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Abstract The multi‐level feature of GeTe/Sb2Te3 interfacial phase change memory was achieved by applying a designed voltage‐based pulse. It stably demonstrated five multi‐level states without interference for 90 cycles by varying the pulse width. GeTe/Sb2Te3 interfacial phase change memory demonstrated retention time of > 1.0 × 103 s, presenting the significantly low drift coefficient (ν) of

The utility of a quantum computer is highly dependent on the ability to reliably perform accurate quantum logic operations. For finding optimal control solutions, it is of particular interest to explore model-free approaches, since their quality is not constrained by the limited accuracy of theoretical models for the quantum processor—in contrast to many established gate implementation strategies. In this work, we utilize a continuous control reinforcement learning algorithm to design entangling two-qubit gates for superconducting qubits; specifically, our agent constructs cross-resonance and CNOT gates without any prior information about the physical system. Using a simulated environment of fixed-frequency fixed-coupling transmon qubits, we demonstrate the capability to generate novel pulse sequences that outperform the standard cross-resonance gates in both fidelity and gate duration, while maintaining a comparable susceptibility to stochastic unitary noise. We further showcase an augmentation in training and input information that allows our agent to adapt its pulse design abilities to drifting hardware characteristics, importantly, with little to no additional optimization. Our results exhibit clearly the advantages of unbiased adaptive-feedback learning-based optimization methods for transmon gate design.

Abstract Transcranial brain stimulation is a promising technology for safe modulation of brain function without invasive procedures. Recent advances in transcranial optogenetic techniques with external light sources, using upconversion particles and highly sensitive opsins, have shown promise for precise neuromodulation with improved spatial resolution in deeper brain regions. However, these methods have not yet been used to selectively excite or inhibit specific neural populations in multiple brain regions. In this study, we created a wireless transcranial optogenetic brain modulator that combines highly sensitive opsins and upconversion particles and allows for precise bimodal neuromodulation of multiple brain regions without optical crosstalk. We demonstrate the feasibility of our approach in freely behaving mice. Furthermore, we demonstrate its usefulness in studies of complex behaviors and brain dysfunction by controlling extorting behavior in mice in food competition tests and alleviating the symptoms of Parkinson’s disease. Our approach has potential applications in the study of neural circuits and development of treatments for various brain disorders.

Abstract Irritable bowel syndrome is a chronic disorder affecting the gastrointestinal tract, negatively impacting patients’ quality of life. Here, we aimed to evaluate the effects of Lacticaseibacillus rhamnosus IDCC 3201 (RH 3201) on irritable bowel syndrome with constipation (IBS-C). In this randomised, double-blind, placebo-controlled trial, a total of 30 subjects with IBS-C were randomly assigned (1:1) to receive 8 weeks of probiotics administration or placebo. Concerning bowel activities, both irritant bowel movements and discomfort caused by constipation showed significant improvement with RH 3201 at 8 weeks. Symptoms including severity of abdominal bloating, frequency of abdominal bloating, and satisfaction of bowel habits based on the irritable bowel syndrome-severity scoring system also ameliorated in the probiotic group. Analysis of the fecal microbiome revealed that the abundance of Bacteroides cellulosilyticus and Akkermansia muciniphila was higher during the period of RH 3201 administration compared to the placebo. Untargeted metabolome analysis further suggested a correlation between specific metabolites, such as N-acetylornithine, xanthine, and 3-phenylpropionic acid, and the improvement of clinical symptoms. These results indicate that RH 3201 was effective in ameliorating IBS-C, potentially by enriching beneficial microbes and associated metabolites in the gut environment.

