Trophoblastic signals facilitate endometrial interferon response and lipid metabolism, ensuring normal decidualization.

The decidua plays a crucial role in providing structural and trophic support to the developing conceptus before placentation. Following embryo attachment, embryonic components intimately interact with the decidual tissue. While evidence indicates the participation of embryo-derived factors in crosstalk with the uterus, the extent of their impact on post-implantation decidual development requires further investigation. Here, we utilize transgenic mouse models to selectively eliminate primary trophoblast giant cells (pTGCs), the embryonic cells that interface with maternal tissue at the forefront. pTGC ablation impairs decidualization and compromises decidual interferon response and lipid metabolism. Mechanistically, pTGCs release factors such as interferon kappa (IFNK) to strengthen the decidual interferon response and lipoprotein lipase (LPL) to enhance lipid accumulation within the decidua, thereby promoting decidualization. This study presents genetic and metabolomic evidence reinforcing the proactive role of pTGC-derived factors in mobilizing maternal resources to strengthen decidualization, facilitating the normal progression of early pregnancy.

Enhancing Transcriptome Mapping with Rapid PRO-seq Profiling of Nascent RNA.

Precision nuclear run-on (PRO) sequencing (PRO-seq) is a powerful technique for mapping polymerase active sites with nucleotide resolution and measuring newly synthesized transcripts at both promoters and enhancer elements. The current PRO-seq protocol is time-intensive, technically challenging, and requires a large amount of starting material. To overcome these limitations, we developed rapid PRO-seq (rPRO-seq) which utilizes pre-adenylated single-stranded DNAs (AppDNA), a dimer blocking oligonucleotide (DBO), on-bead 5' RNA end repair, and column-based purification. These modifications enabled efficient transcriptome mapping within a single day (∼12 hours) increasing ligation efficiency, abolished adapter dimers, and reduced sample loss and RNA degradation. We demonstrate the reproducibility of rPRO-seq in measuring polymerases at promoters, gene bodies, and enhancers as compared to original PRO-seq protocols. Additionally, rPRO-seq is scalable, allowing for transcriptome mapping with as little as 25,000 cells. We apply rPRO-seq to study the role of Integrator in mouse hematopoietic stem and progenitor cell (mHSPC) homeostasis, identifying Ints11 as an essential component of transcriptional regulation and RNA processing in mHSPC homeostasis. Overall, rPRO-seq represents a significant advance in the field of nascent transcript analyses and will be a valuable tool for generating patient-specific genome-wide transcription profiles with minimal sample requirements.

pH responsive fabrication of PVA-stabilized selenium nano formulation encapsulated with luteolin to reduce diabetic ureteral injury by decreasing NLRP3 inflammasome via Nrf2/ARE signaling.

Diabetic ureteral injury (DUI) is a condition characterized by damage to the ureter, causing functional and morphological changes in the urinary system, which have a significant impact on a quality of life and requires appropriate medical treatment. The present study describes to novel design of luteolin (LT), a type of natural flavonoid, encapsulated selenium nanoparticles (Se NPs) to attain therapeutic potential for DUI. The physico-chemical characterizations of prepared Se NPs have benefitted zeta potential (-18 mV) and particle size (10-50 nm). In vitro assays were demonstrated the potential of LT-SeNPs by HEK 293 cells stimulated by STZ for DUI. Cytotoxicity assays on HEK 293 and NIH-3T3 showed >90% cell viability, which demonstrates the suitability of the nanoformulation for DUI treatment. The LT-SeNPs significantly inhibits the NLRP3 inflammasome through Nrf2/ARE pathway, which benefits for DUI treatment. The developed LT-SeNPs could be an effective formulation for the DUI therapy.

Understanding the multi-functionality and tissue-specificity of decellularized dental pulp matrix hydrogels for endodontic regeneration.

