Flavonoid gossypetin protects alveolar bone and limits inflammation in ligature-induced periodontitis in mice.

BACKGROUND: Bacterial-induced inflammation instigates the destruction of hard and soft tissues surrounding teeth in periodontitis. In severe cases, the increased number and activity of osteoclasts induces the resorption of alveolar bones, ultimately leading to tooth loss. Because of their diverse chemical structures and bioactivities, natural compounds are often suggested to treat a wide variety of diseases, including inflammatory disorders. METHODS: In the present study, we demonstrated an inhibitory effect of gossypetin, a hexahydroxy flavone, on osteoclast differentiation and bone resorption using in vitro culture of osteoclasts from mouse bone marrow macrophage (BMM) precursors and in vivo model of ligature-induced periodontitis in mice. RESULTS: Gossypetin significantly reduced the differentiation of osteoclasts from mouse BMM precursors in the presence of the receptor activator of nuclear factor κB ligand (RANKL). In vitro, gossypetin inhibited critical signaling events downstream of RANKL including the auto-amplification of nuclear factor of activated T-cells, cytoplasmic 1, Ca2+ oscillations, and the generation of reactive oxygen species. In a mouse ligature-induced periodontitis model, the administration of gossypetin significantly reduced osteoclastogenesis and alveolar bone resorption. Furthermore, gossypetin prevented the ligature-induced increase in macrophages and T cells and reduced the production of tumor necrosis factor-α and interleukin-6. CONCLUSION: Taken together, these results show anti-osteoclastogenic and anti-inflammatory effects of gossypetin, suggesting the potential use of this natural compound in periodontitis.

iMAX FRET (Information Maximized FRET) for Multipoint Single-Molecule Structural Analysis.

Understanding the structure of biomolecules is vital for deciphering their roles in biological systems. Single-molecule techniques have emerged as alternatives to conventional ensemble structure analysis methods for uncovering new biology in molecular dynamics and interaction studies, yet only limited structural information could be obtained experimentally. Here, we address this challenge by introducing iMAX FRET, a one-pot method that allows ab initio 3D profiling of individual molecules using two-color FRET measurements. Through the stochastic exchange of fluorescent weak binders, iMAX FRET simultaneously assesses multiple distances on a biomolecule within a few minutes, which can then be used to reconstruct the coordinates of up to four points in each molecule, allowing structure-based inference. We demonstrate the 3D reconstruction of DNA nanostructures, protein quaternary structures, and conformational changes in proteins. With iMAX FRET, we provide a powerful approach to advance the understanding of biomolecular structure by expanding conventional FRET analysis to three dimensions.

Molecular insights into regulatory RNAs in the cellular machinery.

It is apparent that various functional units within the cellular machinery are derived from RNAs. The evolution of sequencing techniques has resulted in significant insights into approaches for transcriptome studies. Organisms utilize RNA to govern cellular systems, and a heterogeneous class of RNAs is involved in regulatory functions. In particular, regulatory RNAs are increasingly recognized to participate in intricately functioning machinery across almost all levels of biological systems. These systems include those mediating chromatin arrangement, transcription, suborganelle stabilization, and posttranscriptional modifications. Any class of RNA exhibiting regulatory activity can be termed a class of regulatory RNA and is typically represented by noncoding RNAs, which constitute a substantial portion of the genome. These RNAs function based on the principle of structural changes through cis and/or trans regulation to facilitate mutual RNA‒RNA, RNA‒DNA, and RNA‒protein interactions. It has not been clearly elucidated whether regulatory RNAs identified through deep sequencing actually function in the anticipated mechanisms. This review addresses the dominant properties of regulatory RNAs at various layers of the cellular machinery and covers regulatory activities, structural dynamics, modifications, associated molecules, and further challenges related to therapeutics and deep learning.

Superior outcomes and high-risk features with carfilzomib, lenalidomide, and dexamethasone combination therapy for patients with relapsed and refractory multiple myeloma: Results of the multicenter KMMWP2201 study.

