Skin Improvement Effects of Ultrasound-Enzyme-Treated Collagen Peptide Extracts from Flatfish (Paralichthys olivaceus) Skin in an In Vitro Model.

Collagen is considered to be an intercellular adhesive that prevents tissue stretching or damage. It is widely utilized in cosmetic skin solutions, drug delivery, vitreous substitutions, 3D cell cultures, and surgery. In this study, we report the development of a green technology for manufacturing collagen peptides from flatfish skin using ultrasound and enzymatic treatment and a subsequent assessment on skin functionality. First, flatfish skin was extracted using ultrasound in distilled water (DW) for 6 h at 80 °C. Molecular weight analysis via high-performance liquid chromatography (HPLC) after treatment with industrial enzymes (alcalase, papain, protamex, and flavourzyme) showed that the smallest molecular weight (3.56 kDa) was achieved by adding papain (0.5% for 2 h). To determine functionality based on peptide molecular weight, two fractions of 1100 Da and 468 Da were obtained through separation using Sephadex™ G-10. We evaluated the effects of these peptides on protection against oxidative stress in human keratinocytes (HaCaT) cells, inhibition of MMP-1 expression in human dermal fibroblast (HDF) cells, reduction in melanin content, and the inhibition of tyrosinase enzyme activity in murine melanoma (B16F10) cells. These results demonstrate that the isolated low-molecular-weight peptides exhibit superior skin anti-oxidant, anti-wrinkle, and whitening properties.

L-Fucose-Rich Sulfated Glycans from Edible Brown Seaweed: A Promising Functional Food for Obesity and Energy Expenditure Improvement.

The global obesity epidemic, exacerbated by the sedentary lifestyle fostered by the COVID-19 pandemic, presents a growing socioeconomic burden due to decreased physical activity and increased morbidity. Current obesity treatments show promise, but they often come with expensive medications, frequent injections, and potential side effects, with limited success in improving obesity through increased energy expenditure. This study explores the potential of a refined sulfated polysaccharide (SPSL), derived from the brown seaweed Scytosiphon lomentaria (SL), as a safe and effective anti-obesity treatment by promoting energy expenditure. Chemical characterization revealed that SPSL, rich in sulfate and L-fucose content, comprises nine distinct sulfated glycan structures. In vitro analysis demonstrated potent anti-lipogenic properties in adipocytes, mediated by the downregulation of key adipogenic modulators, including 5' adenosine monophosphate-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor γ (PPARγ) pathways. Inhibiting AMPK attenuated the anti-adipogenic effects of SPSL, confirming its involvement in the mechanism of action. Furthermore, in vivo studies using zebrafish models showed that SPSL increased energy expenditure and reduced lipid accumulation. These findings collectively highlight the therapeutic potential of SPSL as a functional food ingredient for mitigating obesity-related metabolic dysregulation by promoting energy expenditure. Further mechanistic and preclinical investigations are warranted to fully elucidate its mode of action and evaluate its efficacy in obesity management, potentially offering a novel, natural therapeutic avenue for this global health concern.

Co-existing Mediastinal Venous Malformation and Fusiform Superior Vena Cava Aneurysm in a Patient with Ischemic Stroke: A Case Report and Review of Literature.

BACKGROUND: Mediastinal venous malformation (MVM) and fusiform superior vena cava aneurysm (F-SVCA) are both rare congenital vascular anomalies. CASE PRESENTATIONS: A 46-year-old male presented with acute ischemic stroke of unknown etiology. Computed tomography (CT) angiography revealed the coexistence of MVM and F-SVCA. Diagnostic venography demonstrated a significant reduction in blood flow velocity within the F-SVCA, but failed to identify a direct connection to the left heart system or pulmonary vein. The patient expired due to extensive brain damage caused by a stroke. CONCLUSION: This case may increase the necessity of meticulous radiological evaluation and preventive management for these anomalies, as mediastinal vascular anomalies can result in thromboembolic complications.

The oxidative stress-dependent pulmonary inflammation of inhalable multi-walled carbon nanotube-containing nano-concrete dust and its comparison with conventional concrete dust and DQ12.

