Sugarcane streak mosaic virus P1 protein inhibits unfolded protein response through direct suppression of bZIP60U splicing.

The unfolded protein response (UPR) is a cell-designated strategy that maintains the balance of protein folding in the endoplasmic reticulum (ER). UPR features a network of signal transduction pathways that reprogram the transcription, mRNA translation, and protein post-translational modification to relieve the ER stresses from unfolded/misfolded proteins. Infection with plant viruses can induce the UPR, and activated UPR often promotes plant viral infections in turn. However, the mechanism used by plant viruses to balance UPR and achieve robust infection remain largely unknown. In this study, P1SCSMV was identified as a virus-encoded RNA silencing suppressor (VSR). Heterologous overexpression of P1SCSMV via potato virus X (PVX) was found lead to programmed cell death (PCD) in Nicotiana benthamiana. Furthermore, P1SCSMV was also found to inhibit the PVX infection-triggered UPR by downregulating UPR-related genes and directly induced the distortion and collapse of the ER polygonal meshes on PVX-P1SCSMV infected N. benthamiana. Moreover, self-interaction, VSR activity, UPR inhibition, and cell death phenotype of P1SCSMV were also found to be dependent on its bipartite nuclear localization signal (NLS) (251RKRKLFPRIPLK262). P1SCSMV was found to directly bind to the stem-loop region of NbbZIP60U via its NLS and inhibit the UPR pathways, ultimately resulting in a PCD phenotype in PVX-P1SCSMV infected N. benthamiana leaves. This study also revealed the balancing role of potyviruses encoded P1SCSMV in the UPR pathway to achieve robust viral infection. This may represent a novel virulence strategy for plant viruses.

Single-cell transcriptome analyses reveal disturbed decidual homoeostasis in obstetric antiphospholipid syndrome.

OBJECTIVES: Obstetric antiphospholipid syndrome (OAPS) is an autoimmune disease characterised by the presence of antiphospholipid antibodies in circulation and pathological pregnancy. However, the pathogenesis of OAPS remains unknown. We aimed to reveal cellular compositions and molecular features of decidual cells involved in the development of OAPS using single-cell RNA sequencing (scRNA-seq). METHODS: We performed unbiased scRNA-seq analysis on the first-trimester decidua from five OAPS patients and five healthy controls (HCs), followed by validations with flow cytometry, immunohistochemical staining and immunofluorescence in a larger cohort. Serum chemokines and cytokines were measured by using ELISA. RESULTS: A higher ratio of macrophages but a lower ratio of decidual natural killer (dNK) cells was found in decidua from OAPS compared with HCs. Vascular endothelial cells shrinked in OAPS decidua while having upregulated chemokine expression and conspicuous responses to IFN-γ and TNF-α. Macrophages in OAPS had stronger phagocytosis function, complement activation signals and relied more on glycolysis. dNK cells were more activated in OAPS and had enhanced cytotoxicity and IFN-γ production. Downregulation of granules in OAPS dNK cells could be associated with suppressed glycolysis. Moreover, stromal cells had a prosenescent state with weakened immune surveillance for senescent cells in OAPS. In addition, the cellular interactions between decidual immune cells and those of immune cells with non-immune cells under disease state were altered, especially through chemokines, IFN-γ and TNF-α. CONCLUSION: This study provided a comprehensive decidual cell landscape and identified aberrant decidual microenvironment in OAPS, providing some potential therapeutic targets for this disease.

Dual-Mode Patterns Enabled by Photofluidization of an Azobenzene-Containing Linear Liquid Crystal Copolymer.

Creating dual-mode patterns in the same area of the material is an advanced method to increase the dimension of information storage, improve the level of encryption security, and promote the development of encoding technology. However, in situ, different patterns may lead to serious mutual interference in the process of manufacturing and usage. New materials and patterning techniques are essential for the advancement of noninterfering dual-mode patterns. Herein, noninterfering dual-mode patterns are demonstrated by combining the structural color and chromatic polarization, which is designed with an azobenzene-containing linear liquid crystal copolymer featuring a photofluidization effect. On the one hand, structural color patterns are imprinted via silicon templates with periodic microstructures after a UV-light-induced local transition of the polymer surface from a glassy to rubbery state. On the other hand, different polarization patterns based on the local photoinduced orientation of mesogens are created within the photofluidized region by the Weigert effect. Especially, the secondary imprinting is used to eliminate the partial damage to the structural color patterns during writing of the polarization patterns, thus obtaining dual-mode patterns without interference. This study provides a blueprint for the creation of advanced materials and sophisticated photopatterning techniques with potential cross-industry applications.

