Function of a Foxp3 cis-element in protecting regulatory T cell identity.

The homeostasis of multicellular organisms requires terminally differentiated cells to preserve their lineage specificity. However, it is unclear whether mechanisms exist to actively protect cell identity in response to environmental cues that confer functional plasticity. Regulatory T (Treg) cells, specified by the transcription factor Foxp3, are indispensable for immune system homeostasis. Here, we report that conserved noncoding sequence 2 (CNS2), a CpG-rich Foxp3 intronic cis-element specifically demethylated in mature Tregs, helps maintain immune homeostasis and limit autoimmune disease development by protecting Treg identity in response to signals that shape mature Treg functions and drive their initial differentiation. In activated Tregs, CNS2 helps protect Foxp3 expression from destabilizing cytokine conditions by sensing TCR/NFAT activation, which facilitates the interaction between CNS2 and Foxp3 promoter. Thus, epigenetically marked cis-elements can protect cell identity by sensing key environmental cues central to both cell identity formation and functional plasticity without interfering with initial cell differentiation.

CCR2 monocytes as therapeutic targets for acute disc herniation and radiculopathy in mouse models.

OBJECTIVE: Back pain and radiculopathy caused by disc herniation are major health issues worldwide. While macrophages are key players in disc herniation induced inflammation, their roles and origins in disease progression remain unclear. We aim to study the roles of monocytes and derivatives in a mouse model of disc herniation. METHODS: Using a CCR2-CreER; R26R-EGFP (Ai6) transgenic mouse strain, we fate-mapped C-C chemokine receptor type 2 (CCR2) expressing monocytes and derivatives at disc herniation sites, and employed a CCR2RFP/RFP mouse strain and a CCR2-specific antagonist to study the effects of CCR2+ monocytes on local inflammatory responses, pain level, and disc degeneration by immunostaining, flow cytometry, and histology. RESULTS: CCR2+ monocytes (GFP+) increased at the sites of disc hernia over postoperative day 4, 6, and 9 in CCR2-CreER; Ai6 mice. F4/80+ cells increased, and meanwhile, CD11b+ cells trended downward. Co-localization analysis revealed that both GFP+CD11b+ and GFP+F4/80+ constituted the majority of CD11b+ and F4/80+ cells at disc hernia sites. Fluorescence activated cell sorter purified GFP+ cells exhibited higher cytokine expressions than GFP- cells. Inhibition of CCR2 signaling reduced infiltration of monocytes and macrophages, alleviated pain, maintained disc height, and reduced osteoclast activity in adjacent cortical bone for up to 1 month. CONCLUSION: Our findings suggest that circulating CCR2+ monocytes play important roles in initiating and promoting the local inflammatory responses, pain sensitization, and degenerative changes after disc herniation, and thus may serve as therapeutic targets for disc herniation induced back and leg pain.

RNA-binding protein MAC5A interacts with the 26S proteasome to regulate DNA damage response in Arabidopsis.

DNA damage response (DDR) in eukaryotes is essential for the maintenance of genome integrity in challenging environments. The regulatory mechanisms of DDR have been well-established in yeast and humans. However, increasing evidence supports the idea that plants seem to employ different signaling pathways that remain largely unknown. Here, we report the role of MODIFIER OF SNC1, 4-ASSOCIATED COMPLEX SUBUNIT 5A (MAC5A) in DDR in Arabidopsis (Arabidopsis thaliana). Lack of MAC5A in mac5a mutants causes hypersensitive phenotypes to methyl methanesulfonate (MMS), a DNA damage inducer. Consistent with this observation, MAC5A can regulate alternative splicing of DDR genes to maintain the proper response to genotoxic stress. Interestingly, MAC5A interacts with the 26S proteasome (26SP) and is required for its proteasome activity. MAC core subunits are also involved in MMS-induced DDR. Moreover, we find that MAC5A, the MAC core subunits, and 26SP may act collaboratively to mediate high-boron-induced growth repression through DDR. Collectively, our findings uncover the crucial role of MAC in MMS-induced DDR in orchestrating growth and stress adaptation in plants.

