Ovarian multi-omics analysis reveals key rate-limiting enzymes FASN, SCD5, FADS1, 3BHSD, and STAR as potential targets for regulating kidding traits in goats.

The kidding traits of goats are an important index of production. However, the molecular regulatory mechanisms of kidding traits in goats have not been fully elucidated. This study aimed to investigate the molecular regulatory network of kidding traits in goats. Multi-omics revealed the enrichment of 10 signaling pathways, with fatty acid biosynthesis, biosynthesis of unsaturated fatty acids, and steroid hormone biosynthesis pathways being closely related to reproduction. Interestingly, the key rate-limiting enzymes, fatty acid synthase (FASN), stearoyl-CoA desaturase 5 (SCD5), fatty acid desaturase 1 (FADS1), 3ß-hydroxysteroid dehydrogenase/isomerase (3BHSD), and steroidogenic acute regulatory protein (STAR) enriched in these pathways regulate changes in reproduction-related metabolites. In interference experiments, it was observed that suppressing these key rate-limiting enzymes inhibited the expression of CYP19A1, ESR2, and FSHR. Furthermore, interference inhibited granulosa cell proliferation, caused cell cycle arrest, and promoted apoptosis. Thus, these results suggest that the specific markers of nanny goats with multiple kids are the key rate-limiting enzymes FASN, SCD5, FADS1, 3BHSD, and STAR. These findings may greatly enhance the understanding of regulatory mechanisms that govern goat parturition.

Diagnostic performance of metagenomic sequencing in patients with suspected infection: a large-scale retrospective study.

Background: Metagenomic next-generation sequencing (mNGS) has been widely reported to identify pathogens in infectious diseases (IDs). In this work, we intended to investigate the diagnostic value and clinical acceptance of paired-samples mNGS as compared to the culture method. Methods: A total of 361 patients with suspected infection were retrospectively included. With reference to the clinical diagnosis, we compared the diagnostic performance and clinical acceptance in pathogen detection between mNGS and culture tests. Moreover, the pathogen concordance of paired blood and respiratory tract (RT) samples in mNGS assay was investigated. Results: Among 511 samples, 62.04% were shown to be pathogen positive by mNGS, and that for clinical diagnosis was 51.86% (265/511). When compared to culture assay (n = 428), mNGS had a significantly higher positivity rate (51.87% vs. 33.18%). With reference to the clinical diagnosis, the sensitivity of mNGS outperformed that of culture (89.08% vs. 56.72%). Importantly, mNGS exhibited a clinically accepted rate significantly superior to that of culture. In addition, the mNGS result from 53 paired blood and RT samples showed that most pairs were pathogen positive by both blood and RT, with pathogens largely being partially matched. Conclusion: Through this large-scale study, we further illustrated that mNGS had a clinically accepted rate and sensitivity superior to those of the traditional culture method in diagnosing infections. Moreover, blood and paired RT samples mostly shared partial-matched positive pathogens, especially for pathogens with abundant read numbers in RT, indicating that both blood and RT mNGS can aid the identification of pathogens for respiratory system infection.

A hierarchical ubiquitination-mediated regulatory module controls bamboo lignin biosynthesis.

The lignocellulosic feedstock of woody bamboo shows promising potential as an alternative to conventional wood, attributed to its excellent properties. The content and distribution of lignin serve as the foundation of these properties. While the regulation of lignin biosynthesis in bamboo has been extensively studied at the transcriptional level, its posttranslational control has remained poorly understood. This study provides a ubiquitinome dataset for moso bamboo (Phyllostachys edulis), identifying 13015 ubiquitinated sites in 4849 unique proteins. We further identified Kelch repeat F-boxprotein 9 (PeKFB9) that plays a negative role in lignin biosynthesis. Heterologous expression of PeKFB9 resulted in reduced accumulation of lignin and decreased phenylalanine ammonia-lyase (PAL) activities. Both in vitro and in vivo assays identified interaction between PeKFB9 and PePAL10. Further examination revealed that SCFPeKFB9 mediated the ubiquitination and degradation of PePAL10 via the 26S proteasome pathway. Moreover, PebZIP28667 could bind to the PePAL10 promoter to significantly inhibit its transcription, and ubiquitination of PebZIP28667 weakened this inhibition. Collectively, our findings reveal a PeKFB9-PePAL10/PebZIP28667-PePAL10 module that acts as a negative regulator of lignin biosynthesis. This study advances our understanding of posttranslational regulation in plant lignification, which will facilitate the improvement of the properties of bamboo wood and the breeding of varieties.