BackgroundData on the clinical impact of beta-blockers (BBs) in patients with myocardial infarction (MI) who had non-reduced left ventricular ejection fraction (LVEF) after percutaneous coronary intervention are limited.MethodsFrom 2016 to 2020, we evaluated a cohort of 12,101 myocardial infarction patients with a non-reduced LVEF (≥40%) from the Korean Acute Myocardial Infarction Registry V. Patients were divided into two groups based on their BB (carvedilol, bisoprolol, or nebivolol) treatment at discharge: with beta-blocker treatment (BB, n = 9,468) and without beta-blocker treatment (non-BB, n = 2,633). The primary endpoint after discharge was the occurrence of patient-oriented composite endpoints (POCEs), including all-cause mortality, any MI, or any revascularization at 1-year follow-up.ResultsThe median follow-up period was 353 days (interquartile range, 198–378 days). At 1-year follow-up, no significant differences were observed in the primary endpoint between the BB group and the non-BB group. Before propensity score (PS) matching, the POCE incidence was 3.1% in the BB group vs. 3.4% in the non-BB group [hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.68–1.09, p = 0.225]. After PS matching, the POCE incidence remained similar between the two groups (3.7% vs. 3.4%, HR 1.01, 95% CI 0.76–1.35, p = 0.931). Individual outcomes, including all-cause mortality, myocardial infarction, and revascularization, also showed no significant differences between the two groups. Independent predictors of 1-year POCEs after discharge were age, chronic kidney disease, reduced LVEF, and multivessel disease.ConclusionBB treatment in patients with acute MI and non-reduced LVEF was not associated with a significant reduction in cardiovascular outcomes at 1-year follow-up.

Abstract Despite clinical data stretching over millennia, the neurobiological basis of the effectiveness of acupuncture in treating diseases of the central nervous system has remained elusive. Here, using an established model of acupuncture treatment in Parkinson's disease (PD) model mice, we show that peripheral acupuncture stimulation activates hypothalamic melanin‐concentrating hormone (MCH) neurons via nerve conduction. We further identify two separate neural pathways originating from anatomically and electrophysiologically distinct MCH neuronal subpopulations, projecting to the substantia nigra and hippocampus, respectively. Through chemogenetic manipulation specifically targeting these MCH projections, their respective roles in mediating the acupuncture‐induced motor recovery and memory improvements following PD onset are demonstrated, as well as the underlying mechanisms mediating recovery from dopaminergic neurodegeneration, reactive gliosis, and impaired hippocampal synaptic plasticity. Collectively, these MCH neurons constitute not only a circuit‐based explanation for the therapeutic effectiveness of traditional acupuncture, but also a potential cellular target for treating both motor and non‐motor PD symptoms.

Interest in thermosetting resins for polymer applications in extreme environments, such as aerospace, is increasing. The construction of oligoimide-based crosslinking systems has been the focus of considerable research over the past 30 years, but the analysis of chemical structure and molecular weight dependence has not been systematically performed. In this study, we established both theoretical and experimental frameworks by performing simulations based on a deep understanding of the crosslinking structure and conducted a systematic investigation of the properties of bulk specimens by synthesizing and preparing samples with various molecular weights. Theoretical investigations suggested clear differences and tendencies depending on molecular weight and crosslinking reaction pathways. Furthermore, experimental results showed excellent agreement with the simulations and clearly revealed the correlation between the molecular weights of pristine resin and thermal properties, such as glass transition and decomposition. In addition, we successfully obtained a thermosetting resin with superior thermal properties under optimized conditions, including a glass transition temperature exceeding 350 °C and a decomposition temperature exceeding 570 °C.

Abstract Neuropathic pain is a debilitating condition caused by the hyperexcitability of spinal dorsal horn neurons and is often characterized by allodynia. Although neuron-independent mechanisms of hyperexcitability have been investigated, the contribution of astrocyte-neuron interactions remains unclear. Here, we show evidence of reactive astrocytes and their excessive GABA release in the spinal dorsal horn, which paradoxically leads to the tonic excitation of neighboring neurons in a neuropathic pain model. Using multiple electrophysiological methods, we demonstrated that neuronal hyperexcitability is attributed to both increased astrocytic GABA synthesis via monoamine oxidase B (MAOB) and the depolarized reversal potential of GABA-mediated currents (EGABA) via the downregulation of the neuronal K+/Cl− cotransporter KCC2. Furthermore, longitudinal 2-deoxy-2-[18F]-fluoro-D-glucose microPET imaging demonstrated increased regional glucose metabolism in the ipsilateral dorsal horn, reflecting neuronal hyperexcitability. Importantly, inhibiting MAOB restored the entire astrocytic GABA-mediated cascade and abrogated the increased glucose metabolism and mechanical allodynia. Overall, astrocytic GABA-mediated tonic excitation is critical for neuronal hyperexcitability, leading to mechanical allodynia and neuropathic pain.