Nano-concrete, which is an admixture of nanomaterials in concrete recipes, has been investigated to overcome the limitations of existing concrete, such as its stability and strength. However, there is no information on the human health effects of broken-down dust released during the construction and demolition efforts. In this study, we prepared an inhalable fraction of multi-walled carbon nanotube-containing nano-concrete dust and performed comparative toxicity studies with conventional concrete dust and DQ12 using a rat intratracheal instillation model. Although the recipes for concrete and nano-concrete are entirely different, the pulverized dust samples showed similar physicochemical properties, such as 0.46-0.48 µm diameter and chemical composition. Both concrete and nano-concrete dust exhibited similar patterns and magnitudes, representing acute neutrophilic inflammation and chronic active inflammation with lymphocyte infiltration. The toxicity endpoints of the tested particles at both time points showed an excellent correlation with the reactive oxygen species levels released from the alveolar macrophages, highlighting that alveolar macrophages are the primary target cells and that the oxidative stress paradigm is the main toxicity mechanism of the tested particles. In addition, the toxicity potentials of both concrete and nano-concrete dust were more than 10 times lower than that of DQ12.

Crystallographic Pathways to Tailoring Metal-Insulator Transition through Oxygen Transport in VO2.

The metal-insulator (MI) transition of vanadium dioxide (VO2) is effectively modulated by oxygen vacancies, which decrease the transition temperature and insulating resistance. Oxygen vacancies in thin films can be driven by oxygen transport using electrochemical potential. This study delves into the role of crystallographic channels in VO2 in facilitating oxygen transport and the subsequent tuning of electrical properties. A model system is designed with two types of VO2 thin films: (100)- and (001)-oriented, where channels align parallel and perpendicular to the surface, respectively. Growing an oxygen-deficient TiO2 layer on these VO2 films prompted oxygen transport from VO2 to TiO2. Notably, in (001)-VO2 film, where oxygen ions move along the open channels, the oxygen migration deepens the depleted region beyond that in (100)-VO2, leading to more pronounced changes in metal-insulator transition behaviors. The findings emphasize the importance of understanding the intrinsic crystal structure, such as channel pathways, in controlling ionic defects and customizing electrical properties for applications.

Evaluating the anticancer potential of Polygonum multiflorum root-derived stilbenes against H2452 malignant pleural mesothelioma cells.

A naturally occurring stilbene, resveratrol, shows promising effects in the treatment of malignant pleural mesothelioma (MPM) both as a single agent and in combination with chemotherapeutic drugs. To discover new anticancer agents targeting MPM, stilbene-targeted isolation was performed on the roots of Polygonum multiflorum Thunb., an herbal medicine rich in stilbene compounds. In this study, seven stilbene glycosides (1-7) were isolated, along with four non-stilbenes (8-11), of which compounds 4 and 9-11 have not previously been isolated from this species. Stiquinoside A (1) is a previously undescribed stilbene glycoside, and its structure was elucidated as (E)-2,3,5,4'-tetrahydroxystilbene 2-O-ß-d-quinovopyranoside based on 1D and 2D-NMR, HR-ESI-MS, and acid hydrolysis experiments. Compounds 1, 4, 6, and 8 significantly inhibit the growth of MPM cancer cells H2452. These results demonstrate the potential utility of stilbenes in new strategies for the treatment of MPM.

Synergistic Tailoring of Electronic and Thermal Transports in Thermoelectric Se-Free n-Type (Bi,Sb)2Te3.

Se-free n-type (Bi,Sb)2Te3 thermoelectric materials, outperforming traditional n-type Bi2(Te,Se)3, emerge as a compelling candidate for practical applications of recovering low-grade waste heat. A 100% improvement in the maximum ZT of n-type Bi1.7Sb0.3Te3 is demonstrated by using melt-spinning and excess Te-assisted transient liquid phase sintering (LPS). Te-rich sintering promotes the formation of intrinsic defects (TeBi), elevating the carrier concentration and enhancing the electrical conductivity. Melt-spinning with excess Te fine-tunes the electronic band, resulting in a high power-factor of 0.35 × 10-3 W·m-1 K-2 at 300 K. Rapid volume change during sintering induces the formation of dislocation networks, significantly suppressing the lattice thermal conductivity (0.4 W·m-1 K-1). The developed n-type legs achieve a high maximum ZT of 1.0 at 450 K resulting in a 70% improvement in the output power of the thermoelectric device (7.7 W at a temperature difference of 250 K). This work highlights the synergy between melt-spinning and transient LPS, advancing the tailored control of both electronic and thermal properties in thermoelectric technology.

