Modality-dependent distortion effects of temporal frequency on time perception.

Time perception has been known to depend on the temporal frequency of the stimulus. Previously, the effect of temporal frequency modulation was assumed to be monotonically lengthening or shortening. However, this study shows that temporal frequency affects time perception in a non-monotonic and modality-dependent manner. Four experiments investigated the time distortion effects induced by modulation of temporal frequency across auditory and visual modalities. Critically, the temporal frequency was parametrically manipulated across four levels (steady stimulus, 10-, 20-, and 30/40-Hz intermittent auditory/visual stimulus). Experiment 1, 2, and 3 consistently showed that a 10-Hz auditory stimulus was perceived as shorter than a steady auditory stimulus. Meanwhile, as the temporal frequency increased, the perceived duration of the intermittent auditory stimulus was lengthened. A 40-Hz auditory stimulus was perceived as longer than a 10- Hz auditory stimulus, but did not differ significantly from a steady one. Experiment 4 showed that, for the visual modality, a 10-Hz visual stimulus was perceived as longer than a steady stimulus, and the perceived duration was lengthened as temporal frequency increased. This study demonstrated that within the scope of the temporal frequencies examined in this study, there were differential distortion effects observed across sensory modalities.

Efficacy and safety of generic pomalidomide plus low-dose dexamethasone in relapsed or refractory multiple myeloma: a multicenter, open-label, single-arm trial.

This multicenter, open-label, single-arm trial (ClinicalTrials.gov, NCT05236621) was conducted to confirm the efficacy and safety of generic pomalidomide plus dexamethasone in Chinese patients with relapsed or refractory multiple myeloma (RRMM). Total 79 eligible RRMM patients were planned to be included. Patients were treated with generic pomalidomide (4 mg daily on days 1-21, orally) and low-dose dexamethasone (40 mg/day on days 1, 8, 15, and 22, orally; 20 mg for patients aged > 75 years) in 28-day cycles until disease progression with a maximum treatment duration of 2 years. The primary endpoint is the overall response rate (ORR) assessed by the independent review committee per the 2016 International Myeloma Working Group guidelines. A total of 85 eligible patients were included in this study from 32 centers in China, with a median age of 62.0 (range, 39-76) years, a median prior line of therapy of 4 (range, 1-16), and 41.2% patients with high-risk cytogenetics. The ORR was 38.8% (95% confidence interval (CI), 28.44-50.01). The disease control rate was 67.1% (95% CI, 56.02-76.87), meanwhile, the median progression-free survival was 5.55 months (95% CI, 3.68-7.52). Among the treatment-related adverse events (TRAEs), infective pneumonia (17.6%) was the most frequent non-hematologic adverse event, while a decrease in neutrophil count (52.9%) was the most common grade ≥ 3 TRAE. The study results indicated that the generic pomalidomide demonstrated consistent efficacy and a safety profile similar to the branded pomalidomide when combined with low-dose dexamethasone in Chinese RRMM patients.Registration number ClinicalTrials.gov NCT05236621, retrospectively registered on February 11, 2022.

Hierarchical Nickel Cobalt Phosphide @ Carbon Nanofibers Composite Microspheres: Ultrahigh Energy Densities of Electrodes for Supercapacitors.

