Swd2/Cps35 determines H3K4 tri-methylation via interactions with Set1 and Rad6.

BACKGROUND: Histone H3K4 tri-methylation (H3K4me3) catalyzed by Set1/COMPASS, is a prominent epigenetic mark found in promoter-proximal regions of actively transcribed genes. H3K4me3 relies on prior monoubiquitination at the histone H2B (H2Bub) by Rad6 and Bre1. Swd2/Cps35, a Set1/COMPASS component, has been proposed as a key player in facilitating H2Bub-dependent H3K4me3. However, a more comprehensive investigation regarding the relationship among Rad6, Swd2, and Set1 is required to further understand the mechanisms and functions of the H3K4 methylation. RESULTS: We investigated the genome-wide occupancy patterns of Rad6, Swd2, and Set1 under various genetic conditions, aiming to clarify the roles of Set1 and Rad6 for occupancy of Swd2. Swd2 peaks appear on both the 5' region and 3' region of genes, which are overlapped with its tightly bound two complexes, Set1 and cleavage and polyadenylation factor (CPF), respectively. In the absence of Rad6/H2Bub, Set1 predominantly localized to the 5' region of genes, while Swd2 lost all the chromatin binding. However, in the absence of Set1, Swd2 occupancy near the 5' region was impaired and rather increased in the 3' region. CONCLUSIONS: This study highlights that the catalytic activity of Rad6 is essential for all the ways of Swd2's binding to the transcribed genes and Set1 redistributes the Swd2 to the 5' region for accomplishments of H3K4me3 in the genome-wide level.

Strategic combination of bacteriophages with highly susceptible cells for enhanced intestinal settlement and resistant cell killing.

Avian pathogenic Escherichia coli (APEC) causes enormous economic losses and is a primary contributor to the emergence of multidrug resistance (MDR)-related problems in the poultry industry. Bacteriophage (phage) therapy has been successful in controlling MDR, but phage-resistant variants have rapidly emerged through the horizontal transmission of diverse phage defense systems carried on mobile genetic elements. Consequently, while multiple phage cocktails are recommended for phage therapy, there is a growing need to explore simpler and more cost-effective phage treatment alternatives. In this study, we characterized two novel O78-specific APEC phages, φWAO78-1 and φHAO78-1, in terms of their morphology, genome, physicochemical stability and growth kinetics. Additionally, we assessed the susceptibility of thirty-two O78 APEC strains to these phages. We analyzed the roles of highly susceptible cells in intestinal settlement and fecal shedding (susceptible cell-assisted intestinal settlement and shedding, SAIS) of phages in chickens via coinoculation with phages. Furthermore, we evaluated a new strategy, susceptible cell-assisted resistant cell killing (SARK), by comparing phage susceptibility between resistant cells alone and a mixture of resistant and highly susceptible cells in vitro. As expected, high proportions of O78 APEC strains had already acquired multiple phage defense systems, exhibiting considerable resistance to φWAO78-1 and φHAO78-1. Coinoculation of highly susceptible cells with phages prolonged phage shedding in feces, and the coexistence of susceptible cells markedly increased the phage susceptibility of resistant cells. Therefore, the SAIS and SARK strategies were demonstrated to be promising both in vivo and in vitro.

Surgical Outcomes in Non-Small Cell Lung Cancer with Distant Metastasis: The Prognostic Significance of Delayed Metastasis Diagnosis.

BACKGROUND: The diagnosis of distant metastasis on preoperative examinations for non-small cell lung cancer (NSCLC) can be challenging, leading to surgery for some patients with uncertain metastasis. This study evaluated the prognostic impact of delayed diagnosis of metastasis on patients who underwent upfront surgery. METHODS: The study enrolled patients who underwent lobectomy or pneumonectomy for NSCLC between June 2010 and December 2017 and evaluated the presence of distant metastasis before surgery. Overall survival (OS) for patients with stage IV cancer was compared with that for patients without metastasis, and the prognostic factors were analyzed. RESULTS: Of 3046 patients (mean age, 63 years; 1770 men), 100 (3.3 %) had distant metastasis, diagnosed preoperatively in 1.4 % (42/3046) and postoperatively in 1.9 % (58/3046) of the patients. The two most common metastasis sites diagnosed after surgery were contralateral lung (22/58, 37.9 %) and ipsilateral pleura (16/58, 27.6 %). The OS (median, 42.7 months) for the patients with stage IV cancer diagnosed postoperatively was comparable with that for the patients with stage IIIB cancer (P = 0.865), whereas the OS (median OS, 91.7 months) for the patients with stage IV cancer diagnosed preoperatively was better than for the patients with stage IIIB cancer (P = 0.001). Among the patients with distant metastasis, squamous cell type (hazard ratio [HR], 3.15; P = 0.002) and systemic treatment for metastasis (HR, 2.42; P = 0.002) were independent predictors of worse OS. CONCLUSIONS: Among NSCLC patients undergoing upfront surgery, the OS for the patients with stage IV cancer diagnosed postoperatively was comparable with that for the patients with stage IIIB cancer. For patients with stage IV disease, squamous cell type and systemic treatment for metastasis were prognostic factors for poorer OS.

