy isosexual cohabitor for four weeks. While in the other PH group, their drinking water was replaced with antibiotic water. On day 35 to day 40, anxiety- and depression-like behaviors (sucrose consumption, open field test, forced swim test, and tail-suspension test) were conducted. Results showed pair-housed mice had better performance on anxiety- and depression-like behaviors than the PSD mice, and the richness and diversity of intestinal flora were also improved. However, drinking antibiotic water reversed the effects of pair-housing. Furthermore, pair-housing had an obvious improvement in gut barrier disorder and inflammation caused by PSD. Particularly, they showed significant decreases in CD8 lymphocytes and mRNA levels of pro-inflammatory cytokines (TNF-a, IL-1ß and IL-6), while IL-10 mRNA was upregulated. In addition, pair-housing significantly reduced activated microglia and increased Nissl's body in the hippocampus of PSD mice. However, all these improvements were worse in the pair-housed mice administrated with antibiotic water. We conclude that pair-housing significantly improves PSD in association with enhanced functions of microbiota-gut-brain axis, and homeostasis of gut microbiota is indispensable for the protective effect of pair-housing on PSD.

One-Dimensional Covalent Organic Framework with Improved Charge Transfer for Enhanced Electrochemiluminescence.

We present a dimensional regulating charge transfer strategy to achieve an enhanced electrochemiluminescence (ECL) by constructing a one-dimensional pyrene-based covalent organic framework (1D-COF). The dual-chain-like edge architecture in 1D-COF facilitates the stabilization of aromatic backbones, the enhancement of electronic conjugations, and the decrease of energy loss. The 1D-COF generates enhanced anodic (92.5-fold) and cathodic (3.2-fold) signals with tripropylamine (TPrA) and K2S2O8 as the anodic and cathodic coreactants, respectively, compared with 2D-COF. The anodic and cathodic ECL efficiencies of 1D-COF are 2.08- and 3.08-fold higher than those of 2D-COF, respectively. According to density functional theory (DFT), the rotational barrier energy (ΔE) of 1D-COF enhances sharply with the increase of dihedral angle, suggesting that the architecture in 1D-COF restrains the intramolecular spin of aromatic chains, which facilitates the decrease of nonradiative transitions and the enhancement of ECL. Furthermore, 1D-COF can be used to construct an ECL biosensor for sensitive detection of dopamine.

The oxytocin receptor is essential for the protective effect of pair housing on post-stroke depression in mice.

The beneficial effect of social interaction in mitigating the incidence of post-stroke depression (PSD) and ameliorating depressive symptoms has been consistently demonstrated through preclinical and clinical studies. However, the underlying relationship with oxytocin requires further investigation. In light of this, the present study aimed to explore the protective effect of pair housing on the development of PSD and the potential relationship with oxytocin receptors. The PSD model was induced by middle cerebral artery occlusion (MCAO) for 50 min, followed by 4-week isolated housing and restrained stress. Subsequently, each mouse in the pair-housing group (PH) was pair-housed with an isosexual healthy partner. Another group was continuously administrated fluoxetine (10 mg/Kg, i.p, once a day) for 3 weeks. To elucidate the potential role of oxytocin, we subjected pair-housed PSD mice to treatment with an oxytocin receptor (OXTR) antagonist (L368,889) (5 mg/Kg, i.p, once a day) for 3 weeks. At 31 to 32 days after MCAO, anxiety- and depressive-like behaviors were assessed using sucrose consumption, forced swim test, and tail-suspension test. The results showed that pair housing significantly improved post-stroke depression to an extent comparable to that of fluoxetine treatment. Furthermore, pair housing significantly decreased corticosterone in serum, increasing OXT mRNA expression in the hypothalamus. Treatment with L368,889 essentially reversed the effect of pair housing, with no discernible sex differences apart from changes in body weight. Pair housing increased hippocampal serotonin (5-HT), but treatment with L368,889 had no significant impact. Additionally, pair housing effectively reduced the number of reactive astrocytes and increased Nissl's body in the cortex and hippocampal CA3 regions. Correspondingly, treatment with L368,889 significantly reversed the changes in the Nissl's body and reactive astrocytes. Moreover, pair housing downregulated mRNA levels of TNF-α, IL-1ß, and IL-6 in the cortex caused by PSD, which was also reversed by treatment with L368,889. In conclusion, pair housing protects against the development of PSD depending on OXT and OXTR in the brain, with no significant divergence based on sex. These findings provide valuable insights into the potential of social interaction and oxytocin as therapeutic targets for PSD. Further research into the underlying mechanisms of these effects may contribute to the development of novel treatments for PSD.