Sub-THz High Spin Precession Frequency in van der Waals Ferromagnet Fe3GaTe2.

The 2D magnet Fe3GaTe2 has received considerable attention for its high Curie temperature (TC), robust intrinsic ferromagnetism, and significant perpendicular magnetic anisotropy (PMA). In this study, the dynamic magnetic properties of Fe3GaTe2 are systematically investigated using an all-optical pump-probe technique. We find that the spin precession frequency (f) is as high as 351.2 GHz at T = 10 K under a field of H = 70 kOe. However, it decreases to 242.8 GHz at 300 K, mainly due to the reduced effective PMA field (Hkeff). The Gilbert damping factor (α) is modest, which increases from 0.039 (10 K) to 0.075 (300 K) owing to the enhanced scattering rate. Interestingly, when Fe3GaTe2 is coupled with 2 nm of Co, the Hkeff, f, and α just decrease slightly, highlighting the dominant influence of Fe3GaTe2. These findings substantially deepen our understanding of Fe3GaTe2, promoting the development of spintronic devices based on advanced 2D magnetic materials.

Crowd-sourced machine learning prediction of long COVID using data from the National COVID Cohort Collaborative.

BACKGROUND: While many patients seem to recover from SARS-CoV-2 infections, many patients report experiencing SARS-CoV-2 symptoms for weeks or months after their acute COVID-19 ends, even developing new symptoms weeks after infection. These long-term effects are called post-acute sequelae of SARS-CoV-2 (PASC) or, more commonly, Long COVID. The overall prevalence of Long COVID is currently unknown, and tools are needed to help identify patients at risk for developing long COVID. METHODS: A working group of the Rapid Acceleration of Diagnostics-radical (RADx-rad) program, comprised of individuals from various NIH institutes and centers, in collaboration with REsearching COVID to Enhance Recovery (RECOVER) developed and organized the Long COVID Computational Challenge (L3C), a community challenge aimed at incentivizing the broader scientific community to develop interpretable and accurate methods for identifying patients at risk of developing Long COVID. From August 2022 to December 2022, participants developed Long COVID risk prediction algorithms using the National COVID Cohort Collaborative (N3C) data enclave, a harmonized data repository from over 75 healthcare institutions from across the United States (U.S.). FINDINGS: Over the course of the challenge, 74 teams designed and built 35 Long COVID prediction models using the N3C data enclave. The top 10 teams all scored above a 0.80 Area Under the Receiver Operator Curve (AUROC) with the highest scoring model achieving a mean AUROC of 0.895. Included in the top submission was a visualization dashboard that built timelines for each patient, updating the risk of a patient developing Long COVID in response to clinical events. INTERPRETATION: As a result of L3C, federal reviewers identified multiple machine learning models that can be used to identify patients at risk for developing Long COVID. Many of the teams used approaches in their submissions which can be applied to future clinical prediction questions. FUNDING: Research reported in this RADx® Rad publication was supported by the National Institutes of Health. Timothy Bergquist, Johanna Loomba, and Emily Pfaff were supported by Axle Subcontract: NCATS-STSS-P00438.

Neuron-derived Netrin-1 deficiency aggravates spinal cord injury through activating the NF-κB signaling pathway.

