Modeling nitrogen removal performance based on novel microbial activity indicators in WWTP by machine learning and biological interpretation.

Modeling the pollutant removal performance of wastewater treatment plants (WWTPs) plays a crucial role in regulating their operation, mitigating effluent anomalies and reducing operating costs. Pollutants removal in WWTPs is closely related to microbial activity. However, there is extremely limited knowledge on the models accurately characterizing pollutants removal performance by microbial activity indicators. This study proposed a novel specific oxygen uptake rate (SOURATP) with adenosine triphosphate (ATP) as biomass. Firstly, it was found that SOURATP and total nitrogen (TN) removal rate showed similar fluctuated trends, and their correlation was stronger than that of TN removal rate and common SOURMLSS with mixed liquor suspended solids (MLSS) as biomass. Then, support vector regressor (SVR), K-nearest neighbor regressor (KNR), linear regressor (LR), and random forest (RF) models were developed to predict TN removal rate only with microbial activity as features. Models utilizing the novel SOURATP resulted in better performance than those based on SOURMLSS. A model fusion (MF) algorithm based on the above four models was proposed to enhance the accuracy with lower root mean square error (RMSE) of 2.25 mg/L/h and explained 75% of the variation in the test data with SOURATP as features as opposed to other base learners. Furthermore, the interpretation of predictive results was explored through microbial community structure and metabolic pathway. Strong correlations were found between SOURATP and the proportion of nitrifiers in aerobic pool, as well as between heterotrophic bacteria respiratory activity (SOURATP_HB) and the proportion of denitrifies in anoxic pool. SOURATP also displayed consistent positive responses with most key enzymes in Embden-Meyerhof-Parnas pathway (EMP), tricarboxylic acid cycle (TCA) and oxidative phosphorylation cycle. In this study, SOURATP provides a reliable indication of the composition and metabolic activity of nitrogen removal bacteria, revealing the potential reasons underlying the accurate predictive result of nitrogen removal rates based on novel microbial activity indicators. This study offers new insights for the prediction and further optimization operation of WWTPs from the perspective of microbial activity regulation.

Acute exposure of triclocarban affects early embryo development in mouse through disrupting maternal-to-zygotic transition and epigenetic modifications.

Triclocarban (TCC) is a broad-spectrum antibacterial agent used globally, and high concentrations of this harmful chemical exist in the environment. The human body is directly exposed to TCC through skin contact. Moreover, TCC is also absorbed through diet and inhaled through breathing, which results in its accumulation in the body. The safety profile of TCC and its potential impact on human health are still not completely clear; therefore, it becomes imperative to evaluate the reproductive toxicity of TCC. Here, we explored the effect of TCC on the early embryonic development of mice and its associated mechanisms. We found that acute exposure of TCC affected the early embryonic development of mice in a dose-dependent manner. Approximately 7600 differentially expressed genes (DEGs) were obtained by sequencing the transcriptome of 2-cell mouse embryos; of these, 3157 genes were upregulated and 4443 genes were downregulated in the TCC-treated embryos. GO and KEGG analysis revealed that the enriched genes were mainly involved in redox processes, RNA synthesis, DNA damage, apoptosis, mitochondria, endoplasmic reticulum, Golgi apparatus, cytoskeleton, peroxisome, RNA polymerase, and other components or processes. Moreover, the Venn analysis showed that the zygotic genome activation (ZGA) was affected and the degradation of maternal effector genes was inhibited. TCC induced changes in the epigenetic modification of 2-cell embryos. The level of DNA methylation increased significantly. Further, the levels of H3K27ac, H3K9ac, and H3K27me3 histone modifications decreased significantly, whereas those of H3K4me3 and H3K9me3 modifications increased significantly. Additionally, TCC induced oxidative stress and DNA damage in the 2-cell embryos. In conclusion, acute exposure of TCC affected early embryo development, destroyed early embryo gene expression, interfered with ZGA and maternal gene degradation, induced changes in epigenetic modification of early embryos, and led to oxidative stress and DNA damage in mouse early embryos.

Zinc pyrithione exposure compromises oocyte maturation through involving in spindle assembly and zinc accumulation.

