Current research and evidence gaps on placental development in iron deficiency anemia.

Studying the effects of maternal iron deficiency anemia (IDA) is complex owing to its diverse causes, each independently impacting the placenta and fetus. Simple treatment with iron supplements does not always resolve the anemia. Therefore, delving into how IDA alters placental development at a molecular level is crucial to further optimize treatment. This review addresses the effects of IDA on placental structures and functions, including changes in oxygen levels, blood vessels, and the immune system. Profound understanding of physiological characteristics and regulatory mechanisms of placental development is key to explain the mechanisms of abnormal placental development in pregnancy-associated disorders. In turn, future strategies for the prevention and treatment of pregnancy complications involving the placenta can be devised. These studies are significant for improving human reproductive health, enhancing sociodemographic qualities, and even lifelong wellbeing, a focal point in future placental research.

Design of a Novel Lysine Isopeptide 1018KI11 with Potent Antimicrobial Activity as a Safe and Stable Food Preservative Candidate.

Antimicrobial peptides are potent food additive candidates, but most of them are sensitive to proteases, which limits their application. Therefore, we substituted arginine for lysine and introduced a lysine isopeptide bond to peptide IDR-1018 in order to improve its enzymatic stability. Subsequently, the protease stability and antimicrobial/antibiofilm activity of the novel peptides (1018K2-1018KI11) were investigated. The data revealed that the antienzymatic potential of 1018KI11 to bromelain and papain increased by 2-8 folds and 16 folds, respectively. The minimum inhibitory concentration (MIC) of 1018KI11 against methicillin-resistant Staphylococcus aureus (MRSA) ATCC43300 and Escherichia coli (E. coli) ATCC25922 was reduced 2-fold compared to 1018K11. Mechanism exploration suggested that 1018KI11 was more effective than 1018K11 in disrupting the cell barrier and damaging genomic DNA. Additionally, 1018KI11 at certain concentration conditions (2-64 µg/mL) reduced biofilm development of MRSA ATCC43300 by 4.9-85.9%. These data indicated that novel peptide 1018KI11 is a potential food preservative candidate.

A novel phthalein component ameliorates neuroinflammation and cognitive dysfunction by suppressing the CXCL12/CXCR4 axis in rats with vascular dementia.

ETHNOPHARMACOLOGICAL RELEVANCE: Chuanxiong, a plant of the Umbelliferae family, is a genuine medicinal herb from Sichuan Province. Phthalides are one of its main active components and exhibit good protective effect against cerebrovascular diseases. However, the mechanism by which phthalides exert neuroprotective effects is still largely unclear. AIM OF THE STUDY: In this study, we extracted a phthalein component (named as QBT) from Ligusticum Chuanxiong, and investigated its neuroprotective effects against vascular dementia (VaD) rats and the underlying mechanism, focusing on the chemokine 12 (CXCL12)/chemokine (C-X-C motif) receptor 4 (CXCR4) axis. METHODS: A rat model of VaD was established, and treated with QBT. Cognitive dysfunction in VaD rats was assessed using the Y-maze, new object recognition, and Morris water maze tests. Neuronal damage and inflammatory response in VaD rats were examined through Nissl staining, immunofluorescence, enzyme-linked immunospecific assay, and western blotting analysis. Furthermore, the effects of QBT on CXCL12/CXCR4 axis and its downstream signaling pathways, Janus kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) and phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT)/nuclear factor-κB (NF-κB), were investigated in VaD rats and BV2 microglial cells exposed to oxygen glucose deprivation. RESULTS: QBT significantly alleviated cognitive dysfunction and neuronal damage in VaD rats, along with inhibition of VaD-induced over-activation of microglia and astrocytes and inflammatory response. Moreover, QBT exhibited anti-inflammatory effects by inhibiting the CXCL12/CXCR4 axis and its downstream JAK2/STAT3 and PI3K/AKT/NF-κB pathways, thereby attenuating the neuroinflammatory response both in vivo and in vitro. CONCLUSION: QBT effectively mitigated neuronal damage and cognitive dysfunction in VaD rats, exerting neuroprotective effects by suppressing neuroinflammatory response through inhibition of the CXCL12/CXCR4 axis.

