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.

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.

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.

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.

Multiplex cerebrospinal fluid proteomics identifies biomarkers for diagnosis and prediction of Alzheimer's disease.

Recent expansion of proteomic coverage opens unparalleled avenues to unveil new biomarkers of Alzheimer's disease (AD). Among 6,361 cerebrospinal fluid (CSF) proteins analysed from the ADNI database, YWHAG performed best in diagnosing both biologically (AUC = 0.969) and clinically (AUC = 0.857) defined AD. Four- (YWHAG, SMOC1, PIGR and TMOD2) and five- (ACHE, YWHAG, PCSK1, MMP10 and IRF1) protein panels greatly improved the accuracy to 0.987 and 0.975, respectively. Their superior performance was validated in an independent external cohort and in discriminating autopsy-confirmed AD versus non-AD, rivalling even canonical CSF ATN biomarkers. Moreover, they effectively predicted the clinical progression to AD dementia and were strongly associated with AD core biomarkers and cognitive decline. Synaptic, neurogenic and infectious pathways were enriched in distinct AD stages. Mendelian randomization did not support the significant genetic link between CSF proteins and AD. Our findings revealed promising high-performance biomarkers for AD diagnosis and prediction, with implications for clinical trials targeting different pathomechanisms.

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.

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.

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.

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.

The symbiotic experiences of residents with and without dementia co-living in Taiwan's long-term care facilities: a phenomenological study.

BACKGROUND: In Taiwan, residents with and without dementia mostly co-live in long-term care facilities. The behavioral and psychiatric symptoms of dementia residents often pose challenges for others living together. This study explored the symbiotic experiences of residents without dementia co-living with those with dementia in long-term care facilities in Taiwan to present their experiences of living together. METHODS: This was a cross-sectional descriptive study with a phenomenological design. Semi-structured face-to-face interviews were conducted with 30 residents without dementia from three long-term care institutions in Taiwan. Colaizzi's data processing steps were used for analysis. RESULTS: The analysis of interview transcripts revealed that the experiences of residents who lived with those with dementia were that of a "symbiosis." Three core themes were found: "the impact of co-living," "facing difficulties and coping," and "companionship and reciprocity." This study showed that residents without dementia may be affected by the behavioral and psychiatric symptoms of residents with dementia when co-living in long-term care facilities. However, there are also positive and mutually beneficial interactions between them. By helping people with dementia in their daily lives, residents without dementia feel happy and accomplished and their self-worth is enhanced. Furthermore, residents with dementia have more opportunities for social engagement and co-living interactions. CONCLUSION: These results can guide long-term care facilities without special care dementia units to support residents without dementia, reduce the interference of the behavioral and psychiatric symptoms of residents with dementia, and promote mutual benefits. However, these findings warrant further investigation.

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.

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.

Comparison of the burden of digestive diseases between China and the United States from 1990 to 2019.

Introduction: China has experienced unprecedented transformations unseen in a century and is gradually progressing toward an emerging superpower. The epidemiological trends of digestive diseases in the United States (the US) have significant prescient effects on China. Methods: We extracted data on 18 digestive diseases from the Global Burden of Diseases 2019 Data Resource. Linear regression analysis conducted by the JoinPoint software assessed the average annual percentage change of the burden. We performed subgroup analyses based on sex and age group. Results: In 2019, there were 836.01 and 180.91 million new cases of digestive diseases in China and the US, causing 1558.01 and 339.54 thousand deaths. The age-standardized incidence rates of digestive diseases in China and the US were 58417.87/100,000 and 55018.65/100,000 respectively, resulting in age-standardized mortality rates of 81.52/100,000 and 60.88/100,000. The rates in China annually decreased by 2.149% for mortality and 2.611% for disability-adjusted life of year (DALY). The mortality and DALY rates of the US, respectively, had average annual percentage changes of -0.219 and -0.251. Enteric infections and cirrhosis and other chronic liver diseases accounted for the highest incidence and prevalence in both counties, respectively. The burden of multiple digestive diseases exhibited notable sex disparities. The middle-old persons had higher age-standardized prevalence rates. Conclusion: China bore a greater burden of digestive diseases, and the evolving patterns were more noticeable. Targeted interventions and urgent measures should be taken in both countries to address the specific burden of digestive diseases based on their different epidemic degree.

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.

Chemical constituents from a marine medicinal brown alga-derived Xylaria acuta SC1019.

In this study, a marine medicinal brown alga Sargassum cristaefolium-derived fungal strain Xylaria acuta SC1019 was isolated and identified. Column chromatography of the extracts from liquid- and solid-fermented products of the fungal strain was carried out, and led to the isolation of twenty-one compounds. Their structures were characterized by spectroscopic analysis, and the absolute configurations were further established by single X-ray diffraction analysis or modified Mosher's method as nine previously undescribed compounds, namely xylarilactones A-C (1-3), ent-gedebic acid 8-O-α-D-glucopyranoside (4), 5R-hydroxylmethylmellein 11-O-α-D-glucopyranoside (5), ent-hymatoxin E 16-O-α-D-mannopyranoside (6), 19,20-epoxycytochalasin S (7), 19,20-epoxycytochalasin T (8), and (2R)-butylitaconic acid (9), along with twelve known compounds 10-21. All the isolates were subjected to anti-inflammatory and anti-angiogenic assays. Compounds 1, 5, 7, 10, and 17 showed moderate nitric oxide production inhibitory activities in lipopolysaccharide-activated BV-2 microglial cells with IC50 values of 19.55 ± 0.35, 16.10 ± 0.57, 15.20 ± 0.87, 11.76 ± 0.49, and 11.30 ± 0.32 µM, respectively, as compared to curcumin (IC50 = 2.69 ± 0.34 µM) without any significant cytotoxicity. Compounds 7, 8, and 21 displayed potent anti-angiogenic activities by suppressing the growth of human endothelial progenitor cells with IC50 values of 0.44 ± 0.01, 0.47 ± 0.03, and 0.53 ± 0.01 µM, respectively, as compared to sorafenib (IC50 = 5.50 ± 1.50 µM).

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.