Production and evaluation of anti-BP26 monoclonal antibodies for the serological detection of animal brucellosis.

Brucella BP26 proves to be a highly immunogenic antigen with excellent specificity in brucellosis detection. In China, the authorized use of the Bp26-deleted vaccine M5ΔBP26 for preventing small ruminant brucellosis highlights the importance of developing accurate detection methods targeting BP26, particularly for the diagnosis of differentiation between infected and vaccinated animals (DIVA). Using the traditional mouse hybridoma technique, we successfully obtained 12 monoclonal antibodies (mAbs) targeting BP26. The efficacy of these mAbs in detecting various animal brucellosis cases using the competitive ELISA method was evaluated. Among them, only the E10 mAb exhibited significant efficiency, being inhibited by 100, 97.62, and 100% of brucellosis-positive sera from cattle, small ruminants, and canines, respectively. The E10-based competitive enzyme-linked immunosorbent assay (cELISA) outperformed the BP26-based indirect enzyme-linked immunosorbent assay (iELISA) in accuracy, particularly for cattle and small ruminant brucellosis, with cELISA sensitivity reaching 97.62% compared to 64.29% for iELISA for small ruminants. Although cELISA showed slightly lower specificity than iELISA, it still maintained high accuracy in canine brucellosis detection. The epitope of mAb E10 was identified in the amino acid sequence QPIYVYPDDKNNLKEPTITGY, suggesting its potential as a diagnostic antigen for brucellosis. In conclusion, the E10-based cELISA presents an effective means of detecting animal brucellosis, particularly significant for DIVA diagnosis in China, where the BP26-mutant vaccine is widely used.

Magnetic lanthanide sensor with self-ratiometric time-resolved luminescence for accurate detection of epithelial cancerous exosomes.

Fluorescence-based LB (liquid biopsy) offers a rapid means of detecting cancer non-invasively. However, the widespread issue of sample loss during purification steps will diminish the accuracy of detection results. Therefore, in this study, we introduce a magnetic lanthanide sensor (MLS) designed for sensitive detection of the characteristic protein, epithelial cell adhesion molecule (EpCAM), on epithelial tumor exosomes. By leveraging the inherent multi-peak emission and time-resolved properties of the sole-component lanthanide element, combined with the self-ratiometric strategy, MLS can overcome limitations imposed by manual operation and/or sample complexity, thereby providing more stable and reliable output results. Specifically, terbium-doped NaYF4 nanoparticles (NaYF4:Tb) and deformable aptamers terminated with BHQ1 were sequentially introduced onto superparamagnetic silica-decorated Fe3O4 nanoparticles. Prior to target binding, emission from NaYF4:Tb at 543 nm was partially quenched due to the fluorescence resonance energy transfer (FRET) from NaYF4:Tb to BHQ1. Upon target binding, changes in the secondary structure of aptamers led to the fluorescence intensity increasing since the deconfinement of distance-dependent FRET effect. The characteristic emission of NaYF4:Tb at 543 nm was then utilized as the detection signal (I1), while the less changed emission at 583 nm served as the reference signal (I2), further reporting the self-ratiometric values of I1 and I2 (I1/I2) to illustrate the epithelial cancerous features of exosomes while ignoring possible sample loss. Consequently, over a wide range of exosome concentrations (2.28 × 102-2.28 × 108 particles per mL), the I1/I2 ratio exhibited a linear increase with exosome concentration [Y(I1/I2) = 0.166 lg (Nexosomes) + 3.0269, R2 = 0.9915], achieving a theoretical detection limit as low as 24 particles per mL. Additionally, MLS effectively distinguished epithelial cancer samples from healthy samples, showcasing significant potential for clinical diagnosis.

Structure, function, and research progress of primary cilia in reproductive physiology and reproductive diseases.

Primary cilia, serving as the central hub for cellular signal transduction, possess the remarkable ability to translate diverse extracellular signals, both chemical and mechanical, into intracellular responses. Their ubiquitous presence in the reproductive system underscores their pivotal roles in various cellular processes including development, differentiation, and migration. Emerging evidence suggests primary cilia as key players in reproductive physiology and associated pathologies. Notably, primary cilia have been identified in granulosa cells within mouse ovaries and uterine stromal cells, and perturbations in their structure and function have been implicated in a spectrum of reproductive dysfunctions and ciliary-related diseases. Furthermore, disruptions in primary cilia-mediated signal transduction pathways under pathological conditions exacerbate the onset and progression of reproductive disorders. This review provides a comprehensive overview of current research progress on primary cilia and their associated signaling pathways in reproductive physiology and diseases, with the aim of furnishing theoretical groundwork for the prevention and management of primary cilia-related structural and functional abnormalities contributing to reproductive system pathologies.

