[Microfluidic Chip and Flow Cytometry for Examination of the Antiplatelet Effect of Ticagrelor].

Objective To examine the antiplatelet effect of ticagrelor by microfluidic chip and flow cytometry under shear stress in vitro. Methods Microfluidic chip was used to examine the effect of ticagrelor on platelet aggregation at the shear rates of 300/s and 1500/s.We adopted the surface coverage of platelet aggregation to calculate the half inhibition rate of ticagrelor.The inhibitory effect of ticagrelor on ADP-induced platelet aggregation was verified by optical turbidimetry.Microfluidic chip was used to construct an in vitro vascular stenosis model,with which the platelet reactivity under high shear rate was determined.Furthermore,the effect of ticagrelor on the expression of fibrinogen receptor (PAC-1) and P-selectin (CD62P) on platelet membrane activated by high shear rate was analyzed by flow cytometry. Results At the shear rates of 300/s and 1500/s,ticagrelor inhibited platelet aggregation in a concentration-dependent manner,and the inhibition at 300/s was stronger than that at 1500/s (both P<0.001).Ticagrelor at a concentration ≥4 µmol/L almost completely inhibited platelet aggregation.The inhibition of ADP-induced platelet aggregation by ticagrelor was similar to the results under flow conditions and also in a concentration-dependent manner.Ticagrelor inhibited the expression of PAC-1 and CD62P. Conclusion We employed microfluidic chip to analyze platelet aggregation and flow cytometry to detect platelet activation,which can reveal the responses of different patients to ticagrelor.

SNAP29 mediates the assembly of histidine-induced CTP synthase filaments in proximity to the cytokeratin network.

Under metabolic stress, cellular components can assemble into distinct membraneless organelles for adaptation. One such example is cytidine 5'-triphosphate synthase (CTPS, for which there are CTPS1 and CTPS2 forms in mammals), which forms filamentous structures under glutamine deprivation. We have previously demonstrated that histidine (His)-mediated methylation regulates the formation of CTPS filaments to suppress enzymatic activity and preserve the CTPS protein under glutamine deprivation, which promotes cancer cell growth after stress alleviation. However, it remains unclear where and how these enigmatic structures are assembled. Using CTPS-APEX2-mediated in vivo proximity labeling, we found that synaptosome-associated protein 29 (SNAP29) regulates the spatiotemporal filament assembly of CTPS along the cytokeratin network in a keratin 8 (KRT8)-dependent manner. Knockdown of SNAP29 interfered with assembly and relaxed the filament-induced suppression of CTPS enzymatic activity. Furthermore, APEX2 proximity labeling of keratin 18 (KRT18) revealed a spatiotemporal association of SNAP29 with cytokeratin in response to stress. Super-resolution imaging suggests that during CTPS filament formation, SNAP29 interacts with CTPS along the cytokeratin network. This study links the cytokeratin network to the regulation of metabolism by compartmentalization of metabolic enzymes during nutrient deprivation.

Transcriptome profiling of the nonlactating mammary glands of dairy goats reveals the molecular genetic mechanism of mammary cell remodeling.

The mammary gland redevelops to the prepregnancy state during involution, which shows the mammary cells have the characteristics of remodeling. The rapidity and degree of mammary gland involution vary across species (e.g., between model organism mice and dairy livestock). However, the molecular genetic mechanism of involution and remodeling of goat mammary gland has not yet been clarified. This work investigated the structural changes and transcriptome characteristics of the mammary gland tissue of nonlactating dairy goats during the late lactation (LL), the dry period (DP), and late gestation (LG). Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining revealed significant changes in the structure of the nonlactating goat mammary gland, and obvious cell apoptosis occurred at LL and DP. Sequencing identified 1,381 genes that are differentially expressed in mammary gland tissue at the 3 developmental stages. Genes related to cell growth, apoptosis, immunity, nutrient transport, synthesis, and metabolism exhibited adaptive transcriptional changes to meet the needs of a new set of mammary gland lactation functions. The significant enrichment of Gene Ontology terms such as humoral immune response, complement activation, and neutrophil-mediated immunity indicates that the innate immune system plays an important role in maintaining the health of degenerative mammary glands and eliminating apoptotic cells. The peroxisome proliferator-activated receptor signaling pathway plays an important regulatory role in lipid metabolism, especially the adaptive changes in expression of genes encoded lipid transport and enzymes, which promote the formation of milk fat during the lactation. The mammary gland development gene module revealed that pregnancy hormone receptors, cell growth factors and their receptors, and genes encoding insulin-like growth factor binding proteins regulate the physiological process of mammary gland involution through adaptive transcriptional changes. Interestingly, ERBB4 was identified as the hub gene of the network that regulates mammary gland growth and development. Overexpression of ERBB4 in mammary epithelial cells cultured in vitro can reduce cell cycle arrest in G1/S phase and apoptosis by regulating the PI3K/Akt signaling pathway and promote the proliferation of mammary epithelial cells. The gene ERBB4 also affects the expression of genes that initiate mammary gland involution and promote mammary gland remodeling. These findings contribute to an in-depth understanding of the molecular mechanisms involved in mammary gland involution and remodeling.

