A lissencephaly-associated BAIAP2 variant causes defects in neuronal migration during brain development.

Lissencephaly is a neurodevelopmental disorder characterized by a loss of brain surface convolutions caused by genetic variants that disrupt neuronal migration. However, the genetic origins of the disorder remain unidentified in nearly one-fifth of people with lissencephaly. Using whole-exome sequencing, we identified a de novo BAIAP2 variant, p.Arg29Trp, in an individual with lissencephaly with a posterior more severe than anterior (P>A) gradient, implicating BAIAP2 as a potential lissencephaly gene. Spatial transcriptome analysis in the developing mouse cortex revealed that Baiap2 is expressed in the cortical plate and intermediate zone in an anterior low to posterior high gradient. We next used in utero electroporation to explore the effects of the Baiap2 variant in the developing mouse cortex. We found that Baiap2 knockdown caused abnormalities in neuronal migration, morphogenesis and differentiation. Expression of the p.Arg29Trp variant failed to rescue the migration defect, suggesting a loss-of-function effect. Mechanistically, the variant interfered with the ability of BAIAP2 to localize to the cell membrane. These results suggest that the functions of BAIAP2 in the cytoskeleton, cell morphogenesis and migration are important for cortical development and for the pathogenesis of lissencephaly in humans.

Male allocation to ejaculation and mating effort imposes different life history trade-offs.

When males compete, sexual selection favors reproductive traits that increase their mating or fertilization success (pre- and postcopulatory sexual selection). It is assumed that males face a trade-off between these 2 types of sexual traits because they both draw from the same pool of resources. Consequently, allocation into mate acquisition or ejaculation should create similar trade-offs with other key life history traits. Tests of these assumptions are exceedingly rare. Males only ejaculate after they mate, and the costs of ejaculation are therefore highly confounded with those of mating effort. Consequently, little is known about how each component of reproductive allocation affects a male's future performance. Here, we ran an experiment using a novel technique to distinguish the life history costs of mating effort and ejaculation for mosquitofish (Gambusia holbrooki). We compared manipulated males (mate without ejaculation), control males (mate and ejaculate), and naïve males (neither mate nor ejaculate) continuously housed with a female and 2 rival males. We assessed their growth, somatic maintenance, mating and fighting behavior, and sperm traits after 8 and 16 weeks. Past mating effort significantly lowered a male's future mating effort and growth, but not his sperm production, while past sperm release significantly lowered a male's future ejaculate quantity, but not his mating effort. Immune response was the only trait impacted by both past mating effort and past ejaculation. These findings challenge the assumption that male reproductive allocation draws from a common pool of resources to generate similar life history costs later in life. Instead, we provide clear evidence that allocation into traits under pre- and postcopulatory sexual selection have different trait-specific effects on subsequent male reproductive performance.

Phosphorylation of OsTGA5 by casein kinase II compromises its suppression of defense-related gene transcription in rice.

Plants manage the high cost of immunity activation by suppressing the expression of defense genes during normal growth and rapidly switching them on upon pathogen invasion. TGAs are key transcription factors controlling the expression of defense genes. However, how TGAs function, especially in monocot plants like rice with continuously high levels of endogenous salicylic acid (SA) remains elusive. In this study, we characterized the role of OsTGA5 as a negative regulator of rice resistance against blast fungus by transcriptionally repressing the expression of various defense-related genes. Moreover, OsTGA5 repressed PTI responses and the accumulation of endogenous SA. Importantly, we showed that the nucleus-localized casein kinase II (CK2) complex interacts with and phosphorylates OsTGA5 on Ser-32, which reduces the affinity of OsTGA5 for the JIOsPR10 promoter, thereby alleviating the repression of JIOsPR10 transcription and increasing rice resistance. Furthermore, the in vivo phosphorylation of OsTGA5 Ser-32 was enhanced by blast fungus infection. The CK2 α subunit, depending on its kinase activity, positively regulated rice defense against blast fungus. Taken together, our results provide a mechanism for the role of OsTGA5 in negatively regulating the transcription of defense-related genes in rice and the repressive switch imposed by nuclear CK2-mediated phosphorylation during blast fungus invasion.

Loss of threonyl-tRNA synthetase-like protein Tarsl2 has little impact on protein synthesis but affects mouse development.

