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Toll-like receptor 1/2 activation reduces immunoglobulin free light chain production by multiple myeloma cells in the context of bone marrow stromal cells and fibronectin

Toll-like receptor (TLRs) activation in multiple myeloma (MM) cells induces heterogeneous functional responses including cell growth and proliferation, survival or apoptosis. These effects have been suggested to be partly due to increase in secretion of cytokines such as IL-6 or IFNα among others from MM cells following TLR activation. However, whether triggering of these receptors also modulates production of immunoglobulin free light chains (FLCs), which largely contribute to MM pathology, has not been investigated in MM cells before. This study explored the effect of TLR1/2 ligand (Pam3CSK4) alone or combined with bortezomib (BTZ) on production of FLCs in human myeloma cell lines, L363, OPM-2, U266 and NCI-H929. It also investigated the above effect when MM cells were exposed to bone marrow stromal cells (BMSCs) or fibronectin (FN). Adhesion to BMSCs or FN increased secretion of FLC in MM cells. Pam3CSK4 decreased FLC production, and this effect was enhanced in combination with BTZ but attenuated when MM cells adhered to BMSCs or FN. The findings of this study imply that activation of TLR1/2 downregulates FLC production in MM cells even in the context of bone marrow microenvironment components and suggest that targeting some TLRs such as TLR1/2 might have therapeutic potential.

Ferromagnetic Fe-TiO2 spin catalysts for enhanced ammonia electrosynthesis

Abstract Magnetic field effects (MFE) of ferromagnetic spin electrocatalysts have attracted significant attention due to their potential to enhance catalytic activity under an external magnetic field. However, no ferromagnetic spin catalysts have demonstrated MFE in the electrocatalytic reduction of nitrate for ammonia (NO3RR), a pioneering approach towards NH3 production involving the conversion from diamagnetic NO3 − to paramagnetic NO. Here, we report the ferromagnetic Fe-TiO2 to investigate MFE on NO3RR. Fe-TiO2 possesses a high density of atomically dispersed Fe sites and exhibits an intermediate-spin state, resulting in magnetic ordering through ferromagnetism. Assisted by a magnetic field, Fe-TiO2 achieves a Faradaic efficiency (FE) of up to 97% and an NH3 yield of 24.69 mg mgcat − 1 at −0.5 V versus reversible hydrogen electrode. Compared to conditions without an external magnetic field, the FE and NH3 yield for Fe-TiO2 under an external magnetic field is increased by ~21.8% and ~ 3.1 times, respectively. In-situ characterization and theoretical calculations show that spin polarization enhances the critical step of NO hydrogenation to NOH by optimizing electron transfer pathways between Fe and NO, significantly boosting NO3RR activity.

onEEGwaveLAD: A fully automated online EEG wavelet-based learning adaptive denoiser for artefacts identification and mitigation

Electroencephalographic signals are obtained by amplifying and recording the brain’s spontaneous biological potential using electrodes positioned on the scalp. While proven to help find changes in brain activity with a high temporal resolution, such signals are contaminated by non-stationary and frequent artefacts. A plethora of noise reduction techniques have been developed, achieving remarkable performance. However, they often require multi-channel information and additional reference signals, are not fully automated, require human intervention and are mostly offline. With the popularity of Brain-Computer Interfaces and the application of Electroencephalography in daily activities and other ecological settings, there is an increasing need for robust, online, near real-time denoising techniques, without additional reference signals, that is fully automated and does not require human supervision nor multi-channel information. This research contributes to the body of knowledge by introducing onEEGwaveLAD, a novel, fully automated, ONline, EEG wavelet-based Learning Adaptive Denoiser pipeline for artefact identification and reduction. It is a specific framework that can be instantiated for various types of artefacts paving the path towards real-time denoising. As the first of its kind, it is described and instantiated for the particular problem of blink detection and reduction, and evaluated across a general and a specific analysis of the signal to noise ratio across 30 participants.