Transcriptome Analysis of Goat Mammary Gland Tissue Reveals the Adaptive Strategies and Molecular Mechanisms of Lactation and Involution.

To understand how genes precisely regulate lactation physiological activity and the molecular genetic mechanisms underlying mammary gland involution, this study investigated the transcriptome characteristics of goat mammary gland tissues at the late gestation (LG), early lactation (EL), peak lactation (PL), late lactation (LL), dry period (DP), and involution (IN) stages. A total of 13,083 differentially expressed transcripts were identified by mutual comparison of mammary gland tissues at six developmental stages. Genes related to cell growth, apoptosis, immunity, nutrient transport, synthesis, and metabolism make adaptive transcriptional changes to meet the needs of mammary lactation. Notably, platelet derived growth factor receptor beta (PDGFRB) was screened as a hub gene of the mammary gland developmental network, which is highly expressed during the DP and IN. Overexpression of PDGFRB in vitro could slow down the G1/S phase arrest of goat mammary epithelial cell cycle and promote cell proliferation by regulating the PI3K/Akt signaling pathway. In addition, PDGFRB overexpression can also affect the expression of genes related to apoptosis, matrix metalloproteinase family, and vascular development, which is beneficial to the remodeling of mammary gland tissue during involution. These findings provide new insights into the molecular mechanisms involved in lactation and mammary gland involution.

A Semiconductive Nature of Bis(dithiolato)nickelate Radical Salt Exhibiting Broadband Photoconduction.

The fractional oxidation state [M(dmit)2] (dmit2- = 2-thioxo-1, 3-dithiole-4, 5-dithiolate) salts have long attracted attention in the molecular metal area owing to high conductivity and even superconductivity. In this study, we achieved a mixed-valence salt (1) of [Ni(dmit)2]0.5- with monovalent 1,3-N,N-dimethyl-imidazolium (DiMIm+) by a solvent evaporation approach under ambient conditions. The mixed valence of [Ni(dmit)2]0.5- has been characterized by an analysis of the IR spectrum and crystal structure. In the crystal structure of 1, two [Ni(dmit)2]0.5- anions overlap in an eclipsed mode to form a [Ni(dmit)2]21- dimer, featuring a radical bearing an S = 1/2 spin; the dimeric radicals stack into a column along the b axis, and the adjacent columns connect together via the lateral-to-lateral S···S contacts along the a axis, and through the head-to-head S···S contacts along the [101] direction. Salt 1 shows the magnetic behavior of an S = 1/2 Heisenberg antiferromagnetic uniform linear chain with J/kB = -47.5(4) K and a semiconducting feature with σ = 2.52 × 10-3 S cm-1 at 293 K, 2.32 × 10-2 S cm-1 at 373 K, and Ea = 0.22 eV, as well as broadband photoconductivity under irradiation of green and white lights. This study suggests the possibility of designing new photoconductors based on the mixed-valence [Ni(dmit)2]0.5- salt.

Genome­wide integrated analysis demonstrates widespread functions of lncRNAs in mammary gland development and lactation in dairy goats.