Aminoacyl-tRNA synthetases (aaRSs) are essential components for mRNA translation. Two sets of aaRSs are required for cytoplasmic and mitochondrial translation in vertebrates. Interestingly, TARSL2 is a recently evolved duplicated gene of TARS1 (encoding cytoplasmic threonyl-tRNA synthetase) and represents the only duplicated aaRS gene in vertebrates. Although TARSL2 retains the canonical aminoacylation and editing activities in vitro, whether it is a true tRNA synthetase for mRNA translation in vivo is unclear. In this study, we showed that Tars1 is an essential gene since homozygous Tars1 KO mice were lethal. In contrast, when Tarsl2 was deleted in mice and zebrafish, neither the abundance nor the charging levels of tRNAThrs were changed, indicating that cells relied on Tars1 but not on Tarsl2 for mRNA translation. Furthermore, Tarsl2 deletion did not influence the integrity of the multiple tRNA synthetase complex, suggesting that Tarsl2 is a peripheral member of the multiple tRNA synthetase complex. Finally, we observed that Tarsl2-deleted mice exhibited severe developmental retardation, elevated metabolic capacity, and abnormal bone and muscle development after 3 weeks. Collectively, these data suggest that, despite its intrinsic activity, loss of Tarsl2 has little influence on protein synthesis but does affect mouse development.

Investigating the role of county-level colorectal cancer screening rates on stage at diagnosis of colorectal cancer in rural Georgia.

BACKGROUND: To examine the impact of county-level colorectal cancer (CRC) screening rates on stage at diagnosis of CRC and identify factors associated with stage at diagnosis across different levels of screening rates in rural Georgia. METHODS: We performed a retrospective analysis utilizing data from 2004 to 2010 Surveillance, Epidemiology, and End Results Program. The 2013 United States Department of Agriculture rural-urban continuum codes were used to identify rural Georgia counties. The 2004-2010 National Cancer Institute small area estimates for screening behaviors were applied to link county-level CRC screening rates. Descriptive statistics and multinominal logistic regressions were performed. RESULTS: Among 4,839 CRC patients, most patients diagnosed with localized CRC lived in low screening areas; however, many diagnosed with regionalized and distant CRC lived in high screening areas (p-value = 0.009). In multivariable analysis, rural patients living in high screening areas were 1.2-fold more likely to be diagnosed at a regionalized and distant stage of CRC (both p-value < 0.05). When examining the factors associated with stage at presentation, Black patients who lived in low screening areas were 36% more likely to be diagnosed with distant diseases compared to White patients (95% CI, 1.08-1.71). Among those living in high screening areas, patients with right-sided CRC were 38% more likely to have regionalized disease (95% CI, 1.09-1.74). CONCLUSION: Patients living in high screening areas were more likely to have a later stage of CRC in rural Georgia. IMPACT: Allocating CRC screening/treatment resources and improving CRC risk awareness should be prioritized for rural patients in Georgia.

The relationship of cancer history and chronic disease status to colorectal cancer screening: A cross-sectional analysis of 2020-2021 Behavioral Risk Factor Surveillance System.

PURPOSE: We examined whether having a history of cancer and chronic diseases was associated with guideline-concordant colorectal cancer (CRC) screening utilization. METHODS: Self-reported data from the 2020 and 2021 Behavioral Risk Factor Surveillance System in Oregon and West Virginia were used. Guideline-concordant CRC screening was the outcome of interest. The exposure was having a personal history of cancer, chronic diseases, or both. Multivariable logistic regressions were applied to assess the abovementioned association. RESULTS: Among 10,373 respondents aged 45-75 years, 75.5% of those with a history of cancer and chronic diseases had guideline-concordant CRC screening use versus 52.8% of those without any history (p-value < 0.05). In multivariable analysis, having a history of cancer (OR 1.74; 95% CI 1.11-2.71), chronic diseases (OR 1.35; 95% CI 1.14-1.59), and both cancer and chronic diseases (OR 2.14; 95% CI 1.62-2.82) were positively associated with screening uptake compared to respondents without any history. Regardless of disease history, older age was associated with greater CRC screening uptake (p-value < 0.05). Among respondents with chronic diseases only or without any condition, those with a health care provider had 1.7-fold and 2.7-fold increased odds of receiving CRC screening, respectively. However, current smokers were 28% and 34% less likely to be screened for CRC among those with chronic diseases only and without any conditions, respectively. CONCLUSION: Having a personal history of cancer and chronic diseases appears to be positively associated with guideline-concordant CRC screening use. Effective implementation of patient-centered communication through primary care initiatives may increase adherence to CRC screening recommendations.