Role of the PARP1/NF-κB Pathway in DNA Damage and Apoptosis of TK6 Cells Induced by Hydroquinone.

Hydroquinone(HQ) is a widely used industrial raw material and is a topical lightening product found in over-the-counter products. However, inappropriate exposure to HQ can pose certain health hazards. This study aims to explore the mechanisms of DNA damage and cell apoptosis caused by HQ, with a focus on whether HQ activates the nuclear factor-κB (NF-κB) pathway to participate in this process and to investigate the correlation between the NF-κB pathway activation and poly(ADP-ribose) polymerase 1(PARP1). Through various experimental techniques, such as DNA damage detection, cell apoptosis assessment, cell survival rate analysis, immunofluorescence, and nuclear-cytoplasmic separation, the cytotoxic effects of HQ were verified, and the activation of the NF-κB pathway was observed. Simultaneously, the relationship between the NF-κB pathway and PARP1 was verified by shRNA interference experiments. The results showed that HQ could significantly activate the NF-κB pathway, leading to a decreased cell survival rate, increased DNA damage, and cell apoptosis. Inhibiting the NF-κB pathway could significantly reduce HQ-induced DNA damage and cell apoptosis and restore cell proliferation and survival rate. shRNA interference experiments further indicated that the activation of the NF-κB pathway was regulated by PARP1. This study confirmed the important role of the NF-κB pathway in HQ-induced DNA damage and cell apoptosis and revealed that the activation of the NF-κB pathway was mediated by PARP1. This research provides important clues for a deeper understanding of the toxic mechanism of HQ.

Van der Waals Encapsulation by Ultra-thin Oxide for Air-Sensitive 2D Materials.

The ambient stability is one of the focal points for applications of 2D materials, especially for those well-known air-sensitive ones such as black phosphorus (BP) and transitional metal telluride. Traditional methods of encapsulation, such as atomic layer deposition of oxides and heterogeneous integration of hexagonal boron nitride, can hardly avoid removal of encapsulation layer when the 2D materials are encapsulated for further device fabrication, which causes complexity and damage during the procedure. Here, a van der Waals encapsulation method that allows direct device fabrication without removal of encapsulation layer is introduced using Ga2O3 from liquid gallium. Taking advantage of the robust isolation ability against ambient environment of the dense native oxide of gallium, hundreds of times longer retention time of (opto)electronic properties of encapsulated BP and MoTe2 devices is realized than unencapsulated devices. Due to the ultra-thin high-κ properties of Ga2O3, top-gated devices are directly fabricated with the encapsulation layer, simultaneously as a dielectric layer. This direct device fabrication is realized by selective etching of Ga2O3, leaving the encapsulated materials intact. Encapsulated 1T' MoTe2 exhibits high conductivity even after 150 days in ambient environment. This method is therefore highlighted as a promising and distinctive one compared with traditional passivation approaches. This article is protected by copyright. All rights reserved.

Coxsackievirus A10 impairs nail regeneration and induces onychomadesis by mimicking DKK1 to attenuate Wnt signaling.

Coxsackievirus A10 (CV-A10) infection, a prominent cause of childhood hand-foot-and-mouth disease (HFMD), frequently manifests with the intriguing phenomenon of onychomadesis, characterized by nail shedding. However, the underlying mechanism is elusive. Here, we found that CV-A10 infection in mice could suppress Wnt/ß-catenin signaling by restraining LDL receptor-related protein 6 (LRP6) phosphorylation and ß-catenin accumulation and lead to onychomadesis. Mechanistically, CV-A10 mimics Dickkopf-related protein 1 (DKK1) to interact with Kringle-containing transmembrane protein 1 (KRM1), the CV-A10 cellular receptor. We further found that Wnt agonist (GSK3ß inhibitor) CHIR99021 can restore nail stem cell differentiation and protect against nail shedding. These findings provide novel insights into the pathogenesis of CV-A10 and related viruses in onychomadesis and guide prognosis assessment and clinical treatment of the disease.

Vapor Deposition of Bilayer 3R MoS2 with Room-Temperature Ferroelectricity.