Docosahexaenoic and Eicosapentaenoic Acids Promote the Accumulation of Browning-Related Myokines via Calcium Signaling in Insulin-Resistant Mice.

BACKGROUND: Myokines have a prominent effect on improving insulin resistance (IR) by inducing browning of white adipose tissue (WAT). Although docosahexaenoic acids (DHA) and eicosapentaenoic acids (EPA) play roles in improving IR and stimulating browning, whether they mediate myokines directly remains unknown. OBJECTIVE: This study aims to investigate the effects of DHA and EPA on browning-related myokines under IR and clarify the mechanism via Ca2+ signaling. METHODS: The expression and secretion levels of myokines in IR mice and IR myotubes were detected after DHA/EPA treatment. The crosstalk between myotubes and adipocytes was evaluated through a method in which IR adipocytes were treated with the culture medium supernatant of myotubes treated with DHA/EPA. The expression of browning markers in the WAT of IR mice and adipocytes was determined. A calcium chelator was used to determine whether DHA and EPA regulate myokine production through a calcium ion-dependent pathway. RESULTS: In vivo experiments: 3:1 and 1:3 DHA/EPA promoted the mRNA levels of Irisin, IL-6, IL-15, and FGF21 in skeletal muscle, stimulated WAT browning, reduced lipid accumulation; 3:1 DHA/EPA upregulated the serum concentration of Irisin; 1:3 DHA/EPA upregulated the serum concentrations of Irisin, IL-6, and FGF21. In vitro experiments: the levels of Irisin and IL-6 in C2C12 myotubes and their medium supernatant were significantly elevated in the 3:1 and 1:3 groups and the upregulation of browning markers and reduction in fat accumulation were observed in adipocytes treated with the medium supernatant of C2C12 myotubes in the 3:1 and 1:3 groups. However, the above phenomena disappeared when Ca2+ signaling was inhibited. CONCLUSIONS: Treatment with DHA and EPA at composition ratios of 3:1 and 1:3 induces browning of WAT in IR mice, which is likely related to the promotion of the accumulation of myokines, especially Irisin and IL-6, via Ca2+ signaling.

Application of CMV-IVIg as prophylaxis against cytomegalovirus reactivation in allogeneic hematopoietic stem cell transplantation patients.

Cytomegalovirus (CMV) reactivation remains one of the major and life-threatening complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Yet, there is still a lack of safe and effective ways to prevent CMV reactivation in allo-HSCT patients. Here, we retrospectively analyzed a cohort of patients who underwent HSCT at our transplant center between 2018 and 2022 to evaluate the efficacy of prophylactic CMV-specific intravenous immunoglobulin (CMV-IVIg) against CMV reactivation. After Propensity Score Matching, the CMV reactivation rate was significantly decreased in the CMV-IVIg group (HR, 2.952; 95% CI,1.492-5.841; P = .002) compared with the control group. Additionally, the time duration of CMV reactivation (P = .001) and bacterial infection rate (P = .013) were significantly lower in the CMV-IVIg group. Moreover, prophylactic CMV-IVIg was more effective in CMV seropositive patients who received ATG as part of GVHD prevention (HR, 8.225; 95% CI,1.809-37.39; P = .006). In conclusion, CMV-IVIg is considered an effective and safe way to prevent CMV reactivation in HSCT recipients, which may be related to the acceleration of immune reconstitution in the early stage after transplantation.

A one-step process for multi-gradient wettability modification on a polymer surface.

The surface modification technique is applied in microfluidic devices to modify wettability and achieve different flow velocities. Currently available methods for poly(dimethylsiloxane) (PDMS) surfaces may reliably induce wettability changes, but only one area can be altered at a time. This work introduces the controlled gradient oxygen plasma modification (CGPM) technique, which layers several resin masks with varying porosities on top of the PDMS surface. Selective wettability of the PDMS surface can be achieved by varying the oxygen plasma density above the modified material's surface by manipulation of the porosity value. Through the implementation of the COMSOL plasma module, the impact of the mask's porosity, through-hole size, distribution, and distance from the PDMS surface on wettability was studied. The suggested CGPM approach was characterized by contact angle measurements. During the 25-second CGPM procedure, the PDMS surface's contact angle continually changed from 8.77° to 76.98°. An integrated microfluidic device was created and manufactured to identify D-dimers to illustrate this method. In comparison with standard oxygen plasma treatment, the D-dimer assay was finished in 10 minutes and had a dynamic range of 1-1000 ng mL-1, with a peak fluorescence signal augmentation of 78.3% and an average fluorescence intensity enhancement of 31.1%.

