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Introduction: Clinical trials are a fundamental tool in evidence-based medicine, with participant recruitment being a critical factor for their execution. Low participation in a study leads to inadequate sample size. Older adults constitute a minority in clinical trials, and various factors influence their level of participation and retention during the study process. Our objective is to determine the willingness of older adults to participate in clinical trials and identify their main barriers and facilitator., Methods: A cross-sectional study was carried out on outpatient adults over 60 years of age. The rate of desire for voluntary participation in clinical trials was determined and through a validated survey "National Health Information Trends Survey (HINTS 5, cycle 4)" the knowledge, rate of prior participation in CE and the influence of different factors that could be associated with a positive attitude to participate. These factors were analyzed using ordinal logistic regression., Results: 251 older adults were surveyed. Of them, 171 (68%) reported not having any knowledge about clinical trials and 80 (31.87%) reported having it to some degree. 12 patients (5%) previously participated in a CS and up to 88 patients (35%) expressed that they would probably or definitely participate in one. It was observed that, the older the age, the less willingness to participate in CE [OR]: 0.55 (CI 95% 0.34-0.88). Likewise, male sex was associated with a greater desire to participate [OR]: 1.74 (CI 95% 1.06-2.84), respectively. The scenarios that were associated with a greater desire to participate in CE were knowing that by participating you could help others [OR]: 1.95 (95% CI 1.36-2.178), the possibility of receiving help for participating [OR]: 1.69 (95% CI 1.26-2.26) and the possibility of trying a new type of medical care [OR]: 1.71 (95% CI 1.20-2.42)., Conclusions: The level of knowledge about CE among older adults is low and up to a third of them would participate as volunteers in a CE. The dissemination of information about ECs could encourage a higher participation rate., (Copyright © 2024 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.)

Intensive aquaculture causes a decline in the health status of fish, resulting in an increased disease incidence. To counteract this, feed additives have been utilized to improve the growth performance and health of aquaculture species. This work specifically investigates the impact of powdered Ficus deltoidea (FD) on various parameters related to growth, blood parameters, liver and intestine morphology, body proximate analysis, digestive enzymes, antioxidant capacity, and disease resistance to motile Aeromonad Septicemia (MAS) caused by Aeromonas hydrophila infection in African catfish, Clarias gariepinus. Four formulated diets were prepared: T1 (0% FD), T2 (0.5% FD), T3 (0.75% FD), and T4 (1% FD). After 8 weeks, the African catfish's growth performance fed with the T2 diet exhibited a substantial improvement (p < 0.05), along with a remarkably lower (p < 0.05) feed conversion ratio (FCR) when compared to the other treatment groups. Blood parameter analysis revealed notably higher (p < 0.05) levels of white blood cell (WBC), lymphocytosis (LYM), hemoglobin (HGB), albumin (ALB), globulin (GLOB), as well as total protein (TP) in the T2 diet group. While all treatment groups displayed normal intestinal morphology, liver deterioration was observed in groups supplemented with higher FD. The T2 diet group recorded the highest villus length, width, and crypt depth. Protease and lipase levels were also notably improved in the T2 diet group compared to other treatment groups. Additionally, catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) were remarkably elevated in all FD diet groups than in the control group. The expression of immune-related genes, including transforming growth factor beta 1, heat shock protein 90, nuclear factor kappa-B gene, and lysozyme G, was upregulated in all treatments. Overall, the results of this study indicate that incorporating dietary FD at 0.5% concentration in the diet of African catfish may enhance their productivity in intensive farming., Competing Interests: Declarations Ethics approval Not applicable. Consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests.., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Anthrax is a global health concern, with cutaneous anthrax accounting for over 95% of cases and generally promising outcomes. Nonetheless, the absence of timely intervention can result in mortality rates of 10-40%. This research aims to explore the clinical presentations and phenotypic characteristics of cutaneous anthrax patients and evaluate the efficacy of various therapeutic approaches., Methods: A retrospective study was performed on 76 cutaneous anthrax patients identified at three hospitals from 2017 to 2022. Patients were categorized based on their hospital stay into two groups: those hospitalized for at least seven days and those for shorter durations. We assessed their clinical and phenotypic profiles, including symptoms, general health status, and laboratory findings, alongside treatment outcomes, focusing on corticosteroids therapy and antibiotic regimens., Results: The study encompassed 76 diagnosed individuals, predominantly young adult males (78.9%). A significant gender disparity was noted. Hormonal treatment markedly improved edema regression in patients (P < 0.002), highlighting its therapeutic value. The impact of various antibiotic treatments on disease progression differed significantly based on corticosteroids treatment status, with specific combinations showing more effectiveness in non-corticosteroids-treated patients., Conclusions: The predominance of young male adults among cutaneous anthrax cases was observed, with corticosteroids treatment significantly reducing edema duration. In cases where corticosteroids therapy is not utilized, employing piperacillin-tazobactam alone or in combination with quinolones effectively shortens the illness duration, suggesting a tailored approach to treatment can enhance patient outcomes., (© 2024. The Author(s).)

In recent decades, nanotechnology has significantly advanced drug delivery systems, particularly in targeting subcellular organelles, thus opening new avenues for disease treatment. Mitochondria, critical for cellular energy and health, when dysfunctional, contribute to cancer, neurodegenerative diseases, and metabolic disorders. This has propelled the development of nanomedicines aimed at precise mitochondrial targeting to modulate their function, marking a research hotspot. This review delves into the recent advancements in mitochondrial-targeted nanotherapeutics, with a comprehensive focus on targeting strategies, nanocarrier designs, and their therapeutic applications. It emphasizes nanotechnology's role in enhancing drug delivery by overcoming biological barriers and optimizing drug design for specific mitochondrial targeting. Strategies exploiting mitochondrial membrane potential differences and specific targeting ligands improve the delivery and mitochondrial accumulation of nanomedicines. The use of diverse nanocarriers, including liposomes, polymer nanoparticles, and inorganic nanoparticles, tailored for effective mitochondrial targeting, shows promise in anti-tumor and neurodegenerative treatments. The review addresses the challenges and future directions in mitochondrial targeting nanotherapy, highlighting the need for precision, reduced toxicity, and clinical validation. Mitochondrial targeting nanotherapy stands at the forefront of therapeutic strategies, offering innovative treatment perspectives. Ongoing innovation and research are crucial for developing more precise and effective treatment modalities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Li, Wei and Ye.)

