Merging Quinoxalin-2(1H)-ones Excitation with Cobaloxime Catalysis: C3 Alkylation of Quinoxalin-2(1H)-ones with Unactivated Alkyl Iodides and Carboxylic Acids under Light.

Reported herein is a practical, economical, and efficient construction of 3-alkylated quinoxalin-2(1H)-ones with alkyl carboxylic acids and alkyl iodides by quinoxalin-2(1H)-one excitation and cobaloxime catalysis. Primary, secondary, and tertiary alkyl iodides and carboxylic acids all could be efficiently transferred into target products with excellent functional group tolerance. Mechanism studies reveal that the quinoxalin-2(1H)-one derivatives could be directly excited and yield alkyl carbon radicals from alkyl carboxylic acids and alkyl iodides with the aid of the cobaloxime complex.

Metabolomic assessment of African snail (Achatina fulica) meal on growth performance of giant river prawn (Macrobrachium rosenbergii).

This study aimed to investigate the effects of replacing fishmeal (FM) with African giant snail (Achatina fulica) meal (SM) on the growth performance of giant river prawn (Macrobrachium rosenbergii), as well as to analyze the associated metabolomic changes. Six diets were formulated, replacing FM with SM at different inclusion levels ranging from 0 % to 100 %. Growth performance and feed conversion ratio of prawns fed diets with FM replaced by SM up to 80 % were not significantly different from control. In contrast, significantly decreased growth performance and higher feed conversion ratio (FCR) occurred with diets containing 100 % SM. To gain insights into the metabolic regulation of prawns fed different diets, a 1H NMR metabolomics approach was used to assess the metabolic changes in prawns fed diets containing 0 % and 80 % SM. The results revealed up-regulated metabolites significantly involved in several metabolic pathways, including alanine, aspartate, and glutamate metabolism; citrate cycle (TCA cycle); aminoacyl-tRNA biosynthesis; and valine, leucine, and isoleucine biosynthesis. These findings imply that including SM in the diet might modulate the regulation of muscle amino acids and tRNA synthesis, suggesting a potential impact on protein biosynthesis mechanisms. Additionally, alterations in the TCA cycle may reflect changes in carbon utilization, potentially contributing to the growth performance of giant river prawns when fishmeal is replaced with SM without adversely affecting their growth. In conclusion, this study demonstrated that SM could be a promising alternative protein source in aquafeed. The metabolomic approach provides valuable insights into the metabolic changes in prawns fed different diets, aiding in the development of more effective aquafeeds in the future. The study's limitations, such as the simplified diet formulation and the limited scope of the metabolomic analysis, were acknowledged and discussed, highlighting the need for further research to build upon these findings.

[Distribution Characteristics and Risk Assessment of PPCPs in Surface Water and Sediments of Lakes in the Lower Reaches of the Huaihe River].

In order to understand the occurrence characteristics and ecological risks of pharmaceuticals and personal care products (PPCPs) in surface water and sediments of Hongze Lake and Gaoyou Lake in the lower reaches of the Huaihe River, 43 surface water and sediment samples from 23 sampling sites were collected, and 61 PPCPs were detected in the samples. The concentration level and spatial distribution of target PPCPs in Hongze Lake and Gaoyou Lake were analyzed, the distribution coefficient of typical PPCPs in the water/sediment system in the study area was calculated, and the ecological risk of target PPCPs was evaluated using the entropy method. The results showed that the PPCPs in surface water of Hongze Lake and Gaoyou Lake were 1.56-2534.44 ng·L-1 and 3.32-1027.47 ng·L-1, respectively, and those in sediment were 1.7-926.7 ng·g-1 and 1.02-289.37 ng·g-1, respectively. The concentrations of lincomycin (LIN) in surface water and doxycycline (DOX) in sediment were the highest, and antibiotics were the main components. The spatial distribution of PPCPs was higher in Hongze Lake and lower in Gaoyou Lake. The distribution characteristics of typical PPCPs in the study area showed that typical PPCPs tended to stay in the water phase, and there was a significant correlation between lg Koc and lg Kd, indicating that total organic carbon (TOC) played an important role in the distribution of typical PPCPs in the water/sediment system. The ecological risk assessment results showed that the ecological risk of PPCPs to algae in surface water and sediment was significantly higher than that of fleas and fish, the ecological risk value of PPCPs in surface water was higher than that in sediment, and the ecological risk of Hongze Lake was higher than that of Gaoyou Lake.