Netrin-1 (NTN1) is involved in psychological alterations caused by central nerve system diseases. The primary objective of this research was to investigate whether a deficiency of neuron-derived NTN1 in the remote brain regions affects SCI outcomes. To examine the roles and mechanisms of neuron-derived NTN1 during SCI, Western blots, Nissl staining, immunochemical technique, RNA-sequence, and related behavioral tests were conducted in the study. Our study revealed that mice lacking NTN1 exhibited normal morphological structure of the spinal cords, hippocampus, and neurological function. While neuron-derived NTN1deletion mechanistically disrupted neuronal regeneration and aggregates neuronal apoptosis and ferroptosis in the intermediate phase following SCI. Additionally, neuroinflammation was significantly enhanced in the early phase, which could be related to activation of the NF-κB signaling pathway. Overall, our findings indicate that the deletion of neuron-derived NTN1 leads to the activation of the NF-κB pathway, contributing to the promotion of neuronal apoptosis and ferroptosis, and the pathological progression of SCI.

Methods to Monitor Nucleophagy in Yeast.

The selective degradation of nuclear components via autophagy, termed nucleophagy, is an essential process observed from yeasts to mammals and crucial for maintaining nucleus homeostasis and regulating nucleus functions. In the budding yeast Saccharomyces cerevisiae, nucleophagy occurs in two different manners: one involves autophagosome formation for the sequestration and vacuolar transport of nucleus-derived vesicles (NDVs), and the other proceeds with the invagination of the vacuolar membrane for the uptake of NDVs into the vacuole, termed macronucleophagy and micronucleophagy, respectively. This chapter describes methods to analyze and quantify activities of these nucleophagy pathways in yeast.

DISCRET: Synthesizing Faithful Explanations For Treatment Effect Estimation.

Designing faithful yet accurate AI models is challenging, particularly in the field of individual treatment effect estimation (ITE). ITE prediction models deployed in critical settings such as healthcare should ideally be (i) accurate, and (ii) provide faithful explanations. However, current solutions are inadequate: state-of-the-art black-box models do not supply explanations, post-hoc explainers for black-box models lack faithfulness guarantees, and self-interpretable models greatly compromise accuracy. To address these issues, we propose DISCRET, a self-interpretable ITE framework that synthesizes faithful, rule-based explanations for each sample. A key insight behind DISCRET is that explanations can serve dually as database queries to identify similar subgroups of samples. We provide a novel RL algorithm to efficiently synthesize these explanations from a large search space. We evaluate DISCRET on diverse tasks involving tabular, image, and text data. DISCRET outperforms the best self-interpretable models and has accuracy comparable to the best black-box models while providing faithful explanations. DISCRET is available at https://github.com/wuyinjun-1993/DISCRET-ICML2024.

Microneedles-Based Theranostic Platform: From the Past to the Future.

Fully integrated theranostic devices are highly esteemed in clinical applications, offering immense potential in real-time disease monitoring and personalized care. Microneedles (MNs), as innovative and wearable devices, boast important advantages in biosensing and therapy, thus holding significant promise in the advancement of diagnostic and therapeutic platforms. Encouragingly, advancements in electrochemical sensing technology, micronano fabrication, and biocompatible materials are propelling momentum for MNs-based closed-loop systems, enhancing detection capabilities, biocompatibility, and cost-effectiveness. Moreover, the notable progress in integrating MN chips with other biochips signifies a frontier for growth. Successful clinical trials in target molecule monitoring and drug delivery domains herald excellent clinical translational prospects for the aforementioned theranostic platform. Finally, we delineate both challenges and opportunities in the development of integrated diagnostic and therapeutic MN systems, including continuous monitoring, intelligent control algorithms, safety, and regulatory considerations.

Anisotropic phonon dynamics in Dirac semimetal PtTe2 thin films enabled by helicity-dependent ultrafast light excitation.

Coherent phonons have aroused considerable attention in condensed matter physics owing to their extraordinary capacity of reflecting and controlling the physical properties of matter. However, the investigation on the interaction between coherent phonons and other microscopic particles on the ultrafast timescale within topological systems continues to be an active and unresolved area. Here, we show the energy transfer of coherent optical phonons (COP) in Dirac semimetal PtTe2 thin films using ultrafast optical pump-probe spectroscopy. Specifically, the helicity-dependent light-driven anisotropic COP signals disclose their direct connection with the light-excited anisotropic spin-polarized electrons via an angular momentum transfer. Furthermore, we observe the notable decreases in the COP oscillation frequency and the decay rate with increasing temperatures due to the anharmonic phonon-phonon scattering and electron-phonon scattering in the COP dissipation process, respectively. Our work paves the way for uncovering the coherent phonons in Dirac semimetals for the potential applications in optoelectronics and opto-spintronics.