Carfilzomib, lenalidomide, and dexamethasone (KRd) combination therapy improves the survival of patients with relapsed and/or refractory multiple myeloma (RRMM). Nonetheless, evidence on the use of KRd in Asian populations remains scarce. Accordingly, this study aimed at investigating this regimen's efficacy in a large group of patients. This retrospective study included patients with RRMM who were treated with KRd at 21 centers between February 2018 and October 2020. Overall, 364 patients were included (median age: 63 years). The overall response rate was 90% in responseevaluable patients, including 69% who achieved a very good partial response or deeper responses. With a median follow-up duration of 34.8 months, the median progression-free survival (PFS) was 23.4 months and overall survival (OS) was 59.5 months. Among adverse factors affecting PFS, highrisk cytogenetics, extramedullary disease, and doubling of monoclonal protein within 2 to 3 months prior to start of KRd treatment significantly decreased PFS and overall survival (OS) in multivariate analyses. Patients who underwent post-KRd stem cell transplantation (i.e.delayed transplant) showed prolonged PFS and OS. Grade 3 or higher adverse events (AEs) were observed in 56% of the patients, and non-fatal or fatal AE's that resulted in discontinuation of KRd were reported in 7% and 2% of patients, respectively. Cardiovascular toxicity was comparable to that reported in the ASPIRE study. In summary, KRd was effective in a large real-world cohort of patients with RRMM with long-term follow-up. These findings may further inform treatment choices in the treatment of patients with RRMM.

Early dose reduction of dasatinib does not compromise clinical outcomes in patients with chronic myeloid leukemia: A comparative analysis of two prospective trials.

Dasatinib is a potent second-generation tyrosine kinase inhibitor (TKI) used as a first-line treatment option for patients with chronic myeloid leukemia (CML). Currently, dose modification due to adverse events (AEs) is common in patients treated with dasatinib. This study compared the outcomes of two sequential prospective trials that enrolled patients with newly diagnosed chronic phase of CML (CP-CML) and initiated dasatinib at a starting dose of 100 mg daily. In the PCR-DEPTH study, CP-CML patients who started dasatinib 100 mg daily were enrolled and followed up, while in the DAS-CHANGE study, when patients achieved early molecular response with any grade of AEs were enrolled and treated with dasatinib 80 mg once daily. A total of 102 patients (PCR-DEPTH) and 90 patients (DAS-CHANGE) were compared. Although the median value of the relative dose intensity (RDI) of dasatinib was significantly higher in PCR-DEPTH than in DAS-CHANGE (99.6 % vs. 80.1 %, p <0.001), the MMR rate at 12months showed a trend toward superiority in DAS-CHANGE compared to PCR-DEPTH (77.1 % vs 65.2 %, p = 0.084). The frequencies of MR4.0 at 24 and 36 months were higher in DAS-CHANGE than in PCR-DEPTH (44.4 % vs 28.8 %, p = 0.052 and 63.6 % vs 40.3 %, p= 0.013, respectively). RDIs were not different according to the MMR, MR4.0 or MR4.5 in analyses using a pooled population. Our results suggest that early dose reduction of dasatinib does not compromise efficacy in patients achieving EMR at 3 months and could be an interventional strategy for improving long term outcomes.

Relationship between sleep disturbance and developmental status in preschool-aged children with developmental disorder.

BACKGROUND: Sleep has been known to affect childhood development. Sleep disturbance is likely more common in children with developmental delay (DD) than in typical development. There are few studies on the correlation between sleep disturbance and developmental features in children with DD. Therefore, this study aimed to evaluate the associations between the two in children with DD. METHODS: A total of 45 children (age range 27.0 ± 11.1) with DD were recruited and evaluated using the Sleep Disturbance Scale for Children (SDSC) and Bayley Scales of Infant and Toddler Development (BSID-III). The outcomes are expressed as means and standard deviations. The correlation between SDSC and BSID-III was assessed using Spearman's rank correlation test. Multiple regression analysis was performed to investigate the relationship between BSID-III domains and SDSC questionnaire subscales. Statistical significance was set at p < 0.05. RESULTS: Based on the correlation analysis and subsequent hierarchical regression analysis, cognition and socio-emotional domains of BSID-III were significantly associated with the DOES subscale of the SDSC questionnaire. In addition, the expressive language domain of the BSID-III was found to be associated with the DA subscale of the SDSC questionnaire. It seems that excessive daytime sleepiness might negatively affect emotional and behavioral problems and cognitive function. Also, arousal disorders seem to be related to memory consolidation process, which is thought to affect language expression. CONCLUSION: This study demonstrated that DA and DOES subscales of the SDSC questionnaire were correlated with developmental aspects in preschool-aged children with DD. Sleep problems in children with DD can negatively affect their development, thereby interfering with the effectiveness of rehabilitation. Identifying and properly managing the modifiable factors of sleep problems is also crucial as a part of comprehensive rehabilitation treatment. Therefore, we should pay more attention to sleep problems, even in preschool-aged children with DD.