Heat inactive Bacillus subtilis var. natto regulate Nile tilapia (Oreochromis niloticus) intestine microbiota and metabolites involved in the intestine phagosome response.

In this study, we evaluated the intestinal microbiota, intestinal and fecal metabolites production and the intestinal RNA-seq analysis of the Nile tilapia intestine after feeding with 105and 107 of the inactive Bacillus subtilis var. natto. First, we assessed the influence of heat inactive Bacillus subtilis var. natto on the growth performance, biochemical blood analysis, and evaluated the liver/body, spleen/body and intestine/body ratio. This evidence was known feeding with inactive Bacillus subtilis var. natto was able to improve the growth performance after 4 weeks, but not to affect the inflammatory biochemical blood parametres total protein (T-pro), albumin (Alb), Alb/T-pro ratio, creatine-phospho-kinase (CPK) and lactate dehydrogenase (LDH). Further, in the intestine microbiota, the Lactobacillaceae, Firmicutes, Chromatiales, and Rhodobacteria, was significantly higher than the control and the Firmicutes/Bacteroidetes ratio (F/B), which was indicated with a significantly increased. The intestine tissue metabolites OPLS-DA analysis indicated that the prominent bioactive metabolites changed. The peonidin-3-glucoside, l-Tyrosine, 1-Deoxy-1-(N6-lysino)-d-fructose was significantly increased. The feces metabolite OPLS-DA analysis indicated that the palmitelaidic acid, 5-KETE, tangeritin was significantly increased. In the transcriptome, the Gene Ontology (GO) analysis was found to enhance the intestine intestinal immune network. Combine of these evidence, feeding of the heat inactive Bacillus subtilis var. natto exactly improved the O. niloticus growth performance and regulation of the microbiota to promote the metabolites. In the transcriptome analysis, it was found to involve in the intestine immune phagosome response. Summarized of this study, the heat inactive Bacillus subtilis var. natto was reported to affect Nile tilapia intestine microbiota, and could positively regulate the intestine and fecal metabolites production to improve the intestine immune network.

Red Algae "Sarcodia suieae" Acetyl-Xylogalactan Downregulate Heat-Induced Macrophage Stress Factors Ddit3 and Hyou1 Compared to the Aquatic Animal Model of Nile Tilapia (Oreochromis niloticus) Brain Arachidonic Acid Expression

Anthropogenic climate change is known to be an increased stress that affects aquatic animal behavior and physiological alternations, which can induce the animal's death. In order to known whether the extracted acetyl-xylogalactan function on the regulation of the external high temperature induced death, we first selected the mammalian cell line "RAW 264.7" used in the previous experiment to evaluate the extracted acetyl-xylogalactan function. We aimed to evaluate the effects of the acetyl-xylogalactan on the RAW 264.7 macrophages and Nile Tilapia stress factor expression under the heat environment. In the in vitro cell observation, we assessed the cell survival, phagocytic activity, intracellular Ca2+ level, mitochondria potential exchange, apoptotic assay findings, galactosidase activity, RNA-seq by NGS and real-time polymerase chain reaction (QPCR) expression. In the in vivo Nile Tilapia observation aimed to evaluate the blood biochemical indicator, brain metabolites exchange and the liver morphology. In our evaluation of RAW 264.7 macrophages, the RNA sequencing and real-time polymerase chain reaction (PCR) was shown to upregulate the expression of the anti-apoptosis Cflar gene and downregulate the expression of the apoptosis factors Ddit3 and Hyou1 to protect macrophages under heat stress. We already knew the extracted acetyl-xylogalactan function on the mammalian "RAW 264.7" system. Following, we used the aquatic Nile Tilapia model as the anthropogenic climate change high temperature experiment. After feeding the Nile Tilapia with the acetyl-xylogalactan, it was found to reduce the brain arachidonic acid (AA) production, which is related to the NF-κB-induced apoptosis mechanism. Combined with the in vitro and in vivo findings, the acetyl-xylogalactan was able to reduce the heat induced cell or tissue stress.

