Effect of modification methods on the physical properties and immunomodulatory activity of particulate ß-glucan.

ß-Glucan is an immunoenhancing agent whose biological activities are linked to molecular structure. On that basis, the polysaccharide can be physiochemically modified to produce valuable functional materials. This study investigated the physical properties and immunostimulatory activity of modified ß-glucan. Alkali-treated ß-glucan had a distinct shape and smaller particle size than untreated ß-glucan. The reduced particle size was conducive to the stability of the suspension because the ß-glucan appeared to be completely dissolved by this treatment, forming an amorphous mass. Furthermore, alkali treatment improved the immunostimulating activity of ß-glucan, whereas exposure of macrophages to heat-treated ß-glucan decreased their immune activity. ß-Glucan with reduced particle size by wet-grinding also displayed immunomodulatory activities. These results suggested that the particle size of ß-glucan is a key factor in ß-glucan-induced immune responses of macrophages. Thus, the modification of the ß-glucan particle size provides new opportunities for developing immunoenhancing nutraceuticals or pharmacological therapies in the future.

Analysis of forest cover change and its driving factors in Senan district, Amhara Region, Ethiopia.

Forests are pivotal in upholding and stabilizing ecosystem functions and services globally. Assessing changes in forest cover serves as a crucial indicator to comprehend the scope, scale, and dynamics of land use and land cover alterations on regional and global scales. This study evaluates the forest cover changes between 2005 and 2021, pinpointing the key drivers of forest land changes within the Senan district in Ethiopia's Amhara region. The analysis incorporated Landsat satellite images from 2005, 2011, and 2021, supplemented by field surveys using questionnaire data. Results reveal a shift: forest cover declined from 13.6% (2005) to 11.2% (2011) but rose to 15.4% by 2021, averaging a 12.9% annual change. Several crucial factors were identified as contributors to this forest cover change. These include expanding agricultural land, population growth, urbanization, and using wood as a fuel source. Poverty, exacerbated by population growth, climate change impacts, and a scarcity of food resources, directly linked to a shortage of farmlands, emerged as significant drivers of forest cover change. In light of these findings, an in-depth analysis of land use and land cover dynamics should be conducted, particularly at the expense of forest lands. Moreover, implementing sustainable management practices by developing strategies for intensive agriculture and fostering environmentally friendly non-farm income-generating activities is essential. This study provides reference material to policymakers and land-use planners setting sustainable development goals, advocating for balanced economic growth and environmental conservation to foster a harmonious relationship between humans and forests.

Delayed Pulsatile Tinnitus by an Ascending Pharyngeal Artery-Internal Jugular Vein Fistula Caused by Blunt Trauma: A Case Report and Review of the Literature.

Head and neck trauma-induced pulsatile tinnitus (PT) should be approached with caution, as it can rarely be attributed to an arteriovenous fistula (AVF). We present a 26-year-old male with a history of blunt trauma who presented delayed PT with direct AVF between the ascending pharyngeal artery (APA) and the internal jugular vein (IJV). The patient underwent occlusion of the fistula with transarterial embolization using coils and PT was completely resolved, confirming successful treatment. The delayed manifestation of PT in the APA-IJV fistula is probably due to the gradual formation of a pseudoaneurysm and subsequent AVF. This case highlights the importance of investigating PT in head trauma patients, as it can be a sign of AVF and possible complications. Overall, this case contributes to understanding delayed PT with AVF and emphasizes the importance of prompt diagnosis and treatment of AVF in patients with head and neck trauma.

Current technologies for heavy metal removal from food and environmental resources.

Exposure to heavy metals in water and food poses a significant threat to human well-being, necessitating the efficient removal of these contaminants. The process of urban development exacerbates heavy metal pollution, thereby increasing risks to both human health and ecosystems. Heavy metals have the capacity to enter the food chain, undergo bioaccumulation and magnify, ultimately resulting in adverse effects on human health. Therefore, implementing effective pollution control measures and adopting sustainable practices are crucial for mitigating exposure and associated health risks. Various innovative approaches, including adsorption, ion exchange, and electrochemical technology, are currently being actively investigated to cope with the issue of heavy metal contamination. These innovative methods offer benefits such as efficient recycling, cost-effectiveness and environmental friendliness. In this review, we summarize recent advances for removing heavy metals from water, soil and food, providing valuable guidance for environmental engineers and researchers seeking to address contamination challenges.