Supercapacitors (SCs) are widely used in energy storage devices due to their superior power density and long cycle lifetime. However, the limited energy densities of SCs hinder their industrial application to a great extent. In this study, we present a new combination of metallic phosphide-carbon composites, synthesized by directly carbonizing (Ni1-xCox)5TiO7 nanowires via thermal chemical vapor deposition (TCVD) technology. The new method uses one-dimensional (1D) (Ni1-xCox)TiO7 nanowires as precursors and supporters for the in situ growth of intertwined porous CNF microspheres. These 1D nanowires undergo microstructure transformation, resulting in the formation of CoNiP nanoparticles, which act as excellent interconnected catalytic nanoparticles for the growth of porous 3D CNF microspheres. Benefiting from the synergistic effect of a unique 1D/3D structure, the agglomeration of nanoparticles can effectively be prevented. The resulting CNF microspheres exhibit an interconnected conductive matrix and provide a large specific surface area with abundant ion/charge transport channels. Consequently, at a scanning rate of 10 mV s-1, its specific capacitance in 1.0 M Na2SO4 + 0.05 M Fe(CN)63-/4- aqueous solution is as high as 311.7 mF cm-2. Furthermore, the CoNiP@CNFs composite film-based symmetrical SCs show an ultrahigh energy density of 20.08 Wh kg-1 at a power density of 7.20 kW kg-1, along with outstanding cycling stability, with 87.2% capacity retention after 10,000 cycles in soluble redox electrolytes. This work provides a new strategy for designing and applying high-performance binary transition metal phosphide/carbon composites for next-generation energy storage devices.

An Overview of Stimuli-Responsive Intelligent Antibacterial Nanomaterials.

Drug-resistant bacteria and infectious diseases associated with biofilms pose a significant global health threat. The integration and advancement of nanotechnology in antibacterial research offer a promising avenue to combat bacterial resistance. Nanomaterials possess numerous advantages, such as customizable designs, adjustable shapes and sizes, and the ability to synergistically utilize multiple active components, allowing for precise targeting based on specific microenvironmental variations. They serve as a promising alternative to antibiotics with diverse medical applications. Here, we discuss the formation of bacterial resistance and antibacterial strategies, and focuses on utilizing the distinctive physicochemical properties of nanomaterials to achieve inherent antibacterial effects by investigating the mechanisms of bacterial resistance. Additionally, we discuss the advancements in developing intelligent nanoscale antibacterial agents that exhibit responsiveness to both endogenous and exogenous responsive stimuli. These nanomaterials hold potential for enhanced antibacterial efficacy by utilizing stimuli such as pH, temperature, light, or ultrasound. Finally, we provide a comprehensive outlook on the existing challenges and future clinical prospects, offering valuable insights for the development of safer and more effective antibacterial nanomaterials.

Association of dyslipidemia and hypoxemia in patients with obstructive sleep apnea hypopnea syndrome: a cross-sectional study.

OBJECTIVE: Studies have shown that dyslipidemia may contribute to chronic tissue hypoxia. However, it remains unclear whether dyslipidemia affects chronic hypoxia in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). Therefore, from a clinical practice perspective, the purpose of this study was to investigate the effect of dyslipidemia on chronic hypoxia in OSAHS patients. METHOD: In athis cross-sectional survey, 320 consecutive OSAHS patients were enrolled. By screening under different conditions, 211 patients were finally enrolled in the study. Patients were grouped according to apnea-hypopnea index (AHI), into a mild-to-moderate (AHI < 30) group and severe OSAHS group (AHI ≥ 30). RESULTS: Comparative analysis shows that 45% of mild-to-moderate OSAHS patients had severe hypoxemia. Univariate and multivariate regression analyses showed that AHI, triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) had independent effects on lowest oxygen saturation (LSpO2), and that AHI and TG levels had independent effects on mean oxygen saturation (MSpO2). The patients were stratified by AHI and further grouped by TG and HDL-C abnormalities in each subgroup. A difference analysis showed that LSpO2 and MSpO2 were significantly decreased in OSAHS patients with dyslipidemia (high TG and low HDL-C levels) in the AHI ≥ 30 subgroup (P < 0.05). Finally, in order to further clarify the impact of the selected indicators of hypoxemia in OSAHS patients with different degrees of airway obstruction, subgroup analysis was conducted based on OSAHS severity. In the AHI < 30 subgroup, LSpO2 was significantly decreased in patients with abnormal HDL-C. CONCLUSION: The results of this study indicate that abnormalities in TG and HDL-C, in addition to upper airway obstruction, are among the factors that aggravate chronic hypoxia in tissues from OSAHS patients.

