Overview of the interplay between m6A methylation modification and non-coding RNA and their impact on tumor cells.

N6-methyladenosine (m6A) is one of the most common internal modifications in eukaryotic RNA. The presence of m6A on transcripts can affect a series of fundamental cellular processes, including mRNA splicing, nuclear transportation, stability, and translation. The m6A modification is introduced by m6A methyltransferases (writers), removed by demethylases (erasers), and recognized by m6A-binding proteins (readers). Current research has demonstrated that m6A methylation is involved in the regulation of malignant phenotypes in tumors by controlling the expression of cancer-related genes. Non-coding RNAs (ncRNAs) are a diverse group of RNA molecules that do not encode proteins and are widely present in the human genome. This group includes microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and PIWI interaction RNAs (piRNAs). They function as oncogenes or tumor suppressors through various mechanisms, regulating the initiation and progression of cancer. Previous studies on m6A primarily focused on coding RNAs, but recent discoveries have revealed the significant regulatory role of m6A in ncRNAs. Simultaneously, ncRNAs also exert their influence by modulating the stability, splicing, translation, and other biological processes of m6A-related enzymes. The interplay between m6A and ncRNAs collectively contributes to the occurrence and progression of malignant tumors in humans. This review provides an overview of the interactions between m6A regulatory factors and ncRNAs and their impact on tumors.

A novel semi-flexible coaxial nozzle based on fluid dynamics effects and its self-centering performance study.

Coaxial nozzles are widely used to produce fibers with core-shell structures. However, conventional coaxial nozzles cannot adjust the coaxiality of the inner and outer needles in real-time during the fiber production process, resulting in uneven fiber wall thickness and poor quality. Therefore, we proposed an innovative semi-flexible coaxial nozzle with a dynamic self-centering function. This new design addresses the challenge of ensuring the coaxiality of the inner and outer needles of the coaxial nozzle. First, based on the principles of fluid dynamics and fluid-structure interaction, a self-centering model for a coaxial nozzle is established. Second, the influence of external fluid velocity and inner needle elastic modulus on the centering time and coaxiality error is analyzed by finite element simulation. Finally, the self-centering performance of the coaxial nozzle is verified by observing the coaxial extrusion process online and measuring the wall thickness of the formed hollow fiber. The results showed that the coaxiality error increased with the increase of Young's modulus E and decreased with the increase of flow velocity. The centering time required for the inner needle to achieve force balance decreases with the increase of Young's modulus ( E ) and fluid velocity ( v f ). The nozzle exhibits significant self-centering performance, dynamically reducing the initial coaxiality error from 380 to 60 µm within 26 s. Additionally, it can mitigate the coaxiality error caused by manufacturing and assembly precision, effectively controlling them within 8 µm. Our research provides valuable references and solutions for addressing issues such as uneven fiber wall thickness caused by coaxiality errors.

Structures and dynamics of 8-oxo-7,8-dihydro-2'-deoxyguanosine in neutral and basic aqueous solutions by spectroscopy.

8-oxo-7,8-dihydro-2'-dexyoguanine (8-oxo-dG) can be tautomerized to a 6-enolate,8-keto tautomer through nearby-NH deprotonation at elevated pH. In this work, the N3-protonated 8-oxo-dG tautomers in deuterated pH-buffer solutions were studied using steady-state UV/Vis, FTIR, and ultrafast two-dimensional IR spectroscopies. The presence of 6,8-diketo and C6-anionic tautomers at neutral to basic conditions (pD = 7.4-12.0) was revealed by UV/Vis and FTIR results and was further confirmed by 2D IR signals in both diagonal and off-diagonal regions. However, the C6-enol tautomer, which may be an intermediate during the transition from 6,8-diketo to C6-enolate,C8-keto, was not observed appreciably due to its extreme low population. Furthermore, the neutral-to-anionic tautomeric transition of N3H-8-oxo-dG studied in this work occurs under more basic conditions than the N1H-8-oxo-dG reported previously, showing a higher pKa value for N3H than N1H. Finally, vibrational relaxation of the carbonyl stretching mode was found to be both molecular site dependent and pD dependent for 8oxo-dG. Taken together, this work shows that the ultrafast infrared spectroscopic method is effective for examining tautomers and their dynamics in nucleic acids.

