ErbB4 deficiency exacerbates olfactory dysfunction in an early-stage Alzheimer's disease mouse model.

Olfactory dysfunction is increasingly recognized as an early indicator of Alzheimer's disease (AD). Aberrations in GABAergic function and the excitatory/inhibitory (E/I) balance within the olfactory bulb (OB) have been implicated in olfactory impairment during the initial stages of AD. While the neuregulin 1 (NRG1)/ErbB4 signaling pathway is known to regulate GABAergic transmission in the brain and is associated with various neuropsychiatric disorders, its specific role in early AD-related olfactory impairment remains incompletely understood. This study demonstrated that olfactory dysfunction preceded cognitive decline in young adult APP/PS1 mice and was characterized by reduced levels of NRG1 and ErbB4 in the OB. Further investigation revealed that deletion of ErbB4 in parvalbumin interneurons reduced GABAergic transmission and increased hyperexcitability in mitral and tufted cells (M/Ts) in the OB, thereby accelerating olfactory dysfunction in young adult APP/PS1 mice. Additionally, ErbB4 deficiency was associated with increased accumulation of Aß and BACE1-mediated cleavage of APP, along with enhanced CDK5 signaling in the OB. NRG1 infusion into the OB was found to enhance GABAergic transmission in M/Ts and alleviate olfactory dysfunction in young adult APP/PS1 mice. These findings underscore the critical role of NRG1/ErbB4 signaling in regulating GABAergic transmission and E/I balance within the OB, contributing to olfactory impairment in young adult APP/PS1 mice, and provide novel insights for early intervention strategies in AD. This work has shown that ErbB4 deficiency increased the burden of Aß, impaired GABAergic transmission, and disrupted the E/I balance of mitral and tufted cells (M/Ts) in the OB, ultimately resulting in olfactory dysfunction in young adult APP/PS1 mice. NRG1 could enhance GABAergic transmission, rescue E/I imbalance in M/Ts, and alleviate olfactory dysfunction in young adult APP/PS1 mice. OB: olfactory bulb, E/I: excitation/inhibition, Pr: probability of release, PV: parvalbumin interneurons, Aß: ß-amyloid, GABA: gamma-aminobutyric acid.

Optimal extent of lymphadenectomy improves prognosis and guides adjuvant chemotherapy in esophageal cancer: A propensity score-matched analysis.

BACKGROUND: The optimal extent of lymphadenectomy in esophageal squamous cell carcinoma (ESCC) patients remained debatable. AIM: To explore the ideal number of cleared lymph nodes in ESCC patients undergoing upfront surgery. METHODS: In this retrospective, propensity score-matched study, we included 1042 ESCC patients who underwent esophagectomy from November 2008 and October 2019. Patients who underwent neoadjuvant therapy were excluded. We collected patients' clinicopathological features and information regarding lymph nodes, including the total number of resected lymph nodes (NRLN), and pathologically diagnosed positive lymph nodes (RPLN). SPSS and R software were used for statistical analysis. RESULTS: Among the included 1042 patients, two cohorts: ≤ 21 (n = 664) and > 21 NRLN (n = 378) were identified. The final prognostic model included four variables: T stage, N, venous thrombus, and the number of removed lymph nodes. Among them, NRLN > 21 was determined as an independent prognosticator after surgery for esophageal cancer (hazards regression = 0.66, 95% confidence interval: 0.50-0.87, P = 0.004). A nomogram was created based on the regression coefficients of the variables in the final model. In the training cohort, the predictive model displayed an uncorrected five-year overall survival C-index of 0.659, with a bootstrap-corrected C-index of 0.654. In the subgroup analysis, adjuvant chemotherapy was beneficial in the subgroup with NRLN > 21 and RPLN ≤ 0.16 and NRLN ≤ 21 and RPLN > 0.16. CONCLUSION: NRLN > 21 was an independent prognostic factor after ESCC surgery. The combination of NRLN and RPLN may provide a reference for adjuvant chemotherapy use in potential beneficiaries.

Landscape genomics reveals genetic signals of environmental adaptation of African wild eggplants.