A multi-omic assessment of the mechanisms of intestinal microbes used to treat diarrhea in early-weaned lambs.

Transplant of donor microbiota can significantly alter the structure of the host's intestinal microbiota and alleviate early weaning stress. Screening for alternative-resistant products by transplanting fecal bacteria from healthy lambs is a current research trend in the livestock industry. In the present study, fecal microbiota transplantation was performed in lambs with diarrhea during early weaning. The transplanted fecal microbiota greatly reduced the diarrhea and serum inflammatory factor levels caused by early weaning. Transcriptome sequencing revealed that fecal microbiota transplantation alleviated colonic inflammation and increased the expression of colonic ion transport proteins. In addition, the levels of Streptococcus, Enterococcus, and Escherichia Shigella decreased in the jejunum, cecum, and colon of the lambs; meanwhile, the levels of Bifidobacterium and multiple secondary bile acids, such as ursodeoxycholic acid, increased in the colon. Furthermore, the abundance of Bifidobacterium was significantly negatively correlated with the diarrhea index. The fecal microbiota transplantation reshaped the intestinal microbiota of early-weaned lambs, protected the intestinal physiology and immune barrier, and reduced weaning stress. In addition to making available bacteriological products for controlling intestinal inflammation in young lambs, this study offers a theoretical framework and technical system for the mechanisms by which microbiota transplantation regulates intestinal health in young lambs.IMPORTANCEBefore weaning, the digestive system of lambs is not well developed; hence, its resistance to infectious diseases is weak. Under intensive feeding systems, lambs can easily be stressed and the risk of bacterial infection is high, which causes diarrhea, which in turn may cause mortality and significant economic losses to the livestock industry. With the elimination of antibiotics in animal feed, the incidence of mortality due to intestinal illnesses in lambs has gradually increased. There are several types of probiotics routinely used in young animals, but the effects and processes of their usage have only been assessed in monogastric animals. The lack of data on ruminants, particularly sheep, has severely hampered the process of efficient and healthy sheep breeding. Therefore, there is an urgent need to identify effective and safe functional supplements for lambs.

Programmable Aptasensor for Regulating CRISPR/Cas12a Activity.

CRISPR-mediated aptasensors have gained prevalence for detecting non-nucleic acid targets. However, there is an urgent need to develop an easily customizable design to improve the signal-to-noise ratio, enhance universality, and expand the detection range. In this article, we report a CRISPR-mediated programmable aptasensor (CPAS) platform. The platform includes single-stranded DNA comprising the aptamer sequence, locker DNA, and a crRNA recognition region, forming a hairpin structure through complementary hybridization. With T4 DNA polymerase, the crRNA recognition region was transformed into a complete double-stranded DNA through stem-loop extension, thereby activating the trans-cleavage activity of Cas 12a and generating fluorescence signals. The specific binding between the target molecule and aptamer disrupted the formation of the hairpin structure, altering the fluorescence signals. Notably, the CPAS platform allows for easy customization by simply changing the aptamer sequence and locker DNA, without entailing adjustments to the crRNA. The optimal number of bases in the locker DNA was determined to be seven nucleotides for the SARS-CoV-2 spike (S) protein and four nucleotides for ATP. The CPAS platform exhibited high sensitivity for S protein and ATP detection. Integration with a lateral flow assay enabled sensitive detection within 1 h, revealing its excellent potential for portable analysis.

Metabolic Engineering of Pichia pastoris for High-Level Production of Lycopene.