Tuning the Metal-Support Interaction by Modulating CeO2 Oxygen Vacancies to Enhance the Toluene Oxidation Activity of Pt/CeO2 Catalysts.

In this research, a range of Pt/CeO2 catalysts featuring varying Pt-O-Ce bond contents were developed by modulating the oxygen vacancies of the CeO2 support for toluene abatement. The Pt/CeO2-HA catalyst generated a maximum quantity of Pt-O-Ce bonds (possessed the strongest metal-support interaction), as evidenced by the visible Raman results, which demonstrated outstanding toluene catalytic performance. Additionally, the UV Raman results revealed that the strong metal-support interaction stimulated a substantial increase in oxygen vacancies, which could facilitate the activation of gaseous oxygen to generate abundant reactive oxygen species accumulated on the Pt/CeO2-HA catalyst surface, a conclusion supported by the H2-TPR, XPS, and toluene-TPSR results. Furthermore, the results from quasi-in situ XPS, in situ DRIFTS, and DFT indicated that the Pt/CeO2-HA catalyst with a strong metal-support interaction led to improved mobility of reactive oxygen species and lower oxygen activation energies, which could transfer a large number of activated reactive oxygen species to the reaction interface to participate in the toluene oxidation, resulting in the relatively superior catalytic performance. The approach of tuning the metal-support interaction of catalysts offers a promising avenue to develop highly active catalysts for toluene degradation.

Responses of composition and metabolism of microbial communities during the remediation of black and odorous water using bioaugmentation and aeration.

This study elucidated the effect patterns of aeration and bioaugmentation on indigenous microbial communities, metabolites, and metabolic pathways in the remediation of black and odorous water. This is crucial for the precise formulation and targeted development of effective microbial consortia, as well as for tracking and forecasting the bioremediation of black and odorous water. The results confirmed that combining bioaugmentation with aeration markedly enhanced the degradation of COD, NH4+-N, and TN and the conversion of Fe and Mn. Aeration significantly increased the relative abundance of Flavobacterium and Diaphorobacter, and the positive interbacterial interaction in the effective microbial consortia EM31 gave the constituent strain Klebsiella and Bacillus a dominant niche in the bioaugmentation. Furthermore, bioaugmentation improved the capacity of the indigenous microbial consortia to utilize basic carbon source, particularly the utilization of L-glycerol, I-erythritol, glucose-1-phosphate, and the catabolism of cysteine and methionine. Moreover, during the remediation of black and odorous water by aeration and bioaugmentation, Glucosinolate biosynthesis (map00966), Steroid hormone biosynthesis (map00140), Folate biosynthesis (map00790), One carbon pool by folate (map00670), and Tyrosine metabolism (map00350) were identified as key functional metabolic pathways in microbial communities.

Reading the mind in the eyes in patients with idiopathic REM sleep behavior disorder.