Fish protein hydrolysate (FPH) has shown immense potential as a dietary protein supplement and immunostimulant in aquaculture, especially in Nile tilapia production. Four isoproteic diets (30% crude protein) were prepared by including FPH at varying percentages (0%, 0.5%, 1%, and 2%). Nile tilapia fed with FPH diets for 90 days, and their growth performance, feed utilization, blood biochemistry, liver and gut morphology, and resistance against Streptococcus iniae were investigated. The findings revealed that diets physical attributes such as pellet durability index and water stability were remarkably (p < 0.05) varied between experimental diet groups. Furthermore, the test diets were more palatable when FPH was included at 1% and 2%. Fish that were fed with a 2% FPH-treated diet had significantly (p < 0.05) greater growth indices than other treatments. Additionally, their feed utilization was significantly (p < 0.05) improved. The experimental diets and intestinal total bacteria count (TBC) exhibited a rising trend with FPH levels, where the 2% FPH-treated diet recorded the highest TBC. Neutrophil (10 9 /L), lymphocyte (10 9 /L), eosinophil (10 9 /L), and red blood cell(10 12 /L) counts were significantly (p < 0.05) higher in the 2% FPH-treated group, while the white blood cell (10 9 /L), and basophil (10 9 /L) counts were not influenced by the FPH inclusion. Moreover, the FPH-treated groups displayed lower creatinine, bilirubin, and urea levels than the control. The histological examination demonstrated that themid-intestine of 2% FPH-fed Nile tilapia had an unbroken epithelial wall, more villi with frequent distribution of goblet cells, wider tunica muscularis, and stronger stratum compactum bonding than other treatments. Additionally, this group exhibited more nuclei and erythrocytes and less vacuolar cytoplasm in liver than their counterparts. Nile tilapia that were given a diet containing 2% FPH had significantly (p < 0.05) higher resistance (83.33%) to S. iniae during the bacterial challenge test. A significant (p < 0.05) enhancement in farm economic efficiency was observed in the higher inclusion of FPH in diets. In summary, 2% FPH supplementation in Nile tilapia diets improved their growth performance, feed utilization, health status, disease resistance, and farm economic efficiency., Competing Interests: Declarations Ethical Approval The experiments were approved by Animal Ethics Committee of Sylhet Agricultural University, and performed according to the Animal Ethics Procedures and Guidelines of the People’s Republic of Bangladesh. Consent to Participate Not applicable. Consent for Publication Not applicable Competing Interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Carp is a key aquaculture species worldwide. The intensification of carp farming, aimed at meeting the high demand for protein sources for human consumption, has resulted in adverse effects such as poor water quality, increased stress, and disease outbreaks. While antibiotics have been utilized to mitigate these issues, their use poses risks to both public health and the environment. As a result, alternative and more sustainable practices have been adopted to manage the health of farmed carp, including the use of probiotics, prebiotics, phytobiotics, and vaccines to prevent disease outbreaks. Phytobiotics, being both cost-effective and abundant, have gained widespread acceptance. They offer various benefits in carp farming, such as improved growth performance, enhanced immune system, increased antioxidant capacity, stress alleviation from abiotic factors, and enhanced disease resistance. Currently, a focal point of research involves employing molecular approaches to assess the impacts of phytobiotics in aquatic animals. Gene expression, the process by which genetic information encoded is translated into function, along with transcription profiling, serves as a crucial tool for detecting changes in gene expression within cells. These changes provide valuable insights into the growth rate, immune system, and flesh quality of aquatic animals. This review delves into the positive impacts of phytobiotics on immune responses, growth, antioxidant capabilities, and flesh quality, all discerned through gene expression changes in carp species. Furthermore, this paper explores existing research gaps and outlines future prospects for the utilization of phytobiotics in aquaculture., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease, notably resistant to existing therapies. Current research indicates that PDAC patients deficient in homologous recombination (HR) benefit from platinum-based treatments and poly-ADP-ribose polymerase inhibitors (PARPi). However, the effectiveness of PARPi in HR-deficient (HRD) PDAC is suboptimal, and significant challenges remain in fully understanding the distinct characteristics and implications of HRD-associated PDAC. We analyzed 16 PDAC patient-derived tissues, categorized by their homologous recombination deficiency (HRD) scores, and performed high-plex immunofluorescence analysis to define 20 cell phenotypes, thereby generating an in-situ PDAC tumor-immune landscape. Spatial phenotypic-transcriptomic profiling guided by regions-of-interest (ROIs) identified a crucial regulatory mechanism through localized tumor-adjacent macrophages, potentially in an HRD-dependent manner. Cellular neighborhood (CN) analysis further demonstrated the existence of macrophage-associated high-ordered cellular functional units in spatial contexts. Using our multi-omics spatial profiling strategy, we uncovered a dynamic macrophage-mediated regulatory axis linking HRD status with SIGLEC10 and CD52. These findings demonstrate the potential of targeting CD52 in combination with PARPi as a therapeutic intervention for PDAC., Competing Interests: Declaration of interests N.W is a full-time employee of Cosmos Wisdom Biotech and worked for Fynn Biotechnologies. ZT.S is a full-time employee of Fynn Biotechnologies. G.B.M. is one of the SAB (Scientific Advisory Board) members or consults with AstraZeneca, Chrysallis Biotechnology, GSK, ImmunoMET, Ionis, Lilly, PDX Pharmaceuticals, Signalchem Lifesciences, Symphogen, Tarveda, Turbine, Zentalis Pharmaceuticals. G.B.M has stock options with Catena Pharmaceuticals, ImmunoMet, SignalChem, Tarveda. Other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This study explores the beneficial effects of Auricularia auricula (AA) as a feed additive in promoting growth, digestive enzyme activities, antioxidative responses, heat tolerance, and disease resistance against Edwardsiella tarda in African catfish ( Clarias gariepinus ) farming. The application of feed additives is a hot topic in recent aquaculture studies aimed at promoting the growth and health of aquaculture species. After 8 weeks of feeding trial, the results of the present study revealed that fish-fed AA diets performed significantly better ( p  < 0.05) compared to the control group in growth performances, including final weight, weight gain, and specific growth rate. The highest performances were observed in the fish-fed AA at 3 and 4 %. A similar trend was also observed in the values of feed conversion ratio, hepatosomatic index, and visceral somatic index, with the lowest values ( p  < 0.05) in the fish-fed AA at 3 and 4 %. AA diets enhanced the activities of all tested digestive enzymes (amylase, protease, and lipase) significantly ( p  < 0.05), with the highest activities in the fish-fed AA at 3 and 4 %. Meanwhile, fish-fed AA diets exhibited significantly higher ( p  < 0.05) catalase, superoxide dismutase, and glutathione peroxidase activities both before and after heat stress, with the highest activities in the fish that received AA at 3 and 4 %. Furthermore, AA diets stimulated disease resistance in African catfish, with the fish-fed AA at 4 % performing the highest cumulative survival rate (73.3 ± 5.77 %) post-infection with E. tarda in African catfish. The findings of the current study suggest that AA has huge potential as a feed additive in African catfish farming., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Lee Seong Wei, Associate Editor, Heliyon If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Alzheimer's disease (AD) is increasingly becoming a major public health concern in our society. While many studies have explored the use of natural polyketides, alkaloids, and other chemical components in AD treatment, there is an urgent need to clarify the concept of multi-target treatment for AD. This study focuses on using network pharmacology approach to elucidate how secondary metabolites from Dictyostelium discoideum affect AD through multi-target or indirect mechanisms. The secondary metabolites produced by D. discoideum during their development were obtained from literature sources and PubChem. Disease targets were selected using GeneCards, DisGeNET, and CTD databases, while compound-based targets were identified through Swiss target prediction and Venn diagrams were used to find intersections between these targets. A network depicting the interplay among disease, drugs, active ingredients, and key target proteins (PPI network) was formed utilizing the STRING (Protein-Protein Interaction Networks Functional Enrichment Analysis) database. To anticipate the function and mechanism of the screened compounds, GO and KEGG enrichment analyses were conducted and visually presented using graphs and bubble charts. After the screening phase, the top interacting targets in the PPI network and the compound with the most active target were chosen for subsequent molecular docking and molecular dynamic simulation studies. This study identified nearly 50 potential targeting genes for each of the screened compounds and revealed multiple signaling pathways. Among these pathways, the inflammatory pathway stood out. COX-2, a receptor associated with neuroinflammation, showed differential expression in various stages of AD, particularly in pyramidal neurons during the early stages of the disease. This increase in COX-2 expression is likely induce by higher levels of IL-1, which is associated with neuritic plaques and microglial cells in AD. Molecular docking investigations demonstrated a strong binding interaction between the terpene compound PQA-11 and the neuroinflammatory receptor COX2, with a substantial binding affinity of -8.4 kcal/mol. Subsequently, a thorough analysis of the docked complex (COX2-PQA11) through Molecular Dynamics Simulation showed lower RMSD, minimal RMSF fluctuations, and a reduced total energy of -291.35 kJ/mol compared to the standard drug. These findings suggest that the therapeutic effect of PQA-11 operates through the inflammatory pathway, laying the groundwork for further in-depth research into the role of secondary metabolites in AD treatment., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Lee Seong Wei, Associate Editor, Heliyon If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Seaweed research has gained substantial momentum in recent years, attracting the attention of researchers, academic institutions, industries, policymakers, and philanthropists to explore its potential applications and benefits. Despite the growing body of literature, there is a paucity of comprehensive scientometric analyses, highlighting the need for an in-depth investigation. In this study, we utilized CiteSpace to examine the global seaweed research landscape through the Web of Science Core Collection database, assessing publication trends, collaboration patterns, network structures, and co-citation analyses across 48,278 original works published since 1975. Our results demonstrate a diverse and active research community, with a multitude of authors and journals contributing to the advancement of seaweed science. Thematic co-citation cluster analysis identified three primary research areas: "Coral reef," "Solar radiation," and "Mycosporine-like amino acid," emphasizing the multidisciplinary nature of seaweed research. The increasing prominence of "Chemical composition" and "Antioxidant" keywords indicates a burgeoning interest in characterizing the nutritional value and health-promoting properties of seaweed. Timeline co-citation analysis unveils that recent research priorities have emerged around the themes of coral reefs, ocean acidification, and antioxidants, underlining the evolving focus and interdisciplinary approach of the field. Moreover, our analysis highlights the potential of seaweed as a functional food product, poised to contribute significantly to addressing global food security and sustainability challenges. This study underscores the importance of bibliometric analysis in elucidating the global seaweed research landscape and emphasizes the need for sustained knowledge exchange and collaboration to drive the field forward. By revealing key findings and emerging trends, our research offers valuable insights for academics and stakeholders, fostering a more profound understanding of seaweed's potential and informing future research endeavors in this promising domain., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Lee Seong Wei is the Associate Editor for Heliyon., (© 2024 The Authors.)