Transcatheter aortic valve replacement is quickly becoming the standard of care for patients with severe aortic stenosis thanks to its minimally invasive nature and favorable outcomes. Recently, left ventricular pacing has been proposed as a safer alternative to traditional right heart pacing, which could simplify the transcatheter aortic valve replacement procedure overall, although procedural complications may still occur. This report describes a rare case of left ventricular pacing wire–induced acute severe mitral valve regurgitation during transcatheter aortic valve replacement.

Agricultural drought is a major natural disaster affecting biomass accumulation and causing food loss, exacerbated by the increasing frequency of flash droughts and compounded drought-heatwave events. Traditional optical remote sensing indices cannot directly represent the water content of vegetation, resulting in a limited understanding of crop response to drought. To address this gap, we investigated the responsiveness of microwave Vegetation Optical Depth (VOD) with four bands (L-, C-, X-, KU-) and four emerging VOD-derived products to drought conditions in crops in the Midwest US. These products include the normalized Difference Between Night and Day VOD (nVOD), Slope of the Regression of Day and Night VOD (σ), Standardized VOD Index (SVODI), and VOD to estimate Gross Primary Productivity (VOD2GPP). They employ different theoretical modeling approaches to crop growth and water use strategies. We comprehensively analyzed the trend, seasonality, and residual of VODs, using Leaf Area Index (LAI) for comparison, and further assessed the lagged and cumulative effects, quantified drought sensitivity, and captured responsiveness to cumulative drought using thresholds. The results showed a time lag in the response of VOD series to drought as indicated by the Standardized Precipitation Evapotranspiration Index (SPEI). VODs achieved faster responses and higher correlations compared to LAI. Among them, VOD_L exhibited the most statistically significant pixels (39.84%) and positive Rmax-lag with 96.81% of all pixels. For cumulative effects, VOD_L, VOD_C, VOD_X, VOD_KU, and SVODI were highly correlated in the early stages of droughts. We also found that crops in Iowa exhibited medium to high drought sensitivity (average values of 0.55 to 0.74), with the highest drought sensitivity calculated using the isohydricity indicator, σ. Based on threshold comparison, σ showed a timely response in the first month of drought (average of −0.62), whereas VOD_L and VOD_C performed best in the second month (both averaging −1.85), and VOD2GPP (−2.94) was the most responsive in the third month. Due to water use strategy, maize responded more quickly to the onset of drought compared to soybeans. Overall, the results demonstrated that VOD is promising for crop phenology and drought research. This study provides the first comprehensive investigation of the diverse capabilities of multiple VOD-based indices in drought monitoring across various timescales and croplands.

Abstract Bioresorbable neural implants based on emerging classes of biodegradable materials offer a promising solution to the challenges of secondary surgeries for removal of implanted devices required for existing neural implants. In this study, we introduce a fully bioresorbable flexible hybrid opto-electronic system for simultaneous electrophysiological recording and optogenetic stimulation. The flexible and soft device, composed of biodegradable materials, has a direct optical and electrical interface with the curved cerebral cortex surface while exhibiting excellent biocompatibility. Optimized to minimize light transmission losses and photoelectric artifact interference, the device was chronically implanted in the brain of transgenic mice and performed to photo-stimulate the somatosensory area while recording local field potentials. Thus, the presented hybrid neural implant system, comprising biodegradable materials, promises to provide monitoring and therapy modalities for versatile applications in biomedicine.