OBJECTIVES: Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is characterized by vocalizations, jerks, and motor behaviors during REM sleep, often associated with REM-related dream content, which is considered a prodromal stage of α-synucleinopathy. The results of the Reading the Mind in the Eyes (RME) reflecting affective Theory of Mind (ToM) are inconsistent in α-synucleinopathy. The present study tried to investigate the RME in patients with iRBD. METHODS: A total of 35 patients with iRBD and 26 healthy controls were included in the study. All participants were administered the RME and the cognitive assessments according to a standard procedure. The patients with iRBD were further divided into two groups (high or low RME) according to the scores of the RME (> 21, or ≤ 20). RESULTS: The patients with iRBD had worse scores on cognitive tests compared with healthy controls involving global cognitive screening, memory, and visuospatial abilities (p < 0.05), but the scores of the RME were similar between the two groups (20.83 ± 3.38, 20.58 ± 3.43) (p ˃ 0.05). Patients with low RME had more obvious cognitive impairments than healthy controls. After applying Bonferroni correction for multiple tests, the low REM group only performed worse on the Sum of trials 1 to 5 and delayed recall of the RAVLT compared with the healthy control group (p < 0.001, = 0.002). The RME correlated with the scores of cognitive tests involving executive function, attention, memory, and visuospatial function. CONCLUSIONS: The changes in RME had a relationship with cognitive impairments, especially memory, in patients with iRBD.

Occupational noise and hypertension in Southern Chinese workers: a large occupational population-based study.

INTRODUCTION: An increasing number of original studies suggested that occupational noise exposure might be associated with the risk of hypertension, but the results remain inconsistent and inconclusive. In addition, the attributable fraction (AF) of occupational noise exposure has not been well quantified. We aimed to conduct a large-scale occupational population-based study to comprehensively investigate the relationship between occupational noise exposure and blood pressure and different hypertension subtypes and to estimate the AF for hypertension burden attributable to occupational noise exposure. METHODS: A total of 715,135 workers aged 18-60 years were included in this study based on the Key Occupational Diseases Surveillance Project of Guangdong in 2020. Multiple linear regression was performed to explore the relationships of occupational noise exposure status, the combination of occupational noise exposure and binaural high frequency threshold on average (BHFTA) with systolic and diastolic blood pressure (SBP, DBP). Multivariable logistic regression was used to examine the relationshipassociation between occupational noise exposure status, occupational noise exposure combined with BHFTA and hypertension. Furthermore, the attributable risk (AR) was calculated to estimate the hypertension burden attributed to occupational exposure to noise. RESULTS: The prevalence of hypertension among occupational noise-exposed participants was 13·7%. SBP and DBP were both significantly associated with the occupational noise exposure status and classification of occupational noise exposure combined with BHFTA in the crude and adjusted models (all P < 0·0001). Compared with workers without occupational noise exposure, the risk of hypertension was 50% greater among those exposed to occupational noise in the adjusted model (95% CI 1·42-1·58). For participants of occupational noise exposed with BHFTA normal, and occupational noise exposed with BHFTA elevated, the corresponding risks of hypertension were 48% (1·41-1·56) and 56% (1·46-1·63) greater than those of occupational noise non-exposed with BHFTA normal, respectively. A similar association was found in isolated systolic hypertension (ISH) and prehypertension. Subgroup analysis by sex and age showed that the positive associations between occupational noise exposure and hypertension remained statistically significant across all subgroups (all P < 0.001). Significant interactions between occupational noise status, classification of occupational noise exposure combined with BHFTA, and age in relation to hypertension risk were identified (all P for interaction < 0.001). The associations of occupational noise status, classification of occupational noise exposure combined with BHFTA and hypertension were most pronounced in the 18-29 age groups. The AR% of occupational noise exposure for hypertension was 28·05% in the final adjusted model. CONCLUSIONS: Occupational noise exposure was positively associated with blood pressure levels and the prevalence of hypertension, ISH, and prehypertension in a large occupational population-based study. A significantly increased risk of hypertension was found even in individuals with normal BHFTA exposed to occupational noise, with a further elevated risk observed in those with elevated BHFTA. Our findings provide epidemiological evidence for key groups associated with occupational noise exposure and hypertension, and more than one-fourth of hypertension cases would have been prevented by avoiding occupational noise exposure.

A phylogenomic analysis of Limosilactobacillus reuteri reveals ancient and stable evolutionary relationships with rodents and birds and zoonotic transmission to humans.