Autonomous enzymatic synthesis of functional nucleic acids for sensitive measurement of long noncoding RNA in human lung tissues.

Aberrant long noncoding RNA (lncRNA) expression is linked to varied pathological processes and malignant tumors, and lncRNA can serve as potential disease biomarkers. Herein, we demonstrate the autonomous enzymatic synthesis of functional nucleic acids for sensitive measurement of lncRNA in human lung tissues on the basis of multiple primer generation-mediated rolling circle amplification (mPG-RCA). This assay involves two padlock probes that act as both a detection probe for recognizing target lncRNA and a domain for producing complementary DNAzyme. Two padlock probes can hybridize with target lncRNA at different sites, followed by ligation to form a circular template with the aid of RNA ligase. The circular template can initiate mPG-RCA to generate abundant Mg2+-dependent DNAzymes that can specifically cleave signal probes to induce the recovery of Cy3 fluorescence. The inherent characteristics of ligase-based ligation reaction and DNAzymes endow this assay with excellent specificity, and the introduction of multiple padlock probes endows this assay with high sensitivity. This strategy can rapidly and sensitively measure lncRNA with a wide linear range of 1 fM - 1 nM and a detection limit of 678 aM within 1.5 h, and it shows distinct advantages of simplicity and immobilization-free without the need of precise temperature control and tedious procedures of nanomaterial preparation. Moreover, it enables accurate measurement of lncRNA level in normal cells and malignant tumor cells as well as differentiation of lncRNA expressions in tissues of non-small cell lung cancer (NSCLC) patients and normal individuals, with promising applications in biomedical studies and disease diagnosis.

Construction of a glycosylation-mediated fluorescent biosensor for label-free measurement of site-specific 5-hydroxymethylcytosine in cancer cells with zero background signal.

BACKGROUND: 5-hydroxymethylcytosine (5hmC) as an epigenetic modification can regulate gene expression, and its abnormal level is related with various tumor invasiveness and poor prognosis. Nevertheless, the current methods for 5hmC assay usually involve expensive instruments/antibodies, radioactive risk, high background, laborious bisulfite treatment procedures, and non-specific/long amplification time. RESULTS: We develop a glycosylation-mediated fluorescent biosensor based on helicase-dependent amplification (HDA) for label-free detection of site-specific 5hmC in cancer cells with zero background signal. The glycosylated 5hmC-DNA (5ghmC) catalyzed by ß-glucosyltransferase (ß-GT) can be cleaved by AbaSI restriction endonuclease to generate two dsDNA fragments with sticky ends. The resultant dsDNA fragments are complementary to the biotinylated probes and ligated by DNA ligases, followed by being captured by magnetic beads. After magnetic separation, the eluted ligation products act as the templates to initiate HDA reaction, generating abundant double-stranded DNA (dsDNA) products within 20 min. The dsDNA products are measured in a label-free manner with SYBR Green I as an indicator. This biosensor can measure 5hmC with a detection limit of 2.75 fM and a wide linear range from 1 × 10-14 to 1 × 10-8 M, and it can discriminate as low as 0.001% 5hmC level in complex mixture. Moreover, this biosensor can measure site-specific 5hmC in cancer cells, and distinguish tumor cells from normal cells. SIGNIFICANCE: This biosensor can achieve a zero-background signal without the need of either 5hmC specific antibody or bisulfite treatment, and it holds potential applications in biological research and disease diagnosis.