Proteomic Stratification of Prognosis and Treatment Options for Small Cell Lung Cancer.

Small cell lung cancer (SCLC) is a highly malignant and heterogeneous cancer with limited therapeutic options and prognosis prediction models. Here, we analyzed formalin-fixed, paraffin-embedded (FFPE) samples of surgical resections by proteomic profiling, and stratified SCLC into three proteomic subtypes (S-I, S-II, and S-III) with distinct clinical outcomes and chemotherapy responses. The proteomic subtyping was an independent prognostic factor and performed better than current tumor-node-metastasis or Veterans Administration Lung Study Group staging methods. The subtyping results could be further validated using FFPE biopsy samples from an independent cohort, extending the analysis to both surgical and biopsy samples. The signatures of the S-II subtype in particular suggested potential benefits from immunotherapy. Differentially overexpressed proteins in S-III, the worst prognostic subtype, allowed us to nominate potential therapeutic targets, indicating that patient selection may bring new hope for previously failed clinical trials. Finally, analysis of an independent cohort of SCLC patients who had received immunotherapy validated the prediction that the S-II patients had better progression-free survival and overall survival after first-line immunotherapy. Collectively, our study provides the rationale for future clinical investigations to validate the current findings for more accurate prognosis prediction and precise treatments.

Design, Fabrication, and Evaluation of 3D Biopotential Electrodes and Intelligent Garment System for Sports Monitoring.

This study presents the development and evaluation of an innovative intelligent garment system, incorporating 3D knitted silver biopotential electrodes, designed for long-term sports monitoring. By integrating advanced textile engineering with wearable monitoring technologies, we introduce a novel approach to real-time physiological signal acquisition, focusing on enhancing athletic performance analysis and fatigue detection. Utilizing low-resistance silver fibers, our electrodes demonstrate significantly reduced skin-to-electrode impedance, facilitating improved signal quality and reliability, especially during physical activities. The garment system, embedded with these electrodes, offers a non-invasive, comfortable solution for continuous ECG and EMG monitoring, addressing the limitations of traditional Ag/AgCl electrodes, such as skin irritation and signal degradation over time. Through various experimentation, including impedance measurements and biosignal acquisition during cycling activities, we validate the system's effectiveness in capturing high-quality physiological data. Our findings illustrate the electrodes' superior performance in both dry and wet conditions. This study not only advances the field of intelligent garments and biopotential monitoring, but also provides valuable insights for the application of intelligent sports wearables in the future.

Identification of candidate single-nucleotide polymorphisms (SNPs) and genes associated with sugarcane leaf scald disease.

Leaf scald, caused by Xanthomonas albilineans, is a severe disease affecting sugarcane worldwide. One of the most practical ways to control it is by developing resistant sugarcane cultivars. It is essential to identify genes associated with the response to leaf scald. A panel of 170 sugarcane genotypes was evaluated for resistance to leaf scald in field conditions for 2 years, followed by a 1-year greenhouse experiment. The phenotypic evaluation data showed a wide continuous distribution, with heritability values ranging from 0.58 to 0.84. Thirteen single nucleotide polymorphisms (SNPs) were identified, significantly associated with leaf scald resistance. Among these, eight were stable across multiple environments and association models. The candidate genes identified and validated based on RNA-seq and qRT-PCR included two genes that encode NB-ARC leucine-rich repeat (LRR)-containing domain disease-resistance protein. These findings provide a basis for developing marker-assisted selection strategies in sugarcane breeding programs.

Remote Mountainous Area Inevitably Becomes Temporal Sink for Microplastics Driven by Atmospheric Transport.