Aquaculture has intensified tremendously with the increasing demand for protein sources as the global population grows. However, this industry is plagued with major challenges such as poor growth performance, the lack of a proper environment, and immune system impairment, thus creating stress for the aquaculture species and risking disease outbreaks. Currently, prophylactics such as antibiotics, vaccines, prebiotics, probiotics, and phytobiotics are utilized to minimize the negative impacts of high-density farming. One of the promising prophylactic agents incorporated in fish feed is resveratrol, a commercial phytophenol derived via the methanol extraction method. Recent studies have revealed many beneficial effects of resveratrol in aquatic animals. Therefore, this review discusses and summarizes the roles of resveratrol in improving growth performance, flesh quality, immune system, antioxidant capacity, disease resistance, stress mitigation, and potential combination with other prophylactic agents for aquatic animals., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Cuchia eel ( Monopterus cuchia ) is among the most sought-after freshwater fish, owing to its exceptional nutritional profile and high consumer demand. The current research aimed to establish baseline data by comparing the proximate composition, hematological, and plasma biochemical indices of Cuchia eel populations across six different geographical locations in Bangladesh: Bogra, Haluaghat, Jamalpur, Moktagacha, Sylhet, and Tangail. By examining these parameters, we aim to gain valuable insights into the nutritional benefits, physiological responses, and potential adaptations of this species to varying environments. The statistical analysis revealed no significant ( P  > 0.05) variances in the whole-body proximate composition of the fish captured from distinct areas. However, it was observed that different geographical regions had remarkable impacts on the variations of the majority of the hematological parameters, except for some cases. Additionally, there was a notable ( P  < 0.05) increase or decrease in most of the serum biochemical contents in certain localities as compared to others in this study. Light microscopic examination of Cuchia eel blood smears exhibited lower numbers but larger sizes of RBCs. The findings of this study lead to the conclusion that different localities had significant impacts on the hematology and blood biochemical indices of Cuchia eel, even though the whole-body proximate composition showed no significant variations. This research contributes to a deeper understanding of the physiological aspects of Cuchia eel., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Soybean lecithin is extensively used as the dietary supplementation of phospholipids in animal production. Soybean lecithin plays significant roles in aquafeed as growth promoter, feed enhancer, immunity modulator and antioxidant activity stimulator for aquaculture species. Besides, soybean lecithin is also reported to help aquaculture species being resilient to physical and chemical stressors. In this review, common sources, chemical structure and mode of action of lecithin, with highlight on soybean lecithin application in aquaculture over four-decadal studies published between 1983 and 2023, were evaluated and summarized. By far, soybean lecithin is best-known for its beneficial effects, availability yet cost-effective for aquafeed formulation. Findings from this review also demonstrate that although nutritional profile of long-chain polyunsaturated fatty acids and phosphatidylcholine from egg yolk and marine sources are superior to those from plant sources such as soybean, it is rather costly for sustainable application in aquafeed formulation. Moreover, commercially available products that incorporate soybean lecithin with other feed additives are promising to boost aquaculture production. Overall, effects of soybean lecithin supplementation are well-recognized on larval and juvenile of aquaculture species which having limited ability to biosynthesis phospholipids de novo , and correspondingly attribute to phospholipid, a primary component of soybean lecithin, that is essential for rapid growth during early stages development. In addition, soybean lecithin supplementation plays a distinguish role in stimulating maturation of gonadal development in the adults, especially for crustaceans., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer RC declared a shared affiliation with the author GT-I to the handling editor at the time of review., (Copyright © 2023 Wee, Téllez-Isaías, Abdul Kari, Cheadoloh, Kabir, Mat, Mohamad Sukri, Rahman, Rusli and Wei.)

Long-whiskered catfish Sperata aor is a freshwater catfish known for its supreme flesh quality and fast growth, whose captive-reared broodstock denotes a difficult challenge for aquaculture. The reproductive dysfunctions in long-whiskered catfish raised in tank conditions were observed by comparing tissue biochemical composition and ovarian histology of wild female broodstock. Sixty (60) female broodstocks were used in the current study, consisting of 30 reared at sandy-muddy soil tank bottoms in captive conditions and 30 wild individuals collected from the haor basin during the breeding season. The fish reproductive state was investigated using the biometric and reproductive parameters, biochemical composition and levels of amino acids in the different tissues, and histological analysis of ovarian development. Results revealed that the biometrical parameters of wild and captive female broodstocks exhibited no remarkable difference (p > 0.05). Nevertheless, the wild fish had remarkably higher (p < 0.05) GSI (8.73%), oocyte weight (0.45 mg/egg), and ripeness (27.08%) in comparison with captive-reared broodstock. The total length and body weight, body weight and ovary weight, ovipositor diameter and ovary weight, and GSI and HSI displayed a positive relationship with R 2  = 1, R 2  = 1, R 2  = 0.993, and R 2  = 0.973, respectively, for wild broodstock, while R 2  = 0.994, R 2  = 0.806, R 2  = 0.804, and R 2  = 0.896, respectively, for captive broodstock. Additionally, the proximate composition in oocytes and liver tissues in both broodstocks did not differ significantly (p > 0.05). However, two essential amino acids (EAA), i.e., lysine and phenylalanine, and two non-essential amino acids, i.e., glutamic acid and glycine, were highly significant differences (p < 0.05) in the oocytes and liver of wild broodstock compared to the captive-reared broodstock. On the other hand, the EAA, e.g., isoleucine, threonine, leucine, and arginine, were highly dominated in both wild and captive female brood oocytes and liver. The ovarian histological slides from each fish group showed three oocytes developmental stages that indicated the asynchronous-reproductive ovarian oocytes of this fish. This study may be useful to fully understand the factors affecting the spawning and reproduction of S. aor broodstock, crucial for management in captive conditions as well as conservation and protection for sustainable aquaculture management of S. aor., (© 2023. The Author(s).)