Lycopene is widely used in cosmetics, food, and nutritional supplements. Microbial production of lycopene has been intensively studied. However, few metabolic engineering studies on Pichia pastoris have been aimed at achieving high-yield lycopene production. In this study, the CRISPR/Cpf1-based gene repression system was developed and the gene editing system was optimized, which were applied to improve lycopene production successfully. In addition, the sterol regulatory element-binding protein SREBP (Sre) was used for the regulation of lipid metabolic pathways to promote lycopene overproduction in P. pastoris for the first time. The final engineered strain produced lycopene at 7.24 g/L and 75.48 mg/g DCW in fed-batch fermentation, representing the highest lycopene yield in P. pastoris reported to date. These findings provide effective strategies for extended metabolic engineering assisted by the CRISPR/Cpf1 system and new insights into metabolic engineering through transcriptional regulation of related metabolic pathways to enhance carotenoid production in P. pastoris.

Compound enzyme preparation supplementation improves the production performance of goats by regulating rumen microbiota.

Enzyme preparation is one of the widely used additives in ruminant production. However, a suitable method of adding compound enzyme preparation (CEP) to the feeds is still lacking. This study investigated the effect of adding CEP on the diet of goats. Twenty 4-month-old Boer goats were randomly assigned to four groups. The dietary treatments contained different CEPs (Saccharomyces cerevisiae cells, cellulase, xylanase, ß-glucanase amylase, and protease) at the concentrations of 0, 0.25, 0.50, and 0.75 g/kg of feed provided for a period of 56 days. Adding CEP in goat feed significantly increased average daily gain (ADG) during the entire test period. The oxidative indices, hormones, and immune cells did not differ significantly among the different groups. CEP significantly increased the content of total volatile fatty acids measured at the end of the experiment on day 56 of the final normal feeding phase. 16S rDNA sequencing revealed that CEP increased the abundance of Ruminococcaceae in the rumen and g__norank_f__Eubacterium_coprostanoligenes_group, Oscillibacter g__unclassified_f__Ruminococcaceae, and g__unclassified_o__Oscillospirales in fecal matter collected on day 56 of the final normal feeding phase. However, CEP decreased the abundance of unclassified_f__Lachnospiraceae, norank_f__UCG-010, Butyrivibrio, and Saccharofermentans in the rumen. The abundance of Ruminococcaceae in the rumen and propionic acid was positively correlated with ADG. Function prediction showed that carbon fixation, carbohydrate digestion and absorption pathways were significantly enriched in rumen microbiota in the treatment group. The findings indicated that supplementation with 0.5 g CEP/kg of feed for 56 days significantly improves the production performance of goats without adverse health effects. KEY POINTS: • Feeding with compound enzyme preparation for 56 days significantly improved the productive performance but did not affect the antioxidative capacity and immunity of goats. • Supplementing compound enzyme preparation in diet could increase the relative abundance of Ruminococcus to increase the levels of short-chain fatty acids produced. • The most appropriate supplemental amount of compound enzyme preparation per kilogram of the diet was 0.5 g.

Quantification of Cardiomyocyte Contraction In Vitro and Drug Screening by MyocytoBeats.

Cardiomyocyte contractility is the crucial feature of heart function. Quantifying cardiomyocyte contraction in vitro is essential for disease phenotype characterization, mechanism illumination, and drug screening. Although many experimental methods have been employed to determine contraction dynamics in vitro, a time-saving and easy-to-use software is still needed to be developed. We presented a reliable tool, named MyocytoBeats, to measure cardiomyocyte contraction by processing recorded videos. Analysis results by MyocytoBeats of various experimental models have shown a significant linear relationship with another validated software. We also performed pharmacology screen in the platform, and astragaloside IV was identified to stabilize the frequency and amplitude of cardiomyocyte in the arrhythmia model. MyocytoBeats is a high-performance tool for generating cardiomyocyte contraction data of vitro study and shows a great potential in cardiac pharmacology study.

Review on treatment and utilization of barium slag in China.