Prevalences and Interrelationships of Post COVID-19 Fatigue, Sleep Disturbances, and Depression in Healthy Young and Middle-Aged Adults.

Background: An evaluation of the persistence of symptoms following COVID-19 in economically active young and middle-aged adults is crucial due to its significant socioeconomic impact resulting from compromised work performance. Methods: A prospective, multicenter study at 12 South Korean hospitals from January to December 2022 involved telephone interviews along with validated questionnaires. Results: Among 696 participants with a median age of 32 and no prior diagnoses, 30% of participants experienced persistent fatigue, while 21.4% suffered from sleep disturbance at 6 months following infection. Additionally, approximately 25% of the participants exhibited depression that endured for up to 6 months. Symptomatic individuals at 3 months exhibited a significantly higher prevalence of persistent fatigue, sleep disturbances, and depression at 6 months compared to those who remained asymptomatic. Notably, sleep disturbance and persistent fatigue at 3 months emerged as significant independent predictors of the presence of depression at 6 months. Conclusions: Even among young and middle-aged healthy adults, prolonged fatigue, sleep disturbance, and depression exhibit a significant prevalence and persisted for up to 6 months. Therefore, implementing a workplace management protocol for these symptoms is essential to mitigate the socioeconomic burden caused by the impairment of work efficiency.

Optimal surgical management of unifocal vs. multifocal NF-PNETs: a respective cohort study.

BACKGROUND: Pancreatic neuroendocrine tumors (PNETs) represent 1-2% of pancreatic tumors, with recent guidelines recommending active surveillance for non-functioning PNETs (NF-PNETs) smaller than 2 cm. However, the management of multiple NF-PNETs, as well as the influence of tumor number on prognosis, remains under-researched. METHODS: This retrospective study analyzed NF-PNET patients who underwent pancreatic resection at Severance Hospital between February 1993 and August 2023, comparing the characteristics of patients diagnosed with multifocal tumors and those with unifocal tumors. A subgroup analysis of overall survival (OS) and recurrence-free survival (RFS) was performed based on multifocality employing the Kaplan-Meier method and the log-rank test. RESULTS: Of 187 patients, 169 (90.4%) had unifocal and 18 (9.6%) had multifocal tumors. Multifocal tumors were more likely to be diffusely spread, necessitating more total pancreatectomies (diffuse tumor location: 4.7% in unifocal vs. 38.9% in multifocal cases, p < 0.001; total pancreatectomy: 4.1% in unifocal vs. 33.3% in multifocal cases, p < 0.001). In patients with NF-PNET who underwent the same extent of pancreatic resection, no significant difference in the incidence of complication was observed regardless of multifocality. Moreover, no significant difference in OS was seen between the unifocal and multifocal groups (log-rank test: p = 0.93). However, the multifocal group exhibited a poorer prognosis in terms of RFS compared to the unifocal group (log-rank test: p = 0.004) Hereditary syndrome, tumor grade, size, lymphovascular invasion, and lymph node metastasis were key factors in the recurrence. CONCLUSION: This study's findings suggest that the presence of multiple tumors was associated with poorer recurrence-free survival but did not affect long-term survival following surgery. Given the long-term oncologic outcome and quality of life following surgery, resection of tumors over 2 cm is advisable in patients with multifocal PNETs, while a cautious "wait-and-see" approach for smaller tumors (under 2 cm) can minimize the extent of resection and improve the quality of life. In cases with only small multifocal NF-PNETs (< 2 cm), immediate resection may not be crucial, but the higher recurrence rate than that in solitary NF-PNET necessitates intensified surveillance.