Dental pulp is the only soft tissue in the tooth which plays a crucial role in maintaining intrinsic multi-functional behaviors of the dentin-pulp complex. Nevertheless, the restoration of fully functional pulps after pulpitis or pulp necrosis, termed endodontic regeneration, remained a major challenge for decades. Therefore, a bioactive and in-situ injectable biomaterial is highly desired for tissue-engineered pulp regeneration. Herein, a decellularized matrix hydrogel derived from porcine dental pulps (pDDPM-G) was prepared and characterized through systematic comparison against the porcine decellularized nerve matrix hydrogel (pDNM-G). The pDDPM-G not only exhibited superior capabilities in facilitating multi-directional differentiation of dental pulp stem cells (DPSCs) during 3D culture, but also promoted regeneration of pulp-like tissues after DPSCs encapsulation and transplantation. Further comparative proteomic and transcriptome analyses revealed the differential compositions and potential mechanisms that endow the pDDPM-G with highly tissue-specific properties. Finally, it was realized that the abundant tenascin C (TNC) in pDDPM served as key factor responsible for the activation of Notch signaling cascades and promoted DPSCs odontoblastic differentiation. Overall, it is believed that pDDPM-G is a sort of multi-functional and tissue-specific hydrogel-based material that holds great promise in endodontic regeneration and clinical translation. STATEMENT OF SIGNIFICANCE: Functional hydrogel-based biomaterials are highly desirable for endodontic regeneration treatments. Decellularized extracellular matrix (dECM) preserves most extracellular matrix components of its native tissue, exhibiting unique advantages in promoting tissue regeneration and functional restoration. In this study, we prepared a porcine dental pulp-derived dECM hydrogel (pDDPM-G), which exhibited superior performance in promoting odontogenesis, angiogenesis, and neurogenesis of the regenerating pulp-like tissue, further showed its tissue-specificity compared to the peripheral nerve-derived dECM hydrogel. In-depth proteomic and transcriptomic analyses revealed that the activation of tenascin C-Notch axis played an important role in facilitating odontogenic regeneration. This biomaterial-based study validated the great potential of the dental pulp-specific pDDPM-G for clinical applications, and provides a springboard for research strategies in ECM-related regenerative medicine.

Impact of HbA1c control and type 2 diabetes mellitus exposure on the oral microbiome profile in the elderly population.

Objective: To investigate the associations of the oral microbiome status with diabetes characteristics in elderly patients with type 2 diabetes mellitus. Methods: A questionnaire was used to assess age, sex, smoking status, drinking status, flossing frequency, T2DM duration and complications, and a blood test was used to determine the glycated haemoglobin (HbA1c) level. Sequencing of the V3-V4 region of the 16S rRNA gene from saliva samples was used to analyze the oral microbiome. Results: Differential analysis revealed that Streptococcus and Weissella were significantly enriched in the late-stage group, and Capnocytophaga was significantly enriched in the early-stage group. Correlation analysis revealed that diabetes duration was positively correlated with the abundance of Streptococcus (r= 0.369, p= 0.007) and negatively correlated with the abundance of Cardiobacterium (r= -0.337, p= 0.014), and the level of HbA1c was not significantly correlated with the oral microbiome. Network analysis suggested that the poor control group had a more complex microbial network than the control group, a pattern that was similar for diabetes duration. In addition, Streptococcus has a low correlation with other microorganisms. Conclusion: In elderly individuals, Streptococcus emerges as a potential biomarker linked to diabetes, exhibiting elevated abundance in diabetic patients influenced by disease exposure and limited bacterial interactions.

High-Performance Reversible Solid Oxide Cells for Powering Electric Vehicles, Long-Term Energy Storage, and CO2 Conversion.

The rapid population growth coupled with rising global energy demand underscores the crucial importance of advancing intermittent renewable energy technologies and low-emission vehicles, which will be pivotal toward carbon neutralization. Reversible solid oxide cells (RSOCs) hold significant promise as a technology for high-efficiency power generation, long-term chemical energy storage, and CO2 conversion. Herein, RSOCs were, for the first time, studied to power electric vehicles. Based on our experimental results, an ideal RSOC stack was established with reasonable assumptions. Subsequently, through analysis and comparison of important merits, such as power densities, energy densities, charging/refueling time, and fuel economy of RSOC-based electric vehicles (RSOCEVs), conventional internal combustor vehicles (ICEVs), and battery-based electric vehicles (BEVs), the advantages and prospects of RSOCEVs were highlighted. Our H2-H2O RSOCs exhibit high electrochemical performances in both fuel cell (peak power density = 1.6 W cm-2 at 750 °C) and electrolysis modes (current density = 2.0 A cm-2 at 1.3 V and 750 °C), along with durable reversible operation under a wide range of conditions. In CO-CO2, our RSOCs achieved excellent performance in fuel cell mode (peak power density = 0.68 cm-2 at 700 °C). Furthermore, a world record current density of 3.4 A cm-2 at 1.5 V and 750 °C was achieved in the CO2 electrolysis mode. Moreover, an assessment of the CO2 electrolysis efficiency was conducted, offering insights for establishing energy storage strategies and mitigating CO2 emissions. Therefore, the RSOC technology has the potential to assume a central role in a future energy system with abundant renewable power generation while mitigating the CO2 released from fossil fuels.