Novel lissencephaly-associated NDEL1 variant reveals distinct roles of NDE1 and NDEL1 in nucleokinesis and human cortical malformations.

The development of the cerebral cortex involves a series of dynamic events, including cell proliferation and migration, which rely on the motor protein dynein and its regulators NDE1 and NDEL1. While the loss of function in NDE1 leads to microcephaly-related malformations of cortical development (MCDs), NDEL1 variants have not been detected in MCD patients. Here, we identified two patients with pachygyria, with or without subcortical band heterotopia (SBH), carrying the same de novo somatic mosaic NDEL1 variant, p.Arg105Pro (p.R105P). Through single-cell RNA sequencing and spatial transcriptomic analysis, we observed complementary expression of Nde1/NDE1 and Ndel1/NDEL1 in neural progenitors and post-mitotic neurons, respectively. Ndel1 knockdown by in utero electroporation resulted in impaired neuronal migration, a phenotype that could not be rescued by p.R105P. Remarkably, p.R105P expression alone strongly disrupted neuronal migration, increased the length of the leading process, and impaired nucleus-centrosome coupling, suggesting a failure in nucleokinesis. Mechanistically, p.R105P disrupted NDEL1 binding to the dynein regulator LIS1. This study identifies the first lissencephaly-associated NDEL1 variant and sheds light on the distinct roles of NDE1 and NDEL1 in nucleokinesis and MCD pathogenesis.

Clinical and molecular characterization of patients with YWHAG-related epilepsy.

OBJECTIVE: YWHAG variant alleles have been associated with a rare disease trait whose clinical synopsis includes an early onset epileptic encephalopathy with predominantly myoclonic seizures, developmental delay/intellectual disability, and facial dysmorphisms. Through description of a large cohort, which doubles the number of reported patients, we further delineate the spectrum of YWHAG-related epilepsy. METHODS: We included in this study 24 patients, 21 new and three previously described, with pathogenic/likely pathogenic variants in YWHAG. We extended the analysis of clinical, electroencephalographic, brain magnetic resonance imaging, and molecular genetic information to 24 previously published patients. RESULTS: The phenotypic spectrum of YWHAG-related disorders ranges from mild developmental delay to developmental and epileptic encephalopathy (DEE). Epilepsy onset is in the first 2 years of life. Seizure freedom can be achieved in half of the patients (13/24, 54%). Intellectual disability (23/24, 96%), behavioral disorders (18/24, 75%), neurological signs (13/24, 54%), and dysmorphisms (6/24, 25%) are common. A genotype-phenotype correlation emerged, as DEE is more represented in patients with missense variants located in the ligand-binding domain than in those with truncating or missense variants in other domains (90% vs. 19%, p < .001). SIGNIFICANCE: This study suggests that pathogenic YWHAG variants cause a wide range of clinical presentations with variable severity, ranging from mild developmental delay to DEE. In this allelic series, a genotype-phenotype correlation begins to emerge, potentially providing prognostic information for clinical management and genetic counseling.

Raddeanin A Protects the BRB Through Inhibiting Inflammation and Apoptosis in the Retina of Alzheimer's Disease.

Neuroinflammation and endothelial cell apoptosis are prominent features of blood-brain barrier (BBB) disruption, which have been described in Alzheimer's disease (AD) and can predict cognitive decline. Recent reports revealed vascular ß-amyloid (Aß) deposits, Muller cell degeneration and microglial dysfunction in the retina of AD patients. However, there has been no in-depth research on the roles of inflammation, retinal endothelial cell apoptosis, and blood-retinal barrier (BRB) damage in AD retinopathy. We found that Raddeanin A (RDA) could improve pathological and cognitive deficits in a mouse model of Alzheimer's disease by targeting ß-amyloidosis, However, the effects of RDA on AD retinal function require further study. To clarify whether RDA inhibits inflammation and apoptosis and thus improves BRB function in AD-related retinopathy. In vitro we used Aß-treated HRECs and MIO-M1 cells, and in vivo we used 3×Tg-AD mice to investigate the effect of RDA on BRB in AD-related retinopathy. We found that RDA could improve BRB function in AD-related retinopathy by inhibiting NLRP3-mediated inflammation and suppressing Wnt/ß-catenin pathway-mediated apoptosis, which is expected to improve the pathological changes in AD-related retinopathy and the quality of life of AD patients.