Distribution of sika deer (Cervus nippon) and the bioclimatic impact on their habitats in South Korea.

Invasive species and climate change are primary factors influencing biodiversity, and examining the behavior of invasive species is essential for effective conservation management. Here, we report the global distribution of the sika deer (Cervus nippon) based on locations reported in published literature (Google Scholar), the Global Biodiversity Information Facility (GBIF) database, and the International Union for Conservation of Nature report. We used the maximum entropy (Maxent) model to examine the impact of climate change on sika deer habitats in South Korea based on GBIF occurrence data and WorldClim bioclimatic variables. Habitat suitability analysis was performed using the Maxent model under Representative Concentration Pathways (RCPs) 4.5 and 8.5 (for predicted climatic conditions in both 2050 and 2070) to project the effects of different climate change scenarios on South Korean sika deer habitats. We identified that the sika deer is distributed in 39 countries worldwide. Due to climate change effects, South Korean sika deer habitats will decline by approximately 24.98% and 20.63% (under RCP 4.5) and by 50.51% and 57.35% (under RCP 8.5) by 2050 and 2070, respectively. Our findings shed light on sika deer ecology and provide reference data for future conservation management strategies and policy design.

Prevalence and Contributing Factors of Anxiety and Depression in Patients with Vestibular Migraine.

Objective: Anxiety and depression are psychiatric comorbidities potentially associated with dizziness and migraine, which can influence disease state, prognosis, and clinical outcomes. Vestibular migraine (VM) is a disease that causes repeated vestibular symptoms in people with a history of migraines. We investigated the prevalence and contributing factors of anxiety and depression in patients with VM. Methods: A total of 74 patients with VM were enrolled in this study. All patients underwent pure-tone audiometry, the examination of spontaneous nystagmus, Dix-Hallpike maneuver or supine-roll test, video head impulse test, and caloric testing on the day of the visit. We used the Hospital Anxiety and Depression Scale (HADS) to assess the symptoms of anxiety and depression. Dizziness Handicap Inventory was used to measure the intensity of vestibular symptoms. The participants were divided into normal and abnormal groups based on their HADS anxiety and depression scores, and demographic and clinical factors were analyzed. To identify factors associated with anxiety and depression, multivariate logistic regression analyses were performed. Results: A total of 36 (48.6%) patients demonstrated clinically relevant anxiety levels, and 24 (32.4%) demonstrated depression. Twenty-five (33.8%) patients were diagnosed with peripheral vestibular dysfunction. In the multivariable analyses, peripheral vestibular dysfunction and severe intensity vestibular symptoms were significantly associated with anxiety and depression. None of migraine features were significantly associated with anxiety and depression. Conclusion: The prevalence of anxiety in patients with VM is considerably higher than in the depression. VM patients with peripheral vestibular dysfunction are particularly susceptible to anxiety and depression. Therefore, timely screening for vestibular function and psychiatric disorders in VM patients should be considered.

Phytochemical profiling of Symplocos tanakana Nakai and S. sawafutagi Nagam. leaf and identification of their antioxidant and anti-diabetic potential.