Acid external and internal environment exchange the Oreochromis niloticus tissue immune gene expression compared to the mouse macrophage polarization model.

The water environment plays an important role in animal physiology. In this study, we sought to evaluate the effect of the acid environment on the Oreochromis niloticus (Nile tilapia) internal microenvironment immune response compare to the mouse macrophage model (J77A.1). The acid environment treated mouse macrophage J774A.1 model have shown that acidic treatment is able to polarize macrophages into M2-like macrophages via an increase in Ym1, Tgm2, Arg1, Fizz1, and IL-10 expression. Metabolic analysis of mouse macrophages (J774A.1) at pH 2 vs. pH 7 and pH 4 vs. pH 7 have been shown to promote the expression of intracellular acetylcholine, choline, prochlorperazine, L-leucine, and bisphenol A,2-amino-3-methylimidazo[4,5-f] quinolone metabolites in the M2-like macrophage. Immune gene expression of the O. niloticus spleen and liver treated at pH 2, 4, and 7 was shown to reduce TNF-α, IL-1 ß, IL-8, and IL-12 expression compared to pH 7 treatment. Immune gene was induced in O. niloticus following culture at pH 5, 6, and 7 fresh water environment. Taken together, we found that the acid internal environment polarizes tissues into an M2 macrophage developmental microenvironment. However, if the external environment is acid, tissues are exposed to an M1 macrophage developmental microenvironment.

Effect of dietary supplementation with Moringa oleifera leaf extract and Lactobacillus acidophilus on growth performance, intestinal microbiota, immune response, and disease resistance in whiteleg shrimp (Penaeus vannamei).

This study investigated the effect of the moringa (Moringa oleifera) leaf extract and Lactobacillus acidophilus individually or combined on growth performance, enzyme activity, intestinal and hepatopancreatic histology, intestinal microbiota, immune response, and resistance against Vibrio alginolyticus and Vibrio parahaemolyticus in whiteleg shrimp (Penaeus vannamei). Six diets were formulated: three diets without L. acidophilus containining 0 (control, ME0), 2.5 (ME2.5), and 5.0 g/kg of moringa (ME5.0) and the same three diets containing L. acidophilus at 1 × 107 CFU/g of diet (ME0+P, ME2.5 + P, and ME5.0 + P, respectively). Growth performance was measured after 60 days of the rearing period. On the final day, the shrimp were sampled to assess enzyme activity, intestinal and hepatopancreatic histology, and gut microbiota. Shrimp hemocytes were examined on Days 0, 1, 2, 4, 7, 14, 21, and 28 to measure the immune response in terms of the total hemocyte count, phenoloxidase activity, phagocytosis, and superoxide anion production. Furthermore, the shrimp were challenged with V. alginolyticus and V. parahaemolyticus. The results revealed that ME2.5 + P significantly increased (P < 0.05) final weight, weight gain, specific growth rate, enzyme activities, and villi height compared with ME2.5 and control. Wall thickness was increased in the shrimp fed diet supplemented with moringa and L. acidophilus compared with the control shrimp. Hepatopancreatic histology revealed that R cells were more abundant in the shrimp fed diet containing moringa and L. acidophilus compared with those fed diet containing moringa alone (P < 0.05) at the same concentration. High-throughput sequencing analysis indicated that the dietary supplementation with moringa and L. acidophilus affected the gut microbiota composition. All gene functions, members of KEGG level 2, related to metabolism were increased in diet supplemented with moringa with or without L. acidophilus compared with the control group. The immune assay revealed that the total hemocyte count, phenoloxidase activity, phagocytic rate, superoxide anion production, and immune-related gene expression (including those of prophenoloxidase II, alpha-2-macroglobulin, penaeidin2, antilipopolysaccharide factor, crustin, lysozyme, glutathione peroxidase, and superoxide dismutase) were higher in the experimental groups than in the control group on several observed days; however, the increases were observed more often in the ME2.5 + P group than in the other treatment groups. Furthermore, the ME2.5 + P group exhibited a significantly higher survival rate (P < 0.05) in the challenge test against V. alginolyticus and V. parahaemolyticus. In conclusion, supplementation with dietary moringa and L. acidophilus at ME2.5 + P improved growth performance, immune system, and resistance against Vibrio in the shrimp.