Predictive DNA damage signaling for low­dose ionizing radiation.

Numerous studies have attempted to develop biological markers for the response to radiation for broad and straightforward application in the field of radiation. Based on a public database, the present study selected several molecules involved in the DNA damage repair response, cell cycle regulation and cytokine signaling as promising candidates for low­dose radiation­sensitive markers. The HuT 78 and IM­9 cell lines were irradiated in a concentration­dependent manner, and the expression of these molecules was analyzed using western blot analysis. Notably, the activation of ataxia telangiectasia mutated (ATM), checkpoint kinase 2 (CHK2), p53 and H2A histone family member X (H2AX) significantly increased in a concentration­dependent manner, which was also observed in human peripheral blood mononuclear cells. To determine the radioprotective effects of cinobufagin, as an ATM and CHK2 activator, an in vivo model was employed using sub­lethal and lethal doses in irradiated mice. Treatment with cinobufagin increased the number of bone marrow cells in sub­lethal irradiated mice, and slightly elongated the survival of lethally irradiated mice, although the difference was not statistically significant. Therefore, KU60019, BML­277, pifithrin­α, and nutlin­3a were evaluated for their ability to modulate radiation­induced cell death. The use of BML­277 led to a decrease in radiation­induced p­CHK2 and γH2AX levels and mitigated radiation­induced apoptosis. On the whole, the present study provides a novel approach for developing drug candidates based on the profiling of biological radiation­sensitive markers. These markers hold promise for predicting radiation exposure and assessing the associated human risk.

Efficacy of Tegoprazan in Patients With Functional Dyspepsia: A Prospective, Multicenter, Single-arm Study.

Background/Aims: Acid-suppressive drugs, such as proton pump inhibitors (PPIs), are treatment options for functional dyspepsia (FD). However, the efficacy of potassium-competitive acid blockers (P-CABs) in treating FD has not yet been established. This prospective multicenter clinical trial-based study aimed to assess the efficacy and safety of tegoprazan as a P-CAB treatment in patients with FD. Methods: FD was diagnosed using the Rome IV criteria. All patients received tegoprazan 50 mg once daily for 8 weeks. Dyspeptic symptoms were assessed using a dyspepsia symptom questionnaire (5-point Likert scale, Nepean Dyspepsia Index-Korean [NDI-K], and gastroesophageal reflux disease-health-related quality of life [GERD-HRQL]). The main outcome was satisfactory symptom relief rates at 8 weeks. Results: In this study, from the initial screening of 209 patients, 173 were included in the per-protocol set analysis. Satisfactory symptom relief rates at 8 and 4 weeks were 86.7% and 74.6%, respectively. In addition, the NDI-K and GERD-HRQL scores significantly improved at 8 and 4 weeks compared with the baseline scores. The efficacy of tegoprazan was not influenced by the FD subtype or Helicobacter pylori status. In patients with overlapping FD and GERD, there was a greater improvement in the NDI-K and GERD-HRQL scores than in patients with FD symptoms only. No serious drug-related adverse events occurred during this study. Conclusion: Tegoprazan (50 mg) administered once daily provided satisfactory symptom relief for FD.

Actinidia arguta Extract Containing Myo-Inositol Suppresses TNF-α-Induced VCAM-1 Expression and Monocyte Adhesion to Endothelial Cells via Inhibition of the PTEN/Akt/GSK-3ß and NF-κB Signaling Pathways.

The primary inflammatory process in atherosclerosis, a major contributor to cardiovascular disease, begins with monocyte adhering to vascular endothelial cells. Actinidia arguta (kiwiberry) is an edible fruit that contains various bioactive components. While A. arguta extract (AAE) has been recognized for its anti-inflammatory characteristics, its specific inhibitory effect on early atherogenic events has not been clarified. We used tumor necrosis factor-α (TNF-α)-stimulated human umbilical vein endothelial cells (HUVECs) for an in vitro model. AAE effectively hindered the attachment of THP-1 monocytes and reduced the expression of vascular cell adhesion molecule-1 (VCAM-1) in HUVECs. Transcriptome analysis revealed that AAE treatment upregulated phosphatase and tensin homolog (PTEN), subsequently inhibiting phosphorylation of AKT and glycogen synthase kinase 3ß (GSK3ß) in HUVECs. AAE further hindered phosphorylation of AKT downstream of the nuclear factor kappa B (NF-κB) signaling pathway, leading to suppression of target gene expression. Oral administration of AAE suppressed TNF-α-stimulated VCAM-1 expression, monocyte-derived macrophage infiltration, and proinflammatory cytokine expression in C57BL/6 mouse aortas. Myo-inositol, identified as the major compound in AAE, played a key role in suppressing THP-1 monocyte adhesion in HUVECs. These findings suggest that AAE could serve as a nutraceutical for preventing atherosclerosis by inhibiting its initial pathogenesis.