Deepening water scarcity in breadbasket nations

Identity as a resource or a demand

Individuals embody various social identities that can impact how they interface with the social environment. Stigma theories suggest that members of low-status or marginalized groups possess devalued social identities, and therefore, experience more stress. While social identities can lead to increased stress, individuals’ appraisals of their identities are not necessarily perceived as harmful/demanding. Rather, social identities can also be appraised as resources or sources of strength bringing opportunities and facilitating goal attainment. Using the biopsychosocial (BPS) model of challenge and threat as a conceptual foundation, this research developed a novel measure to assess individuals’ appraisals of their social identities. In Study 1 (N = 575), confirmatory factor analysis (CFA) evaluated the theorized factor structure (i.e., resource and demand appraisals) and assessed the overall fit of the model. Structural equation modeling (SEM) tested for associations between the resource and demand latent factors. Individuals appraising their ethnic-racial identity as a resource exhibited improved self and intergroup outcomes, while those perceiving it as a demand reported worse self-based and intergroup outcomes, as well as more distress. Study 2 (N = 743 Black and White Americans), which was preregistered, examined group differences in appraisals of ethnic-racial identity. SEM revealed that Black participants were more likely than White participants to appraise their ethnic-racial identity as demanding, leading to worse social and intergroup outcomes. Even when Black participants perceived their ethnic-racial identity as a resource, they still reported higher levels of discrimination, intergroup anxiety, and behavioral avoidance compared to their White counterparts. Implications for theory development and application to the stress literature are discussed.

High-rate quantum LDPC codes for long-range-connected neutral atom registers

Deciphering the dose-dependent effects of thymoquinone on cellular proliferation and transcriptomic changes in A172 glioblastoma cells

Glioblastoma multiforme (GBM), the most prevalent primary malignant brain tumor in adults, exhibits a dismal 6.9% five-year survival rate post-diagnosis. Thymoquinone (TQ), the most abundant bioactive compound in Nigella sativa, has been extensively researched for its anticancer properties across various human cancers. However, its specific anti-cancer mechanisms and pathways in glioblastoma remain to be completely elucidated. In this study, we assessed the impact of different TQ concentrations on the viability of A172 cells using WST-8 and Toluidine blue assays, followed by RNA sequencing (RNA-Seq) to identify differentially expressed genes (DEGs). We confirmed their expression levels through quantitative RT-PCR and performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses for these DEGs. RNA-seq revealed no significant gene expression changes at 2.5 μM and 5 μM TQ concentrations. However, at 25 μM and 50 μM, TQ significantly reduced cell viability dose-dependently. We identified 1548 DEGs at 25 μM TQ (684 up-regulated, 864 down-regulated) and 2797 DEGs at 50 μM TQ (1528 up-regulated, 1269 downregulated), with 1202 DEGs common to both concentrations. TQ inhibited key pathways such as PI3K-Akt signaling, calcium signaling, focal adhesion, and ECM-receptor interaction in A172 cells. It downregulated several potential oncogenes (e.g., AEBP1, MIAT) and genes linked to GBM proliferation and migration (e.g., SOCS2, HCP5) while modulating Wnt signaling and up-regulating tumor suppressor genes (e.g., SPRY4, BEX2). TQ also affected p53 downstream targets, maintaining p53 levels. This study elucidates the anti-cancer mechanisms of TQ in A172 GBM cells, underscoring its effects on multiple signaling pathways and positioning TQ as a promising candidate for innovative glioblastoma treatment strategies.

Enhanced phosphorus weathering contributed to Late Miocene cooling

Short-term effects of combined environmental factors on respiratory disease mortality in Qingdao city: A time-series investigation