Complete genome sequences of two tombusvirus-like viruses identified in Echinacea purpurea seeds.

Echinacea is an herbaceous plant originating from North America that is cultivated for gardening and landscaping because of its showy flowers. Using high-throughput sequencing, we identified two viral contigs from echinacea seeds that were related to the family Tombusviridae. These two viruses were similar to oat chlorotic stunt virus (OCSV) and other unassigned tombusviruses; therefore, we tentatively named them Echinacea-associated tombusviruses 1 and 2 (EaTV1 and EaTV2, respectively). The EaTVs represent putative readthrough sites and have no poly(A) tails, aligning with the common features of family Tombusviridae. The EaTVs are included in a monophyletic group of OCSV and several unassigned tombusviruses. Because OCSV is the only member of Avenavirus to date, EaTVs are tentative members of Avenavirus, or they are close sister species to OCSV with several unassigned tombusviruses. RNA-dependent RNA polymerases and coat proteins were well conserved among EaTVs and unassigned tombusviruses; however, their similarities were not correlated, implying divergent and complex evolution.

Prevalence and outcomes of chronic comorbid conditions in patients with sepsis in Korea: a nationwide cohort study from 2011 to 2016.

BACKGROUND: Chronic comorbid conditions are common in patients with sepsis and may affect the outcomes. This study aimed to evaluate the prevalence and outcomes of common comorbidities in patients with sepsis. METHODS: We conducted a nationwide retrospective cohort study. Using data from the National Health Insurance Service of Korea. Adult patients (age ≥ 18 years) who were hospitalized in tertiary or general hospitals with a diagnosis of sepsis between 2011 and 2016 were analyzed. After screening of all International Classification of Diseases 10th revision codes for comorbidities, we identified hypertension, diabetes mellitus (DM), liver cirrhosis (LC), chronic kidney disease (CKD), and malignancy as prevalent comorbidities. RESULTS: Overall, 373,539 patients diagnosed with sepsis were hospitalized in Korea between 2011 and 2016. Among them, 46.7% had hypertension, 23.6% had DM, 7.4% had LC, 13.7% had CKD, and 30.7% had malignancy. In-hospital mortality rates for patients with hypertension, DM, LC, CKD, and malignancy were 25.5%, 25.2%, 34.5%, 28.0%, and 33.3%, respectively, showing a decreasing trend over time (P < 0.001). After adjusting for baseline characteristics, male sex, older age, use of mechanical ventilation, and continuous renal replacement therapy, LC, CKD, and malignancy were significantly associated with in-hospital mortality. CONCLUSIONS: Hypertension is the most prevalent comorbidity in patients with sepsis, and it is associated with an increased survival rate. Additionally, liver cirrhosis, chronic kidney disease, and malignancy result in higher mortality rates than hypertension and DM, and are significant risk factors for in-hospital mortality in patients with sepsis.

Changes in the intrinsic severity of severe acute respiratory syndrome coronavirus 2 according to the emerging variant: a nationwide study from February 2020 to June 2022, including comparison with vaccinated populations.