Comparison of Survival Outcomes between Radical Antegrade Modular Pancreatosplenectomy and Conventional Distal Pancreatosplenectomy for Pancreatic Body and Tail Cancer: Korean Multicenter Propensity Score Match Analysis.

(1) Background: The aim of this study was to compare the survival benefit of radical antegrade modular pancreatosplenectomy (RAMPS) with conventional distal pancreatosplenectomy (cDPS) in left-sided pancreatic cancer. (2) Methods: A retrospective propensity score matching (PSM) analysis was conducted on 333 patients who underwent RAMPS or cDPS for left-sided pancreatic cancer at four tertiary cancer centers. The study assessed prognostic factors and compared survival and operative outcomes. (3) Results: After PSM, 99 patients were matched in each group. RAMPS resulted in a higher retrieved lymph node count than cDPS (15.0 vs. 10.0, p < 0.001). No significant differences were observed between the two groups in terms of R0 resection rate, blood loss, hospital stay, or morbidity. The 5-year overall survival rate was similar in both groups (cDPS vs. RAMPS, 44.4% vs. 45.2%, p = 0.853), and disease-free survival was also comparable. Multivariate analysis revealed that ASA score, preoperative CA19-9, histologic differentiation, R1 resection, adjuvant treatment, and lymphovascular invasion were significant prognostic factors for overall survival. Preoperative CA19-9, histologic differentiation, T-stage, adjuvant treatment, and lymphovascular invasion were independent significant prognostic factors for disease-free survival. (4) Conclusions: Although RAMPS resulted in a higher retrieved lymph node count, survival outcomes were not different between the two groups. RAMPS was a surgical option to achieve R0 resection rather than a standard procedure.

TNF receptor 2 knockout mouse had reduced lung cancer growth and schizophrenia-like behavior through a decrease in TrkB-dependent BDNF level.

The relationship between schizophrenia (SCZ) and cancer development remains controversial. Based on the disease-gene association platform, it has been revealed that tumor necrosis factor receptor (TNFR) could be an important mediatory factor in both cancer and SCZ development. TNF-α also increases the expression of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) in the development of SCZ and tumor, but the role of TNFR in mediating the association between the two diseases remains unclear. We studied the vital roles of TNFR2 in the progression of tumor and SCZ-like behavior using A549 lung cancer cell xenografted TNFR2 knockout mice. TNFR2 knockout mice showed significantly decreased tumor size and weight as well as schizophrenia-like behaviors compared to wild-type mice. Consistent with the reduced tumor growth and SCZ-like behaviors, the levels of TrkB and BDNF expression were significantly decreased in the lung tumor tissues and pre-frontal cortex of TNFR2 knockout mice. However, intravenous injection of BDNF (160 µg/kg) to TNFR2 knockout mice for 4 weeks increased tumor growth and SCZ-like behaviors as well as TrkB expression. In in vitro study, significantly decreased cell growth and expression of TrkB and BDNF by siTNFR2 transfection were found in A549 lung cancer cells. However, the addition of BDNF (100 ng/ml) into TNFR2 siRNA transfected A549 lung cancer cells recovered cell growth and the expression of TrkB. These results suggest that TNFR2 could be an important factor in mediating the comorbidity between lung tumor growth and SCZ development through increased TrkB-dependent BDNF levels.

Surgical strategy for incidental intrahepatic cholangiocarcinoma in terms of lymph node dissection.

BACKGROUND: Although many guidelines recommend performing lymph node dissection (LND) during surgery for intrahepatic cholangiocarcinoma (ICC), there is no evidence for patients with incidentally detected ICC who did not undergo LND. This study aimed to identify the role of LND in patients with incidental ICC. METHODS: The data from 284 patients who had undergone radical surgery for ICC from 2000 to 2020 were retrospectively reviewed. The enrolled patients were divided into 3 groups according to their T stage (T1 vs T2 vs T3 + 4). Moreover, the patients of each T group were divided into 3 groups according to their nodal status (N0 vs N1 vs Nx) and their survival outcomes were compared. RESULTS: Survival outcomes of Nx group were statistically similar to that of N0 group in T1 stage (Nx vs N0: disease-free survival [DFS] [months], 129.0 [75.6-182.4] vs 125.0 [65.7-184.3], P = .948; overall survival [OS] [months], 175.0 [153.9-196.1] vs 173.0 [109.0-237.0], P = .443). In contrast, survival outcomes of Nx group in the other T stage (T2 and T3 + 4) were poorer than that of N0 group and were better than that of N1 group. In addition, in the Nx subgroup analysis according to T stage, T1 group showed significantly better survival outcomes than the other groups (T1 vs T2 vs T3 + 4: DFS [months], 129.0 [75.9-182.1] vs 16.0 [9.8-22.2] vs 13.0 [0.3-25.7], P < .001; OS [months], 175.0 [153.9-196.1] vs 53.0 [30.8-75.2] vs 37.0 [17.6-56.4], P < .001). CONCLUSION: Patients with ICC incidentally diagnosed as having T2 or above T stage may consider additional LND.