Associations between vaginal microbiota and endometrial polypoid lesions in women of reproductive age: a cross-sectional study.

RESEARCH QUESTION: What are the different characteristics of vaginal microbial composition between patients with endometrial polypoid lesions and controls? DESIGN: This cohort study compared the pre-operative microbial compositions of vaginal samples in a cohort of 703 women with endometrial polypoid lesions [293 and 410 women diagnosed and not diagnosed with polyps pathologically (polyps group and not-polyps group, respectively] and 703 women in the control group. Bacterial abundance, diversity, differential taxa and microbial network structure were assessed using 16S rRNA gene sequencing. Predictive algorithms were used to determine the functional pathways of vaginal microbiota within the cohort. RESULTS: The control group exhibited higher relative abundance of Lactobacillus crispatus in comparison with the polypoid lesions group (P = 0.0427). Beta diversity of vaginal microbiota differed significantly between the groups (P < 0.05). Comparing the polyps group with the not-polyps group, Leptotrichia spp. and Cutibacterium spp. were more abundant in the polyps group, and Fannyhessea spp., Acinetobacter spp. and Achromobacter spp. were more abundant in the not-polyps group. The control group exhibited higher abundance of Bifidobacterium spp., Achromobacter spp. and Escherichia/Shigella spp. (false discovery rate < 0.05). Furthermore, the polyps group and not-polyps group displayed more complex co-occurrence networks compared with the control group. CONCLUSIONS: The results of this study provide compelling evidence supporting associations between vaginal microbiota and endometrial polypoid lesions, highlighting the potential relationship between a well-balanced vaginal microbial ecosystem and a healthy intrauterine environment.

Rhizopus oryzae causes the leaf rot disease of Epimedium sagittatum in Guizhou, China.

Epimedium sagittatum is a collective term for herbaceous plants belonging to the family Berberidaceae. Their dried leaves and stems have significant therapeutic effects on tumor inhibition, hypertension control, and coronary heart disease (Ke et al. 2023; Zhao et al. 2019). In 2021 and 2022, plants with similar leaf rot symptoms ranging from 30% to 55% was observed on E. sagittatum in Congjiang County, Guizhou province. The initial symptoms of the disease manifest locally on the leaf, with yellowing on the surface edge of the affected tissue, browning in the middle part, and brown-white discoloration in the innermost part (Supplementary Figure S1B). As the disease progresses, the entire infected leaf gradually softens, while the veins remain intact (Supplementary Figure S1C). Ultimately, the leaf withers and dehisces. The nine samples with typical symptoms were collected from Congjiang County, Guizhou province (26.598°N, 106.707°E). Twenty-seven fungi were isolated, including ten isolates of Rhizopus and seventeen isolates of seven other genera. On isolate YYH-CJ-17 many sporangia were formed and turned to a brown-gray to black color on potato dextrose agar medium (PDA) after culturing 5 days under dark at 25 ℃ (Supplementary Figure S2A and S2B). The branches of mycelium were finger-shaped or root-shaped. The sporangium was spherical or nearly spherical, 60-250 µm in diameter, and sporangiospores were elliptical or spherical and 4-8 µm in diameter. The obtained 547 bp ITS fragment (accession OR225970) and 1231 bp EF-1α region (accession OR242258) from isolate YYH-CJ-17 were compared with NR database using the BLAST tool provided by NCBI, which revealed more than 99.5% identity (query cover more than 98%) with the sequences of ITS (accessions MF522822.1) and EF-1α (accession AB281541.1) of Rhizopus oryzae Went & H.C. Prinsen Geerlings (Gao et al. 2022; Zhang et al. 2022). The phylogenetic tree constructed with the ITS and EF-1α gene sequences demonstrates that strain YYH-CJ-17 clusters with R. oryzae in the same branch and the bootstrap value was greater than 99% (Supplementary Figure S3). Based on the morphological characteristics and ITS and EF-1a sequences, the isolate YYH-CJ-17 is identified as R. oryzae. Pathogenicity tests were performed on detached healthy leaves and living plants of E. sagittatum. Healthy leaves of E. sagittatum were subjected to inoculation with isolate YYH-CJ-17 with 5 × 105 CFU mL-1 concentration in sterile culture dishes. The progression of the disease was marked by the gradual softening of the infected leaves and the expansion of the lesions, which ultimately produced black-brown sporangium (Supplementary Figure S4A). Furthermore, the E. sagittatum living plants were sprayed with 5 × 105 CFU mL-1 conidial suspension of isolate YYH-CJ-17, with ddH2O as a negative control, and then were cultivated at 25℃ and 90% humidity for 21 days in the greenhouse. This assay found that the E. sagittatum leaves treated with isolate YYH-CJ-17 exhibited the same symptoms observed on plants in fields (Supplementary Figure S4B). The fungus re-isolated from the inoculated leaves were identified as R. oryzae by ITS sequencing and were blasted with NR database, which highest matched with the sequence of ITS (accessions MF522822.1) mentioned above, thus fulfilling Koch's postulates. R. oryzae has been identified as a causative agent of a diverse array of host diseases, including leaf mildew of tobacco, fruit rot of yellow oleander and pears, and soft rot of bananas (Farooq et al. 2017; Khokhar et al. 2019; Kwon et al. 2012; Pan et al. 2021). To the best of our knowledge, this is the first report of leaf rot on E. sagittatum caused by R. oryzae in China, which will provide clear prevention and management target for the leaf rot disease of E. sagittatum.