Rapid altitude displacement induce zebrafish appearing acute high altitude illness symptoms.

Rapid ascent to high-altitude areas above 2500 m often leads to acute high altitude illness (AHAI), posing significant health risks. Current models for AHAI research are limited in their ability to accurately simulate the high-altitude environment for drug screening. Addressing this gap, a novel static self-assembled water vacuum transparent chamber was developed to induce AHAI in zebrafish. This study identified 6000 m for 2 h as the optimal condition for AHAI induction in zebrafish. Under these conditions, notable behavioral changes including slow movement, abnormal exploration behavior and static behavior in the Novel tank test. Furthermore, this model demonstrated changes in oxidative stress-related markers included increased levels of malondialdehyde, decreased levels of glutathione, decreased activities of superoxide dismutase and catalase, and increased levels of inflammatory markers IL-6, IL-1ß and TNF-α, and inflammatory cell infiltration and mild edema in the gill tissue, mirroring the clinical pathophysiology observed in AHAI patients. This innovative zebrafish model not only offers a more accurate representation of the high-altitude environment but also provides a high-throughput platform for AHAI drug discovery and pathogenesis research.

Simultaneous Rapid Detection of Multiple Physicochemical Properties of Jet Fuel Using Near-Infrared Spectroscopy.

Jet fuel is the primary fuel used in the aviation industry, and its quality has a direct impact on the safety and operational efficiency of aircraft. The accurate quantitative detection and analysis of various physicochemical property indicators are important for improving and ensuring the quality of jet fuel in the domestic market. This study used near-infrared (NIR) spectroscopy to establish a suitable model for the simultaneous and rapid detection of multiple physicochemical properties in jet fuel. Using more than 40 different sources of jet fuel, a rapid detection model was established by optimizing the spectral processing methods. The measurement models were separately built using the partial least-squares (PLS) and orthogonal PLS algorithms, and the model parameters were optimized. The results show that after the Savitzky-Golay second derivative preprocessing, the PLS model built using the feature spectra selected by the uninformative variable elimination wavelength algorithm achieved the best measurement performance. Compared with the PLS model without preprocessing, the range of the resulting accuracy improvement was at least 15.01%. Under the optimal model parameters, the calibration set regression coefficient (Rc2) of the 11 jet fuel property index models ranged from 0.9102 to 0.9763, with the root-mean-square error of calibration values up to 0.8468 °C (for flash points). The regression coefficient (Rp2) of the validation set ranged from 0.8239 to 0.9557, with the root-mean-square error of prediction values up to 1.1354 °C (for flash points). The ratios of prediction to deviation (RPD) values were all in the range of 1.9-3.0, indicating high accuracy and reliability of the model. The rapid NIR analysis method established in this study enables the simultaneous and rapid detection of multiple physicochemical properties of jet fuel, thereby providing effective technical support for ensuring the quality of jet fuel in the market.

Redox-neutral α-functionalization of pyrrolidines: facile access to α-aryl-substituted pyrrolidines.

α-Aryl-substituted pyrrolidine moiety is found in many natural alkaloids. Starting from pyrrolidine, we were able to synthesize α-aryl-substituted pyrrolidines in one step using quinone monoacetal as the oxidizing agent and DABCO as the base. We also discovered the reaction condition needed to efficiently remove the N-aryl moiety from the α-arylated product. When the above reaction was carried out without the addition of an aryl nucleophile, the reaction of pyrrolidine and quinone monoacetal in 2,2,2-trifluoroethanol afforded octahydro-dipyrroloquinoline in high yield, which has the same skeleton as that of natural product incargranine B.