Atmospheric transport drives the widespread distribution of microplastic (MP) in various ecosystems, posing a growing potential threat to environmental safety and human health. Understanding the source and fate of atmospheric MPs is thus crucial to constrain MP's widespread exposure. However, the source-sink dynamics of atmospheric MPs, especially in remote areas, are uncertain, and their transport routes have yet to be identified. Here, we conducted a 13-month monitoring of the atmospheric MPs in the uninhabited area of Mount Taibai, estimated the potential risk of MP exposure to the environment, and modeled the MP trajectory to analyze their transportation. We first found that as many as 15 polymer types of MPs, whose shapes mainly include fiber, fragments, films, and granules, maintained abundance (0.7 and 0.3 particle/m3 for PM10 and PM2.5, respectively) in the mountain atmosphere at respirable sizes. It is worth noting that the risk assessment results that comprehensively consider the influences of abundance and morphological characteristics suggest that the exposure level of MPs exhibits a risk even in this remote mountainous area that is not disturbed by frequent human activities. Backward trajectories revealed the likely source of MPs in the sparsely populated Liupan Mountains and Qinling Mountains of short-range transport. Further, polymer characteristics of MPs and airflow-based source analysis indicated the emission source of MPs in southern Xianyang in a longer-range transport. MPs were directionally transported to Mount Taibai through atmospheric transport under the premise of stable climate and geographical conditions. These suggest that MPs inevitably occur in remote mountainous areas driven by atmospheric transport, and the mountainous areas are persistently bearing the environmental impact of MP exposure. This study reveals the risk impacts of MP exposure and the transport dynamics of atmospheric MPs in a mountain ecosystem.

Experimental data simulating lithium battery charging and discharging tests under different external constraint pressure conditions.

In this paper, the GSP655060Fe soft pack lithium-ion battery with a capacity of 1600 mAh is utilized, employing lithium iron phosphate as the positive electrode and graphite as the negative electrode. In order to comprehensively evaluate the performance of lithium batteries under the conditions of multi-application scenarios, the operating conditions of the battery were simulated under various external confinement pressures of 300 N, 400 N, 500 N, and 600 N, respectively, and the ambient temperatures of 10 ℃, 25 ℃, and 40 ℃, respectively, were controlled to thoroughly test the battery. One charge/discharge test was conducted on six batteries of the same model at multiplicities of 0.5 C, 1 C, 1.5 C, and 2 C, respectively. To ensure the accuracy and reliability of the experimental data, a Battery comprehensive tester Neware BTS-5V12A was utilized, which possesses high-precision voltage and current measurement capabilities with an error rate of only 0.05 %. This data plays an important role in battery research and development, new energy vehicles, electronic products, and other fields.

Osteoporotic osseointegration: therapeutic hallmarks and engineering strategies.

Osteoporosis is a systemic skeletal disease caused by an imbalance between bone resorption and formation. Current treatments primarily involve systemic medication and hormone therapy. However, these systemic treatments lack directionality and are often ineffective for locally severe osteoporosis, with the potential for complex adverse reactions. Consequently, treatment strategies using bioactive materials or external interventions have emerged as the most promising approaches. This review proposes twelve microenvironmental treatment targets for osteoporosis-related pathological changes, including local accumulation of inflammatory factors and reactive oxygen species (ROS), imbalance of mitochondrial dynamics, insulin resistance, disruption of bone cell autophagy, imbalance of bone cell apoptosis, changes in neural secretions, aging of bone cells, increased local bone tissue vascular destruction, and decreased regeneration. Additionally, this review examines the current research status of effective or potential biophysical and biochemical stimuli based on these microenvironmental treatment targets and summarizes the advantages and optimal parameters of different bioengineering stimuli to support preclinical and clinical research on osteoporosis treatment and bone regeneration. Finally, the review addresses ongoing challenges and future research prospects.

Biometric-Tuned E-Skin Sensor with Real Fingerprints Provides Insights on Tactile Perception: Rosa Parks Had Better Surface Vibrational Sensation than Richard Nixon.

