ABSTRACT
Inert inorganic nano-building blocks, such as carbon nanotubes (CNTs) and boron nitride (BN) nanosheets, possess excellent physicochemical properties. However, it remains challenging to build aerogels with these inert nanomaterials unless they are chemically modified or compounded with petrochemical polymers, which affects their intrinsic properties and is usually not environmentally friendly. Here, a universal biomacromolecule-enabled assembly strategy is proposed to construct aerogels with 90 wt% ultrahigh inorganic loading. The super-high inorganic content is beneficial for exploiting the inherent properties of inert nanomaterials in multifunctional applications. Taking chitosan-CNTs aerogel as a proof-of-concept demonstration, it delivers sensitive pressure response as a pressure sensor, an ultrahigh sunlight absorption (94.5%) raising temperature under light (from 25 to 71 °C within 1 min) for clean-up of crude oil spills, and superior electromagnetic interference shielding performance of up to 68.9 dB. This strategy paves the way for the multifunctional application of inert nanomaterials by constructing aerogels with ultrahigh inorganic loading.
ABSTRACT
It is still a great challenge to achieve high selectivity of ethanol in CO2 electroreduction reactions (CO2RR) because of the similar reduction potentials and lower energy barrier of possible other C2+ products. Here, we report a MOF-based supported low-nuclearity cluster catalysts (LNCCs), synthesized by electrochemical reduction of three-dimensional (3D) microporous Cu-based MOF, that achieves a single-product Faradaic efficiency (FE) of 82.5 % at -1.0â V (versus the reversible hydrogen electrode) corresponding to the effective current density is 8.66â mA cm-2. By investigating the relationship between the species of reduction products and the types of catalytic sites, it is confirmed that the multi-site synergism of Cu LNCCs can increase the C-C coupling effect, and thus achieve high FE of CO2-to-ethanol. In addition, density functional theory (DFT) calculation and operando attenuated total reflectance surface-enhanced infrared absorption spectroscopy further confirmed the reaction path and mechanism of CO2-to-EtOH.
ABSTRACT
Millions of patients annually suffer life-threatening illnesses caused by bacterial infections of skin wounds. However, the treatment of wounds infected with bacteria is a thorny issue in clinical medicine, especially with drug-resistant bacteria infections. Therefore, there is an increasing interest in developing wound dressings that can efficiently fight against drug-resistant bacterial infections and promote wound healing. In this work, an anti-drug-resistant bacterial chitosan/cellulose nanofiber/tannic acid (CS/CNF/TA) hydrogel with excellent wound management ability was developed by electrospinning and fiber breakage-recombination. The hydrogel exhibited an outstanding antibacterial property exceeding 99.9 %, even for drug-resistant bacteria. This hydrogel could adhere to the tissue surface due to its abundant catechol groups, which avoided the shedding of hydrogel during the movement. Besides, it exhibited extraordinary hemostatic ability during the bleeding phase of the wound and then regulated the wound microenvironment by absorbing water and moisturizing. Moreover, the CS/CNF/TA also promoted the regrowth of vessels and follicles, accelerating the healing of infected wound tissue, with a healing rate exceeding 95 % within a 14-day timeframe. Therefore, the CS/CNF/TA hydrogel opens a new approach for the healing of drug-resistant bacterial infected wounds.