BACKGROUND: The mammary gland is a unique organ for milk synthesis, secretion and storage, and it undergoes cyclical processes of development, differentiation, lactation and degeneration. At different developmental periods, the biological processes governing mammary gland physiology and internal environmental homeostasis depend on a complex network of genes and regulatory factors. Emerging evidence indicates that lncRNAs have arbitrarily critical functions in regulating gene expression in many organisms; however, the systematic characteristics, expression, and regulatory roles of lncRNAs in the mammary gland tissues of dairy goats have not been determined. RESULT: In the present study, we profiled long noncoding RNA (lncRNA) expression in the mammary gland tissues of Laoshan dairy goats (Capra hircus) from different lactation periods at the whole-genome level, to identify, characterize and explore the regulatory functions of lncRNAs. A total of 37,249 transcripts were obtained, of which 2381 lncRNAs and 37,249 mRNAs were identified, 22,488 transcripts, including 800 noncoding transcripts and 21,688 coding transcripts, differed significantly (p ≤ 0.01) among the different lactation stages. The results of lncRNA-RNA interaction analysis showed that six known lncRNAs belonging to four families were identified as the precursors of 67 known microRNAs; 1478 and 573 mRNAs were predicted as hypothetical cis-regulation elements and antisense mRNAs, respectively. GO annotation and KEGG analysis indicated that the coexpressed mRNAs were largely enriched in biological processes related to such activities as metabolism, immune activation, and stress,., and most genes were involved in pathways related to such phenomena as inflammation, cancer, signal transduction, and metabolism. CONCLUSIONS: Our results clearly indicated that lncRNAs involved in responses to stimuli, multiorganism processes, development, reproductive processes and growth, are closely related to mammary gland development and lactation.

3D Printing of BaTiO3 Piezoelectric Ceramics for a Focused Ultrasonic Array.

BaTiO3 (BTO) ceramics were fabricated based on stereolithography technology. The microstructures and electric properties of the BTO ceramics were studied. X-ray patterns of sintered BTO ceramics indicated that the tetragonal phase had formed, and the grain size increased clearly as BTO weight percentage increased. Moreover, the BTO ceramics exhibited good electric properties, with a piezoelectric constant d33 of 166 pC/N at 80% BTO weight percentage. To evaluate the properties of 3D printed BTO ceramics, a 1.4 MHz focused ultrasonic array was fabricated and characterized. The -6dB bandwidth of the array was 40%, and the insertion loss at the center frequency was 50 dB. The results show that the printed BTO ceramics array have good potential to be used in ultrasonic transducers for various applications.

A Unique Interaction of IVS-I-1 (G>A) (HBA2: c.95+1G>A) with Hb Adana (HBA2: c.179G>A) Presenting as Transfusion-Dependent α-Thalassemia.

Nondeletional α-globin mutations are known to cause more serious clinical effects than deletional ones. A rare IVS-I-1 (G>A) (HBA2: c.95+1G>A) donor splice site mutation interferes with normal splicing of pre mRNA and results in activation of a cryptic splice site as well as a frameshift mutation. Hb Adana [HBA2: c.179G>A (or HBA1)] is a highly unstable variant hemoglobin (Hb) resulting from a mutation at codon 59 on the HBA2 or HBA1 gene, recognized to cause severe α-thalassemia (α-thal) syndromes. We report a unique case of compound heterozygosity for these two mutations in a 9-year-old boy who presented with a Hb level of 5.3 g/dL and hepatomegaly at the age of 15 months. He required regular blood transfusions in view of a Hb level of <7.0 g/dL and failure to thrive. He had thalassemic red cell indices and peripheral blood film. The Hb electrophoresis only showed a raised Hb F level (3.3%) and a pre run peak but the Hb H inclusion test was negative. His father had thalassemic red cell indices but a normal Hb level. His mother had almost normal Hb levels and red cell indices. Hb Adana involving the HBA2 gene was detected by mutiplex amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) in the proband and his father. DNA sequencing of the HBA2 gene confirmed the IVS-I-1 mutation in the proband and his mother. This case highlighted the unique interaction of the IVS-I-1 mutation with Hb Adana in a young Malay boy presenting with transfusion-dependent α-thal.

Cytisine-Pterocarpan-Derived Compounds: Biomimetic Synthesis and Apoptosis-Inducing Activity in Human Breast Cancer Cells.