The dense mechanoreceptors in human fingertips enable texture discrimination. Recent advances in flexible electronics have created tactile sensors that effectively replicate slowly adapting (SA) and rapidly adapting (RA) mechanoreceptors. However, the influence of dermatoglyphic structures on tactile signal transmission, such as the effect of fingerprint ridge filtering on friction-induced vibration frequencies, remains unexplored. A novel multi-layer flexible sensor with an artificially synthesized skin surface capable of replicating arbitrary fingerprints is developed. This sensor simultaneously detects pressure (SA response) and vibration (RA response), enabling texture recognition. Fingerprint ridge patterns from notable historical figures - Rosa Parks, Richard Nixon, Martin Luther King Jr., and Ronald Reagan - are fabricated on the sensor surface. Vibration frequency responses to assorted fabric textures are measured and compared between fingerprint replicas. Results demonstrate that fingerprint topography substantially impacts skin-surface vibrational transmission. Specifically, Parks' fingerprint structure conveyed higher frequencies more clearly than those of Nixon, King, or Reagan. This work suggests individual fingerprint ridge morphological variation influences tactile perception and can confer adaptive advantages for fine texture discrimination. The flexible bioinspired sensor provides new insights into human vibrotactile processing by modeling fingerprint-filtered mechanical signals at the finger-object interface.

Development of an "on-off-on" fluoroprobe utilizing an anthrylimidazole-based fluorescent ionic liquid for sensitive Cr(VI) and ascorbic acid detection.

Developing a rapid detection method of Cr(VI) and ascorbic acid (AA) is vital in the food and environmental fields. Herein, an anthrylimidazole-based fluorescent ionic liquid (AI-FIL) with the advantageous fluorescent properties was successfully prepared and used to construct a promising "on-off-on" fluoroprobe for rapid/sensitive Cr(VI) and AA detection. Cr(VI) could effectively quench the fluorescence of AI-FIL owing to the inner-filter effect and photoinduced electron-transfer process. However, the decreased fluorescence could be rapidly recovered by AA owing to the redox reaction between AA and Cr(VI). For Cr(VI) detection, a satisfactorily linear response (0.03-300 µM) was achieved with the corresponding detection limit of 9 nM. For AA detection, a good linearity from 1 to 1000 µM was obtained with the resultant detection limit of 0.3 µM. Moreover, the AI-FIL based fluoroprobe was successfully utilized for Cr(VI) and AA detection in food and water samples with satisfactory accuracy and precision.

Cultural psychological factors in posttraumatic symptom development and expression: a study protocol.

Introduction: Cultural factors were shown to be particularly relevant for the development and expression of posttraumatic stress. Recently, the concept of cultural scripts of trauma has been introduced, which proposes that trauma sequelae elements may be sequentially linked and specifically associated with cultural factors. Furthermore, a cascade model is proposed, including trauma exposure, demographic characteristics, cultural affiliation, and trauma-related value orientations as influencing factors of posttraumatic development. The purpose of this Network Project is to investigate cultural psychological factors that contribute to the expression of posttraumatic stress.Methods: The present Network Project implements a mixed methods approach and will be conducted in 5 different study sites, including Switzerland, Israel, Georgia, China, and East Africa. In sub-study I, the cultural scripts of traumatic stress inventories (CSTIs) will be developed. These scales provide a pool of trauma sequelae elements for each cultural group. For this purpose, focus groups with trauma survivors and trauma experts will be conducted and analysed using qualitative research methods. Sub-study II implements a validation analysis of the CSTIs and the empirical investigation of a cultural cascade model. This quantitative approach will include a larger sample of individuals who experienced traumatic life events.Discussion: This contribution is timely and enriches the knowledge of trauma and culture. Future publications of this Network Project will address trauma sequelae from a cultural perspective and provide diagnostic and psychotherapeutic implications.

This paper presents a Network Project that investigates cultural factors in posttraumatic sequelae.The Network Project encompasses an innovative research design with both qualitative and quantitative methods.New developments in the field of cultural clinical psychology are introduced, including cultural scripts of trauma and a cascade model of cultural factors in posttraumatic symptom expression.