A real-world multi-center RNA-seq benchmarking study using the Quartet and MAQC reference materials.

Translating RNA-seq into clinical diagnostics requires ensuring the reliability and cross-laboratory consistency of detecting clinically relevant subtle differential expressions, such as those between different disease subtypes or stages. As part of the Quartet project, we present an RNA-seq benchmarking study across 45 laboratories using the Quartet and MAQC reference samples spiked with ERCC controls. Based on multiple types of 'ground truth', we systematically assess the real-world RNA-seq performance and investigate the influencing factors involved in 26 experimental processes and 140 bioinformatics pipelines. Here we show greater inter-laboratory variations in detecting subtle differential expressions among the Quartet samples. Experimental factors including mRNA enrichment and strandedness, and each bioinformatics step, emerge as primary sources of variations in gene expression. We underscore the profound influence of experimental execution, and provide best practice recommendations for experimental designs, strategies for filtering low-expression genes, and the optimal gene annotation and analysis pipelines. In summary, this study lays the foundation for developing and quality control of RNA-seq for clinical diagnostic purposes.

Spinal histamine H4 receptor mediates chronic pruritus via p-ERK in acetone-ether-water (AEW)-induced dry skin mice.

Dry skin is common to many pruritic diseases and is difficult to improve with oral traditional antihistamines. Recently, increasing evidence indicated that histamine H4 receptor (H4R) plays an important role in the occurrence and development of pruritus. Extracellular signal-regulated kinase (ERK) phosphorylation activation in the spinal cord mediates histamine-induced acute and choric itch. However, whether the histamine H4 receptor regulates ERK activation in the dry skin itch remains unclear. In the study, we explore the role of the histamine H4 receptor and p-ERK in the spinal cord in a dry skin mouse model induced by acetone-ether-water (AEW). q-PCR, Western blot, pharmacology and immunofluorescence  were applied in the study. We established a dry skin itch model by repeated application of AEW on the nape of neck in mice. The AEW mice showed typically dry skin histological change and persistent spontaneous scratching behaviour. Histamine H4 receptor, instead of histamine H1 receptor, mediated spontaneous scratching behaviour in AEW mice. Moreover, c-Fos and p-ERK expression in the spinal cord neurons were increased and co-labelled with GRPR-positive neurons in AEW mice. Furthermore, H4R agonist 4-methyhistamine dihydrochloride (4-MH)induced itch. Both 4-MH-induced itch and the spontaneous itch in AEW mice were blocked by p-ERK inhibitor U0126. Finally, intrathecal H4R receptor antagonist JNJ7777120 inhibited spinal p-ERK expression in AEW mice. Our results indicated that spinal H4R mediates itch via ERK activation in the AEW-induced dry skin mice.

[Effects of"Grain for Green "on the Spatial Distribution of Soil Carbon and Nitrogen in Purple Hilly Area of China].

In order to remedy the lack of research on the effect of "Grain for Green" on soil carbon （C） and nitrogen （N） distribution on slope soil in purple hilly areas of Sichuan Basin, China, a study was conducted on a long-term observation site established in the Wanan small watershed of Yanting Agro-ecological Experimental Station of Purple Soil, Chinese Academy of Sciences. The morphology, content, and storage of C and N in soil at different slope positions of farmland and the artificial forests in rehabilitated land with a history of approximately 30 years were compared. Our results showed that "Grain for Green" significantly increased soil organic carbon （SOC） content and SOC stock in all soil layers. The SOC stock of the surface layer （0-20 cm） increased by 25.86 t·hm-2, and the annual SOC stocks ratio was 0.89 t·hm-2. Soil total nitrogen （TN） content increased slightly but only in the 0-20 cm soil layer. Compared with those in sloping farmland, the differences in available C and N nutrients such as soil nitrate N （NO3--N）, ammonia N （NH4+-N）, and dissolved organic C （DOC） in the whole soil profile （0-70 cm） were basically not significant （P > 0.05）. In addition, our research also found that slope position had significant effects on the contents of TN, SOC, NO3--N, NH4+-N, and DOC in farmland soil （P< 0.05）. The variation trend of soil NO3--N, NH4+-N, and DOC contents along the slope was as follows： upper slope < middle slope < lower slope, whereas the soil TN and SOC contents were highest in the lower slope, followed by the upper slope and middle slope. The position of the slope had a significant impact only on DOC content in forest soil, which increased along the slope. This research indicated that when evaluating the impact of land use changes on soil C and N stocks in the purple soil hilly region, the influence of topographic factors cannot be ignored.