[C(NH2)3][B(C2O2H4)2]: An Organic-Inorganic Hybrid Borate Containing Nonlinear-Optical Active Unit [B(C2O2H4)2]- with Solar-Blind-Region Optical Nonlinearity.

We herein report an unprecedented organic-inorganic hybrid borate incorporating a novel nonlinear-optical (NLO) active unit, namely, [C(NH2)3][B(C2O2H4)2]. The novel NLO active unit was derived from the condensation reaction between two glycol molecules and one (BO4)5- group. The title compound exhibits a moderate second-harmonic-generation effect (0.7 × KDP), a significant band gap (5.76 eV), and a suitable birefringence (0.078 at 550 nm). The optical properties are determined by the synergistic interaction between the C(NH2)3+ cation and the [B(C2O2H4)2]- group, as indicated by theoretical calculations.

(C4H6N3O)(HSO4): A Cytosinium Bisulfate with Large Birefringence and Moderate Second Harmonic Generation Effect Produced via Combining a Promising Planar Nonlinear Optical-Active Motif with a Tetrahedral Group.

Investigating novel nonlinear optical (NLO) active units serves as a valuable method for broadening the research landscape of NLO materials. This study showcases the potential of the cytosinium cation (C4H6N3O)+ as a novel NLO-active motif through theoretical calculations. The title compound exhibited a wide band gap of 3.85 eV, along with a moderate second harmonic generation (SHG) response of 1.65 times that of KH2PO4 (KDP) and significant birefringence of 0.47. Its exceptional optical properties are primarily attributed to the synergy interaction between cations and anionic groups in the asymmetric unit.

[C(NH2)3]6Mo7O24: A Guanidinium Molybdate as a UV Nonlinear Optical Crystal with Large Birefringence.

The key to searching novel nonlinear optical (NLO) crystals was effectively combining the NLO-active units to obtain a noncentrosymmetric structure. Nevertheless, the present predicament lies in the growing challenge of discovering novel crystals within conventional inorganic frameworks that surpass the properties of the current NLO materials. In view of this, researchers expanded their research focus to the organic-inorganic hybridization system; it is foreseeable to concentrate the advantages from several kinds of NLO-active units to acquire novel NLO crystals with superior properties. We herein report an organic-inorganic hybrid molybdate crystal, namely, [C(NH2)3]6Mo7O24 (GMO). It was successfully obtained via combining inorganic NLO-active MoO6 octahedra and organic π-conjugated [C(NH2)3]+ groups. GMO demonstrates a moderate second-harmonic-generation response, specifically measuring about 1.3 times the value of KDP. Additionally, it exhibits a significant birefringence value of 0.203 at the wavelength of 550 nm and possesses a wide band gap of 3.31 eV. Theoretical calculations suggest that the optical properties of the GMO are primarily influenced by the synergy effect of [C(NH2)3]+ groups between MoO6 octahedra.

Clinicopathological characteristics and prognosis of Epstein-Barr virus-associated gastric cancer.