Background It is crucial to comprehend the interplay between air pollution and meteorological conditions in relation to population health within the framework of "dual-carbon" targets. The purpose of this study was to investigate the impact of intricate environmental factors, encompassing both meteorological conditions and atmospheric pollutants, on respiratory disease (RD) mortality in Qingdao, a representative coastal city in China. Methods The RD mortality cases were collected from the Chronic Disease Surveillance Monitoring System in Qingdao during Jan 1st, 2014 and Dec 31st, 2020. The distributed-lag nonlinear model and generalized additivity model were used to assess the association between daily mean temperature (DMT), air pollutant exposure and RD mortality. To ascertain the robustness of the model and further investigate this relationship, a stratified analysis and sensitivity analysis were conducted to mitigate potential confounding factors. Results A total of 19,905 mortalities from RD were recorded. The minimum mortality temperature (MMT) was determined to be 23.5°C, and DMT and RD mortality showed an N-shaped relationship. At the MMT of 23.5°C, the cumulative relative risk (cumRR) for mortality within a lag period of 0–14 days from the highest temperature (31°C) was estimated at 2.114 (95% confidence interval [CI]: 1.475 ~ 3.028). The effect value of particulate matter (PM) also increased with a longer cumulative lag time. In the single pollutant model, the highest risk of RD mortality was observed on the lag1-day of per 10 μg/m3 increase in PM2.5 exposure, with an excess risk ratio (ER) of 0.847% (95% CI: 0.335% ~ 1.362%). The largest cumulative effect was found at a lag of 8 days, with an ER of 1.546% (95% CI: 0.483% ~ 2.621%). A similar trend was found for PM10. For O3 exposure, the highest risk was observed on the lag1-day of per 10 μg/m3 increase, with an ER of 1.073% (95% CI: 0.502% ~ 1.647%), and the largest cumulative effect occurred at a lag of 2 days with an ER of 1.113% (95%CI: 0.386% ~ 1.844%). Results from the dual-pollutants model demonstrated that the effect of PM on the risk of RD mortality remained significant and slightly increased in magnitude. Moreover, composite pollutants exhibited a higher risk effect, reaching its peak after one week; however, there was a decrease in single-day cumulative effects as more pollutant types were included. Subgroup analysis showed that females, elderly individuals, and those exposed during warm seasons demonstrated greater susceptibility to PM exposure. Conclusion The present study revealed a significant association between short-term exposure to high temperature, PM2.5, PM10 and O3 and the risk of RD mortality in Qingdao, even in dual- and composite-pollutants models. Furthermore, our findings indicate that females, the elderly population, and warm seasons exhibit heightened sensitivity to PM exposure.

Single-cell transcriptomics of bronchoalveolar lavage during PRRSV infection with different virulence

Beauty of symmetry ‐ The impact of logo symmetry on perceived product quality

In an era of intense brand competition, a successful logo can effectively boost consumer awareness of a company. However, existing research has not thoroughly examined the aspect of symmetry in logo design. Addressing this gap, the present study investigates the impact of logo symmetry on consumers’ perceived product quality. Through three online experiments, the results revealed that symmetrical logos significantly enhance perceived product quality compared to asymmetrical logos, with perceived stability mediating this effect. Furthermore, the study confirmed the moderating role of cognitive load, showing that symmetrical logos positively affect perceived product quality only under low cognitive load, while this effect vanishes under high cognitive load. This study contributes to the field of visual logo design and provides practical insights for companies in product promotion and logo design.

Polygenic burden of short tandem repeat expansions promotes risk for Alzheimer’s disease

Comparative efficacy of robot-assisted therapy associated with other different interventions on upper limb rehabilitation after stroke: A protocol for a network meta-analysis

Introduction Post-stroke movement disorders are common, especially upper limb dysfunction, which seriously affects the physical and mental health of stroke patients. With the continuous development of intelligent technology, robot-assisted therapy has become a research hotspot in the upper limb rehabilitation of stroke patients in recent years. Many scholars have also integrated robot-assisted therapy with other interventions to improve rehabilitation outcomes. However, there is a lack of research to determine which auxiliary intervention is the best. Therefore, this protocol aims to guide the development of a network meta-analysis, which helps determine the most suitable auxiliary interventions for robot-assisted therapy. Methods and analysis Published randomized controlled trials will be included if robot-assisted therapy or robot-assisted therapy associated with other different interventions was applied in stroke patients with upper limb dysfunction in the experimental group and usual rehabilitation treatment and care was applied in the control group. CINAHL, PubMed, Web of Science, MEDLINE, Embase, CNKI, and Wanfang electronic databases will be searched. Studies should be published between January 1, 2013, and December 31, 2023. Two reviewers will independently select studies and extra data, and assess the quality of the included studies. The risk of bias will be evaluated based on the Cochrane Collaboration’s risk of bias tool. The evidence quality will be measured according to the Grading of Recommendations Assessment, Development and Evaluation. A network meta-analysis will be conducted by using STATA version 15.0 and R version 4.1.3. The probabilities of rehabilitation interventions will be ranked according to the surface under the cumulative ranking curve. Ethics and dissemination Ethical approval is not needed for reviewing published studies. The results will be submitted to a journal. Trial registration PROSPERO registration number: CRD42023486570.