Subject(s)
Bacterial Infections , Chitosan , Hemostatics , Nanofibers , Polyphenols , Humans , Hemostatics/pharmacology , Tannins , Cellulose/pharmacology , Hydrogels/pharmacology , Bacteria , Anti-Bacterial Agents/pharmacologyABSTRACT
The mechanism of Cu(I) -catalyzed allylic alkylation and the influence of the leaving groups (OPiv, SPiv, Cl, SPO(OiPr)2 ; Piv: pivavloyl) on the regioselectivity of the reaction have been explored by using density functional theory (DFT). A comprehensive comparison of many possible reaction pathways shows that [(iPr)2 Cu](-) prefers to bind first oxidatively to the double bond of the allylic substrate at the anti position with respect to the leaving group, and this is followed by dissociation of the leaving group. If the leaving group is not taken into account, the reaction then undergoes an isomerization and a reductive elimination process to give the α- or γ-selective product. If OPiv, SPiv, Cl, or SPO(OiPr)2 groups are present, the optimal route for the formation of both α- and γ-substituted products changes from the stepwise elimination to the direct process, in which the leaving group plays a stabilizing role for the reactant and destabilizes the transition state. The differences to the energy barrier for the α- and γ-substituted products are 2.75 kcal mol(-1) with SPO(OiPr)2 , 2.44 kcal mol(-1) with SPiv, 2.33 kcal mol(-1) with OPiv, and 1.98 kcal mol(-1) with Cl, respectively; these values show that α regioselectivity in the allylic alkylation follows a SPO(OiPr)2 >SPiv>OPiv>Cl trend, which is in satisfactory agreement with the experimental findings. This trend mainly originates in the differences between the attractive electrostatic forces and the repelling steric interactions of the SPO(OiPr)2 , SPiv, OPiv, and Cl groups on the Cu group.
Subject(s)
Allyl Compounds/chemistry , Phosphates/chemistry , Alkylation , Catalysis , Copper/chemistry , Esters , Quantum Theory , StereoisomerismABSTRACT
The cycloisomerization of a bicyclo[4.1.0] substrate into 4,5-dihydrobenzo[b]furan was investigated by using density functional theory (DFT). Comparative studies on four models (model I: with W(CO)5 and NEt3; model II: without NEt3; model III: without W(CO)5; model IV: without W(CO)5 and NEt3) indicate that this reaction is the most likely to proceed under model I to give the product. The ring closure process is greatly associated with the H1 and H2 transfer processes, because in the H1 transfer process, the carbene C3 atom is mainly stabilized by W(CO)5, and in the H2 atom transfer process the C3 atom is mainly stabilized by the O1 atom. The rearrangement of 12 to give 14 is the rate-determining step of this reaction with a free energy barrier of 31.0 kcal/mol. The presence of W(CO)5 can not only promote the H1 transfer and the ring closure (1â6-[W]) but can also be slightly favorable for the isomerization of 6-[W] into 11-[W](6-[W]â11-[W]). NEt3 mainly has an effect in the 6-[W]â11-[W] stage, in which it mainly plays proton-transfer bridge and proton-adsorption roles.
Subject(s)
Benzofurans/chemical synthesis , Bridged Bicyclo Compounds/chemistry , Ethylamines/chemistry , Tungsten/chemistry , Benzofurans/chemistry , Catalysis , Isomerism , Protons , Quantum TheoryABSTRACT
This work proposed a facile way to construct cellulose/chitosan-loaded Ag/Ag2O nanocomposite films (ACC) from alkali/urea solution by increasing the content of alkali KOH in the solvent. The saturated alkali and hydroxyl groups of the cellulose and chitosan chains were accelerated to convert AgNO3 to Ag0. Ag2O served as nuclei to lower the energy barrier. The formation of Ag/Ag2O nanoparticles (NPs) endowed the cellulose bio-reduced Ag composites with multifunction and stronger photocatalytic activity. Ag/Ag2O NPs with the diameter of 139-360 nm were uniformly dispersed in the composite films, resulting in superior mechanical properties (64.6 MPa) and thermal stability. Almost 92 % of methyl orange was degraded under UV-irradiation within 40 min by ACC. After 3 runs of degradation, the photocatalytic abilities of ACC remained. Moreover, the films exhibited good antibacterial activities. The width of inhibition zones around ACC reached 9.2-12 mm and 8.6-10.4 mm for S. aureus and E. coli. The strategy provided a new avenue to construct multifunctional cellulose/chitosan materials for various applications, such as wastewater treatment, and electrocatalysis.