Crop wild relatives (CWR) provide a valuable resource for improving crops. They possess desirable traits that confer resilience to various environmental stresses. To fully utilize crop wild relatives in breeding and conservation programs, it is important to understand the genetic basis of their adaptation. Landscape genomics associates environments with genomic variation and allows for examining the genetic basis of adaptation. Our study examined the differences in allele frequency of 15,416 single nucleotide polymorphisms (SNPs) generated through genotyping by sequencing approach among 153 accessions of 15 wild eggplant relatives and two cultivated species from Africa, the principal hotspot of these wild relatives. We also explored the correlation between these variations and the bioclimatic and soil conditions at their collection sites, providing a comprehensive understanding of the genetic signals of environmental adaptation in African wild eggplant. Redundancy analysis (RDA) results showed that the environmental variation explained 6% while the geographical distances among the collection sites explained 15% of the genomic variation in the eggplant wild relative populations when controlling for population structure. Our findings indicate that even though environmental factors are not the main driver of selection in eggplant wild relatives, it is influential in shaping the genomic variation over time. The selected environmental variables and candidate SNPs effectively revealed grouping patterns according to the environmental characteristics of sampling sites. Using four genotype-environment association methods, we detected 396 candidate SNPs (2.5% of the initial SNPs) associated with eight environmental factors. Some of these SNPs signal genes involved in pathways that help adapt to environmental stresses such as drought, heat, cold, salinity, pests, and diseases. These candidate SNPs will be useful for marker-assisted improvement and characterizing the germplasm of this crop for developing climate-resilient eggplant varieties. The study provides a model for applying landscape genomics to other crops' wild relatives.

Covalent Bonding of Salen Metal Complexes with Pyrene Chromophores to Porous Polymers for Photocatalytic Hydrogen Evolution.

The development of low-cost and efficient photocatalysts to achieve water splitting to hydrogen (H2) is highly desirable but remains challenging. Herein, we design and synthesize two porous polymers (Co-Salen-P and Fe-Salen-P) by covalent bonding of salen metal complexes and pyrene chromophores for photocatalytic H2 evolution. The catalytic results demonstrate that the two polymers exhibit excellent catalytic performance for H2 generation in the absence of additional noble-metal photosensitizers and cocatalysts. Particularly, the H2 generation rate of Co-Salen-P reaches as high as 542.5 µmol g-1 h-1, which is not only 6 times higher than that of Fe-Salen-P but also higher than a large amount of reported Pt-assisted photocatalytic systems. Systematic studies show that Co-Salen-P displays faster charge separation and transfer efficiencies, thereby accounting for the significantly improved photocatalytic activity. This study provides a facile and efficient way to fabricate high-performance photocatalysts for H2 production.

Impact of viral filters on accuracy of cardiopulmonary testing and spirometry.

The present study found that using viral filters at the proximal end of a spirometry and CPET test circuit did not significantly alter the test results, with the exception of a marginal decrease noted in peak work rate https://bit.ly/3Vkew95.

Streamlining heterologous expression of top carbonic anhydrases in Escherichia coli: bioinformatic and experimental approaches.

BACKGROUND: Carbonic anhydrase (CA) enzymes facilitate the reversible hydration of CO2 to bicarbonate ions and protons. Identifying efficient and robust CAs and expressing them in model host cells, such as Escherichia coli, enables more efficient engineering of these enzymes for industrial CO2 capture. However, expression of CAs in E. coli is challenging due to the possible formation of insoluble protein aggregates, or inclusion bodies. This makes the production of soluble and active CA protein a prerequisite for downstream applications. RESULTS: In this study, we streamlined the process of CA expression by selecting seven top CA candidates and used two bioinformatic tools to predict their solubility for expression in E. coli. The prediction results place these enzymes in two categories: low and high solubility. Our expression of high solubility score CAs (namely CA5-SspCA, CA6-SazCAtrunc, CA7-PabCA and CA8-PhoCA) led to significantly higher protein yields (5 to 75 mg purified protein per liter) in flask cultures, indicating a strong correlation between the solubility prediction score and protein expression yields. Furthermore, phylogenetic tree analysis demonstrated CA class-specific clustering patterns for protein solubility and production yields. Unexpectedly, we also found that the unique N-terminal, 11-amino acid segment found after the signal sequence (not present in its homologs), was essential for CA6-SazCA activity. CONCLUSIONS: Overall, this work demonstrated that protein solubility prediction, phylogenetic tree analysis, and experimental validation are potent tools for identifying top CA candidates and then producing soluble, active forms of these enzymes in E. coli. The comprehensive approaches we report here should be extendable to the expression of other heterogeneous proteins in E. coli.