OBJECTIVE: Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) is a distinct molecular subtype of gastric cancer (GC). At present, the clinical characteristics and prognostic implications of EBV infection and the potential clinical benefits of immune checkpoint blockade in GC remain to be clarified. Hence, this study was designed to analyze the clinical and pathological characteristics of GC patients with varying EBV infection states and compare their overall survival (OS). METHODS: A retrospective study was performed on 1031 consecutive GC patients who underwent gastrectomy at the Affiliated Hospital of Xuzhou Medical University from February 2018 to November 2022. EBV-encoded RNA (EBER) in situ hybridization (ISH) was used for EBV assessment, and immunohistochemical staining was used for evaluation of human epidermal growth factor receptor 2 (HER2), programmed death ligand 1 (PD-L1), and Ki67 expression. EBVaGC was defined as tumors with EBV positivity. In addition, EBV-negative GC (EBVnGC) patients were matched with EBVaGC patients based on seven clinicopathological parameters (age, gender, anatomic subsite, tumor size, Lauren classification, degree of differentiation, and tumor-node-metastasis [TNM] stage). The correlations of clinical features with HER2, PD-L1, and Ki67 expression were evaluated statistically. The survival of patients was assessed through medical records, telephone, or WeChat communication, and prognostic analysis was performed using the logrank test as well as univariable and multivariable regression analysis. RESULTS: Out of 1031 GC patients tested, 35 (3.4%) were diagnosed with EBVaGC. Notably, the EBVaGC group exhibited a distinct predominance of males and younger patients, significantly higher Ki67 and PD-L1 expression levels, and a lower prevalence of pericancerous nerve invasion than the EBVnGC group (P < 0.01). In the 35 EBVaGC cases, Ki67 expression was negatively correlated with age (P < 0.05), suggesting that a younger onset age was associated with higher Ki67 expression. In addition, PD-L1 expression was correlated with the degree of differentiation, T-stage, and clinical stage of the patient. Furthermore, PD-L1 expression was elevated in tumors with lower differentiation or at later stages (P < 0.05). Using univariate analysis, Ki67, PD-L1, and clinical stage were identified as significant factors influencing the overall survival (OS) of EBVaGC patients (P < 0.05). Moreover, multivariate survival analysis revealed that clinical stage and Ki67 expression were independent risk factors for the OS of the patients (P < 0.05), and the three-year OS rate of EBVaGC patients was 64.2%. CONCLUSION: EBV-ISH is a practical and valuable method to identify EBVaGC. Owing to its unique etiological, pathological, and clinical characteristics, patients with EBVaGC might benefit from immune checkpoint blockade therapy.

THBru attenuates diabetic cardiomyopathy by inhibiting RAGE-dependent inflammation.

Diabetic cardiomyopathy (DCM) is a complication of diabetes mellitus characterized by heart failure and cardiac remodeling. Previous studies show that tetrahydroberberrubine (THBru) retrogrades cardiac aging by promoting PHB2-mediated mitochondrial autophagy and prevents peritoneal adhesion by suppressing inflammation. In this study we investigated whether THBru exerted protective effect against DCM in db/db mice and potential mechanisms. Eight-week-old male db/db mice were administered THBru (25, 50 mg·kg-1·d-1, i.g.) for 12 weeks. Cardiac function was assessed using echocardiography. We showed that THBru administration significantly improved both cardiac systolic and diastolic function, as well as attenuated cardiac remodeling in db/db mice. In primary neonatal mouse cardiomyocytes (NMCMs), THBru (20, 40 µM) dose-dependently ameliorated high glucose (HG)-induced cell damage, hypertrophy, inflammatory cytokines release, and reactive oxygen species (ROS) production. Using Autodock, surface plasmon resonance (SPR) and DARTS analyses, we revealed that THBru bound to the domain of the receptor for advanced glycosylation end products (RAGE), subsequently leading to inactivation of the PI3K/AKT/NF-κB pathway. Importantly, overexpression of RAGE in NMCMs reversed HG-induced inactivation of the PI3K/AKT/NF-κB pathway and subsequently counteracted the beneficial effects mediated by THBru. We conclude that THBru acts as an inhibitor of RAGE, leading to inactivation of the PI3K/AKT/NF-κB pathway. This action effectively alleviates the inflammatory responses and oxidative stress in cardiomyocytes, ultimately leading to ameliorated DCM.

New mitogenomes from the genus Cricotopus (Diptera: Chironomidae, Orthocladiinae): Characterization and phylogenetic implications.

Cricotopus is a large and diverse genus of non-biting midges composed of several subgenera. Complete mitogenome sequences are available for very few Cricotopus species. The subgenus Pseudocricotopus unites species with unusual morphological structures in adult male and pupal stages, however, molecular methods are needed to verify the placement of this subgenus within Cricotopus. We obtained mitogenomes of C. (Pseudocricotopus) cf. montanus and nine other Cricotopus species for phylogenetic analysis, coupled with two Rheocricotopus species and one Synorthocladius species as outgroups. The structure of the mitogenome was similar among these Cricotopus species, exhibiting A+T bias and retaining ancestral gene order. Mutation rate, estimated as Ka/Ks, varied among genes, and was highest for ATP8 and lowest for COI. The phylogenetic relationships among species of Cricotopus, Rheocricotopus and Synorthocladius was reconstructed using Bayesian inference and maximum likelihood estimation. The phylogenetic trees confirmed placement of subgenus Pseudocricotopus, represented by Cricotopus cf. montanus, within Cricotopus. Our study increases the library of chironomid mitogenomes and provides insight into the properties of their constituent genes.