PD-1 blockade enhances the effect of targeted chemotherapy on locally advanced pMMR/MSS colorectal cancer.

BACKGROUND: Patients with DNA mismatch repair-proficient/microsatellite stable (pMMR/MSS) colorectal cancer (CRC), which accounts for 85% of all CRC cases, display a poor respond to immune checkpoint inhibitors (i.e., anti-PD-1 antibodies). pMMR/MSS CRC patients with locally advanced cancers need effective combined therapies. METHODS: In this pilot study, we administered six preoperative doses of each 2-week cycle of the anti-PD-1 antibody sintilimab (at a fixed dose of 200 mg), oxaliplatin, and 5-FU/CF (mFOLFOX6) combined with five doses of bevacizumab (the number of doses was reduced to prevent surgical delays) to patients with cT4NxM0 colon or upper rectal cancers. And radical surgery was performed approximately 2 weeks after the last dose of neoadjuvant therapy. The primary endpoint was a pathologic complete response (pCR). We also evaluated major pathologic response (MPR, ≤10% residual viable tumor), radiological and pathological regression, safety, and tumor mutation burden (TMB), and tumor microenvironment (TME) characteristics. RESULTS: By the cutoff date (September 2023), 22 patients with cT4NxM0 pMMR/MSS colon or upper rectal cancers were enrolled and the median follow-up was 24.7 months (IQR: 21.1-26.1). All patients underwent R0 surgical resection without treatment-related surgical delays. pCR occurred in 12 of 22 resected tumors (54.5%) and MPR occurred in 18 of 22 (81.8%) patients. At the cutoff date, all patients were alive, and 21/22 were recurrence-free. Treatment-related adverse events of grade 3 or higher occurred in of 2/22 (9.1%) patients. Among the pCR tumors, two were found to harbor POLE mutations. The degree of pathological regression was significantly greater than that of radiological regression (p = 1.35 × 10-8). The number of CD3+/CD4+ cells in the tumor and stroma in pretreated biopsied tissues was markedly lower in pCR tumors than in non-pCR tumors (p = 0.038 and p = 0.015, respectively). CONCLUSIONS: Neoadjuvant sintilimab combined with bevacizumab and mFOLFOX6 was associated with few side effects, did not delay surgery, and led to pCR and non-pCR in 54.5% and 81.8% of the cases, respectively. Downregulation of CD3/CD4 expression in the tumor and stroma is related to pCR. However, the molecular mechanisms underlying PD-1 blockade-enhanced targeted chemotherapy require further investigation.

Using a Leroux-prior-based conditional autoregression-based strategy to map the short-term association between temperature and bacillary dysentery and its attributable burden in China.

Background: In China, bacillary dysentery (BD) is the third most frequently reported infectious disease, with the greatest annual incidence rate of 38.03 cases per 10,000 person-years. It is well acknowledged that temperature is associated with BD and the previous studies of temperature-BD association in different provinces of China present a considerable heterogeneity, which may lead to an inaccurate estimation for a region-specific association and incorrect attributable burdens. Meanwhile, the common methods for multi-city studies, such as stratified strategy and meta-analysis, have their own limitations in handling the heterogeneity. Therefore, it is necessary to adopt an appropriate method considering the spatial autocorrelation to accurately characterize the spatial distribution of temperature-BD association and obtain its attributable burden in 31 provinces of China. Methods: A novel three-stage strategy was adopted. In the first stage, we used the generalized additive model (GAM) model to independently estimate the province-specific association between monthly average temperature (MAT) and BD. In the second stage, the Leroux-prior-based conditional autoregression (LCAR) was used to spatially smooth the association and characterize its spatial distribution. In the third stage, we calculate the attribute BD cases based on a more accurate estimation of association. Results: The smoothed association curves generally show a higher relative risk with a higher MAT, but some of them have an inverted "V" shape. Meanwhile, the spatial distribution of association indicates that western provinces have a higher relative risk of MAT than eastern provinces with 0.695 and 0.645 on average, respectively. The maximum and minimum total attributable number of cases are 224,257 in Beijing and 88,906 in Hainan, respectively. The average values of each province in the eastern, western, and central areas are approximately 40,991, 42,025, and 26,947, respectively. Conclusion: Based on the LCAR-based three-stage strategy, we can obtain a more accurate spatial distribution of temperature-BD association and attributable BD cases. Furthermore, the results can help relevant institutions to prevent and control the epidemic of BD efficiently.