Cytisine-pterocarpan-derived compounds were biomimetically synthesized with (-)-cytisine and (-)-maackiain via a N,N-4-dimethyl-4-aminopyridine (DMAP)-mediated synthetic strategy in a mild manner. In the present study, tonkinensine B (4) was elaborated in good and high yields with the optimized reaction conditions. The in vitro cytotoxicity of compound 4 was evaluated against breast cancer cell lines and showed that 4 had a better cytotoxicity against MDA-MB-231 cells (IC50 = 19.2 µM). Depending on the research on cytotoxicities of 4 against RAW 264.7 and BV2 cells, it was suggested that 4 produced low cytotoxic effects on the central nervous system. Further study indicated that 4 demonstrated cytotoxic activity against MDA-MB-231 cells and the cytotoxic activity was induced by apoptosis. The results implied that the apoptosis might be induced by mitochondrion-mediated apoptosis via regulating the ratio of Bax/Bcl-2 and promoting the release of cytochrome c from the mitochondrion to the cytoplasm in MDA-MB-231 cells.

Molecular Characterisation of α- and ß-Thalassaemia among Indigenous Senoi Orang Asli Communities in Peninsular Malaysia.

Thalassaemia is a public health problem in Malaysia, with each ethnic group having their own common mutations. However, there is a lack on data on the prevalence and common mutations among the indigenous people. This cross-sectional study was performed to determine the common mutations of α- and ß-thalassaemia among the subethnic groups of Senoi, the largest Orang Asli group in Peninsular Malaysia. Blood samples collected from six Senoi subethnic groups were analysed for full blood count and haemoglobin analysis (HbAn). Samples with abnormal findings were then screened for α- and ß-globin gene mutations. Out of the 752 samples collected, 255 showed abnormal HbAn results, and 122 cases showing abnormal red cell indices with normal HbAn findings were subjected to molecular screening. DNA analysis revealed a mixture of α- and ß-globin gene mutations with 25 concomitant cases. The types of gene abnormalities detected for α-thalassaemia were termination codon (T>C) Hb CS (αCS α), Cd59 (G>A) haemoglobin Adana (Hb Adana) (αCd59 α), initiation codon (ATG>A-G) (αIniCd α), two-gene deletion (-SEA ), and single-gene 3.7-kb deletion (-α3.7 ). For ß-thalassaemia, there were Cd26 (G>A) Hb E (ßE ), Cd19 (A>G) Haemoglobin Malay (Hb Malay) (ßCd19 ), and IVS 1-5 (G>C) (ßIVS 1-5 ).

Phase Transition, Dielectrics, Single-Ion Conductance, and Thermochromic Luminescence of a Inorganic-Organic Hybrid of [Triethylpropylammonium][PbI3].

In this study, we used the facile solvent evaporation method to achieve the inorganic-organic hybrid crystals of [triethylpropylammonium][PbI3], which have been characterized by elemental analysis, IR spectroscopy, thermogravimetric analysis, and differential scanning calorimetry as well as single-crystal X-ray structure analysis. The hybrid solid crystallizes in the monoclinic space group P21/c at room temperature and is composed of one-dimensional [PbI3]∞ chains, where the neighboring PbI6 coordination octahedra connect together via the face-sharing mode and the organic cations fall in the spaces between [PbI3]∞ chains. The hybrid exhibits a dielectric phase transition with a critical temperature of ca. 432 K, dielectric relaxation at frequencies below 107 Hz, and single-ion conducting behavior, the conductivity of which increases rapidly from 9.43 × 10-10 S cm-1 at 383 K to 4.47 × 10-5 S cm-1 at 473 K. The variable-temperature single-crystal and powder X-ray diffraction analyses revealed that the dielectric phase transition is related to the disorder-to-order transformation of cations in the lattice. The electric modulus and impedance spectral analyses further disclosed that the dielectric relaxation arises from the ionic displacement polarization and molecular dipole orientation of cations. The single-ion conductance is due to the migration of cations that fall in the spaces of rigid inorganic [PbI3]∞ chains. The phase transition gives rise to this hybrid showing switchable ion-conducting nature around the critical temperature of the phase transition. Besides the fascinating functionalities mentioned above, the hybrid also exhibits a thermochromic luminescence feature originating from the electron transition between the valence and conduction bands of the inorganic [PbI3]∞ chain.

