Multiplex Asymmetric PCR by Combining the Amplification Refractory Mutation System with the Homo-Tag-Assisted Nondimer System.

Asymmetric PCR is widely used to produce single-stranded amplicons (ss-amplicons) for various downstream applications. However, conventional asymmetric PCR schemes are susceptible to events that affect primer availability, which can be exacerbated by multiplex amplification. In this study, a new multiplex asymmetric PCR approach that combines the amplification refractory mutation system (ARMS) with the homo-Tag-assisted nondimer system (HANDS) is described. ARMS-HANDS (A-H) PCR utilizes equimolar-tailed forward and reverse primers and an excess Tag primer. The tailed primer pairs initiate exponential symmetric amplification, whereas the Tag primer drives linear asymmetric amplification along fully matched strands but not one-nucleotide mismatched strands, thereby generating excess ss-amplicons. The production of ss-amplicons is validated using agarose gel electrophoresis, sequencing, and melting curve analysis. Primer dimer alleviation is confirmed by both the reduced Loss function value and a 20-fold higher sensitivity in an 11-plex A-H PCR assay than in an 11-plex conventional asymmetric PCR assay. Moreover, A-H PCR demonstrates unbiased amplification by its allele quantitative ability in correct identification of all 31 trisomy 21 samples among 342 clinical samples. A-H PCR is a new generation of multiplex asymmetric amplification approach with various applications, especially when sensitive and quantitative detection is required.

Amygdala dynorphin/κ opioid receptor system modulates depressive-like behavior in mice following chronic social defeat stress.

Major depression disorder is a severe and recurrent neuropsychological disorder characterized by lowered mood and social activity and cognitive impairment. Owing to unclear molecular mechanisms of depression, limited interventions are available in clinic. In this study we investigated the role of dynorphin/κ opioid receptor system in the development of depression. Mice were subjected to chronic social defeat stress for 14 days. Chronic social defeat stress induced significant social avoidance in mice characterized by decreased time duration in the interaction zone and increased time duration in the corner zone. Pre-administration of a κ opioid receptor antagonist norBNI (10 mg/kg, i.p.) could prevent the development of social avoidance induced by chronic social defeat stress. Social avoidance was not observed in κ opioid receptor knockout mice subjected to chronic social defeat stress. We further revealed that social defeat stress activated c-fos and ERK signaling in the amygdala without affecting the NAc, hippocampus and hypothalamus, and ERK activation was blocked by systemic injection of norBNI. Finally, the expression of dynorphin A, the endogenous ligand of κ opioid receptor, was significantly increased in the amygdala following social defeat stress; microinjection of norBNI into the amygdala prevented the development of depressive-like behaviors caused by social defeat stress. The present study demonstrates that upregulated dynorphin/κ opioid receptor system in the amygdala leads to the emergence of depression following chronic social defeat stress, and sheds light on κ opioid receptor antagonists as potential therapeutic agents for the prevention and treatment of depression following chronic stress.

Effects of circadian iron administration on iron bioavailability and biological rhythm in pigs.

BACKGROUND: Iron supplements are limited by their poor absorption and low efficacy. A circadian feeding schedule would affect the circadian rhythm and improve nutrient metabolism. In this study, 18 iron-deficient piglets were randomly assigned to three groups: a control group receiving a constant diet with mid-iron (MI), a 'HL' group receiving a high-iron (HI) diet at 8:00 h and a low-iron (LI) diet at 18:00, and an 'LH' group receiving a LI diet at 8:00 and a HI diet at 18:00. The effects of circadian iron administration on iron absorption, iron status, and biological rhythm in iron-deficient piglets were investigated. RESULTS: Serum iron and hemoglobin improved significantly (P < 0.05) but did not significantly differ in the circadian iron-feeding groups (P > 0.05). Iron concentration in the liver and spleen was significantly higher in the LH group than in the HL group (P < 0.05), and mRNA expression of divalent metal transport 1 (DMT1), cytochrome B (CYBRD1) and ferroportin (FPN) genes in the duodenum was significantly elevated in the LH group (P < 0.05). The clock-related genes showed differential expression in the duodenum, with greater mRNA expression for period (Per2) and cryptochrome (Cry1 and Cry2) in the LH group (P < 0.05). CONCLUSION: Circadian iron administration affected iron absorption and iron storage in pigs. Iron supplementation in the evening might be a more effective pattern for iron utilization. The rhythmic system in the intestine, driven by the time, played an important role in this process. © 2020 Society of Chemical Industry.