FOXO-regulated DEAF1 controls muscle regeneration through autophagy.

The commonality between various muscle diseases is the loss of muscle mass, function, and regeneration, which severely restricts mobility and impairs the quality of life. With muscle stem cells (MuSCs) playing a key role in facilitating muscle repair, targeting regulators of muscle regeneration has been shown to be a promising therapeutic approach to repair muscles. However, the underlying molecular mechanisms driving muscle regeneration are complex and poorly understood. Here, we identified a new regulator of muscle regeneration, Deaf1 (Deformed epidermal autoregulatory factor-1) - a transcriptional factor downstream of foxo signaling. We showed that Deaf1 is transcriptionally repressed by FOXOs and that DEAF1 targets to Pik3c3 and Atg16l1 promoter regions and suppresses their expression. Deaf1 depletion therefore induces macroautophagy/autophagy, which in turn blocks MuSC survival and differentiation. In contrast, Deaf1 overexpression inactivates autophagy in MuSCs, leading to increased protein aggregation and cell death. The fact that Deaf1 depletion and its overexpression both lead to defects in muscle regeneration highlights the importance of fine tuning DEAF1-regulated autophagy during muscle regeneration. We further showed that Deaf1 expression is altered in aging and cachectic MuSCs. Manipulation of Deaf1 expression can attenuate muscle atrophy and restore muscle regeneration in aged mice or mice with cachectic cancers. Together, our findings unveil an evolutionarily conserved role for DEAF1 in muscle regeneration, providing insights into the development of new therapeutic strategies against muscle atrophy.

Bibliometric analysis of the application of deep learning in cancer from 2015 to 2023.

BACKGROUND: Recently, the application of deep learning (DL) has made great progress in various fields, especially in cancer research. However, to date, the bibliometric analysis of the application of DL in cancer is scarce. Therefore, this study aimed to explore the research status and hotspots of the application of DL in cancer. METHODS: We retrieved all articles on the application of DL in cancer from the Web of Science database Core Collection database. Biblioshiny, VOSviewer and CiteSpace were used to perform the bibliometric analysis through analyzing the numbers, citations, countries, institutions, authors, journals, references, and keywords. RESULTS: We found 6,016 original articles on the application of DL in cancer. The number of annual publications and total citations were uptrend in general. China published the greatest number of articles, USA had the highest total citations, and Saudi Arabia had the highest centrality. Chinese Academy of Sciences was the most productive institution. Tian, Jie published the greatest number of articles, while He Kaiming was the most co-cited author. IEEE Access was the most popular journal. The analysis of references and keywords showed that DL was mainly used for the prediction, detection, classification and diagnosis of breast cancer, lung cancer, and skin cancer. CONCLUSIONS: Overall, the number of articles on the application of DL in cancer is gradually increasing. In the future, further expanding and improving the application scope and accuracy of DL applications, and integrating DL with protein prediction, genomics and cancer research may be the research trends.

Shift work effects on incident neuropsychiatric disorders and shift work tolerance.

BACKGROUND: Shift work is associated with susceptibility to several neuropsychiatric disorders. This study aims to investigate the effect of shift work on the incidence of neuropsychiatric disorders, and highlighting how individual variability may influence the association. METHODS: UK Biobank participants with employment information were included. Cox survival was conducted in main and subgroup analyses. Correlation analyses explored the impact of shift work on brain structures, and mediation analyses were performed to elucidate the shared underlying mechanisms. Shift work tolerance was evaluated through survival analyses contrasting the risks associated with five neuropsychiatric disorders in shift versus non-shift workers across different demographic or occupational strata. RESULTS: The analysis encompassed 254,646 participants. Shift work was associated with higher risk of dementia (HR 1.29, 95 % CI 1.10-1.52), anxiety (1.08, 1.01-1.15), depression (1.29, 1.22-1.36), and sleep disorders (1.18, 1.09-1.28), but not stroke (p = 0.20). Shift work was correlated with decreasing volume of various brain regions, particularly in thalamus, lateral orbitofrontal, and middle temporal. Mediation analysis revealed that increased immune response and glucose levels are common pathways linking shift work to these disorders. We observed diversity in shift work tolerance across different individual characteristics, among which socioeconomic status and length of working hours were the most essential. LIMITATIONS: Self-reported employment information may cause misclassification and recall bias. And since we focused on the middle-aged population, the conclusions may not be representative of younger or older populations. CONCLUSIONS: Our findings indicated the need to monitor shift worker health and provide personalized management to help adapt to shift work.