Barium slag (BS) is generated as a by-product waste during the production of barium salts from barite. A large amount of BS is discharged annually threating the ecological environment and restricting the development of the barium salts industry. In China, BS is classified as hazardous waste due to its corrosivity, and more importantly because of its extraction toxicity of barium. Soluble barium is toxic and can result in barium poisoning for environment and human beings. The current review presents a detailed summary on general characteristics, discharge and disposal status, harmless treatment pathways and comprehensive utilization of BS in China. BaO, SiO2, CaO, and SO3 occur as main chemical compositions in BS, especially BaO accounting approximately for 35-40%. The mineral compositions include unreacted barite, quartz, clay minerals, newly-formed phases from the side reactions such as BaCO3, BaSiO3 and BaSO3, and residual carbon. A special attention is given to the assessment of the harmless treatment methods for BS from hazardous waste to general waste, which will decrease its management costs. Precipitation and solidification of soluble barium is the common pathway for harmless treatment of BS, and the using of other industrial waste can realize cost-saving. Methods for comprehensive utilization of BS include recovery of barium and carbon, application in building materials, and using as adsorbents for wastewater treatment. In particular, we analyzed and discussed the advantages and disadvantages of these existing process routes, intending to promote potentials for comprehensive utilization of BS in the future.

Integrated lipidomics and network pharmacology analysis to reveal the mechanisms of berberine in the treatment of hyperlipidemia.

BACKGROUND: Berberine (BBR), an isoquinoline alkaloid isolated from Rhizoma Coptis, is widely used in the treatment of hyperlipidemia (HLP) in China. At present, the efficacy of BBR against HLP is relatively clear, but there are few researches on its mechanism. The purpose of this study was to evaluate the potentially beneficial role of BBR in HLP hamster models, as well as investigate its possible mechanisms and potential lipid biomarkers in combination with network pharmacology. METHODS: HLP hamster model was induced by high-fat diet. Hematoxylin-eosin (HE) staining was used to determine the degree of hepatic pathological injury. Liquid chromatography-mass spectrometry was used to analyze lipid metabolism profiles of liver samples, and multiple statistical analysis methods were used to screen and identify lipid biomarkers. The possible molecular mechanism was unraveled by network pharmacology. RESULTS: The results showed that 13 metabolites, including CE (16:1), HexCer (D18:1/19:0) and LPC (O-22:0) were biomarkers of BBR regulation. CHPT1, PLA2G4A, LCAT and UGCG were predicted as the lipid-linked targets of BBR against HLP, whilst glycerophospholipid and sphingolipid metabolism were the key pathways of BBR against HLP. CONCLUSIONS: In summary, this study provides new insights into the protective mechanism of BBR against HLP through network pharmacology and lipidomic approaches.

Effects of Fuyou Formula on GnRH Secretion and Related Gene Expression in Treating Precocious Puberty.

The Fuyou (Fy) formula is an in-hospital preparation consisting of traditional Chinese medicine (TCM) that has been used for treating precocious puberty (PP) for more than 20 years. In this study, we aimed to clarify the effect of the Fy formula and its major components on PP. To confirm the effect of the Fy formula on the release of hypothalamic gonadotropin-releasing hormone (GnRH), GT1-7 cells were treated with estrogen to build the model group and subsequently treated with the Fy formula and its major components to explore their effects on the secretion of GnRH. The level of GnRH in GT1-7 cells was determined using enzyme-linked immunosorbent assay. The results illustrated that, compared to the model group, the Fy formula inhibited the release of GnRH. In addition, the expression levels of proteins related to GnRH secretion, including GnRH, gonadotropin-releasing hormone receptor (GnRHR), Kiss-1 metastasis-suppressor (Kiss1), G-protein coupled receptor 54 (GPR54), estrogen receptor α (ERα), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor-1 receptor (IGF-1R), were detected by real-time polymerase chain reaction (RT-qPCR). The results demonstrated that the Fy formula significantly reduced the level of GnRH secretion in the GT1-7 cell lines compared with the model group. Moreover, it significantly downregulated the expression of GnRH, GnRHR, Kiss1, GPR54, ERα, IGF-1, and IGF-1R. In summary, our results indicate that the Fy formula and its major components may inhibit the effects of estrogen, which alleviates PP through transcriptional regulation of target genes.

