ABSTRACT
Intracranial electrical stimulation (iES) of auditory cortex can elicit sound experiences with a variety of perceived contents (hallucination or illusion) and locations (contralateral or bilateral side), independent of actual acoustic inputs. However, the neural mechanisms underlying this elicitation heterogeneity remain undiscovered. Here, we collected subjective reports following iES at 3062 intracranial sites in 28 patients (both sexes) and identified 113 auditory cortical sites with iES-elicited sound experiences. We then decomposed the sound-induced intracranial electroencephalogram (iEEG) signals recorded from all 113 sites into time-frequency features. We found that the iES-elicited perceived contents can be predicted by the early high-γ features extracted from sound-induced iEEG. In contrast, the perceived locations elicited by stimulating hallucination sites and illusion sites are determined by the late high-γ and long-lasting α features, respectively. Our study unveils the crucial neural signatures of iES-elicited sound experiences in human and presents a new strategy to hearing restoration for individuals suffering from deafness.
Subject(s)
Auditory Cortex , Illusions , Male , Female , Humans , Auditory Cortex/physiology , Illusions/physiology , Acoustic Stimulation , Brain Mapping , Electric Stimulation , HallucinationsABSTRACT
Neurovascular decoupling plays a significant role in dysfunction following an ischemic stroke. This study aimed to explore the effect of low- and high-frequency repetitive transcranial magnetic stimulation on neurovascular remodeling after ischemic stroke. To achieve this goal, we compared functional hyperemia, cerebral blood flow regulatory factors, and neurochemical transmitters in the peri-infract cortex 21 days after a photothrombotic stroke. Our findings revealed that low- and high-frequency repetitive transcranial magnetic stimulation increased the real-time cerebral blood flow in healthy mice and improved neurobehavioral outcomes after stroke. Furthermore, high-frequency (5-Hz) repetitive transcranial magnetic stimulation revealed stronger functional hyperemia recovery and increased the levels of post-synaptic density 95, neuronal nitric oxide synthase, phosphorylated-endothelial nitric oxide synthase, and vascular endothelial growth factor in the peri-infract cortex compared with low-frequency (1-Hz) repetitive transcranial magnetic stimulation. The magnetic resonance spectroscopy data showed that low- and high-frequency repetitive transcranial magnetic stimulation reduced neuronal injury and maintained excitation/inhibition balance. However, 5-Hz repetitive transcranial magnetic stimulation showed more significant regulation of excitatory and inhibitory neurotransmitters after stroke than 1-Hz repetitive transcranial magnetic stimulation. These results indicated that high-frequency repetitive transcranial magnetic stimulation could more effectively promote neurovascular remodeling after stroke, and specific repetitive transcranial magnetic stimulation frequencies might be used to selectively regulate the neurovascular unit.
Subject(s)
Hyperemia , Ischemic Stroke , Stroke , Animals , Mice , Transcranial Magnetic Stimulation/methods , Vascular Endothelial Growth Factor A , Treatment OutcomeABSTRACT
Germanium-tin (Ge1-xSnx) semiconductors are a front-runner platform for compact mid-infrared devices due to their tunable narrow bandgap and compatibility with silicon processing. However, their large lattice parameter has been a major hurdle, limiting the quality of epitaxial layers grown on silicon or germanium substrates. Herein, we demonstrate that 20 nm Ge nanowires (NWs) act as effective compliant substrates to grow extended defect-free Ge1-xSnx alloys with a composition uniformity over several micrometers along the NW growth axis without significant buildup of the compressive strain. Ge/Ge1-xSnx core/shell NWs with Sn content spanning the 6-18 at. % range are achieved and processed into photoconductors exhibiting a high signal-to-noise ratio at room temperature with a cutoff wavelength in the 2.0-3.9 µm range. The processed NW devices are integrated in an uncooled imaging setup enabling the acquisition of high-quality images under both broadband and laser illuminations at 1550 and 2330 nm without the lock-in amplifier technique.