A Study on the Retrospective Reinterpretation of BRCA1 and BRCA2 Variants.

BACKGROUND: Hereditary breast/ovarian cancer is associated with BRCA gene mutations. As large volumes of clinical data on BRCA variants are continuously updated, their clinical interpretation may change, leading to their reclassification. This study analyzed the class and proportion of the changed clinical interpretations of BRCA variants to validate the need for periodic reviews of these variants. METHODS: This retrospective study reinterpreted previously reported BRCA1 and BRCA2 exon variants according to the 2015 American College of Medical Genetics and Genomics guidelines and the clinical significance of the recent public genomic database. Reanalyzed results were obtained for patients tested for BRCA genetic mutation for 10 years and 4 months. RESULTS: We included data from 4,058 patients, with 595 having at least one pathogenic variant (P), likely pathogenic variant (LP), or variant of uncertain significance (VUS) at a detection rate of 14.66%. The numbers of exon and intron variants were 562 (87.81%) and 78 (12.19%), respectively. BRCA1 exhibited a significantly higher P/LP detection rate of 6.96% compared to that of BRCA2 at 6.89% (p < 0.001). Conversely, BRCA2 demonstrated a significantly higher VUS rate of 10.38% compared to that of BRCA1 at 5.08% (p < 0.001). Among BRCA1 mutations, substitutions were the most prevalent in P/LP and VUS. Among BRCA2 mutations, deletions were most prevalent in P/LP, and substitutions were most prevalent in VUS. Among the 131 patients with P/LP in BRCA1 exons, the clinical interpretation was reclassified in two cases (1.53%), one VUS and one benign/likely benign (B/LB), and 48 cases (48.00%) with VUS were reclassified; one to P/LP and 47 to B/LB. Among the 138 patients with P/LP in BRCA2 exons, the clinical interpretation was reclassified in six (4.35%), five to VUS, and one to B/LB, and all 74 with VUS were reclassified to B/LB. CONCLUSIONS: We determined the class and proportion of reclassified BRCA variants. In conclusion, reviews are required to provide clinical guidance, such as determining treatment direction and preventive measures in the future.

Insight into disparate nonradical mechanisms of peroxymonosulfate and peroxydisulfate activation by N-doped oxygen-rich biochar: Unraveling the role of active sites.

In this study, we first comprehensively studied peroxymonosulfate (PMS) and peroxydisulfate (PDS) activation mechanisms using N, O codoped sludge biochar (NOSB) to degrade organics from water. Among the catalysts, NOSB with a higher content of graphitic N, optimal edge nitrogen (pyridinic N and pyrrolic N), CO groups, sp2-hybridized C, and rich defects were demonstrated to be a superior catalyst. Therefore, by activating PDS and PMS, NOSB exhibited the highest rate of BPA degradation, which was 22-fold and 13-fold that of pristine sludge biochar, respectively. However, owing to different oxidation potentials and molecular structures, PMS and PDS show different degradation performances due to various catalytic mechanisms occurring, even with the same biochar. Due to the asymmetrical structure of PMS, electrons passed from PMS to NOSB and further generated singlet oxygen (1O2), which governs the degradation of bisphenol A with an auxiliary contribution of single electron transfer. Meanwhile, PDS is reduced at the Lewis basic sites of NOSB, forming inner-surface-bound {PDS-NOSB}, which was oxidizing around neighboring carbon and decomposed targets through transferring single and double electrons. NOSB is promising for practical applications because of its adaptation to a wide pH range, anions, high total organic carbon removal, tunable active sites, and re-usability for degrading organics via PMS/PDS activation. This study unveils knowledge about N, O codoped sludge biochar catalysts for activating PMS/PDS and advocates a great approach for organics' degradation in the environment.

Clinical Trial: Efficacy of Mosapride Controlled-release and Nortriptyline in Patients With Functional Dyspepsia: A Multicenter, Double-placebo, Double-blinded, Randomized Controlled, Parallel Clinical Study.