Elevated Blood and Urinary ICAM-1 is a Biomarker for Systemic Lupus Erythematosus: A Systematic Review and Meta-Analysis.

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease with complex etiology. Intercellular cell adhesion molecule-1 (ICAM-1) is critical for leukocyte adhesion to endothelium and migration out of blood vessels and thus participates in many autoimmune diseases. Previous studies of blood and urinary ICAM-1 in SLE have yielded inconsistent results.Methods: The following databases were searched for studies that compared blood and/or urinary ICAM-1 in SLE patients vs. healthy control subjects, and/or in SLE with active vs. inactive diseases: PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure and Web of Science. Standardized mean difference (SMD) and 95% confidence intervals (CI) were calculated using a random-effects model when there was significant heterogeneity (assesses using the Cochrane Q test and I2 statistics), and using a fixed-effects model otherwise. Publication bias was assessed using funnel plot and egger text.Results: The initial screening yielded a total of 1,215 articles; 22 articles (14 reporting blood ICAM-1, 7 reporting urinary ICAM-1 and 1 reporting both) were included in the meta-analysis. In comparison to healthy controls, SLE patients had elevated urinary ICAM-1 (SMD: 0.711; 95% CI: 0.521, 0.901) as well as blood ICAM-1 (SMD: 0.725; 95% CI: 0.385, 1.065). Blood ICAM-1 did not differ significantly between active and inactive SLE (SMD: 0.396; 95% CI: -0.556, 1.347).Conclusion: Elevated blood and urinary ICAM-1 is a biomarker for SLE, but does not differentiate active and inactive SLE.

Rare Deleterious PARD3 Variants in the aPKC-Binding Region are Implicated in the Pathogenesis of Human Cranial Neural Tube Defects Via Disrupting Apical Tight Junction Formation.

Increasing evidence that mutation of planar cell polarity (PCP) genes contributes to human cranial neural tube defect (NTD) susceptibility prompted us to hypothesize that rare variants of genes in the core apical-basal polarity (ABP) pathway are risk factors for cranial NTDs. In this study, we screened for rare genomic variation of PARD3 in 138 cranial NTD cases and 274 controls. Overall, the rare deleterious variants of PARD3 were significantly associated with increased risk for cranial NTDs (11/138 vs.7/274, P < 0.05, OR = 3.3). These NTD-specific variants were significantly enriched in the aPKC-binding region (6/138 vs. 0/274, P < 0.01). The East Asian cohort in the ExAC database and another Chinese normal cohort further supported this association. Over-expression analysis in HEK293T and MDCK cells confirmed abnormal aPKC binding or interaction for two PARD3 variants (p.P913Q and p.D783G), resulting in defective tight junction formation via disrupted aPKC binding. Functional analysis in human neural progenitor cells and chick embryos revealed that PARD3 knockdown gave rise to abnormal cell polarity and compromised the polarization process of neuroepithelial tissue. Our studies suggest that rare deleterious variants of PARD3 in the aPKC-binding region contribute to human cranial NTDs, possibly by disrupting apical tight junction formation and subsequent polarization process of the neuroepithelium.

Focal adhesion kinase activation is required for TNF-α-induced production of matrix metalloproteinase-2 and proinflammatory cytokines in cultured human periodontal ligament fibroblasts.