Subcutaneous daratumumab in Chinese patients with relapsed or refractory multiple myeloma: an open-label, multicenter, phase 1 study (MMY1010).

Despite recent progress in multiple myeloma (MM) treatments, most patients will relapse and require additional treatment. Intravenous daratumumab, a human IgGκ monoclonal antibody targeting CD38, has shown good efficacy in the treatment of MM. A subcutaneous version of daratumumab was formulated to reduce the burden of intravenous infusions. We aimed to investigate the efficacy and safety of subcutaneous daratumumab in Chinese patients with relapsed/refractory MM based on the demonstrated noninferiority of subcutaneous daratumumab to intravenous daratumumab, with a shorter administration time and reduced infusion-related reaction rate in global studies. This phase 1, multicenter study (MMY1010; ClinicalTrials.gov Identifier: NCT04121260) evaluated subcutaneous daratumumab in Chinese patients with relapsed/refractory MM after 1 prior line (n = 1) or ≥2 prior lines (n = 20) of therapy, including a proteasome inhibitor and an immunomodulatory drug. Primary endpoints were pharmacokinetics and safety. Mean (standard deviation) maximum trough concentration of daratumumab was 826 (335) µg/mL, which was consistent with prior studies of subcutaneous daratumumab and intravenous daratumumab. Safety was consistent with safety profiles observed in other daratumumab studies, with no new safety concerns identified. Incidences of infusion-related reactions and injection-site reactions were low and consistent with other subcutaneous daratumumab studies. At a median follow-up of 7.5 months, the overall response rate was 57.1%, with a very good partial response or better rate of 38.1% and complete response or better rate of 19.0%. Our results demonstrate a favorable benefit/risk profile of subcutaneous daratumumab in Chinese patients with relapsed/refractory MM, potentially impacting clinical administration of daratumumab in this population.

Association between hyperuricemia and chronic total coronary occlusion in non-chronic kidney disease populations: a cross-sectional study.

BACKGROUND: Chronic total coronary occlusion (CTO) is an extremely hazardous condition that leads to various clinical phenomena and complications and results in social and economic burdens. Hyperuricemia (HU) is often associated with atherosclerosis. Few studies, however, have investigated the risk of CTO in individuals with HU and the role of traditional cardiovascular risk factors in this setting. METHODS: A cohort of 1245 individuals without chronic kidney disease from southwest China who underwent coronary angiography between February 2018 and June 2021 were enrolled. CTO was defined as a total occlusion of any coronary artery or arteries for more than 3 months. HU was defined as a serum uric acid level of ≥420 µmol/L in men and ≥360 µmol/L in women. Univariate and multivariate logistic regression models and subgroup analyses were applied to assess the relationship between HU and CTO. RESULTS: After adjustment, HU was noted to be associated with a 1.47-fold increase in the risk of CTO [odds ratio (OR), 1.47; 95% confidence interval (CI), 1.06-2.58; P = 0.026]. As a continuous variable, uric acid was an independent predictor of CTO (OR, 1.002; 95% CI, 1.001-1.004; P = 0.047). Subgroup analyses showed that the risk of CTO was higher among individuals under 65 years of age (OR, 2.77; 95% CI, 1.3-5.89), nonobese individuals (OR, 1.9; 95% CI, 1.16-3.1), and those with dyslipidemia (OR, 1.8; 95% CI, 1.04-3.11), while sex, smoking, hypertension, and diabetes did not show similar effects. Interaction analyses revealed no interaction among subgroups. CONCLUSION: Among individuals residing in southwest China, HU was associated with an increased risk of CTO in non-CKD individuals, especially those under 65 years of age and nonobese and dyslipidemic individuals.