Background/Aims: Prokinetic agents and neuromodulators are among the treatment options for functional dyspepsia (FD), but their comparative efficacy is unclear. We aimed to compare the efficacy of mosapride controlled-release (CR) and nortriptyline in patients with FD after 4 weeks of treatment. Methods: Participants with FD were randomly assigned (1:1) to receive mosapride CR (mosapride CR 15 mg and nortriptyline placebo) or nortriptyline (mosapride CR placebo and nortriptyline 10 mg) in double-placebo, double-blinded, randomized controlled, parallel clinical study. The primary endpoint was defined as the proportion of patients with overall dyspepsia improvement after 4 weeks treatment. The secondary endpoints were changes in individual symptom scores, anxiety, depression, and quality of life. Results: One hundred nine participants were recruited and assessed for eligibility, and 54 in the mosapride CR group and 50 in the nortriptyline group were included in the modified intention-to-treat protocol. The rate of overall dyspepsia improvement was similar between groups (53.7% vs 54.0%, P = 0.976). There was no difference in the efficacy of mosapride CR and nortriptyline in a subgroup analysis by FD subtype (59.3% vs 52.5% in postprandial distress syndrome, P = 0.615; 44.4% vs 40.0% in epigastric pain syndrome, P = > 0.999; 50.0% vs 59.1% in overlap, P = 0.565; respectively). Both treatments significantly improved anxiety, depression, and quality of life from baseline. Conclusion: Mosapride CR and nortriptyline showed similar efficacy in patients with FD regardless of the subtype. Both treatments could be equally helpful for improving quality of life and psychological well-being while also relieving dyspepsia.

Saliva-based Proteinase K method: A rapid and reliable diagnostic tool for the detection of SARS-COV-2 in children.

Early and accurate detection of viruses in children might help prevent transmission and severe diseases. In this study, the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) detection in children was evaluated using saliva specimens with a Proteinase K (PTK)-based RNA preparation, as saliva collection is a simple and noninvasive procedure, even in young children, with fewer concerns about sample contamination. The saliva-based PTK and the conventional paired nasopharyngeal aspiration (NPA)-based detection methods were compared between COVID-19-positive and -negative children. In addition, the detection rate for SARS-COV-2 and the difference between admission and discharge by the saliva-based PTK method was tested in COVID-19 patients. The diagnostic accuracy of the saliva-based PTK method was 98.8% compared to NP swab-based reverse transcriptase polymerase chain reaction. Saliva samples showed high sensitivity (94.1%) and specificity (100%) when using the PTK method. Furthermore, the saliva-based PTK method significantly reduced the test processing time by 2 h. Notably, Ct values at discharge increased in saliva samples compared with those at admission, which might indicate patients' clinical conditions or virus activity. In conclusion, the saliva-based PTK implemented in this study streamlines RNA extraction, making the process faster, safer, and more cost-effective, demonstrating that this method is a rapid and reliable diagnostic tool for SARS-CoV-2 detection in children.

Porous Organic Polymers for Selective Palladium Recovery and Heterogeneous Catalysis.

Palladium (Pd) recycling from waste materials is an important approach in order to meet the growing demand for Pd originating from its broad range of applications including automotive industry, electronics and catalysis. In this article, we discuss the design principles of solid-sorbents for efficient recovery of Pd from waste sources with a particular emphasis on porous organic polymers (POPs), which emerged as promising porous materials for Pd recovery due to their tunable chemical functionality, stability and porosity. We discuss the critical role of binding sites and porosity in the Pd uptake capacity, adsorption kinetics and selectivity. We also highlight the use of captured Pd within the polymer networks as heterogeneous catalysts for cross-coupling reactions.

The Antioxidant Activity of Undaria pinnatifida Sporophyll Extract Obtained Using Ultrasonication: A Focus on Crude Polysaccharide Extraction Using Ethanol Precipitation.