Two-dimensional ultrathin ferroelectrics have attracted much interest due to their potential application in high-density integration of non-volatile memory devices. Recently, 2D van der Waals ferroelectric based on interlayer translation has been reported in twisted bilayer h-BN and transition metal dichalcogenides (TMDs). However, sliding ferroelectricity is not well studied in non-twisted homo-bilayer TMD grown directly by chemical vapor deposition (CVD). In this paper, for the first time, experimental observation of a room-temperature out-of-plane ferroelectric switch in semiconducting bilayer 3R MoS2 synthesized by reverse-flow CVD is reported. Piezoelectric force microscopy (PFM) hysteretic loops and first principle calculations demonstrate that the ferroelectric nature and polarization switching processes are based on interlayer sliding. The vertical Au/3R MoS2/Pt device exhibits a switchable diode effect. Polarization modulated Schottky barrier height and polarization coupling of interfacial deep states trapping/detrapping may serve in coordination to determine switchable diode effect. The room-temperature ferroelectricity of CVD-grown MoS2 will proceed with the potential wafer-scale integration of 2D TMDs in the logic circuit.

Prenatal Maternal Psychological Distress During the COVID-19 Pandemic and Newborn Brain Development.

Importance: Elevated maternal psychological distress during pregnancy is associated with altered fetal brain development. During the COVID-19 pandemic, prenatal maternal psychological distress more than doubled. Objective: To examine the association of the pandemic and rising maternal psychological distress with brain growth in newborns using quantitative 3-dimensional volumetric magnetic resonance imaging (MRI). Design, Setting, and Participants: This prospective cross-sectional study recruited mother-infant dyads at Children's National Hospital, Washington, DC, during the COVID-19 pandemic (June 1, 2020, to June 30, 2022) into a longitudinal infant brain development study and compared them with an existing normative healthy cohort (recruited March 1, 2014, to December 31, 2019). Exclusion criteria included multiple gestation pregnancy, known or suspected congenital infection, documented chromosomal abnormalities, or any maternal contraindication to MRI, as well as prenatal COVID-19 exposure. Infants with structural brain abnormalities or a postnatal confirmation of a genetic syndrome were excluded. Exposure: Psychological distress during COVID-19 pandemic. Main Outcomes and Measures: Prenatal maternal mental health was evaluated using the Spielberger State-Trait Anxiety Inventory and the Perceived Stress Scale. Neonates underwent nonsedated brain MRI. An ordinary least squares linear regression model was used to measure the differences in regional brain volumes of neonates born before vs during the pandemic with and without exposure to elevated prenatal maternal psychological distress after adjustment for neonatal sex and gestational age at MRI and maternal age and educational level. Results: A total of 159 mother-infant dyads were included in the analysis: 103 before and 56 during the pandemic (median gestational age of infants, 39.6 [IQR, 38.4-40.4] weeks; median maternal age, 34.5 [IQR, 31.0-37.0] years). Eighty-three infants (52.2%) were female. Among the mothers, 130 (81.8%) had a college degree and 87 (54.7%) had a graduate degree. Forty-four mothers (27.7%) identified as Asian, Hispanic, or multiracial; 27 (17.0%), as Black; and 88 (55.3%), as White. Scores on anxiety and stress measures were significantly increased in the pandemic cohort. Infants of mothers with elevated maternal distress showed median reductions in white matter (-0.36 [95% CI, -0.61 to -0.11] cm3; Q < .001), right hippocampal (-0.35 [95% CI, -0.65 to -0.06] cm3; Q = .04), and left amygdala (-0.49 [95% CI, -0.84 to -0.13] cm3; Q = .03) volumes compared with infants of mothers with low distress levels. After adjusting for the cohort effect of the pandemic, elevated trait anxiety remained significantly associated with decreased left amygdalar volumes (-0.71 [95% CI, -1.12 to -0.29]; Q < .001). Conclusions and Relevance: In this cross-sectional study of maternal-infant dyads prior to and during the COVID-19 pandemic, regional neonatal brain volumes were associated with elevated maternal psychological distress.

Global and Regional Cardiovascular Mortality Attributable to Nonoptimal Temperatures Over Time.

