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Purpose Pediatric patients with inborn errors of immunity (IEI) undergoing umbilical cord blood transplantation (UCBT) are at risk of early mortality. Our aim was to develop and validate a prediction model for early mortality after UCBT in pediatric IEI patients based on pretransplant factors. Methods Data from 230 pediatric IEI patients who received their first UCBT between 2014 and 2021 at a single center were analyzed retrospectively. Data from 2014–2019 and 2020–2021 were used as training and validation sets, respectively. The primary outcome of interest was early mortality. Machine learning algorithms were used to identify risk factors associated with early mortality and to build predictive models. The model with the best performance was visualized using a nomogram. Discriminative ability was measured using the area under the curve (AUC) and decision curve analysis. Results Fifty days was determined as the cutoff for distinguishing early mortality in pediatric IEI patients undergoing UCBT. Of the 230 patients, 43 (18.7%) suffered early mortality. Multivariate logistic regression with pretransplant albumin, CD4 (absolute count), elevated C-reactive protein, and medical history of sepsis showed good discriminant AUC values of 0.7385 (95% CI, 0.5824–0.8945) and 0.827 (95% CI, 0.7409–0.9132) in predicting early mortality in the validation and training sets, respectively. The sensitivity and specificity were 0.5385 and 0.8154 for validation and 0.7667 and 0.7705 for training, respectively. The final model yielded net benefits across a reasonable range of risk thresholds. Conclusion The developed nomogram can predict early mortality in pediatric IEI patients undergoing UCBT.

A new configuration is proposed to improve the sensitivity and temperature stability of the surface acoustic wave (SAW) strain sensor by using a differential dual-chip structure. Each SAW chip with a one-port resonator pattern is prepared by depositing Al interdigital transducers (IDTS) on Y-cut quartz crystal using the photolithographic technique, and positioned orthogonally in the ceramic package. The opposite polarity of the strain sensitivity arises from the directivity of the strain tensor, and enhanced sensitivity will be expected by differencing the response from each sensing chip. Referring to the perturbation theory and finite element modeling (FEM), the sensitivity of the proposed sensor configuration is simulated and predicted, and confirmed by the wirelessly characterization. Excellent temperature compensation at 0 – 120 °C, higher sensitivity of 1.3 kHz/ $\mu \varepsilon $ , and satisfied linearity in a detection range of ± $500~\mu \varepsilon $ are achieved, and estimated detection limit reaches ± $0.7~\mu \varepsilon $ .

Interfaces in perovskite solar cells (PSCs) are closely related to their power conversion efficiency (PCE) and stability. It is highly desirable to minimize the interfacial nonradiative recombination losses through rational interfacial engineering. Herein we develop an effective and easily reproducible interface engineering strategy where three mercaptobenzimidazole (MBI)-based molecules are employed to modify the perovskite/electron transport layer (ETL) interface. MBI and MBI-OCH3 can not only passivate defects at surface and grain boundaries (GBs) of perovskite films but can also improve energy level alignment (ELA), which leads to enhanced PCE and stability. Consequently, the PCE is improved from 19.5% for the control device to 21.2% for MBI-modified device, which is among the best reported inverted MAPbI3-based PSCs. In contrast, incorporation of MBI-NO2 increases defect density and negligibly influences the energy level alignment. This work indicates that defect passivation and ELA modulation can be achieved simultaneously through modulating functional groups in interface modification molecules.

It is commonly believed that the ultimate goal of high throughput production of organic solar cells (OSCs) is the fully solution process in the fabrication. While it is highly desirable to form metal back electrodes to complete OSCs by a solution process instead of high-vacuum evaporation to realize the goal, the complex solvents used in typical metal precursor solutions and the post-treatment required such as high-temperature annealing will easily damage active layers and degrade OSC performances. The power conversion efficiencies (PCE) for evaporation-free OSCs have only reached 8%. Besides, there are limited studies that provide clear evidence to successfully eliminate the solvent issue brought by the directly solution-processed metal back electrode. In this work, we demonstrate a compatible self-sintering approach to connect silver nanoparticles (NPs) into a high-quality back electrode. The as-achieved film exhibits a continuous crystal lattice, high purity, excellent conductivity and smooth morphology. Interestingly, since the self-sintering back electrode process is finished in a short time and uses a chemically compatible solvent, it will not degrade the organic active layer and favors high throughput OSCs fabrication. With the back electrode, the fully solution-processed OSCs achieve a PCE of 9.73% which is the highest reported PCE in evaporation-free OSCs to our best knowledge.

