Single-Cell Sequencing of Peripheral Mononuclear Cells Reveals Distinct Immune Response Landscapes of COVID-19 and Influenza Patients.

The coronavirus disease 2019 (COVID-19) pandemic poses a current world-wide public health threat. However, little is known about its hallmarks compared to other infectious diseases. Here, we report the single-cell transcriptional landscape of longitudinally collected peripheral blood mononuclear cells (PBMCs) in both COVID-19- and influenza A virus (IAV)-infected patients. We observed increase of plasma cells in both COVID-19 and IAV patients and XIAP associated factor 1 (XAF1)-, tumor necrosis factor (TNF)-, and FAS-induced T cell apoptosis in COVID-19 patients. Further analyses revealed distinct signaling pathways activated in COVID-19 (STAT1 and IRF3) versus IAV (STAT3 and NFκB) patients and substantial differences in the expression of key factors. These factors include relatively increase of interleukin (IL)6R and IL6ST expression in COVID-19 patients but similarly increased IL-6 concentrations compared to IAV patients, supporting the clinical observations of increased proinflammatory cytokines in COVID-19 patients. Thus, we provide the landscape of PBMCs and unveil distinct immune response pathways in COVID-19 and IAV patients.

Distinct Effector B Cells Induced by Unregulated Toll-like Receptor 7 Contribute to Pathogenic Responses in Systemic Lupus Erythematosus.

Systemic Lupus Erythematosus (SLE) is characterized by B cells lacking IgD and CD27 (double negative; DN). We show that DN cell expansions reflected a subset of CXCR5- CD11c+ cells (DN2) representing pre-plasma cells (PC). DN2 cells predominated in African-American patients with active disease and nephritis, anti-Smith and anti-RNA autoantibodies. They expressed a T-bet transcriptional network; increased Toll-like receptor-7 (TLR7); lacked the negative TLR regulator TRAF5; and were hyper-responsive to TLR7. DN2 cells shared with activated naive cells (aNAV), phenotypic and functional features, and similar transcriptomes. Their PC differentiation and autoantibody production was driven by TLR7 in an interleukin-21 (IL-21)-mediated fashion. An in vivo developmental link between aNAV, DN2 cells, and PC was demonstrated by clonal sharing. This study defines a distinct differentiation fate of autoreactive naive B cells into PC precursors with hyper-responsiveness to innate stimuli, as well as establishes prominence of extra-follicular B cell activation in SLE, and identifies therapeutic targets.

Allosteric regulation of nitrate transporter NRT via the signaling protein PII.

Coordinated carbon and nitrogen metabolism is crucial for bacteria living in the fluctuating environments. Intracellular carbon and nitrogen homeostasis is maintained by a sophisticated network, in which the widespread signaling protein PII acts as a major regulatory hub. In cyanobacteria, PII was proposed to regulate the nitrate uptake by an ABC (ATP-binding cassette)-type nitrate transporter NrtABCD, in which the nucleotide-binding domain of NrtC is fused with a C-terminal regulatory domain (CRD). Here, we solved three cryoelectron microscopy structures of NrtBCD, bound to nitrate, ATP, and PII, respectively. Structural and biochemical analyses enable us to identify the key residues that form a hydrophobic and a hydrophilic cavity along the substrate translocation channel. The core structure of PII, but not the canonical T-loop, binds to NrtC and stabilizes the CRD, making it visible in the complex structure, narrows the substrate translocation channel in NrtB, and ultimately locks NrtBCD at an inhibited inward-facing conformation. Based on these results and previous reports, we propose a putative transport cycle driven by NrtABCD, which is allosterically inhibited by PII in response to the cellular level of 2-oxoglutarate. Our findings provide a distinct regulatory mechanism of ABC transporter via asymmetrically binding to a signaling protein.

Mesophyll conductance limits photosynthesis in fluctuating light under combined drought and heat stresses.