Abstract Objectives Infertility is a prominent problem affecting millions of couples worldwide. Recently, there has been a hightened emphasis on elucidating the subtle linkages between infertility treatment leveraging assisted reproductive technology and the complex realm of psychological challenges, as well as efforts in implementation of psychological interventions.The Mindful Self-Compassion (MSC) program seeks to improve self-compassion, compassion for others, mindfulness, and life satisfaction while reducing depression, anxiety, and stress. In the current study, an MSC intervention was performed on infertile women (IW) undergoing in vitro fertilization (IVF) to assess the effectiveness of this intervention in reducing psychological distress and psychopathological symptoms and enhancing life expectancy. Methods Fifty-seven IW undergoing IVF were randomly allocated to two groups: MSC (n = 29) or treatment as usual (TAU; n = 28). Participants in MSC met once a week for two hours for eight weeks and attended a half-day meditation retreat. The Synder's Hope questionnaire and the Revised 90-Symptom Checklist (SCL-90-R) were used as the primary outcome measures. Data were obtained before the intervention, immediately after the intervention, and two months post-intervention. Repeated measures of ANCOVA and paired t-tests in all assessment points were used to compare the MSC and the TAU groups in outcomes. Results In the MSC group, hopelessness, anger-hostility, anxiety, interpersonal sensitivity difficulties, and depression were significantly reduced compared with the TAU group, and those improvements persisted at the two-month follow-up. Reliable change index revealed that the MSC group's gains were both clinically significant and durable. Conclusions MSC can facilitate higher life satisfaction and mental well-being for IW undergoing IVF by reducing psychological distress, psychopathological symptoms, and hopelessness. These encouraging findings call for more research into the effectiveness of mindfulness-based therapies in addressing psychological problems among IW undergoing IVF.

This study explored the impacts of various rainfall input types on short-term runoff simulations using the Cell2Flood model in the Waryong Reservoir Basin, South Korea. Six types of rainfall data were assessed: on-site gauge measurements, spatially interpolated data from 39 Automated Synoptic Observing System (ASOS) and 117 Automatic Weather System (AWS) stations using inverse distance weighting (IDW), and Hybrid Surface Rainfall (HSR) data from the Korea Meteorological Administration. The choice of rainfall input significantly affected model accuracy across the three rainfall events. The point-gauged ASOS (P-ASOS) data demonstrated the highest reliability in capturing the observed rainfall patterns, with Pearson’s r values of up to 0.84, whereas the radar-derived HSR data had the lowest correlations (Pearson’s r below 0.2), highlighting substantial discrepancies. For runoff simulation, the P-ASOS and ASOS-AWS combined interpolated dataset (R-AWS) achieved relatively accurate predictions, with P-ASOS and R-AWS exhibiting Normalized Peak Error (NPE) values of approximately 0.03 and Peak Time Error (PTE) within 20 min. In contrast, the HSR data produced large errors, with NPE up to 4.66 and PTE deviations exceeding 200 min, indicating poor temporal accuracy. Although input-specific calibration improved performance, significant errors persisted because of the inherent uncertainty of rainfall data. These findings underscore the importance of selecting and calibrating appropriate rainfall inputs to enhance the reliability of short-term flood modeling, particularly in ungauged and data-sparse basins.

This research investigates the peripheral mechanisms of acupuncture in treating Parkinson’s disease (PD), a progressive neurodegenerative disorder marked by motor impairments. While the central mechanisms of acupuncture have been extensively studied, our focus lies in the peripheral mechanisms at the acupoints, the sites of acupuncture signal initiation. Employing a PD model, we analyzed the local responses to acupuncture stimulation at these points. Our key finding was a significant elevation in both the number and activity of mast cells (MCs) in the peripheral tissues following acupuncture. Intriguingly, pre-treatment with an MC stabilizer diminished the acupuncture’s therapeutic effects on PD symptoms. Similarly, local anesthesia with lidocaine at the acupoints attenuated the symptom improvement typically observed with acupuncture. Meanwhile, the augmentation of MC activity induced by acupuncture was significantly impeded by cromolyn, an MC stabilizer, but remained unaffected by lidocaine. This finding suggests that MC activity is a more upstream regulator of acupuncture effects compared to nerve conduction. This study provides groundbreaking insights into the initiation and transmission of acupuncture signals, highlighting the significant role of peripheral MC modulation in PD treatment.