BACKGROUND: As the population acquires immunity through vaccination and natural infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), understanding the intrinsic severity of coronavirus disease (COVID-19) is becoming challenging. We aimed to evaluate the intrinsic severity regarding circulating variants of SARS-CoV-2 and to compare this between vaccinated and unvaccinated individuals. METHODS: With unvaccinated and initially infected confirmed cases of COVID-19, we estimated the case severity rate (CSR); case fatality rate (CFR); and mortality rate (MR), including severe/critical cases and deaths, stratified by age and compared by vaccination status according to the period regarding the variants of COVID-19 and vaccination. The overall rate was directly standardized with age. RESULTS: The age-standardized CSRs (aCSRs) of the unvaccinated group were 2.12%, 5.51%, and 0.94% in the pre-delta, delta, and omicron period, respectively, and the age-standardized CFRs (aCFRs) were 0.60%, 2.49%, and 0.63% in each period, respectively. The complete vaccination group had lower severity than the unvaccinated group over the entire period showing under 1% for the aCSR and 0.5% for the aCFR. The age-standardized MR of the unvaccinated group was 448 per million people per month people in the omicron period, which was 11 times higher than that of the vaccinated group. In terms of age groups, the CSR and CFR sharply increased with age from the 60 s and showed lower risk reduction in the 80 s when the period changed to the omicron period. CONCLUSIONS: The intrinsic severity of COVID-19 was the highest in the delta period, with over 5% for the aCSR, whereas the completely vaccinated group maintained below 1%. This implies that when the population is vaccinated, the impact of COVID-19 will be limited, even if a new mutation appears. Moreover, considering the decreasing intrinsic severity, the response to COVID-19 should prioritize older individuals at a higher risk of severe disease.

Long-term prognostic factors for cardiovascular events in patients with chest pain without diabetes mellitus nor significant coronary stenosis.

Chest pain is the most common symptom of coronary artery disease (CAD) and diabetes mellitus (DM) is a well-known single strongest risk factor for cardiovascular diseases. Thus, the impact of CAD nor DM on long-term clinical effects is reported widely, but the prognostic factors of non-DM patients presenting with chest pain without significant CAD are limited. A total of 1,046 patients with chest pain without DM and significant CAD who underwent coronary angiography (CAG) and acetylcholine (ACH) provocation tests were finally enrolled. Propensity score matching and multivariate Cox-proportional hazard ratio analysis were performed to adjust for baseline potential confounders. Major adverse cardiac and cerebrovascular events (MACCE) were defined as the composite of total death, myocardial infarction (MI), revascularization, stroke, and recurrent angina. This study aimed to evaluate the long-term prognostic factors for MACCE in patients with chest pain without DM and CAD up to 5 years. Coronary artery spasm (CAS) was the most common cause of chest pain. However, long-term MACCE of CAS was not worse than those of patients with chest pain without CAS when patients with CAS had subsequent optimal antianginal medication therapy. However, a recurrent chest pain remains a problem even with continuous antianginal medication therapy. Up to 5 years, the incidence of MACCE was in 7.3%, including recurrent angina 6.9%. Dyslipidemia (HR: 2.010, 95% CI 1.166-3.466, P = 0.012), mild-moderate (30-70%) coronary stenosis (HR: 2.369, 95% CI 1.118-5.018, P = 0.024), the use of aspirin (HR: 2.885, 95% CI 1.588-5.238, P < 0.001), and the use of nitrates (HR: 1.938, 95% CI 1.094-3.433, P = 0.023) were independent risk factors for MACCE. Among the patients with chest pain without DM and significant CAD, the incidence of MACE were rare, but recurrent angina was still a challenging problem who had treated with antianginal medications.

Feasibility and usefulness of cognitive monitoring using a new home-based cognitive test in mild cognitive impairment: a prospective single arm study.

BACKGROUND: The risk of dementia is increased in subjects with mild cognitive impairment (MCI). Despite the plethora of in-person cognitive tests, those that can be administered over the phone are lacking. We hypothesized that a home-based cognitive test (HCT) using phone calls would be feasible and useful in non-demented elderly. We aimed to assess feasibility and validity of a new HCT as an optional cognitive monitoring tool without visiting hospitals. METHODS: Our study was conducted in a prospective design during 24 weeks. We developed a new HCT consisting of 20 questions (score range 0-30). Participants with MCI (n = 38) were consecutively enrolled and underwent regular HCTs during 24 weeks. Associations between HCT scores and in-person cognitive scores and Alzheimer's disease (AD) biomarkers were evaluated. In addition, HCT scores in MCI participants were cross-sectionally compared with age-matched cognitively normal (n = 30) and mild AD dementia (n = 17) participants for discriminative ability of the HCT. RESULTS: HCT had good intra-class reliability (test-retest Cronbach's alpha 0.839). HCT scores were correlated with the Mini-Mental State Examination (MMSE), verbal memory delayed recall, and Stroop test scores but not associated with AD biomarkers. HCT scores significantly differed among cognitively normal, MCI, and mild dementia participants, indicating its discriminative ability. Finally, 32 MCI participants completed follow-up evaluations, and 8 progressed to dementia. Baseline HCT scores in dementia progressors were lower than those in non-progressors (p = 0.001). CONCLUSION: The feasibility and usefulness of the HCT were demonstrated in elderly subjects with MCI. HCT could be an alternative option to monitor cognitive decline in early stages without dementia.