[Obstetric Antiphospholipid Syndrome: Insights on the Diagnosis, Treatment, and Hot Issues]. / 产科抗磷脂综合征的诊治原则与热点问题述评.

Obstetric antiphospholipid syndrome (OAPS) is an autoimmune disorder associated with various pathological pregnancies, such as recurrent miscarriage, stillbirth, severe pre-eclampsia and severe placental insufficiency. The persistent presence of antiphospholipid antibodies (aPLs) is the most important laboratory characteristic of OAPS. OAPS severely affects the reproductive health of women of childbearing age in China. Reports indicate that approximately 9.6% stillbirths, 11.5% severe pre-eclampsia, and 54% recurrent miscarriages are associated with OAPS or aPLs. However, the pathogenesis of OAPS remains unclear. Previously, thrombosis at the maternal-fetal interface (MFI) was considered the main mechanism of OAPS-related pathological pregnancies. Consequently, the use of low molecular weight heparin and aspirin throughout pregnancy was recommended to improve outcomes in OAPS patient. In recent years, many studies have found that thrombosis in MFI is uncommon, but various inflammatory factors are significantly increased in the MFI of OAPS patients. Based on these findings, some clinicians have started using anti-inflammatory treatments for OAPS, which have preliminarily improved the pregnancy outcomes. Nevertheless, there is no consensus on these second-line treatments of OAPS. Another troubling issue is the clinical diagnosis of OAPS. Similar to other autoimmune diseases, there are only classification criteria for OAPS, and clinical diagnosis of OAPS depends on the clinicians' experience. The present classification criteria of OAPS were established for clinical and basic research purposes, not for patient clinical management. In clinical practice, many patients with both positive aPLs and pathological pregnancy histories do not meet the strict OAPS criteria. This has led to widespread issues of incorrect diagnosis and treatment. Timely and accurate diagnosis of OAPS is crucial for effective treatment. In this article, we reviewed the epidemiological research progress on OAPS and summarized its classification principles, including: 1) the persistent presence of aPLs in circulation; 2) manifestations of OAPS, excluding other possible causes. For the first point, accurate assessment of aPLs is crucial; for the latter, previous studies regarded only placenta-related pregnancy complications as characteristic manifestations of OAPS. However, recent studies have indicated that adverse pregnancy outcomes related to trophoblast damage, such as recurrent miscarriage and stillbirth, also need to be considered in OAPS. We also discussed several key issues in the diagnosis and treatment of OAPS. First, we addressed the definition of non-standard OAPS and offered our opinion on defining non-standard OAPS within the framework of the 2023 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) APS criteria. Then, we discussed the advantages and disadvantages of different aPL testing methods, emphasizing that harmonizing results across platforms and establishing specific reference values are keys to resolving controversies in aPL testing results. We also introduced the application of non-criteria aPLs, especially anti-phosphatidylserine/prothrombin antibody (aPS/PT) and anti-ß2 glycoprotein Ⅰ domain Ⅰ antibody (aß2GPⅠDⅠ). Additionally, we discussed aPL-based OAPS risk classification strategies. Finally, we proposed potential treatment methods for refractory OAPS. The goal is to provide a reference for the clinical management of OAPS.

State-dependent and region-specific alterations of cerebellar connectivity across stable human wakefulness and NREM sleep states.