IntroductionThe white-spotted flower chafer (Protaetia brevitarsis seulensis), which is widely distributed in Asian countries, is traditionally used in oriental medicine. However, its larvae are prone to severe damage by green muscardine disease (caused by Metarhizium anisopliae) during breeding. The aim of this study was to characterize Bacillus velezensis TJS119, which has been isolated from freshwater, and investigate its potential as a biocontrol agent against M. anisopliae in insects.MethodsTJS119 was obtained from freshwater samples in the Republic of Korea and was classified as B. velezensis. We evaluated its in vitro antifungal effect, sequenced the bacterial whole genome, mined genes responsible for the synthesis of secondary metabolites, performed secondary metabolite analysis Ultra performance liquid chromatography-mass spectrometry (UPLC–MS/MS), and conducted bioassays for determining green muscardine disease control ability.ResultsBacillus velezensis TJS119 inhibited the mycelial growth of M. anisopliae in vitro. The size of the B. velezensis TJS119 genome was estimated to be 3,890,913 bp with a GC content of 46.67% and 3,750 coding sequences. Biosynthetic gene clusters for secondary metabolites with antifungal activity were identified in the genome. Lipopeptides, including fengycin secreted by TJS119 exhibit antifungal activity. Application of TJS119 for the biocontrol against green muscardine disease increased the viability of white-spotted flower chafer by 94.7% compared to the control.DiscussionThese results indicate that B. velezensis TJS119 is a potential biocontrol agent for insect pathogens.

BackgroundPerceived social support (PSS) plays a considerable role in mental health. The Multidimensional Scale of Perceived Social Support (MSPSS) is one of the most widely used scales, leading to much research evidence. The present study investigated its measurement model, equivalence across gender (male and female) and age groups (older patients= above 60 and non-older patients= below 60), and concurrent validity.MethodsA cross-sectional survey was conducted between March and October 2020, on patients hospitalized due to COVID-19 in Tehran, Iran. The scales were administered to 328 COVID-19 patients (54.6% male, aged 21 to 92) from two general hospitals; participants completed MSPSS (including friends, family, and significant others subscales), Pittsburgh Sleep Quality Index (PSQI, include sleep latency, subjective sleep quality, habitual sleep efficiency, sleep duration, use of sleep medication, daytime dysfunction, and sleep disturbances subscales), and the Perceived Stress Scale-10 (PSS-10, to assess patients’ appraisal of stressful conditions).ResultsThe MSPSS three-factor structure was confirmed among COVID-19 patients by Confirmatory Factor Analysis (CFA). The results support the MSPSS internal consistency and configural, metric, and scalar invariance across gender and age groups. Nevertheless, small but significant differences were found across ages based on the latent factor mean of the MSPSS from friends, with a lower mean level in older patients. The coefficients of Cronbach’s alpha (ranging from.92 to.96), the ordinal theta (ranging from.95 to.98), and Omega (ranging from.93 to.97) suggested high internal consistency of MSPSS. The concurrent validity of MSPSS was evidenced by its significant negative correlation with PSS-10 (τb = -.13, p

Continuous quantum error correction has been found to have certain advantages over discrete quantum error correction, such as a reduction in hardware resources and the elimination of error mechanisms introduced by having entangling gates and ancilla qubits. We propose a machine learning algorithm for continuous quantum error correction that is based on the use of a recurrent neural network to identify bit-flip errors from continuous noisy syndrome measurements. The algorithm is designed to operate on measurement signals deviating from the ideal behavior in which the mean value corresponds to a code syndrome value and the measurement has white noise. We analyze continuous measurements taken from a superconducting architecture using three transmon qubits to identify three significant practical examples of non-ideal behavior, namely auto-correlation at temporal short lags, transient syndrome dynamics after each bit-flip, and drift in the steady-state syndrome values over the course of many experiments. Based on these real-world imperfections, we generate synthetic measurement signals from which to train the recurrent neural network, and then test its proficiency when implementing active error correction, comparing this with a traditional double threshold scheme and a discrete Bayesian classifier. The results show that our machine learning protocol is able to outperform the double threshold protocol across all tests, achieving a final state fidelity comparable to the discrete Bayesian classifier.