BACKGROUND: Gut microbes play crucial roles in the development and health of their animal hosts. However, the evolutionary relationships of gut microbes with vertebrate hosts, and the consequences that arise for the ecology and lifestyle of the microbes are still insufficiently understood. Specifically, the mechanisms by which strain-level diversity evolved, the degree by which lineages remain stably associated with hosts, and how their evolutionary history influences their ecological performance remain a critical gap in our understanding of vertebrate-microbe symbiosis. RESULTS: This study presents the characterization of an extended collection of strains of Limosilactobacillus reuteri and closely related species from a wide variety of hosts by phylogenomic and comparative genomic analyses combined with colonization experiments in mice to gain insight into the long-term evolutionary relationship of a bacterial symbiont with vertebrates. The phylogenetic analysis of L. reuteri revealed early-branching lineages that primarily consist of isolates from rodents (four lineages) and birds (one lineage), while lineages dominated by strains from herbivores, humans, pigs, and primates arose more recently and were less host specific. Strains from rodent lineages, despite their phylogenetic divergence, showed tight clustering in gene-content-based analyses. These L. reuteri strains but not those ones from non-rodent lineages efficiently colonize the forestomach epithelium of germ-free mice. The findings support a long-term evolutionary relationships of L. reuteri lineages with rodents and a stable host switch to birds. Associations of L. reuteri with other host species are likely more dynamic and transient. Interestingly, human isolates of L. reuteri cluster phylogenetically closely with strains from domesticated animals, such as chickens and herbivores, suggesting zoonotic transmissions. CONCLUSIONS: Overall, this study demonstrates that the evolutionary relationship of a vertebrate gut symbiont can be stable in particular hosts over time scales that allow major adaptations and specialization, but also emphasizes the diversity of symbiont lifestyles even within a single bacterial species. For L. reuteri, symbiont lifestyles ranged from autochthonous, likely based on vertical transmission and stably aligned to rodents and birds over evolutionary time, to allochthonous possibly reliant on zoonotic transmission in humans. Such information contributes to our ability to use these microbes in microbial-based therapeutics.

BODIPY-Based NO Probe for Macrophage-Targeted Immunotherapy Response Monitoring.

Precise and rapid detection of immune responses is critical for timely therapeutic regimen adjustment. Immunomodulation of tumor-associated macrophages (TAMs) from a protumorigenic phenotype (M2) to an antitumorigenic phenotype (M1) is crucial in macrophage-targeted immunotherapy. Herein, we developed a boron dipyrromethene (BODIPY)-based fluorescence probe BDP3 to detect the immune responses after immunotherapy by monitoring the nitric oxide (NO) released by M1 TAMs. With an aromatic primary monoamine structure and a p-methoxyanilin electron donor in the meso-position, BDP3 not only specifically activates stable and sensitive fluorescence by NO via a photoinduced electron transfer (PET) process but also achieves a long emission wavelength for efficient in vitro and in vivo imaging. Such NO-induced fluorescence signals of BDP3 are validated to correlate well with the phenotypes of TAMs detected in macrophage cell lines and tumor tissues. The distinct sensing effects toward two types of clinically used immunotherapeutic drugs further confirm the ability of BDP3 for specific monitoring of the M1/M2 switch in response to the macrophage-targeted immunotherapy. By virtue of good biocompatibility and appropriate tumor retention time, BDP3 could be a potential fluorescent probe for noninvasive evaluation of the immunotherapeutic efficacy of macrophage-targeted immunotherapy in living animals.

Design, fabrication, and evaluation of a large-area hybrid solar simulator for remote sensing applications.

Solar irradiance variations have a direct effect on the accuracy and repeatability of identifying spectral signatures in the remote sensing field experiments. Solar simulators have been deployed to allow for testing under controlled and reproducible laboratory conditions. However, it is difficult and expensive to make a large-area solar simulation with the appropriate spectral content and spatial uniformity of irradiance. In this study, a hybrid solar simulator has been designed and constructed to provide large-area illumination for remote sensing simulation applications. A design method based on the two-phase genetic algorithm is proposed to improve the performance of the spectral match and spatial uniformity, which no longer relies on the traditional trial-and-error technique. The first phase is used to determine the most appropriate configuration of different lamps in order to represent the solar spectrum. The second phase is to accommodate an optimal placement of the multiple sources to achieve irradiance uniformity. Both numerical simulations and experiments were performed to verify the performances. The results showed that the solar simulator provided a good spectral match and spatial irradiance for simulating the variations in direct normal irradiance at different solar zenith angles. In addition, the modular design makes it possible to adjust irradiance on the target area without altering the spectral distribution. This work demonstrates the development and measurement of a hybrid solar simulator with a realizable optimal configuration of multiple lamps, and offers the prospect of a scalable, large-area solar simulation.