BACKGROUND: The association between nonoptimal temperatures and cardiovascular mortality risk is recognized. However, a comprehensive global assessment of this burden is lacking. OBJECTIVES: The goal of this study was to assess global cardiovascular mortality burden attributable to nonoptimal temperatures and investigate spatiotemporal trends. METHODS: Using daily cardiovascular deaths and temperature data from 32 countries, a 3-stage analytical approach was applied. First, location-specific temperature-mortality associations were estimated, considering nonlinearity and delayed effects. Second, a multivariate meta-regression model was developed between location-specific effect estimates and 5 meta-predictors. Third, cardiovascular deaths associated with nonoptimal, cold, and hot temperatures for each global grid (55 km × 55 km resolution) were estimated, and temporal trends from 2000 to 2019 were explored. RESULTS: Globally, 1,801,513 (95% empirical CI: 1,526,632-2,202,831) annual cardiovascular deaths were associated with nonoptimal temperatures, constituting 8.86% (95% empirical CI: 7.51%-12.32%) of total cardiovascular mortality corresponding to 26 deaths per 100,000 population. Cold-related deaths accounted for 8.20% (95% empirical CI: 6.74%-11.57%), whereas heat-related deaths accounted for 0.66% (95% empirical CI: 0.49%-0.98%). The mortality burden varied significantly across regions, with the highest excess mortality rates observed in Central Asia and Eastern Europe. From 2000 to 2019, cold-related excess death ratios decreased, while heat-related ratios increased, resulting in an overall decline in temperature-related deaths. Southeastern Asia, Sub-Saharan Africa, and Oceania observed the greatest reduction, while Southern Asia experienced an increase. The Americas and several regions in Asia and Europe displayed fluctuating temporal patterns. CONCLUSIONS: Nonoptimal temperatures substantially contribute to cardiovascular mortality, with heterogeneous spatiotemporal patterns. Effective mitigation and adaptation strategies are crucial, especially given the increasing heat-related cardiovascular deaths amid climate change.

Implementation and Evaluation of Discharge Planning for Patients Undergoing Umbilical Cord Blood Transplantation.

BACKGROUND Umbilical cord blood transplantation (UCBT) patients have high rates of unplanned readmissions and poor quality of life (QoL). The aim of this study was to evaluate the effects of discharge planning on unplanned readmissions, self-efficacy, QoL, and clinical outcomes. MATERIAL AND METHODS Patients who received their first UCBT from April 2022 to March 2023 were included. Participants (n=72) were assigned to a control group (CG: received usual care) or an intervention group (IG: received discharge planning from admission to 100 days after UCBT). The cumulative readmission rates 30 days after discharge and 100 days after UCBT were analyzed using the log-rank test. Self-efficacy and QoL were assessed at admission and 100 days after UCBT using the General Self-Efficacy Scale and FACT-BMT version 4, clinical outcomes derived from medical records. RESULTS Sixty-six patients completed the study. Discharge planning did not reduce readmission rates 30 days after discharge (20.59% vs 31.25%, P=0.376) or 100 days after UCBT (29.41% vs 34.38%, P=0.629). However, the IG showed significantly better self-efficacy (P<0.001), and except for social and emotional well-being, all the other dimensions and 3 total scores of FACT-BMT in the IG were higher than for the controls at 100 days after UCBT (P<0.05). CONCLUSIONS The discharge planning program can improve self-efficacy and QoL of UCBT recipients. The implementation of discharge planning for patients undergoing UCBT was necessary for successful hospital-to-home transitions.

exo-6b2-Methyl-Substituted Pentabenzocorannulene: Synthesis, Structural Analysis, and Properties.

exo-6b2-Methyl-substituted pentabenzocorannulene (exoPBC-Me) was synthesized by the palladium-catalyzed cyclization of 1,2,3-triaryl-1H-cyclopenta[l]phenanthrene. Its bowl-shaped geometry with an sp3 carbon atom in the backbone and a methyl group located at the convex (exo) face was verified by X-ray crystallography. According to DFT calculations, the observed conformer is energetically more favorable than the endo one by 39.9 kcal/mol. Compared to the nitrogen-doped analogs with intact π-conjugated backbones (see the main text), exo-PBC-Me displayed a deeper bowl depth (avg. 1.93 Å), redshifted and broader absorption (250-620 nm) and emission (from 585 to more than 850 nm) bands and a smaller optical HOMO-LUMO gap (2.01 eV). exo-PBC-Me formed polar crystals where all bowl-in-bowl stacking with close π···π contacts is arranged unidirectionally, providing the potential for applications as organic semiconductors and pyroelectric materials. This unusual structural feature, molecular packing, and properties are most likely associated with the assistance of the methyl group and the sp3 carbon atom in the backbone.