Zinc Pyrithione (ZPT), a Food and Drug Administration (FDA) approved chemical, is widely used for topical antimicrobials and cosmetic consumer products, including anti-dandruff shampoos. ZPT and its degraded byproducts have detected in large quantities in the environment, and identified to pose healthy risks on aquatic organisms and human. However, so far, knowledge about ZPT effects on female reproduction, particularly oocyte maturation and quality, is limited. Herein, we investigated the adverse impact of ZPT on mouse oocyte maturation and quality in vitro and found exposure to ZPT significantly compromises oocyte maturation. The results revealed that ZPT disturbed the meiotic cell cycle by impairing cytoskeletal dynamics, kinetochore-microtubule attachment (K-MT), and causing spindle assembly checkpoints (SAC) continuous activation. Further, we observed the microtubule-organizing centers (MTOCs) associated proteins p-MAPK and Aurora-A were disrupted in ZPT-treated oocytes, signified by decreased expression and abnormal localization, responsible for the severe cytoskeletal defects. In addition, ZPT exposure induced a significant increase in the levels of H3K9me2, H3K9me3, H3K27me1, and H3K27me3, suggesting the alterations of epigenetic modifications. Moreover, the accumulation of zinc ions (Zn2+) was observed in ZPT-treated oocytes, which was detrimental because overmuch intracellular Zn2+ disrupted oocyte meiosis. Finally, these above alterations impaired spindle organization and chromosome alignment in metaphase-II (MII) oocytes, indicative of damaged oocytes quality. In conclusion, ZPT exposure influenced oocyte maturation and quality via involvement in MTOCs-associated proteins mediated spindle defects, altered epigenetic modifications and zinc accumulation.

Bisphenol F exposure affects mouse oocyte in vitro maturation through inducing oxidative stress and DNA damage.

Bisphenol F (BPF), a substitute for bisphenol A (BPA), is progressively used to manufacture various consumer products. Despite the established reproductive toxicity of BPF, the underlying mechanisms remain to elucidate. This in-vitro study deep in sighted the BPF toxicity on mouse oocyte meiotic maturation and quality. After treating oocytes with BPF (300 µM), the oocyte meiotic progression was blocked, accentuated by a reduced rate in the first polar body extrusion (PBE). Next, we illustrated that BPF induced α-tubulin hyper-acetylation disrupted the spindle assembly and chromosome alignment. Concurrently, BPF resulted in severe oxidative stress and DNA damage, which triggered the early apoptosis in mouse oocytes. Further, altered epigenetic modifications following BPF exposure were proved by increased H3K27me3 levels. Concerning the toxic effects on spindle structure, oxidative stress, and DNA damage in mouse oocytes, BPF toxicity was less severe to oocyte maturation and spindle structure than BPA and induced low oxidative stress. However, compared with BPA, oocytes treated with BPF were more prone to DNA damage, indicating not less intense or even more severe toxic effects of BPF than BPA on some aspects of oocytes maturation. In brief, the present study established that like wise to BPA, BPF could inhibit meiotic maturation and reduce oocyte quality, suggesting it is not a safe substitute for BPA.

Model construction and application for effluent prediction in wastewater treatment plant: Data processing method optimization and process parameters integration.

Wastewater treatment based on the activated sludge process is complex process, which is easily affected by influent quality, aeration time and other factors, leading to unstable effluent. Facing increasingly stringent sewage discharge standards in China, it is necessary to build a prediction model for early warning of effluent quality. In this study, nine machine learning algorithms were adopted to construct models for the prediction of effluent Chemical Oxygen Demand (COD). In order to improve the prediction accuracy of the models, model optimization was conducted by introducing the hysteresis condition [Hydraulic Retention Time (HRT) of 18 h], data processing method (K-FOLD) and process parameters [dissolved oxygen (DO), sludge return ratio (SRR) and mixed liquid suspended solids (MLSS)]. Results showed that both K-Nearest Neighbour (KNN) and Gradient Boosting Decision Tree (GBDT) displayed excellent prediction effects, the best results of MAPE, RMSE and R2 were 7.34%/1.29/0.92(COD, KNN). The optimized models were further applied to the prediction of effluent total phosphorus (TP), total nitrogen (TN) and pH. The MAPE/RMSE/R2 were 7.43%/0.92/0.93(TN, GBDT), 17.81%/0.19/0.99(TP, KNN), 0.53%/0.16/0.99 (pH, KNN) respectively, indicating high prediction accuracy. The change and comparison of modeling conditions provide a new insight to wastewater prediction models. In addition, this study is close to the actual application scenario of WWTPs operation and management, also laying a foundation for the reverse regulation of energy saving and consumption reduction of wastewater treatment plants (WWTPs).