Sleep regulation and functioning may rely on systematic coordination throughout the whole brain, including the cerebellum. However, whether and how interactions between the cerebellum and other brain regions vary across sleep stages remain poorly understood. Here, using simultaneous EEG-fMRI recordings captured from 73 participants during wakefulness and non-rapid eye movement (NREM) sleep, we constructed cerebellar connectivity among intrinsic functional networks with intra-cerebellar, neocortical and subcortical regions. We uncovered that cerebellar connectivity exhibited sleep-dependent alterations: slight differences between wakefulness and N1/N2 sleep and greater changes in N3 sleep than other states. Region-specific cerebellar connectivity changes between N2 sleep and N3 sleep were also revealed: general breakdown of intra-cerebellar connectivity, enhancement of limbic-cerebellar connectivity and alterations of cerebellar connectivity with spatially specific neocortices. Further correlation analysis showed that functional connectivity between the cerebellar Control II network and regions (including the insula, hippocampus, and amygdala) correlated with delta power during N3 and beta power during N2 sleep. These findings systematically reveal altered cerebellar connectivity among intrinsic networks from wakefulness to deep sleep and highlight the potential role of the cerebellum in sleep regulation and functioning.

High-throughput precision MRI assessment with integrated stack-ensemble deep learning can enhance the preoperative prediction of prostate cancer Gleason grade.

BACKGROUND: To develop and test a Prostate Imaging Stratification Risk (PRISK) tool for precisely assessing the International Society of Urological Pathology Gleason grade (ISUP-GG) of prostate cancer (PCa). METHODS: This study included 1442 patients with prostate biopsy from two centres (training, n = 672; internal test, n = 231 and external test, n = 539). PRISK is designed to classify ISUP-GG 0 (benign), ISUP-GG 1, ISUP-GG 2, ISUP-GG 3 and ISUP GG 4/5. Clinical indicators and high-throughput MRI features of PCa were integrated and modelled with hybrid stacked-ensemble learning algorithms. RESULTS: PRISK achieved a macro area-under-curve of 0.783, 0.798 and 0.762 for the classification of ISUP-GGs in training, internal and external test data. Permitting error ±1 in grading ISUP-GGs, the overall accuracy of PRISK is nearly comparable to invasive biopsy (train: 85.1% vs 88.7%; internal test: 85.1% vs 90.4%; external test: 90.4% vs 94.2%). PSA ≥ 20 ng/ml (odds ratio [OR], 1.58; p = 0.001) and PRISK ≥ GG 3 (OR, 1.45; p = 0.005) were two independent predictors of biochemical recurrence (BCR)-free survival, with a C-index of 0.76 (95% CI, 0.73-0.79) for BCR-free survival prediction. CONCLUSIONS: PRISK might offer a potential alternative to non-invasively assess ISUP-GG of PCa.

Acetamide- or Formamide-Assisted In Situ Approach to Carbon-Rich or Nitrogen-Deficient Graphitic Carbon Nitride for Notably Enhanced Visible-Light Photocatalytic Redox Performance.

Acetamide- or formamide-assisted in situ strategy is designed to synthesize carbon atom self-doped g-C3 N4 (AHCNx ) or nitrogen vacancy-modified g-C3 N4 (FHCNx ). Different from the direct copolymerization route that suffers from the problem of mismatched physical properties of acetamide (or formamide) with urea, the synthesis of AHCNx (or FHCNx ) starts from a crucial preorganization step of acetamide (or formamide) with urea via freeze drying-hydrothermal treatment so that the chemical structures as well as C-doping level in AHCNx and N-vacancy concentration in FHCNx can be precisely regulated. By using various structural characterization methods, well-defined AHCNx and FHCNx structures are proposed. At the optimal C-doping level in AHCNx or N-vacancy concentration in FHCNx , both AHCNx and FHCNx exhibit remarkably improved visible-light photocatalytic performance in oxidation of emerging organic pollutants (acetaminophen and methylparaben) and reduction of proton to H2 in comparison of unmodified g-C3 N4 . Combination of the experimental results with theoretical calculations, it is confirmed that AHCNx and FHCNx show different charge separation and transfer mechanisms, while the enhanced visible-light harvesting capacity and the localized charge distributions on HOMO and LUMO are responsible for this excellent photocatalytic redox performance of AHCNx and FHCNx .

Association between Sleep Factors and Parkinson's Disease: A Prospective Study Based on 409,923 UK Biobank Participants.