Non-invasive diagnosis of non-alcoholic fatty liver disease: Current status and future perspective.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease throughout the world. Hepatocellular carcinoma (HCC) and liver cirrhosis can result from nonalcoholic steatohepatitis (NASH), the severe stage of NAFLD progression. By some estimates, NAFLD affects almost one-third of the world's population, which is completely new and serious public health issue. Unfortunately, NAFLD is diagnosed by exclusion, and the gold standard for identifying NAFLD/NASH and reliably measuring liver fibrosis remains liver biopsy, which is an invasive, costly, time-consuming procedure and involves variable inter-observer diagnosis. With the progress of omics and imaging techniques, numerous non-invasive serological assays have been generated and developed. On the basis of these developments, non-invasive biomarkers and imaging techniques have been combined to increase diagnostic accuracy. This review provides information for the diagnosis and assessment of NAFLD/NASH in clinical practice going forward and may assist the clinician in making an early and accurate diagnosis and in proposing a cost-effective patient surveillance. We discuss newly identified and validated non-invasive diagnostic methods from biopsy-confirmed NAFLD patient studies and their implementation in clinical practice, encompassing NAFLD/NASH diagnosis and differentiation, fibrosis assessment, and disease progression monitoring. A series of tests, including 20-carboxy arachidonic acid (20-COOH AA) and 13,14-dihydro-15-keto prostaglandin D2 (dhk PGD2), were found to be potentially the most accurate non-invasive tests for diagnosing NAFLD. Additionally, the Three-dimensional magnetic resonance imaging (3D-MRE), combination of the FM-fibro index and Liver stiffness measurement (FM-fibro LSM index) and the machine learning algorithm (MLA) tests are more accurate than other tests in assessing liver fibrosis. However, it is essential to use bigger cohort studies to corroborate a number of non-invasive diagnostic tests with extremely elevated diagnostic values.

Assessing the ecotoxicity of florfenicol exposure at environmental levels: A case study of histology, apoptosis and microbiota in hepatopancreas of Eriocheir sinensis.

The intensification of production practices in the aquaculture industry has led to the indiscriminate use of antibiotics to combat diseases and reduce costs, which has resulted in environmental pollution, posing serious threats to aquaculture sustainability and food safety. However, the toxic effect of florfenicol (FF) exposure on the hepatopancreas of crustaceans remains unclear. Herein, by employing Chinese mitten crab (Eriocheir sinensis) as subjects to investigate the toxic effects on histopathology, oxidative stress, apoptosis and microbiota of hepatopancreas under environment-relevant (0.5 and 5 µg/L), and extreme concentrations (50 µg/L) of FF. Our results revealed that the damage of hepatopancreas tissue structure caused by FF exposure in a dose-and time-dependent manner. Combined with the increased expression of apoptosis-related genes (Caspase 3, Caspase 8, p53, Bax and Bcl-2) at mRNA and protein levels, activation of catalase (CAT) and superoxide dismutase (SOD), and malondialdehyde (MDA) accumulation, FF exposure also induced oxidative stress, and apoptosis in hepatopancreas. Interestingly, 7 days exposure triggered more pronounced toxic effect in crabs than 14 days under environment-relevant FF concentration. Integrated biomarker response version 2 (IBRv2) index indicated that 14 days FF exposure under extreme concentration has serious toxicity effect on crabs. Furthermore, 14 days exposure to FF changed the diversity and composition of hepatopancreas microbiota leading remarkable increase of pathogenic microorganism Spirochaetes following exposure to 50 µg/L of FF. Taken together, our study explained potential mechanism of FF toxicity on hepatopancreas of crustaceans, and provided a reference for the concentration of FF to be used in culture of Chinese mitten crab.

Ultrathin-FeOOH-coated MnO2 nanozyme with enhanced catalase-like and oxidase-like activities for photoelectrochemical and colorimetric detection of organophosphorus pesticides.

Herein, we develop a dual-mode biosensor for photoelectrochemical and colorimetric detection of organophosphate pesticides (OPPs) based on ultrathin-FeOOH-coated MnO2 (MO@FHO) nanozyme. In this biosensor, OPPs can inhibit the alkaline phosphatase (ALP) activity and hinder the dephosphorylation of l-ascorbic acid-2-phosphate, preventing the decomposition of MO@FHO nanozyme and inducing both a photoelectrochemical (PEC) signal and the colorimetric change. The MO@FHO nanozyme not only possesses an enhanced catalase-like activity to degrade H2O2 for the generation of an improved cathodic photocurrent, but also exhibits an excellent oxidase-like activity to oxidize 3,3,5,5-tetramethylbenzidine with high catalytic efficiency. This biosensor displays a detection limit of 50 pmol/L for the PEC mode and a detection limit of 0.8 nmol/L for the colorimetric mode. Moreover, this biosensor exhibits excellent performance in complex biological matrices, and the smartphone-based visual sensing platform facilitates rapid and sensitive detection of OPPs, holding promising applications in food safety monitoring, and on-site detection.

Measuring early adolescents' prosocial behavior toward diverse others: Considering multiple social identities.