Synthesis of constrained bicycloalkanes through bibase-promoted brook rearrangement/radical-polar crossover cyclization.

Highly constrained bicyclic scaffolds are ubiquitous and attracting increasing interest in pharmaceutical and biotechnology discoveries owing to the enhanced activities. Herein, we report a protocol to access highly substituted constrained bicycloalkanes from readily accessible α-silyl alcohols and olefins through a bibase-promoted Brook rearrangement/radical-polar crossover cyclization (RPCC) process. Of note, the practical procedure features broad substrate scope and good group tolerance under mild and operationally simple conditions, using an inexpensive organic photocatalyst. Gram-scale preparation and diverse synthetic transformations demonstrate opportunities to rapidly construct molecular complexity. Mechanistic studies have indicated that the transformation involves a bibase-promoted radical transfer rearrangement addition/radical-polar crossover cyclization relay sequence, which differs from traditional solitary RPCC reactions.

The effects of sequencing strategies on Metagenomic pathogen detection using bronchoalveolar lavage fluid samples.

Objectives: Metagenomic next-generation sequencing (mNGS) is a powerful tool for pathogen detection. The accuracy depends on both wet lab and dry lab procedures. The objective of our study was to assess the influence of read length and dataset size on pathogen detection. Methods: In this study, 43 clinical BALF samples, which tested positive via clinical mNGS and were consistent with the diagnosis, were subjected to re-sequencing on the Illumina NovaSeq 6000 platform. The raw re-sequencing data, consisting of 100 million (M) paired-end 150 bp (PE150) reads, were divided into simulated datasets with eight different data sizes (5 M, 10 M, 15 M, 20 M, 30 M, 50 M, 75 M, 100 M) and five different read lengths (single-end 50 bp (SE50), SE75, SE100, PE100, and PE150). Both Kraken2 and IDseq bioinformatics pipelines were employed to analyze the previously diagnosed pathogens in the simulated data. Detection of pathogens was based on read counts ranging from 1 to 10 and RPM values ranging from 0.2 to 2. Results: Our results revealed that increasing dataset sizes and read lengths can enhance the performance of mNGS in pathogen detection. However, a larger data sizes for mNGS require higher economic costs and longer turnaround time for data analysis. Our findings indicate 20 M reads being sufficient for SE75 mode to achieve high recall rates. Additionally, high nucleic acid loads in samples can lead to increased stability in pathogen detection efficiency, reducing the impact of sequencing strategies. The choice of bioinformatics pipelines had a significant impact on recall rates achieved in pathogen detection. Conclusions: Increasing dataset sizes and read lengths can enhance the performance of mNGS in pathogen detection but increase the economic and time costs of sequencing and data analysis. Currently, the 20 M reads in SE75 mode may be the best sequencing option.

Prognostic Factors and Survival Outcomes in Squamous Cell Carcinoma of the Thyroid: A Surveillance, Epidemiology, and End Results (SEER) Database Analysis.