Neuroprotective effect of whey protein hydrolysate containing leucine-aspartate-isoleucine-glutamine-lysine on HT22 cells in hydrogen peroxide-induced oxidative stress.

This study aimed to investigate the neuroprotective effects of whey protein hydrolysate (WPH) containing the pentapeptide leucine-aspartate-isoleucine-glutamine-lysine (LDIQK). Whey protein hydrolysate (50, 100, and 200 µg/mL) demonstrated the ability to restore the viability of HT22 cells subjected to 300 µM hydrogen peroxide (H2O2)-induced oxidative stress. Furthermore, at a concentration of 200 µg/mL, it significantly reduced the increase in reactive oxygen species production and calcium ion (Ca2+) influx induced by H2O2 by 46.1% and 46.2%, respectively. Similarly, the hydrolysate significantly decreased the levels of p-tau, a hallmark of tauopathy, and BCL2 associated X (BAX), a proapoptosis factor, while increasing the protein levels of choline acetyltransferase (ChAT), an enzyme involved in acetylcholine synthesis, brain-derived neurotrophic factor (BDNF), a nerve growth factor, and B-cell lymphoma 2 (BCL2, an antiapoptotic factor. Furthermore, it increased nuclear factor erythroid 2-related factor 2 (Nrf2)-hemoxygenase-1(HO-1) signaling, which is associated with the antioxidant response, while reducing the activation of mitogen-activated protein kinase (MAPK) signaling pathway components, namely phosphor-extracellular signal-regulated kinases (p-ERK), phosphor-c-Jun N-terminal kinases (p-JNK), and p-p38. Column chromatography and tandem mass spectrometry analysis identified LDIQK as a compound with neuroprotective effects in WPH; it inhibited Ca2+ influx and regulated the BAX/BCL2 ratio. Collectively, WPH containing LDIQK demonstrated neuroprotective effects against H2O2-induced neuronal cell damage, suggesting that WPH or its active peptide, LDIQK, may serve as a potential edible agent for improving cognitive dysfunction.

Epidemiology of Respiratory Viruses in Korean Children Before and After the COVID-19 Pandemic: A Prospective Study From National Surveillance System.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic led to a decrease in the seasonal incidence of many respiratory viruses worldwide due to the impact of nonpharmaceutical interventions (NPIs). However, as NPI measures were relaxed, respiratory viral infections re-emerged. We aimed to characterize the epidemiology of respiratory viruses in Korean children during post-COVID-19 pandemic years compared to that before the pandemic. METHODS: A nationwide prospective ongoing surveillance study has been conducted for detection of respiratory viruses between January 2017 and June 2023. We included data on adenovirus (AdV), human bocavirus (HBoV), human coronavirus (HCoV), human metapneumovirus (HMPV), human rhinovirus (HRV), influenza virus (IFV), parainfluenza virus (PIV), and respiratory syncytial virus (RSV), which were detected in children and adolescents younger than 20 years. We analyzed the weekly detection frequency of individual viruses and the age distribution of the affected children. The study period was divided into prepandemic (2017-2019) and postpandemic (2021-2023) periods. RESULTS: A total of 19,589 and 14,068 samples were collected in the pre- and postpandemic periods, respectively. The overall detection rate of any virus throughout the study period was 63.1%, with the lowest occurring in the 2nd half of 2020 (50.6%) and the highest occurring in the 2nd half of 2021 (72.3%). Enveloped viruses (HCoV, HMPV, IFV, PIV, and RSV) almost disappeared, but nonenveloped viruses (AdV, HBoV, and HRV) were detected even during the peak of the COVID-19 pandemic. The codetection rate increased from 15.0% prepandemic to 19.1% postpandemic (P < 0.001). During the postpandemic period, a large out-of-season PIV and HMPV epidemic occurred, but the usual seasonality began to be restored in 2023. The mean age of children with each virus detected in 2023 was significantly greater than that in prepandemic years (P = 0.003 and 0.007 for AdV and HCoV, respectively; P < 0.001 for others). The mean age of children with IFV increased in 2022 (11.1 ± 5.2 years) from prepandemic years (7.9 ± 4.6 years) but decreased to 8.7 ± 4.1 years in 2023. CONCLUSION: With the relaxation of NPI measures, several seasonal respiratory viruses cocirculated with unusual seasonal epidemic patterns and were associated with increasing age of infected children.