Simultaneous determination of four fungicide residues in figs using liquid chromatography tandem mass spectrometry.

Dissipative behavior and final residue levels of difenoconazole, prochloraz, propiconazole, and pyraclostrobin in figs were investigated using field trials and laboratory assays. A three-factor, three-level orthogonal test was designed to optimize the pretreatment conditions of the method. A method was established using high-performance liquid chromatography tandem mass spectrometry for the determination of difenoconazole, prochloraz, propiconazole, and pyraclostrobin residues in figs. The limit of quantification for all four targets in figs was 0.002 mg/kg. Difenoconazole, prochloraz, propiconazole, and pyraclostrobin are readily digestible pesticides in figs with half-lives of 6.4, 6.2, 4.8, and 7.9 days, respectively. Residues of difenoconazole, prochloraz, propiconazole, and pyraclostrobin in figs were below the European Union established residue levels of 0.1, 0.03, 0.01, and 0.02 mg/kg, respectively, at day 7 after application. Pyraclostrobin, propiconazole, difenoconazole, and prochloraz were applied twice at doses of 75, 125, 150, and 200 mg a.i./kg at 7-day intervals, and the residues of the four fungicides in figs were acceptable 7 days after the last application. Therefore, the safety interval can be set at 7 days for 70% difenoconazole-prochloraz wettable powder and 40% pyraclostrobin-propiconazole aqueous emulsion according to the protocol.

Application of Biosensors and Biomimetic Sensors in Dairy Products Testing.

This article summarizes the applications of biosensors and biomimetic sensors in the detection of residues in dairy products. Biosensors utilize biological molecules such as enzymes or antibodies to detect residual substances in dairy products, demonstrating high specificity and sensitivity. Biomimetic sensors, inspired by biosensors, use synthetic materials to mimic biological sensing mechanisms, enhancing stability and reproducibility. Both sensor types have achieved significant success in detecting pesticide residues, veterinary drugs, bacteria, and other contaminants in dairy products. The applications of biological and biomimetic sensors not only improve the efficiency of residue detection in dairy products but also have the potential to reduce the time and cost of traditional methods. Their specificity and high sensitivity make them powerful tools in the dairy industry, thus contributing to ensuring the quality and safety of dairy products and meeting the growing consumer demands for health and food safety.

Low Gilbert damping and high perpendicular magnetic anisotropy in an Ir-coupled L10-FePd-based synthetic antiferromagnet.

Thin ferromagnetic films possessing perpendicular magnetic anisotropy derived from the crystal lattice can deliver the requisite magnetocrystalline anisotropy density for thermally stable magnetic memory and logic devices at the single-digit-nm lateral size. Here, we demonstrate that an epitaxial synthetic antiferromagnet can be formed from L10 FePd, a candidate material with large magnetocrystalline anisotropy energy, through insertion of an ultrathin Ir spacer. Tuning of the Ir spacer thickness leads to synthetic antiferromagnetically coupled FePd layers, with an interlayer exchange field upwards of 0.6 T combined with a perpendicular magnetic anisotropy energy of 0.95 MJ/m3 and a low Gilbert damping of 0.01. Temperature-dependent ferromagnetic resonance measurements show that the Gilbert damping is mostly insensitive to temperature over a range of 20 K up to 300 K. In FePd|Ir|FePd trilayers with lower interlayer exchange coupling, optic and acoustic dynamic ferromagnetic resonance modes are explored as a function of temperature. The ability to engineer low damping and large interlayer exchange coupling in FePd|Ir|FePd synthetic antiferromagnets with high perpendicular magnetic anisotropy could prove useful for high performance spintronic devices.