ABSTRACT
Rapid detection of a threat or its symbol (e.g., fearful face), whether visible or invisible, is critical for human survival. This function is suggested to be enabled by a subcortical pathway to the amygdala independent of the cortex. However, conclusive electrophysiological evidence in humans is scarce. Here, we explored whether the amygdala can rapidly encode invisible fearful faces. We recorded intracranial electroencephalogram (iEEG) responses in the human (both sexes) amygdala to faces with fearful, happy, and neutral emotions rendered invisible by backward masking. We found that a short-latency intracranial event-related potential (iERP) in the amygdala, beginning 88 ms poststimulus onset, was preferentially evoked by invisible fearful faces relative to invisible happy or neutral faces. The rapid iERP exhibited selectivity to the low spatial frequency (LSF) component of the fearful faces. Time-frequency iEEG analyses further identified a rapid amygdala response preferentially for LSF fearful faces at the low gamma frequency band, beginning 45 ms poststimulus onset. In contrast, these rapid responses to invisible fearful faces were absent in cortical regions, including early visual areas, the fusiform gyrus, and the parahippocampal gyrus. These findings provide direct evidence for the existence of a subcortical pathway specific for rapid fear detection in the amygdala and demonstrate that the subcortical pathway can function without conscious awareness and under minimal influence from cortical areas.SIGNIFICANCE STATEMENT Automatic detection of biologically relevant stimuli, such as threats or dangers, has remarkable survival value. Here, we provide direct intracranial electrophysiological evidence that the human amygdala preferentially responds to fearful faces at a rapid speed, despite the faces being invisible. This rapid, fear-selective response is restricted to faces containing low spatial frequency information transmitted by magnocellular neurons and does not appear in cortical regions. These results support the existence of a rapid subcortical pathway independent of cortical pathways to the human amygdala.
Subject(s)
Fear , Magnetic Resonance Imaging , Male , Female , Humans , Fear/physiology , Emotions/physiology , Happiness , Amygdala/physiology , Facial ExpressionABSTRACT
BACKGROUND: According to Chinese ancient books, both fruits and rhizomes of Polygonatum cyrtonema Hua have medicinal and edible values. Up to now, there is no report about the metabolite profiles and regulatory network in fruits and different year-old rhizomes of P. cyrtonema. RESULTS: In this study, we performed integrative analyses of metabolome and transcriptome to reveal the dynamic accumulation and regulatory network of fruits and different year-old rhizomes in P. cyrtonema. The relative content of phenolic acids, lignans and coumarins, flavonoids and alkaloids increased with growth years, while steroids and lipids decreased with it. In addition, the relative content of nucleotides and derivatives, flavonoids, organic acids, steroids and lipids in fruits were higher than rhizomes. Genes that might relate to the biosynthesis of polysaccharides, flavonoids, triterpene saponins and alkaloids biosynthesis were further analyzed by transcriptome analysis, including sacA, GMPP, PMM, CCoAOMT, CHI, ANR, CHS, DXS, GGPS, ZEP, CYP72A219 and so on, for their expressions were positively correlated with the relative content of the metabolites. Additionally, the correlation network in sugar and aromatic amino acids metabolites were constructed to further illustrate the biosynthesis of polysaccharides, flavonoids and alkaloids in P. cyrtonema, and some transcription factors (TFs) were screened, such as C2C2, MYB, bZIP, GRAS and NAC. CONCLUSIONS: This study can deepen our understanding of the accumulation patterns and molecular mechanism of the main compounds in P. cyrtonema, and provide reference for the standardize production of P. cyrtonema.
Subject(s)
Fruit , Gene Regulatory Networks , Metabolome , Polygonatum , Rhizome , Transcriptome , Rhizome/metabolism , Rhizome/genetics , Polygonatum/genetics , Polygonatum/metabolism , Fruit/metabolism , Fruit/genetics , Gene Expression Profiling , Gene Expression Regulation, Plant , Flavonoids/metabolismABSTRACT
A yeast strain (CGMCC 2.6937T) belonging to the ascomycetous yeast genus Saturnispora was recently isolated from soil collected in Xinghuacun, Shanxi Province, PR China. The strain produces one or two ellipsoid or spherical ascospores in asci formed by the conjugation between a cell and its bud. Phylogenetic analyses of the internal transcribed spacer (ITS) region and the D1/D2 domain of the large subunit rRNA gene suggest that this strain is conspecific with strains NYNU 14639 isolated from rotten wood collected in Funiu Mountain, Henan province and ES13S05 from soil collected in Nantou County, Taiwan. The CGMCC 2.6937T group is most closely related to Saturnispora dispora and Saturnispora zaruensis. However, strain CGMCC 2.6937T differs from S. dispora by 17 (3.2â%, 13 substitutions and four gaps) and 77 (18.8â%, 52 substitutions and 25 gaps) mismatches, and from S. zaruensis by 15 (2.9â%, 12 substitutions and three gaps) and 64 (15.6â%, 44 substitutions and 20 gaps) mismatches, in the D1/D2 domain and ITS region, respectively. The results suggest that the CGMCC 2.6937T group represents an undescribed species in the genus Saturnispora, for which the name Saturnispora sinensis sp. nov. is proposed. The holotype strain is CGMCC 2.6937T.