Since focal adhesion kinase (FAK) was proposed as a mediator of the inflammatory response, we have investigated the role of this molecule in the release of inflammatory cytokines by cultured human periodontal ligament fibroblasts (HPDLFs), cells that are thought to be important in the patient's response to periodontal infection. Human periodontal ligament fibroblasts were stimulated by tumor necrosis factor alpha (TNF-α) and its effects on interleukin (IL)-6 and IL-8 release were measured by ELISA. Expression of matrix metalloproteinase 2 (MMP-2) protein was analysed by western blotting. The levels of IL6, IL8, and MMP2 mRNA were evaluated by real-time PCR. Tumor necrosis factor alpha dose-dependently induced the phosphorylation of FAK, whereas small interfering FAK (siFAK) inhibited TNF-α-induced FAK phosphorylation. Tumor necrosis factor alpha also stimulated the production of IL-6, IL-8, and MMP-2 in a dose-dependent manner. Knockdown of FAK significantly suppressed TNF-α-induced expression of IL6 and IL8 mRNA and release of IL-6 and IL-8 protein in HPDLFs. Similarly, MMP-2 down-regulation was significantly prevented by siFAK. Our results strongly suggest that knockdown of FAK can decrease the production of TNF-α-induced IL-6, IL-8, and MMP-2 in HPDLFs. These effects may help in understanding the mechanisms that control expression of inflammatory cytokines in the pathogenesis of periodontitis.

Leucine regulates lipid metabolism in adipose tissue through adipokine-mTOR-SIRT1 signaling pathway and bile acid-microbe axis in a finishing pig model.

This study was conducted to explore the regulatory mechanism of leucine (Leu) on lipid metabolism of finishing pigs. Twenty-four Duroc × Landrace × Large cross pigs with an average body weight of 68.33 ± 0.97 kg were randomly allocated into 3 treatment groups with 8 replicates per group (1 pig per replicate). The dietary treatments were as follows: control group (CON), 0.25% Leu group and 0.50% Leu group. The experimental period was 42 d. The results showed as follows. (1) Compared with the CON, 0.25% and 0.50% Leu increased (P < 0.01) the average daily gain (ADG), while the average backfat thickness (ABT) and the ratio of feed intake to body weight gain (F:G ratio) were decreased (P < 0.05). (2) In the 0.25% Leu group, the relative mRNA expression levels of sterol regulatory element binding protein-1c (SREBP1c), recombinant fatty acid transport protein 1 (FATP1), chemerin and peroxisome proliferator-activated receptor γ (PPARγ) were decreased but the level of fatty acid binding protein 4 (FABP4) and fatty acid translocase (FAT/CD36) were increased in backfat tissue. In the 0.25% Leu group, the protein levels of p-Rictor, p-Raptor, p-eIF4E-binding protein 1 (p-4EBP1), p-silent mating type information regulator 2 homolog 1 (p-SIRT1) and acetylation ribosome s6 protein kinase 1 (Ac-S6K1) were increased (P < 0.05). (3) Compared to the CON, the diversity of gut microbiota in the 0.25% Leu group was increased. Principal component analysis showed that the relative abundance of Bacteroidetes, Lactobacillus and Desulfovibrio was higher in the 0.25% Leu group than the CON, but the relative abundance of Firmicutes, Treponema and Shigella was lower than in the CON (P < 0.05). (4) Four different metabolites were screened out from the serum of finishing pigs including allolithocholic acid (alloLCA), isolithocholic acid (isoLCA), ursodeoxycholic acid (UDCA) and hyodeoxycholic acid (HDCA), which correlate to various degrees with the above microorganisms. In conclusion, Leu could promote adipose tissue lipolysis of finishing pigs through the mTOR-SIRT1 signaling pathway, and S6K1 is acetylated at the same time, and the interaction between gut microbiota and bile acid metabolism is also involved.

[The tendency of prevalence of hypertension in two countries in Gansu province from 1990 to 2012].