INTRODUCTION: Limited evidence indicates an association between sleep factors and the risk of Parkinson's disease (PD). However, large prospective cohort studies including both sexes are needed to verify the association between daytime sleepiness, sleep duration, and PD risk. Furthermore, other sleep factors like chronotype and snoring and their impact on increased PD risk should be explored by simultaneously considering daytime sleepiness and snoring. METHODS: This study included 409,923 participants from the UK Biobank. Data on five sleep factors (chronotype, sleep duration, sleeplessness/insomnia, snoring, and daytime sleepiness) were collected using a standard self-administered questionnaire. PD occurrence was identified using linkages with primary care, hospital admission, death register, or self-report. Cox proportional hazard models were used to investigate the association between sleep factors and PD risk. Subgroup (age and sex) and sensitivity analyses were performed. RESULTS: During a median follow-up of 11.89 years, 2,158 incident PD cases were documented. The main association analysis showed that prolonged sleep duration (hazard ratio [HR]: 1.20, 95% confidence interval [CI]: 1.05, 1.37) and occasional daytime sleepiness (HR: 1.15, 95% CI: 1.04, 1.26) increased the PD risk. Compared to those who self-reported never or rarely having sleeplessness/insomnia, participants who reported usually having sleeplessness/insomnia had a decreased risk of PD (HR: 0.85, 95% CI: 0.75, 0.96). Subgroup analysis revealed that women who self-reported no snoring had a decreased PD risk (HR: 0.85; 95% CI: 0.73, 0.99). Sensitivity analyses indicated that the robustness of the results was affected by potential reverse causation and data completeness. CONCLUSION: Long sleep duration increased the PD risk, especially among men and participants ≥60 years, while snoring increased the risk of PD in women. Additional studies are needed to (i) further consider other sleep traits (e.g., rapid eye movement sleep behavior disorder and sleep apnea) that might be related to PD, (ii) objectively measure sleep-related exposure, and (iii) confirm the effects of snoring on PD risk by considering the impact of obstructive sleep apnea and investigating its underlying mechanisms.

Comparative analysis of the vaginal microbiome of healthy and polycystic ovary syndrome women: a large cross-sectional study.

RESEARCH QUESTION: What are the different features of the vaginal microbiome (VMB) between patients with polycystic ovary syndrome (PCOS) and healthy women? DESIGN: A cross-sectional study was conducted at a single academic university-affiliated centre. A total of 1446 participants were recruited (PCOS group, n =713, control group, n = 733). Vaginal swabs were analysed using 16S rRNA gene sequencing. The diversity and composition of the microbiome were compared between the PCOS group and the control group. Microbial interaction networks and functional prediction were investigated. RESULTS: The PCOS group had a higher alpha diversity than the control group (Shannon P = 0.03, Simpson P = 0.02), and higher intra-group variability was observed in PCOS group (P < 2.2E-16). At the genus level, the proportion of Lactobacillus decreased (85.1% versus 89.3%, false discovery rate [FDR] = 0.02), whereas the proportion of Gardnerella vaginalis and Ureaplasma increased in the PCOS group (5.1% versus 3.3%, FDR = 0.006; 1.2% versus 0.6%, FDR = 0.002, respectively). Lactobacillus acidophilus, Prevotella buccalis and G. vaginalis were identified as the main differential species. L. acidophilus was positively correlated with serum levels of anti-Müllerian hormone (AMH), and triglyceride (P = 2.01E-05, P = 0.004, respectively). P. buccalis was negatively correlated with serum levels of AMH and testosterone (P = 0.002, P = 0.003, respectively). G. vaginalis was positively correlated with serum levels of AMH, oestradiol and progesterone (P = 0.004, P = 0.005, P = 0.03, respectively). The VMB interaction network indicated that Lactobacillus crispus, Prevotella timonensis, and P. buccalis could be key drivers in the PCOS group. Overall, 55 predicted genes were found to be differentially abundant between PCOS and the control (FDRs < 0.25). CONCLUSIONS: The PCOS group had a higher diversity of vaginal microbiome and showed an enhanced level of heterogeneity. The proportion of Lactobacillus in the PCOS group decreased, whereas the proportions of Gardnerella and Ureaplasma increased. These results warrant further research that can validate the correlation between PCOS and VMB.

Neurodevelopmental effects of maternal folic acid supplementation: a systematic review and meta-analysis.