Subject(s)
Ascomycota , Phylogeny , Soil Microbiology , Wood , Ascomycota/classification , Ascomycota/genetics , Base Composition , Sequence Analysis, DNA , Wood/microbiology , Mycological Typing TechniquesABSTRACT
A case-crossover study among 511,767 cardiovascular disease (CVD) deaths in Jiangsu province, China, during 2015-2021 was conducted to assess the association of exposure to ambient ozone (O3) and heat wave with CVD mortality and explore their possible interactions. Heat wave was defined as extreme high temperature for at least two consecutive days. Grid-level heat waves were defined by multiple combinations of apparent temperature thresholds and durations. Residential O3 and heat wave exposures were assessed using grid data sets (spatial resolution: 1 km × 1 km for O3; 0.0625° × 0.0625° for heat wave). Conditional logistic regression models were applied for exposure-response analyses and evaluation of additive interactions. Under different heat wave definitions, the odds ratios (ORs) of CVD mortality associated with medium-level and high-level O3 exposures ranged from 1.029 to 1.107 compared with low-level O3, while the ORs for heat wave exposure ranged from 1.14 to 1.65. Significant synergistic effects on CVD mortality were observed for the O3 and heat wave exposures, which were generally greater with higher levels of the O3 exposure, higher temperature thresholds, and longer durations of heat wave exposure. Up to 5.8% of the CVD deaths were attributable to O3 and heat wave. Women and older adults were more vulnerable to the exposure to O3 and heat wave exposure. Exposure to both O3 and heat wave was significantly associated with an increased odds of CVD mortality, and O3 and heat wave can interact synergistically to trigger CVD deaths.
Subject(s)
Air Pollutants , Air Pollution , Cardiovascular Diseases , Ozone , Humans , Female , Aged , Ozone/analysis , Cardiovascular Diseases/epidemiology , Air Pollutants/analysis , Cross-Over Studies , Hot Temperature , China/epidemiology , Air Pollution/analysis , Environmental Exposure/analysis , Particulate Matter/analysisABSTRACT
By applying the phosphonic acid ligand to the solvothermal reaction of nitrobenzylphosphonic acid (H2L) with Cd(NO3)2·4H2O in a mixed solvent of water and DMF, a novel Cd(II)-based coordination polymer, {[Cd(L)(H2O)2](H2O)}n (1), was successfully synthesized in this study. The excellent fluorescence performance of complex 1 was confirmed through fluorescence spectroscopy testing, and the obtained CIE standard coordinates (0.1599, 0.0786) positioned it in the blue fluorescence region. Transparent hyaluronic acid/carboxymethyl chitosan hydrogels were prepared using chemical synthesis, and their internal microstructure was observed. Using budesonide as a drug model, a new budesonide metal gel was prepared, and its therapeutic efficacy in treating pediatric asthma was evaluated. Molecular docking simulations indicated that the Cd complex formed three hydrogen bonding interactions with the target protein through its nitro group, revealing the potential origin of its biological activity.
ABSTRACT
The envelope is essential for speech perception. Recent studies have shown that cortical activity can track the acoustic envelope. However, whether the tracking strength reflects the extent of speech intelligibility processing remains controversial. Here, using stereo-electroencephalogram technology, we directly recorded the activity in human auditory cortex while subjects listened to either natural or noise-vocoded speech. These 2 stimuli have approximately identical envelopes, but the noise-vocoded speech does not have speech intelligibility. According to the tracking lags, we revealed 2 stages of envelope tracking: an early high-γ (60-140 Hz) power stage that preferred the noise-vocoded speech and a late θ (4-8 Hz) phase stage that preferred the natural speech. Furthermore, the decoding performance of high-γ power was better in primary auditory cortex than in nonprimary auditory cortex, consistent with its short tracking delay, while θ phase showed better decoding performance in right auditory cortex. In addition, high-γ responses with sustained temporal profiles in nonprimary auditory cortex were dominant in both envelope tracking and decoding. In sum, we suggested a functional dissociation between high-γ power and θ phase: the former reflects fast and automatic processing of brief acoustic features, while the latter correlates to slow build-up processing facilitated by speech intelligibility.