First report of a rust disease of Lycium chinense caused by Puccinia tumidipes in Korea.

Lycium chinense Mill is a deciduous broad-leaved shrub belonging to the Solanaceae family and, is widely distributed throughout Korea. This plant is native to, or cultivated for various oriental medicinal purposes in, multiple regions of Asia, including Korea, China, and Japan (Lee 1982; Kim et al. 1994). Eleven Puccinia species have been reported to infect Lycium species (Otálora et al. 2018). In May and October 2022, symptoms of rust disease caused by Puccinia sp. were observed on almost all the leaves of about 60 sprawling stems of L. chinense plants on the seashore of Jeju island, Korea (33°14'15.0835″N, 126°30'53.40E). Brownish red (uredinium) or blackish brown (telium) pustules were observed on upper and lower surfaces of infected leaves. These symptoms were observed on about 40 L. chinense plants, barely growing between rocks on the seashore of Ulsan Metropolitan City, and on the about 20 L. chinense plants on a small home garden of Jindo-gun, Korea, in June and October 2023, respectively. Uredinia were amphigenous, individually scattered, but sometimes formed groups of two or three on leaves and sepals, ferruginous, pulverulent, and surrounded by a ruptured epidermis, often developing into blackish telia. Urediniospores were either ellipsoid or ovoid, approximately 29.3-34.9 × 17-24.3 µm, with yellowish walls, 1-2 µm thick. The germ pores were bizonate, and each band contained four pores covered by low papillae. Blackish-brown telia were observed on both leaf surfaces. Teliospores were broadly ellipsoidal, and rounded at the apex and towards the base. They were measured approximately 37.1-53.4 × 25-34.5 µm. The walls were light chestnut-brown and 2-3.7 µm thick, apically up to 5-9 µm thick. The swollen pedicel was persistent, basal, hyaline, smooth, and similar in length to the spores (Fig. 1). These morphological characteristics were similar to those of P. tumidipes, as described by Otálora et al. (2018). The representative specimens were preserved at the Animal and Plant Quarantine Agency Herbarium (PQK220531, -230605, and -231026). The fungal internal transcribed spacer (ITS2) and cytochrome oxidase subunit 3(CO3) regions were amplified from the total DNA of the isolates, using the primer pairs ITS5, ITS4, CO3F1, and CO3R1 for phylogenetic analysis (White et al. 1990; Vialle et al. 2009). PCR products were sequenced (Celemics, Seoul, Korea), and deposited in GenBank (Accession numbers are shown in Fig. 2.). The combined ITS2 and CO3 sequences were grouped with those of other isolates of P. tumidipes in the phylogenetic tree (Fig. 2). In November 2022, three pathogenicity tests were conducted using a urediniospore suspension made with the PQK220531 isolate in sterile distilled water. The suspension was smeared onto the upper surface of healthy L. chinense leaves. The three inoculated plants were kept in the dark at saturated moisture levels for 24 hours and placed in an isolated glasshouse together with the three control plants. After two weeks, uredinia of P. tumidipes were observed on the leaves of the inoculated plants, but not on the control plants. Although no spermogonial or aecial stage has been observed in Korea, our study has proven that P. tumidipes is the causal fungus of rust disease in L. chinense. This result is also the first discovery of the New-World P. tumidipes in Asia, showing this fungus is not limitedly distributed in America and suggesting further surveys be done on its exact geographical distribution.

First report of Puccinia xanthii causing rust disease on Xanthium orientale in Korea.