Efficacy and safety of biosimilar trastuzumab (CT-P6) in routine clinical practice in the Republic of Korea: a real-world post-marketing surveillance study.

BACKGROUND: The trastuzumab biosimilar CT-P6 is approved for human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC), metastatic breast cancer (MBC), and metastatic gastric cancer (MGC). The objective of this post-marketing surveillance (PMS) study was to evaluate the real-world safety and effectiveness of CT-P6 in patients with HER2-positive cancers. RESEARCH DESIGN AND METHODS: This open-label, observational, prospective, PMS study collected data via investigator surveys from 35 centers in the Republic of Korea (5 October 2018-4 October 2022). Eligible patients with HER2-positive EBC, MBC, or MGC started CT-P6 treatment during routine clinical practice, followed by 1-year observation. Evaluations included adverse events (AEs), adverse drug reactions (ADRs), and effectiveness. RESULTS: Safety was analyzed in 642 patients (494 EBC, 94 MBC, 54 MGC). Overall, 325 (50.6%) patients experienced 1316 AEs, and 550 ADRs occurred in 199 (31.0%) patients. Unexpected ADRs occurred in 62 (9.7%) patients. Unexpected ADRs and ADRs of special interest did not raise any new safety signals. Among trastuzumab-naïve patients, 34/106 (32.1%) with EBC achieved pathological complete response; 30/74 (40.5%) MBC and 24/49 (49.0%) MGC patients achieved complete or partial response. CONCLUSIONS: In a real-world setting, CT-P6 demonstrated safety and efficacy findings consistent with previous CT-P6 studies.

Minimally invasive pancreatoduodenectomy by junior surgeon: Initial experience of the next generation.

BACKGROUND: Several guidelines exist for minimally invasive pancreatoduodenectomy (MIPD) regarding its prerequisites and learning curve. However, these guidelines are based on the experience of the pioneers of MIPD; minimal data exist on the experience of the next generation of surgeons. The aim of this study was to compare the two surgeon types (veteran and junior) for MIPD in terms of immediate postoperative outcomes. METHODS: The postoperative outcomes of 22 patients who underwent robot-assisted pancreatoduodenectomy (RAPD) by a junior surgeon from July 2021 to December 2022 were retrospectively reviewed. The outcomes were compared with the initial postoperative outcomes and the contemporary postoperative outcomes of RAPD by a veteran surgeon. RESULTS: In comparing the initial outcomes between the two surgeon types, the veteran surgeons showed a shorter operation time (junior surgeon vs. veteran surgeon: 606 ± 89 vs. 467 ± 77 min, p < 0.001). However, there was no significant difference in terms of postoperative outcomes, such as blood loss (300 [200-600] ml. vs. 200 [100-500] ml, p = 0.208), major complications (≥CDC IIIa: 4 (18.2%) vs. 4 (18.2%), p = 1.000), postoperative pancreatic fistula (POPF; ≥ISGPF Grade B: 2 (9.1%) vs. 3 (13.6%), p > 0.999), and length of hospital stay (18.0 ± 8.9 days vs. 18.3 ± 7.9 days, p = 0.915), between the two surgeon types. In addition, in a comparison of the contemporary outcomes, there was no significant difference in terms of postoperative outcome (complications: 4 (18.2%) vs 11 (11.1%), p = 0.580; POPF: 2 (9.1%) vs. 3 (3.0%), p = 0.484; length of hospital stay: 18.0 ± 8.9 vs. 15.0 ± 6.5 days, p = 0.065). CONCLUSION: The initial outcomes of MIPD by a well-trained junior surgeon were found to be comparable to those of MIPD by a veteran surgeon.