Self-powered Pt/a-Ga2O3/ITO vertical Schottky junction solar-blind photodetector with excellent detection performance.

Self-powered solar-blind photodetectors (PDs) are promising for military and civilian applications owing to convenient operation, easy preparation, and weak-light sensitivity. In the present study, the solar-blind deep-ultraviolet (DUV) photodetector based on amorphous Ga2O3 (a-Ga2O3) and with a simple vertical stack structure is proposed by applying the low-cost magnetron sputtering technology. By tuning the thickness of the amorphous Ga2O3 layer, the device exhibits excellent detection performance. Under 3 V reverse bias, the photodetector achieves a high responsivity of 671A/W, a high detectivity of 2.21 × 1015 Jones, and a fast response time of 27/11 ms. More extraordinary, with the help of the built-in electric field at the interface, the device achieves an excellent performance in detection when self-powered, with an ultrahigh responsivity of 3.69 A/W and a fast response time of 2.6/6.6 ms under 254 nm light illumination. These results demonstrate its superior performance to most of the self-powered Schottky junction UV photodetectors reported to date. Finally, the Pt/a-Ga2O3/ITO Schottky junction photodiode detector is verified as a good performer in imaging, indicating its applicability in such fields as artificial intelligence, machine vision, and solar-blind imaging.

LncRNA MEG3 alleviates interstitial cystitis in rats by upregulating Nrf2 and inhibiting the p38/NF-κB pathway.

PURPOSE: Interstitial cystitis (IC), a chronic pain syndrome characterized by urinary frequency, urgency, and bladder or pelvic floor pain, severely affects the quality of life of patients. The aim of this study was to investigate the role and mechanism of long noncoding RNA Maternally Expressed Gene3 (lncRNA MEG3) in IC. METHODS: An IC rat model was established by intraperitoneal injection of cyclophosphamide combined with bladder perfusion of fisetin and tumor necrosis factor-α (TNF-α) to mimic IC. An in vitro model was established using TNF-α-induced rat bladder epithelium cells. H&E staining was used to assess bladder tissue damage and ELISA was used to measure inflammatory cytokine levels. Western blot analysis was used to examine Nrf2, Bax, Bcl-2, cleaved caspase-3, p-p38, p38, p-NF-κB and NF-κB protein expression levels. RNA immunoprecipitation and RNA pull-down assays were used to examine the interaction between MEG3 and Nrf2. RESULTS: MEG3 levels were upregulated in IC tissues and bladder epithelial cells, whereas Nrf2 expression was found to be downregulated. Knockdown of MEG3 reduced bladder tissue injury, inflammation, oxidative stress and apoptosis. MEG3 was negatively correlated with Nrf2. Downregulation of MEG3 alleviated IC inflammation and injury by upregulating Nrf2 and inhibiting the p38/NF-κB pathway. CONCLUSION: Downregulation of MEG3 alleviated inflammation and injury in IC rats by upregulating Nrf2 and inhibiting the p38/NF-κB pathway.

Tunable Stress Relaxing Biomimetic Matrices: Hyaluronan/Hydroxyapatite Hybridization Mediates Assembly of Collagen Fibrils.