Correlation of serum nicotinamide phosphoribosyl transferase with hypoxia and Framingham risk score in patients with obstructive sleep apnea-hypopnea syndrome.

BACKGROUND: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is an independent risk factor for atherosclerosis (AS), but the mechanism is different from classical AS risk factors. Nicotinamide phosphoribosyltransferase (NAMPT) is involved in the pathophysiology of AS via multiple pathways, and its expression is closely related to hypoxia. The association of NAMPT with hypoxia and the risk of cardiovascular morbidity in the patients of OSAHS remains to be defined. Therefore, we carried out this study to investigate the association of NAMPT with hypoxia and the risk of early cardiovascular disease [based on the Framingham risk score (FRS)] in patients with OSAHS. METHODS: A total of 82 patients diagnosed with OSAHS were enrolled in this cross-sectional survey design, along with 18 healthy controls who were age- and gender-matched. The general characteristic parameters including height and weight as well as biochemical parameters including blood glucose and lipid were collected from the subjects. The Framingham vascular risk score calculates the risk of developing vascular disease based on the above indicators. Polysomnography was performed in patients with OSAHS, and blood oxygen saturation and apnea-hypopnea index (AHI) were collected, and patients were grouped by disease extent by AHI. The serum NAMPT level of the research subjects was detected using an enzyme-linked immunosorbent assay. Spearman correlation analysis and multiple linear regression to explore the independent correlations of hypoxia on serum NAMPT activity in OSAHS patients. RESULTS: Serum NAMPT level in patients with OSAHS increased with the severity of the disease. Correlation analysis showed that NAMPT was significantly positively correlated with FRS in patients with OSAHS (r=0.829, P<0.05). Multiple linear regression analysis with FRS as the outcome measure showed that NAMPT activity and minimum blood oxygen saturation were independent associated with the risk of developing cardiovascular disease (ß=0.03, P=0.000; ß=-0.13, P=0.034). Univariate and multivariate regression analyses revealed that hypoxia was significantly associated with NAMPT levels in OSAHS patients, and the oxygen desaturation index (ODI) was independent associated with the expression of NAMPT activity (ß=4.09, P=0.000). CONCLUSIONS: In patients with OSAHS, hypoxia is independently associated with NAMPT. NAMPT increases the risk of cardiovascular morbidity in this population may be influenced by hypoxia.

Light-Promoted Arylsilylation of Alkenes with Hydrosilanes.

Herein, we report light-promoted photo/hydrogen atom transfer dual catalysis for arylsilylation of alkenes via the radical-radical cross-coupling with diverse hydrosilanes, which provides a simple and efficient method to prepare various organosilicon compounds with a wide range of substrate scope and good functional group tolerance under transition-metal- and chemical-oxidant-free conditions. Furthermore, the arylsilylation of alkenes can also proceed via the possible electron donor-acceptor complex under exogenous photocatalyst-free conditions.

Genome-Wide Association Analysis for Salt-Induced Phenotypic and Physiologic Responses in Rice at Seedling and Reproductive Stages.

Salinity is one of the main adverse environmental factors severely inhibiting rice growth and decreasing grain productivity. Developing rice varieties with salt tolerance (ST) is one of the most economical approaches to cope with salinity stress. In this study, the salt tolerance of 220 rice accessions from rice diversity panel l (RDP1), representing five subpopulations, were evaluated based on 16 ST indices at both seedling and reproductive stages under salt stress. An apparent inconsistency was found for ST between the two stages. Through a gene-based/tightly linked genome-wide association study with 201,332 single nucleotide polymorphisms (SNPs) located within genes and their flanking regions were used, a total of 214 SNPs related to 251 genes, significantly associated with 16 ST-related indices, were detected at both stages. Eighty-two SNPs with low frequency favorable (LFF) alleles in the population were proposed to hold high breeding potential in improving rice ST. Fifty-four rice accessions collectively containing all these LFF alleles were identified as donors of these alleles. Through the integration of meta-quantitative trait locus (QTL) for ST and the response patterns of differential expression genes to salt stress, thirty-eight candidate genes were suggested to be involved in the regulation of rice ST. In total, the present study provides valuable information for further characterizing ST-related genes and for breeding ST varieties across whole developmental stages through marker-assisted selection (MAS).