We aimed to predict the mortality of patients with craniotomy in ICU by using predictive models to extract the high-risk factors leading to the death of patients from a retrospective a study. Five machine-learning (ML) algorithms were applied for training on mortality predictive models with the data from a surgical intensive care unit (ICU) database of the Fujian Provincial Hospital in China. The accuracy, precision, recall, f1 score and the area under the receiver operator characteristic curve (AUC) were used to evaluate the performance of different models, and the calibration of the model was evaluated by brier score. We demonstrated that eXtreme Gradient Boosting (XGBoost) was more suitable for the task, demonstrating a AUC of 0.84. We analyzed the feature importance with the Local Interpretable Model-agnostic Explanations (LIME) analysis and further identified the high-risk factors of mortality in ICU through this study. This study established the mortality predictive model of patients who had undergone craniotomy in ICU. Identification of the factors that had great influence on mortality has the potential to provide auxiliary decision support for clinical medical staff on their practices.

Electron donors and acceptors in organic solar cells (OSCs) shall strike a favorable vertical phase separation that acceptors and donors have sufficient contact and gradient accumulation near the cathodes and anodes, respectively. Random mixing of donors/acceptors at surface will result in charge accumulation and severe recombination for low carrier-mobility organic materials. However, it is challenging to tune the vertical distribution in bulk-heterojunction films as they are usually made from a well-mixed donor/acceptor solution. Here, for the first time, it presents with solid evidence that the commonly used 1-chloronaphthalene (CN) additive can tune the donor/acceptor vertical distribution and establish the mechanism. Different from the previous understanding that ascribed the efficiency enhancement brought by CN to the improved molecular stacking/crystallization, it is revealed that the induced vertical distribution is the dominant factor leading to the significantly increased performance. Importantly, the vertical distribution tunability is effective in various hot nonfullerene OSC systems and creates more channels for the collection of dissociated carriers at corresponding organic/electrode interfaces, which contributes the high efficiency of 18.29%. This study of the material vertical distribution and its correlation with molecular stacking offers methods for additives selection and provides insights for the understanding and construction of high-performance OSCs.

The transcriptional regulator Runx2 (runt-related transcription factor 2) has essential but distinct roles in osteoblasts and chondrocytes in skeletal development. However, Runx2-mediated regulatory mechanisms underlying the distinctive programming of osteoblasts and chondrocytes are not well understood. Here, we perform an integrative analysis to investigate Runx2-DNA binding and chromatin accessibility ex vivo using neonatal osteoblasts and chondrocytes. We find that Runx2 engages with cell-type-distinct chromatin-accessible regions, potentially interacting with different combinations of transcriptional regulators, forming cell-type-specific hotspots, and potentiating chromatin accessibility. Genetic analysis and direct cellular reprogramming studies suggest that Runx2 is essential for establishment of chromatin accessibility in osteoblasts. Functional enhancer studies identify an Sp7 distal enhancer driven by Runx2-dependent binding and osteoblast-specific chromatin accessibility, contributing to normal osteoblast differentiation. Our findings provide a framework for understanding the regulatory landscape encompassing Runx2-mediated and cell-type-distinct enhancer networks that underlie the specification of osteoblasts.

How agriculture can better adapt to climate change has been a key topic of interest for scholars. This study provides insights from the eastern agricultural region of the Tibetan Plateau (TP). The Yellow River-Huangshui River valley (YHV) is an important food-producing region on the TP. The agricultural production of small households has been affected by significant climate change and by a series of interventions on the part of the local government. Five main adaptation strategies adopted by households include crop rotation (86.71%), increasing agricultural inputs (74.21%), changing the sowing time of crops (61.51%), expanding cropland area (32.94%) and raising more livestock (16.27%) to adapt to the effects of climate change. Regression analysis revealed that households’ perceptions of climate change and five types of livelihood capital are important factors influencing their adoption of various livelihood strategies. In addition, the adaptation strategies used by households in the YHV are incremental adjustments to their existing production, while transformative adaptation strategies (e.g., irrigation facilities, improved crop varieties, agricultural insurance), which are larger in scale and could fundamentally reduce households’ vulnerability to climate change have been planned by the government. Due to the presence of government interventions, households in the YHV area are more proactive in adapting to climate change. Finally, the results of this paper are conducive to guiding the local government to enhance its intervention role to promote households’ climate change adaptation behavior.