OBJECTIVE: To study the variation tendency of hypertension in two rural areas in Gansu, and provide epidemiological evidence to evaluate the hypertension of rural residents. METHODS: Using equidistant random sampling method and cross-sectional sentinel monitoring, two remote natural villages, Yangzhuang and Xiangming, at Yellow river and Yangtze river valley were selected as hypertension monitoring site. From 1990 to 2012, clinical examination to the resident above 18 years old was carried out continuously for 23 years, 11 164 cases were included. RESULTS: Hypertension prevalence of tested cases increased with years, Yangzhuang monitoring site increased from 6.9% (16/232) in 1990 to 36.7% (216/597) in 2012 with an increase of 29.8%, and Xiangming monitoring site increased from 3.4% (16/474) in 1995 to 20.6% (120/582) in 2011 with an increase of 17.2%. Total prevalence of Yangzhuang (24.1%, 1505/6240) was significantly higher than Xiangming (11.4%, 578/4924) (χ(2) = 277.9, P < 0.01). Total hypertension prevalence of 18 - 35 years old group was 9.9% (292/2944) in Yangzhuang and 4.2% (63/1495) in Xiangming, Yangzhuang was higher than Xiangming (χ(2) = 43.7, P < 0.01). Total hypertension prevalence of above 35 years old group was 36.8% (1213/3296) in Yangzhuang and 14.1% (515/3429) in Xiangming, Yangzhuang was higher than Xiangming (χ(2) = 417.7, P < 0.01). The growth rates of hypertension prevalence in 18 - 35 years old group of both areas (Yangzhuang: 823.5%, Xiangming: 614.3%) were higher than 35 years old group (Yangzhuang:310.5%, Xiangming: 368.0%), but the hypertension prevalence of above 35 years old group was higher than 18 - 35 years old group. Hypertension prevalence of male was 25.4% (761/2992) in Yangzhuang and 11.7% (238/2047) in Xiangming, Yangzhuang was higher than Xiangming (χ(2) = 145.8, P < 0.01), hypertension prevalence of female was 22.7% (738/3248) in Yangzhuang and 11.2% (340/2877)in Xiangming, Yangzhuang was higher than Xiangming (χ(2) = 125.1, P < 0.01). While the difference between male and female had no statistical significance in both areas. CONCLUSION: Hypertension of the two monitoring points was in high epidemic trend, but with different epidemic trend. From different region and environment research to discuss the cause of hypertension can provide scientific evidence for prevention and control.

Cytokines and exosomal miRNAs in skeletal muscle-adipose crosstalk.

Skeletal muscle and adipose tissues (ATs) are secretory organs that release secretory factors including cytokines and exosomes. These factors mediate muscle-adipose crosstalk to regulate systemic metabolism via paracrine and endocrine pathways. Myokines and adipokines are cytokines secreted by skeletal muscle and ATs, respectively. Exosomes loaded with nucleic acids, proteins, lipid droplets, and organelles can fuse with the cytoplasm of target cells to perform regulatory functions. A major regulatory component of exosomes is miRNA. In addition, numerous novel myokines and adipokines have been identified through technological innovations. These discoveries have identified new biomarkers and sparked new insights into the molecular regulation of skeletal muscle growth and adipose deposition. The knowledge may contribute to potential diagnostic and therapeutic targets in metabolic disease.

Dietary leucine and fish oil cooperatively regulate skeletal myofiber type transformation via the CaMKII signaling pathway of pigs.