INTRODUCTION: In a diverse society, individuals often need to make prosocial decisions toward others who vary on a range of intertwined social identities. Adolescence is a prime time to promote intergroup prosociality due to identity salience during this developmental stage. In this study, our goal was to develop and provide initial validation, of a novel measure on intergroup prosocial behavior considering gender and race/ethnicity. METHOD: We used two independent samples of early adolescents (N1 = 118, Mage = 12.21 years, 55% boys, 59% White collected nationally in the United States.; N2 = 133, Mage = 12.77, 51.1% boys, 77% White collected locally in Arizona). RESULTS: Using the data from Sample 1, Exploratory Factor Analyses revealed a two-factor solution capturing intergroup prosociality and personal distress. Confirmatory Factor Analyses with data from Sample 2 confirmed the factor structure. The reliability of intergroup prosociality was acceptable. Prosociality subscale was positively correlated with adolescents' empathy, sympathy, compliant, emotional, dire, and anonymous prosocial behaviors indicating convergent validity and negatively correlated with adolescents' public prosocial behavior indicating discriminant validity. Further, we examined whether youth engage in differential intergroup prosocial behavior using both variable-centered and person-centered approaches, combining data from Samples 1 and 2. While adolescents did not engage in differential intergroup prosocial behavior, Latent Profile Analyses revealed five distinct profiles of early adolescents' intergroup prosociality. Overall, this study advances research on youth's intergroup prosociality across two intersectional social identities, moving beyond the conceptualization of single social identities in intergroup research.

Exogenous Co-Reactant-Free Electrochemiluminescent Biosensor for Ratiometric Measurement of α-Glucosidase Based on a ZIF-67-Regulated Hydrogen-Bonded Organic Framework.

The development of highly sensitive and selective analytical approaches for monitoring enzymatic activity is critical for disease diagnosis and biomedical research. Herein, we develop an exogenous co-reactant-free electrochemiluminescence (ECL) biosensor for the ratiometric measurement of α-glucosidase (α-Glu) based on a zeolitic imidazolate framework (ZIF-67)-regulated pyrene-based hydrogen-bonded organic framework (HOF-101). Target α-Glu can hydrolyze maltose to α-d-glucose, which can subsequently react with GOx to produce gluconic acid. The resultant gluconic acid can dissolve ZIF-67, leading to the recovery of the HOF-101 cathodic ECL signal and the decrease of the luminol anodic ECL signal. The long-range ordered structure of HOF-101 can speed up charge transfer, resulting in a stable and strong cathodic ECL signal. Moreover, ZIF-67 can not only efficiently quench the ECL signal of HOF-101 due to ECL resonance energy transfer between HOF-101 and ZIF-67 as well as the steric hindrance effect of ZIF-67 but also enhance the anodic ECL emission of luminol in dissolved O2 system because of its ordered and porous crystalline structure and the atomically dispersed Co2+. Notably, HOF-101 possesses a higher ECL efficiency (32.22%) compared with the Ru(bpy)32+ standard. Importantly, this ratiometric ECL biosensor shows high sensitivity (a detection limit of 0.19 U L-1) and a broad linear range (0.2-50 U L-1). This biosensor can efficiently eliminate systematic errors and enhance detection reliability without the involvement of exogenous co-reactants, and it displays good assay performance in human serum samples, holding great promise in biomedical research studies.

Protective Effects of Sesamol on Renal Ischemia-Reperfusion Injury Via Regulation of Nuclear Factor Erythroid 2-Related Factor 2 Pathway.

BACKGROUND: Sesamol is a natural antioxidant known for its potent antioxidant and free radical scavenging properties. This study aimed to explore the therapeutic effects and underlying mechanisms of sesamol in the development of renal ischemia-reperfusion injury (IRI) in mice. METHODS: C57BL/6J wild-type mice were divided into 3 groups: IR group, treated with normal saline after undergoing the IRI procedure; Sesamol + IR group, treated with 30 mg/kg/d of sesamol after the IRI procedure; and Sham group, treated with normal saline but not subjected to the IRI process. Renal IRI was induced by performing a right kidney nephrectomy and subjecting the left kidney to 30-minute ischemia, followed by 24-hour reperfusion. Kidney tissues and serum were collected 24 hours post-IRI to assess the impact of sesamol on renal function after IRI. Serum creatinine and blood urea nitrogen levels were assessed, and renal cell apoptosis was detected through terminal deoxynucleotidyl transferase dUTP nick-end labeling staining. The levels of interleukin 1ß and interleukin 18 in kidney tissues, as well as indicators of oxidative stress, were also measured. Furthermore, Nrf2-deficient mice were used to examine the protective function of the nuclear factor erythroid 2-related factor 2 (Nrf2)/hemeoxygenase-1 (HO-1) and NAD(P)H dehydrogenase quinone 1 (NQO1) signaling pathways induced by sesamol, as determined by western blot assay. RESULTS: Sesamol demonstrated significant improvement in renal function, along with reductions in renal tubular injury, cell necrosis, and apoptosis in mice. It also effectively lowered key inflammatory mediator levels. Sesamol exhibited antioxidant properties by reducing malondialdehyde levels and enhancing superoxide dismutase activities 24 hours after IRI. Western blot assay revealed increased Nrf2, HO-1, and NQO-1 protein levels with sesamol treatment. Notably, Nrf2-deficient mice did not exhibit the beneficial effects of sesamol. CONCLUSIONS: This study demonstrates that sesamol effectively alleviates renal IRI by enhancing antioxidant defenses and reducing inflammation potentially through the Nrf2/HO-1 and NQO1 signaling pathways.