Puccinia xanthii Schw. is a microcyclic rust fungus, first found on Xanthium strumarium Lour in North Carolina, the United States. This rust fungus is native to the continental United States, Hawaii, Mexico, and the West Indies (Arthur 1934). It has become notoriously invasive and is now distributed in the Europe (Bulgaria, France, Hungary, Italy, Romania, Spain, and the former Yugoslavia), India, Indonesia, Australia, and South Africa (Parmelee 1969; Alcorn 1976; Wahyuno 2012). In East Asia, the fungus has been reported in Japan (Hiratsuka et al. 1992) and China (Zhao et al. 2014) but not in Korea. It has been reported mainly on the invasive weeds Xanthium and Ambrosia species. In addition, it rarely occurs on sunflowers (Helianthus spp.) in Australia (Alcorn 1976), South Africa (Pretorius et al. 2000), and North America (Gulya and Charlet 2002). In Korea, rust disease symptoms caused by a Puccinia fungus were first found on X. orientale L. at the roadside of Okcheon-gun, Chungcheongbuk-do (36 27'95.428"N 127 66'26.378"E) in October 2021 and were repeatedly observed in the same site in 2022. The similar symptom was additionally found on X. orientale in Yesan-gun, Oct. 2022. The symptoms were brown spots on round chlorotic haloes on the adaxial leaf surface and dark brown pustules on the abaxial leaf surface. Telia were brown to dark brown, round, mostly grouped, 0.28-0.61 mm in diameter, and mainly formed on the abaxial leaf surface but sometimes on the adaxial leaf surface. Teliospores were two-celled, pedicellate, and measured 37.6-110 × 12.4-21.5 µm in size; the wall was yellowish or almost colorless, smooth, 1.2-2.6 µm thick at the sides, and up to 7.4 µm thick at the apex. The morphological characteristics of the teliospores were identical to those of P. xanthii described by Arthur (1934) and Parmelee (1969). Based on phylogenetic analyses (e-Xtra 2) of the internal transcribed spacer (ITS) and partial large subunit (LSU) rDNA extracted from the teliospores, they were identified as P. xanthii. BLAST analysis showed that the sequences had high homologies (over 99.82%) with the reference strains of P. xanthii (EF635903 and KX999896). The representative specimens were preserved at the Animal and Plant Quarantine Agency Herbarium (PQK211005 for Okcheon-gun isolate and PQK220913 for Yesan-gun) and the sequences were deposited in GenBank (OR958716 and OR958692). A pathogenicity test was performed by dropping a suspension of germinating teliospores and basidiospores onto the adaxial leaf surfaces of apparently healthy X. orientale plants in Oct. 2022, using the isolate PQK220913 (OR958692). The three inoculated plants were placed together with three controls treated with only distilled water, in the dark at saturated humidity for 24 hours in an isolated greenhouse. After two weeks, typical rust symptoms were observed in the three infected plants, whereas no symptoms appeared in the control plants (e-Xtra 1). The causal fungus was identified as P. xanthii based on host relationships, successful experimental inoculation, morphological characteristics, and sequence similarity of partial DNA fragments. To our knowledge, this is the first report of P. xanthii on X. orientale in Korea. P. xanthii was additionally confirmed on X. orientale in Gumi-si, Boeun-gun, Seongju-gun, Naju-si, and Gunsan-si in 2023, indicating its wide distribution in Korea. It is expected that P. xanthii could be a candidate as a biological agent for controlling the invasive weed, X. orientale.

Traumatic Neuroma in the External Auditory Canal.

Traumatic neuroma is the reparative proliferation of axons and Schwann cells at the proximal end of a severed nerve following injury or surgery. Traumatic neuromas with or without clinical symptoms have rarely been reported in the external auditory canal. A 50-year-old woman with a history of trauma visited our otorhinolaryngology clinic with a 7 × 5-mm mass localized on the anterior wall of the external auditory canal. The mass was easily removed via surgical excision and was histopathologically diagnosed as a neuroma. No signs of recurrence were observed after excision. Herein, the authors present this case, along with a review of the literature.

Pb2+ Ion Sensors Employing Gold Etching Process: Comparative Investigation on Au Nanorods and Au Nanotriangles.