Edwardsiellosis caused by Edwardsiella tarda resulted in significant economic losses in aquaculture operations worldwide. This disease could infect a wide range of hosts, including freshwater, brackish water, and marine aquatic animals. Currently, antibiotics and vaccines are being used as prophylactic agents to overcome Edwardsiellosis in aquaculture. However, application of antibiotics has led to antibiotic resistance among pathogenic bacteria, and the antibiotic residues pose a threat to public health. Meanwhile, the use of vaccines to combat Edwardsiellosis requires intensive labor work and high costs. Thus, phytobiotics were attempted to be used as antimicrobial agents to minimize the impact of Edwardsiellosis in aquaculture. These phytobiotics may also provide farmers with new options to manage aquaculture species' health. The impact of Edwardsiellosis in aquaculture worldwide was elaborated on and highlighted in this review study, as well as the recent application of phytobiotics in aquaculture and the status of vaccines to combat Edwardsiellosis. This review also focuses on the potential of phytobiotics in improving aquatic animal growth performance, enhancing immune system function, and stimulating disease resistance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Goh, Abdul Kari, Wee, Zakaria, Rahman, Kabir, Abdul Hamid, Tahiluddin, Kamarudin, Téllez–Isaías and Wei.)

Insects such as black soldier fly larvae (BSFL) are gaining interest among researchers and the aquafeed industry due to the fluctuating price and supply of fish meal (FM). This study evaluated the growth performance, feed stability, blood biochemistry, and liver and gut morphology of Betta splendens using BSFL as an alternative to FM. Five formulated diets were prepared: 0% BSFL, 6.5% BSFL, 13% BSFL, 19.5% BSFL, and 24.5% BSFL. The expansion rate, pellet durability index, floatability, bulk density, and water stability of the prepared feed have been assessed. Except for the diameter of the feed, all the parameters studied differed significantly ( p < 0.05) across the experimental diets. After 60 days, the fish fed with 13% BSFL had the highest final length, final weight, net weight gain, specific growth rate, weight gain, and gastrointestinal weight, with mean and standard deviation values of 3.97 ± 0.43 cm, 3.95 ± 0.1 g, 2.78 ± 0.1 g, 4.63 ± 0.17, 4.65 ± 0.13, 237.26 ± 7.9%, and 0.04 ± 0.01 mg, respectively. Similar blood haematology and biochemical properties, including corpuscular volume, lymphocytes, white blood cells, red blood cells, haematocrit, albumin, and alkaline phosphatase, were the highest ( p < 0.05) in the 13% BSFL diet group compared to the other treatment groups. In addition, BSFL had a significant impact ( p < 0.05) on villus length, width, and crypt depth for the anterior and posterior guts of B. splendens . The 13% BSFL diet group had an intact epithelial barrier in the goblet cell arrangement and a well-organized villus structure and tunica muscularis, compared to the other treatment groups. Furthermore, the liver cell was altered with different BSFL inclusions; the 13% FM group demonstrated better nuclei and cytoplasm structure than the other treatment groups. In conclusion, replacing 13% FM with BSFL could improve the growth performance, blood parameters, and liver and intestine morphology of B. splendens , thus providing a promising alternative diet for ornamental freshwater fish., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Zulhisyam Abdul Kari et al.)

Translocase of outer mitochondrial membrane 40 ( TOMM40 ) is located in the outer membrane of mitochondria. TOMM40 is essential for protein import into mitochondria. TOMM40 genetic variants are believed to increase the risk of Alzheimer's disease (AD) in different populations. In this study, three exonic variants (rs772262361, rs157581, and rs11556505) and three intronic variants (rs157582, rs184017, and rs2075650) of the TOMM40 gene were identified from Taiwanese AD patients using next-generation sequencing. Associations between the three TOMM40 exonic variants and AD susceptibility were further evaluated in another AD cohort. Our results showed that rs157581 (c.339T > C, p.Phe113Leu, F113L) and rs11556505 (c.393C > T, p.Phe131Leu, F131L) were associated with an increased risk of AD. We further utilized cell models to examine the role of TOMM40 variation in mitochondrial dysfunction that causes microglial activation and neuroinflammation. When expressed in BV2 microglial cells, the AD-associated mutant (F113L) or (F131L) TOMM40 induced mitochondrial dysfunction and oxidative stress-induced activation of microglia and NLRP3 inflammasome. Pro-inflammatory TNF-α, IL-1β, and IL-6 released by mutant (F113L) or (F131L) TOMM40-activated BV2 microglial cells caused cell death of hippocampal neurons. Taiwanese AD patients carrying TOMM40 missense (F113L) or (F131L) variants displayed an increased plasma level of inflammatory cytokines IL-6, IL-18, IL-33, and COX-2. Our results provide evidence that TOMM40 exonic variants, including rs157581 (F113L) and rs11556505 (F131L), increase the AD risk of the Taiwanese population. Further studies suggest that AD-associated mutant (F113L) or (F131L) TOMM40 cause the neurotoxicity of hippocampal neurons by inducing the activation of microglia and NLRP3 inflammasome and the release of pro-inflammatory cytokines.

Aim: To investigate the potential value of ultrasonography in evaluating the pathophysiology of obstructive sleep apnoea-hypopnoea syndrome (OSAHS) by assessing the correlation of critical ultrasonic anatomical characteristics of the oropharynx with the severity of OSAHS., Materials and Methods: One hundred and seventy-one patients with suspected OSAHS underwent oropharyngeal sonographic examination and overnight polysomnography. Ultrasonic measurement was compared with the apnoea-hypopnoea index (AHI) and other parameters. An ordinal logistic regression model was used to identify potential ultrasonic anatomical markers for OSAHS., Results: The AHI was significantly correlated with lingual height (r=0.40, p<0.01), maximal width of the tongue (r=0.35, p<0.01), and distance from the symphysis of the mandible to the hyoid bone (M-HB) (r=0.24, p<0.01). A positive relationship between Friedman tongue position (FTP) grades and lingual height (r=0.24, p<0.01), between FTP grades and maximal width of the tongue (r=0.23, p<0.01), and between FTP grades and width of tongue base (TB; r=0.17, p<0.05) was found. Multivariate models adjusted for sex, age, and body mass index (BMI) revealed that lingual height (95% confidence interval [CI]: 1.04-1.24; p=0.004) is independently associated with a higher risk for the severity of OSAHS., Conclusions: Ultrasonography may be a potential imaging method for providing additional useful information about the correlation between ultrasound findings and the severity of OSAHS. Lingual height could be considered an ultrasonic anatomical marker for determining the severity of OSAHS patients independent of age, sex, and BMI., (Copyright © 2022 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Background/objective: SARS-CoV-2 continues to spread widely in the US and worldwide. Pregnant women are more likely to develop severe or critical illness than their non-pregnant counterparts. Known risk factors for severe and critical disease outside of pregnancy, such as asthma, diabetes, and obesity have not been well-studied in pregnancy. We aimed to determine which clinical and pregnancy-related factors were associated with severe and critical COVID illness in pregnancy., Study Design: This was a retrospective cohort study of women with confirmed intrauterine pregnancy and positive nasopharyngeal swab for SARS-CoV-2 who presented to an academic medical center in New York City from 1 March 2020 to 1 July 2020. Severe and critical COVID-19 disease was defined by World Health Organization criteria. Women with severe/critical disease were compared to women with asymptomatic/mild disease. Continuous variables were compared with Mann-Whitney or t -test and categorical variables were compared using chi-square and Fisher's exact. Statistical significance was set at p  < .05. Multivariable logistic regression was performed including variables that were significantly different between groups., Results: Two hundred and thirty-three patients were included, 186 (79.8%) with asymptomatic/mild disease and 47 (20.2%) with severe/critical disease. Women with asymptomatic/mild disease were compared to those with severe/critical disease. Women with severe/critical disease were more likely to have a history of current or former smoking (19.6 vs. 5.4%, p = .004), COVID-19 diagnosis in the 2nd trimester (42.6 vs. 11.8%, p = .001), and asthma or other respiratory condition (21.3 vs. 7.0%, p = .01). Women with severe/critical disease were more likely to have cesarean delivery (35.5 vs. 15.6%, p < .01) and preterm delivery <37 weeks (25.8 vs. 3.8%, p < .01). After adjustment, history of smoking remained significantly predictive of severe/critical disease [aOR 3.84 (95% CI, 1.25-11.82)]., Conclusion: Pregnant women with a history of smoking, asthma, or other respiratory condition, and COVID-19 diagnosis in the second trimester of pregnancy were more likely to develop severe/critical disease. These findings may be useful in counseling women on their individual risk of developing the severe or critical disease in pregnancy and may help determine which women are good candidates for vaccination during pregnancy.