Symplocos sp. contains various phytochemicals and is used as a folk remedy for treatment of diseases such as enteritis, malaria, and leprosy. In this study, we discovered that 70% ethanol extracts of Symplocos sawafutagi Nagam. and S. tanakana Nakai leaves have antioxidant and anti-diabetic effects. The components in the extracts were profiled using high-performance liquid chromatography coupled to electrospray ionization and quadrupole time-of-flight mass spectrometry; quercetin-3-O-(6''-O-galloyl)-ß-d-galactopyranoside (6) and tellimagrandin II (7) were the main phenolic compounds. They acted as strong antioxidants with excellent radical scavenging activity and as inhibitors of non-enzymatic advanced glycation end-products (AGEs) formation. Mass fragmentation analysis demonstrated that compounds 6 and 7 could form mono- or di-methylglyoxal adducts via reaction with methylglyoxal, which is a reactive carbonyl intermediate and an important precursor of AGEs. In addition, compound 7 effectively inhibited the binding between AGE2 and receptor for AGEs as well as the activity of α-glucosidase. Enzyme kinetic study revealed that compound 7 acts as a competitive inhibitor of α-glucosidase, through interaction with the active site of the enzyme. Therefore, compounds 6 and 7, the major constituents of S. sawafutagi and S. tanakana leaves, are promising for developing drugs for preventing or treating diseases caused by aging and excessive sugar consumption.

Climate Change Influences the Spread of African Swine Fever Virus.

Climate change is an inevitable and urgent issue in the current world. African swine fever virus (ASFV) is a re-emerging viral animal disease. This study investigates the quantitative association between climate change and the potential spread of ASFV to a global extent. ASFV in wild boar outbreak locations recorded from 1 January 2019 to 29 July 2022 were sampled and investigated using the ecological distribution tool, the Maxent model, with WorldClim bioclimatic data as the predictor variables. The future impacts of climate change on ASFV distribution based on the model were scoped with Representative Concentration Pathways (RCP 2.6, 4.5, 6.0, and 8.5) scenarios of Coupled Model Intercomparison Project 5 (CMIP5) bioclimatic data for 2050 and 2070. The results show that precipitation of the driest month (Bio14) was the highest contributor, and annual mean temperature (Bio1) was obtained as the highest permutation importance variable on the spread of ASFV. Based on the analyzed scenarios, we found that the future climate is favourable for ASFV disease; only quantitative ratios are different and directly associated with climate change. The current study could be a reference material for wildlife health management, climate change issues, and World Health Organization sustainability goal 13: climate action.

Phytoestrogen Coumestrol Selectively Inhibits Monoamine Oxidase-A and Amyloid ß Self-Aggregation.

Pueraria lobata leaves contain a variety of phytoestrogens, including flavonoids, isoflavonoids, and coumestan derivatives. In this study, we aimed to identify the active ingredients of P. lobata leaves and to elucidate their function in monoamine oxidase (MAO) activation and Aß self-aggregation using in vitro and in silico approaches. To the best of our knowledge, this is the first study to elucidate coumestrol as a selective and competitive MAO-A inhibitor. We identified that coumestrol, a coumestan-derivative, exhibited a selective inhibitory effect against MAO-A (IC50 = 1.99 ± 0.68 µM), a key target protein for depression. In a kinetics analysis with 0.5 µg MAO-A, 40-160 µM substrate, and 25 °C reaction conditions, coumestrol acts as a competitive MAO-A inhibitor with an inhibition constant of 1.32 µM. During an in silico molecular docking analysis, coumestrol formed hydrogen bonds with FAD and pi-pi bonds with hydrophobic residues at the active site of the enzyme. Moreover, based on thioflavin-T-based fluorometric assays, we elucidated that coumestrol effectively prevented self-aggregation of amyloid beta (Aß), which induces an inflammatory response in the central nervous system (CNS) and is a major cause of Alzheimer's disease (AD). Therefore, coumestrol could be used as a CNS drug to prevent diseases such as depression and AD by the inhibition of MAO-A and Aß self-aggregation.

Functional Characterization of a Regiospecific Sugar-O-Methyltransferase from Nocardia.