Anisotropic hydrogel microelectrodes for intraspinal neural recordings in vivo

Racial disparities in extended venous thromboembolism prophylaxis after hysterectomy

Background Venous thromboembolism (VTE) is a significant preventable cause of postoperative morbidity and mortality after major abdominopelvic surgery that calls for extended VTE prophylaxis (eVTEp). Literature suggests that significant racial disparities may exist in post-operative care. Objective The study sought to examine if racial disparities exist in the administration of eVTEp after hysterectomy in a statewide collaborative. Methods We conducted a retrospective cohort study of post-hysterectomy patients across 69 hospitals in the Michigan Surgical Quality Collaborative from January 2016 to February 2020. The variable of interest was race (Black/African or White American). The primary outcome was administration or absence of eVTEp. Descriptive statistics and mixed effects logistic regression were performed for risk adjustment with covariates such as age, cancer occurrence, inflammatory bowel disease, American Society of Anesthesiologists physical status classification, perioperative VTE prophylaxis, postoperative VTE prophylaxis, surgical approach, and surgical duration, among other variables. Results In total, 24,513 patients underwent hysterectomy. Of these patients, 1,107 (4.45%) received eVTEp, 153 (13.24%) of which were Black and 954 (82.53%) of which were White. Mixed effects logistic regression analysis suggested that Black patients were significantly less likely to receive eVTEp than White patients (odds ratio = 0.776; 95% CI: 0.615–0.979; P = 0.039). Additionally, tobacco use, coronary artery disease, bleeding disorder, cancer occurrence, functional status, perioperative VTE prophylaxis, surgical duration, length of stay, and surgical approach were associated with a higher likelihood of receiving eVTEp. Conclusion eVTEp is recommended for the prevention of post-discharge VTE in select patients after hysterectomy. Regression analysis showed that, compared to their White counterparts, Black females were significantly less likely to receive eVTEp. The underlying reasons for this disparity require further investigation into possible socioeconomic influences and inherent biases.

Quantification and optimization of platinum–molybdenum carbide interfacial sites to enhance low-temperature water-gas shift reaction

Abstract Pt/α-MoC1-x catalysts exhibit exceptional activity in low-temperature water-gas shift reactions. However, quantitatively identifying and fine-tuning the active sites has remained a significant challenge. In this study, we reveal that fully exposed monolayer Pt nanoclusters on molybdenum carbides demonstrate mass activity that exceeds that of bulk molybdenum carbide catalysts by one to two orders of magnitude at 100–200 °C for low-temperature water-gas shift reactions. This advancement is driven by the precise quantification and elucidation of active sites along the Pt-molybdenum carbide interfacial perimeter. By combining sacrificial CO adsorption per Pt atom, Density Functional Theory calculations, and CO chemisorption measurements, we establish a direct correlation between the monolayer Pt nanocluster size and the number of interfacial perimeters on Pt/α-MoC1-x catalysts. In this work, these findings provide key insights into the active site configuration of Pt/α-MoC1-x catalysts and open pathways for innovative catalyst design, with the interfacial perimeter identified as a crucial factor in enhancing catalytic performance.