Background: Beka ( Oroxylum indicum (L.) Kurz) has been used as a culinary herb and natural remedy by the local communities in Malaysia. The leaf of O. indicum is traditionally used for the treatment of diarrhea, high blood pressure, and improving digestive health. Objectives: The present study was conducted to evaluate the phytochemical constituents and wound healing properties ( in vitro and in vivo models) of aqueous and ethanol extracts of O. indicum leaves. Methods: The total phenolic (TPC) and total flavonoid (TFC) contents in the plant extracts were determined by the spectrophotometric methods. Further, the extract was characterized by Liquid Chromatography Time-of-Flight Mass Spectrometry (LC-TOF-MS/MS) and Gas Chromatography-Mass Spectrometry (GC-MS). The wound healing activity was assessed using the in vitro scratch wound-healing assay and in vivo excisional wound model. Results: The results show the ethanol leaves extract had the higher TPC (164 mg GAE/g) when compared with the aqueous leaves extract (30 mg gallic acid equivalents/g). The ethanol leaves extract was also found to have higher TFC (101 mg Catechin equivalents/g) than the aqueous leaves extract (76 mg Catechin equivalents/g). The ethanol leaves extract was then used for further chemical analysis. The LC-TOF-MS/MS analysis showed that the leaves extracts of O. indicum contains many important compounds such as Orientin, Chrysin, Pinoquercetin, Cupressuflavone, Puerarin xyloside, Forsythiaside and Paederoside. In GC-MS analysis, 19 compounds were identified in ethanolic leaves extract. The wound healing studies shows that O. indicum has promising wound healing activity by increasing the rate of wound contraction significantly ( p < 0.05). Conclusion: In conclusion, the present study showed that O. indicum leaf contains important phytochemicals and the wound healing potential of the O. indicum extract may probably be as a result of the presence of various phytoconstituents., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Abdulhafiz, Reduan, Hisam, Mohammad, Abdul Wahab, Abdul Hamid, Mohammed, Nordin, Shaari, Bakar, Kari, Wei, Goh and Ahmad Mohd Zain.)

The study revealed the potential of fermented soybean meal (FSBM) as a fish meal (FM) replacement in African catfish (Clarias gariepinus) feed formulation. Five isonitrogenous diets (32% crude protein) were prepared with five different levels of FSBM as FM replacement, namely 0% FSBM (T1), 40% FSBM (T2), 50% FSBM (T3), 60% FSBM (T4), and 70% (T5). The experimental fish was given the formulated diet for eight consecutive weeks. At the end of the feeding trial, the fish were subjected to growth performance, blood parameters, blood chemical, liver histology, and gut microbiota assessment. The study findings demonstrated that the experimental fish that received the T2 diet exhibited significantly higher (p < 0.05) growth performance. Experimental fish that received diet T2 had significantly higher (p < 0.05) white blood cell (WBC) and significantly lower (p < 0.05) in terms of cholesterol (CHOL), albumin (ALB), globulin (GLOB), and total protein (TP). The replacement of FSBM to FM significantly affected liver morphology on the sinusoid, vacuole, nucleus, and erythrocytes. Gut microbiota composition analysis showed a significantly high abundance (p < 0.05) of Akkermansia muciniphila in the experimental fish that received the T2 diet. The gut microbiota indicates that the experimental fish is in a healthy condition. In conclusion, replacing 40% FSBM with FM in aquafeed could enhance C. gariepinus growth performance and health conditions.

The aquaculture industry is geared toward intensification and successfully meets half of the world's demand for fish protein. The intensive farming system exposes the animal to the risk of disease outbreaks, which has economic consequences. Antibiotics are commonly used for the health management of aquaculture species. However, this has several drawbacks, including the increase in antibiotic resistance in pathogenic bacteria and the entry of antibiotic residues into the human food chain, which is a public health and environmental concern. The potential of probiotics, prebiotics, synbiotics, and medicinal herbs as alternatives to antibiotics for the health management of aquaculture species has been investigated in numerous studies. This review discusses the potential use of combinations of probiotics and medicinal herbs as prophylactic agents in aquaculture, along with the definitions, sources, and modes of action. The positive aspects of combining probiotics and medicinal herbs on growth performance, the immune system, and disease resistance of aquaculture species are also highlighted. Overall, this review addresses the potential of combinations of probiotics and medicinal herbs as feed additives for aquaculture species and the key role of these feed additives in improving the welfare of aquaculture species., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wei, Goh, Abdul Hamid, Abdul Kari, Wee and Van Doan.)

The call to cater for the hungry is a worldwide problem in the 21st century. Food security is the utmost prime factor for the increasing demand for food. Awareness of human health when using chemical preservatives in food has increased, resulting in the use of alternative strategies for preserving food and enhancing its shelf-life. New preservatives along with novel preservation methods have been instigated, due to the intensified demand for extended shelf-life, along with prevention of food spoilage of dairy products. Bacteriocins are the group of ribosomally synthesized antimicrobial peptides; they possess a wide range of biological activities, having predominant antibacterial activity. The bacteriocins produced by the lactic acid bacteria (LAB) are considered to be of utmost importance, due to their association with the fermentation of food. In recent times among various groups of bacteriocins, leaderless and circular bacteriocins are gaining importance, due to their extensive application in industries. These groups of bacteriocins have been least studied as they possess peculiar structural and biosynthetic mechanisms. They chemically possess N-to-C terminal covalent bonds having a predominant peptide background. The stability of the bacteriocins is exhibited by the circular structure. Up till now, very few studies have been performed on the molecular mechanisms. The structural genes associated with the bacteriocins can be combined with the activity of various proteins which are association with secretion and maturation. Thus the stability of the bacteriocins can be used effectively in the preservation of food for a longer period of time. Bacteriocins are thermostable, pH-tolerant, and proteolytically active in nature, which make their usage convenient to the food industry. Several research studies are underway in the domain of biopreservation which can be implemented in food safety and food security., Competing Interests: SP is associated with NatNov Bioscience Private Limited, Balasore, India. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lahiri, Nag, Dutta, Sarkar, Pati, Basu, Abdul Kari, Wei, Smaoui, Wen Goh and Ray.)

The price of traditional sources of nutrients used in animal feed rations is increasing steeply in developed countries due to their scarcity, high demand from humans for the same food items, and expensive costs of raw materials. Thus, one of the alternative sources is coconut parts or coconut as a whole fruit. Coconut is known as the 'tree of abundance', 'tree of heaven', and 'tree of life' owing to its numerous uses, becoming a very important tree in tropical areas for its provision of food, employment, and business opportunities to millions of people. Coconut contains a rich profile of macro and micronutrients that vary depending on the parts and how they are used. It is frequently chosen as an alternative source of protein and fiber. Its uses as an antibacterial agent, immunomodulant, and antioxidant further increase its importance. Using coconut oil in ruminant feed helps to minimize methane gas emissions by 18-30%, and to reduce dry matter intake up to 4.2 kg/d. The aquaculture sectors also use coconut palm as an alternative source because it significantly improves the digestion, growth, lipid metabolism, health, and antioxidative responses. However, coconut is not widely used in poultry diets although it has adequate amount of protein and carbohydrate due to anti-nutritional factors such cellulose (13%), galactomannan (61%), and mannan (26%). This review considered the importance and potential of coconut usage as an alternative ingredient in feed and supplements in various livestock sectors as it has plentiful nutrients and functional qualities, simultaneously leading to reduced feed cost and enhanced production.