Thalassospira aquimaris sp. nov. and Winogradskyella marincola sp. nov. two marine bacteria isolated from an agar-degrading co-culture.

Two novel Gram-stain-negative, aerobic, and non-motile strains, designated FZY0004T and YYF002T, were isolated from an agar-degrading co-culture, which was obtained from seawater of the intertidal zone of Yancheng City, the Yellow Sea of China. Strain FZY0004T optimally grew at 28 °C, pH 7.0, and 2-6% NaCl, while strain YYF002T optimally grew at 28 °C, pH 7.5, and 2-4% NaCl. Strain FZY0004T possessed Q-9 as the major respiratory quinone, and its major fatty acids (> 10%) were summed feature 8 (C18:1 ω7c), C16:0, and summed feature 3 (C16:1 ω7c/C16:1 ω6c). The polar lipids identified in strain FZY0004T were phosphatidylethanolamine (PE), phosphatidylglycerol (PG), and several unidentified phospholipids (PL) and lipids (L). On the other hand, strain YYF002T had MK-6 as the predominant respiratory quinone and its major fatty acids consisted of iso-C15:0, iso-C15:1 G, and iso-C15:0 3-OH. The polar lipids identified in strain YYF002T were aminolipid (AL), PE, and several unidentified lipids. Strain FZY0004T shared 99.5% 16S rRNA gene sequence similarity and 90.1% average nucleotide identity (ANI) with T. povalilytica Zumi 95T, and strain YYF002T shared 99.2% 16S rRNA gene sequence similarity and 88.2% ANI with W. poriferorum JCM 12885T. The genomic DNA G + C contents of strains FZY0004T and YYF002T were 54.5% and 33.5%, respectively. The phylogenetic, phenotypic, and physiological characteristics permitted the distinction of the two strains from their neighbors, and we thus propose the names Thalassospira aquimaris sp. nov. (type strain FZY0004T = JCM 35895T = MCCC 1K08380T) and Winogradskyella marincola sp. nov. (type strain YYF002T = JCM 35950T = MCCC 1K08382T).

Molecular basis for human mitochondrial tRNA m3C modification by alternatively spliced METTL8.

METTL8 has recently been identified as the methyltransferase catalyzing 3-methylcytidine biogenesis at position 32 (m3C32) of mitochondrial tRNAs. METTL8 also potentially participates in mRNA methylation and R-loop biogenesis. How METTL8 plays multiple roles in distinct cell compartments and catalyzes mitochondrial tRNA m3C formation remain unclear. Here, we discovered that alternative mRNA splicing generated several isoforms of METTL8. One isoform (METTL8-Iso1) was targeted to mitochondria via an N-terminal pre-sequence, while another one (METTL8-Iso4) mainly localized to the nucleolus. METTL8-Iso1-mediated m3C32 modification of human mitochondrial tRNAThr (hmtRNAThr) was not reliant on t6A modification at A37 (t6A37), while that of hmtRNASer(UCN) critically depended on i6A modification at A37 (i6A37). We clarified the hmtRNAThr substrate recognition mechanism, which was obviously different from that of hmtRNASer(UCN), in terms of requiring a G35 determinant. Moreover, SARS2 (mitochondrial seryl-tRNA synthetase) interacted with METTL8-Iso1 in an RNA-independent manner and modestly accelerated m3C modification activity. We further elucidated how nonsubstrate tRNAs in human mitochondria were efficiently discriminated by METTL8-Iso1. In summary, our results established the expression pattern of METTL8, clarified the molecular basis for m3C32 modification by METTL8-Iso1 and provided the rationale for the involvement of METTL8 in tRNA modification, mRNA methylation or R-loop biogenesis.

A photoelectrochemical aptasensing platform assembled at the heterojunction interface of Cu3BiS3 sensitized CuV2O6 for bisphenol A.