A specific super-enhancer actuated by berberine regulates EGFR-mediated RAS-RAF1-MEK1/2-ERK1/2 pathway to induce nasopharyngeal carcinoma autophagy.

Nasopharyngeal carcinoma (NPC), primarily found in the southern region of China, is a malignant tumor known for its highly metastatic characteristics. The high mortality rates caused by the distant metastasis and disease recurrence remain unsolved clinical problems. In clinic, the berberine (BBR) compound has widely been in NPC therapy to decrease metastasis and disease recurrence, and BBR was documented as a main component with multiple anti-NPC effects. However, the mechanism by which BBR inhibits the growth and metastasis of nasopharyngeal carcinoma remains elusive. Herein, we show that BBR effectively inhibits the growth, metastasis, and invasion of NPC via inducing a specific super enhancer (SE). From a mechanistic perspective, the RNA sequencing (RNA-seq) results suggest that the RAS-RAF1-MEK1/2-ERK1/2 signaling pathway, activated by the epidermal growth factor receptor (EGFR), plays a significant role in BBR-induced autophagy in NPC. Blockading of autophagy markedly attenuated the effect of BBR-mediated NPC cell growth and metastasis inhibition. Notably, BBR increased the expression of EGFR by transcription, and knockout of EGFR significantly inhibited BBR-induced microtubule associated protein 1 light chain 3 (LC3)-II increase and p62 inhibition, proposing that EGFR plays a pivotal role in BBR-induced autophagy in NPC. Chromatin immunoprecipitation sequencing (ChIP-seq) results found that a specific SE existed only in NPC cells treated with BBR. This SE knockdown markedly repressed the expression of EGFR and phosphorylated EGFR (EGFR-p) and reversed the inhibition of BBR on NPC proliferation, metastasis, and invasion. Furthermore, BBR-specific SE may trigger autophagy by enhancing EGFR gene transcription, thereby upregulating the RAS-RAF1-MEK1/2-ERK1/2 signaling pathway. In addition, in vivo BBR effectively inhibited NPC cells growth and metastasis, following an increase LC3 and EGFR and a decrease p62. Collectively, this study identifies a novel BBR-special SE and established a new epigenetic paradigm, by which BBR regulates autophagy, inhibits proliferation, metastasis, and invasion. It provides a rationale for BBR application as the treatment regime in NPC therapy in future.

Extracellular cold-inducible RNA-binding protein mediated neuroinflammation and neuronal apoptosis after traumatic brain injury.

Background: Extracellular cold-inducible RNA-binding protein (eCIRP) plays a vital role in the inflammatory response during cerebral ischaemia. However, the potential role and regulatory mechanism of eCIRP in traumatic brain injury (TBI) remain unclear. Here, we explored the effect of eCIRP on the development of TBI using a neural-specific CIRP knockout (KO) mouse model to determine the contribution of eCIRP to TBI-induced neuronal injury and to discover novel therapeutic targets for TBI. Methods: TBI animal models were generated in mice using the fluid percussion injury method. Microglia or neuron lines were subjected to different drug interventions. Histological and functional changes were observed by immunofluorescence and neurobehavioural testing. Apoptosis was examined by a TdT-mediated dUTP nick end labelling assay in vivo or by an annexin-V assay in vitro. Ultrastructural alterations in the cells were examined via electron microscopy. Tissue acetylation alterations were identified by non-labelled quantitative acetylation via proteomics. Protein or mRNA expression in cells and tissues was determined by western blot analysis or real-time quantitative polymerase chain reaction. The levels of inflammatory cytokines and mediators in the serum and supernatants were measured via enzyme-linked immunoassay. Results: There were closely positive correlations between eCIRP and inflammatory mediators, and between eCIRP and TBI markers in human and mouse serum. Neural-specific eCIRP KO decreased hemispheric volume loss and neuronal apoptosis and alleviated glial cell activation and neurological function damage after TBI. In contrast, eCIRP treatment resulted in endoplasmic reticulum disruption and ER stress (ERS)-related death of neurons and enhanced inflammatory mediators by glial cells. Mechanistically, we noted that eCIRP-induced neural apoptosis was associated with the activation of the protein kinase RNA-like ER kinase-activating transcription factor 4 (ATF4)-C/EBP homologous protein signalling pathway, and that eCIRP-induced microglial inflammation was associated with histone H3 acetylation and the α7 nicotinic acetylcholine receptor. Conclusions: These results suggest that TBI obviously enhances the secretion of eCIRP, thereby resulting in neural damage and inflammation in TBI. eCIRP may be a biomarker of TBI that can mediate the apoptosis of neuronal cells through the ERS apoptotic pathway and regulate the inflammatory response of microglia via histone modification.