The study investigated the effects of dietary leucine (Leu) and fish oil (FO) on skeletal myofiber type transformations in pigs and their potential interactions. The results showed that Leu increased the content of Leu, upregulated myocyte enhancer factor-2C (MEF2C) and activated the CaMKII-AMPK/SIRT1-PGC-1α pathway in the longissimus dorsi (LD) muscle. FO increased adiponectin and fatty acid beta-oxidation of LD muscle. Activation of the adiponectin signaling pathway by FO further enhanced the CaMKII pathway and upregulated the expression of MEF2C. Moreover, we found that Leu increased cyclic AMP and caffeine, and FO increased linoleic acid and glutamine in muscle metabolites, which may be the cause of myofiber conversion. In conclusion, this study demonstrated that dietary Leu and FO co-regulated the transformation from glycolytic to oxidative skeletal myofiber type. It is hypothesized that there is an interaction between amino acids and polyunsaturated fatty acids, possibly via the CaMKII signaling pathway to upregulate MEF2 and mitochondrial biogenesis.

Modulating Exchange Bias, Anisotropic Magnetoresistance, and Planar Hall Resistance of Flexible Co/MnN Epitaxial Bilayers on Mica by Bending Strain.

The integration of ferromagnetic/antiferromagnetic bilayers with exchange bias effect on flexible substrates is crucial for flexible spintronics. Here, the epitaxial Co/MnN bilayers are deposited on mica by facing-target sputtering. A large in-plane exchange bias field (HEB) of 1800 Oe with a coercive field (HC) of 2750 Oe appears in the Co (3.8 nm)/MnN (15.0 nm) bilayer at 5 K after field cooling from 300 to 5 K. Effective interfacial exchange energy Jeff of the Co/MnN bilayer is 0.83 erg/cm2. The strain-induced maximum increase of HEB and HC reaches 18% and 21%, respectively, in the Co(3.8 nm)/MnN(15.0 nm) bilayer. Strain-modulated HEB is attributed to the change of interfacial exchange coupling between Co and MnN layers. HEB is inversely proportional to Co thickness but independent of MnN thickness. The change of HEB is less than 5% after 100 bending cycles, indicating mechanical durability. The out-of-plane exchange bias also appears since Co spins are not fully reversed due to the strong pinning effect. Anisotropic magnetoresistance (AMR) and planar Hall resistance (Rxy) show obvious hysteresis due to HEB. Exchange bias-induced phase difference of AMR and Rxy almost remains unchanged at different bending strains. The results provide the basis for understanding the bending strain tailored exchange bias.

Insights into the effects of natural pyrite-activated sodium percarbonate on tetracycline removal from groundwater: Mechanism, pathways, and column studies.

In-situ chemical oxidation based on sodium percarbonate (SPC) has received much attention for remediation of groundwater contaminated with organic pollutants due to the high efficiency, stable reaction, and sustainability of SPC. Currently, metal ions and their composite materials, are mainly employed for the activation of SPC. However, due to its narrow pH range, slow Fe3+/Fe2+ circulation, and generation of refractory sludge, its application in groundwater is limited. In this study, SPC was activated with natural pyrite (FeS2) to remove tetracycline, which was selected as the target pollutant. FeS2 exhibited excellent catalytic activity and stability towards the degradation of tetracycline. The tetracycline degradation efficiency of SPC/FeS2 system reached 70 % within 10 min, and nearly half of the tetracycline was degraded in the first 5 min of the reaction. The optimum SPC dosage for the tetracycline removal was 8 mM, with FeS2 dosage of 0.5 g/L. The tetracycline removal efficiency remained above 60 % after 4 cycles, indicating its good recycling efficiency of the system. SPC/FeS2 system was not significantly affected by the initial pH or the presence of Cl-, SO42-, NO3- while, HCO3-, Ca2+, Mg2+, and humid acid suppressed the reaction. The electron paramagnetic resonance spectroscopy and quenching experiments demonstrated that OH and O2- played a dominant role in tetracycline removal by the system. S22-, as an electron donor, was able to participate in the Fe3+/Fe2+ cycle. In addition, the 13 transformation products were determined by liquid chromatography-mass spectrometry predicted that the degradation pathway of tetracycline consisted of hydroxylation, demethylation, and decarbonylation reactions. Finally, the dynamic simulation experiments of SPC/FeS2 sand column showed that FeS2 effectively activated SPC and significantly reduced the toxicity in groundwater after the packed column treatment. This study reveals that FeS2 can efficiently activate SPC and has good prospects for tetracycline-contaminated groundwater remediation applications.