Using activated attapulgite as sorbent for solid-phase extraction of melamine in milk formula samples.

In this study, a simple solid-phase extraction (SPE) approach by using activated attapulgite as sorbent was successfully developed for the determination of melamine in milk formula samples. Crucial factors impacting the extraction efficiency, including sample solvent, elution solvent, and sample loading volume, were investigated. Under the optimal extraction conditions, the sample loading volume was up to 200 mL and the adsorption capacity of the melamine gave rise to 1154 µg g(-1). Excellent linear calibration curves (r (2) > 0.999) were achieved, and then the limit of detection (S/N = 3) and the limit of quantification (S/N = 10) were found to be 0.15 and 0.5 ng mL(-1), respectively. The recoveries of the melamine spiked in four milk formula samples at three concentration levels ranged from 83.5 to 111.0 % with relative standard deviations (RSDs) less than 10.2 %. Furthermore, RSDs of batch to batch (n = 4) of the acidified attapulgite used in this developed method were in the range of 2.3∼7.3 %. In comparison to the commercial Oasis MCX, the acidified attapulgite sorbent even outperformed (at least in terms of reproducibility) for melamine analysis in real food samples. Because of its simplicity, the newly developed SPE method based on acidified attapulgite nanoparticles should provide a promising tool for daily monitoring of doped melamine in milk formula or other complex matrices.

Fabrication of Natural Sensitizer Extracted from Mixture of Purple Cabbage, Roselle, Wormwood and Seaweed with High Conversion Efficiency for DSSC.

This study aims to deal with the influence of different solvent in extraction of natural sensitizer and different thickness of photoelectrode thin film on the photoelectric conversion efficiency and the electron transport properties for the prepared dye-sensitized solar cells (DSSC). The natural dyes of anthocyanin and chlorophyll dyes are extracted from mixture of purple cabbage and roselle and mixture of wormwood and seaweed, respectively. The experimental results show the cocktail dye extracted with ethanol and rotating speed of spin coating at 1000 rpm can achieve the greatest photoelectric conversion efficiency up to 1.85%. Electrochemical impedance result shows that the effective diffusion coefficient for the prepared DSSC with the thickness of photoelectrode thin film at 21 microm are 5.23 x 10(-4) cm2/s.

[Validation of subjective and objective evaluation methods for orthodontic treatment outcome].

OBJECTIVE: To assess the correlations between objective measurements of 108 finished orthodontic cases and subjective assessments made by 69 orthodontic specialists, to explore the statistically significant measuring categories of cast and cephalogram and to validate the regression model. METHODS: A stratified random sample of 108 cases was drawn from the large sample of 2 383 patients who finished orthodontic treatment between July 2006 and August 2008 in six orthodontic treatment centers around China. For each patient, the post-treatment information sources evaluated in this study included standardized plaster study casts and a lateral cephalometric X-ray image. These information sources were evaluated both singly and in combination by a panel of 69 orthodontic specialists. The average subjective grading scores of 69 orthodontists were regarded as the gold standard. Six examiners used the peer assessment rating (PAR) index and American board of orthodontics-objective grading system (ABO-OGS) to measure all the study casts respectively and three other examiners measured all the lateral cephalometric X-ray images by using customized software. The objective measuring data were correlated with the gold standard. The correlations between the objective measurement and the subjective evaluation were assessed, the statistically significant measuring categories of cast and cephalogram were explored and the regression model was validated. RESULTS: The ABO-OGS scores of "occlusal relationship" correlated most strongly with the subjective scores of cast (r=0.655, P<0.01), and the secondarily correlated category with those were the PAR scores of "overjet" (r=0.525, P<0.01). The proclination of the lower incisors correlated most strongly with the subjective scores of cephalogram (r=0.446, P<0.01), and the secondarily correlated category with those was the protrusion of the lower lips (r=0.436, P<0.01). Nine components were predictive for the post-treatment model and lateral ephalometric film (Post-M+C) outcome: alignment (ABO-OGS), occlusal relationship (ABO-OGS), interproximal contact(ABO-OGS), L1/NB°, overjet (PAR), SNB°, occlusal contacts (ABO-OGS), U1/SN2° and centerline (PAR). These 9 components accounted for 72% of the variability in the average subjective grading scores. CONCLUSION: The objective regression model could replace the averaged opinion of Chinese orthodontic experts effectively, making objective assessment of orthodontic treatment outcome for Chinese patients.