Subject(s)
Auditory Cortex , Speech Perception , Humans , Speech/physiology , Auditory Cortex/physiology , Speech Intelligibility , Acoustic Stimulation , Electroencephalography , Speech Perception/physiologyABSTRACT
Daqu is used as the fermentation starter of Baijiu and contributes diversified functional microbes for saccharifying grains and converting sugars into ethanol and aroma components in Baijiu products. Daqu is mainly classified into three types, namely low (LTD), medium (MTD) and high (HTD) temperature Daqu, according to the highest temperatures reached in their fermentation processes. In this study, we used the PacBio small-molecule real-time (SMRT) sequencing technology to determine the full-length 16 S rRNA gene sequences from the metagenomes of 296 samples of different types of Daqu collected from ten provinces in China, and revealed the bacterial diversity at the species level in the Daqu samples. We totally identified 310 bacteria species, including 78 highly abundant species (with a relative abundance >0.1% each) which accounted for 91.90% of the reads from all the Daqu samples. We also recognized the differentially enriched bacterial species in different types of Daqu, and in the Daqu samples with the same type but from different provinces. Specifically, Lactobacillales, Enterobacterales and Bacillaceae were significantly enriched in the LTD, MTD and HTD groups, respectively. The potential co-existence and exclusion relationships among the bacteria species involved in all the Daqu samples and in the LTD, MTD and HTD samples from a specific region were also identified. These results provide a better understanding of the bacterial diversity in different types of Daqu at the species level.
Subject(s)
Bacteria , Fermentation , RNA, Ribosomal, 16S , RNA, Ribosomal, 16S/genetics , Bacteria/genetics , Bacteria/classification , Bacteria/isolation & purification , Bacteria/metabolism , China , Microbiota , Phylogeny , DNA, Bacterial/genetics , Biodiversity , Alcoholic Beverages/microbiology , Alcoholic Beverages/analysis , Food Microbiology , Metagenome , Fermented Foods/microbiologyABSTRACT
A neutral Polygonatum cyrtonema polysaccharide (NPCP) was isolated and purified from Polygonatum cyrtonema by various chromatographic techniques, including DEAE-52 and Sephadex-G100 chromatography. The structure of NPCP was characterized by HPLC, HPGPC, GC-MS, FT-IR, NMR, and SEM. Results showed that NPCP is composed of glucose (55.4%) and galactose (44.6%) with a molecular weight of 3.2 kDa, and the sugar chain of NPCP was â1)-α-D-Glc-(4â1)-ß-D-Gal-(3â. In vitro bioactivity experiments demonstrated that NPCP significantly enhanced macrophages proliferation and phagocytosis while inhibiting the M1 polarization induced by LPS as well as the M2 polarization induced by IL-4 and IL-13 in macrophages. Additionally, NPCP suppressed the secretion of IL-6 and TNF-α in both M1 and M2 cells but promoted the secretion of IL-10. These results suggest that NPCP could serve as an immunomodulatory agent with potential applications in anti-inflammatory therapy.
Subject(s)
Macrophages , Phagocytosis , Polygonatum , Polysaccharides , Macrophages/drug effects , Macrophages/metabolism , Macrophages/immunology , Polygonatum/chemistry , Mice , Polysaccharides/pharmacology , Polysaccharides/chemistry , Polysaccharides/isolation & purification , Animals , Phagocytosis/drug effects , Immunologic Factors/pharmacology , Immunologic Factors/chemistry , Immunologic Factors/isolation & purification , RAW 264.7 Cells , Cytokines/metabolism , Cell Proliferation/drug effects , Immunomodulating Agents/pharmacology , Immunomodulating Agents/chemistry , Immunomodulating Agents/isolation & purification , Molecular WeightABSTRACT
BACKGROUND: Selection of high-quality blastocysts is the most important factor determining the success of assisted reproductive technology. The objective of this study is to assess the values of blastocyst morphological quality and development speed for predicting euploidy and clinical pregnancy outcome. METHODS: A total of 155 preimplantation genetic testing cycles including 959 blastocysts and 154 euploid blastocyst transfer cycles conducted between January 2018 and December 2019 were retrospectively analysed. The associations of blastocyst morphological quality and development speed (D) with chromosomal status, clinical pregnancy rate, early miscarriage rate, and ongoing pregnancy rate were evaluated by univariate and multivariate regression. RESULTS: The euploidy rate of development speed D5 blastocysts was significantly greater than that of D6 blastocysts (61.4% vs. 38.1%, P < 0.001), and the euploid rate of morphologically high-grade blastocysts was significantly greater than that of non-high-grade blastocysts. Development speed D5 (OR = 1.6, 95% CI 1.2-2.2, P = 0.02) and high-grade morphology (OR = 2.1, 95% CI 1.5-2.9, P = 0.01) were independent predictors of euploidy. The ongoing pregnancy rate of D5 blastocysts was significantly higher than that of D6 blastocysts (62.3% vs. 43.8%, P = 0.04). Transfer of euploid blastocysts with high-grade morphology resulted in a greater ongoing pregnancy rate than transfer of non-high-grade euploid blastocysts (60.7% vs. 43.2%, P = 0.049). Alternatively, D6 development speed was an independent risk factor for early pregnancy loss after euploid blastocyst transfer. Multivariate regression analysis adjusting for confounding factors identified maternal age, blastocyst development speed, and blastocyst morphological grade as independent predictors of euploidy but not of clinical pregnancy. CONCLUSION: The recommended sequence of embryo transfer based on the present study is D5 high-grade > D6 high-grade > D5 non-high-grade > D6 non-high-grade.