Risk Factors and Clinical Significance of Ultra-Long-Term Microischemia After Intracranial Aneurysm Embolization.

INTRODUCTION: This study aimed to explore influencing factors and clinical significance of ultra-long-term microischemia following intracranial aneurysm (IA) embolization and establish a theoretical foundation for reducing both the incidence of ultra-long-term microischemia and cognitive dysfunction in patients post embolization. METHODS: A retrospective analysis was conducted on data from 147 patients who received endovascular treatment for IAs. Patients were categorized into microischemic and control (non-microischemic) groups on the based on the findings of high-resolution magnetic resonance vessel wall imaging (HR-VWI) examinations performed 3 days postoperatively and 6 months postoperatively. Risk factors for the occurrence of ultra-long-term microischemia were determined by univariate analysis and multivariate logistic regression analysis. RESULTS: Out of 147 patients included in the study, 51 (34.69%) developed microischemia while the remaining 96 (65.31%) did not experience this condition. Analysis revealed that factors such as sex, age, history of underlying diseases (hypertension, diabetes mellitus), aneurysmal site characteristics, the presence or absence of stenosis in the aneurysm-bearing artery, modified Fisher score at admission, Barthel's index at discharge, immunoinflammatory index at 3 days postoperatively and at the 6-month follow-up, the presence or absence of aneurysmal wall enhancement, and the presence or absence of aneurysmal lumen showed no statistically significant differences between the two groups (all P > 0.05). By contrast, variables like in operative time, rupture status of the aneurysm before surgery according to World Federation of Neurologic Surgeons (WFNS) grade, aneurysm size, number of stents used, number of guidewires and catheters used, and Evans index between the two groups were found to have statistically significant disparities between those who developed microischemia and those who did not (P < 0.05). A subsequent multivariate analysis revealed that aneurysm size, Evans index, and the number of stents used were independent risk factors for the occurrence of ultra-long-term microischemia after surgical intervention of aneurysms (P < 0.05). The receiver operating characteristic (ROC) curves of the patients were constructed on the basis of risk factors determined through multivariate logistic regression analysis. Results indicated that aneurysm size (area under ROC curve (AUC) 0.619, sensitivity 94.7%, specificity 17.1%, P = 0.049), Evans index (AUC 0.670, sensitivity 96.4%, specificity 26.8%, P = 0.004), and number of stents (AUC 0.639, sensitivity 44.6%, specificity 90.2%, P < 0.001) effectively predicted the occurrence of microischemia. The incidence of cognitive dysfunction was higher in the microischemic group than in the control group (P < 0.05), and a greater number of microischemic foci was associated with a higher incidence of cognitive dysfunction. The proportion of microschemia foci in the thalamus and basal ganglia in patients with cognitive dysfunction (60.87%) was significantly higher than that in patients without cognitive dysfunction (34.55%) (P < 0.05). CONCLUSION: Aneurysm size, Evans index > 0.3, and the quantity of stents were independent risk factors for the occurrence of ultra-long-term microischemia after aneurysm embolization and provided good predictive performance. Cognitive dysfunction was closely associated with microischemia, with its severity increasing with an increase in the number of ischemic foci.

Visual and colorimetric detection of microRNA in clinical samples based on strand displacement amplification and nanozyme-mediated CRISPR-Cas12a system.