Abstract Atmospheric blocking is a crucial driver of extreme weather events, but its climatological frequency is largely underestimated in state-of-the-art climate models, especially around the North Atlantic. While air-sea interaction along the North Atlantic oceanic frontal region is known to influence Atlantic blocking activity, remote effects from the Pacific have been less studied. Here we use semi-idealised experiments with an atmospheric general circulation model to demonstrate that the mid-latitude Pacific oceanic front is crucial for climatological Atlantic blocking activity. The front intensifies the Pacific eddy-driven jet that extends eastward towards the North Atlantic. The eastward-extended Pacific jet reinforces the North Atlantic circulation response to the Atlantic oceanic front, including the storm track activity and the eddy-driven jet. The strengthening of the eddy-driven jet reduces the Greenland blocking frequency. Moreover, the Pacific oceanic front greatly strengthens the stationary planetary-scale ridge in Europe. Together with a stronger northeastward extension of the Atlantic storm track, enhanced interaction between extratropical cyclones and the European ridge favours the occurrence of Euro-Atlantic blocking. Therefore, the North Atlantic circulation response amplified remotely by the Pacific oceanic front substantially increases Euro-Atlantic blocking frequency while decreasing Greenland blocking frequency.

Abstract Background In this randomized phase II study, we evaluated the efficacy and safety of sorafenib in combination with capecitabine and cisplatin (XP) as first‐line chemotherapy in advanced gastric cancer. Patients and Methods Patients with metastatic gastric or gastroesophageal junction adenocarcinoma were randomized (1:1) to receive either sorafenib plus XP (S + XP) or XP alone. In cases of disease progression in the XP arm, crossover to sorafenib alone was allowed. The primary endpoint was progression‐free survival (PFS). The secondary endpoints included overall survival (OS), response rates, safety profiles, and biomarkers, and the response rates and PFS with secondline sorafenib alone after progression in the XP arm. Results Between Jan 2011 and Feb 2013, a total of 195 patients were accrued (97 in the S + XP arm and 98 in the XP alone arm). The overall response rate was 54% with S + XP, and 52% with XP alone (p = 0.83). With a median follow‐up of 12.6 months (range, 0.1–29.2), the median PFS assessed by independent review was 5.6 months in the S + XP arm and 5.3 months in the XP arm (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.67–1.27, p = 0.61). Overall survival was not different between the two arms (median 11.7 vs. 10.8 months; HR 0.93, 95% CI 0.65–1.31, p = 0.66). Frequencies of grade 3/4 toxicities were similar between the S + XP and XP alone arms, except for neutropenia (21% vs. 37%), anorexia (0% vs. 5%), and hand‐foot skin reaction (7% vs. 1%). Among 51 patients who crossed over to sorafenib alone after disease progression in the XP arm, there was no objective response and their median PFS was 1.3 months (95% CI, 1.2–1.7). Conclusion The addition of sorafenib to XP chemotherapy was safe but not more effective than XP alone for first‐line treatment of metastatic gastric cancer.

ABSTRACTIn this study, Eco-hydrometeorological Remote Sensing-based Penman-Monteith algorithm (Eh-RSPM) was developed by implementing the gross primary productivity into the revised Remote Sensing based Penman-Monteith algorithm (RS-PM). Evaluation of Eh-RSPM was conducted through comparison with in-situ measurements as well as model-based products (e.g. MODerate resolution Imaging Spectroradiometer (MODIS) 16 global ET products (MOD16 ET) and Surface Energy Balance System (SEBS)) during two years (2004 and 2012) in Northeast Asia. Comparison of ET from Eh-RSPM algorithm with five flux tower measurement agreed well with the flux tower datasets at the entire validation sites. Especially, Eh-RSPM showed advantages in improving the accuracy of ET at stations with relatively short canopy height (e.g. QHB and KBU site) as well as the forest site (e.g. SMK). Focusing on the forest site, Eh-RSPM exhibited slightly better statistical performance compared to MOD16. Specifically, the temporal mean bias and RMSD showed a slight improvement, decreasing from −15.40 W m−2 to −12.58 W m−2 and from 28.41 W m−2 to 25.26 W m−2, respectively. This is a key finding of this study, demonstrating the applicability of the improved ET algorithm to regions with significant forest cover. Similarly, spatial distribution of Eh-RSPM showed similar patterns with MOD16 and SEBS. Eh-RSPM strongly showed advantages over the land cover types with relatively shorter canopy height (e.g. grassland and alpine meadow) as well as the heterogeneous forest showed significant improvement in Eh-RSPM through considering the actual physiological behavior variation and influence of photosynthesis into ET calculation.