Erectile dysfunction (ED) is closely associated with smooth muscle dysfunction, but its underlying mechanisms remains incompletely understood. We here reported that the reduced expression of myosin phosphatase target subunit 1 (MYPT1), the main regulatory unit of myosin light chain phosphatase, was critical for the development of vasculogenic ED. Male MYPT1 knockout mice had reduced fertility and the penises displayed impaired erections as evidenced by reduced intracavernous pressure (ICP). The penile smooth muscles of the knockout mice displayed enhanced response to G-Protein Couple Receptor agonism and depolarization contractility and resistant relaxation. We further identified a natural compound lotusine that increased the MYPT1 expression by inhibiting SIAH1/2 E3 ligases-mediated protein degradation. This compound sufficiently restored the ICP and improved histological characters of the penile artery of Mypt1 haploinsufficiency mice. In diabetic ED mice (db/db), the decreased expression of MYPT1 was measured, and ICP was improved by lotusine treatment. We conclude that the reduction of MYPT1 is the major pathogenic factor of vasculogenic ED. The restoration of MYPT1 by lotusine improved the function of injured penile smooth muscles, and could be a novel strategy for ED therapy., (© 2022. The Author(s).)

Intractable functional constipation (IFC) is the most severe form of constipation, but its etiology has long been unknown. We hypothesized that IFC is caused by refractory infection by a pathogenic bacterium. Here, we isolated from patients with IFC a Shigella species - peristaltic contraction-inhibiting bacterium (PIB) - that significantly inhibited peristaltic contraction of the colon by production of docosapentenoic acid (DPA). PIB colonized mice for at least 6 months. Oral administration of PIB was sufficient to induce constipation, which was reversed by PIB-specific phages. A mutated PIB with reduced DPA was incapable of inhibiting colonic function and inducing constipation, suggesting that DPA produced by PIB was the key mediator of the genesis of constipation. PIBs were detected in stools of 56% (38 of 68) of the IFC patients, but not in those of non-IFC or healthy individuals (0 of 180). DPA levels in stools were elevated in 44.12% (30 of 68) of the IFC patients but none of the healthy volunteers (0 of 97). Our results suggest that Shigella sp. PIB may be the critical causative pathogen for IFC, and detection of fecal PIB plus DPA may be a reliable method for IFC diagnosis and classification.

The purpose of this experiment was to examine the potential use of Carica papaya leaf extract as a supplement to promote growth and improve feed utilization in red hybrid tilapia. Five diets were formulated containing isolipidic (80 g/kg) and isonitrogenic (350 g/kg) levels. All feeds contained similar types and amounts of raw materials but differed in the inclusion of papaya leaf extract (0, 5, 10, 20 and 40 g/kg feed). The initial size of fish used was 2.3 ± 0.01 g. Each diet was performed in triplicate tanks, and the feeding period was 12 weeks. Fish fed diet containing 2% papaya leaf extract (PLE) had the highest final weight, 31.14 ± 1.47 g, followed by 1% PLE (27.27 ± 1.75 g). These two diets (1% and 2%) were also showed significant improvements of weight gain, SGR, and feed efficiency of the red hybrid tilapia (p < 0.05). However, papaya leaf extract did not affect the HSI, VSI, PER, digestive enzymes activity, blood composition, and survival rate. Supplementing the diets with papaya leaf extract lowered serum urea. Findings of this research suggest that adding papaya leaf extract to the diet of red hybrid tilapia improves growth and feed efficiency without adversely affecting blood parameters. Therefore, an inclusion level between 1% and 2% of the papaya leaf extract is recommended as a feed additive to promote red hybrid tilapia fry growth., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

In the present study described the impact of water quality on the Asian clam, Corbicula fluminea , distribution in man - made Pergau Lake was carried out. Recently, Pergau Lake was gazette as state park and any activities related to fishery and agricultural were not allowed in the park. Subsequently, the nearby lake community was affected as many of them earn a living by carrying fisheries activity in the lake especially harvesting Asian clam. 10 sampling sites were selected in the lake to monitor water quality and Asian clam distribution. Water parameters data were also subjected to cluster analysis by using Ward's method with squared Euclidean distances as a measure of similarity and a dendrogram was successfully generated. The water quality of the lake is under good condition and suitable to carry fishery activities by referred to Malaysia National Water Quality Standards (NWQS). The dendrogram revealed that the sampling sites can be divided into 2 clusters where Location 1 alone in its own cluster. Another cluster possesses 2 sub-clusters where Location 2 and 3 shared similar sub cluster. Another sub-cluster has two groups namely Location 5, 6 and 8 in one group whereas Location 4, 7, 9 and 10 shared similar group. The findings of the present study showed most of sampled Asian clam in Pergau Lake was semi mature indicating highly exploitation of Asian clam in the Lake. Furthermore, there were no correlation was detected between the population of Asian clam and water quality of the lake. Hence, we suggest that seasonal harvesting Asian clam should be implemented in order to conserve the population of Asian clam in the lake at the mean time the community to continue earn a living through carrying fishery activities in the lake., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

The thymus is the central immune organ, but it is known to progressively degenerate with age. As thymus degeneration is paralleled by the wasting of aging skeletal muscle, we speculated that the thymus may play a role in muscle wasting. Here, using thymectomized mice, we show that the thymus is necessary for skeletal muscle regeneration, a process tightly associated with muscle aging. Compared to control mice, the thymectomized mice displayed comparable growth of muscle mass, but decreased muscle regeneration in response to injury, as evidenced by small and sparse regenerative myofibers along with inhibited expression of regeneration-associated genes myh3, myod, and myogenin. Using paired box 7 (Pax7)-immunofluorescence staining and 5-Bromo-2'-deoxyuridine-incorporation assay, we determined that the decreased regeneration capacity was caused by a limited satellite cell pool. Interestingly, the conditioned culture medium of isolated thymocytes had a potent capacity to directly stimulate satellite cell expansion in vitro. These expanded cells were enriched in subpopulations of quiescent satellite cells (Pax7 high MyoD low EdU pos ) and activated satellite cells (Pax7 high MyoD high EdU pos ), which were efficiently incorporated into the regenerative myofibers. We thus propose that the thymus plays an essential role in muscle regeneration by directly promoting satellite cell expansion and may function profoundly in the muscle aging process., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

The aim of this study was to investigate the effects of longan flower (LF) water extract on cardiac apoptotic and survival pathways in rat models of fructose-induced metabolic syndrome. The study findings revealed that the levels of glucose, insulin, triglyceride, and cholesterol and TUNEL-positive apoptotic cells were significantly increased in the HF group compared with the control group; whereas, the levels were decreased in the HFLF group. The expressions of Fas, FADD, and activated caspases 8 and 3, as well as the expressions of Bax, Bak, Bax/Bcl-2, Bak/Bcl-xL, cytosolic cytochrome c, and activated caspases 9 and 3 were increased in the HF group were significantly reversed in HFLF administrated group. Furthermore, LF extract increased IGF-1R, p-PI3K, p-Akt, Bcl-2, and Bcl-xL expression compared to HF group. Taken together, the present findings help identify LF as a potential cardioprotective agent that can be effectively used in treating fructose-induced metabolic syndrome., (© 2021 Wiley Periodicals LLC.)