Analysis of blood methylation quantitative trait loci in East Asians reveals ancestry-specific impacts on complex traits.

Methylation quantitative trait loci (mQTLs) are essential for understanding the role of DNA methylation changes in genetic predisposition, yet they have not been fully characterized in East Asians (EAs). Here we identified mQTLs in whole blood from 3,523 Chinese individuals and replicated them in additional 1,858 Chinese individuals from two cohorts. Over 9% of mQTLs displayed specificity to EAs, facilitating the fine-mapping of EA-specific genetic associations, as shown for variants associated with height. Trans-mQTL hotspots revealed biological pathways contributing to EA-specific genetic associations, including an ERG-mediated 233 trans-mCpG network, implicated in hematopoietic cell differentiation, which likely reflects binding efficiency modulation of the ERG protein complex. More than 90% of mQTLs were shared between different blood cell lineages, with a smaller fraction of lineage-specific mQTLs displaying preferential hypomethylation in the respective lineages. Our study provides new insights into the mQTL landscape across genetic ancestries and their downstream effects on cellular processes and diseases/traits.

Cross-link assisted spatial proteomics to map sub-organelle proteomes and membrane protein topologies.

The functions of cellular organelles and sub-compartments depend on their protein content, which can be characterized by spatial proteomics approaches. However, many spatial proteomics methods are limited in their ability to resolve organellar sub-compartments, profile multiple sub-compartments in parallel, and/or characterize membrane-associated proteomes. Here, we develop a cross-link assisted spatial proteomics (CLASP) strategy that addresses these shortcomings. Using human mitochondria as a model system, we show that CLASP can elucidate spatial proteomes of all mitochondrial sub-compartments and provide topological insight into the mitochondrial membrane proteome. Biochemical and imaging-based follow-up studies confirm that CLASP allows discovering mitochondria-associated proteins and revising previous protein sub-compartment localization and membrane topology data. We also validate the CLASP concept in synaptic vesicles, demonstrating its applicability to different sub-cellular compartments. This study extends the scope of cross-linking mass spectrometry beyond protein structure and interaction analysis towards spatial proteomics, and establishes a method for concomitant profiling of sub-organelle and membrane proteomes.

Current examining methods and mathematical models of horizontal transfer of antibiotic resistance genes in the environment.

The increasing prevalence of antibiotic resistance genes (ARGs) in the environment has garnered significant attention due to their health risk to human beings. Horizontal gene transfer (HGT) is considered as an important way for ARG dissemination. There are four general routes of HGT, including conjugation, transformation, transduction and vesiduction. Selection of appropriate examining methods is crucial for comprehensively understanding characteristics and mechanisms of different HGT ways. Moreover, combined with the results obtained from different experimental methods, mathematical models could be established and serve as a powerful tool for predicting ARG transfer dynamics and frequencies. However, current reviews of HGT for ARG spread mainly focus on its influencing factors and mechanisms, overlooking the important roles of examining methods and models. This review, therefore, delineated four pathways of HGT, summarized the strengths and limitations of current examining methods, and provided a comprehensive summing-up of mathematical models pertaining to three main HGT ways of conjugation, transformation and transduction. Finally, deficiencies in current studies were discussed, and proposed the future perspectives to better understand and assess the risks of ARG dissemination through HGT.

Extensive protein pyrophosphorylation revealed in human cell lines.

Reversible protein phosphorylation is a central signaling mechanism in eukaryotes. Although mass-spectrometry-based phosphoproteomics has become routine, identification of non-canonical phosphorylation has remained a challenge. Here we report a tailored workflow to detect and reliably assign protein pyrophosphorylation in two human cell lines, providing, to our knowledge, the first direct evidence of endogenous protein pyrophosphorylation. We manually validated 148 pyrophosphosites across 71 human proteins, the most heavily pyrophosphorylated of which were the nucleolar proteins NOLC1 and TCOF1. Detection was consistent with previous biochemical evidence relating the installation of the modification to inositol pyrophosphates (PP-InsPs). When the biosynthesis of PP-InsPs was perturbed, proteins expressed in this background exhibited no signs of pyrophosphorylation. Disruption of PP-InsP biosynthesis also significantly reduced rDNA transcription, potentially by lowering pyrophosphorylation on regulatory proteins NOLC1, TCOF1 and UBF1. Overall, protein pyrophosphorylation emerges as an archetype of non-canonical phosphorylation and should be considered in future phosphoproteomic analyses.