Synthesis of silica-encapsulated tetraphenylethylene with aggregation-induced electrochemiluminescence resonance energy transfer for sensitively sensing microcystin-LR.

The reported organic electrochemiluminescence (ECL) luminophors for the detection of various markers often suffer from intermolecular π-π stacking-induced luminophore quenching. Herein, we demonstrate one-pot synthesis of a new aggregation-induced electrochemiluminescence (AIECL) emitter (i.e., TPE@SiO2/rGO composite) for sensitive measurement of microcystin-leucine arginine (MC-LR). The TPE@SiO2/rGO composite is constructed by embedding the silica-encapsuled 1,1,2,2-tetra(4-carboxylphenyl)ethylene (TPE) in the reduced graphene oxide. In comparison with the monomer TPE, this composite exhibit high luminescence efficiency and strong ECL emission, because the AIECL phenomenon triggered by the spatial confinement effect in the SiO2 cage induces the restriction of the internal motion and vibration of molecules. Notably, this composite has distinct advantages of easy preparation, simple functionalization, and stable luminescence. Especially, the TPE@SiO2/rGO-based ECL-RET system exhibits a high quenching efficiency (ΦET) of 69.7%. When target MC-LR is present, it triggers DNA strand displacement reaction (SDR), inducing the quenching of the ECL signal of TPE@SiO2/rGO composite due to ECL resonance energy transfer between TPE@SiO2/rGO composite and methylene blue (MB). The proposed biosensor enables highly sensitive, low-cost, and robust measurement of MC-LR with a large dynamic range of 7 orders of magnitude and a detection limit of 3.78 fg/mL, and it displays excellent detection performance in complex biological matrices, holding potential applications in food safety and water monitoring.

Reciprocal regulation of lncRNA MEF and c-Myc drives colorectal cancer tumorigenesis.

More than half of all cancers demonstrate aberrant c-Myc expression, making this arguably the most important human oncogene. Deregulated long non-coding RNAs (lncRNAs) are also commonly implicated in tumorigenesis, and some limited examples have been established where lncRNAs act as biological tuners of c-Myc expression and activity. Here, we demonstrate that the lncRNA denoted c-Myc Enhancing Factor (MEF) enjoys a cooperative relationship with c-Myc, both as a transcriptional target and driver of c-Myc expression. Mechanistically, MEF functions by binding to and stabilizing the expression of hnRNPK in colorectal cancer cells. The MEF-hnRNPK interaction serves to disrupt binding between hnRNPK and the E3 ubiquitin ligase TRIM25, which attenuates TRIM25-dependent hnRNPK ubiquitination and proteasomal destruction. In turn, the stabilization of hnRNPK through MEF enhances c-Myc expression by augmenting the translation c-Myc. Moreover, modulating the expression of MEF in shRNA-mediated knockdown and overexpression studies revealed that MEF expression is essential for colorectal cancer cell proliferation and survival, both in vitro and in vivo. From the clinical perspective, we show that MEF expression is differentially increased in colorectal cancer tissues compared to normal adjacent tissues. Further, correlations exist between MEF, c-Myc, and hnRNPK suggesting the MEF-c-Myc positive feedback loop is active in patients. Together these data demonstrate that MEF is a pivotal partner of the c-Myc network and propose MEF as a valuable therapeutic target for colorectal cancer.

Examining changes in adolescents' high school math and science motivational beliefs and their relations to parental STEM support and STEM major choice at the intersectionality of gender and college generation status.