A dual-stream model based on PRNU and quaternion RGB for detecting fake faces

The forensic examination of AIGC(Artificial Intelligence Generated Content) faces poses a contemporary challenge within the realm of color image forensics. A myriad of artificially generated faces by AIGC encompasses both global and local manipulations. While there has been noteworthy progress in the forensic scrutiny of fake faces, current research primarily focuses on the isolated detection of globally and locally manipulated fake faces, thus lacking a universally effective detection methodology. To address this limitation, we propose a sophisticated forensic model that incorporates a dual-stream framework comprising quaternion RGB and PRNU(Photo Response Non-Uniformity). The PRNU stream extracts the “camera fingerprint” feature by discerning the non-uniform response of the image sensor under varying lighting conditions, thereby encapsulating the overall distribution characteristics of globally manipulated faces. The quaternion RGB stream leverages the inherent nonlinear properties of quaternions and their informative representation capabilities to accurately describe changes in image color, background, and spatial structure, facilitating the meticulous capture of nuanced local distinctions between locally manipulated faces and real faces. Ultimately, we integrate the two streams to establish the exchange of feature information between PRNU and quaternion RGB streams. This strategic integration fully exploits the complementarity between two streams to amalgamate local and global features effectively. Experimental results obtained from diverse datasets underscore the advantages of our method in terms of accuracy, achieving a detection accuracy of 96.81%.

Lateral olivocochlear neurons modulate cochlear responses to noise exposure

The sense of hearing originates in the cochlea, which detects sounds across dynamic sensory environments. Like other peripheral organs, the cochlea is subjected to environmental insults, including loud, damage-inducing sounds. In response to internal and external stimuli, the central nervous system directly modulates cochlear function through olivocochlear neurons (OCNs), which are located in the brainstem and innervate the cochlear sensory epithelium. One population of OCNs, the lateral olivocochlear (LOC) neurons, target spiral ganglion neurons (SGNs), the primary sensory neurons of the ear. LOCs alter their transmitter expression for days to weeks in response to noise exposure (NE), suggesting that they could tune SGN excitability over long time periods in response to auditory experience. To examine how LOCs affect auditory function after NE, we characterized OCN transcriptional profiles and found transient LOC-specific gene expression changes after NE, including upregulation of multiple neuropeptide-encoding genes. Next, by generating intersectional mouse lines that selectively target LOCs, we chemogenetically ablated LOCs and assayed auditory responses at baseline and after NE. Compared to controls, mice with reduced LOC innervation showed greater NE-induced functional deficits 1 d later and had worse auditory function after a 2-wk recovery period. The number of remaining presynaptic puncta at the SGN synapse with inner hair cells did not differ between control and LOC-ablated animals, suggesting that the primary role of LOCs after NE is likely not to protect but instead to compensate, ensuring that SGN function is enhanced during periods of need.

Activation of lysophagy by a TBK1-SCFFBXO3-TMEM192-TAX1BP1 axis in response to lysosomal damage

Investigating Pb2 CAP-binding domain inhibitors from marine bacteria for targeting the influenza A H5N1

The ongoing increase in the prevalence and mutation rate of the influenza virus remains a critical global health issue. A promising strategy for antiviral drug development involves targeting the RNA-dependent RNA polymerase, specifically the PB2-cap binding domain of Influenza A H5N1. This study employs an in-silico approach to inhibit this domain, crucial for viral replication, using potential inhibitors derived from marine bacterial compounds. Utilizing the MTi-OpenScreen web server, we screened a library of compounds to assess their molecular interactions with the target. This process identified four potential inhibitors: CMNPD25830, CMNPD18675, CMNPD18676, and CMNPD27216. Subsequent molecular dynamics simulations, conducted using the Amber software suite, evaluated their binding affinities and dynamic interactions with the PB2 protein. Notably, CMNPD25830 and CMNPD27216 emerged as the most promising candidates, exhibiting higher binding affinities and more favourable interaction profiles compared to the control molecule. Additional analyses, including post-simulation free energy calculations and free energy landscape analysis, strengthened the potential of these compounds as effective PB2-cap binding domain inhibitors. This comprehensive computational investigation identifies CMNPD27216 and CMNPD25830 as standout candidates due to their superior binding energies and dynamic stability, suggesting their strong potential as therapeutic agents against influenza. This research sets the stage for further in vitro validation and optimization of these lead compounds, potentially supporting the development of more effective influenza treatments.