Effects of dietary Lactobacillus reuteri and Pediococcus acidilactici on the cultured water qualities, the growth and non-specific immune responses of Penaeus vannamei.

This study discussed the effects of two types of lactic acid bacteria, Lactobacillus reuteri (L. reuteri) and Pediococcus acidilactici (P. acidilactici), on the growth and nonspecific immunity of Penaeus vannamei (P. vannamei) and developed probiotic applications for shrimp cultivation. This study incorporated two types of lactic acid bacteria in shrimp feed through spraying. The shrimps were grouped according to the type and concentration of effective bacteria incorporated into their feed. This research was separated into 3 individual feeding treatment as control, L. reuteri (Lr groups) and P. acidilactici (Pa groups). The shrimp was feeding with 103, 105, and 107 cfu/feed (g) L. reuteri namely as Lr3, Lr5, and Lr7. The shrimp was feeding with 103, 105, and 107 cfu/feed (g) P. acidilactici were named Pa3, Pa5, and Pa7, respectively. Through 8 weeks of feeding, the results revealed that the use of shrimp feed incorporated with lactic acid bacteria did not cause negative effects on water quality. The testing items include ammonia-nitrogen concentration, nitrite-nitrogen concentration, and total vibrio count in the water. In addition, the lactic acid bacteria concentration in the water were in the range of 1.33 ± 0.58 × 101 to 9.77 ± 1.34 × 102 cfu/mL. Observations of the growth performance of the white shrimps after 8 weeks of feeding revealed that both bacteria were beneficial to shrimp growth. In particular, group Lr7 had the highest percentage weight gain (107.99 ± 3.92%), special growth rate (1.93 ± 0.07%), feed conversion ratio (3.34 ± 0.05), and survival rate (97.22 ± 4.81%). Furthermore, observations of the nonspecific immunity reactions of the white shrimps after 4 weeks of feeding indicated that on day 4, the total number of haemocyte in shrimps in groups Lr5, Lr7, Pa3, and Pa5 significantly increased. On days 1 and 4, the phenoloxidase activity and superoxide axion production rates of the Lr group and Ls group increased. This phenomenon was the most significant in group Lr7, and the effect continued until day 28. After day 7, the phagocytic rate of groups Lr5 and Lr7 significantly increased. In addition, Lr and Pa groups exhibited significant increases in the phagocytic index after days 4 and 14, respectively. This phenomenon was also the most significant in group Lr7.

Bioaccumulation of arsenic and immunotoxic effect in white shrimp (Penaeus vannamei) exposed to trivalent arsenic.

Trivalent arsenic (As (III)) contamination in the marine environment can produce adverse effects in crustaceans. The present study investigated the chronic toxicity of As (III) in white shrimp (Penaeus vannamei) by analyzing the tissue bioaccumulation and non-specific immune responses. Shrimps were exposed to 0 (control), 50, 500, and 2500 µg/L of As (III) for 21 days. The results showed that the hepatopancreas was the main tissue of arsenic accumulation in white shrimp. The cumulative concentration of total arsenic and inorganic arsenic but not arsenobetaine was positively correlated with the exposure concentration. In vitro As (III) treatment (0-2500 µg/L) with haemocytes isolated from healthy shrimp did not cause the cytotoxicity, but this arsenic treatments inhibited the phagocytic rate and O2- production. Moreover, the decrease of total haemocyte count and the inhibition of phagocytic rate, phagocytic index, O2- production and phenoloxidase activity were observed in white shrimp under the exposure of As (III) over a period of 21 days. This study revealed that chronic As (III) stress could disturb arsenic metabolism and immune responses in P. vannamei.

Effect of Methylmercury Exposure on Bioaccumulation and Nonspecific Immune Respsonses in Hybrid Grouper Epinephelus fuscoguttatus × Epinephelus lanceolatus.