How enterprises' public welfare low-carbon behavior affects consumers' green purchase behavior.

The Chinese economy has undergone high-speed, high-quality growth, and the concept of low-carbon technology has gained popular support. Businesses and consumers must jointly endeavor to achieve low-carbon economic development. Moreover, it is important to investigate whether enterprises' low-carbon behavior is correlated with consumers' green consumption behavior. We built a theoretical model to depict the relationship between corporate public welfare low-carbon behavior, consumers' green purchase intention, and green purchase behavior. We then divided corporate public welfare low-carbon behavior into three dimensions. We proposed hypotheses, collected data through a questionnaire survey, and analyzed the data using statistical analysis software of SPSS 26.0 and AMOS 24.0. Public welfare low-carbon behavior was significantly correlated with consumers' green purchase intention, and public welfare low-carbon participation and public welfare low-carbon motivation were significantly correlated with green purchase intention. Finally, we proposed suggestions from three perspectives: the public welfare low-carbon mechanism, public welfare low-carbon participation, and public welfare low-carbon motivation. The results provide theoretical support for research methods related to the low-carbon growth of enterprises and green consumption, as well as guidance and decision-making support for enterprises in carrying out cause marketing.

Genome-wide screening identifies Trim33 as an essential regulator of dendritic cell differentiation.

The development of dendritic cells (DCs), including antigen-presenting conventional DCs (cDCs) and cytokine-producing plasmacytoid DCs (pDCs), is controlled by the growth factor Flt3 ligand (Flt3L) and its receptor Flt3. We genetically dissected Flt3L-driven DC differentiation using CRISPR-Cas9-based screening. Genome-wide screening identified multiple regulators of DC differentiation including subunits of TSC and GATOR1 complexes, which restricted progenitor growth but enabled DC differentiation by inhibiting mTOR signaling. An orthogonal screen identified the transcriptional repressor Trim33 (TIF-1γ) as a regulator of DC differentiation. Conditional targeting in vivo revealed an essential role of Trim33 in the development of all DCs, but not of monocytes or granulocytes. In particular, deletion of Trim33 caused rapid loss of DC progenitors, pDCs, and the cross-presenting cDC1 subset. Trim33-deficient Flt3+ progenitors up-regulated pro-inflammatory and macrophage-specific genes but failed to induce the DC differentiation program. Collectively, these data elucidate mechanisms that control Flt3L-driven differentiation of the entire DC lineage and identify Trim33 as its essential regulator.

Tyrosine phosphorylation of CARM1 promotes its enzymatic activity and alters its target specificity.

An important epigenetic component of tyrosine kinase signaling is the phosphorylation of histones, and epigenetic readers, writers, and erasers. Phosphorylation of protein arginine methyltransferases (PRMTs), have been shown to enhance and impair their enzymatic activity. In this study, we show that the hyperactivation of Janus kinase 2 (JAK2) by the V617F mutation phosphorylates tyrosine residues (Y149 and Y334) in coactivator-associated arginine methyltransferase 1 (CARM1), an important target in hematologic malignancies, increasing its methyltransferase activity and altering its target specificity. While non-phosphorylatable CARM1 methylates some established substrates (e.g. BAF155 and PABP1), only phospho-CARM1 methylates the RUNX1 transcription factor, on R223 and R319. Furthermore, cells expressing non-phosphorylatable CARM1 have impaired cell-cycle progression and increased apoptosis, compared to cells expressing phosphorylatable, wild-type CARM1, with reduced expression of genes associated with G2/M cell cycle progression and anti-apoptosis. The presence of the JAK2-V617F mutant kinase renders acute myeloid leukemia (AML) cells less sensitive to CARM1 inhibition, and we show that the dual targeting of JAK2 and CARM1 is more effective than monotherapy in AML cells expressing phospho-CARM1. Thus, the phosphorylation of CARM1 by hyperactivated JAK2 regulates its methyltransferase activity, helps select its substrates, and is required for the maximal proliferation of malignant myeloid cells.