The leaching phenomenon of gold (Au) nanomaterials by Pb2+ ions in the presence of 2-mercaptoethanol (2-ME) and thiosulfate (S2O32- ion) has been systematically applied to a Pb2+ ion sensor. To further investigate the role of Pb2+ ions in sensors containing Au nanomaterials, we revisited the leaching conditions for Au nanorods and compared them with the results for Au nanotriangles. By monitoring the etching rate, it was revealed that Pb2+ ions were important for the acceleration of the etching rate mainly driven by 2-ME and S2O32- pairs, and nanomolar detection of Pb2+ ions were shown to be promoted through this catalytic effect. Using the etchant, the overall size of the Au nanorods decreased but showed an unusual red-shift in UV-Vis spectrum indicating increase of aspect ratio. Indeed, the length of Au nanorods decreased by 9.4% with the width decreasing by 17.4% over a 30-min reaction time. On the other hand, the Au nanotriangles with both flat sides surrounded mostly by dense Au{111} planes showed ordinary blue-shift in UV-Vis spectrum as the length of one side was reduced by 21.3%. By observing the changes in the two types of Au nanomaterials, we inferred that there was facet-dependent alloy formation with lead, and this difference resulted in Au nanotriangles showing good sensitivity, but lower detection limits compared to the Au nanorods.

Broncho-Vaxom Attenuates Lipopolysaccharide-Induced Inflammation in a Mouse Model of Acute Lung Injury.

Acute lung injury (ALI) is a condition associated with acute respiratory failure, resulting in significant morbidity and mortality. It involves cellular changes such as disruption of the alveolar-capillary membrane, excessive neutrophil migration, and release of inflammatory mediators. Broncho-Vaxom® (BV), a lyophilized product containing cell membrane components derived from eight bacteria commonly found in the respiratory tract, is known for its potential to reduce viral and bacterial lung infections. However, the specific effect of BV on ALI has not been clearly defined. This study explored the preventive effects of BV and its underlying mechanisms in a lipopolysaccharide (LPS)-induced ALI mouse model. Oral BV (1 mg/kg) gavage was administered one hour before the intratracheal injection of LPS to evaluate its preventive effect on the ALI model. The pre-administration of BV significantly mitigates inflammatory parameters, including the production of inflammatory mediators, macrophage infiltration, and NF-κB activation in lung tissue, and the increase in inflammatory cells in bronchoalveolar lavage fluid (BALF). Moreover, BV (3 µg/mL) pretreatment reduced the expression of M1 macrophage markers, interleukins (IL-1ß, IL-6), tumor necrosis factor α, and cyclooxygenase-2, which are activated by LPS, in both mouse alveolar macrophage MH-S cells and human macrophage THP-1 cells. These findings showed that BV exhibits anti-inflammatory effects by suppressing inflammatory mediators through the NF-κB pathway, suggesting its potential to attenuate bronchial and pulmonary inflammation.

Enhancing Human Cutaneous Wound Healing through Targeted Suppression of Large Conductance Ca2+-Activated K+ Channels.

The modulation of K+ channels plays a crucial role in cell migration and proliferation, but the effect of K+ channels on human cutaneous wound healing (CWH) remains underexplored. This study aimed to determine the necessity of modulating K+ channel activity and expression for human CWH. The use of 25 mM KCl as a K+ channel blocker markedly improved wound healing in vitro (in keratinocytes and fibroblasts) and in vivo (in rat and porcine models). K+ channel blockers, such as quinine and tetraethylammonium, aided in vitro wound healing, while Ba2+ was the exception and did not show similar effects. Single-channel recordings revealed that the Ba2+-insensitive large conductance Ca2+-activated K+ (BKCa) channel was predominantly present in human keratinocytes. NS1619, an opener of the BKCa channel, hindered wound healing processes like proliferation, migration, and filopodia formation. Conversely, charybdotoxin and iberiotoxin, which are BKCa channel blockers, dramatically enhanced these processes. The downregulation of BKCa also improved CWH, whereas its overexpression impeded these healing processes. These findings underscore the facilitative effect of BKCa channel suppression on CWH, proposing BKCa channels as potential molecular targets for enhancing human cutaneous wound healing.

Identification of Short-Chain Fatty Acids for Predicting Preterm Birth in Cervicovaginal Fluid Using Mass Spectrometry.