Comprehensive geriatric assessment in newly diagnosed older myeloma patients: a multicentre, prospective, non-interventional study.

BACKGROUND: Multiple myeloma is a disease of the older people, whose prognoses are highly heterogeneous. The International Myeloma Working Group (IMWG) proposed a geriatric assessment (GA) based on age, functional status and comorbidities to discriminate between fit and frail patients. Given the multidimensional nature of frailty and the relatively recent exploration of frailty in the field of MM, reaching a consensus on the measurement of frailty in MM patients remains challenging. OBJECTIVE: We sought to assess the feasibility of performing a comprehensive GA (CGA) in older MM patients in a real-world and multicentre setting and to evaluate their baseline CGA profiles. RESULTS: We studied 349 older patients with newly diagnosed MM (age range, 65-86 years). Our results showed that a CGA is feasible for older MM patients. Using the IMWG-GA criteria, we identified significantly more frail patients in our cohort comparing to in the IMWG cohort (43% vs 30%, P = 0.002). In the IMWG-GA 'fit' group, risk of malnutrition, depression and cognitive impairment remains. The median follow-up time was 26 months (range 1-38). The median overall survival (OS) was 34.7 months, and the estimated 3-year OS rate was 50%. A high MNA-SF score (MNA-SF ≥ 12), low GDS score (GDS ≤ 5) and high CCI score (CCI ≥ 2) can be used to predict the OS of older patients with newly diagnosed MM. This study is registered at www.clinicaltrials.gov (NCT03122327). CONCLUSIONS: Our study justifies the need for a CGA in older patients with newly diagnosed MM.

Perceptual Representations in L1, L2 and L3 Comprehension: Delayed Sentence-Picture Verification.

We used delayed sentence-picture verification tasks to investigate multilingual perceptual representations. In experiment 1, participants listened to sentences with implied shapes. After a 10-min interval, they judged whether pictures had been mentioned in the preceding sentences or not. Results in experiment 1 showed significant match effect in L1, but not in high proficient L2 or low proficient L3. In experiment 2, Participants listened to one language block, then immediately judged one picture block, totally three language-picture blocks. Results in experiment 2 were parallel to results in experiment 1. Our study supports the view of distributed conception: L2 and L3 are associated with less perceptual symbols than L1, indicating great impact of acquisition styles on perceptual representations. Our results show little impact of language proficiency levels on perceptual representations in delayed tasks.

Regulatory T cells in allogeneic hematopoietic stem cell transplantation: From the lab to the clinic.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curable strategy for the treatment of hematological malignancies and nonmalignant diseases. However, graft-versus-host disease (GVHD) and relapse are still two major causes of morbidity and mortality after allo-HSCT, and both restrict the improvement of transplant outcomes. Regulatory T cells (Tregs) has been successfully used in allo-SCT settings. In this review, we summarize recent advances in experimental studies that have evaluated the roles played by Tregs in the establishment of novel transplant modalities, the prevention of GVHD and the enhancement of immune reconstitution. We also discuss the application of Tregs in clinical to prevent acute GVHD, treat chronic GVHD, as well as enhance immune reconstitution and decrease leukemia relapse, all of which lead to improving transplant outcomes.

Association of increased microvessel density with skeletal extramedullary disease relapse in multiple myeloma patients who have skeletal extramedullary disease at diagnosis.