Mercury (Hg) is a dangerous heavy metal that can accumulate in fish and is harmful when consumed by humans. This study investigated the bioaccumulation of mercury in the form of methylmercury (MeHg) and evaluated nonspecific immune responses such as phagocytic activity and superoxide anion (O2-) production in hybrid grouper (Epinephelus fuscoguttatus × E. lanceolatus). The hybrid grouper leukocytes were incubated with methylmercury chloride (CH3HgCl) at concentrations of 10-10,000 µg/L to determine cell viability, phagocytic activity, and O2- production in vitro. Subsequently, the grouper were exposed daily to CH3HgCl mixed in the experimental diets at concentrations of 0, 1, 5, and 10 mg/kg for 28 days. The bioaccumulation of MeHg in the liver, head kidney, and muscle tissue was measured, and the phagocytic activity and O2- production were evaluated. In vitro results indicated that cell viability was significantly lower than that of the control group at concentrations > 500 µg/L. The phagocytic rate and O2- production at concentrations ˃ 500 and ˃ 200 µg/L, respectively, were significantly lower than those of the control group. The dietary exposure demonstrated that MeHg accumulated more substantially in the liver and head kidney compared with the muscle tissue in the treatment groups. Moreover, the cumulative concentration significantly increased with higher concentrations and more days of exposure. The phagocytic rate and O2- production in the treatment groups were significantly lower than those in the control group from days 2 and 1, respectively. In conclusion, hybrid grouper accumulated significant MeHg in the liver and head kidney compared with the muscle tissue, and higher concentrations and more exposure days resulted in decreased cell viability, phagocytic activity, and O2- production.

[Distribution of Typical Pollutants from Rainwater Sewer Sediments in Suzhou City].

In this study, we separately collected rainwater sewer sediments from typical samples in Suzhou city, such as the urban commercial district, historical and cultural protection area, cultural and educational area, and living area, and analyzed the particle size distribution of the sediments and the characteristics of carbon, nitrogen, phosphorus content, and pollution load distribution under each graded particle size. The median particle size D50 of each sample point was 16.55-327.50 µm, and the particle size trend was as follows:commercial area > living area > historical and cultural protection area > cultural and educational area. D50 was related to the total organic carbon (TOC). The total nitrogen (TN), total phosphorus (TP), and ammonia nitrogen (NH4+-N) were significantly positively correlated, as were the pollutants. The spatial difference of ω(TOC), ω(TN), ω(TP), and ω(NH4+-N) in rainwater sewer sediments from different regions was as follows:commercial area > historical and cultural protection area > living area > cultural and educational area, in which ω(TOC) was 0.84%-6.76%, and ω(TN), ω(TP), and ω(NH4+-N) were 917.5-12707.1, 196.1-2524.8, and 9.3-156.8 mg·kg-1, respectively. TOC, TP, and NH4+-N pollution loads were mainly concentrated on particles ≤ 75 µm and 250-1000 µm. Street dust pollutants highly differed spatially, with a high content of attached pollutants on street dust particles with a particle size of ≤ 75 µm. Various pollutants migrated into the street dust-pipes, and TP and TN showed certain enrichment characteristics in the sewer. Controlling the transportation of street dust and the accumulation of sediments in the sewer can reduce the pollution of sediment into the rivers during the rainy season.

Agrobacterium-Mediated Genetic Transformation of Taiwanese Isolates of Lemna aequinoctialis.

Duckweed (Lemna aequinoctialis) is one of the smallest flowering plants in the world. Due to its high reproduction rate and biomass, duckweeds are used as biofactors and feedstuff additives for livestock. It is also an ideal system for basic biological research and various practical applications. In this study, we attempt to establish a micropropagation technique and Agrobacterium-mediated transformation in L. aequinoctialis. The plant-growth regulator type and concentration and Agrobacterium-mediated transformation were evaluated for their effects on duckweed callus induction, proliferation, regeneration, and gene transformation efficiency. Calli were successfully induced from 100% of explants on Murashige and Skoog (MS) medium containing 25.0 µM 2,4-dichlorophenoxyacetic acid (2,4-D) and 2.0 µM thidiazuron (TDZ). MS medium containing 4.5 µM 2,4-D and 2.0 µM TDZ supported the long-lasting growth of calli. Fronds regenerated from 100% of calli on Schenk and Hildebrandt (SH) medium containing 1.0 µM 6-benzyladenine (6-BA). We also determined that 200 µM acetosyringone in the cocultivation medium for 1 day in the dark was crucial for transformation efficiency (up to 3 ± 1%). Additionally, we propose that both techniques will facilitate efficient high-throughput genetic manipulation in Lemnaceae.