Cation/Anion Dual-Vacancy Pair Modulated Atomically-Thin Sex -Co3 S4 Nanosheets with Extremely High Water Oxidation Performance in Ultralow-Concentration Alkaline Solutions.

The density functional theory calculation results reveal that the adjacent defect concentration and electronic spin state can effectively activate the CoIII sites in the atomically thin nanosheets, facilitating the thermodynamic transformation of *O to *OOH, thus offering ultrahigh charge transfer properties and efficiently stabilizing the phase. This undoubtedly evidences that, for metal sulfides, the atom-scale cation/anion vacancy pair and surface electronic spin state can play a great role in enhancing the oxygen evolution reaction. Inspired by the theoretical prediction, interconnected selenium (Se) wired ultrathin Co3 S4 (Sex -Co3 S4 ) nanosheets with Co/S (Se) dual-vacancies (Se1.0 -Co3 S4 -VS/Se -VCo ) pairs are constructed by a simple approach. As an efficient sulfur host material, in an ultralow-concentration KOH solution (0.1 m), Se1.0 -Co3 S4 -VS/Se -VCo presents outstanding durability up to 165 h and a low overpotential of 289.5 mV at 10 mA cm-2 , which outperform the commercial Co3 S4 nanosheets (NSs) and RuO2 . Moreover, the turnover frequency of Se1.0 -Co3 S4 -VS/Se -VCo is 0.00965 s-1 at an overpotential of 0.39 V, which is 5.7 times that of Co3 S4 NSs, and 5.8 times that of commercial RuO2 . The finding offers a rational design strategy to create the multi-defect structure in catalysts toward high-efficiency water electrolysis.

Berberine attenuates choline-induced atherosclerosis by inhibiting trimethylamine and trimethylamine-N-oxide production via manipulating the gut microbiome.

Trimethylamine-N-oxide (TMAO), a derivative from the gut microbiota metabolite trimethylamine (TMA), has been identified to be an independent risk factor for promoting atherosclerosis. Evidences suggest that berberine (BBR) could be used to treat obesity, diabetes and atherosclerosis, however, its mechanism is not clear mainly because of its poor oral bioavailability. Here, we show that BBR attenuated TMA/TMAO production in the C57BL/6J and ApoE KO mice fed with choline-supplemented chow diet, and mitigated atherosclerotic lesion areas in ApoE KO mice. Inhibition of TMA/TMAO production by BBR-modulated gut microbiota was proved by a single-dose administration of d9-choline in vivo. Metagenomic analysis of cecal contents demonstrated that BBR altered gut microbiota composition, microbiome functionality, and cutC/cntA gene abundance. Furthermore, BBR was shown to inhibit choline-to-TMA conversion in TMA-producing bacteria in vitro and in gut microbial consortium from fecal samples of choline-fed mice and human volunteers, and the result was confirmed by transplantation of TMA-producing bacteria in mice. These results offer new insights into the mechanisms responsible for the anti-atherosclerosis effects of BBR, which inhibits commensal microbial TMA production via gut microbiota remodeling.

Graphene Oxide-Template Gold Nanosheets as Highly Efficient Near-Infrared Hyperthermia Agents for Cancer Therapy.

INTRODUCTION: Near-infrared (NIR) hyperthermia agents are promising in cancer photothermal therapy due to their deeper penetration ability and less side effects. Spherical gold nanoshell and graphene-based nanomaterials are two major NIR hyperthermia agents that have been reported for photothermal therapy of cancer. Herein, we constructed a two-dimensional graphene oxide-template gold nanosheet (GO@SiO2@AuNS) hybrid that could destruct cancer cells with efficient photothermal effect. METHODS: Graphene oxide was coated with a layer of mesoporous silica, which provided binding sites for gold seeds. Then, seed-growth method was utilized to grow a layer of gold nanosheet to form the GO@SiO2@AuNS hybrid, which possessed great biocompatibility and high photothermal conversion efficiency. RESULTS: With the irradiation of NIR laser (808 nm) with low power density (0.3 W/cm2), GO@SiO2@AuNS hybrid showed a photothermal conversion efficiency of 30%, leading to a temperature increase of 16.4 °C in water. Colorectal cancer cells (KM12C) were killed with the treatment of GO@SiO2@AuNS hybrid under NIR irradiation. CONCLUSION: The GO@SiO2@AuNS hybrid may expand the library of the 2D nanostructures based on gold for cancer photothermal therapy.