Drought and heat stresses usually occur concomitantly in nature, with increasing frequency and intensity of both stresses expected due to climate change. The synergistic agricultural impacts of these compound climate extremes are much greater than those of the individual stresses. However, the mechanisms by which drought and heat stresses separately and concomitantly affect dynamic photosynthesis have not been thoroughly assessed. To elucidate this, we used tomato (Solanum lycopersicum) seedlings to measure dynamic photosynthesis under individual and compound stresses of drought and heat. Individual drought and heat stresses limited dynamic photosynthesis at the stages of diffusional conductance to CO2 and biochemistry, respectively. However, the primary limiting factor for photosynthesis shifted to mesophyll conductance under the compound stresses. Compared with the control, photosynthetic carbon gain in fluctuating light decreased by 38%, 73%, and 114% under the individual drought, heat, and compound stresses, respectively. Therefore, compound stresses caused a greater reduction in photosynthetic carbon gain in fluctuating light conditions than individual stress. These findings highlight the importance of mitigating the effects of compound climate extremes on crop productivity by targeting mesophyll conductance and improving dynamic photosynthesis.

Reduction of circulating IgE and allergens by a pH-sensitive antibody with enhanced FcγRIIb binding.

Allergen-crosslinked IgE triggers allergy by interacting with its receptor on basophils and mast cells. The anti-IgE monoclonal antibody omalizumab can alleviate allergy by competing with the receptor for IgE binding. However, along with neutralization, omalizumab also inhibits IgE degradation, which is clinically associated with high-dose and total IgE accumulation problems. In this study, we have developed an IgE-eliminating antibody on the basis of omalizumab, which has pH-dependent Fabs and an Fc with high affinity for FcγRIIb. In mice, the antibody rapidly eliminated total serum IgE to baseline levels and caused lower free IgE levels than omalizumab. At low dosages, the antibody also exhibited favorable IgE elimination effects. In addition, the antibody can degrade the corresponding allergen with the removal of IgE, addressing the allergy from its source. Introduction of the M252Y/S254T/T256E (YTE) mutation into this antibody prolongs its serum half-life without reducing potency. Thus, this engineered antibody holds a promising therapeutic option for allergy patients. Mechanistic insights are also included in this study.

Oteseconazole versus fluconazole for the treatment of severe vulvovaginal candidiasis: a multicenter, randomized, double-blinded, phase 3 trial.

Vulvovaginal candidiasis (VVC) is a common condition among women. Fluconazole remains the dominant treatment option for VVC. Oteseconazole is a highly selective inhibitor of fungal CYP51. This randomized, double-blinded, phase 3 trial was conducted to evaluate the efficacy and safety of oteseconazole compared with fluconazole in treating severe VVC. Female subjects presenting with vulvovaginal signs and symptoms score of ≥7 and positive Candida infection determined by potassium hydroxide test or Gram staining were randomly assigned to receive oteseconazole (600 mg on D1 and 450 mg on D2) or fluconazole (150 mg on D1 and D4) in a 1:1 ratio. The primary endpoint was the proportion of subjects achieving therapeutic cure [defined as achieving both clinical cure (absence of signs and symptoms of VVC) and mycological cure (negative culture of Candida species)] at D28. A total of 322 subjects were randomized and 321 subjects were treated. At D28, a statistically significantly higher proportion of subjects achieved therapeutic cure in the oteseconazole group than in the fluconazole group (66.88% vs 45.91%; P = 0.0002). Oteseconazole treatment resulted in an increased proportion of subjects achieving mycological cure (82.50% vs 59.12%; P < 0.0001) and clinical cure (71.25% vs 55.97%; P = 0.0046) compared with fluconazole. The incidence of treatment-emergent adverse events was similar between the two groups. No subjects discontinued study treatment or withdrew study due to adverse events. Oteseconazole showed statistically significant and clinically meaningful superiority over fluconazole for the treatment of severe VVC and was generally tolerated.

Well-Dispersed CsPbBr3@TiO2 Heterostructure Nanocrystals from Asymmetric to Symmetric.

Metal halide perovskites (MHPs) have undergone rapid development in the fields of solar cells, light diodes, lasing, photodetectors, etc. However, the MHPs still face significant challenges, such as poor stability and heterocompositing with other functional materials at the single nanoparticle level. Herein, the successful synthesis of well-dispersed CsPbBr3@TiO2 heterostructure nanocrystals (NCs) is reported, in which each heterostructure NC has only one CsPbBr3 with a precise anatase TiO2 coating ranging from asymmetric to symmetric. Due to the protection of anatase TiO2, CsPbBr3 shows dramatically improved chemical stability and photostability. More significantly, the synthesized CsPbBr3@TiO2 heterostructure NCs form a type II heterojunction, which strongly promoted efficient photogenerated carrier separation between anatase TiO2 and CsPbBr3, hence leading to improved optoelectronic activity. This study provides a robust avenue for synthesizing stable and highly efficient MHPs@metal oxide heterostructure NCs, paving the way for the practical application of all inorganic perovskites.