The alluring correlations of cellular behaviors with viscoelastic extracellular matrices have driven increasing endeavors directed toward the understanding of mechanical cues on cell growth and differentiation via preparing biomimetic scaffolds/gels with viscoelastic controllability. Indeed, systematic investigations, especially into calcium phosphate-containing biomimetics, are relatively rare. Here, oxidized hyaluronic acid/hydroxyapatite hybrids (OHAHs) were synthesized by hyaluronan-mediated biomimetic mineralization with confined ion diffusion and subsequent oxidization treatment. The collagen self-assembly was applied to fabricate tunable stress relaxing fibrillar matrices in the presence of OHAHs in which the incorporated hyaluronic acid with aldehyde groups acted to improve the component compatibility as well as to supplement the molecular interactions with the occurrence of a Schiff-base reaction. With the addition of varying OHAH contents, the self-assembly behavior of collagen was altered, and the obtained collagen-hybrid (CH) matrices presented a heterogeneous fibrillar structure interspersed with OHAHs, characterized by large fibrillar bundles coexisting with small fibrils. The OHAHs improved the hydrogel stability of pure collagen, and according to rheological and nanoindentation measurements, CH matrices also exhibited tunable stress relaxation rates, following an OHAH concentration-dependent fashion. The proliferation and spreading of MC3T3-E1 cells cultured onto such CH matrices were further found to increase with the stress relaxing rate of the matrices. The present study showed that the introduction of hydroxyapatite incorporated with active hyaluronic acid during collagen reconstitution was a simple and effective strategy to realize the preparation of tunable stress relaxing biomimetic matrices potentially used for further appraising the regulation of mechanical cues on cell behaviors.

Nest box entrance hole size can influence nest site selection and nest defence behaviour in Japanese tits.

Birds have the ability to assess the risk of predation in their environment and adjust their antipredation strategies based on this risk information. However, whether nest site selection has effect on subsequent nest defence behaviour has not been studied. In this study, we aimed to determine whether the Japanese tit (Parus minor) exhibits a nest-box hole size preference and whether the entrance hole sizes of nest boxes influence the nest defence behaviour of tits. We hung nest boxes with three different entrance hole sizes (diameters: 6.5 cm, 4.5 cm and 2.8 cm) in our study sites and investigated which nest boxes were occupied by tits. In addition, by using dummy-presentation experiments, we observed the nest defence behaviours of tits that nested in boxes with 2.8 cm and 4.5 cm entrance holes towards common chipmunks (Tamias sibiricus, a small nest predator able to enter these holes) and Eurasian red squirrels (Sciurus vulgaris, a large nest predator unable to enter the 2.8 cm entrance hole). The tits that bred in nest boxes with 2.8 cm entrance holes exhibited more intense nest defence responses to chipmunks than to squirrels. In contrast, the tits that bred in nest boxes with 4.5 cm entrance holes exhibited similar nest defence responses to chipmunks and squirrels. Additionally, Japanese tits that bred in nest boxes with 2.8 cm entrance holes exhibited more intense behavioural responses to chipmunks than those that bred in nest boxes with 4.5 cm entrance holes. Our results suggested that Japanese tits prefer to occupy nest boxes with small holes for breeding and that nest-box characteristics influenced their nest defence behaviour.

White matter hyperintensities in cognitive impairment with Lewy body disease: a multicentre study.

BACKGROUND AND PURPOSE: White matter hyperintensities (WMHs) are associated with cognitive deficits and worse clinical outcomes in dementia, but rare studies have been carried out of cognitive impairment in Lewy body disease (CI-LB) patients. The objective was to investigate the associations between WMHs and clinical manifestations in patients with CI-LB. METHODS: In this retrospective multicentre cohort study, 929 patients (486 with dementia with Lewy bodies [DLB], 262 with Parkinson's disease dementia [PDD], 74 with mild cognitive impairment [MCI] with Lewy bodies [MCI-LB] and 107 with Parkinson's disease with MCI [PD-MCI]) were analysed from 22 memory clinics between January 2018 and June 2022. Demographic and clinical data were collected by reviewing medical records. WMHs were semi-quantified according to the Fazekas method. Associations between WMHs and clinical manifestations were investigated by multivariate linear or logistic regression models. RESULTS: Dementia with Lewy bodies patients had the highest Fazekas scores compared with PDD, MCI-LB and PD-MCI. Multivariable regressions showed the Fazekas score was positively associated with the scores of Unified Parkinson's Disease Rating Scale Part III (p = 0.001), Hoehn-Yahn stage (p = 0.004) and total Neuropsychiatric Inventory (p = 0.001) in MCI-LB and PD-MCI patients. In patients with DLB and PDD, Fazekas scores were associated with the absence of rapid eye movement sleep behaviour disorder (p = 0.041) and scores of Unified Parkinson's Disease Rating Scale Part III (p < 0.001), Hoehn-Yahn stage (p < 0.001) and the Montreal Cognitive Assessment (p = 0.014). CONCLUSION: White matter hyperintensity burden of DLB was higher than for PDD, MCI-LB and PD-MCI. The greater WMH burden was significantly associated with poorer cognitive performance, worse motor function and more severe neuropsychiatric symptoms in CI-LB.