Aflatoxin B1 as a complicit in intestinal damage caused by Eimeria ovinoidalis in lambs: Novel insights to reveal parasite-gut battle.

Mycotoxins, unavoidable contaminants in feed and feed ingredients, have the potential to influence the incidence and severity of various diseases upon ingestion. Sheep coccidiosis is an enteric disease caused by protozoa of Eimeria spp. However, the extent to which the presence of aflatoxin b1 (AFB1) synergistically exacerbates damage to intestinal health in lambs with Eimeria remains unclear. 50-day-old female lambs were randomly assigned to a 2 × 2 factorial arrangement of treatments for 15 days to assess the impact of AFB1 exposure on lambs with or without Eimeria (E.) ovinoidalis infection. Our findings reveal that AFB1 synergistically intensifies damage to intestinal health in lambs challenged by E. ovinoidalis. This is evidenced by disruptions to the intestinal microbiota and reductions in the production of short-chain fatty acids. AFB1 further aggravates damage to the cecal mechanical barrier. Additionally, AFB1 contributes to the entry of lipopolysaccharide into the bloodstream, activating the inflammatory response. Interestingly, AFB1 exposure history results in an early peak of oocyst excretion and a decreased number of oocyst excretion in E. ovinoidalis infected lambs. This may be closely linked to the destruction of the intestinal epithelial cell structure and its apoptosis, as indicated by a decreased ratio of Bcl-2 to Bax and increased caspase-3 levels. Mechanistically, proteomics analysis identified mitochondrial dysfunction (inhibition of the oxidative phosphorylation pathway) as the primary factor intensifying intestinal epithelial cell destruction caused by coccidia, exacerbated by AFB1 through the inhibiting the conversion of NADH to NAD+ in the cecum of lambs via down-regulation of the PGC-1α/NRF1/TFAM pathway. Overall, these results offer novel insights into the AFB1 complicity in accelerating intestinal damage caused by E. ovinoidalis in lambs. Targeting the mitochondrial oxidative phosphorylation pathway of the intestine may represent a new therapeutic strategy against the detrimental effects of mycotoxin and coccidia.

Clinical Significance of the Plasma Biomarker Panels in Amyloid-Negative and Tau PET-Positive Amnestic Patients: Comparisons with Alzheimer's Disease and Unimpaired Cognitive Controls.

The purpose of this study was to investigate whether plasma biomarkers can help to diagnose, differentiate from Alzheimer disease (AD), and stage cognitive performance in patients with positron emission tomography (PET)-confirmed primary age-related tauopathy, termed tau-first cognitive proteinopathy (TCP) in this study. In this multi-center study, we enrolled 285 subjects with young-onset AD (YOAD; n = 55), late-onset AD (LOAD; n = 96), TCP (n = 44), and cognitively unimpaired controls (CTL; n = 90) and analyzed plasma Aß42/Aß40, pTau181, neurofilament light (NFL), and total-tau using single-molecule assays. Amyloid and tau centiloids reflected pathological burden, and hippocampal volume reflected structural integrity. Receiver operating characteristic curves and areas under the curves (AUCs) were used to determine the diagnostic accuracy of plasma biomarkers compared to hippocampal volume and amyloid and tau centiloids. The Mini-Mental State Examination score (MMSE) served as the major cognitive outcome. Logistic stepwise regression was used to assess the overall diagnostic accuracy, combining fluid and structural biomarkers and a stepwise linear regression model for the significant variables for MMSE. For TCP, tau centiloid reached the highest AUC for diagnosis (0.79), while pTau181 could differentiate TCP from YOAD (accuracy 0.775) and LOAD (accuracy 0.806). NFL reflected the clinical dementia rating in TCP, while pTau181 (rho = 0.3487, p = 0.03) and Aß42/Aß40 (rho = -0.36, p = 0.02) were significantly correlated with tau centiloid. Hippocampal volume (unstandardized ß = 4.99, p = 0.01) outperformed all of the fluid biomarkers in predicting MMSE scores in the TCP group. Our results support the superiority of tau PET to diagnose TCP, pTau181 to differentiate TCP from YOAD or LOAD, and NFL for functional staging.