Subject(s)
Chitosan , Metal Nanoparticles , Nanocomposites , Cellulose , Escherichia coli , Staphylococcus aureus , Anti-Bacterial Agents/pharmacologyABSTRACT
The industrial wastewater contaminants including dyes and bacteria have caused serious environmental pollutions. Herein, ternary Ag/Ag2O/ZnO heterostructure decorating cellulose-chitosan films were constructed via in situ synthesis. Cellulose and chitosan dissolved in alkali/urea solvent and regenerated in ethylene glycol to form cellulose/chitosan nanofiber network, which was an ideal supporter for ZnO and Ag nanoparticles and beneficial for recycle usage. The hydroxyl groups of cellulose and chitosan chains exposed and were utilized for the synthesis of Ag particles, as well as ZnO nanoparticles by biomineralization. The Ag/Ag2O/ZnO decorating cellulose/chitosan (AZ@CC) films exhibited excellent antibacterial activity against Staphylococcus aureus and Escherichia coli. The width of inhibition zones around AZ@CC films reached 10.0-19.6 mm and 12.4-15.0 mm for S. aureus and E. coli, respectively. Moreover, AZ@CC films exhibited good photocatalytic activity against methyl orange (MO), almost 97% degradation of methyl orange (MO) within 50 min was achieved with the assistance of AZ@CC film. Importantly, the nanocomposite films exhibited excellent tensile strength and thermal stability. This facile and eco-friendly approach provided a new route to utilize cellulose and chitosan advantages for constructing multifunctional materials.
Subject(s)
Chitosan , Metal Nanoparticles , Nanocomposites , Zinc Oxide , Anti-Bacterial Agents/pharmacology , Cellulose , Escherichia coli , Silver/pharmacology , Staphylococcus aureusABSTRACT
Boron-containing organosilicon polymers are widely used under harsh environments as preceramic polymers for advanced ceramics fabrication. However, harmful chemicals released during synthesis and the complex synthesis routes have limited their applications. To solve the problems, a two-component route was adopted to synthesize cross-linked boron-containing silicone polymer (CPBCS) via a solventless process. The boron content and CPBCSs' polymeric structures could be readily tuned through controlling the ratio of multifunctional boron hybrid silazane monomers (BSZ12) and poly[imino(methylsilylene)]. The CPBCSs showed high thermal stability and good mechanical properties. The CPBCS with Si-H/C=C ratio of 10:1 showed 75 wt% char yields at 1000 °C in argon, and the heat release capacity (HRC) and total heat release (THR) are determined to be 37.9 J/g K and 6.2 KJ/g, demonstrating high thermal stability and flame retardancy. The reduced modulus and hardness of CPBCS are 0.30 GPa and 2.32 GPa, respectively. The novel polysilazanes can be potentially used under harsh environments, such as high temperatures or fire hazards.
ABSTRACT
Gelatin-UPy based on gelatin with ureidopyrimidinone (UPy) side chains was prepared with varying content of UPy units. On increasing the UPy content, the glass transition temperature, crystallinity and swelling decreased. Gelatin-UPy demonstrated self-healing properties as the UPy units could reversibly form dimers. At the same time, the gelatin-UPy and gelatin-UPy hydrogels demonstrated thermal responsive shape memory behaviors. The introduction of coordination crosslinking by introducing Fe3+ in gelatin-UPy hydrogels not only enhanced the crosslinking degree of gelatin-UPy and decreased the swelling degree, but also significantly improved the self-healing properties. As a drug carrier, gelatin-UPy hydrogels could achieve controlled release of 5-fluorouracil (5-FU) drug on increasing the content of UPy and concentration of Fe3+. The gelatin-UPy based materials are expected to find significant use as suppository and tissue engineering materials to treat tumors.