The novel HLA-A*02:07:23 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-A*02:07:23 differs from HLA-A*02:07:01:01 by one nucleotide in exon 2.

Dietary iron regulates intestinal goblet cell function and alleviates Salmonella typhimurium invasion in mice.

Iron is an important micronutrient that plays a vital role in host defenses and bacterial pathogenicity. As iron treatments increase the risk of infection by stimulating the growth and virulence of bacterial pathogens, their roles in anti-infection immunity have frequently been underestimated. To estimate whether adequate dietary iron intake would help defend against pathogenic bacterial infection, mice were fed iron-deficient (2 mg kg-1 feed), iron-sufficient (35 mg kg-1 feed), or iron-enriched diet (350 mg kg-1 feed) for 12 weeks, followed by oral infection with Salmonella typhimurium. Our results revealed that dietary iron intake improved mucus layer function and decelerated the invasion of the pathogenic bacteria, Salmonella typhimurium. Positive correlations between serum iron and the number of goblet cells and mucin2 were found in response to total iron intake in mice. Unabsorbed iron in the intestinal tract affected the gut microbiota composition, and the abundance of Bacteroidales, family Muribaculaceae, was positively correlated with their mucin2 expression. However, the results from antibiotic-treated mice showed that the dietary iron-regulated mucin layer function was not microbial-dependent. Furthermore, in vitro studies revealed that ferric citrate directly induced mucin2 expression and promoted the proliferation of goblet cells in both ileal and colonic organoids. Thus, dietary iron intake improves serum iron levels, regulates goblet cell regeneration and mucin layer function, and plays a positive role in the prevention of pathogenic bacteria.

The conscious processing of emotion in depression disorder: a meta-analysis of neuroimaging studies.

Background: Depression is generally accompanied by a disturbed conscious processing of emotion, which manifests as a negative bias to facial/voice emotion information and a decreased accuracy in emotion recognition tasks. Several studies have proved that abnormal brain activation was responsible for the deficit function of conscious emotion recognition in depression. However, the altered brain activation related to the conscious processing of emotion in depression was incongruent among studies. Therefore, we conducted an activation likelihood estimation (ALE) analysis to better understand the underlying neurophysiological mechanism of conscious processing of emotion in depression. Method: Electronic databases were searched using the search terms "depression," "emotion recognition," and "neuroimaging" from inceptions to April 10th, 2023. We retrieved trials which explored the neuro-responses of depressive patients to explicit emotion recognition tasks. Two investigators independently performed literature selection, data extraction, and risk of bias assessment. The spatial consistency of brain activation in conscious facial expressions recognition was calculated using ALE. The robustness of the results was examined by Jackknife sensitivity analysis. Results: We retrieved 11,365 articles in total, 28 of which were included. In the overall analysis, we found increased activity in the middle temporal gyrus, superior temporal gyrus, parahippocampal gyrus, and cuneus, and decreased activity in the superior temporal gyrus, inferior parietal lobule, insula, and superior frontal gyrus. In response to positive stimuli, depressive patients showed hyperactivity in the medial frontal gyrus, middle temporal gyrus, and insula (uncorrected p < 0.001). When receiving negative stimuli, a higher activation was found in the precentral gyrus, middle frontal gyrus, precuneus, and superior temporal gyrus (uncorrected p < 0.001). Conclusion: Among depressive patients, a broad spectrum of brain areas was involved in a deficit of conscious emotion processing. The activation of brain regions was different in response to positive or negative stimuli. Due to potential clinical heterogeneity, the findings should be treated with caution. Systematic review registration: https://inplasy.com/inplasy-2022-11-0057/, identifier: 2022110057.

Correlations of gestational hemoglobin level, placental trace elements content, and reproductive performances in pregnant sows.