Guava (Psidium guajava) leaf extract enhances immunity, growth, and resistance against Vibrio parahaemolyticus in white shrimp Penaeus vannamei.

This study investigated the effects of guava leaf extract (GLE) on immune responses, growth performance, and resistance to Vibrio parahaemolyticus in white shrimp (Penaeus vannamei). To examine the effect of GLE on the immune response of white shrimps, they were treated with various concentrations of GLE on hemocyte (in vitro) and were orally administered (in vivo) feed containing various concentrations of 0, 1, 5, and 10 g kg-1 GLE (control, GLE1, GLE5, and GLE10, respectively) for 28 days. Furthermore, their growth performance was evaluated for 56 days. In a separate experiment, the shrimps were challenged with V. parahaemolyticus injection after 7 days of culture. In vitro experiments indicated that GLE is nontoxic and can activate immune response. In vivo experiments revealed that the GLE5 led to the highest total hemocyte count, phenoloxidase activity, phagocytic activity, and superoxide anion production and the highest upregulation of lipopolysaccharide, ß-1,3-glucan-binding protein, peroxinectin, lysozyme, crustin, penaeidin 2, penaeidin 3, clotting protein, superoxide dismutase, and glutathione peroxidase. Moreover, better growth performance was observed in the GLE groups, with GLE5 exhibiting the highest specific growth rate, weight gain, and feed conversion rate. In addition, GLE5 enhanced resistance to V. parahaemolyticus, with a survival rate of 72.27%. In conclusion, GLE was found to be effective in enhancing nonspecific immune response and growth performance and in reducing V. parahaemolyticus infection in white shrimp.

Efficiently Classifying Lung Sounds through Depthwise Separable CNN Models with Fused STFT and MFCC Features.

Lung sounds remain vital in clinical diagnosis as they reveal associations with pulmonary pathologies. With COVID-19 spreading across the world, it has become more pressing for medical professionals to better leverage artificial intelligence for faster and more accurate lung auscultation. This research aims to propose a feature engineering process that extracts the dedicated features for the depthwise separable convolution neural network (DS-CNN) to classify lung sounds accurately and efficiently. We extracted a total of three features for the shrunk DS-CNN model: the short-time Fourier-transformed (STFT) feature, the Mel-frequency cepstrum coefficient (MFCC) feature, and the fused features of these two. We observed that while DS-CNN models trained on either the STFT or the MFCC feature achieved an accuracy of 82.27% and 73.02%, respectively, fusing both features led to a higher accuracy of 85.74%. In addition, our method achieved 16 times higher inference speed on an edge device and only 0.45% less accuracy than RespireNet. This finding indicates that the fusion of the STFT and MFCC features and DS-CNN would be a model design for lightweight edge devices to achieve accurate AI-aided detection of lung diseases.

Moringa oleifera Leaves' Extract Enhances Nonspecific Immune Responses, Resistance against Vibrio alginolyticus, and Growth in Whiteleg Shrimp (Penaeus vannamei).

Moringa is widely known as a plant with high medicinal properties. Therefore, moringa has a high potential for use as an immunostimulant in shrimp. This study investigated the effect of a moringa water extract on the immune response, resistance against V. alginolyticus, and growth performance of whiteleg shrimp. To perform the in vitro assay, hemocytes were incubated with different concentrations of the moringa extract. Furthermore, the moringa extract was incorporated at 0 (control), 1.25 g (ME1.25), 2.5 g (ME2.5), and 5.0 g (ME5.0) per kg of diet for the in vivo assay. During the rearing period, immune responses, namely the total hemocyte count (THC), phenoloxidase (PO) activity, phagocytosis activity, superoxide anion production, and immune-related gene expression were examined on days 0, 1, 2, 4, 7, 14, 21, and 28. Growth performance was measured 60 days after the feeding period. Furthermore, the shrimp were challenged with V. alginolyticus after being fed for different feeding durations. The results of the in vitro assay revealed that 100-250 ppm of the moringa extract enhanced the PO activity, phagocytic rate (PR), and superoxide anion production. The findings of the in vivo assay demonstrated that the THC, PO activity, PR, and immune-related gene expression, including alpha-2-macroglobulin, prophenoloxidase II, penaeidin2, penaeidin3, anti-lipopolysaccharide factor, crustin, lysozyme, superoxide dismutase, and clotting protein, were higher in the group of ME.25 and ME5.0 than in the control and ME1.25 at several time points. Growth performance was significantly increased (p < 0.05) in the ME2.5 group compared to the control group. Furthermore, the dietary ME2.5 resulted in a higher survival rate compared to that of the control group after challenging with V. alginolyticus, especially at ME2.5 administered for 4 and 7 days. This study indicated that the incorporation of the moringa extract at 2.5 g per kg of diet enhanced the immune response, the growth performance of the whiteleg shrimp, and the resistance against V. alginolyticus infection.