Assisted reproductive technology physicians are actively exploring methods to improve the accuracy of embryo selection for successful pregnancy. We evaluated the associations of embryo morphological grade and development speed with chromosomal status and clinical outcome for couples without a history of infertility, in vitro fertilisation failure, or recurrent miscarriage receiving euploid embryo transfer. Blastocysts from females younger than 35 years, of high morphological grade, and demonstrating faster development speed were most likely to be euploid (least likely to have chromosomal abnormalities). Alternatively, patients implanted with slower developing euploid blastocysts were at higher risk of early pregnancy loss. To maximise the probability of implanting euploid embryos and minimise the risk of pregnancy loss, the selection order of embryo transferred should be based on embryo development speed followed by morphological grades.
Subject(s)
Abortion, Spontaneous , Pregnancy Outcome , Pregnancy , Female , Humans , Pregnancy Outcome/epidemiology , Single Embryo Transfer , Retrospective Studies , Blastocyst , Embryo, Mammalian , Abortion, Spontaneous/epidemiology , Abortion, Spontaneous/etiologyABSTRACT
Glyphosate is an ingredient widely used in various commercial formulations, including Roundup®. This study focused on tight junctions and the expression of inflammatory genes in the small intestine of chicks. On the sixth day of embryonic development, the eggs were randomly assigned to three groups: the control group (CON, n = 60), the glyphosate group (GLYP, n = 60), which received 10 mg of active glyphosate/kg egg mass, and the Roundup®-based glyphosate group also received 10 mg of glyphosate. The results indicated that the chicks exposed to glyphosate or Roundup® exhibited signs of oxidative stress. Additionally, histopathological alterations in the small intestine tissues included villi fusion, complete fusion of some intestinal villi, a reduced number of goblet cells, and necrosis of some submucosal epithelial cells in chicks. Genes related to the small intestine (ZO-1, ZO-2, Claudin-1, Claudin-3, JAM2, and Occludin), as well as the levels of pro-inflammatory cytokines (IFNγ, IL-1ß, and IL-6), exhibited significant changes in the groups exposed to glyphosate or Roundup® compared to the control group. In conclusion, the toxicity of pure glyphosate or Roundup® likely disrupts the small intestine of chicks by modulating the expression of genes associated with tight junctions in the small intestine.
Subject(s)
Glyphosate , Herbicides , Animals , Herbicides/toxicity , Herbicides/metabolism , Glycine/toxicity , Tight Junctions/metabolism , Chickens/geneticsABSTRACT
This study established an HPLC fingerprint and multi-component content determination method for salt-fired Eucommiae Cortex, and evaluated the quality of salt-fired Eucommiae Cortex from different sources using fingerprint similarity evaluation, cluster analysis(CA), principal component analysis(PCA), and orthogonal partial least square discriminate analysis(OPLS-DA). HPLC was launched on a Cosmosil 5C_(18)-MS-â ¡ column(4.6 mm×250 mm, 5 µm) by gradient elution with a mobile phase of methanol-0.2% phosphoric acid aqueous solution at a flow rate of 1.0 mL·min~(-1), detection wavelength of 238 nm, column temperature of 30 â, and an injection volume of 10 µL. The results of fingerprint similarity evaluation for 20 batches of salt-fired Eucommiae Cortex indicated that, except for batch S3 with a similarity of 0.893, the similarity of the other 19 batches was of ≥ 0.919, suggesting good similarity. Fourteen common peaks were calibrated and seven common peaks were identified including geniposidic acid. The mass fractions of geniposidic acid, chlorogenic acid, geniposide, genipin, pinoresinol diglucoside, liriodendrin, and pinoresinol-4-O-ß-D-glucopyranoside were 0.062 0%-0.426 9%, 0.024 9%-0.116 5%, 0.009 5%-0.052 9%, 0.005 5%-0.034 8%, 0.115 9%-0.317 8%, 0.016 4%-0.108 8%, and 0.026 4%-0.039 8%, respectively. Using CA, PCA, and OPLS-DA, the 20 batches of salt-fired Eucommiae Cortex were classified into three categories. Additionally, through the analysis of variable importance in projection(VIP) under OPLS-DA, two differential quality markers, geniposidic acid and chlorogenic acid, were identified. The established HPLC fingerprint and multi-component content determination method is stable and reliable, providing a reference for quality control of salt-fired Eucommiae Cortex.