Transcriptome analysis revealed the characteristics and functions of long non-coding RNAs in the hypothalamus during sexual maturation in goats.

The hypothalamus is an essential neuroendocrine area in animals that regulates sexual development. Long non-coding RNAs (lncRNAs) are hypothesized to regulate physiological processes related to animal reproduction. However, the regulatory mechanism by which lncRNAs participate in sexual maturity in goats is poorly known, particularly from birth to sexual maturation. In this study, RNAseq analysis was conducted on the hypothalamus of four developmental stages (1day (D1, n = 5), 2 months (M2, n = 5), 4 months (M4, n = 5), and 6 months (M6, n = 5)) of Jining grey goats. The results showed that a total of 237 differentially expressed lncRNAs (DELs) were identified in the hypothalamus. Among these, 221 DELs exhibited cis-regulatory effects on 693 target genes, while 24 DELs demonstrated trans-regulatory effects on 63 target genes. The target genes of these DELs are mainly involved in biological processes related to energy metabolism, signal transduction and hormone secretion, such as sphingolipid signaling pathway, adipocytokine signaling pathway, neurotrophic signaling pathway, glutamatergic synapse, P53 signaling pathway and GnRH signaling pathway. In addition, XR_001918477.1, TCONS_00077463, XR_001918760.1, and TCONS_00029048 and their potential target genes may play a crucial role in the process of goat sexual maturation. This study advances our understanding of lncRNA in hypothalamic tissue during sexual maturation in goats and will give a theoretical foundation for improving goat reproductive features.

Expression and clinical significance of short-chain fatty acids in patients with intrahepatic cholestasis of pregnancy.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver condition that typically arises in the middle and late stages of pregnancy. Short-chain fatty acids (SCFAs), prominent metabolites of the gut microbiota, have significant connections with various pregnancy complications, and some SCFAs hold potential for treating such complications. However, the metabolic profile of SCFAs in patients with ICP remains unclear. AIM: To investigate the metabolic profiles and differences in SCFAs present in the maternal and cord blood of patients with ICP and determine the clinical significance of these findings. METHODS: Maternal serum and cord blood samples were collected from both patients with ICP (ICP group) and normal pregnant women (NP group). Targeted metabolomics was used to assess the SCFA levels in these samples. RESULTS: Significant differences in maternal SCFAs were observed between the ICP and NP groups. Most SCFAs exhibited a consistent declining trend in cord blood samples from the ICP group, mirroring the pattern seen in maternal serum. Correlation analysis revealed a positive correlation between maternal serum SCFAs and cord blood SCFAs [r (Pearson) = 0.88, P = 7.93e-95]. In both maternal serum and cord blood, acetic and caproic acids were identified as key metabolites contributing to the differences in SCFAs between the two groups (variable importance for the projection > 1). Receiver operating characteristic analysis demonstrated that multiple SCFAs in maternal blood have excellent diagnostic capabilities for ICP, with caproic acid exhibiting the highest diagnostic efficacy (area under the curve = 0.97). CONCLUSION: Compared with the NP group, significant alterations were observed in the SCFAs of maternal serum and cord blood in the ICP group, although they displayed distinct patterns of change. Furthermore, the SCFA levels in maternal serum and cord blood were significantly positively correlated. Notably, certain maternal serum SCFAs, specifically caproic and acetic acids, demonstrated excellent diagnostic efficiency for ICP.

Comparative metabolomics reveals serum metabolites changes in goats during different developmental stages.