Preterm birth (PTB) refers to delivery before 37 weeks of gestation. Premature neonates exhibit higher neonatal morbidity and mortality rates than term neonates; therefore, predicting and preventing PTB are important. In this study, we investigated the potential of using short-chain fatty acid (SCFA) levels, specific vaginal microbiota-derived metabolites, as a biomarker in predicting PTB using gas chromatography/mass spectrometry. Cervicovaginal fluid (CVF) was collected from 89 pregnant women (29 cases of PTB vs. 60 controls) without evidence of other clinical infections, and SCFA levels were measured. Furthermore, the PTB group was divided into two subgroups based on birth timing after CVF sampling: delivery ≤ 2 days after sampling (n = 10) and ≥2 days after sampling (n = 19). The concentrations of propionic acid, isobutyric acid, butyric acid, valeric acid, hexanoic acid, and heptanoic acid were significantly higher in the PTB group than in the term birth (TB) group (p < 0.05). In particular, the concentrations of propionic acid, isobutyric acid, hexanoic acid, and heptanoic acid were continuously higher in the PTB group than in the TB group (p < 0.05). In the delivery ≤ 2 days after sampling group, the propionic acid, isobutyric acid, hexanoic acid, and heptanoic acid levels were significantly higher than those in the other groups (p < 0.05). This study demonstrated a significant association between specific SCFAs and PTB. We propose these SCFAs as potential biomarkers for the prediction of PTB.

Ibulocydine Inhibits Migration and Invasion of TNBC Cells via MMP-9 Regulation.

Triple-negative breast cancer (TNBC) accounts for approximately 15-20% of all breast cancer types, indicating a poor survival prognosis with a more aggressive biology of metastasis to the lung and a short response duration to available therapies. Ibulocydine (IB) is a novel (cyclin-dependent kinase) CDK7/9 inhibitor prodrug displaying potent anti-cancer effects against various cancer cell types. We performed in vitro and in vivo experiments to determine whether IB inhibits metastasis and eventually overcomes the poor drug response in TNBC. The result showed that IB inhibited the growth of TNBC cells by inducing caspase-mediated apoptosis and blocking metastasis by reducing MMP-9 expression in vitro. Concurrently, in vivo experiments using the metastasis model showed that IB inhibited metastasis of MDA-MB-231-Luc cells to the lung. Collectively, these results demonstrate that IB inhibited the growth of TNBC cells and blocked metastasis by regulating MMP-9 expression, suggesting a novel therapeutic agent for metastatic TNBC.

Information Geometry Theoretic Measures for Characterizing Neural Information Processing from Simulated EEG Signals.

In this work, we explore information geometry theoretic measures for characterizing neural information processing from EEG signals simulated by stochastic nonlinear coupled oscillator models for both healthy subjects and Alzheimer's disease (AD) patients with both eyes-closed and eyes-open conditions. In particular, we employ information rates to quantify the time evolution of probability density functions of simulated EEG signals, and employ causal information rates to quantify one signal's instantaneous influence on another signal's information rate. These two measures help us find significant and interesting distinctions between healthy subjects and AD patients when they open or close their eyes. These distinctions may be further related to differences in neural information processing activities of the corresponding brain regions, and to differences in connectivities among these brain regions. Our results show that information rate and causal information rate are superior to their more traditional or established information-theoretic counterparts, i.e., differential entropy and transfer entropy, respectively. Since these novel, information geometry theoretic measures can be applied to experimental EEG signals in a model-free manner, and they are capable of quantifying non-stationary time-varying effects, nonlinearity, and non-Gaussian stochasticity presented in real-world EEG signals, we believe that they can form an important and powerful tool-set for both understanding neural information processing in the brain and the diagnosis of neurological disorders, such as Alzheimer's disease as presented in this work.

Minimum Information Variability in Linear Langevin Systems via Model Predictive Control.

Controlling the time evolution of a probability distribution that describes the dynamics of a given complex system is a challenging problem. Achieving success in this endeavour will benefit multiple practical scenarios, e.g., controlling mesoscopic systems. Here, we propose a control approach blending the model predictive control technique with insights from information geometry theory. Focusing on linear Langevin systems, we use model predictive control online optimisation capabilities to determine the system inputs that minimise deviations from the geodesic of the information length over time, ensuring dynamics with minimum "geometric information variability". We validate our methodology through numerical experimentation on the Ornstein-Uhlenbeck process and Kramers equation, demonstrating its feasibility. Furthermore, in the context of the Ornstein-Uhlenbeck process, we analyse the impact on the entropy production and entropy rate, providing a physical understanding of the effects of minimum information variability control.