Abstract The toxicity and biological activity of arsenic depend on its chemical form. In particular, inorganic arsenics are more toxic than organic ones. Apart from the determination of total arsenics, their accurate speciation is important for toxicity assessment. To separate arsenic species using a cation or an anion separation column, at least 0.5–1.0 mL of sample is required because conventional ion chromatography columns use a sample loop of 100–200 μL. It is thus difficult to analyze samples with small volumes, such as clinical and biological samples. In this study, a method for separating arsenic species using a 5-μL sample loop combined with a capillary ion exchange column has been developed for analyzing small volume of samples. The separated arsenics were determined by inductively coupled plasma mass spectrometry. By oxidizing As(III) to As(V) prior to analysis, the total inorganic arsenics, As(III) and As(V), could be well separated from the organic ones. Linear calibration curves (0.5–50 μg/kg) were obtained for total inorganic arsenics dissolved in water. Sub-picogram-level detection limit was obtained. The analytical capability of this method was successfully validated for certified reference materials, namely water and human urine, with total inorganic arsenic recovery efficiencies of 100% and 121%, respectively. Our method requires less than ~ 10 μL of sample and will be very useful to analyze valuable samples available in limited amounts.

Abstract Oxysterols are oxygenated derivatives of cholesterol that contain an additional hydroxy, epoxide, or ketone group in the sterol nucleus and/or a hydroxyl group in the side chain of the cholesterol molecule. 27-Hydroxycholesterol (27HC) is a side-chain oxysterol that is oxygenated at the 27th carbon atom of cholesterol. The oxysterol (27HC) is produced via oxidation by sterol 27-hydroxylase (CYP27A1) and metabolized via oxysterol 7a-hydroxylase (CYP7B1) for bile acid synthesis in the liver. A previous study has demonstrated that treatment with the alternative Estrogen receptor alpha (ERα) ligand 27HC induces ERα-dependent hematopoietic stem cell (HSC) mobilization. In addition, Cyp27a1-deficient mice demonstrate significantly reduced 27HC levels and HSC mobilization. Here, we report that exogenous 27HC treatment leads to a substantial reduction in the hematopoietic stem and progenitor cell (HSPC) population owing to significantly increased reactive oxygen species (ROS) levels and apoptosis in the bone marrow (BM). However, 27HC does not influence the population of mature hematopoietic cells in the BM. Furthermore, exogenous 27HC treatment suppresses cell growth and promotes ROS production and apoptosis in leukemic cells. Moreover, acute myeloid leukemia (AML) patients with high CYP7B1 expression (expected to have inhibition of 27HC) had significantly shorter survival than those with low CYP7B1 expression (expected to have an elevation of 27HC). Single-cell RNA-sequencing (scRNA seq) analysis revealed that the expression of CYP7B1 was significantly increased in AML patients. Thus, our study suggests that 27HC may serve as a potent agent for regulating pools of HSPCs and may have an application as a novel therapeutic target for hematological malignancies. Collectively, pharmacological inhibition of CYP7B1 (expected to have an elevation of 27HC) would potentially have fewer long-term hematological side effects, particularly when used in combination with chemotherapy or radiation for the treatment of leukemia patients.