Introduction Squamous cell carcinoma of the thyroid (SCCT) is a rare, aggressive thyroid cancer distinguished by the emergence of squamous cells due to chronic inflammation or metaplasia. It poses diagnostic and therapeutic challenges, often identified at an advanced stage with a poor prognosis. The rarity of SCCT underscores the necessity for advanced research on effective treatments and diagnostic strategies. The current data utilized the Surveillance, Epidemiology, and End Results (SEER) database to determine the characteristics and outcomes of patients with primary SCCT. Methods De-identified data from patients with primary SCCT from 2000 to 2020 were collected using the SEER database. Demographic data, including age, sex, race, income, and housing, and clinical data including tumor size, tumor stage, nodal status, metastases, treatment modality, survival, and the patient's status, were extracted. Exclusion criteria were patients with unknown outcomes and missing death certificates. A detailed comparison of the two patient cohorts and univariate and multivariate Cox proportional hazard regression survival analyses were conducted. Results Among the 159 primary SCCT patients, the median age was 71 ± 21 years, with 83 females (52.2%) and 76 males (47.8%). The median overall follow-up was 6.0 years (4.41-7.59). The majority were White (108, 67.9%), followed by Hispanic (19, 11.9%). The five-year overall survival (OS) of the study group was 17.6% (95% CI = 14.5-20.7). The five-year disease-specific survival (DSS) was 37.6% (95% CI = 32.7-42.5). There was no significant difference based on surgery, chemotherapy, or radiation (p = 0.134). Age, tumor stage, nodal status, and distant metastases were negative prognostic factors. Sex, race, income, and housing were not predictive of survival. Conclusion The current study on SCCT highlights a low five-year OS rate of 17.6% and a DSS rate of 37.6%, with no significant difference in survival based on surgery, chemotherapy, or radiation. The negative prognostic factors included age, tumor stage, nodal status, and distant metastases, whereas sex, race, income, and housing did not significantly predict survival outcomes. These findings underscore the critical need for early detection and the development of more effective treatment strategies to manage SCCT.

Cavernous Malformation From Cranial Nerves: A Systematic Review With a Novel Classification and Patient-Level Analysis.

BACKGROUND AND OBJECTIVES: Cavernous malformations (CMs) occurring in the cranial nerve (CN) are extremely rare, and there is currently no comprehensive review on CN CMs, leading to a lack of sufficient understanding of CN CMs. We aimed to systematically review all published CN CM cases; summarize the epidemiology, clinical manifestations, treatment, and prognosis of CN CMs; and identify factors influencing the prognosis of CN CMs. METHODS: This systematic review identified all cases potentially diagnosed with CN CM through a systematic search of PubMed, SCOPUS, Web of Science, and Cochrane databases. This represents the most comprehensive systematic review to date. We classified CN CMs based on their anatomic origins. Patient characteristics, disease manifestations, treatment approaches, and prognosis were summarized descriptively. Further analysis was conducted to identify factors influencing the prognosis of CN CMs. RESULTS: The final analysis included 108 articles (127 individual patient cases). The optic nerve (49/128, 38.3%) is the most commonly affected nerve. Notably, CN CMs can be categorized into 3 types: Intraneural, Perineural, and Extraneural. Preoperative nerve function status and novel classification were associated with the prognosis of CN CMs (P = .001; P < .001). The postoperative neurological deterioration rate for the Intraneural type was 19/37 (51.4%); for the Extraneural type, it was 13/69 (18.8%); and for the Perineural type, it was 1/22 (4.5%) (P < .001). CONCLUSION: We reviewed all the published CN CMs to date, offering a comprehensive description of CN CMs for the first time and identifying prognostic factors. The classification of CN CMs proposed in this study could serve as guidance for the selection of intraoperative treatment regimens. The findings of this systematic review are expected to provide a foundation for clinical decision-making in this crucial rare disease and lay the groundwork for developing relevant clinical guidelines.

[Impact of Land Use Change on Carbon Storage in Urban Agglomerations in the Guanzhong Plain].