Berberine: A Traditional Natural Product With Novel Biological Activities.

CONTEXT: Having been used for thousands of years to treat gastrointestinal diseases, the natural isoquinoline alkaloid, berberine, has exhibited a wide spectrum of biochemical and pharmacological effects in studies of recent years. OBJECTIVE: The review intended to examine the many novel bioactivities of berberine, including antidiabetic, anticancer, neuroprotective, anti-inflammatory, and anti-atherosclerotic actions. DESIGN: The research team searched the MEDLINE database using PubMed, using different keyword combinations, including berberine AND diabetes, berberine AND cancer, berberine AND (neuron OR brain), berberine AND inflammation, and "berberine AND atherosclerosis to find studies evaluating the various effects exerted berberine. CONCLUSION: Berberine is a promising multipotent agent to combat diabetes, cancer, Alzheimer's disease, and other diseases.

Sarcodia suieae acetyl-xylogalactan regulate RAW 264.7 macrophage NF-kappa B activation and IL-1 beta cytokine production in macrophage polarization.

In this study, the effects of acetyl-xylogalactan extracted from Sarcodia suieae on RAW 264.7 macrophage polarisation were evaluated. This extracted acetyl-xylogalactan had a monosaccharide composition of 91% galactose and 9% xylose, with polysaccharide and acetyl contents of 80.6% and 19.3%, respectively. MALDI-TOF mass spectrometry and NMR spectroscopy revealed the molecular weight of the acetyl-xylogalactan to be 88.5 kDa. After acetyl-xylogalactan treatment, RAW 264.7 macrophage polarisation was noted, along with enhanced phagocytic ability. Furthermore, the Cell Counting Kit-8 (CCK-8) assay was performed and the results demonstrated non-significant alteration in lactate dehydrogenase levels in the treated cells. Next, interleukin (IL) 1ß, TNF, and Malt-1 expression in RAW 264.7 macrophages treated with the S. suieae acetyl-xylogalactan was investigated through real-time quantitative polymerase chain reaction, and the results demonstrated that S. suieae acetyl-xylogalactan induced IL-1ß and Malt-1 expression. RNA sequencing analysis results indicated the S. suieae acetyl-xylogalactan positively regulated cytokine production and secretion, protein secretion, and response to IL-1 activation, based on the observed GO terms. The predicted target genes in the GO enrichment analysis were found to upregulate NF-κB signalling and M0 to M1 macrophage conversion through the observed cytokine production. Thus, acetyl-xylogalactan can positively regulate RAW 264.7 macrophage polarisation.

ORKAMBI-Mediated Rescue of Mucociliary Clearance in Cystic Fibrosis Primary Respiratory Cultures Is Enhanced by Arginine Uptake, Arginase Inhibition, and Promotion of Nitric Oxide Signaling to the Cystic Fibrosis Transmembrane Conductance Regulator Channel.