Both smooth muscle (SM) and non-muscle (NM) myosin II are expressed in hollow organs such as the bladder and uterus, but their respective roles in contraction and corresponding physiological functions remain to be determined. In this report, we assessed their roles by analyzing mice deficient of Myl9 , a gene encoding the SM myosin regulatory light chain (SM RLC). We find that global Myl9 -deficient bladders contracted with an apparent sustained phase, despite no initial phase. This sustained contraction was mediated by NM myosin RLC (NM RLC) phosphorylation by myosin light chain kinase (MLCK). NM myosin II was expressed abundantly in the uterus and young mice bladders, of which the force was accordingly sensitive to NM myosin inhibition. Our findings reveal distinct roles of SM RLC and NM RLC in SM contraction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Sun, Qiao, Tao, Zhao, Wei, Li, Wang, Wang, Zhou, Zheng, Chen, Pan, Zhang and Zhu.)

Magnolia officinalis is widely used in Southeast Asian countries for the treatment of fever, headache, diarrhea, and stroke. Magnolol is a phenolic compound extracted from M. officinalis , with proven antibacterial, antioxidant, anti-inflammatory, and anticancer activities. In this study, we modified magnolol to synthesize a methoxylated derivative, 2-O-methylmagnolol (MM1), and investigated the use of MM1, and magnolol in the treatment of liver cancer. We found that both magnolol and MM1 exhibited inhibitory effects on the growth, migration, and invasion of hepatocellular carcinoma (HCC) cell lines and halted the cell cycle at the G1 phase. MM1 also demonstrated a substantially better tumor-suppressive effect than magnolol. Further analysis suggested that by inhibiting class I histone deacetylase expression in HCC cell lines, magnolol and MM1 induced p21 expression and p53 activation, thereby causing cell cycle arrest and inhibiting HCC cell growth, migration, and invasion. Subsequently, we verified the significant tumor-suppressive effects of magnolol and MM1 in an animal model. Collectively, these findings demonstrate the anti-HCC activities of magnolol and MM1 and their potential for clinical use., (Copyright © 2020 Chen, Fang, Chen, Chuang, Leu, Ueng, Wei, Cheng, Hsueh and Wang.)

Many chemical and physical equilibrium conditions can be determined from minimizing the Gibbs free energies of the system. Efficient analytical representations of the entropy and Gibbs free energy of carbonyl sulfide remain elusive in the communality of science and engineering. Here, we report two analytical representations of the entropy and Gibbs free energy for carbonyl sulfide, and the prediction procedures only involve six molecular constants of the carbonyl sulfide molecule. In the temperature range from 300 to 6000 K, the average relative deviations of the predicted molar entropy and reduced Gibbs free energy values of carbonyl sulfide from the National Institute of Standards and Technology database are arrived at 0.150 and 0.189%, respectively., Competing Interests: The authors declare no competing financial interest., (Copyright © 2019 American Chemical Society.)

To investigate the feasibility of ultrasonography in detecting the oropharynx movement during deep breathing and to quantitatively analyze oropharynx airway lumen changes during deep breathing. The motions of oropharynx were monitored, and sonographic measurements of airway lumen were obtained during deep breathing in 448 healthy volunteers. Adequate visualization of oropharynx movement was obtained on all healthy volunteers. The anterior-posterior (AP) diameters and AP/transverse (T) diameter ratios were greater at the end of deep inspiration than that at the end of deep expiration for each sex (p < 0.01). The anterior-posterior dimensional changes were greater than lateral airway dimensional changes each sex (p < 0.05). Ultrasonography could provide realistic impression of the process on the oropharynx movement during deep breathing and perform the quantitative analysis of the oropharynx airway lumen changes during deep breathing. The results were encouraging and supported the utility of ultrasonography in future studies., (Copyright © 2019 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Skin diseases have a serious impact on people's life and health. Current research proposes an efficient approach to identify singular type of skin diseases. It is necessary to develop automatic methods in order to increase the accuracy of diagnosis for multitype skin diseases. In this paper, three type skin diseases such as herpes, dermatitis, and psoriasis skin disease could be identified by a new recognition method. Initially, skin images were preprocessed to remove noise and irrelevant background by filtering and transformation. Then the method of grey-level co-occurrence matrix (GLCM) was introduced to segment images of skin disease. The texture and color features of different skin disease images could be obtained accurately. Finally, by using the support vector machine (SVM) classification method, three types of skin diseases were identified. The experimental results demonstrate the effectiveness and feasibility of the proposed method.

The wire myograph technique is used to assess the contractility of vascular smooth muscles in response to depolarization, GPCR agonists/inhibitors and drugs. It is widely used in many studies on the physiological functions of vascular smooth muscle, the pathogenesis of vascular diseases such as hypertension, and the development of smooth muscle relaxant drugs. The mouse is a widely used model animal with a large pool of disease models and genetically modified strains. We introduced this method to measure the isometric contraction of mouse mesenteric artery in detail. A 1.4-mm segment of mouse mesenteric resistance artery was isolated and mounted on a myograph chamber by passing two steel wires through its lumen. After equilibration and normalization steps, the vessel segment was potentiated by a high-K + solution twice prior to the contraction assay. As an example of the application of this method in drug development, we measured the relaxant effect of a novel natural substance, neoliensinine, isolated from a Chinese herb, embryos of the lotus seed (Nelumbo nucifera Gaertn.) on mouse mesenteric arteries. The vessel segments mounted on the myograph chamber were stimulated with a high-K + solution. When the force tension reached a stable sustained phase, cumulative doses of neoliensinine were added to the chamber. We found that neoliensinine had a dose-dependent relaxant effect on smooth muscle contraction, thus suggesting that it bears potential activity against hypertension. In addition, as the vessel segment can survive at least 4 hours after mounting and maintain contractility induced by the high-K + solution for many times, we suggest that the wire myograph system may be used for the time-consuming process of drug screening.

Physical exercise has been reported to increase neurotrophin in brain tissues as hippocampus as well as increased neurotrophic level peripherally in blood plasma and might have an effect on/or affect molecular processes of energy metabolism (and homeostasis). In this study, using quantitative proteomic analysis, we obtained a plasma protein profile from the rat with long-term moderate exercise. A total of 752 proteins were identified in the plasma. Among them, 54 proteins were significant up-regulated and 47 proteins were down-regulated in the plasma of exercise group compared with the control group. Bioinformatic analyses showed that these altered proteins are widely involved in multiple biological processes, molecular functions and cellular components, which connect with 11 signaling pathways. Interestingly, 5 up-regulated proteins Rap1b, PTPN11, ARHGDIA, Cdc42 and YWHAE, confirmed by Western blots, are involved in the neurotrophin signaling pathway which shows the lowest P value among the identified pathways. Further analyses showed that the 5 neurotrophin-signaling-pathway-related proteins participate in two important protein-protein interaction networks associated to cell survival and apoptosis, axonal development, synapse formation and plasticity. This study provides an exercise-induced plasma protein profile, suggesting that long-term exercise enhances the proteins involved in neurotrophin signaling pathway which may contribute to health benefit., Significance: Physical activity contributes to myriad benefits on body health across the lifespan. The changes in plasma proteins after chronic moderate exercise may be used as biomarkers for health and may also play important roles in increase of cardiovascular fitness, enhancement of immune competence, prevention of obesity, decrease of risk for neurological disorders, cancer, stroke, diabetes and other metabolic disorders. Using a TMT-based proteomic method, this study identified 101 altered proteins in the plasma of rats after long-term moderate treadmill running, which may provide novel biomarkers for further investigation of the underlying mechanism of physical exercise. We confirmed that exercise enhances 5 proteins of the neurotrophin signaling pathway that may contribute to health benefits., (Copyright © 2018. Published by Elsevier B.V.)