The aim of the study was to investigate whether microvessel density (MVD) could be associated with skeletal extramedullary disease relapse (skeletal-EMDR) in patients with multiple myeloma (MM) who have skeletal-EMD at diagnosis. Seventy-nine newly diagnosed MM patients who have skeletal-EMD were retrospectively enrolled in this study. The 4-year cumulative incidence of skeletal-EMDR was 35.0%±8.3%. The 4-year probability of overall survival (OS) was 54.0%±7.6%. Multivariate analysis showed that skeletal-EMDR (HR = 4.144; 95% CI: 1.608-10.685; P = 0.003) was independently associated with inferior OS for the MM patients who have skeletal-EMD at diagnosis. The factors associated with skeletal-EMDR were MVD (HR = 3.990, 95%CI:1.136-14.018; P = 0.031), white blood cell (WBC) (HR = 0.262, 95% CI:0.090-0.769; P = 0.015), and the EMD sites involved at onset (HR = 0.263, 95% CI: 0.074-0.937; P = 0.039). The MVD in patients with thoracic and lumbar vertebrae as the involved sites at diagnosis was significantly lower than those with other sites involved (41.59 ± 14.39 vs. 60.82 ± 35.14, P=0.001). Our data suggest that increased MVD could be used to predict skeletal-EMDR, which is associated with inferior survival in patients with MM who have skeletal-EMD at diagnosis.

Effects of Naming Language and Switch Predictability on Switch Costs in Bilingual Language Production.

Switch costs are defined as the phenomenon that bilinguals have worse performance in switch trials relative to non-switch trials. Bilinguals' naming language and switch predictability have been found to influence the magnitude of switch costs. However, how these two factors modulate switch costs in different phases (i.e., lemma activation and language selection) during language production remains unclear. Most previous studies using the language switching paradigm did not dissociate lemma activation from language selection, because the language cue was either presented simultaneously with or prior to a stimulus. Therefore, here we modified the language switching paradigm by presenting a digit stimulus prior to a visual cue. This allowed us to dissociate lemma activation from language selection, and thus we were able to investigate the mechanisms underlying the effects of naming language and switch predictability on switch costs during the two different phases in language production. Unbalanced Indonesian-Chinese bilinguals were required to name digits in either their L1 (Indonesian) or L2 (Chinese), and their reaction times and electrophysiological responses were recorded. The behavioral results showed the effects of switch predictability on switch costs, with responses in switch trials being slower than those in non-switch trials in the low switch predictability condition, while there was no significant difference in response times between switch trials and non-switch trials in the high switch predictability condition. The event-related potential results showed that neither naming language nor switch predictability affected switch costs during the lemma activation phase, but both did so during the language selection phase, particularly at the language task schema competition stage. The results imply that naming language and switch predictability affect switch costs mainly during the language task schema competition stage.

An integrated bioinformatical analysis of miR-19a target genes in multiple myeloma.

MicroRNA (miR)-19a, as an oncomiR, has been studied in several types of cancer; however, its role in the development and progression of multiple myeloma (MM) remains unclear. The present study used a bioinformatics approach to investigate the involvement of miR-19a in MM. miR-19a targets were predicted using target prediction programs, followed by screening for differentially expressed genes in MM. The function of these genes was then annotated using gene ontology term enrichment, signaling pathway enrichment and protein-protein interaction (PPI) analysis. In addition, natural language processing (NLP) was performed to identify genes associated with MM. A total of 715 putative targets of miR-19a were identified in the present study, of which 40 were experimentally validated. A total of 121 genes were identified to be differentially expressed in MM, including 80 upregulated genes and 41 downregulated genes. Among the differentially expressed genes, ras homolog family member B, clathrin heavy chain, prosaposin and protein phosphatase 6 regulatory subunit 2 were predicted target genes of miR-19a. The results of NLP revealed that 2 of the differentially expressed genes, Y-box binding protein 1 and TP53 regulated inhibitor of apoptosis 1, were reported to be associated with MM. In addition, 41 target genes of miR-19a were identified to be associated with the development and progression of MM. These results may aid in understanding the molecular mechanisms of miR-19a in the development and progression of MM. In addition, the results of the present study indicate that targets genes of miR-19a are potential candidate biomarkers for MM.