Wetland ecosystems play one of the most crucial roles in the world. Wetlands have the functions of ecological water storage, water supply, and climate regulation, which plays an indispensable role in global environmental security. The Pumqu River Basin (PRB) is located in an area with extremely vulnerable ecological environment, where climate change is obvious. Understanding wetland distribution, changes and causes in the PRB are of great importance to the rational management and protection of wetlands. Using the Landsat series satellite images, wetlands of this area in 2000, 2010, and 2018 were extracted. The results showed that (1) there were obvious regional differences in wetland types and their distribution patterns in the basin. Wetlands were mainly distributed in areas with slopes less than 12° and at elevations between 4000 m and 5500 m. (2) During the past 20 years, the wetland area in the basin decreased, and the changing trend of wetlands was different. Palustrine wetlands decreased tremendously, riverine and lacustrine wetlands first decreased and then increased, while floodplain wetlands first increased and then decreased. Palustrine wetlands were reclaimed to cultivated land, but the proportion of reclamation is small. (3) Climate dominated wetland changes in the PRB. The changes in riverine and lacustrine wetlands were mainly affected by the warm-season average temperature, the change in palustrine wetlands was mainly related to the annual precipitation and the warm-season average temperature, and the change in floodplain wetlands was related to the warm-season precipitation. To achieve sustainable development, the government plays a guiding role and actively formulates and implements wetland protection policies, such as restricting or prohibiting grazing on wetlands, which play an important role in wetland protection and restoration.

Cropland expansion has become a prominent feature in developing countries and regions. A comprehensive clarification of the causes of cropland expansion is conducive to the adoption of appropriate actions to intervene and adapt to climate change, support rational land use, and balance ecosystem services. Using the Pumqu River Basin (PRB) in the Tibetan Plateau as the study area, we constructed a conceptual model that emphasizes the role of households and explored the causes of cropland expansion based on field survey data. Our results indicate that households’ perception of climate change, families’ non-agricultural income, the numbers of agricultural labor force, and the population pressure faced were the causes of cropland expansion in the PRB. Based on these findings, corresponding policy recommendations to limit the spontaneous cropland expansion behaviors of local households and reduce the ecological loss caused by cropland expansion are proposed.

The double-row layout problem (DRLP) is a well-known optimization problem that generally deals with the arrangement of machines or other such entities on the two sides along a corridor. Based on the placement of the machinery and equipment in a factory, this study analyzes the DRLP from a new perspective that addresses the arrangement of the given machines subject to the condition that certain designated positions are allocated to certain machines and specific relationships are enforced among the machines. This DRLP is termed as a constrained DRLP (cDRLP). In this study, considering the practical applications, four variations of the cDRLP have been developed for the first time and solved. Additionally, to solve this problem, some constraints (positioning, ordering, and relation constraints) have been defined and classified. Furthermore, mathematical models have been built with the objective of minimizing the total material handling cost. Next, the CPLEX software has been adopted to solve the above variations. Finally, a series of numerical instances have been employed to evaluate the efficiency of the proposed models and obtain the exact results.

The rapid development of 2019-2020 Wuhan seafood market pneumonia currently posed a major public health concern in China. Genome sequencing identified a novel beta-coronavirus closely related to SARS-CoV, named 2019-nCoV by WHO, as the cause of this pandemic disease. Viruses with single stranded RNA genome are prone to evolve quickly by accumulation of mutations, such as SNV, INDEL and cross viral recombination, aiding fast transmission among hosts and cross species. Here we collected related genome sequences and investigated variations shared by different strains of 2019-nCoV, identified reoccurrence of SNV mutations in clusters of patients, an indication of rapid evolution of 2019-nCoV at the transmission from animal host to human. The information collected herein would help to understand the dynamics of current pandemic.

CsPbI

Herein, we present a new and available Ti doping and surface self-passivation strategy to significantly boost the PEC performance of the Fe2O3 nanorods for both solar water splitting and formaldehyde (HCHO) oxidation. Upon Ti doping and surface passivation with KOH treatment, the self-passived Ti4+ doped Fe2O3 nanorods exhibit substantially higher PEC performance compared to the pristine Fe2O3 and Ti4+ doped Fe2O3 nanorods, achieving a remarkable photocurrent of 3.7 mA cm−2 at 1.5 V vs. RHE. Furthermore, these self-passived Ti4+ doped Fe2O3 nanorods also show a 100 mV cathodic shift in onset potential than that of Ti4+ doped Fe2O3 nanorods and excellent durability. Such the substantially improved photoelectrochemical performance is ascribed to the dramatically increased donor densities and reduced electron-hole recommendation as a result of Ti doping and surface passivation layer that formed after KOH treatment.