The relationship between substrate topography and stem cell differentiation in the musculoskeletal system.

It is well known that biomaterial topography can exert a profound influence on various cellular functions such as migration, polarization, and adhesion. With the development and refinement of manufacturing technology, much research has recently been focused on substrate topography-induced cell differentiation, particularly in the field of tissue engineering. Even without biological and chemical stimuli, the differentiation of stem cells can also be initiated by various biomaterials with different topographic features. However, the underlying mechanisms of this biological phenomenon remain elusive. During the past few decades, many researchers have demonstrated that cells can sense the topography of materials through the assembly and polymerization of membrane proteins. Following the activation of RHO, TGF-b or FAK signaling pathways, cells can be induced into various differentiation states. But these signaling pathways often coincide with canonical mechanical transduction pathways, and no firm conclusion has been reached among researchers in this field on topography-specific signaling pathways. On the other hand, some substrate topographies are reported to have the ability to inhibit differentiation and maintain the 'stemness' of stem cells. In this review, we will summarize the role of topography in musculoskeletal system regeneration and explore possible topography-related signaling pathways involved in cell differentiation.

Small molecule therapeutics for inflammation-associated chronic musculoskeletal degenerative diseases: Past, present and future.

Inflammation-associated chronic musculoskeletal degenerative diseases (ICMDDs) like osteoarthritis and tendinopathy often results in morbidity and disability, with consequent heavy socio-economic burden. Current available therapies such as NSAIDs and glucocorticoid are palliative rather than disease-modifying. Insufficient systematic research data on disease molecular mechanism also makes it difficult to exploit valid therapeutic targets. Small molecules are designed to act on specific signaling pathways and/or mechanisms of cellular physiology and function, and have gradually shown potential for treating ICMDDs. In this review, we would examine and analyze recent developments in small molecule drugs for ICMDDs, suggest possible feasible improvements in treatment modalities, and discuss future research directions.

Unlocking the Design Paradigm of In-Plane Heterojunction with Built-in Bifunctional Anion Vacancy for Unexpectedly Fast Sodium Storage.

Transition metal chalcogenide (TMD) electrodes in sodium-ion batteries exhibit intrinsic shortcomings such as sluggish reaction kinetics, unstable conversion thermodynamics, and substantial volumetric strain effects, which lead to electrochemical failure. This report unlocks a design paradigm of VSe2- x /C in-plane heterojunction with built-in anion vacancy, achieved through an in situ functionalization and self-limited growth approach. Theoretical and experimental investigations reveal the bifunctional role of the Se vacancy in enhancing the ion diffusion kinetics and the structural thermodynamics of Nax VSe2 active phases. Moreover, this in-plane heterostructure facilitates complete face contact between the two components and tight interfacial conductive contact between the conversion phases, resulting in enhanced reaction reversibility. The VSe2- x /C heterojunction electrode exhibits remarkable sodium-ion storage performance, retaining specific capacities of 448.7 and 424.9 mAh g-1 after 1000 cycles at current densities of 5 and 10 A g-1 , respectively. Moreover, it exhibits a high specific capacity of 353.1 mAh g-1 even under the demanding condition of 100 A g-1 , surpassing most previous achievements. The proposed strategy can be extended to other V5 S8- x and V2 O5- x -based heterojunctions, marking a conceptual breakthrough in advanced electrode design for constructing high-performance sodium-ion batteries.

Findings on agricultural cleaner production in the three Gorges Reservoir Area.