Subject(s)
Chemometrics , Drugs, Chinese Herbal , Chromatography, High Pressure Liquid/methods , Drugs, Chinese Herbal/analysis , Iridoid Glucosides/analysis , Sodium ChlorideABSTRACT
Chemoradiation-induced hearing loss (CRIHL) is one of the most devasting side effects for nasopharyngeal carcinoma (NPC) patients, which seriously affects survivors' long-term quality of life. However, few studies have comprehensively characterized the risk factors for CRIHL. In this study, we found that age at diagnosis, tumor stage, and concurrent cisplatin dose were positively associated with chemoradiation-induced hearing loss. We performed a genome-wide association study (GWAS) in 777 NPC patients and identified rs1050851 (within the exon 2 of NFKBIA), a variant with a high deleteriousness score, to be significantly associated with hearing loss risk (HR = 5.46, 95% CI 2.93-10.18, P = 9.51 × 10-08). The risk genotype of rs1050851 was associated with higher NFKBIA expression, which was correlated with lower cellular tolerance to cisplatin. According to permutation-based enrichment analysis, the variants mapping to 149 hereditary deafness genes were significantly enriched among GWAS top signals, which indicated the genetic similarity between hereditary deafness and CRIHL. Pathway analysis suggested that synaptic signaling was involved in the development of CRIHL. Additionally, the risk score integrating genetic and clinical factors can predict the risk of hearing loss with a relatively good performance in the test set. Collectively, this study shed new light on the etiology of chemoradiation-induced hearing loss, which facilitates high-risk individuals' identification for personalized prevention and treatment.
Subject(s)
Deafness , Hearing Loss , Nasopharyngeal Neoplasms , Humans , Nasopharyngeal Carcinoma/genetics , Cisplatin/adverse effects , Genome-Wide Association Study , Quality of Life , Hearing Loss/chemically induced , Hearing Loss/genetics , Nasopharyngeal Neoplasms/genetics , Nasopharyngeal Neoplasms/therapy , Nasopharyngeal Neoplasms/chemically inducedABSTRACT
Cultivated peanut (Arachis hypogaea L.) is an important oil and cash crop. Pod size is one of the major traits determining yield and commodity characteristic of peanut. Fine mapping of quantitative trait locus (QTL) and identification of candidate genes associated with pod size are essential for genetic improvement and molecular breeding of peanut varieties. In this study, a major QTL related to pod size, qAHPS07, was fine mapped to a 36.46 kb interval on chromosome A07 using F2 , recombinant inbred line (RIL) and secondary F2 populations. qAHPS07 explained 38.6%, 23.35%, 37.48%, 25.94% of the phenotypic variation for single pod weight (SPW), pod length (PL), pod width (PW) and pod shell thickness (PST), respectively. Whole genome resequencing and gene expression analysis revealed that a RuvB-like 2 protein coding gene AhRUVBL2 was the most likely candidate for qAHPS07. Overexpression of AhRUVBL2 in Arabidopsis led to larger seeds and plants than the wild type. AhRUVBL2-silenced peanut seedlings represented small leaves and shorter main stems. Three haplotypes were identified according to three SNPs in the promoter of AhRUVBL2 among 119 peanut accessions. Among them, SPW, PW and PST of accessions carrying Hap_ATT represent 17.6%, 11.2% and 26.3% higher than those carrying Hap_GACï¼respectively. In addition, a functional marker of AhRUVBL2 was developed. Taken together, our study identified a key functional gene of peanut pod size, which provides new insights into peanut pod size regulation mechanism and offers practicable markers for the genetic improvement of pod size-related traits in peanut breeding.