LAIR1 promotes hepatocellular carcinoma cell metastasis and induces M2-macrophage infiltration through activating AKT-IKKß-p65 axis.

LAIR1, a receptor found on immune cells, is capable of binding to collagen and is involved in immune-related diseases. However, the precise contribution of LAIR1 expressed on hepatocellular carcinoma (HCC) cells to tumor microenvironment is still unclear. In our study, bioinformatics analysis and immunofluorescence were employed to study the correlation between LAIR1 levels and clinical indicators. Transwell and scratch tests were used to evaluate how LAIR1 affected the migration and invasion of HCC cells. The chemotactic capacity and alternative activation of macrophages were investigated using RT-qPCR, transwell, and immunofluorescence. To investigate the molecular mechanisms, transcriptome sequencing analysis, Western blot, nucleus/cytoplasm fractionation, ELISA, and cytokine microarray were employed. We revealed a significant correlation between the presence of LAIR1 and an unfavorable outcome in HCC. We indicated that LAIR1 promoted migration and invasion of HCC cells through the AKT-IKKß-p65 axis. Additionally, the alternative activation and infiltration of tumor-associated macrophages induced by LAIR1 were reliant on the upregulation of IL6 and CCL5 within this axis, respectively. In conclusion, blocking LAIR1 was found to be an effective approach in combating the cancerous advancement of HCC.

Multi-omics analysis reveals a feedback loop amplifying immune responses in acute graft-versus-host disease due to imbalanced gut microbiota and bile acid metabolism.

Acute graft-versus-host disease (aGVHD) is primarily driven by allogeneic donor T cells associated with an altered composition of the host gut microbiome and its metabolites. The severity of aGVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is not solely determined by the host and donor characteristics; however, the underlying mechanisms remain unclear. Using single-cell RNA sequencing, we decoded the immune cell atlas of 12 patients who underwent allo-HSCT: six with aGVHD and six with non-aGVHD. We performed a fecal microbiota (16SrRNA sequencing) analysis to investigate the fecal bacterial composition of 82 patients: 30 with aGVHD and 52 with non-aGVHD. Fecal samples from these patients were analyzed for bile acid metabolism. Through multi-omic analysis, we identified a feedback loop involving "immune cell-gut microbes-bile acid metabolites" contributing to heightened immune responses in patients with aGVHD. The dysbiosis of the gut microbiota and disruption of bile acid metabolism contributed to an exaggerated interleukin-1 mediated immune response. Our findings suggest that resistin and defensins are crucial in mitigating against aGVHD. Therefore, a comprehensive multi-omic atlas incorporating immune cells, gut microbes, and bile acid metabolites was developed in this study and used to propose novel, non-immunosuppressive approaches to prevent aGVHD.

The SUMO E3 ligase activity of ORF45 determines KSHV lytic replication.

RSK1, an essential cellular kinase for Kaposi's sarcoma-associated herpesvirus (KSHV) replication, is highly phosphorylated and SUMOylated during KSHV lytic cycle, which determine the substrate phosphorylation and specificity of RSK1, respectively. However, the SUMO E3 ligase responsible for attaching SUMO to RSK1 has not yet been identified. By genome-wide screening, we found that KSHV ORF45 is necessary and sufficient to enhance RSK1 SUMOylation. Mechanistically, KSHV ORF45 binds to SUMOs via two classic SUMO-interacting motifs (SIMs) and functions as a SIM-dependent SUMO E3 ligase for RSK1. Mutations on these ORF45 SIMs resulted in much lower lytic gene expressions, viral DNA replication, and mature progeny virus production. Interestingly, KSHV ORF45 controls RSK1 SUMOylation and phosphorylation via two separated functional regions: SIMs and amino acid 17-90, respectively, which do not affect each other. Similar to KSHV ORF45, ORF45 of Rhesus Macaque Rhadinovirus has only one SIM and also increases RSK1 SUMOylation in a SIM-dependent manner, while other ORF45 homologues do not have this function. Our work characterized ORF45 as a novel virus encoded SUMO E3 ligase, which is required for ORF45-RSK1 axis-mediated KSHV lytic gene expression.

Gender Differences in the Prevalence and Clinical Correlates of Metabolic Syndrome in First-Episode and Drug-Naïve Patients With Major Depressive Disorder.