The 'rural revitalization strategy' is important to achieve sustainable development in the Three Gorges Reservoir Area (TGRA), the largest reservoir in China, located in the poverty alleviation region of the Qinling-Daba mountains, and characterized as mountainous and hilly dominated by backwards resettlements. Pig farming around the reservoir area is a key industry, accounting for 0.90% of the arable land area in the country, while the annual pig market represents a 1.37% share of the national figure. Here, 12 study sites were investigated on-site for understanding agricultural green development in the TGRA. We found two main prevailing models: one of ecological circulation (EC), based on animal husbandry and recycling. Of the 12 site, six cases of the ecological circulation model relied on pig husbandry, combined with cropping (grains/fruits/vegetables) by eco-industrial chains, such as pig-biogas-fruit (grain/vegetables), to prevent environmental pollution, while promoting agricultural economic growth by recycling fecal residues and wastewater (FSW) from pig-husbandry facilities to the fields. Our analysis predicted that a farm holding 10,000 pigs may save inorganic nitrogen and phosphorus fertilizers by as much as 74.36 and 11.15 ton·a-1, respectively. On the other hand, five cases of ecological models oriented towards agritourism provided tourists with high-quality ecological products while coordinating environment protection with economic development. In addition, 11 research points applied water and fertilizer integration system for the purpose of saving water. However, lack of sufficient supporting arable land made intensive pig farming a risk of ecological degradation. Green control technologies are rarely used leading to an increase in the type and amount of pesticides. Our study has theoretical and practical significance for decision-makers to promote agricultural cleaner production (ACP).

Lighting the way to sustainable development: Physiological response and light control strategy in microalgae-based wastewater treatment under illumination.

The Sustainable Development Goals link pollutant control with carbon dioxide reduction. Toward the goal of pollutant and carbon reduction, microalgae-based wastewater treatment (MBWT), which can simultaneously remove pollutants and convert carbon dioxide into biomass with value-added metabolites, has attracted considerable attention. The photosynthetic organism microalgae and the photobioreactor are the functional body and the operational carrier of the MBWT system, respectively; thus, light conditions profoundly influence its performance. Therefore, this review takes the general rules of how light influences the performance of MBWT systems as a starting point to elaborate the light-influenced mechanisms in microalgae and the light control strategies for photobioreactors from the inside out. Wavelength, light intensity and photoperiod solely or interactively affect biomass accumulation, pollutant removal, and value-added metabolite production in MBWT. Physiological processes, including photosynthesis, photooxidative damage, light-regulated gene expression, and nutrient uptake, essentially explain the performance influence of MBWT and are instructive for specific microalgal strain improvement strategies. In addition, light causes unique reactions in MBWT systems as it interacts with components such as photooxidative damage enhancers present in types of wastewater. In order to provide guidance for photobioreactor design and light control in a large-scale MBWT system, wavelength transformation, light transmission, light source distribution, and light-dark cycle should be considered in addition to adjusting the light source characteristics. Finally, based on current research vacancies and challenges, future research orientation should focus on the improvement of microalgae and photobioreactor, as well as the integration of both.

Co-cultivation of microalgae-activated sludge for municipal wastewater treatment: Exploring the performance, microbial co-occurrence patterns, microbiota dynamics and function during the startup stage.

Microalgae consortium is a promising technology for achieving low-carbon and resource utilization goals in municipal wastewater treatment. However, little is known about how the consortium affects the treatment performance in the startup stage of co-cultivation. Herein, photobioreactors were constructed with different contents of microalgae and activated sludge (AS) (wt.microalgae: wt.AS ≥ 50 %). The results showed that the concentration of microalgae increased by more than 20 % with AS, and the effluents were close or lower than Chinese discharge standards within HRT 24 h (NH4+-N, TP, and COD ≤ 5.0, 0.5, and 50 mg L-1). Furthermore, the co-occurrence pattern of microbial populations experienced inhibition-reconstruction and reconstruction-inhibition processes, respectively, and the inter-species relationship was directly related to the effluent quality. Microalgal concentration and temperature were the key factors to the microbial community profiling. The potential microorganisms in AS could promote the growth of microalgae, and the bacteria and fungi formed co-metabolism through functional complementation.