The sensitive and accurate detection of target microRNA is especially important for the diagnosis, staging, and treatment of hepatocellular carcinoma (HCC). Herein, we report a simple strand displacement and CRISPR-Cas12a amplification strategy with nanozymes as a signal reporter for the binary visual and colorimetric detection of the HCC related microRNA. Pt@Au nanozymes with excellent peroxidase enzyme activity were prepared and linked to magnetic beads via a single-stranded DNA (ssDNA) linker. The target microRNA was designed to trigger strand displacement amplification and release a DNA promoter to activate the CRISPR-Cas12a system. The activated CRISPR-Cas12a system efficiently cleaved the linker ssDNA and released Pt@Au nanozymes from magnetic beads to induce the colorimetric reaction of 3,3',5,5'-tetramethylbenzidine. The strand displacement amplification converted the single microRNA input into abundant DNA promoter output, which improved the detection sensitivity by over two orders of magnitude. Through integration of strand displacement amplification and the nanozyme-mediated CRISPR-Cas12a system, limits of detection of 0.5 pM and 10 pM for miRNA-21 were achieved with colorimetric and visual readouts, respectively. The proposed strategy can achieve accurate quantitative detection of miRNA-21 in the range from 1 pM to 500 pM. The detection results for miRNA-21 using both colorimetric and visual readouts were validated in 40 clinical serum samples. Significantly, the proposed strategy achieved visual HCC diagnosis with the naked eye and could distinguish distinct Barcelona clinical HCC stages by colorimetric detection, showing good application prospects for sensitive and facile point-of-care testing for HCC.

Strong nonlinear optical processes with extraordinary polarization anisotropy in inversion-symmetry broken two-dimensional PdPSe.

Nonlinear optical activities, especially second harmonic generation (SHG), are key phenomena in inversion-symmetry-broken two-dimensional (2D) transition metal dichalcogenides (TMDCs). On the other hand, anisotropic nonlinear optical processes are important for unique applications in nano-nonlinear photonic devices with polarization functions, having become one of focused research topics in the field of nonlinear photonics. However, the strong nonlinearity and strong optical anisotropy do not exist simultaneously in common 2D materials. Here, we demonstrate strong second-order and third-order susceptibilities of 64 pm/V and 6.2×10-19 m2/V2, respectively, in the even-layer PdPSe, which has not been discovered in other common TMDCs (e.g., MoS2). Strikingly, it also simultaneously exhibited strong SHG anisotropy with an anisotropic ratio of ~45, which is the largest reported among all 2D materials to date, to the best of our knowledge. In addition, the SHG anisotropy ratio can be harnessed from 0.12 to 45 (375 times) by varying the excitation wavelength due to the dispersion of χ ( 2 ) values. As an illustrative example, we further demonstrate polarized SHG imaging for potential applications in crystal orientation identification and polarization-dependent spatial encoding. These findings in 2D PdPSe are promising for nonlinear nanophotonic and optoelectronic applications.

Cancer mortality risk from short-term PM2.5 exposure and temporal variations in Brazil.

Although some studies have found that short-term PM2.5 exposure is associated with lung cancer deaths, its impact on other cancer sites is unclear. To answer this research question, this time-stratified case-crossover study used individual cancer death data between January 1, 2000, and December 31, 2019, extracted from the Brazilian mortality information system to quantify the associations between short-term PM2.5 exposure and cancer mortality from 25 common cancer sites. Daily PM2.5 concentration was aggregated at the municipality level as the key exposure. The study included a total of 34,516,120 individual death records, with the national daily mean PM2.5 exposure 15.3 (SD 4.3) µg/m3. For every 10-µg/m3 increase in three-day average PM2.5 exposure, the odds ratio (OR) for all-cancer mortality was 1.04 (95% CI 1.03-1.04). Apart from all-cancer deaths, PM2.5 exposure may impact cancers of oesophagus (1.04, 1.00-1.08), stomach (1.05, 1.02-1.08), colon-rectum (1.04, 1.01-1.06), lung (1.04, 1.02-1.06), breast (1.03, 1.00-1.06), prostate (1.07, 1.04-1.10), and leukaemia (1.05, 1.01-1.09). During the study period, acute PM2.5 exposure contributed to an estimated 1,917,994 cancer deaths, ranging from 0 to 6,054 cases in each municipality. Though there has been a consistent downward trend in PM2.5-related all-cancer mortality risks from 2000 to 2019, the impact remains significant, indicating the continued importance of cancer patients avoiding PM2.5 exposure. This nationwide study revealed a notable association between acute PM2.5 exposure and heightened overall and site-specific cancer mortality for the first time to our best knowledge. The findings suggest the importance of considering strategies to minimize such exposure in cancer care guidelines. ENVIRONMENTAL IMPLICATION: The 20-year analysis of nationwide death records in Brazil revealed that heightened short-term exposure to PM2.5 is associated with increased cancer mortality at various sites, although this association has gradually decreased over time. Despite the declining impact, the research highlights the persistent adverse effects of PM2.5 on cancer mortality, emphasizing the importance of continued research and preventive measures to address the ongoing public health challenges posed by air pollution.