The iron status of sows has a great influence on reproductive performance. Iron deficiency reduces reproductive performance and newborn piglet survival rate of sow. The hemoglobin is a potential predictor for the iron status of sows and is convenient for rapid detection in pig farms. However, the relationship between iron status, hemoglobin, placental trace elements, and reproductive performance remains unclear. In this study, the hemoglobin and reproductive performance of more than 500 sows with first to sixth parities at different gestation stages (25, 55, 75, 95, and 110 d of gestation) in two large-scale sow farms were collected, and the content of placental Fe, Zn, Mn, and Cu was analyzed. The results show that hemoglobin levels of sows during pregnancy (days 75, 95, and 110) decreased significantly (P < 0.001). As the parity increases, the hemoglobin levels of sows at days 25 and 55 of gestation and placental mineral element contents including Fe, Zn, Mn, and Cu at delivery decreased (P < 0.05), while the litter size, birth alive, and litter weights increased gradually (P < 0.001). Furthermore, hemoglobin during pregnancy had a negative linear correlation with litter weight and average weight (P < 0.05), and higher hemoglobin at day 25 of gestation may reduce the number of stillbirths (P = 0.05), but higher hemoglobin at day 110 of gestation may tend to be a benefit for the birth (P = 0.01). And there was a significant positive linear correlation between hemoglobin at day 110 of gestation and placental Fe and Mn levels (P = 0.002, P = 0.013). There was also a significant positive linear correlation among Fe, Zn, Mn, and Cu in the placenta (P < 0.001). The levels of Fe, Zn, and Mn in the placental at delivery were positively related to the average weight of the fetus (P = 0.048, P = 0.027, P = 0.047), and placental Cu was linearly correlated with litter size (P = 0.029). Our research revealed that the requirements for iron during gestation were varied in different gestation periods and parities. The feeds should be adjusted according to the gestation periods, parities, or iron status to meet the iron requirements of sows and fetal pigs.

Iron deficiency and iron excess may cause adverse outcomes during pregnancy. In sows' feed, iron is added as ferrous sulfate, ferrous glycine, or other forms to improve their reproductive performance and prevent iron-deficiency anemia in their offspring. However, it is always ineffective and iron-deficiency anemia often occurs in piglets. To explore the iron requirements in pregnant sows, we conducted a large-scale farm study to track the hemoglobin levels, placental trace element content, and reproductive performances of hundreds of sows. The correlation between the hemoglobin levels, placental trace element content, and reproductive performance indicators of sows during pregnancy at different parities was analyzed. We found that pregnancy hemoglobin level of sows decreases during the gestation and varies at different parities. The hemoglobin level of sows during pregnancy was linearly negatively correlated with reproductive performance. The content of iron, zinc, manganese, and copper in the placenta was linearly positively correlated. Our results revealed that iron deficiency or excess in sows' feed may not be conducive to the improvement of reproductive performance, and the optimal iron supplementation dose during pregnancy may depend on the iron status and number of fetuses of sow.

Maternal iron supplementation during pregnancy affects placental function and iron status in offspring.

BACKGROUND: Iron deficiency and overload during pregnancy damage to maternal and fetal health. Placenta as an organ for the transport of nutrients between mother and fetus protects fetus from the harmful effects of iron deficiency and iron overload through regulation of placental iron homeostasis. METHODS: To determine the effect of dietary iron supplementation during pregnancy on reproduction and the mechanism of placental iron regulation, we designed dietary high iron (HI: 344 mg/kg), medium iron (MI: 40 mg/kg), low iron (LI: 2 mg/kg) groups of pregnant female mice fed ferrous citrate 2 weeks before mating to 18.5 days of gestation. RESULTS: We find dietary iron supplementation during pregnancy effect maternal liver iron, placental iron, hemoglobin and fetal iron. Dietary iron significantly improves reproductive performance as litter weight and fetal weight. Correlation analysis suggest placental iron increased with liver iron, higher and lower liver iron is not conducive to the accumulation of fetal iron, placental iron deficiency and excess reduce litter weight. Placental transcriptome analysis revealed DEGs with the same trend in HI and LI groups compared with MI group, dietary iron may change biology process of ion transport and gland development in placenta. Granzyme may affect the placental trophoblast structure prior to delivery with iron overload uniquely. CONCLUSION: This research highlights the importance of moderate iron supplements in pregnancy due to damage of reproduction by affecting placental function under different dose of maternal iron supplementation.