Insights of microalgal municipal wastewater treatment at low temperatures: Performance, microbiota patterns, and cold-adaptation of tubular and aeration column photobioreactors.

In order to refine the treatment of microalgae consortium (MC) for municipal wastewater (MWW) during the winter, this study investigated the effectiveness of tubular and aeration column photobioreactors (TPBR and APBR) in wastewater treatment plant (WWTP) during winter by two start-up modes: microalgae/microalgae-activated sludge (AS). The operation results showed that under 5.7-13.1 °C, TPBR enhanced the assimilation of N and P pollutant by microalgal accumulation, meeting the Chinese discharge standard within 24 h (NH4+-N, TP, and COD ≤8.0, 0.5, and 50 mg·L-1). The microbial community profiles were identified and showed that inoculating AS under low-temperature still promoted bacterial interspecific association, but influenced by the inhibition of microbial diversity by the homogeneous circulation of TPBR, the nitrogen transfer function of MC was lower than that of APBR at low temperatures, except nitrogen fixation (K02588), nitrosification (K10944, K10945, and K10946), assimilatory nitrate reduction (K00366), and ammonification (K01915 and K05601). And the intermittent aeration in the APBR was still beneficial in increasing microbial diversity, which was more beneficial for reducing COD through microbial collaboration. In the treatment, the cryotolerant MGPM were Delftia, Romboutsia, Rhizobiales, and Bacillus, and the cold stress-related genes that were highly up-regulated were defense signaling molecules (K03671 and K00384), cold shock protein gene (K03704), and cellular protector (K01784) were present in both PBRs. This study provided a reference for the feasibility of the low temperature treatment of MC with the different types of PBR, which improved the application of wastewater treatment in more climatic environments.

Biomimetic Intrafibrillar Mineralization of Native Tendon for Soft-Hard Interface Integration by Infiltration of Amorphous Calcium Phosphate Precursors.

Soft and hard tissues possess distinct biological properties. Integrating the soft-hard interface is difficult due to the inherent non-osteogenesis of soft tissue, especially of anterior cruciate ligament and rotator cuff reconstruction. This property makes it difficult for tendons to be mineralized and integrated with bone in vivo. To overcome this challenge, a biomimetic mineralization strategy is employed to engineer mineralized tendons. The strategy involved infiltrating amorphous calcium phosphate precursors into collagen fibrils, resulting in hydroxyapatite deposition along the c-axis. The mineralized tendon presented characteristics similar to bone tissue and induced osteogenic differentiation of mesenchymal stem cells. Additionally, the interface between the newly formed bone and tendon is serrated, suggesting a superb integration between the two tissues. This strategy allows for biomineralization of tendon collagen and replicating the hallmarks of the bone matrix and extracellular niche, including nanostructure and inherent osteoinductive properties, ultimately facilitating the integration of soft and hard tissues.

COD/TN ratios shift the microbial community assembly of a pilot-scale shortcut nitrification-denitrification process for biogas slurry treatment.

In this study, effects of carbon to nitrogen (COD/TN) ratios of biogas slurry on shortcut nitrification-denitrification in a pilot-scale integrated fixed film activated sludge (IFAS) system were investigated. Lowering the COD/TN ratio from 11.7 to 6.2 exerted a negative impact on shortcut nitrification-denitrification performance. Accordingly, the NH3-N and TN removal rates decreased from 94.4 to 91.2% and 92.3 to 85.9%, respectively. The dynamics of microbial assembly was analyzed by MiSeq sequencing, and the denitrifying functional genes were quantified by qPCR. The results showed that ammonia oxidizing bacteria and amoA gene were more abundant on the biofilm of oxic tank, indicating they play a key role in NH3-N removal. Autotrophic, endogenous, and fast heterotrophic kinetics denitrifiers were coexisted and enriched in the IFAS system with a decreasing of COD/TN ratio. TN removal was mainly affected by denitrifiers (including Arenimonas, Acidovorax, and Thaurea) harboring narG and nirS genes. Canonical correspondence analysis proved that COD/TN ratio was the most critical factor driving the succession of microbial community. Dissolved oxygen (DO) and pH were found positively correlated with denitrifiers at low COD/TN ratio conditions. As a result, NH3-N and TN removal were effectively enhanced when the DO level in the oxic tank of IFAS system was increased to 1.0-3.0 mg/L.