Methyltransferases transfer a methyl group to a diverse group of natural products, thus providing structural diversity, stability, and altered pharmacological properties to the molecules. A limited number of regiospecific sugar-O-methyltransferases are functionally characterized. Thus, discovery of such an enzyme could solve the difficulties of biological production of methoxy derivatives of glycosylated molecules. In the current study, a regiospecific sugar-O-methyltransferase, ThnM1, belonging to the biosynthetic gene cluster (BGC) of 1-(α-L-(2-O-methyl)-6-deoxymannopyranosyloxy)-3,6,8-trimethoxynaphthalene produced by Nocardia sp. strain CS682, was analyzed and functionally characterized. ThnM1 demonstrated promiscuity to diverse chemical structures such as rhamnose-containing anthraquinones and flavonoids with regiospecific methylation at the 2'-hydroxyl group of the sugar moiety. Compared with other compounds, anthraquinone rhamnosides were found to be the preferred substrates for methylation. Thus, the enzyme was further employed for whole-cell biotransformation using engineered Escherichia coli to produce a methoxy-rhamnosyl derivative of quinizarin, an anthraquinone derivative. The structure of the newly generated derivative from Escherichia coli fermentation was elucidated by liquid chromatography-mass spectrometry and nuclear magnetic resonance spectroscopic analyses and identified as quinizarin-4-O-α-l-2-O-methylrhamnoside (QRM). Further, the biological impact of methylation was studied by comparing the cytotoxicity of QRM with that of quinizarin against the U87MG, SNU-1, and A375SM cancer cell lines. IMPORTANCE ThnM1 is a putative sugar-O-methyltransferase produced by the Nocardia sp. strain CS682 and is encoded by a gene belonging to the biosynthetic gene cluster (BGC) of 1-(α-l-(2-O-methyl)-6-deoxymannopyranosyloxy)-3,6,8-trimethoxynaphthalene. We demonstrated that ThnM1 is a promiscuous enzyme with regiospecific activity at the 2'-OH of rhamnose. As regiospecific methylation of sugars by chemical synthesis is a challenging step, ThnM1 may fill the gap in the potential diversification of natural products by methylating the rhamnose moiety attached to them.

UPLC-PDA coupled HR-TOF ESI/MS2 -based identification of derivatives produced by whole-cell biotransformation of epothilone A using Nocardia sp. CS692 and a cytochrome P450 overexpressing strain.

Epothilone A, a microtubule-stabilizing agent used as therapeutics for the treatment of cancers, was biotransformed into three metabolites using Nocardia sp. CS692 and recombinant Nocardia overexpressing a cytochrome P450 from Streptomyces venezuelae (PikC). Among three metabolites produced in the biotransformation reaction mixtures, ESI/MS2 analysis predicted two metabolites (M1 and M2) as novel hydroxylated derivatives (M1 is hydroxylated at the C-8 position and M2 is hydroxylated at C-10 position), each with an opened-epoxide ring in their structure. Interestingly, metabolite M3 lacks an epoxide ring and is known as deoxyepothilone A, which is also called epothilone C. Metabolite M1 was produced only in PikC overexpressing strain. The endogenous enzymes of Nocardia sp. catalyzed hydroxylation of epothilone A to produce metabolite M2 and removed epoxide ring to produce metabolite M3. All the metabolites were identified based on UV-vis analysis and rigorous ESI/MS2 fragmentation based on epothilone A standard. The newly produced metabolites are anticipated to display novel cytotoxic effects and could be subjects of further pharmacological studies.

Advances in biochemistry and the biotechnological production of taxifolin and its derivatives.

Taxifolin (dihydroquercetin) and its derivatives are medicinally important flavanonols with a wide distribution in plants. These compounds have been isolated from various plants, such as milk thistle, onions, french maritime, and tamarind. In general, they are commercially generated in semisynthetic forms. Taxifolin and related compounds are biosynthesized via the phenylpropanoid pathway, and most of the biosynthetic steps have been functionally characterized. The knowledge gained through the detailed investigation of their biosynthesis has provided the foundation for the reconstruction of biosynthetic pathways. Plant- and microbial-based platforms are utilized for the expression of such pathways for generating taxifolin-related compounds, either by whole-cell biotransformation or through reconfiguration of the genetic circuits. In this review, we summarize recent advances in the biotechnological production of taxifolin and its derivatives.

Postoperative results of ventilation tube insertion: a retrospective multicenter study for suggestion of grading system of otitis media with effusion.