INTRODUCTION: The phases of fracture healing have been well characterized. However, the exact source and genetic profile of the skeletal progenitors that participate in bone repair is somewhat unclear. Sox9 expression in skeletal elements precedes bone and cartilage formation and a Sox9(+) cell type is retained in the adult periosteum. We hypothesized that Sox9(+) periosteal cells are multipotent skeletal progenitors normally participating in fracture repair. METHODS: To test this hypothesis we used tamoxifen (TM)-mediated lineage tracing of Sox9(+) cells in Sox9CreErt2:Td-Tomato mice. Intact femora were analyzed with immunostaining and RNA sequencing to evaluate the skeletal distribution and gene expression profile of Td-Tomato positive, Sox9-descendent cells in the adult femur. To assess the role of Td-tomato+ cells in the fracture healing process, mice underwent a closed mid-diaphyseal femoral fracture. Fractured hind limbs were analyzed by X-ray, histology and immuno-staining at 3, 9 or 56 days post-fracture. RESULTS: In the intact adult mouse femur, Td-Tomato-labeled cells were observed in the primary spongiosa, periosteum and endosteum. RNA sequencing showed that Td-Tomato positive periosteal cells were co-enriched for Sox9 transcripts, and mRNAs for osteoblast and chondrocyte specific genes. In a femoral fracture model, we showed that pre-labeled Td-Tomato positive descendent cells were mobilized during the early stages of bone repair (day 3 post-op) contributing to the fracture repair process by differentiating into chondrocytes, osteoblasts and osteocytes. CONCLUSION: A Sox9(+) skeletal progenitor population resides in the adult periosteum. Fate tracing studies show that descendants of the Sox9(+) periosteal progenitors give rise to chondrocytes, osteoblasts and mature cortical osteocytes in repair of the fractured femur. To our knowledge this is the first report of a reparative Sox9(+) progenitor population in the periosteum of the adult long bone. Taken together with developmental studies, our data suggest a broad role for Sox9(+) osteochondroprogenitors in development and repair of the mammalian skeleton.

Free-standing porous MoO2 nanowires with extraordinary capacitive performance are developed as high-performance electrodes for electrochemical capacitors. The as-obtained MoO2 electrode exhibits a remarkable capacitance of 424.4 mF cm−2 with excellent electrochemical durability (no capacitance decay after 10 000 cycles at various scan rates).

In extant species, bone formation is restricted to vertebrate species. Sp7/Osterix is a key transcriptional determinant of bone-secreting osteoblasts. We performed Sp7 chromatin immunoprecipitation sequencing analysis identifying a large set of predicted osteoblast enhancers and validated a subset of these in cell culture and transgenic mouse assays. Sp family members bind GC-rich target sequences through their zinc finger domain. Several lines of evidence suggest that Sp7 acts differently, engaging osteoblast targets in Dlx-containing regulatory complexes bound to AT-rich motifs. Amino acid differences in the Sp7 zinc finger domain reduce Sp7's affinity for the Sp family consensus GC-box target; Dlx5 binding maps to this domain of Sp7. The data support a model in which Dlx recruitment of Sp7 to osteoblast enhancers underlies Sp7-directed osteoblast specification. Because an Sp7-like zinc finger variant is restricted to vertebrates, the emergence of an Sp7 member within the Sp family was likely closely coupled to the evolution of bone-forming vertebrates.

Hematite (α-Fe2O3) photoanodes has received considerable attention to produce hydrogen and oxygen by the photoelectrochemical (PEC) reaction due to its chemical stability, appropriate band and abundance. Although various sizes and morphologies of α-Fe2O3 had been synthesized to enhance the photoanode performance, their photoactivity is still unsatisfactory for their inefficient charge transfer or light harvesting. In this work, we utilized a facile hydrothermal method to tune the size and morphology of the α-Fe2O3 nanostructures by simply controlling the reaction temperature, and found that the 500 nm 3D nanospheres (NSs) exhibit highest catalytic activity for the PEC water splitting. We systematically studied the morphology and growth mechanism of α-Fe2O3 nanorods (NRs) and NSs, and found the temperature can greatly influence the final morphology. In comparison to 1D NRs, the 3D NSs can make the PEC activity enhanced for five times due to the optimal charge transfer and light harvesting. This report provides a new insight on the relationships between nanostructures and photoanode performances, and can be applied in other PEC water splitting materials.