Drawing on the situated expectancy-value, dimensional comparison theories, and the intersectionality approach, this article examined the changes in adolescents' math and science motivational beliefs, the parental and college correlates of those beliefs, and the differences at the intersection of gender and college generation status (i.e., female and male first- and continuing-generation college students). Findings based on the nationally representative high-school longitudinal study data (N = 12,070; Mage = 14 years; 54% female students; 28% first-generation college students; and 14% Latinx, 9% Black, 10% Asian, and 57% White) suggest that although adolescents' math and science ability self-concepts declined during high school, their science interest remained stable, and their math and science utility values increased. Adolescents' motivational beliefs in ninth grade and the changes from ninth to 11th grade positively predicted whether they declared a science, technology, engineering, and mathematics (STEM) college major. Parents' ninth-grade STEM support was more consistently associated with adolescents' concurrent beliefs compared to the changes in their beliefs. Finally, we found that female first-generation college students, who were more likely to be Latinx and Black students, tended to have lower math and science motivational beliefs, received less parental STEM support, and were less likely to choose a STEM major than their peers. The findings of this study indicate adolescents' math and science motivational development in high school matters for their college majors and that certain understudied groups, including female first-generation college students, may experience acute marginalization in STEM and warrant further attention. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Copper homeostasis and cuproptosis in mitochondria.

Mitochondria serve as sites for energy production and are essential for regulating various forms of cell death induced by metal metabolism, targeted anticancer drugs, radiotherapy and immunotherapy. Cuproptosis is an autonomous form of cell death that depends on copper (Cu) and mitochondrial metabolism. Although the recent discovery of cuproptosis highlights the significance of Cu and mitochondria, there is still a lack of biological evidence and experimental verification for the underlying mechanism. We provide an overview of how Cu and cuproptosis affect mitochondrial morphology and function. Through comparison with ferroptosis, similarities and differences in mitochondrial metabolism between cuproptosis and ferroptosis have been identified. These findings provide implications for further exploration of cuproptotic mechanisms. Furthermore, we explore the correlation between cuproptosis and immunotherapy or radiosensitivity. Ultimately, we emphasize the therapeutic potential of targeting cuproptosis as a novel approach for disease treatment.

Bioorthogonal Reaction-Mediated Enzymatic Elongation-Driven Dendritic Nanoassembly for Genome-Wide Analysis of 5-Hydroxymethyluracil in Breast Tissues.

5-Hydroxymethyluracil (5hmU) is an oxidation derivative of thymine in the genomes of various organisms and may serve as both an epigenetic mark and a cancer biomarker. However, the current 5hmU assays usually have drawbacks of laborious procedures, low specificity, and unsatisfactory sensitivity. Herein, we demonstrate the click chemistry-mediated hyperbranched amplification-driven dendritic nanoassembly for genome-wide analysis of 5hmU in breast cell lines and human breast tissues. The proposed strategy possesses good selectivity, ultralow background, and high sensitivity with a detection limit of 83.28 aM. This method can accurately detect even a 0.001% 5hmU level in the mixture. Moreover, it can determine 5hmU at single-cell level and distinguish the expressions of 5hmU in tissues of normal persons and breast cancer patients, holding great promise in 5hmU-related biological research and clinical diagnosis.

Assessment of visual function in blind mice and monkeys with subretinally implanted nanowire arrays as artificial photoreceptors.

Retinal prostheses could restore image-forming vision in conditions of photoreceptor degeneration. However, contrast sensitivity and visual acuity are often insufficient. Here we report the performance, in mice and monkeys with induced photoreceptor degeneration, of subretinally implanted gold-nanoparticle-coated titania nanowire arrays providing a spatial resolution of 77.5 µm and a temporal resolution of 3.92 Hz in ex vivo retinas (as determined by patch-clamp recording of retinal ganglion cells). In blind mice, the arrays allowed for the detection of drifting gratings and flashing objects at light-intensity thresholds of 15.70-18.09 µW mm-2, and offered visual acuities of 0.3-0.4 cycles per degree, as determined by recordings of visually evoked potentials and optomotor-response tests. In monkeys, the arrays were stable for 54 weeks, allowed for the detection of a 10-µW mm-2 beam of light (0.5° in beam angle) in visually guided saccade experiments, and induced plastic changes in the primary visual cortex, as indicated by long-term in vivo calcium imaging. Nanomaterials as artificial photoreceptors may ameliorate visual deficits in patients with photoreceptor degeneration.