OBJECTIVE: Major depressive disorder (MDD) is a severe psychiatric symptom worldwide, and the coexistence of MDD with metabolic syndrome (MetS) is common in clinical practice. However, gender differences in comorbid MetS in first-episode and drug-naïve (FEDN) MDD patients have not been reported. Here, we explored potential gender differences in the prevalence and clinical correlates of comorbid MetS in FEDN MDD patients. METHODS: A cross-sectional study of 1718 FEDN MDD patients was conducted. Demographic and clinical data were collected. The Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale, and Positive and Negative Syndrome Scale positive subscale were used to evaluate depression, anxiety, and psychotic symptoms, respectively. RESULTS: The prevalence of MetS was 1.645-fold higher in female MDD patients (38.50%) than in male patients (26.53%). Patients with MetS had higher HAMD score, Hamilton Anxiety Scale score, and Positive and Negative Syndrome Scale positive subscale score than patients without MetS (p values < .001). Furthermore, suicide attempts (male: odds ratio [OR] = 1.706, p = .034; female: OR = 1.639, p = .004) and HAMD score (male: OR = 1.251, p < .001; female: OR = 1.148, p < .001) were independently associated with MetS in male and female patients, whereas age of onset was independently associated with MetS only in female patients (OR = 1.744, p = .047). CONCLUSIONS: Our findings suggest significant gender differences in the prevalence and clinical correlates of comorbid MetS in FEDN MDD patients. Clinical variables (suicide attempts and HAMD scores) may be independently associated with MetS in MDD patients.

Optimizing CAR-T cell Culture: Differential effects of IL-2, IL-12, and IL-21 on CAR-T cells.

BACKGROUND: Chimeric antigen receptor (CAR)-T therapy has demonstrated sustained clinical remission in numerous hematologic malignancies and has expanded to encompass solid tumors and autoimmune diseases. While progress is being made in establishing optimal culture conditions for CAR-T cells, the identification of the most effective cytokine for promoting their persistence in vitro remains elusive. METHODS: Here, we employed scRNA-seq (single-cell RNA sequencing) analysis to investigate the potential alterations in biological processes within CAR-T cells following exposure to cytokines (IL-2, IL-12, and IL-21) and antigens. Transcriptomic changes in diverse CAR-T groups were compared following various treatments, with a focus on epigenetic modifications, metabolic shifts, cellular senescence, and exhaustion. RESULTS: Our study reveals that CAR-T cells treated with antigen, IL-2, and IL-12 exhibit signs of exhaustion and senescence, whereas those treated with IL-21 do not display these characteristics. The activities of glycolysis and epigenetic changes were significantly increased by treatments with antigens, IL-2, and IL-12, while IL-21 treatment maintained the oxidative phosphorylation (OXPHOS) of CAR-T cells. CONCLUSIONS: Our findings suggest that IL-21 may play a role in preventing senescence and could be utilized in combination with other strategies, such as IL-2 and IL-12, for CAR-T culture.

Wide field-of-view laser-based white light transmitter for visible light communications.

The advancement demands of high-speed wireless data link ask for higher requirements on visible light communication (VLC), where wide coverage stands as a critical criterion. Here, we present the design and implementation of a transmitter structure capable of emitting a high-power wide-coverage white light laser. This laser source exhibits excellent stability, with an irradiation range extending to a half-angle of 20°. Its high brightness satisfies the needs of indoor illumination while maintaining excellent communication performance. Utilizing bit-loading discrete multi-tone modulation, a peak data transmission rate of 3.24 Gbps has been achieved, spanning 1 to 5 m. Remarkably, the data rates exceed 2.5 Gbps within a 40° range at a distance of 5 m, enabling a long-distance, wide coverage, high-speed VLC link for future mobile network applications.

Efficacy and safety of oral ibrexafungerp in Chinese patients with vulvovaginal candidiasis: a phase III, randomized, double-blind study.