BACKGROUND: In otitis media with effusion (OME), it is important to know when to surgically intervene and when careful monitoring is more appropriate. This study aimed to visualize and classify the clinical manifestations of OME and the correlation between the new grading system and postoperative results after ventilation tube insertion (VTI). METHODS: We classified the collective 1,012 ears from 506 patients into six groups: grade 0 (no effusion), grade I (scant effusion, but abnormal), grade II (effusion less than half of the tympanic cavity), grade III (effusion over half of the tympanic cavity, with air bubbles), grade IV (complete effusion), and grade V (retracted tympanic membrane or hemotympanum without air bubbles). RESULTS: The mean age at VTI was 5.2 (±2.9) years and mean duration between diagnosis and operation was 4.1 (±1.8) months. Between the grades, the nature of the middle ear effusion was also significantly different (p < 0.001). The duration of ventilation tube retention after VTI was significantly different when compared between two groups: grade I-IV and grade V (p = 0.019). Our results showed that the recurrence rate, as well as rate of revision VTI, increased as the grade increased (p < 0.001). CONCLUSIONS: The new grading system of OME using endoscopic otoscope evaluation had a significant correlation with the age at VTI, the nature of middle ear effusion, the recurrence rate of OME, and the rate of revision VTI.

Genome mining Streptomyces sp. KCTC 0041BP as a producer of dihydrochalcomycin.

Streptomyces sp. KCTC 0041BP, which was isolated from a soil sample in Cheolwon, Republic of Korea, is a dihydrochalcomycin producer. In this study, we obtained the genome of S. sp. KCTC 0041BP with 7.54 Mb genome size. antiSMASH and the dbCAN2 meta server predicted that the genome would contain 26 secondary metabolite biosynthetic gene clusters (BGCs) and 285 carbohydrate-active enzymes. Besides dihydrochalcomycin, 21 compounds were successfully identified from S. sp. KCTC 0041BP, and among them, the structure of 8 compounds were proven by high-resolution electrospray ionization mass spectrometry (HRESIMS) and nuclear magnetic resonance (NMR). The identification of chalcomycin analogs led to a better understanding of the biosynthetic pathway of dihydrochalcomycin/chalcomycin. From the analysis of cluster 2 and solvent selection, linearmycins were determined. Linearmycins showed antibacterial activity with both Gram-positive and Gram-negative bacteria and antifungal activity. One strain many compounds (OSMAC) strategy was applied to activate the salicylic acid production in this strain. A salicylic acid biosynthetic pathway was also predicted, but not by antiSMASH. These results showed that this strain can produce many useful compounds and potentially produce novel compounds with most secondary BGCs yet to be experimentally identified.

Identification and enhancing production of a novel macrolide compound in engineered Streptomyces peucetius.

Streptomyces peucetius produces doxorubicin and daunorubicin, which are important anticancer drugs. In this study, we activate peucemycin, a new antibacterial compound, using an OSMAC strategy. In general, bioactive compounds are produced in a higher amount at room temperature; however, in this study, we have demonstrated that a bioactive novel compound was successfully activated at a low temperature (18 °C) in S. peucetius DM07. Through LC-MS/MS, IR spectroscopy, and NMR analysis, we identified the structure of this compound as a γ-pyrone macrolide. This compound was found to be novel, thus named peucemycin. It is an unusual 14-membered macrocyclic γ-pyrone ring with cyclization. Also, peucemycin exhibits potential antibacterial activity and a suppressive effect on the viability of various cancer cell lines.

Genome-enabled discovery of anthraquinone biosynthesis in Senna tora.

Senna tora is a widely used medicinal plant. Its health benefits have been attributed to the large quantity of anthraquinones, but how they are made in plants remains a mystery. To identify the genes responsible for plant anthraquinone biosynthesis, we reveal the genome sequence of S. tora at the chromosome level with 526 Mb (96%) assembled into 13 chromosomes. Comparison among related plant species shows that a chalcone synthase-like (CHS-L) gene family has lineage-specifically and rapidly expanded in S. tora. Combining genomics, transcriptomics, metabolomics, and biochemistry, we identify a CHS-L gene contributing to the biosynthesis of anthraquinones. The S. tora reference genome will accelerate the discovery of biologically active anthraquinone biosynthesis pathways in medicinal plants.