Cerebellum neuropathology and motor skill deficits in fragile X syndrome.

Fragile X syndrome (FXS) is a leading form of inherited intellectual disability and single-gene cause of autism spectrum disorder (ASD) and is characterized by core deficits in cognitive flexibility, sensory sensitivity, emotion, and social interactions. Motor deficits are a shared feature of FXS and autism. The cerebellum has emerged as one of the target brain areas affected by neurodevelopmental diseases. Alterations in the cerebellar structure, circuits, and function may be the key drivers of impaired fine and gross motor skills in FXS and fragile X-associated tremor/ataxia syndrome (FXTAS). In this review, we briefly examined recent findings in FXS and present a discussion on the literature supporting motor skill deficits in FXS. Subsequently, we focused on neuropathological alterations in the cerebellum in FXS and FXTAS. We highlight studies that have directly examined the function of fragile X mental retardation protein and related epigenetic variations in the cerebellum. Overall, we obtained considerable supporting evidence for the hypothesis that cerebellar dysfunction is evident in FXS and FXTAS; however, compared with studies on other ASD models, studies on motor skills related to fragile X disorders are particularly rare and inconclusive. Hence, future research should address FXS-related motor and behavioral trajectories and examine the underlying mechanisms at both the cell and circuit levels.

The effects of acupuncture therapy in migraine: An activation likelihood estimation meta-analysis.

Background: Previous functional magnetic resonance imaging studies indicated that acupuncture could activate the brain regions in patients with migraine. However, these studies showed inconsistent results. This activation likelihood estimation (ALE) meta-analysis aimed to investigate the consistent activated change of brain regions between pre- and post-acupuncture treatment in migraineurs. Methods: We conducted a literature search in PubMed, Embase, Web of Science, the Cochrane Library, the China National Knowledge Infrastructure, the Chinese Science and Technology Periodical Database, the Wanfang Database, and the Chinese Biomedical Literature Database from their inception to 18 August, 2022, to obtain articles assessing the functional magnetic resonance imaging changes of acupuncture for migraine. Two investigators independently performed literature selection, data extraction, and quality assessment. The methodological quality was assessed with a modified version of the checklist. The reporting quality of interventions among included studies was evaluated by the Revised Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA). Our meta-analysis was conducted according to the GingerALE software. The Jackknife sensitivity analysis was used to assess the robustness of the results. Results: 14 articles were finally included according to the eligible criteria. Regarding the immediate effect of acupuncture on migraine, the ALE meta-analysis demonstrated that the deactivation regions were mainly located in the superior frontal gyrus, and middle frontal gyrus (uncorrected P < 0.001). The ALE meta-analysis of the cumulative effect showed that the activation regions were the thalamus, superior frontal gyrus, posterior lobe of the cerebellum, insula, middle frontal gyrus, precentral gyrus, anterior cingulate, and the deactivation brain regions were located in the transverse temporal gyrus, postcentral gyrus, superior temporal gyrus, anterior cingulate, parahippocampal gyrus, inferior parietal lobule, and inferior occipital gyrus (uncorrected P < 0.001). Conclusion: Acupuncture could activate multiple brain areas related with the regulation of pain conduction, processing, emotion, cognition, and other brain regions in patients with migraine. In the future, the combination of multiple imaging technologies could be a new approach to deeply investigate the central mechanism of acupuncture for migraine.