Validation of the 2022 European LeukemiaNet risk stratification for acute myeloid leukemia.

This study aimed to validate the 2022 European LeukemiaNet (ELN) risk stratification for acute myeloid leukemia (AML). A total of 624 newly diagnosed AML patients from 1998 to 2014 were included in the analysis. Genetic profiling was conducted using targeted deep sequencing of 45 genes based on recurrent driver mutations. In total, 134 (21.5%) patients had their risk classification reassessed according to the 2022 ELN risk stratification. Among those initially classified as having a favorable risk in 2017 (n = 218), 31 and 3 patients were reclassified as having intermediate risk or adverse risk, respectively. Among the three subgroups, the 2022 ELN favorable-risk group showed significantly longer survival outcomes than the other groups. Within the 2017 ELN intermediate-risk group (n = 298), 21 and 46 patients were reclassified as having favorable risk or adverse risk, respectively, and each group showed significant stratifications in survival outcomes. Some patients initially classified as having adverse risk in 2017 were reclassified into the intermediate-risk group (33 of 108 patients), but no prognostic improvements were observed in this group. A multivariable analysis identified the 2022 ELN risk stratification, age, and receiving allogeneic hematopoietic cell transplantation as significant prognostic factors for survival. The 2022 ELN risk stratification enables more precise decisions for proceeding with allogeneic hematopoietic cell transplantation for AML patients.

Automated assessment of pelvic radiographs using deep learning: A reliable diagnostic tool for pelvic malalignment.

Pelvic malalignment leads to general imbalance and adversely affects leg length. Timely and accurate diagnosis of pelvic alignment in patients is crucial to prevent additional complications arising from delayed treatment. Currently, doctors typically assess pelvic alignment either manually or through radiography. This study aimed to develop and assess the validity of a deep learning-based system for automatically measuring 10 radiographic parameters necessary for diagnosing pelvic displacement using standing anteroposterior pelvic X-rays. Between March 2016 and June 2021, pelvic radiographs from 1215 patients were collected. After applying specific selection criteria, 550 pelvic radiographs were chosen for analysis. These data were utilized to develop a deep learning-based system capable of automatically measuring radiographic parameters relevant to pelvic displacement diagnosis. The system's diagnostic accuracy was evaluated by comparing automatically measured values with those assessed by a clinician using 200 radiographs selected from the initial 550. The results indicated that the system exhibited high reliability, accuracy, and reproducibility, with a Pearson correlation coefficient of ≥0.9, an intra-class correlation coefficient of ≥0.9, a mean absolute error of ≤1 cm, mean square error of ≤1 cm, and root mean square error of ≤1 cm. Moreover, the system's measurement time for a single radiograph was found to be 18 to 20 times faster than that required by a clinician for manual inspection. In conclusion, our proposed deep learning-based system effectively utilizes standing anteroposterior pelvic radiographs to precisely and consistently measure radiographic parameters essential for diagnosing pelvic displacement.

Dimorphostylispilocorpus sp. nov. (Crustacea, Cumacea, Diastylidae), a new cumacean from Korean waters.

A new species of Cumacea belonging to the genus Dimorphostylis Zimmer was collected from the Dokdo and Ulleung Islands in the East Sea of Korea. The new species, Dimorphostylispilocorpussp. nov., can be distinguished from all other Dimorphostylis species by the combination of the body surface covered with numerous slender simple setae; carapace with one transverse, a pair of frontal, and three pairs of oblique ridges; three pairs of oblique ridges connected on a submedian carina; telson of the female with 1 pair of short simple and 1 short, stout simple seta centrally; 1 pair of stout simple and 3 pairs of short simple setae on the post-anal section; pleonite 5 of male with 1 spiniform seta on the ventral margin; post-anal section with 2 pairs of stout simple setae bearing a single subterminal setule on both sides; terminal margin with 3 stout simple setae; and a central seta slightly longer than the outer pair of setae. Full illustrations of the new species, including the mouthparts, are given in this paper. A key to the Korean species of Dimorphostylis is also provided.