Undaria pinnatifida, a marine biological resource from which antioxidants such as polysaccharides can be obtained, is primarily distributed in the coastal areas of East Asia. Reactive oxygen species (ROS) are essential for physiological processes; however, excess ROS levels in the body result in cellular oxidative damage. Several extraction methods exist; however, factors such as long extraction times and high temperatures degrade polysaccharides. Therefore, this study aimed to increase the yield of U. pinnatifida sporophyll extract (UPE), a U. pinnatifida byproduct, using ultrasonication, an environmentally friendly extraction method, and identify UPE components with antioxidant activity. UPE_2, 4, 6, and 8 extracts were obtained at extraction times of 2, 4, 6, and 8 h, respectively. UPE_8 had the highest yield (31.91%) and polysaccharide (69.22%), polyphenol, (8.59 GAE µg/mg), and fucoxanthin contents (2.3 µg/g). UPE_8 showed the greatest protective and inhibitory effects on ROS generation in H2O2-damaged Vero cells. Ethanol precipitation of UPE_8 confirmed that UPE_8P (precipitate) had superior antioxidant activity in Vero cells compared to UPE_8S (supernatant). UPE_8P contained a large amount of polysaccharides, a major contributor to the antioxidant activity of UPE_8. This study shows that UPE_8 obtained using ultrasonication can be a functional food ingredient with excellent antioxidant activity.

The Neuroprotective Effects of Dendropanax morbifera Water Extract on Scopolamine-Induced Memory Impairment in Mice.

This study investigated the neuroprotective effects of Dendropanax morbifera leaves and stems (DMLS) water extract on scopolamine (SCO)-induced memory impairment in mice. First, we conducted experiments to determine the protective effect of DMLS on neuronal cells. Treatment with DMLS showed a significant protective effect against neurotoxicity induced by Aß(25-35) or H2O2. After confirming the neuroprotective effects of DMLS, we conducted animal studies. We administered DMLS orally at concentrations of 125, 250, and 375 mg/kg for 3 weeks. In the Y-maze test, SCO decreased spontaneous alternation, but treatment with DMLS or donepezil increased spontaneous alternation. In the Morris water-maze test, the SCO-treated group showed increased platform reach time and decreased swim time on the target platform. The passive avoidance task found that DMLS ingestion increased the recognition index in short-term memory. Furthermore, memory impairment induced by SCO reduced the ability to recognize novel objects. In the Novel Object Recognition test, recognition improved with DMLS or donepezil treatment. In the mouse brain, except for the cerebellum, acetylcholinesterase activity increased in the SCO group and decreased in the DMLS and donepezil groups. We measured catalase and malondialdehyde, which are indicators of antioxidant effectiveness, and found that oxidative stress increased with SCO but was mitigated by DMLS or donepezil treatment. Thus, our findings suggest that ingestion of DMLS restored memory impairment by protecting neuronal cells from Aß(25-35) or H2O2-induced neurotoxicity, and by reducing oxidative stress.

Incidence and Distribution of the Pathogens Causing GI Infections at a University Hospital of Korea.

BACKGROUND: Gastrointestinal (GI) infections, caused by various pathogens such as bacteria, viruses, protozoa, and parasites, are the second most common infectious diseases. Molecular diagnostics that can simultaneously detect these pathogens are commonly used in syndromic approaches. The authors aimed to identify the causative pathogens of GI infections to provide clinically useful information. METHODS: This retrospective study used molecular diagnostic methods to determine the incidence and distribution of GI pathogens according to gender, age, and season and analyze their coinfection from August 2020 to December 2022. RESULTS: The overall incidence of at least one GI pathogen was 40.1% (991/2, 471). The positivity rates for bacteria and viruses were 33.1% (817/2, 471) and 9.2% (227/2,471), respectively; the positivity rate for bacteria was significantly higher than that for viruses (p < 0.001). The incidence of GI pathogens according to age group was highest in group 3 (59.9%), followed by group 4 (57.0%). The most common bacterial pathogen associated with GI infections was C. difficile, followed by diarrheagenic E. coli, Campylobacter spp., and Salmonella spp. Enteropathogenic E. coli accounted for a large percentage of diarrheagenic E. coli (63.6%, 157/247). Among the viral pathogens, norovirus GI/GII was the most commonly detected virus, followed by adenovirus F40/41 and rotavirus A. For bacterial- or viral-positive cases, the distribution of GI pathogens according to age group showed the highest proportion of C. difficile in all groups, except for group 2. In group 2, rotavirus A accounted for the highest percentage (61.1%, 22/36). The incidence of GI pathogens was the highest in summer (36.1%), followed by autumn (32.7%), and winter (18.0%). The co-infection rate with two or more pathogens was 16.9% (167/991). The rates of co-infection with two or more bacteria, bacteria and viruses, and two viruses were 58.1%, 31.7%, and 10.2%, re-spectively. CONCLUSIONS: Information on the incidence and distribution of GI pathogens might be clinically useful; however, unlike the distribution of other infectious pathogens, it is necessary to consider that microorganisms identified through molecular diagnostics can be detected even in healthy people without clinical symptoms.