The interaction between the sensitive interfaces of photoelectrochemical (PEC) semiconductor nanomaterials and microscopic matter creates endless potential for the efficient detection of endocrine disruptor. This work presents the development of a high-efficiency PEC aptasensor for bisphenol A (BPA) monitoring based on Cu3BiS3 sensitized CuV2O6 nanocomposites with exceptional visible-light PEC activity. We implemented the integration of Cu3BiS3 nanosheet photosensitizer to sensitize the CuV2O6 nanowire structure that was synthesized utilizing a facile hydrothermal approach. The band gap alignment between Cu3BiS3 and CuV2O6 facilitated enduring PEC response yielding an efficient interfacial structure. The surface of the CuV2O6/Cu3BiS3 electrode was modified with BPA aptamer, enabling specific binding with BPA and precise quantification of its content. The developed aptamer sensors possess a wide detection range of 5.00 × 10-1 to 5.00 × 104 ng/mL, and a low detection limit of 1.60 × 10-1 ng/mL (at S/N = 3). After undergoing 20 testing cycles and enduring long-term storage, the sensor maintained its stability and showcased excellent repeatability and reproducibility. This study presents a promising methodology for the detection of BPA in environmental settings.

Rural-Urban Disparities in Telemedicine Use Among U.S. Adults with Cancer.

Introduction: The COVID-19 pandemic has resulted in significant changes in health care delivery worldwide, including the widespread adoption of telemedicine. This study examines the prevalence of telemedicine use among cancer survivors in the United States based on rurality and investigates its association with telemedicine use. Methods: The 2021 National Health Interview Survey was used to analyze telemedicine use among cancer survivors during the pandemic. Telemedicine use was the primary outcome, and rurality was the main exposure. Descriptive statistics and multiple logistic regression models were used to examine the association. Results: Out of 27,500 eligible cancer survivors, 51.6% reported using telemedicine in 2021. Telemedicine usage varied across rural areas, with 41.4% of rural cancer survivors using telemedicine compared with 57.5% of cancer survivors in large metropolitan areas (p < 0.001). Rural cancer survivors had significantly lower odds of using telemedicine during the pandemic compared with large metropolitan cancer survivors. Cancer survivors residing in rural areas were 0.56 times less likely (odds ratio [OR] = 0.56; 95% confidence interval [CI] = 0.41-0.75), and those residing in medium and small metropolitan areas were 0.69 times less likely (OR = 0.69; 95% CI = 0.56-0.86) to report telemedicine use compared with cancer survivors in large metropolitan areas. Conclusions: Substantial disparities in telemedicine use were observed between rural and urban areas among cancer survivors. Rural cancer survivors were less likely to utilize telemedicine during the COVID-19 pandemic. Ensuring equitable access to telemedicine requires continued reimbursement for telemedicine services, along with additional efforts to improve access to and utilization of health care for rural cancer survivors.

The Slack Channel Regulates Anxiety-Like Behaviors via Basolateral Amygdala Glutamatergic Projections to Ventral Hippocampus.

Anxiety disorders are a series of mental disorders characterized by anxiety and fear, but the molecular basis of these disorders remains unclear. In the present study, we find that the global Slack KO male mice exhibit anxious behaviors, whereas the Slack Y777H male mice manifest anxiolytic behaviors. The expression of Slack channels is rich in basolateral amygdala (BLA) glutamatergic neurons and downregulated in chronic corticosterone-treated mice. In addition, electrophysiological data show enhanced excitability of BLA glutamatergic neurons in the Slack KO mice and decreased excitability of these neurons in the Slack Y777H mice. Furthermore, the Slack channel deletion in BLA glutamatergic neurons is sufficient to result in enhanced avoidance behaviors, whereas Kcnt1 gene expression in the BLA or BLA-ventral hippocampus (vHPC) glutamatergic projections reverses anxious behaviors of the Slack KO mice. Our study identifies the role of the Slack channel in controlling anxious behaviors by decreasing the excitability of BLA-vHPC glutamatergic projections, providing a potential target for anxiolytic therapies.SIGNIFICANCE STATEMENT Anxiety disorders are a series of mental disorders characterized by anxiety and fear, but the molecular basis of these disorders remains unclear. Here, we examined the behaviors of loss- and gain-of-function of Slack channel mice in elevated plus maze and open field tests and found the anxiolytic role of the Slack channel. By altering the Slack channel expression in the specific neuronal circuit, we demonstrated that the Slack channel played its anxiolytic role by decreasing the excitability of BLA-vHPC glutamatergic projections. Our data reveal the role of the Slack channel in the regulation of anxiety, which may provide a potential molecular target for anxiolytic therapies.