Resolving conjunctival prolapse following severe blepharoptosis correction: A simple sutureless direct excision technique and systematic review.

BACKGROUND: Conjunctival prolapse (CP) is an uncommon but challenging condition following maximal levator resection (MLR) and other extensive periorbital procedures. MLR extending beyond the Whitnall's ligament is frequently performed to address severe blepharoptosis with poor levator function (LF). Patients with CP may encounter symptoms such as ocular discomfort, tearing, vision impairment, persistent conjunctival chemosis, lagophthalmos, or exposure keratopathy. Typically, surgical intervention becomes necessary if conservative measures prove to be ineffective; nevertheless, there is no consensus regarding the optimal treatment approach. OBJECTIVES: This study aimed to propose a simple sutureless direct excision method and explore the surgical advancements in CP correction through a systematic review. METHODS: Patients with recurrent CP after MLR who underwent sutureless direct excision of the conjunctiva using loupe magnifiers at a tertiary hospital were included in this study. The clinical evolution and surgical results were recorded. PubMed, MEDLINE, EMBASE, and Web of Science databases were queried following The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. RESULTS: The comprehensive analysis of 1858 articles identified 88 patients from 24 studies, highlighting that blepharoptosis surgery is predominantly associated with CP (36.6%). Surgically treated CP showed a higher resolution rate compared to those managed conservatively (54.8% vs. 45.2%; p = 0.034). No relapse was observed in patients treated with sutureless direct excision of CP in long-term follow-up. CONCLUSION: We proposed a simple sutureless direct excision technique that offers a straightforward and efficient approach in treating CP, which is particularly suitable for cases requiring excision lengths >16 mm during MLR. Furthermore, stitch removal can be obviated after surgery.

Subsequent maternal sleep deprivation aggravates cognitive impairment by modulating hippocampal neuroinflammatory responses and synaptic function in maternal isoflurane-exposed offspring mice.

INTRODUCTION: Pregnant women may need to undergo non-obstetric surgery under general anesthesia owing to medical needs, and pregnant women frequently experience sleep disturbances during late gestation. Preclinical studies demonstrated that maternal isoflurane exposure (MISO) or maternal sleep deprivation (MSD) contributed to cognitive impairments in offspring. Research studies in mice have revealed that SD can aggravate isoflurane-induced cognitive deficits. However, it remains unclear whether MSD aggravates MISO-induced cognitive deficits in offspring. The purpose of this research was to explore the combined effects of MSD and MISO on offspring cognitive function and the role of neuroinflammation and synaptic function in the process of MSD + MISO. METHODS: Pregnant mice were exposed to 1.4% isoflurane by inhalation for 4 h on gestational day (GD) 14. Dams were then subjected to SD for 6 h (12:00-18:00 h) during GD15-21. At 3 months of age, the offspring mice were subjected to the Morris water maze test to assess cognitive function. Then the levels of inflammatory and anti-inflammatory markers and synaptic function-related proteins were assessed using molecular biology methods. RESULTS: The results of this study demonstrated that MISO led to cognitive dysfunction, an effect that was aggravated by MSD. In addition, MSD exacerbated the maternal isoflurane inhalation, leading to an enhancement in the expression levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor-alpha and a reduction in the hippocampal levels of IL-10, synaptophysin, post-synaptic density-95, growth-associated protein-43, and brain-derived neurotrophic factor. CONCLUSION: Our findings revealed that MSD aggravated the cognitive deficits induced by MISO in male offspring mice, and these results were associated with neuroinflammation and alternations in synaptic function.

Integrated bioinformatic analysis and experimental validation for exploring the key immune checkpoint of COPD.