Fe-Co heteronuclear atom pairs as catalytic sites for efficient oxygen electroreduction.

Single-site Fe-N-C catalysts are the most promising Pt-group catalyst alternatives for the oxygen reduction reaction, but their application is impeded by their relatively low activity and unsatisfactory stability as well as production costs. Here, cobalt atoms are introduced into an Fe-N-C catalyst to enhance its catalytic activity by utilizing the synergistic effect between Fe and Co atoms. Meanwhile, phenanthroline is employed as the ligand, which favours stable pyridinic N-coordinated Fe-Co sites. The obtained catalysts exhibit excellent ORR performance with a half-wave potential of 0.892 V and good stability under alkaline conditions. In addition, the excellent ORR activity and durability of FeCo-N-C enabled the constructed zinc-air battery to exhibit a high power density of 247.93 mW cm-2 and a high capacity of 768.59 mA h gZn-1. Moreover, the AEMFC based on FeCo-N-C also achieved a high open circuit voltage (0.95 V) and rated power density (444.7 mW cm-2), surpassing those of many currently reported transition metal-based cathodes. This work emphasizes the feasibility of this non-precious metal catalyst preparation strategy and its practical applicability in fuel cells and metal-air batteries.

Yeast TLDc domain proteins regulate assembly state and subcellular localization of the V-ATPase.

Yeast vacuoles perform crucial cellular functions as acidic degradative organelles, storage compartments, and signaling hubs. These functions are mediated by important protein complexes, including the vacuolar-type H+-ATPase (V-ATPase), responsible for organelle acidification. To gain a more detailed understanding of vacuole function, we performed cross-linking mass spectrometry on isolated vacuoles, detecting many known as well as novel protein-protein interactions. Among these, we identified the uncharacterized TLDc-domain-containing protein Rtc5 as a novel interactor of the V-ATPase. We further analyzed the influence of Rtc5 and of Oxr1, the only other yeast TLDc-domain-containing protein, on V-ATPase function. We find that both Rtc5 and Oxr1 promote the disassembly of the vacuolar V-ATPase in vivo, counteracting the role of the RAVE complex, a V-ATPase assembly chaperone. Furthermore, Oxr1 is necessary for the retention of a Golgi-specific subunit of the V-ATPase in this compartment. Collectively, our results shed light on the in vivo roles of yeast TLDc-domain proteins as regulators of the V-ATPase, highlighting the multifaceted regulation of this crucial protein complex.

Functional and esthetic reconstruction of composite lower lip defects with a motor-innervated chimeric facial artery buccinator myomucosal-submental island flap.

OBJECTIVE: This study aimed to assess the functional and esthetic outcomes of a chimeric innervated buccinator myomucosal-submental island flap (BMM-SIF) for large composite lower lip reconstruction. METHODS: This retrospective study included five patients who underwent lower lip tumor resection and BMM-SIF reconstruction at the Hospital of Stomatology, Sun Yat-sen University, between August 2021 and February 2023. Lip function was evaluated using water leakage, cheek puffing tests, and superficial electromyography. Lip appearance was observed using photographs and evaluated through subjective interviews. Donor-site conditions, including facial symmetry and mouth opening, were monitored. RESULTS: All the BMM-SIFs survived. Drooling was the main complication observed shortly after surgery. The water leakage test showed complete oral competence for liquid holding in the 7th month; however, moderate air leakage was present in two patients. Electromyography revealed myoelectric signals from the innervated buccinator at the recipient site. Facial expression and food intake were typically managed. The shape and projection of the vermilion were harmonious and satisfactory for each patient. Neither microstomia nor mouth opening limitation was observed, with an average inter-incisor distance of 37.25±4.4 mm. CONCLUSION: Chimeric motor-innervated BMM-SIF effectively reconstructed large full-thickness lower-lip defects with satisfactory functional and esthetic outcomes.