CsPbI3 inorganic perovskite has exhibited some special properties particularly crystal structure distortion and quantum confinement effect, yet the poor phase stability of CsPbI3 severely hinders its applications. Herein, the nature of the photoactive CsPbI3 phase transition from the perspective of PbI6 octahedra is revealed. A facile method is also developed to stabilize the photoactive phase and to reduce the defect density of CsPbI3 . CsPbI3 is decorated with multifunctional 4-aminobenzoic acid (ABA), and steric neostigmine bromide (NGBr) is subsequently used to further mediate the thin films' surface (NGBr-CsPbI3 (ABA)). The ABA or NG cation adsorbed onto the grain boundaries/surface of CsPbI3 anchors the PbI6 octahedra via increasing the energy barriers of octahedral rotation, which maintains the continuous array of corner-sharing PbI6 octahedra and kinetically stabilizes the photoactive phase CsPbI3 . Moreover, the added ABA and NGBr not only interact with shallow- or deep-level defects in CsPbI3 to significantly reduce defect density, but also lead to improved energy-level alignment at the interfaces between the CsPbI3 and the charge transport layers. Finally, the champion NGBr-CsPbI3 (ABA)-based inorganic perovskite solar cell delivers 18.27% efficiency with excellent stability. Overall, this work demonstrates a promising concept to achieve highly phase-stabilized inorganic perovskite with suppressed defect density for promoting its optoelectronic applications.

The growth plate mediates bone growth where SOX9 and GLI factors control chondrocyte proliferation, differentiation and entry into hypertrophy. FOXA factors regulate hypertrophic chondrocyte maturation. How these factors integrate into a Gene Regulatory Network (GRN) controlling these differentiation transitions is incompletely understood. We adopted a genome-wide whole tissue approach to establish a Growth Plate Differential Gene Expression Library (GP-DGEL) for fractionated proliferating, pre-hypertrophic, early and late hypertrophic chondrocytes, as an overarching resource for discovery of pathways and disease candidates. De novo motif discovery revealed the enrichment of SOX9 and GLI binding sites in the genes preferentially expressed in proliferating and prehypertrophic chondrocytes, suggesting the potential cooperation between SOX9 and GLI proteins. We integrated the analyses of the transcriptome, SOX9, GLI1 and GLI3 ChIP-seq datasets, with functional validation by transactivation assays and mouse mutants. We identified new SOX9 targets and showed SOX9-GLI directly and cooperatively regulate many genes such as Trps1, Sox9, Sox5, Sox6, Col2a1, Ptch1, Gli1 and Gli2. Further, FOXA2 competes with SOX9 for the transactivation of target genes. The data support a model of SOX9-GLI-FOXA phasic GRN in chondrocyte development. Together, SOX9-GLI auto-regulate and cooperate to activate and repress genes in proliferating chondrocytes. Upon hypertrophy, FOXA competes with SOX9, and control toward terminal differentiation passes to FOXA, RUNX, AP1 and MEF2 factors., Author summary In the development of the mammalian growth plate, while several transcription factors are individually well known for their key roles in regulating phases of chondrocyte differentiation, there is little information on how they interact and cooperate with each other. We took an unbiased genome wide approach to identify the transcription factors and signaling pathways that play dominant roles in the chondrocyte differentiation cascade. We developed a searchable library of differentially expressed genes, GP-DGEL, which has fine spatial resolution and global transcriptomic coverage for discovery of processes, pathways and disease candidates. Our work identifies a novel regulatory mechanism that integrates the action of three transcription factors, SOX9, GLI and FOXA. SOX9-GLI auto-regulate and cooperate to activate and repress genes in proliferating chondrocytes. Upon entry into prehypertrophy, FOXA competes with SOX9, and control of hypertrophy passes to FOXA, RUNX, AP1 and MEF2 factors.

SummaryAn early event in skeletal joint development is the specification of articular chondrocytes at the joint surface. Articular chondrocytes are distinct in producing lower levels of cartilage matrix and not being replaced by bone, yet how they acquire these properties remains poorly understood. Here, we show that two members of the Iroquois transcriptional repressor family, Irx7 and Irx5a, function to block chondrocyte maturation at the developing hyoid joint of zebrafish. These Irx factors suppress the production of cartilage matrix at the joint in part by preventing the activation of a col2a1a enhancer by Sox9a. Further, both zebrafish Irx7 and mouse IRX1 are able to repress cartilage matrix production in a murine chondrogenic cell line. Iroquois proteins may therefore have a conserved role in keeping chondrocytes in an immature state, with the lower levels of cartilage matrix produced by these immature cells contributing to joint flexibility.