Baicalin alleviates collagen­induced arthritis and suppresses TLR2/MYD88/NF­κB p65 signaling in rats and HFLS­RAs.

Baicalin is a flavonoid isolated from the root of Scutellaria baicalensis with anti­inflammatory, antioxidant and antiapoptotic pharmacological properties. however, the therapeutic effect of baicalin on rheumatoid arthritis (RA) is not completely understood. The present study aimed to explore the therapeutic potential and mechanisms underlying baicalin in collagen­induced arthritis (CIA) model rats. CIA was induced in male SD rats. The hind paw thickness and severity of joint injury were monitored to assess the onset of arthritis. At 28 days after the initial immunization, different doses of baicalin were administered once daily via oral gavage for 40 days. The radiologic and pathological alterations were examined using X­ray, and hematoxylin and eosin staining, respectively. ELISA was employed to measure the serum levels of proinflammatory cytokines. Reverse transcription­quantitative PCR and western blotting were conducted to determine the expression of toll­like receptor (TLR)2, myeloid differentiation factor 88 (MYD88) and NF­κB p65. Baicalin treatment noticeably alleviated radiographic and histologic abnormalities in the hind paw joints of CIA model rats in a dose­dependent manner. The serum levels of proinflammatory cytokines were significantly decreased in baicalin­treated CIA model rats compared with vehicle­treated CIA model rats. The mRNA expression levels of TLR2 and MYD88, as well as the protein expression levels of TLR2, MYD88 and NF­κB p65 were significantly decreased by baicalin treatment in the synovial tissue of CIA model rats and human RA fibroblast­like synoviocytes. The results suggested that baicalin may exert a beneficial effect on CIA, which may be mediated by inhibiting the TLR2/MYD88/NF­κB signaling pathway.

Coexpression and secretion of endoglucanase and phytase genes in Lactobacillus reuteri.

A multifunctional transgenic Lactobacillus with probiotic characteristics and an ability to degrade ß-glucan and phytic acid (phytate) was engineered to improve nutrient utilization, increase production performance and decrease digestive diseases in broiler chickens. The Bacillus subtilis WL001 endoglucanase gene (celW) and Aspergillus fumigatus WL002 phytase gene (phyW) mature peptide (phyWM) were cloned into an expression vector with the lactate dehydrogenase promoter of Lactobacillus casei and the secretion signal peptide of the Lactococcus lactis usp45 gene. This construct was then transformed into Lactobacillus reuteri XC1 that had been isolated from the gastrointestinal tract of broilers. Heterologous enzyme production and feed effectiveness of this genetically modified L. reuteri strain were investigated and evaluated. Sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis showed that the molecular mass of phyWM and celW was approximately 48.2 and 55 kDa, respectively, consistent with their predicted molecular weights. Endoglucanase and phytase activities in the extracellular fraction of the transformed L. reuteri culture were 0.68 and 0.42 U/mL, respectively. Transformed L. reuteri improved the feed conversion ratio of broilers from 21 to 42 days of age and over the whole feeding period. However, there was no effect on body weight gain and feed intake of chicks. Transformed L. reuteri supplementation improved levels of ash, calcium and phosphorus in tibiae at day 21 and of phosphorus at day 42. In addition, populations of Escherichia coli, Veillonella spp. and Bacteroides vulgatus were decreased, while populations of Bifidobacterium genus and Lactobacillus spp. were increased in the cecum at day 21.