Idarubicin plus BuCy versus BuCy conditioning regimens for intermediate-risk acute myeloid leukemia in first complete remission undergoing auto-HSCT: An open-label, multicenter, randomized phase 3 trial.

We report a randomized prospective phase 3 study, designed to evaluate the efficacy and tolerability of idarubicin plus busulfan and cyclophosphamide (IDA-BuCy) versus BuCy in autologous hematopoietic stem-cell transplantation (auto-HSCT) for intermediate-risk acute myeloid leukemia (IR-AML) patients in first complete remission (CR1). One hundred and fifty-four patients were enrolled and randomized to receive IDA-BuCy (IDA 15 mg/m2/day on days -12 to -10, Bu 3.2 mg/kg/day on days -7 to -4, and Cy 60 mg/kg/day on days -3 to -2) or BuCy. The 2-year incidence of relapse was 15.6% and 19.5% in IDA-BuCy and BuCy groups (p = 0.482), respectively. There was no significant overall survival (OS) and disease-free survival (DFS) benefit for IR-AML patients receiving IDA-BuCy (2-year OS 81.8% in IDA-BuCy vs. 83.1% in BuCy, p = 0.798; 2-year DFS 76.6% in IDA-BuCy vs. 79.2% in BuCy, p = 0.693). Grade 3 or worse regimen-related toxicity (RRT) was reported for 22 (28.9%) of 76 and 9 (12.0%) of 75 patients in two groups (p = 0.015), respectively. AEs within 100 days with an outcome of death were reported for 4 (5.3%) and 0 patients in two groups. In conclusion, IDA-BuCy has higher RRT and similar anti-leukemic activity compared with BuCy in IR-AML patients in CR1 undergoing auto-HSCT. Thus, caution should be taken when choosing IDA-BuCy for IR-AML patients in CR1 with auto-HSCT. This trial is registered with ClinicalTrials.gov, NCT02671708, and is complete.

Costs of dementia with lewy bodies: A Chinese multicenter cross-sectional study.

INTRODUCTION: Dementia with Lewy bodies (DLB) significantly increases the economic burden on caregivers and society, but few studies have focused on the costs. This study aims to evaluate the current economic costs of DLB and its related factors. METHODS: A total of 193 patients diagnosed with probable DLB were consecutively enrolled from 6 memory clinics between August 2017 to July 2021. Data were collected from August to December of 2021, patients' per capita annual economic costs related to DLB in the year preceding the interview were evaluated, and factors related to the costs were assessed using regression analysis. RESULTS: Patients with DLB led to per capita annual total costs of US $21,378.3 in 2021, with direct medical costs, direct non-medical costs and indirect costs of US $3471.4, US $3946.4 and US $13,960.5, respectively, accounting for 16.2%, 18.5% and 65.3%, of total costs. Factors related to the costs of DLB showed that impairments in activities of daily living (ADL) and caregivers' subjective burden had a greater impact on the total, direct medical and indirect costs. CONCLUSION: The economic burden of DLB in China is huge, and indirect costs account for the largest proportion, serious impairment of the ADL and the subjective burden of caregivers, which possibly has a greater effect on costs. The substantial contributions made by family members and other unpaid caregivers of DLB should be fully recognized in strategic policy discussions and in case-level planning and assessments.