Refining and in-situ growth of polyaniline endows the cellulose fibers with electrical stimulation sterilization.

Bacteria and virus infections have posed a great threat to public health and personnel safety. For realizing rapid sterilization of the bacteria and virus, electrical stimulation sterilization was adopted to endow cellulose fibers with instantaneous antibacterial and antiviral properties. In the proposed strategy, the fiber is fluffed by mechanical refining, and then by means of the hydrogen bond between hydroxyl and aniline, the polyaniline (PANI) directionally grows vertically along the fine fibers via in-situ oxidative polymerization. Benefiting from the conductive polyaniline nanorod arrays on the fiber stem, the paper made from PANI modified refined fibers (PANI/BCF/P) exhibited excellent antibacterial and antiviral activity, the inhibition rates against S. aureus, E. coli, and bacteriophage MS2 can up to 100 %, 100 %, and 99.89 %, respectively when a weak voltage (2.5 V) was applied within 20 min. This study provides a feasible path for plant fiber to achieve efficient antibacterial and antiviral activity with electrical stimulation, which is of great significance for the preparation of electroactive antibacterial and antiviral green health products.

Comparison for the effects of different components of temperature variability on mortality: A multi-country time-series study.

BACKGROUND: Temperature variability (TV) is associated with increased mortality risk. However, it is still unknown whether intra-day or inter-day TV has different effects. OBJECTIVES: We aimed to assess the association of intra-day TV and inter-day TV with all-cause, cardiovascular, and respiratory mortality. METHODS: We collected data on total, cardiovascular, and respiratory mortality and meteorology from 758 locations in 47 countries or regions from 1972 to 2020. We defined inter-day TV as the standard deviation (SD) of daily mean temperatures across the lag interval, and intra-day TV as the average SD of minimum and maximum temperatures on each day. In the first stage, inter-day and intra-day TVs were modelled simultaneously in the quasi-Poisson time-series model for each location. In the second stage, a multi-level analysis was used to pool the location-specific estimates. RESULTS: Overall, the mortality risk due to each interquartile range [IQR] increase was higher for intra-day TV than for inter-day TV. The risk increased by 0.59% (95% confidence interval [CI]: 0.53, 0.65) for all-cause mortality, 0.64% (95% CI: 0.56, 0.73) for cardiovascular mortality, and 0.65% (95% CI: 0.49, 0.80) for respiratory mortality per IQR increase in intra-day TV0-7 (0.9 °C). An IQR increase in inter-day TV0-7 (1.6 °C) was associated with 0.22% (95% CI: 0.18, 0.26) increase in all-cause mortality, 0.44% (95% CI: 0.37, 0.50) increase in cardiovascular mortality, and 0.31% (95% CI: 0.21, 0.41) increase in respiratory mortality. The proportion of all-cause deaths attributable to intra-day TV0-7 and inter-day TV0-7 was 1.45% and 0.35%, respectively. The mortality risks varied by lag interval, climate area, season, and climate type. CONCLUSIONS: Our results indicated that intra-day TV may explain the main part of the mortality risk related to TV and suggested that comprehensive evaluations should be proposed in more countries to help protect human health.

Temperature frequency and mortality: Assessing adaptation to local temperature.

Assessing the association between temperature frequency and mortality can provide insights into human adaptation to local ambient temperatures. We collected daily time-series data on mortality and temperature from 757 locations in 47 countries/regions during 1979-2020. We used a two-stage time series design to assess the association between temperature frequency and all-cause mortality. The results were pooled at the national, regional, and global levels. We observed a consistent decrease in the risk of mortality as the normalized frequency of temperature increases across the globe. The average increase in mortality risk comparing the 10th to 100th percentile of normalized frequency was 13.03% (95% CI: 12.17-13.91), with substantial regional differences (from 4.56% in Australia and New Zealand to 33.06% in South Europe). The highest increase in mortality was observed for high-income countries (13.58%, 95% CI: 12.56-14.61), followed by lower-middle-income countries (12.34%, 95% CI: 9.27-15.51). This study observed a declining risk of mortality associated with higher temperature frequency. Our findings suggest that populations can adapt to their local climate with frequent exposure, with the adapting ability varying geographically due to differences in climatic and socioeconomic characteristics.