Folic acid, a water-soluble vitamin B nutrient, plays an important role not only in maintaining a healthy pregnancy but also in offspring brain development and function, however, it remains unclear whether maternal folic acid (FA) supplementation associated with the risk of different postnatal neurodevelopmental outcomes. Here, we performed a systematic review and meta-analysis on the impact of maternal FA supplementation on a wide range of postnatal neurodevelopmental outcomes which include intellectual development, risk of autistic traits, ADHD, behavior, language, and psychomotor problems, using studies extracted from the following databases, including MEDLINE, Web of Science, Cochrane Library, Scopus, EMBASE, and PsychInfo. Thirty-two cohort studies and seven case-control studies were included in this meta-analysis. In the present study, we found that prenatal FA supplementation had a positive impact on offspring's neurodevelopmental outcomes, including improved intellectual development and reduced risk of autism traits, ADHD, behavioral, and language problems. We also found that FA over-supplementation was not associated with an improvement in offspring's brain development, and may have a negative impact on offspring's neurodevelopmental outcomes. This study proved the first panoramic review on the relationship of FA supplementation with offspring's neurodevelopment. Further studies focusing on different dosages and periods of FA supplementation are needed.Supplemental data for this article is available online at https://doi.org/10.1080/10408398.2021.1993781 .

Three-dimensional liquid crystal polymer actuators assembled by athermal photo-welding.

Photodeformable liquid crystal polymers (LCPs) exhibit shape changes of different modes like bending, twisting, and oscillation, which depend on the orientation of liquid crystals. However, it is challenging to create a three-dimensional (3D) actuator with distinct actuation modes due to the difficulty of local orientation in a complex bulk architecture. Here we propose a strategy based on athermal photo-welding to integrate different orientations into a single flexible actuator by the photofluidization of azobenzene-containing linear LCPs. Stretch-induced uniaxial films are cut in different directions and subsequently welded via local photofluidization, during which the LCP transitions from a high-modulus glassy state to a rubbery state upon photoisomerization of azobenzene at room temperature. As a consequence, a cucumber vine-like structure with the opposite handedness and a lifting gripper are constructed by such a cut-and-weld process, demonstrating diverse deformation modes of winding, unwinding, and curling. This strategy provides an athermal process for the fabrication of seamless 3D flexible actuators without structural defects, which have potential applications in micromechanical systems, soft robotics, and artificial muscles.

Analysis of Hematological Indices and Splenectomy Rates in 2,130 Patients with Hemoglobin H Diseases or ß-Thalassemia.

INTRODUCTION: Splenomegaly and hypersplenism are common complications of thalassemia patients due to the excessive clearance of defective red blood cells from the spleen. To date, splenectomy has been considered one of the most effective treatments for splenomegaly, reducing clinical severity among thalassemia patients. Thus, we aim to investigate the differences in splenectomy rates and hematological indices among thalassemia patients with different genotypes. METHOD: In this study, we analyzed the clinical data of thalassemia in 2,130 patients admitted to the 923rd Hospital of the People's Liberation Army from January 2006 to December 2020, and the statistical software SPSS 26.0 was applied to analyze the data. RESULT: Of the 2,130 patients with thalassemia, 265 patients underwent splenectomy. It was determined that significantly more patients with hemoglobin H (HbH) disease, a form of α-thalassemia, have undergone splenectomy than ß-thalassemia patients (20% vs. 7%). Further, HbH disease patients were diagnosed at a significantly older age than ß-thalassemia patients. CONCLUSION: The greater probability of HbH disease patients undergoing splenectomy is likely influenced by multiple factors, including their lower dependency on transfusion, leading to high spleen compensatory stress on the spleen, and the destruction of defective erythrocytes. In contrast, ß-thalassemia is clinically more severe and less tolerant of hemoglobin fluctuations. Based on these findings, clinicians are suggested to pay more attention to HbH disease patients as many of them are still under-transfused, which could lead to chronic hemolysis and more severe hepatosplenomegaly. These results might offer insight for improving the clinical management of patients with different types of thalassemia.

Comparative effectiveness of non-pharmacological interventions for frailty: a systematic review and network meta-analysis.

BACKGROUND: Frailty endangers the health of older adults. Furthermore, the prevalence of frailty continues to increase as the global population ageing. OBJECTIVE: To update evidence on the effectiveness of non-pharmacological interventions for frailty by conducting a network meta-analysis (NMA) of randomised controlled trials (RCTs). METHODS: Eight databases were searched from January 1, 2000, until September 24, 2021. RCTs of interventions for frailty among participants aged ≥60 years were considered eligible. The primary outcome was frailty. Pairwise meta-analysis and NMA were performed, with the pooled standardised mean difference (SMD) and 95% confidence interval (CI) being reported. RESULTS: A total of 69 RCTs were included after screening 16,058 retrieved citations. There were seven types of interventions (11 interventions) for frailty among the included RCTs. Physical activity (PA) (pooled SMD = 0.43, 95% CI: 0.34-0.51), multicomponent intervention (pooled SMD = 0.34, 95% CI: 0.23-0.45) and nutrition intervention (pooled SMD = 0.21, 95% CI: 0.06-0.35) were associated with reducing frailty compared to control, of which PA was the most effective type of intervention. In terms of specific types of PA, resistance training (pooled SMD = 0.58, 95% CI: 0.33-0.83), mind-body exercise (pooled SMD = 0.57, 95% CI: 0.24-0.90), mixed physical training (pooled SMD = 0.47, 95% CI: 0.37-0.57) and aerobic training (pooled SMD = 0.36, 95% CI: 0.09-0.62) were associated with a reduction in frailty compared to usual care. Resistance training was the most effective PA intervention. CONCLUSION: Resistance training has the best potential to reduce frailty in older adults. This finding might be useful to clinicians in selecting interventions for older adults with frailty.