BACKGROUND: There is growing evidence indicating immune inflammation is a key factor in the progression of chronic obstructive pulmonary disease (COPD). Immune checkpoints (ICs) are crucial targets for modulating the functional activation and differentiation of immune cells, particularly in relation to immune inflammation and the regulation of T cell activation and exhaustion. However, the precise mechanisms of ICs in COPD remain understood. METHODS: COPD datasets were obtained from the Gene Expression Omnibus (GEO) and analyzed using GEO2R and Limma to identify differentially expressed genes. LASSO regression was then applied to screen ICs closely associated with COPD. Finally, target genes were selected based on gene expression profiles. Gene ontology (GO), immune infiltration analysis, and gene set enrichment analysis (GSEA) were utilized to assess the relationship between IC genes (ICGs) and immune cells. Subsequently, tobacco-exposed mice, anti-Tim3-treated mice, and HAVCR2-knockout mice were generated, with flow cytometry being used to confirm the results. RESULTS: Through the analysis of GSE38974 and LASSO regression, five ICGs were identified. Subsequent validation using GSE20257 and GSE76925 confirmed these findings. Gene expression profiling highlighted HAVCR2 as having the strongest correlation with COPD. Further investigation through immune infiltration analysis, GO, and GSEA indicated a link between HAVCR2 and CD8+ T cells in COPD. Flow cytometry experiments demonstrated high Tim3 expression in CD8+ T cells of mice exposed to tobacco, promoting Tc1 and inhibiting Tc17, thus affecting CD8+ Tem activation and CD8+ Tcm formation, leading to an immune imbalance within CD8+ T cells. CONCLUSION: Prolonged exposure to tobacco upregulates Tim3 in CD8+ T cells, triggering its regulatory effects on Tc1/Tc17. Knocking out HAVCR2 further upregulated the expression of CD8+ Tem while suppressing the expression of CD8+ Tcm, indicating that Tim3 plays a role in the activation and differentiation of CD8+ T cells in the context of tobacco exposure.

Manipulating the Crosstalk between Cancer and Immunosuppressive Cells with Phototherapeutic Gold-Nanohut for Reprogramming Tumor Microenvironment.

Photoimmunotherapy faces challenges due to insufficient intratumoral accumulation of photothermal agents and the reversion of the cancer-immunity cycle during treatment. In this study, an anti-PD-L1-immobilized magnetic gold nanohut, AuNH-2-Ab, with photoresponsive, thermosensitive, and immunomodulatory properties to effectively suppress the growth of primary tumors, elevate immunogenic cell death (ICD) levels, reverse the tumor immune microenvironment (TIME), and consequently inhibit metastases are developed. AuNH-2-Ab achieves high tumor accumulation (9.54% injected dose) following systemic administration, allowing the modulation of hyperthermia dose of over 50 °C in the tumor. By optimizing the hyperthermia dose, AuNH-2-Ab simultaneously target and eliminate cancer cells and tumor-associated macrophages, thereby activating potent antitumor immunity without being compromised by immunosuppressive elements. Hyperthermia/pH induced morphological transformation of AuNH-2-Ab involving the detachment of the surface antibody for in situ PD-L1 inhibition, and exposure of the inner fucoidan layer for natural killer (NK) cell activation. This precision photoimmunotherapy approach reprograms the TIME, significantly prolongs survival in a murine hepatocellular carcinoma model (Hep55.1c), and harnesses the synergistic effects of ICD production and checkpoint inhibitors by utilizing a single nanoplatform.

Real-world safety and effectiveness of radium-223 in patients with metastatic castration-resistant prostate cancer: Interim analyses of the prospective, observational RAPIT study.