Objective: To investigate the impact of TGF-β3 on the chondrogenesis of bone marrow mesenchymal stem cells (BM-MSCs) under hypoxia environment. Methods: BM-MSCs were obtained from SD rat tibias and femora and cultured with whole bone marrow adherent method. Cell surface antigens were analyzed by flow cytometry and the multiple-directional differentiation capabilities were detected with special differentiation agents to affirm the reality of BM-MSCs. Under normoxia or hypoxia condition, BM-MSCs were induced with TGF-β3 or not. Then, alcian blue and immunofluorescence staining were performed to evaluate the expression level of aggrecan, collagen Ⅱ. qRT-PCR analysis were performed to analyze the expression of aggrecan, collagen Ⅱ and collagen Ⅹ. qRT-PCR and Western blot analysis was performed to detect the mRNA and protein level of HIF-1α, collagenⅡ and β-catenin. Results: BM-MSCs were fibroblast-like shape and had ablities of osteogeic, adipogenic and chondrogenic differentiation, with the expression of CD(29, )CD(44) and CD(90) but not CD(45). Alcian blue and immunofluorescence staining showed that BM-MSCs strongly expressed the aggrecan and collagen Ⅱ with the presence of TGF-β3 under hypoxia condition. qRT-PCR analysis showed the mRNA expression levels of collagen Ⅱ, aggrecan and collagen Ⅹ were up-regulated at 2.46, 2.20 and 1.80 folds, comparing with control group (all P <0.05). Western blot analysis showed that the protein levels of HIF-1α, collagenⅡ in BM-MSCs were up-regulated with the presence of TGF-β3 under hypoxia condition, but β-catenin level was down-regulated. Conclusion: TGF-β3 promotes the chondrogenic differentiation ability of BM-MSCs under hypoxia condition, which may be relative with the inhibition of Wnt/β-catenin signaling pathway.

A series of 1,2- and 2,3-fused quinazolinones have been synthesized in good to excellent yields through gold-catalyzed selective hydroarylations of alkynyl quinazolinone-tethered pyrroles. The studies revealed that 1,2-fused quinazolinones were obtained through a 1,3-rearrangement and sequential 6- exo-trig cyclization of N1-alkynyl quinazolinone-tethered pyrroles, while N3-alkynyl quinazolinone-tethered pyrroles went through 6- exo-dig or 7- endo-dig cyclizations directly to afford 2,3-fused quinazolinones. The fused quinazolinones could be prepared at gram scale in three steps from commercial ortho-aminobenzamide.

Background: Allergic inflammation has long been implicated in asthmatic hyperresponsiveness of airway smooth muscle (ASM), but its underlying mechanism remains incompletely understood. Serving as G protein-coupled receptor agonists, several inflammatory mediators can induce membrane depolarization, contract ASM, and augment cholinergic contractile response. We hypothesized that the signal cascade integrating on membrane depolarization by the mediators might involve asthmatic hyperresponsiveness., Objective: We sought to investigate the signaling transduction of inflammatory mediators in ASM contraction and assess its contribution in the genesis of hyperresponsiveness., Methods: We assessed the capacity of inflammatory mediators to induce depolarization currents by electrophysiological analysis. We analyzed the phenotypes of transmembrane protein 16A (TMEM16A) knockout mice, applied pharmacological reagents, and measured the Ca 2+ signal during ASM contraction. To study the role of the depolarization signaling in asthmatic hyperresponsiveness, we measured the synergistic contraction by methacholine and inflammatory mediators both ex vivo and in an ovalbumin-induced mouse model., Results: Inflammatory mediators, such as 5-hydroxytryptamin, histamine, U46619, and leukotriene D 4 , are capable of inducing Ca 2+ -activated Cl - currents in ASM cells, and these currents are mediated by TMEM16A. A combination of multiple analysis revealed that a G protein-coupled receptor-TMEM16A-voltage-dependent Ca 2+ channel signaling axis was required for ASM contraction induced by inflammatory mediators. Block of TMEM16A activity may significantly inhibit the synergistic contraction of acetylcholine and the mediators and hence reduces hypersensitivity., Conclusions: A G protein-coupled receptor-TMEM16A-voltage-dependent Ca 2+ channel axis contributes to inflammatory mediator-induced ASM contraction and synergistically activated TMEM16A by allergic inflammatory mediators with cholinergic stimuli., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objective: To study the expression of the gene of myosin regulatory light chain-2 (MYL2) in the development of rat testis tissue., Methods: Using real-time PCR and immunohistochemistry, we determined the mRNA transcription level and protein expression of MYL2 in the rat testis., Results: The mRNA expression of the MYL2 gene changed in an age-dependent manner, reaching the highest value on postnatal day (PND) 2, then dropped rapidly till PND 8, increased slowly on PNDs 10 and 12, decreased on PND 14, rose slightly from PND 15 and rapidly on PNDs 20 and 25, and declined slowly from PND 65. Immunohistochemistry showed that the MYL2 protein was mainly expressed in testicular sperm cells., Conclusions: The MYL2 gene may be involved in the proliferation of spermatogonial stem cells and the process of sperm cells developing into mature sperm.

Congenital thoracic lordosis or lordoscoliosis are rare deformities which causes severe cardiopulmonary problems in early ages. PVCR is effective in restoring thoracal kyphosis in treatment of these rare deformities and avoids morbidity of combined surgeries.

The solubility limitations of phenolic acids in many lipidic environments are now greatly improved by their enzymatic esterification in ionic liquids (ILs). Herein, four different ILs were tested for the esterification of dihydrocaffeic acid with hexanol and the best IL was selected for the synthesis of four other n-alkyl esters with different chain-lengths. The effect of alkyl chain length on the anti-oxidative properties of the resulted purified esters was investigated using β-carotene bleaching (BCB) and free radical scavenging method DPPH and compared with butylated hydroxytoluene (BHT) as reference compound. All four esters (methyl, hexyl, dodecyl and octadecyl dihydrocaffeates) exhibited relatively strong radical scavenging abilities. The scavenging activity of the test compounds was in the following order: methyl ester>hexyl ester⩾dodecyl ester>octadecyl ester>BHT while the order for the BCB anti-oxidative activity was; BHT>octadecyl ester>dodecyl ester>hexyl ester>methyl ester., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Developing an efficient lipophilization reaction system for phenolic derivatives could enhance their applications in food processing. Low solubility of phenolic acids reduces the efficiency of phenolic derivatives in most benign enzyme solvents. The conversion of phenolic acids through esterification alters their solubility and enhances their use as food antioxidant additives as well as their application in cosmetics., Results: This study has shown that lipase-catalyzed esterification of dihydrocaffeic acid with hexanol in ionic liquid (1-butyl-3-methylimidazoliumbis (trifluoromethylsulfonyl) imide) was the best approach for esterification reaction. In order to achieve the maximum yield, the process was optimized by response surface methodology (RSM) based on a five-level and four independent variables such as: dosage of enzyme; hexanol/dihydrocaffeic acid mole ratio; temperature and reaction time. The optimum esterification condition (Y = 84.4%) was predicted to be obtained at temperature of 39.4 °C, time of 77.5 h dosage of enzyme at 41.6% and hexanol/dihydrocaffeic acid mole ratio of 2.1., Conclusion: Finally, this study has produced an efficient enzymatic esterification method for the preparation of hexyl dihydrocaffeate in vitro using a lipase in an ionic liquid system. Concentration of hexanol was the most significant (p < 0.05) independent variable that influenced the yield of hexyl dihydrocaffeate. Graphical abstract Synthesis of different Hexyl dihydrocaffeates in ionic liquid.