Subject(s)
Arachis , Plant Breeding , Arachis/genetics , Chromosome Mapping , Quantitative Trait Loci/genetics , PhenotypeABSTRACT
STUDY QUESTION: Can blastocyst aneuploidy be predicted for patients with previous aneuploid pregnancy loss (PAPL) and receiving preimplantation genetic testing for aneuploidy (PGT-A)? SUMMARY ANSWER: Multivariable logistic regression models were established to predict high risk of blastocyst aneuploidy using four identified factors, presenting good predictive performance. WHAT IS KNOWN ALREADY: Aneuploidy is the most common embryonic chromosomal abnormality leading to pregnancy loss. Several studies have demonstrated a higher embryo aneuploidy rate in patients with PAPL, which has suggested that PGT-A should have benefits in PAPL patients intending to improve their pregnancy outcomes. However, recent studies have failed to demonstrate the efficacy of PGT-A for PAPL patients. One possible way to improve the efficacy is to predict the risk of blastocyst aneuploidy risk in order to identify the specific PAPL population who may benefit from PGT-A. STUDY DESIGN, SIZE, DURATION: We conducted a multicenter retrospective cohort study based on data analysis of 1119 patients receiving PGT-A in three reproductive medical centers of university affiliated teaching hospitals during January 2014 to June 2020. A cohort of 550 patients who had one to three PAPL(s) were included in the PAPL group. In addition, 569 patients with monogenic diseases without pregnancy loss were taken as the non-PAPL group. PARTICIPANTS/MATERIALS, SETTING, METHODS: PGT-A was conducted using single nucleotide polymorphism microarrays and next-generation sequencing. Aneuploidy rates in Day 5 blastocysts of each patient were calculated and high-risk aneuploidy was defined as a rate of ≥50%. Candidate risk factors for high-risk aneuploidy were selected using the Akaike information criterion and were subsequently included in multivariable logistic regression models. Overall predictive accuracy was assessed using the confusion matrix, discrimination by area under the receiver operating characteristic curve (AUC), and calibration by plotting the predicted probabilities versus the observed probabilities. Statistical significance was set at P < 0.05. MAIN RESULTS AND THE ROLE OF CHANCE: Blastocyst aneuploidy rates were 30 ± 25% and 21 ± 19% for PAPL and non-PAPL groups, respectively. Maternal age (odds ratio (OR) = 1.31, 95% CI 1.24-1.39, P < 0.001), number of PAPLs (OR = 1.40, 95% CI 1.05-1.86, P = 0.02), estradiol level on the ovulation trigger day (OR = 0.47, 95% CI 0.30-0.73, P < 0.001), and blastocyst formation rate (OR = 0.13, 95% CI 0.03-0.50, P = 0.003) were associated with high-risk of blastocyst aneuploidy. The predictive model based on the above four variables yielded AUCs of 0.80 using the training dataset and 0.83 using the test dataset, with average and maximal discrepancies of 2.89% and 12.76% for the training dataset, and 0.98% and 5.49% for the test dataset, respectively. LIMITATIONS, REASONS FOR CAUTION: Our conclusions might not be compatible with those having fewer than four biopsied blastocysts and diminished ovarian reserves, since all of the included patients had four or more biopsied blastocysts and had exhibited good ovarian reserves. WIDER IMPLICATIONS OF THE FINDINGS: The developed predictive model is critical for counseling PAPL patients before PGT-A by considering maternal age, number of PAPLs, estradiol levels on the ovulation trigger day, and the blastocyst formation rate. This prediction model achieves good risk stratification and so may be useful for identifying PAPL patients who may have higher risk of blastocyst aneuploidy and can therefore acquire better pregnancy outcomes by PGT-A. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Natural Science Foundation of China under Grant (81871159). No competing interest existed in the study. TRIAL REGISTRATION NUMBER: N/A.
Subject(s)
Abortion, Spontaneous , Preimplantation Diagnosis , Pregnancy , Humans , Female , Preimplantation Diagnosis/methods , Retrospective Studies , Blastocyst/pathology , Genetic Testing/methods , Pregnancy Outcome , Abortion, Spontaneous/genetics , Abortion, Spontaneous/pathology , Aneuploidy , EstradiolABSTRACT
Stroke is a common cerebrovascular disease with high morbidity, mortality, and disability worldwide. Post-stroke dysfunction is related to the death of neurons and impairment of synaptic structure, which results from cerebral ischemic damage. Currently, transcranial magnetic stimulation (TMS) techniques are available to provide clinically effective interventions and quantitative diagnostic and prognostic biomarkers. The development of TMS has been 40 years and a range of repetitive TMS (rTMS) protocols are now available to regulate neuronal plasticity in many neurological disorders, such as stroke, Parkinson disease, psychiatric disorders, Alzheimer disease, and so on. Basic studies in an animal model with ischemic stroke are significant for demonstrating potential mechanisms of neural restoration induced by rTMS. In this review, the mechanisms were summarized, involving synaptic plasticity, neural cell death, neurogenesis, immune response, and blood-brain barrier (BBB) disruption in vitro and vivo experiments with ischemic stroke models. Those findings can contribute to the understanding of how rTMS modulated function recovery and the exploration of novel therapeutic targets. The mechanisms of rTMS in treating ischemic stroke from animal models. rTMS can prompt synaptic plasticity by increasing NMDAR, AMPAR and BDNF expression; rTMS can inhibit pro-inflammatory cytokines TNF and facilitate the expression of anti-inflammatory cytokines IL-10 by shifting astrocytic phenotypes from A1 to A2, and shifting microglial phenotypes from M1 to M2; rTMS facilitated the release of angiogenesis-related factors TGFß and VEGF in A2 astrocytes, which can contribute to vasculogenesis and angiogenesis; rTMS can suppress apoptosis by increasing Bcl-2 expression and inhibiting Bax, caspase-3 expression; rTMS can also suppress pyroptosis by decreasing caspase-1, IL-1ß, ASC, GSDMD and NLRP1 expression. rTMS, repetitive transcranial magnetic stimulation; NMDAR, N-methyl-D-aspartic acid receptors; AMPAR: α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors; BDNF, brain-derived neurotrophic factor; VEGF, vascular endothelial growth factor; GSDMD: cleaved Caspase-1 cleaves Gasdermin D; CBF: cerebral blood flow.