Mechanisms for T cell tolerance induced with granulocyte colony-stimulating factor.

Granulocyte colony-stimulating factor (G-CSF) has been widely accepted as a mediator of T cell tolerance. The immune modulatory effect of G-CSF on T cells is believed to be mediated exclusively through other effector cells, such as monocytes, tolerogenic dendritic cells (DC), and myeloid-derived suppressor cells. Recent advances confirmed the direct effects of G-CSF in inducing immune tolerance of T cells through the G-CSF-G-CSF receptor pathway and related molecular mechanisms. This review aims to summarize the findings associated with the direct and indirect mechanisms for T cell tolerance induced with G-CSF. The role of G-CSF in preventing graft-versus-host disease (GVHD) and in treating autoimmune diseases (ADs) is also discussed. It is conceivable that G-CSF and immune cell compositions, such as tolerogenic DC and CD4(+)CD25(+)Foxp3(+) T cells, modulated by G-CSF could become an integral part of the immunomodulatory therapies against GVHD and ADs in the future.

Interleukin-17 receptor expression on vascular endothelial cells of masses of skeletal extramedullary disease in myeloma patients.

The goal of the study was to investigate the expression of interleukin-17 (IL-17) and IL-17 receptor (IL-17R) in patients with myeloma bone diseases (MBD) and skeletal extramedullary disease (skeletal EMD). The levels of IL-17 were determined using ELISA. The expression of IL-17R on vascular endothelial cells of bone marrow (BM) and masses of skeletal EMD was detected using immunohistochemistry. The results showed an elevated IL-17 level in BM of BMD and skeletal EMD patients. The microvessel density (MVD) was significantly increased in the masses of skeletal EMD. IL-17R was almost exclusively expressed by endothelial cells, not by myeloma cells in the masses of skeletal EMD patients. We concluded that EMD masses showed increased angiogenesis mediated by IL-17 pathway and in part this may help in myeloma cell-growth under these conditions.

The optimal velocity criterion in the diagnosis of unilateral middle cerebral artery stenosis by transcranial Doppler.

We evaluated the optimal flow velocity of transcranial doppler (TCD) in detecting unilateral middle cerebral artery (MCA) stenosis and stenosis grading by magnetic resonance angiography (MRA) as the reference standard. 302 nonconsecutive patients with unilateral MCA stenosis detected by TCD underwent MRA of the intracranial arteries. The peak systolic velocity (PSV), mean flow velocity (MFV), and end-diastolic velocity (EDV) of each MCA were recorded. 604 MCA were categorized into four groups depending on the stenosis severity: normal MCA (n = 319, 52.8%), mild stenosis (n = 94, 15.6%), moderate stenosis (n = 66, 10.9%), and severe stenosis (n = 125, 20.7%). Significant differences in PSV, MFV, and EDV between these four groups were observed (P < 0.001, respectively). The optimal cutoff velocities for detecting MCA stenosis were: PSV = 160 cm/s, MFV = 100 cm/s, EDV = 60 cm/s; the optimal cutoff points to distinguish mild from moderate stenosis were: PSV = 200 cm/s, MFV = 120 cm/s, EDV = 80 cm/s; the cutoffs to distinguish moderate from severe stenosis were: PSV = 280 cm/s, MFV = 180 cm/s, EDV = 110 cm/s. Using PSV as the diagnostic criteria, the correlation for diagnosing MCA stenosis using TCD and MCA was good (Kappa number κ = 0.668); using as MFV criteria, κ = 0.641. The optimal cutoff PSV values in stenosis grading on TCD were 160, 200, and 280 cm/s. The optimal cutoff MFV values were 100, 120, and 180 cm/s. PSV is more accurate than MFV in detecting and grading MCA stenosis.