Depression symptoms and assessment in China are influenced by unique cultural values of collectivism and by social-political factors specific to China. This study validated the Chinese version of the 52-item Multidimensional Depression Assessment Scale (MDAS) with clinically depressed patients in Inner Mongolia. The study sought to examine the psychometric properties of the MDAS and understand the construct of depression in a specific collectivistic cultural context using a scale with comprehensive dimensions of depressive symptoms in the emotional, cognitive, somatic and interpersonal domains. A total of 171 clinically depressed participants in Inner Mongolia completed the Chinese versions of the MDAS and the Beck Depressive Inventory (BDI). The reliability and validity of the MDAS were tested, and an exploratory factor analysis (EFA) was conducted on the MDAS to examine the underlying structure of the measure. The MDAS and BDI were compared in terms of sensitivity and reactivity on the basis of the cut-off value of BDI. The Chinese-MDAS was found to have good psychometric properties, including high Cronbach's alphas for the total scale and for each subscale (0.90-0.97), indicating good reliability, as well as a high and significant correlation with the BDI (r = 0.72; p < .001), suggesting good validity. The factor analysis indicated the emergence of a salient factor of interpersonal symptoms in Chinese depressed patients, suggesting the importance of interpersonal symptoms in Chinese depressed individuals. A cut-off value of 118.5 with high sensitivity and specificity was found on the MDAS based on the cut-off value of the BDI. The Chinese-MDAS demonstrated good psychometric properties among depressed individuals in Inner Mongolia. This study paves the way for the measure's further development and cultural adaptation in a Chinese depressed population., Author(s): Ho Nam Cheung [sup.1] [sup.2] , Joanne M. Williams [sup.1] , Stella W. Y. Chan [sup.1] Author Affiliations: (1) grid.4305.2, 0000 0004 1936 7988, Department of Clinical Psychology, University [...]

Psoriasis is a chronic inflammatory skin disease characterized by hyperplasia of keratinocytes and immune cell infiltration. The IL-17-producing T cells play a key role in psoriasis pathogenesis, while regulatory T (Treg) cells are diminished during psoriatic inflammation. Current psoriasis treatments largely focus on IL-17 and IL-23, however, few studies have explored therapeutic drugs targeting an increase of Treg cells to control immune homeostasis. In this study, we investigated the effects of a cytotoxic T lymphocyte antigen-4 (CTLA-4) signaling peptide (dNP2-ctCTLA-4) in Th17, Tc17, γδ T cells, Treg cells in vitro and a mouse model of psoriasis. Treatment with dNP2-ctCTLA-4 peptide showed a significant reduction of psoriatic skin inflammation with increased Treg cell proportion and reduced IL-17 production by T cells, indicating a potential role in modulating psoriatic skin disease. We compared dNP2-ctCTLA-4 with CTLA-4-Ig and found that only dNP2-ctCTLA-4 ameliorated the psoriasis progression, with increased Treg cells and inhibited IL-17 production from γδ T cells. In vitro experiments using a T cell-antigen presenting cell co-culture system demonstrated the distinct mechanisms of dNP2-ctCTLA-4 compared to CTLA-4-Ig in the induction of Treg cells. These findings highlight the therapeutic potential of dNP2-ctCTLA-4 peptide in psoriasis by augmenting Treg/Teff ratio, offering a new approach to modulating the disease.

The fire weather index (FWI) is a widely used metric for fire danger based on meteorological observations. However, even though it simulates the nonlinear relationship between the meteorological observations and fire intensity, the ability of the FWI to accurately represent global satellite-derived fire intensity observations is limited due to its empirical formulation based on a specific region. In this study, we propose a regionally-fitted fire parameterization method using feed-forward neural networks (FFNNs) to understand the nonlinear relationship between the meteorological variables and the fire intensity, which eventually improves the parameterization accuracy. These FFNNs for each grid point utilize daily-averaged meteorological variables (2 m relative humidity (RH2m), precipitation (PRCP), 2 m temperature, and wind speed) as inputs to estimate the satellite-derived fire radiative power (FRP) values. Applying the proposed FFNNs for fire parameterization during the 2001–2020 period revealed a marked enhancement in cross-validated skill compared to fire intensity estimation based on the FWI. This improvement was particularly notable across East Asia, Russia, the eastern US, southern South America, and central Africa. The sensitivity experiments demonstrated that the RH2m is the most critical variable in estimating the FRP. Conversely, the FWI-based estimations were primarily influenced by PRCP. The FFNNs accurately captured the observed nonlinear RH2m-FRP and PRCP-FRP relationship compared to that of the FWI-based estimations.