Subject(s)
Ischemic Stroke , Stroke , Animals , Transcranial Magnetic Stimulation/methods , Brain-Derived Neurotrophic Factor/metabolism , Vascular Endothelial Growth Factor A/metabolism , Ischemic Stroke/therapy , Brain/metabolism , Stroke/therapy , Disease Models, Animal , Caspases/metabolismABSTRACT
Aromatic organoboron compounds are highly valuable building blocks in organic chemistry. They were mainly synthesized through aromatic C-H and C-Het borylation, in which transition metal-catalysis dominate. In the past decade, with increasing attention to sustainable chemistry, numerous transition metal-free C-H and C-Het borylation transformations have been developed and emerged as efficient methods towards the synthesis of aromatic organoboron compounds. This account mainly focuses on recent advances in transition metal-free aromatic C-H, C-N, C-S, and C-O borylation transformations and provides insights to where further developments are required.
ABSTRACT
BACKGROUND: Previous studies have suggested that trophoblast cells inhibit the proliferation of peripheral natural killer cells and that the level of peripheral natural killer cells decrease in the middle and late pregnancy stage among healthy women. The change in peripheral natural killer cell level during early pregnancy and the relationship between the change in peripheral natural killer cell level and pregnancy outcomes among women with unexplained recurrent pregnancy loss have not been sufficiently explored. OBJECTIVE: This study aimed to characterize the level of prepregnancy peripheral natural killer cells in comparison with those in early pregnancy among women with unexplained recurrent pregnancy loss and to determine if the change in the level of peripheral natural killer cells from prepregnancy to early pregnancy can predict pregnancy outcomes. STUDY DESIGN: In this prospective cohort study, 1758 women with recurrent pregnancy loss were recruited between January 2017 and December 2021 among whom 252 women with unexplained recurrent pregnancy loss had prepregnancy and early pregnancy (4-6 weeks gestation) peripheral natural killer cell measurements. These 252 women were divided into 2 groups, namely those with a lower gestational peripheral natural killer cell level (group 1) when compared with prepregnancy levels and those who did not (group 2). The respective outcomes of these groups in terms of live birth and pregnancy loss were comparatively analyzed using chi-square and Student's t tests. Candidate factors that could influence live birth were selected using the Akaike information criterion. The participates were then randomly divided into training and testing groups. A multivariable logistic regression analysis was performed and a nomogram was created to assess the possibility of live birth. The predictive accuracy was determined by the area under the receiver operating characteristic curve and validated by plotting the predicted probabilities and the observed probabilities. A Hosmer-Lemeshow test was used to assess the goodness of fit. RESULTS: When early gestational peripheral natural killer cell levels were compared with prepregnancy peripheral natural killer cell levels, 61.5% (154) of women had a comparatively lower early-gestational peripheral natural killer cell level and 38.9% (98) of women had an increase or no change in the peripheral natural killer cell level. The live birth rate in group 1 was 89.0% (137/154), which was significantly higher than the rate of 49.0% (48/98) in group 2 (P<.001). A decrease in the peripheral natural killer cell level (odds ratio, 1.36; 95% confidence interval, 1.22-1.55; P<.001) and the anti-Muellerian hormone level (odds ratio, 1.41; 95% confidence interval, 1.14-1.81; P=.003) were important predicting factors for a higher live birth rate. Female body mass index (odds ratio, 0.97; 95% confidence interval, 0.82-1.15; P=.763) and parity (odds ratio, 1.61; 95% confidence interval, 0.71-4.12; P=.287) also were predicting factors. Furthermore, the area under the receiver operating characteristic curve of the model to diagnose of live birth was 0.853 with a sensitivity of 81.6% and a specificity of 78.0% using the training data set. And the Hosmer-Lemeshow test showed that the model was a good fit (p=6.068). CONCLUSION: We report a comparative decrease in the peripheral natural killer cell levels in early gestation when compared with prepregnancy cell levels in more than 60% of women with unexplained recurrent pregnancy loss at 4 to 6 weeks of gestation. When compared with prepregnancy peripheral natural killer cell levels, a decrease in the peripheral natural killer cell level during early pregnancy might be a useful predictor of the live birth rate among women with unexplained recurrent pregnancy loss.