Dynamics of antibiotic resistance genes and microbial community in shortcut nitrification-denitrification process under antibiotic stresses.

In this study, the performance of shortcut nitrification-denitrification (SCND) at different TC and SD stress conditions (0 µg/L, 1-97 days; 100 µg/L, 98-138 days; 500 µg/L, 139-175 days) was investigated. Higher level antibiotic stress (500 µg/L) led to the serious deterioration of nitrogen removal, and denitrification was more sensitive to antibiotic stress than nitrification. The dynamics of antibiotic resistance genes (ARGs) and microbial community were revealed by quantitative real-time PCR and 16S rDNA high-throughput sequencing, respectively. Tet-genes (tetA, tetQ, tetW), sul-genes (sulI, sulII), and mobile genetic element (intI1) in activated sludge increased by 1.2 ~ 2.5 logs with long-term exposure of antibiotic stress, and sulI, tetA, tetQ, and tetW were significantly positively correlated with intI1. Long-term antibiotics stress caused the decrease of most denitrifiers, and five genera were identified as the potential host of ARGs. The key impact factors of SCND drove the dynamics of ARGs and microbial community. Except for sulII gene, DO and FA were significantly positively correlated with ARGs, while FNA, NAR, and NO2--N showed opposite effects to ARGs. Overall, maintaining relative lower DO, higher FNA, NAR, and NO2--N conditions are not only benefit to the stable operation of SCND, but may also conducive to the control of ARG dissemination. This study provides theoretical basis on the control of ARGs in the SCND process.

Enhancement of black and odorous water treatment coupled with accelerated lipid production by microalgae exposed to 12C6+ heavy-ion beam irradiation.

In this study, Auxenochlorella protothecoides (AP-CK) was selected due to its reported high growth potential in sterilized black and odorous water (SBOW). In order to improve the resource utilization level of microalgae for wastewater treatment, AP-CK was mutated using 12C6+ heavy-ion beam irradiation, and a high lipid-containing mutant (AP-34#) was isolated and further evaluated to treat original black and odorous water (OBOW). Compared with the wild type, the maximum removal rates of COD, NH4+-N and TP of the mutant increased by 8.12 ± 0.33%, 10.43 ± 0.54% and 11.97 ± 0.16%, respectively, while maximum dissolved oxygen content increased from 0 to 4.36 ± 0.25 mg/L. Besides, the mutant lipid yield increased by 115.87 ± 3.22% over the wild type in OBOW. The fatty acid profile of AP-34# grown in SBOW and OBOW showed higher proportion of saturated fatty acids (C16:0 and C18:0) and valuable polyunsaturated fatty acids (mainly C20:5n3 and C22:6n3) which are more suitable for biodiesel production and value-added products, respectively. This work provides a new perspective on improving the characteristics of microalgae and an innovative approach for resource-based microalgae wastewater treatment through bioremediation of black and odorous water.

A Multifunctional Anti-Proton Electrolyte for High-Rate and Super-Stable Aqueous Zn-Vanadium Oxide Battery.

Large volumetric expansion of cathode hosts and sluggish transport kinetics in the cathode-electrolyte interface, as well as dendrite growth and hydrogen evolution at Zn anode side are considered as the system problems that cause the electrochemical failure of aqueous Zn-vanadium oxide battery. In this work, a multifunctional anti-proton electrolyte was proposed to synchronously solve all those issues. Theoretical and experimental studies confirm that PEG 400 additive can regulate the Zn2+ solvation structure and inhibit the ionization of free water molecules of the electrolyte. Then, smaller lattice expansion of vanadium oxide hosts and less associated by-product formation can be realized by using such electrolyte. Besides, such electrolyte is also beneficial to guide the uniform Zn deposition and suppress the side reaction of hydrogen evolution. Owing to the integrated synergetic modification, a high-rate and ultrastable aqueous Zn-V2O3/C battery can be constructed, which can remain a specific capacity of 222.8 mAh g-1 after 6000 cycles at 5 A g-1, and 121.8 mAh g-1 even after 18,000 cycles at 20 A g-1, respectively. Such "all-in-one" solution based on the electrolyte design provides a new strategy for developing high-performance aqueous Zn-ion battery.