Protective Effects of Glucose-Related Protein 78 and 94 on Cisplatin-Mediated Ototoxicity.

Cisplatin is a widely used chemotherapeutic drug for treating various solid tumors. Ototoxicity is a major dose-limiting side effect of cisplatin, which causes progressive and irreversible sensorineural hearing loss. Here, we examined the protective effects of glucose-related protein (GRP) 78 and 94, also identified as endoplasmic reticulum (ER) chaperone proteins, on cisplatin-induced ototoxicity. Treating murine auditory cells (HEI-OC1) with 25 µM cisplatin for 24 h increased cell death resulting from excessive intracellular reactive oxygen species (ROS) accumulation and caspase-involved apoptotic signaling pathway activation with subsequent DNA fragmentation. GRP78 and GRP94 expression was increased in cells treated with 3 nM thapsigargin or 0.1 µg/mL tunicamycin for 24 h, referred to as mild ER stress condition. This condition, prior to cisplatin exposure, attenuated cisplatin-induced ototoxicity. The involvement of GRP78 and GRP94 induction was demonstrated by the knockdown of GRP78 or GRP94 expression using small interfering RNAs, which abolished the protective effect of mild ER stress condition on cisplatin-induced cytotoxicity. These results indicated that GRP78 and GRP94 induction plays a protective role in remediating cisplatin-ototoxicity.

Clinical Manifestations of Allergic Rhinitis by Age and Gender: A 12-Year Single-Center Study.

OBJECTIVES: Currently, epidemiological data on allergic rhinitis collected through the skin prick test are scarce. Moreover, the relationship of age and sex to allergic rhinitis is not comprehensively understood. This study aimed to characterize allergic rhinitis and the associated clinical manifestations by age and sex. METHODS: We retrospectively investigated data from 2883 patients who visited a single university hospital for rhinitis symptoms between January 2003 and December 2014. Of these 2883 patients, 1964 who underwent a skin prick test with 11 standardized allergen extracts and completed a nasal symptom questionnaire were enrolled. The clinical characteristics of allergen sensitization and nasal symptoms were analyzed by sex and age distribution. RESULTS: The prevalence of allergen sensitization progressively decreased with age after peaking at between 20 and 29 years. The sensitization rate was higher in males than in females (P = .046). The sensitization rate to house dust mites decreased with age, while sensitization to mugwort and ragweed increased. Six allergens (Dermatophagoides pteronyssinus, Dermatophagoides farinae, mugwort, trees, ragweed, and cats) were sufficient to identify >96% of patients with allergen sensitization. Nasal obstruction tended to decrease with age and was more prevalent in males (P = .002) than in females, while rhinorrhea (P = .007) and itching (P = .013) were more prevalent in females. Total nasal symptom scores did not differ by sex. CONCLUSIONS: The clinical characteristics of allergic rhinitis, including allergen-sensitization patterns and related symptoms, varied by age and sex. Six common allergens could be sufficient to generate a cost-effective tool to identify allergic rhinitis.

Exploring the Nucleophilic N- and S-Glycosylation Capacity of Bacillus licheniformis YjiC Enzyme.

YjiC, a glycosyltransferase from Bacillus licheniformis, is a well-known versatile enzyme for glycosylation of diverse substrates. Although a number of O-glycosylated products have been produced using YjiC, no report has been updated for nucleophilic N-, S-, and C- glycosylation. Here, we report the additional functional capacity of YjiC for nucleophilic N- and S- glycosylation using a broad substrate spectrum including UDP-α-D-glucose, UDP-N-acetyl glucosamine, UDP-N-acetylgalactosamine, UDP-α-D-glucuronic acid, TDP-α-L-rhamnose, TDP-α-D-viosamine, and GDP-α-Lfucose as donor and various amine and thiol groups containing natural products as acceptor substrates. The results revealed YjiC as a promiscuous enzyme for conjugating diverse sugars at amine and thiol functional groups of small molecules applicable for generating glycofunctionalized chemical diversity libraries. The glycosylated products were analyzed using HPLC and LC/MS and compared with previous reports.