PURPOSE: To evaluate the efficacy and safety of oral ibrexafungerp (HS-10366) versus placebo in Chinese patients with vulvovaginal candidiasis (VVC). METHODS: A double-blind, placebo-controlled, randomized, multicenter phase III study was conducted in symptomatic VVC patients. Patients received (2:1) twice-daily oral ibrexafungerp 300 mg or matching placebo for 1 day. The primary endpoint was clinical cure (vulvovaginal signs and symptoms [VSS] score = 0) at test-of-cure (TOC) on day 11 ± 3. The secondary endpoints included mycological eradication, overall response, and clinical improvement (VSS score ≤ 1) at TOC, and vulvovaginal symptom resolution at follow-up on day 25 ± 4. RESULTS: In total, 360 patients were included in the modified intention-to-treat set (defined as positive Candida cultured and receiving at least one study drug; 239 for ibrexafungerp, 121 for placebo). Compared with placebo, patients receiving ibrexafungerp had a significantly higher proportion of clinical cure (51.0% vs. 25.6%), mycological eradication (55.6% vs. 18.2%), overall response (33.9%, vs. 8.3%) at TOC and complete symptom resolution (74.5% vs. 39.7%, all P < 0.001) at follow-up. Subgroup analysis of clinical cure indicated that patients with C. albicans could benefit from ibrexafungerp over placebo. A similar benefit trend was also observed in those with non-albicans Candida by post-hoc analysis. Further analyses revealed similar efficacy of ibrexafungerp between patients with fluconazole non-susceptible C. albicans and fluconazole susceptible C. albicans regarding clinical cure and mycological eradication. Ibrexafungerp was generally well tolerated. Adverse events were primarily gastrointestinal and were mainly mild in severity. CONCLUSIONS: As a first-in-class antifungal agent, ibrexafungerp demonstrated promising efficacy and favorable safety for VVC treatment in Chinese patients. CHINADRUGTRIALS.ORG. CN REGISTRY NUMBER: CTR20220918.

Genotype selection identified elite lines through quantitative trait loci mapping of agronomically important traits in wheat.

Wheat is one of the most important staple foods in the world. Genetic characterization of wheat agronomically important traits is crucial for yield improvement through molecular breeding. In this study, a recombinant inbred line (RIL) population was developed by crossing a local adapted high yield variety Jimai 22 (JM22) with an external variety Cunmai no.1 (CM1). A high-density genetic map containing 7,359 single nucleotide polymorphism (SNP) markers was constructed. Quantitative trait loci (QTL) mapping identified 61 QTL for eight yield-related traits under six environments (years). Among them, 17 QTL affecting spike number per plant, grain number per spike and thousand grain weight showed high predictability for theoretical yield per plant (TYP), of which, 12 QTL alleles positively contributed to TYP. Nine promising candidate genes for seven of the 12 QTL were identified including three known wheat genes and six rice orthologs. Four elite lines with TYP increased by 5.6%-15.2% were identified through genotype selection which carried 7-9 favorable alleles from JM22 and 2-3 favorable alleles from CM1 of the 12 QTL. Moreover, the linked SNPs of the 12 QTL were converted to high-throughput kompetitive allele-specific PCR (KASP) markers and validated in the population. The mapped QTL, identified promising candidate genes, developed elite lines and KASP markers are highly valuable in future genotype selection to improve wheat yield. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01496-3.

Design, synthesis and antitumor activities of phthalazinone derivatives as PARP-1 inhibitors and PARP-1/HDAC-1 inhibitors.

In recent years, poly(ADP-ribose)polymerase-1 (PARP-1) and histone deacetylase (HDAC) have emerged as significant targets in tumor therapy, garnering widespread attention. In this study, we designed and synthesized two novel phthalazinone PARP-1 inhibitors and dual PARP-1/HDAC-1 inhibitors, named DLC-1-46 containing dithiocarboxylate fragments and DLC-47-63 containing hydroxamic acid fragments, and evaluated their inhibitory activities on enzymes and cells. Among the PARP-1 inhibitors, most compounds exhibited high inhibitory activity against the PARP-1 enzyme, with DLC-1-6 being particularly notable, showing IC50 values <0.2 nM. Notably, DLC-1 demonstrated significant anti-proliferative activity, with IC50 values for inhibiting the proliferation of MDA-MB-436, MDA-MB-231, and MCF-7 cells reaching 0.08, 26.39, and 1.01 µM, respectively. Further investigation revealed that DLC-1 arrested MDA-MB-231 cells in the G1 phase and induced apoptosis in a dose-dependent manner. Among the designed dual PARP-1/HDAC-1 inhibitors, several compounds exhibited potent dual-target inhibitory activity, with DLC-49 displaying IC50 values of 0.53 nM and 17 nM for PARP-1 and HDAC-1, respectively. DLC-50 demonstrated the most potent anti-proliferative activity, with IC50 values for inhibiting the proliferation of MDA-MB-436, MDA-MB-231, and MCF-7 cells at 0.30, 2.70, and 2.41 µM, respectively. Cell cycle arrest and apoptosis assays indicated that DLC-50 arrested the cell cycle in the G2 phase and induced apoptosis in HCT-116 cells. Our findings present a novel avenue for further exploration of PARP-1 inhibitors and dual PARP-1/HDAC-1 inhibitors.