Androgen receptor and hyaluronan-mediated motility receptor as new molecular targets of baicalein: new molecular mechanisms for its anticancer properties.

Natural compounds known as phytochemicals have served as valuable resources for the development of new anti-cancer drugs and treatment of malignancies. Among these phytochemicals, baicalein is an emerging anti-tumor flavonoid obtained from Scutellaria baicaleinsis (Lamiaceae), but its underlying mechanisms of action and molecular targets have not yet been completely elucidated. Here, we identified new mechanisms for the anti-tumor activities of baicalein, providing evidence that hyaluronan-mediated motility receptor (HMMR) and androgen receptor (AR) are new molecular targets of baicalein in human cancer cells. We observed that HMMR, known to be highly associated with poor prognosis in a wide range of human cancers, was substantially downregulated by baicalein at mRNA and protein levels. Reporter assays further revealed that the suppression of HMMR by baicalein might occur through a transcriptional regulatory mechanism with the participation of Egr-1, E2F3α, and serum response factor (SRF). We also found that baicalein significantly inhibits androgenic responses in hormone-responsive prostate cancer cells, indicating that this might be attributed to the downregulation of AR promoter activity by baicalein. Additionally, baicalein markedly induced the expression of tumor suppressive miR-30C, which might be partly involved in baicalein-mediated autophagy and anti-cancer effects. Overall, our study sheds light on new diverse mechanisms of the anti-cancer effects exhibited by baicalein, implying that baicalein could be a potential therapeutic agent against human cancers and function as an inhibitor of HMMR and AR.

Metagenomics and proteomics profiling of extracellular polymeric substances from municipal waste sludge and their application for soil and water bioremediation.

This study assessed the components of anaerobically digested sludge, activated sludge, and microbial and extracellular polymeric substance (EPS) enzymes to identify the mechanisms underlying nitrogen removal and soil regeneration. 16S rRNA gene amplicon-based sequencing was used to determine the microbial community composition and the related National Center for Biotechnology Information (NCBI) protein database was used to construct a conventional library from the observed community. EPS components were identified using gel-free proteomic (Liquid Chromatography with tandem mass spectrometry-LC/MS/MS) methods. Alginate-like EPS from aerobically activated sludge have strong potential for soil aggregation and water-holding capacity, whereas total EPS from anaerobic sludge have significant potential for ammonia removal under salt stress. Fourier transform infrared spectroscopy (FTIR) revealed that both EPS may contain proteins, carbohydrates, humic compounds, uronic acid, and DNA and determined the presence of O-H, N-H, C-N, CO, and C-H functional groups. These results demonstrate that the overall enzyme activity may be inactivated at 30 g L-1 of salinity. An annotation found in Kyoto Encyclopedia of Genes and Genomes (KEGG)- KEGG Automatic Annotation Server (KAAS) revealed that the top two metabolic activities in the EPS generated from the anaerobic sludge were methane and nitrogen metabolism. Therefore, we focused on the nitrogen metabolism reference map 00910. EPS from the anaerobically digested sludge exhibited nitrate reductase, nitrite reductase, and dehydrogenase activities. Assimilatory nitrate reduction, denitrification, nitrification, and anammox removed ammonia biochemically. The influence of microbial extracellular metabolites on water-holding capacity and soil aggregation was also investigated. The KAAS-KEGG annotation server was used to identify the main enzymes in the activated sludge-derived alginate-like extracellular EPS (ALE-EPS) samples. These include hydrolases, oxidoreductases, lyases, ligases, and transporters, which contribute to soil fertility and stability. This study improves our understanding of the overall microbial community structure and the associated biochemical processes, which are related to distinct functional genes or enzymes involved in nitrogen removal and soil aggregation. In contrast to conventional methods, microbial association with proteomics can be used to investigate ecological relationships, establishments, key player species, and microbial responses to environmental changes. Linking the metagenome to off-gel proteomics and bioinformatics solves the problem of analyzing metabolic pathways in complex environmental samples in a cost-effective manner.