Bortezomib, thalidomide, and dexamethasone with or without daratumumab and followed by daratumumab maintenance or observation in transplant-eligible newly diagnosed multiple myeloma: long-term follow-up of the CASSIOPEIA randomised controlled phase 3 trial.

BACKGROUND: CASSIOPEIA part 1 demonstrated superior depth of response and prolonged progression-free survival with daratumumab in combination with bortezomib, thalidomide, and dexamethasone (D-VTd) versus bortezomib, thalidomide, and dexamethasone (VTd) alone as an induction and consolidation regimen in transplant-eligible patients newly diagnosed with myeloma. In CASSIOPEIA part 2, daratumumab maintenance significantly improved progression-free survival and increased minimal residual disease (MRD)-negativity rates versus observation. Here, we report long-term study outcomes of CASSIOPEIA. METHODS: CASSIOPEIA was a two-part, open-label, phase 3 trial of patients done at 111 European academic and community-based centres. Eligible patients were aged 18-65 years with transplant-eligible newly diagnosed myeloma and an Eastern Cooperative Oncology Group performance status of 0-2. In part 1, patients were randomly assigned (1:1) to pre-transplant induction and post-transplant consolidation with D-VTd or VTd. Patients who completed consolidation and had a partial response or better were re-randomised (1:1) to intravenous daratumumab maintenance (16 mg/kg every 8 weeks) or observation for 2 years or less. An interactive web-based system was used for both randomisations, and randomisation was balanced using permuted blocks of four. Stratification factors for the first randomisation (induction and consolidation phase) were site affiliation, International Staging System disease stage, and cytogenetic risk status. Stratification factors for the second randomisation (maintenance phase) were induction treatment and depth of response in the induction and consolidation phase. The primary endpoint for the induction and consolidation phase was the proportion of patients who achieved a stringent complete response after consolidation; results for this endpoint remain unchanged from those reported previously. The primary endpoint for the maintenance phase was progression-free survival from second randomisation. Efficacy evaluations in the induction and consolidation phase were done on the intention-to-treat population, which included all patients who underwent first randomisation, and efficacy analyses in the maintenance phase were done in the maintenance-specific intention-to-treat population, which included all patients who were randomly assigned at the second randomisation. This analysis represents the final data cutoff at the end of the study. The trial is registered with ClinicalTrials.gov, NCT02541383. FINDINGS: Between Sept 22, 2015 and Aug 1, 2017, 1085 patients were randomly assigned to D-VTd (n=543) or VTd (n=542); between May 30, 2016 and June 18, 2018, 886 were re-randomised to daratumumab maintenance (n=442) or observation (n=444). At the clinical cutoff date, Sept 1, 2023, median follow-up was 80·1 months (IQR 75·7-85·6) from first randomisation and 70·6 months (66·4-76·1) from second randomisation. Progression-free survival from second randomisation was significantly longer in the daratumumab maintenance group than the observation-alone group (median not reached [95% CI 79·9-not estimable (NE)] vs 45·8 months [41·8-49·6]; HR 0·49 [95% CI 0·40-0·59]; p<0·0001); benefit was observed with D-VTd with daratumumab maintenance versus D-VTd with observation (median not reached [74·6-NE] vs 72·1 months [52·8-NE]; 0·76 [0·58-1·00]; p=0·048) and VTd with daratumumab maintenance versus VTd with observation (median not reached [66·9-NE] vs 32·7 months [27·2-38·7]; 0·34 [0·26-0·44]; p<0·0001). INTERPRETATION: The long-term follow-up results of CASSIOPEIA show that including daratumumab in both the induction and consolidation phase and the maintenance phase led to superior progression-free survival outcomes. Our results confirm D-VTd induction and consolidation as a standard of care, and support the option of subsequent daratumumab monotherapy maintenance, for transplant-eligible patients with newly diagnosed multiple myeloma. FUNDING: Intergroupe Francophone du Myélome, Dutch-Belgian Cooperative Trial Group for Hematology Oncology, and Janssen Research & Development.