Several life-prolonging therapies for metastatic castration-resistant prostate cancer (mCRPC) are available, including radium-223 dichloride (223Ra), which was approved based on phase 3 data demonstrating improved overall survival (OS) and a favorable safety profile. To date, real-world evidence for 223Ra use in Taiwan is from three studies of <50 patients. This observational study (NCT04232761) enrolled male patients with histologically/cytologically confirmed mCRPC with bone metastases from centers across Taiwan. 223Ra was prescribed as part of routine practice by investigators. Patients with prior 223Ra treatment were excluded. The primary objective was to assess 223Ra safety; secondary objectives evaluated efficacy parameters, including OS. Overall, 224 patients were enrolled. Most patients had an Eastern Cooperative Oncology Group performance status of 0/1 (79.0%) and ≤20 bone metastases (69.2%); no patients had visceral metastases. 223Ra was first- or second-line therapy in 23.2% and 47.7% of patients, respectively. The total proportion of patients who received 5-6 223Ra cycles was 68.8%; this proportion was greater with first-line use (84.3%) than second- (65.7%) or third-/fourth-line use (64.1%). More chemotherapy-naïve patients (61.9%) completed the 6-cycle 223Ra treatment than chemotherapy-exposed patients (56.7%). Any-grade treatment-emergent adverse events (TEAEs) and serious TEAEs occurred in 54.0% and 28.6% of patients, respectively, while 12% experienced 223Ra-related adverse events. Median OS was 15.7 months (95% confidence interval 12.13-19.51); patients receiving 5-6 223Ra injections and earlier 223Ra use had longer OS than those receiving fewer injections and later 223Ra use. 223Ra provides a well-tolerated and effective treatment for Taiwanese patients with mCRPC and bone metastases.

[Impact of Mild SARS-CoV-2 Infection on Hematological Parameters and Suitability of Apheresis Platelets Donation in Blood Donors].

OBJECTIVE: To investigate the effects of mild SARS-CoV-2 infection on hematological parameters of adult blood donors and the suitability of apheresis platelet donation, the changes of the hematological parameters in blood donors with mild infection of the SARS-CoV-2 Omicron variant strain were evaluated. METHODS: Seventy-two blood donors with mild COVID-19 symptoms who donated consecutive apheresis platelets for 3 times from December 2022 to January 2023, 42 cases among which were included in the infection-positive group, and 30 cases in the suspected infection group. Forty-two donors un-vaccinated against SARS-CoV-2, un-infected, and donated three consecutive apheresis platelets from October to November 2022 were included in the control group. The changes of blood routine testing in the positive group and the suspected infection group were retrospectively compared before (Time1) and after (Time2 and Time3) the onset of symptoms, three consecutive times (Time1, Time2, Time3) in the control group by repeated measures analysis of variance. The Bayesian discriminant method was used to establish a discriminant equation to determine whether the recent infection of SARS-CoV-2 occurred or not. RESULTS: Simple effect of the number times of tests in the positive and suspected infection groups was significant（ Finfection-positive group=6.98, P < 0.001, partial η2=0.79, Fsuspected infection group=4.31, P < 0.001, partial η2=0.70）. The positive group and the suspected infection group had lower RBC, HCT, and HGB, and higher PLT and PCT at Time2 compared to Time1 and Time3(P < 0.05). The positive group and the suspected infection group showes RDW-CV and RDW-SD at Time3 higher than Time1 and Time2 (P < 0.001). The simple effect of the number times of tests in the control group was not significant ( F=0.96, P =0.55, partial η2=0.34). The difference of the whole blood count parameters in the control group for three times was not statistically significant (P >0.05). We established a discriminant equation to determine whether the recent infection of SARS-CoV-2 occurred or not. The equation had an eigenvalue of 0.22, a canonical correlation of 0.43 (χ2=27.81, P < 0.001), and an analysis accuracy of 72.9%. CONCLUSION: The hematological indicators of RBC, HCT, HGB, PLT, PCT, RDW-CV and RDW-SD in blood donors who had infected with mild COVID-19 showed dynamic changes. The discriminant equation for whether they are infected recently with COVID-19 has a high accuracy rate.

Enhancing Optical and Thermal Stability of Blue-Emitting Perovskite Nanocrystals through Surface Passivation with Sulfonate or Sulfonic Acid Ligands.