It is important to study the impact of land use change on terrestrial ecosystem carbon stocks in urban agglomerations for the optimization of land use structure and sustainable development in urban agglomerations. Based on the patch-generating land use simulation (PLUS) model and integrated valuation of ecosystem services and trade-offs (InVEST) model, a simulation was developed that predicted the land use change and carbon stock of the Guanzhong Plain urban agglomeration in 2040 under different scenarios and further analyzed the impact of land use change on carbon stock. The results showed that:① The land use types of the Guanzhong Plain urban agglomeration were mainly cultivated land, forest land, and grassland, which accounted for more than 90 % of the total study area. ② From 2000 to 2020, the carbon stock in the Guanzhong Plain showed a continuous downward trend, with cropland, woodland, and grassland being the main sources of carbon stock in the Guanzhong Plain, and the overall carbon stock declined by 15.12×106 t, with the spatial distribution presenting the distribution characteristics of "high in the north and south and low in the middle." ③ By 2040, the carbon stock would decrease the most under the urban development scenario, with a total reduction of 27.08×106 t, and the least under the ecological development scenario, with a total reduction of 4.14×106t. The research results can provide data support for the high-quality development and rational land use planning of the Guanzhong Plain urban agglomeration.

Attenuation of osteoarthritis progression via locoregional delivery of Klotho-expressing plasmid DNA and Tanshinon IIA through a stem cell-homing hydrogel.

BACKGROUND: Osteoarthritis (OA) is an aging-related degenerative joint disorder marked by joint discomfort and rigidity. Senescent chondrocytes release pro-inflammatory cytokines and extracellular matrix-degrading proteins, creating an inflammatory microenvironment that hinders chondrogenesis and accelerates matrix degradation. Targeting of senescent chondrocytes may be a promising approach for the treatment of OA. Herein, we describe the engineering of an injectable peptide-hydrogel conjugating a stem cell-homing peptide PFSSTKT for carrying plasmid DNA-laden nanoparticles and Tanshinon IIA (pPNP + TIIA@PFS) that was designed to attenuate OA progression by improving the senescent microenvironment and fostering cartilage regeneration. RESULTS: Specifically, pPNP + TIIA@PFS elevates the concentration of the anti-aging protein Klotho and blocks the transmission of senescence signals to adjacent healthy chondrocytes, significantly mitigating chondrocyte senescence and enhancing cartilage integrity. Additionally, pPNP + TIIA@PFS recruit bone mesenchymal stem cells and directs their subsequent differentiation into chondrocytes, achieving satisfactory chondrogenesis. In surgically induced OA model rats, the application of pPNP + TIIA@PFS results in reduced osteophyte formation and attenuation of articular cartilage degeneration. CONCLUSIONS: Overall, this study introduces a novel approach for the alleviation of OA progression, offering a foundation for potential clinical translation in OA therapy.

In-situ sonochemical formation of N-graphyne modulated porous g-C3N4 for boosted photocatalysis degradation of pollutants and nitrogen fixation.

Herein, Nitrogen-doped graphyne/porous g-C3N4 composites are firstly in-situ synthesized via the ultrasound vibration of CaC2, triazine, and porous g-C3N4 in absolute ethanol. A variety of characterizations are performed to investigate the morphology, microstructure, composition, and electrical/optical features of the obtained composites, such as transmission electron microscopy, scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectra, X-ray photoelectron spectroscopy, and so forth. It is found that N-doped graphyne with flexible folds lamellar structure is intimately attached to flake g-C3N4 in the as-prepared composites. An enlargement of 1.68 and 1.44 folds for the photocatalytic degradation of levofloxacin, rhodamine B, Methylene blue, and Tetracycline is realized by N-doped graphyne/g-C3N4 in comparison with that of pristine g-C3N4, respectively. In addition, the highest NH3 production rate attains 1.71 mmol⋅gcat-1⋅h-1 for N-doped graphyne/g-C3N4, which is 5.89 times larger than that of g-C3N4 (0.29 mmol⋅gcat-1⋅h-1). The improved mechanism of photocatalysis including higher photo-response and carrier separation rate is verified by transient photo-current, transient photo-potential, Mott-Schottky plots, Tafel plots, electrochemical impedance spectroscopy, turn-over frequency, photoluminescence spectra, and UV-vis diffuse absorption spectra, etc. Overall, the current study shows that N-doped graphyne synthesized from CaC2 and triazine is a useful decoration to modulate the photocatalytic features of g-C3N4, which can also be widely extended for in-situ modification of other photocatalysts.