Content Quality of Web-Based Short-Form Videos for Fire and Burn Prevention in China: Content Analysis.

BACKGROUND: Web-based short-form videos are increasingly popular for disseminating fire and burn prevention information, but their content quality is unknown. OBJECTIVE: We aimed to systematically assess the characteristics, content quality, and public impact of web-based short-form videos offering primary and secondary (first aid) prevention recommendations for fires and burns in China between 2018 and 2021. METHODS: We retrieved short-form videos offering both primary and secondary (first aid) information to prevent fire and burn injuries published on the 3 most popular web-based short-form video platforms in China: TikTok, Kwai, and Bilibili. To assess video content quality, we calculated the proportion of short-form videos that included information on each of the 15 recommendations for burn prevention education from the World Health Organization (WHO; P1) and that correctly disseminated each recommendation (P2). High P1 and P2 indicated better content quality. To assess their public impact, we calculated the median (IQR) of 3 indicators: the number of comments, likes, and saves as a favorite by viewers. Chi-square test, trend chi-square test, and Kruskal-Wallis H test examined differences in indicators across the 3 platforms, years, content, and time duration of videos and between videos disseminating correct versus incorrect information. RESULTS: Overall, 1459 eligible short-form videos were included. The number of short-form videos increased by 16 times between 2018 and 2021. Of them, 93.97% (n=1371) were about secondary prevention (first aid) and 86.02% (n=1255) lasted <2 minutes. The proportion of short-form videos including each of the 15 WHO recommendations ranged from 0% to 77.86% (n=1136). Recommendations 8, 13, and 11 had the highest proportions (n=1136, 77.86%; n=827, 56.68%; and n=801, 54.9%, respectively), whereas recommendations 3 and 5 were never mentioned. Among the short-form videos that included the WHO recommendations, recommendations 1, 2, 4, 6, 9, and 12 were always disseminated correctly, but the other 9 recommendations were correctly disseminated in 59.11% (120/203) to 98.68% (1121/1136) of videos. The proportion of short-form videos including and correctly disseminating the WHO recommendations varied across platforms and years. The public impact of short videos varied greatly across videos, with a median (IQR) of 5 (0-34) comments, 62 (7-841) likes, and 4 (0-27) saves as a favorite. Short-form videos disseminating correct recommendations had larger public impact than those disseminating either partially correct or incorrect knowledge (median 5 vs 4 comments, 68 vs 51 likes, and 5 vs 3 saves as a favorite, respectively; all P<.05). CONCLUSIONS: Despite the rapid increase in the number of web-based short-form videos about fire and burn prevention available in China, their content quality and public impact were generally low. Systematic efforts are recommended to improve the content quality and public impact of short-form videos on injury prevention topics such as fire and burn prevention.

Enhancing CO2 Electroreduction Selectivity toward Multicarbon Products via Tuning the Local H2O/CO2 Molar Ratio.

Mass transfer plays an important role in controlling the surface coverage of reactants and the kinetics of surface reactions, thus significantly adjusting the catalytic performance. Herein, we reported that H2O diffusion was modulated by controlling the thicknesses of the carbon black (CB) layer between the gas diffusion electrode (GDE) of Cu and the electrolyte. As a consequence, the product distribution over the GDE of Cu was effectively regulated during CO2 electroreduction. Interestingly, a volcano-type relationship between the thickness of the CB layer and the faradaic efficiency (FE) for multicarbon (C2+) products was observed over the GDE of Cu. Especially, when the applied total current density was set as 800 mA cm-2, the FE for the C2+ products over the GDE of Cu coated by a CB layer with a thickness of 6.6 µm reached 63.2%, which was 2.8 times higher than that (16.8%) over the GDE of Cu without a CB layer.