This study aims to enhance the optical and thermal properties of cesium-based perovskite nanocrystals (NCs) through surface passivation with organic sulfonate (or sulfonic acid) ligands. Four different phenylated ligands, including sodium ß-styrenesulfonate (SbSS), sodium benzenesulfonate (SBS), sodium p-toluenesulfonate (SPTS), and 4-dodecylbenzenesulfonic acid (DBSA), were employed to modify blue-emitting CsPbBr1.5Cl1.5 perovskite NCs, resulting in improved size uniformity and surface functionalization. Transmission electron microscopy and X-ray photoelectron spectroscopy confirmed the successful anchoring of sulfonate or sulfonic acid ligands on the surface of perovskite NCs. Moreover, the photoluminescence quantum yield increased from 32% of the original perovskite NCs to 63% of the SPTS-modified ones due to effective surface passivation. Time-resolved photoluminescence decay measurements revealed extended PL lifetimes for ligand-modified NCs, indicative of reduced nonradiative recombination. Thermal stability studies demonstrated that the SPTS-modified NCs retained nearly 80% of the initial PL intensity when heated at 60 °C for 10 min, surpassing the performance of the original NCs. These findings emphasize the optical and thermal stability enhancement of cesium-based perovskite NCs through surface passivation with suitable sulfonate ligands.

Distinct biological property of tau in tau-first cognitive proteinopathy: Evidence by longitudinal clinical neuroimaging profiles and compared with late-onset Alzheimer disease.

BACKGROUND: Tau-first cognitive proteinopathy (TCP) denotes a clinical phenotype of Alzheimer disease (AD) showing Florzolotau(18F) positron emission tomography (PET) positivity but a negative amyloid status. AIM: We explored the biological property of tau using longitudinal cognitive and neuroimaging data in TCP and compared with late-onset AD (LOAD). METHOD: We enrolled 56 patients with LOAD, 34 patients with TCP, and 26 cognitive unimpaired controls. All of the participants had historical data of 2 to 4 three-dimensional T1 images and 2 to 6 annual cognitive evaluations over a follow-up period of 7 years. Tau topography was measured using Florzolotau(18F) PET. In the LOAD and TCP groups, we constructed tau or gray matter clusters covarying with the cognitive measurements. We used mediator analysis to explore the regional tau load as predictor, gray matter partitions as mediators, and significant cognitive test scores as outcomes. Longitudinal cognitive decline and cortical thickness degeneration pattern were analyzed using a linear mixed-effects model. RESULTS: The TCP group had longitudinal declines in nonexecutive domains. The deterministic factor predicting the short-term memory score in TCP was the hippocampal volume and not directly via the medial and lateral temporal tau load. These features formed the conceptual differences with LOAD. DISCUSSION: The biological properties of tau and the longitudinal cognitive-imaging trajectory support the conceptual distinction between TCP and LOAD. TCP represents one specific entity featuring salient short-term memory impairment, declines in nonexecutive domains, a slower gray matter degenerative pattern, and a restricted impact of tau.

Bioinformatics Analysis Reveals HIST1H2BH as a Novel Diagnostic Biomarker for Atrial Fibrillation-Related Cardiogenic Thromboembolic Stroke.

Atrial fibrillation (AF) is a significant precursor to cerebral embolism. Our study sought to unearth new diagnostic biomarkers for atrial fibrillation-related cerebral embolism (AF-CE) by meticulously examining multiple GEO datasets and meta-analysis. The gene expression omnibus (GEO) database provided RNA sequencing data associated with AF and stroke. We began by pinpointing genes with varied expressions in AF-CE patient blood samples. A meta-analysis was subsequently undertaken using several RNA sequencing datasets to verify these genes. LASSO regression discerned key genes for AF-CE, with their diagnostic prowess verified through ROC curve examination. Active signaling pathways within stroke patients were discerned via GO and KEGG enrichment, with PPI interactions detailing gene interplay. Differential gene analysis revealed an upregulation of sixteen genes and a downregulation of four in stroke patient blood samples. Eight genes showcased varied expression in the meta-analysis. LASSO regression zeroed in on five of these, culminating in HIST1H2BH's identification as a characteristic gene. HIST1H2BH's prowess in predicting AF-CE was confirmed through ROC. Integrin signaling, platelet activation, ECM interactions, and the PI3K-Akt pathway were found active in stroke victims. HIST1H2BH's interaction with the notably upregulated ITGA2B was spotlighted by PPI. Additionally, HIST1H2BH exhibited links with NK cells and eosinophils. HIST1H2BH emerges as an insightful diagnostic beacon for AF-CE. Its presence, post AF, potentially modulates pathways, accentuating platelet activation and consequent thrombus generation, leading to cerebral embolism.