Prevalence and risk factors for subclinical hypothyroidism in older patients with major depressive disorder.

BACKGROUND: Subclinical hypothyroidism (SCH) is highly correlated with major depressive disorder (MDD). However, the prevalence and risk factors for SCH in older patients with MDD have rarely been reported in China. METHODS: This cross-sectional study included 266 older MDD patients with SCH was performed. Clinical and anthropometric, biochemical, and thyroid function data were collected. Depression, anxiety, and psychotic symptoms were assessed using the Hamilton Depression Scale, the Hamilton Anxiety Scale, and the Positive and Negative Syndrome Scale positive subscale, respectively. RESULTS: Among older patients with MDD, the prevalence of SCH was 64.7% (172/266). Compared to patients without SCH, older MDD patients with SCH had a longer disease course and higher TSH, A-TG, A-TPO, HDL-C, LDL-C, TC, FPG, and systolic pressure levels (all P ≤ 0.002). Furthermore, disease progression (OR 1.082, 95% CI 1.020-1.147, P = 0.009), A-TG (OR 1.005, 95% CI 1.001-1.009, P = 0.017), TC (OR 2.024, 95% CI 1.213-3.377, P = 0.007), FPG (OR 2.916, 95% CI 1.637-5.194, P < 0.001), systolic pressure (OR 1.053, 95% CI 1.008-1.100, P = 0.022) were independently associated with SCH, in older patients with MDD. CONCLUSIONS: Our findings suggest a high prevalence of SCH in older patients with MDD. Several demographic and clinical variables were independently associated with SCH in older patients with MDD.

Effect of Baduanjin exercise on executive function in older adults with cognitive frailty: A randomized controlled trial.

OBJECTIVE: To investigate the effectiveness of Baduanjin exercise on executive function in community-dwelling older adults with cognitive frailty. DESIGN: Randomized controlled trial. SETTING: Community residential centers. SUBJECTS: 120 eligible older adults. INTERVENTIONS: Baduanjin training group received supervised Baduanjin training, 60 min sessions three times per week for 24 weeks. The control group did not receive any exercise intervention. MAIN MEASURES: Primary outcome was executive function, assessed using Clock Drawing Test. Secondary outcomes included the subcomponents of executive function (working memory, inhibitory control and cognitive flexibility), attention and cognitive frailty (global cognitive function, physical frailty) assessed using Verbal Fluency Test, Trail Making Test-A/B, Stroop Test, Montreal Cognitive Assessment and Edmonton Frailty Scale, respectively, at baseline and 24 weeks after intervention. RESULTS: After the 24-week intervention, the scores of Clock Drawing Test and Verbal Fluency Test, the Trail Making Test-B time and the Card correct numbers of Stroop Test in Baduanjin training group showed significant improvement compared with control group (all P < 0.05) with small to moderate effect sizes and the significant interaction effect of group by time in the Clock Drawing Test and Trail Making Test-B test (P = 0.003 and P = 0.043); cognitive frailty variables, including Montreal Cognitive Assessment and Edmonton Frail Scale scores, also showed significant improvement (P = 0.002 and P = 0.004) with a moderate effect sizes and a significant interaction effect (P < 0.001, P = 0.013). No adverse events were reported. CONCLUSION: Regular Baduanjin training may be an effective and safe intervention to improve cognitive frailty and executive function in community-dwelling older adults with cognitive frailty. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2100050857. Data of registration: 8/5/2020, https://www.chictr.org.cn/showproj.html?proj = 133037.

A W-Shaped Self-Supervised Computational Ghost Imaging Restoration Method for Occluded Targets.

We developed a novel method based on self-supervised learning to improve the ghost imaging of occluded objects. In particular, we introduced a W-shaped neural network to preprocess the input image and enhance the overall quality and efficiency of the reconstruction method. We verified the superiority of our W-shaped self-supervised computational ghost imaging (WSCGI) method through numerical simulations and experimental validations. Our results underscore the potential of self-supervised learning in advancing ghost imaging.