ORKAMBI, a combination of the corrector, lumacaftor, and the potentiator, ivacaftor, partially rescues the defective processing and anion channel activity conferred by the major cystic fibrosis-causing mutation, F508del, in in vitro studies. Clinically, the improvement in lung function after ORKAMBI treatment is modest and variable, prompting the search for complementary interventions. As our previous work identified a positive effect of arginine-dependent nitric oxide signaling on residual F508del-Cftr function in murine intestinal epithelium, we were prompted to determine whether strategies aimed at increasing arginine would enhance F508del-cystic fibrosis transmembrane conductance regulator (CFTR) channel activity in patient-derived airway epithelia. Now, we show that the addition of arginine together with inhibition of intracellular arginase activity increased cytosolic nitric oxide and enhanced the rescue effect of ORKAMBI on F508del-CFTR-mediated chloride conductance at the cell surface of patient-derived bronchial and nasal epithelial cultures. Interestingly, arginine addition plus arginase inhibition also enhanced ORKAMBI-mediated increases in ciliary beat frequency and mucociliary movement, two in vitro CF phenotypes that are downstream of the channel defect. This work suggests that strategies to manipulate the arginine-nitric oxide pathway in combination with CFTR modulators may lead to improved clinical outcomes. SIGNIFICANCE STATEMENT: These proof-of-concept studies highlight the potential to boost the response to cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulators, lumacaftor and ivacaftor, in patient-derived airway tissues expressing the major CF-causing mutant, F508del-CFTR, by enhancing other regulatory pathways. In this case, we observed enhancement of pharmacologically rescued F508del-CFTR by arginine-dependent, nitric oxide signaling through inhibition of endogenous arginase activity.

Augmentation of Cystic Fibrosis Transmembrane Conductance Regulator Function in Human Bronchial Epithelial Cells via SLC6A14-Dependent Amino Acid Uptake. Implications for Treatment of Cystic Fibrosis.

SLC6A14-mediated l-arginine transport has been shown to augment the residual anion channel activity of the major mutant, F508del-CFTR, in the murine gastrointestinal tract. It is not yet known if this transporter augments residual and pharmacological corrected F508del-CFTR in primary airway epithelia. We sought to determine the role of l-arginine uptake via SLC6A14 in modifying F508del-CFTR channel activity in airway cells from patients with cystic fibrosis (CF). Human bronchial epithelial (HBE) cells from lung explants of patients without CF (HBE) and those with CF (CF-HBE) were used for H3-flux, airway surface liquid, and Ussing chamber studies. We used α-methyltryptophan as a specific inhibitor for SLC6A14. CFBE41o-, a commonly used CF airway cell line, was employed for studying the mechanism of the functional interaction between SLC6A14 and F508del-CFTR. SLC6A14 is functionally expressed in CF-HBE cells. l-arginine uptake via SLC6A14 augmented F508del-CFTR function at baseline and after treatment with lumacaftor. SLC6A14-mediated l-arginine uptake also increased the airway surface liquid in CF-HBE cells. Using CFBE41o cells, we showed that the positive SLC6A14 effect was mainly dependent on the nitric oxide (NO) synthase activity, nitrogen oxides, including NO, and phosphorylation by protein kinase G. These finding were confirmed in CF-HBE, as inducible NO synthase inhibition abrogated the functional interaction between SLC6A14 and pharmacological corrected F508del-CFTR. In summary, SLC6A14-mediated l-arginine transport augments residual F508del-CFTR channel function via a noncanonical, NO pathway. This effect is enhanced with increasing pharmacological rescue of F508del-CFTR to the membrane. The current study demonstrates how endogenous pathways can be used for the development of companion therapy in CF.

SLC6A14, an amino acid transporter, modifies the primary CF defect in fluid secretion.

The severity of intestinal disease associated with Cystic Fibrosis (CF) is variable in the patient population and this variability is partially conferred by the influence of modifier genes. Genome-wide association studies have identified SLC6A14, an electrogenic amino acid transporter, as a genetic modifier of CF-associated meconium ileus. The purpose of the current work was to determine the biological role of Slc6a14, by disrupting its expression in CF mice bearing the major mutation, F508del. We found that disruption of Slc6a14 worsened the intestinal fluid secretion defect, characteristic of these mice. In vitro studies of mouse intestinal organoids revealed that exacerbation of the primary defect was associated with reduced arginine uptake across the apical membrane, with aberrant nitric oxide and cyclic GMP-mediated regulation of the major CF-causing mutant protein. Together, these studies highlight the role of this apical transporter in modifying cellular nitric oxide levels, residual function of the major CF mutant and potentially, its promise as a therapeutic target.