Antioxidant and anti-hepatitis A virus activities of Ecklonia cava Kjellman extracts.

Ecklonia cava is a nutrient-rich algae species that contains abundant physiological phytochemicals, including peptides, carotenoids, fucoidans, and phlorotannins. However, elucidation of the antiviral effects of this algae and identification of new functional ingredients warrant further investigation. This study was aimed at investigating the potential anti-hepatitis A virus activities of extracts of E. cava prepared in different solvents. E. cava extracts were prepared using hot water and 70 % ethanol. The antioxidant activities of the extracts were confirmed by analyzing the total phenolic content, as well as 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid radical scavenging activities. The inhibitory effects of the extracts against hepatitis A virus were analyzed using real-time polymerase chain reaction. The E. cava extract yield was 22.5-27.2 % depending on the extraction solvent. The 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity was 70.44 % and 91.05 % for hot water and ethanol extracts at a concentration of 1000 ppm. The 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid radical scavenging activity of the ethanol extract was the highest (93.57 %) at 1000 µg/mL. Fourier-transform infrared was used to identify the functional groups (phlorotannin and alginate) in the extraction solvents. Ultra-high performance liquid chromatography with quadrupole time-of-flight tandem mass spectrometry analysis revealed a potential bioactive compound previously unidentified in E. cava. Finally, we identified the antiviral activity of E. cava extracts against hepatitis A virus replication. These findings demonstrate that E. cava could be used as an anti-hepatitis A virus functional food and biological material.

Inhibition of the Alternative Complement Pathway May Cause Secretion of Factor B, Enabling an Early Detection of Pancreatic Cancer.

This study aims to elucidate the cellular mechanisms behind the secretion of complement factor B (CFB), known for its dual roles as an early biomarker for pancreatic ductal adenocarcinoma (PDAC) and as the initial substrate for the alternative complement pathway (ACP). Using parallel reaction monitoring analysis, we confirmed a consistent ∼2-fold increase in CFB expression in PDAC patients compared with that in both healthy donors (HD) and chronic pancreatitis (CP) patients. Elevated ACP activity was observed in CP and other benign conditions compared with that in HD and PDAC patients, suggesting a functional link between ACP and PDAC. Protein-protein interaction analyses involving key complement proteins and their regulatory factors were conducted using blood samples from PDAC patients and cultured cell lines. Our findings revealed a complex control system governing the ACP and its regulatory factors, including Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation, adrenomedullin (AM), and complement factor H (CFH). Particularly, AM emerged as a crucial player in CFB secretion, activating CFH and promoting its predominant binding to C3b over CFB. Mechanistically, our data suggest that the KRAS mutation stimulates AM expression, enhancing CFH activity in the fluid phase through binding. This heightened AM-CFH interaction conferred greater affinity for C3b over CFB, potentially suppressing the ACP cascade. This sequence of events likely culminated in the preferential release of ductal CFB into plasma during the early stages of PDAC. (Data set ID PXD047043.).

Full-length single-molecule protein fingerprinting.

Proteins are the primary functional actors of the cell. While proteoform diversity is known to be highly biologically relevant, current protein analysis methods are of limited use for distinguishing proteoforms. Mass spectrometric methods, in particular, often provide only ambiguous information on post-translational modification sites, and sequences of co-existing modifications may not be resolved. Here we demonstrate fluorescence resonance energy transfer (FRET)-based single-molecule protein fingerprinting to map the location of individual amino acids and post-translational modifications within single full-length protein molecules. Our data show that both intrinsically disordered proteins and folded globular proteins can be fingerprinted with a subnanometer resolution, achieved by probing the amino acids one by one using single-molecule FRET via DNA exchange. This capability was demonstrated through the analysis of alpha-synuclein, an intrinsically disordered protein, by accurately quantifying isoforms in mixtures using a machine learning classifier, and by determining the locations of two O-GlcNAc moieties. Furthermore, we demonstrate fingerprinting of the globular proteins Bcl-2-like protein 1, procalcitonin and S100A9. We anticipate that our ability to perform proteoform identification with the ultimate sensitivity may unlock exciting new venues in proteomics research and biomarker-based diagnosis.