Goats can provide meat, milk and skins for humans and are livestock with high economic benefits. However, despite their economic significance, the comprehensive analysis of goats' serum metabolic profile and its intricate alterations throughout their developmental journey remains conspicuously absent. To investigate the stage-specificity and dynamic change characteristics of metabolites during the growth and development of goats, this study compared the alterations in serum hormone levels and serum biochemical markers across different developmental stages of female goats (1, 60, 120 and 180 days old; n = 5). Additionally, a serum untargeted LC-MS metabolomics analysis was conducted. A total of 504 DAMs were identified with age. The results indicated that PE, PC, Lyso-PE, Lyso-PC and FAFHA may play important roles in lipid metabolism in goats after birth. Weighted gene co-expression network analysis (WGCNA) identified two metabolite modules (Turquoise and Yellow) and key metabolites within these modules that were significantly associated with phenotypic features. L-carnitine may be a metabolite related to muscle development in goats. The findings of this study demonstrate notable variations in serum metabolites across distinct developmental phases in goats. Lipids and organic acids play important roles in different developmental stages of goats.

Transcriptomic and metabolomic data of goat ovarian and uterine tissues during sexual maturation.

The ovaries and uterus are crucial reproductive organs in mammals, and their coordinated development ensures the normal development of sexual maturity and reproductive capacity. This study aimed to comprehensively capture the different physiological stages of the goat's sexual maturation by selecting four specific time points. We collected samples of ovarian and uterine tissues from five female Jining Gray goats at each time point: after birth (D1), 2-month-old (M2), 4-month-old (M4), and 6-month-old (M6). By combining transcriptomic sequencing of 40 samples (including rRNA-depleted RNA-seq libraries with 3607.8 million reads and miRNA-seq libraries with 444.0 million reads) and metabolomics analysis, we investigated the transcriptomic mechanisms involved in reproductive regulation in the ovary and uterus during sexual maturation, as well as the changes in metabolites and their functional potential. Additionally, we analyzed blood hormone indices and uterine tissue sections to examine temporal changes. These datasets will provide a valuable reference for the reproductive regulation of the ovary and uterus, as well as the regulation of metabolites during sexual maturation in goats.

Reductive Sn2+ Compensator for Efficient and Stable Sn-Pb Mixed Perovskite Solar Cells.

Tin-lead (Sn-Pb) mixed perovskite with a narrow bandgap is an ideal candidate for single-junction solar cells approaching the Shockley-Queisser limit. However, due to the easy oxidation of Sn2+, the efficiency and stability of Sn-Pb mixed perovskite solar cells (PSCs) still lag far behind that of Pb-based solar cells. Herein, highly efficient and stable FA0.5MA0.5Pb0.5Sn0.5I0.47Br0.03 compositional PSCs are achieved by introducing an appropriate amount of multifunctional Tin (II) oxalate (SnC2O4). SnC2O4 with compensative Sn2+ and reductive oxalate group C2O4 2- effectively passivates the cation and anion defects simultaneously, thereby leading to more n-type perovskite films. Benefitting from the energy level alignment and the suppression of bulk nonradiative recombination, the Sn-Pb mixed perovskite solar cell treated with SnC2O4 achieves a power conversion efficiency of 21.43%. More importantly, chemically reductive C2O4 2- effectively suppresses the notorious oxidation of Sn2+, leading to significant enhancement in stability. Particularly, it dramatically improves light stability.

NME3 is a gatekeeper for DRP1-dependent mitophagy in hypoxia.

NME3 is a member of the nucleoside diphosphate kinase (NDPK) family localized on the mitochondrial outer membrane (MOM). Here, we report a role of NME3 in hypoxia-induced mitophagy dependent on its active site phosphohistidine but not the NDPK function. Mice carrying a knock-in mutation in the Nme3 gene disrupting NME3 active site histidine phosphorylation are vulnerable to ischemia/reperfusion-induced infarction and develop abnormalities in cerebellar function. Our mechanistic analysis reveals that hypoxia-induced phosphatidic acid (PA) on mitochondria is essential for mitophagy and the interaction of DRP1 with NME3. The PA binding function of MOM-localized NME3 is required for hypoxia-induced mitophagy. Further investigation demonstrates that the interaction with active NME3 prevents DRP1 susceptibility to MUL1-mediated ubiquitination, thereby allowing a sufficient amount of active DRP1 to mediate mitophagy. Furthermore, MUL1 overexpression suppresses hypoxia-induced mitophagy, which is reversed by co-expression of ubiquitin-resistant DRP1 mutant or histidine phosphorylatable NME3. Thus, the site-specific interaction with active NME3 provides DRP1 a microenvironment for stabilization to proceed the segregation process in mitophagy.