A Cd9+Cd271+ stem/progenitor population and the SHP2 pathway contribute to neonatal-to-adult switching that regulates tendon maturation.

Tendon maturation lays the foundation for postnatal tendon development, its proper mechanical function, and regeneration, but the critical cell populations and the entangled mechanisms remain poorly understood. Here, by integrating the structural, mechanical, and molecular properties, we show that post-natal days 7-14 are the crucial transitional stage for mouse tendon maturation. We decode the cellular and molecular regulatory networks at the single-cell level. We find that a nerve growth factor (NGF)-secreting Cd9+Cd271+ tendon stem/progenitor cell population mainly prompts conversion from neonate to adult tendon. Through single-cell gene regulatory network analysis, in vitro inhibitor identification, and in vivo tendon-specific Shp2 deletion, we find that SHP2 signaling is a regulator for tendon maturation. Our research comprehensively reveals the dynamic cell population transition during tendon maturation, implementing insights into the critical roles of the maturation-related stem cell population and SHP2 signaling pathway during tendon differentiation and regeneration.

Cell-subpopulation alteration and FGF7 activation regulate the function of tendon stem/progenitor cells in 3D microenvironment revealed by single-cell analysis.

Three dimensional (3D) microenvironments more accurately replicate native microenvironments for stem cell maintenance and function compared with two dimensional (2D) microenvironments. However, the molecular mechanisms by which 3D microenvironments regulate stem cell function remain largely unexplored at the single-cell level. Here, using a single-cell analysis and functional analysis, we found not all cell-subpopulations respond to 3D microenvironments based on a systematically 3D gelatin microcarrier culture system we developed for the expansion and function maintenance of hTSPCs. 3D microenvironments alter the cell-subpopulation distribution of human tendon stem/progenitor cells (hTSPCs) by improving the proportion of ICAM1+ITGB8+ and FGF7+CYGB+ subpopulations. We also revealed the activated FGF7 signaling in the two subpopulations is responsible for the enhanced tenogenesis of hTSPCs through cell-cell interactions. The hTSPCs cultured in 3D niche with a specific cell-subpopulation structure exhibited superior stem-cell characteristics and functions both in vitro and in vivo. Together, our study demonstrates that 3D microenvironments can regulate stem-cell function by modulating the critical cell subpopulation and identifies FGF7 as a novel regulator for tenogenic differentiation and tendon regeneration.

WDR62 regulates mouse oocyte meiotic maturation related to p-JNK and H3K9 trimethylation.

WDR62 (WD40-repeat protein 62) participates in diverse biological process, especially mitotic spindle organization via regulating centriole biogenesis and the function of centriole-associated protein. However, the role of WDR62 exerts in spindle assembly and meiotic progression control in oocytes lacking typical centrosomes remains obscure. In a previous study, we reported that WDR62 is involved in spindle migration and asymmetric cytokinesis in mouse oocyte meiosis. In the current study, another novel function of WDR62 regulating cell cycle progression through meiotic spindle formation during oocyte meiotic maturation was found. Knockdown of WDR62 through siRNA microinjection disrupted the meiotic cell cycle and induced metaphase-I (MI) arrest coupled with severe spindle abnormality, chromosome misalignment, and aneuploid generation. Moreover, WDR62 depletion induced defective kinetochore-microtubule attachments (K-MT) and activated spindle assembly checkpoint (SAC), which could trigger the arrest of meiotic progression. Further study demonstrated that depletion of WDR62 was associated with an aberrant location of p-JNK and reduced its expression level; concomitantly, status of H3K9 trimethylation was also altered. In addition, phenotypes similar to WDR62 depletion were observed during the function-loss analysis of p-JNK using a specific inhibitor (SP600125), which signifies that WDR62 is important for spindle organization and meiotic progression, and this function might be via its regulation of p-JNK. In conclusion, this study revealed that WDR62 functions in multiple ways during oocyte meiotic maturation, which could be related to p-JNK and H3K9 trimethylation.