Surface-Oxygen-Rich Bi@C Nanoparticles for High-Efficiency Electroreduction of CO2 to Formate.

The electrochemical CO2 reduction reaction (CO2RR) is a promising strategy to alleviate excessive CO2 levels in the atmosphere and produce value-added feedstocks and fuels. However, the synthesis of high-efficiency and robust electrocatalysts remains a great challenge. This work reports the green preparation of surface-oxygen-rich carbon-nanorod-supported bismuth nanoparticles (SOR Bi@C NPs) for an efficient CO2RR toward formate. The resultant SOR Bi@C NPs catalyst displays a Faradaic efficiency of more than 91% for formate generation over a wide potential range of 440 mV. Ex situ XPS and XANES and in situ Raman spectroscopy demonstrate that the Bi-O/Bi (110) structure in the pristine SOR Bi@C NPs can remain stable during the CO2RR process. DFT calculations reveal that the Bi-O/Bi (110) structure can facilitate the formation of the *OCHO intermediate. This work provides an approach to the development of high-efficiency Bi-based catalysts for the CO2RR and offers a unique insight into the exploration of advanced electrocatalysts.

[Analysis of TUBB4A gene variant in a patient with adolescent-onset hypomyelinating leukodystrophy with atrophy of basal ganglia and cerebellum].

OBJECTIVE: To explore the clinical characteristics and genetic etiology of a patient with adolescent-onset hypomyelinated leukodystrophy with atrophy of basal ganglia and cerebellum (H-ABC). METHODS: A patient who was diagnosed with H-ABC in March 2018 at the First Affiliated Hospital of Nanjing Medical University was selected as the study subject. Clinical data was collected. Peripheral venous blood samples of the patient and his parents were collected. The patient was subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. RESULTS: The patient, a 31-year-old male, had manifested with developmental retardation, cognitive decline and abnormal gait. WES revealed that he has harbored a heterozygous c.286G>A variant of the TUBB4A gene. Sanger sequencing confirmed that neither of his parents has carried the same variant. Analysis with SIFT online software indicated the amino acid encoded by this variant is highly conserved among various species. This variant has been recorded by the Human Gene Mutation Database (HGMD) with a low population frequency. The 3D structure constructed by PyMOL software showed that the variant has a harmful effect on the structure and function of the protein. According to the guidelines formulated by the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic. CONCLUSION: The c.286G>A (p.Gly96Arg) variant of the TUBB4A gene probably underlay the hypomyelinating leukodystrophy with atrophy of basal ganglia and cerebellum in this patient. Above finding has enriched the spectrum of TUBB4A gene variants and enabled early definitive diagnosis of this disorder.

A Heteromodal Word-Meaning Binding Site in the Visual Word Form Area under Top-Down Frontoparietal Control.

The integral capacity of human language together with semantic memory drives the linkage of words and their meaning, which theoretically is subject to cognitive control. However, it remains unknown whether, across different language modalities and input/output formats, there is a shared system in the human brain for word-meaning binding and how this system interacts with cognitive control. Here, we conducted a functional magnetic resonance imaging experiment based on a large cohort of subjects (50 females, 50 males) to comprehensively measure the brain responses evoked by semantic processing in spoken and written word comprehension and production tasks (listening, speaking, reading, and writing). We found that heteromodal word input and output tasks involved distributed brain regions within a frontal-parietal-temporal network and focally coactivated the anterior lateral visual word form area (VWFA), which is located in the basal occipitotemporal area. Directed connectivity analysis revealed that the VWFA was invariably under significant top-down modulation of the frontoparietal control network and interacts with regions related to attention and semantic representation. This study reveals that the VWFA is a key site subserving general semantic processes linking words and meaning, challenging the predominant emphasis on this area's specific role in reading or more general visual processes. Our findings also suggest that the dynamics between semantic memory and cognitive control mechanisms during word processing are largely independent of the modalities of input or output.SIGNIFICANCE STATEMENT Binding words and their meaning into a coherent whole during retrieval requires accessing semantic memory and cognitive control, allowing our thoughts to be expressed and comprehended through mind-external tokens in multiple modalities, such as written or spoken forms. However, it is still unknown whether multimodal language comprehension and production share a common word-meaning binding system in human brains and how this system is connected to a cognitive control mechanism. By systematically measuring brain activity evoked by spoken and written verbal input and output tasks tagging word-meaning binding processes, we demonstrate a general word-meaning binding site within the visual word form area (VWFA) and how this site is modulated by the frontal-parietal control network.