SummarySox9 encodes an essential transcriptional regulator of chondrocyte specification and differentiation. When Sox9 nuclear activity was compared with markers of chromatin organization and transcriptional activity in primary chondrocytes, we identified two distinct categories of target association. Class I sites cluster around the transcriptional start sites of highly expressed genes with no chondrocyte-specific signature. Here, Sox9 association reflects protein-protein association with basal transcriptional components. Class II sites highlight evolutionarily conserved active enhancers that direct chondrocyte-related gene activity through the direct binding of Sox9 dimer complexes to DNA. Sox9 binds through sites with sub-optimal binding affinity; the number and grouping of enhancers into super-enhancer clusters likely determines the levels of target gene expression. Interestingly, comparison of Sox9 action in distinct chondrocyte lineages points to similar regulatory strategies. In addition to providing insights into Sox family action, our comprehensive identification of the chondrocyte regulatory genome will facilitate the study of skeletal development and human disease.

Hydrogen gas is emerging as an attractive fuel with high energy density for the direction of energy resources in the future. Designing integrated devices based on a photoelectrochemical (PEC) cell and a microbial fuel cell (MFC) represents a promising strategy to produce hydrogen fuel at a low price. In this work, we demonstrate a new solar-microbial (PEC–MFC) hybrid device based on the oxygen-deficient Nb2O5 nanoporous (Nb2O5−x NPs) anodes for sustainable hydrogen generation without external bias for the first time. Owing to the improved conductivity and porous structure, the as-prepared Nb2O5−x NPs film yields a remarkable photocurrent density of 0.9 mA cm−2 at 0.6 V (vs. SCE) in 1 M KOH aqueous solution under light irradiation, and can achieve a maximum power density of 1196 mW m−2 when used as an anode in a MFC device. More importantly, a solar-microbial hybrid system by combining a PEC cell with a MFC is designed, in which the Nb2O5−x NPs electrodes function as both anodes. The as-fabricated PEC–MFC hybrid device can simultaneously realize electricity and hydrogen using organic matter and solar light at zero external bias. This novel design and attempt might provide guidance for other materials to convert and store energy.

Free-standing porous MoO

Bone morphogenetic proteins (BMPs) are important elements in bone biology. We herein report the expression profiles of zebrafishbmp3(zbmp3) as demonstrated by real-time PCR andin situhybridization. The expression ofzbmp3was highly detectable by real-time PCR from 1 day post-fertilization (1 dpf) to 2 weeks post-fertilization (2 wpf) and peaked at 1 wpf. Forin situhybridization experiments,zbmp3was expressed in the otic vesicle at 1 dpf, 2 dpf, 3 dpf, and 5 dpf. It was also expressed in the pharyngeal arches, including the opercle, branchiostegal ray, and pectoral fins, at 2 dpf. Our results suggest thatzbmp3may play an important role in the skeletal biology of developing zebrafish.

An analysis of Sox9 binding profiles in developing chondrocytes identified marked enrichment of an AP-1-like motif. Here, we have explored the functional interplay between Sox9 and AP-1 in mammalian chondrocyte development. Among AP-1 family members, Jun and Fosl2 were highly expressed within prehypertrophic and early hypertrophic chondrocytes. Chromatin immunoprecipitation followed by DNA sequencing (ChIP-seq) showed a striking overlap in Jun- and Sox9-bound regions throughout the chondrocyte genome. The similar profiles reflect direct binding of each factor to the same enhancers and a potential for protein-protein interactions within AP-1 and Sox9 containing complexes. In vitro reporter analysis indicated that direct co-binding of Sox9 and AP-1 at target motifs promoted gene activity. In contrast, where only one factor can engage its DNA target, the presence of the other factor suppresses target activation consistent with protein-protein interactions attenuating transcription. Analysis of prehypertrophic chondrocyte removal of Sox9 confirmed the requirement of Sox9 for hypertrophic chondrocyte development, while in vitro and ex vivo analyses showed AP-1 promotes chondrocyte hypertrophy. Sox9 and Jun co-bound and co-activated a Col10a1 enhancer in Sox9 and AP-1 motif-dependent manners consistent with their combined action promoting hypertrophic gene expression. Together, the data support a model where AP-1-family members contribute to Sox9-action in the transition of chondrocytes to the hypertrophic program.