Subject(s)
Drug Carriers/chemistry , Fluorouracil/chemistry , Gelatin/chemistry , Hydrogels/chemistry , Drug Liberation , Hydrogen Bonding , TemperatureABSTRACT
BACKGROUND: Thalassemia is one of the most common monogenic hemolytic disorders in the world. Hong Kongαα (HKαα) thalassemia was initially found among the people of southern China. Because of the complexity of genetic changes in HKαα thalassemia, we lack a precise sequence analysis of the HKαα allele. Here we aim to detect the specific genotype and trace the law of inheritance of this rare genotype. METHODS: We recruited an unprecedented huge pedigree containing 11 individuals carrying the HKαα thalassemia gene and 4 nongenetic-related patients suffering from HKαα from south China. Regular hematological analysis and routine genetic screening were performed on the pedigree and two-round nested PCR (polymerase chain reaction) for HKαα thalassemia were performed on each individual. The first-generation gene sequencing was performed on six individuals, including four nongenetic-related patients. RESULT: We found that five family members were positive for the HKαα allele. Patients â ¡-2, â ¢-1, and â ¡-3 with only HKαα/--SEA or HKαα/-α4.2 presented with α-thalassemia minor trait. â -1, the carrier of both HKαα/-α3.7 and ß41-42 /ßN , showed a typical ß-thalassemia trait. Fetus with genotype HKαα/-α4.2 alone was not likely to suffer from any deleterious effects after birth. The whole sequence of HKαα allele revealed that HKαα alleles in the six patients shared a high similarity, implying that all HKαα alleles are likely from the same ancestor. Moreover, pedigree and sequencing analyses demonstrated that the HKαα allele contained αααanti4.2 mutation, -α3.7 mutation, and a fragment from α-hemoglobin gene; thus, the composition and formation of HKαα allele was revealed. Finally, the high similarity and composition of HKαα alleles implies that once HKαα formed, αααanti4.2 and -α3.7 mutations tended to be a fusion gene and quite impossible to be inherited separately. CONCLUSION: The two-round nested PCR is an effective method to detect HKαα allele. Besides, our study for the first time revealed the sequence of the HKαα allele, the evidence of the same ancestor with HKαα thalassemia and enriched the composition as well as the formation mechanism of HKαα allele, and immediately opened up novel potential diagnosis and prenatal counseling for HKαα thalassemia.
Subject(s)
Hemoglobins/genetics , alpha-Thalassemia/genetics , Adult , Alleles , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Pedigree , Pregnancy , Prenatal Diagnosis , alpha-Thalassemia/diagnosisABSTRACT
Flavivirus non-structural protein 4A (NS4A) induces membrane rearrangements to form viral replication complex and functions as interferon antagonist. However, other non-structural roles of NS4A protein in relation to virus life-cycle are poorly defined. This study elucidated if dengue virus (DENV) NS4A protein interacts with host proteins and contributes to viral pathogenesis by screening human liver cDNA yeast-two-hybrid library. Our study identified polypyrimidine tract-binding protein (PTB) as a novel interacting partner of DENV NS4A protein. We reported for the first time that PTB influenced DENV production. Gene-silencing studies showed that PTB did not have an effect on DENV entry and DENV RNA translation. Further functional studies revealed that PTB influenced DENV production by modulating negative strand RNA synthesis. This is the first study that enlightens the interaction of DENV NS4A protein with PTB, in addition to demonstrating the novel role of PTB in relation to mosquito-borne flavivirus life-cycle.
Subject(s)
Dengue Virus/physiology , Dengue/virology , Polypyrimidine Tract-Binding Protein/metabolism , RNA, Viral/biosynthesis , Viral Nonstructural Proteins/metabolism , Virus Replication , Cell Line , Dengue/metabolism , Dengue Virus/metabolism , Gene Knockdown Techniques , Humans , Polypyrimidine Tract-Binding Protein/genetics , RNA, Viral/metabolismABSTRACT
Graft copolymerization of rosin-(2-acryloyloxy)ethyl ester (RAEE) onto chitosan (Cts) was carried out under microwave irradiation using potassium persulfate as an initiator. The structures, morphology, and thermal properties of the Cts graft copolymer (Cts-g-PRAEE) were characterized by means of FT-IR, XRD, SEM, and TG. Also, Cts and Cts-g-PRAEE copolymer were used as carriers of fenoprofen calcium (FC), and their controlled release behavior in artificial intestinal juice were studied. The results show that the rate of release of fenoprofen calcium from the carrier of Cts-g-PRAEE copolymer becomes very slower than that of Cts in artificial intestinal juice.
ABSTRACT
In the mol-ecule of the title compound, C(23)H(18)ClN(3)O(3), the essentially planar benzotriazole ring makes dihedral angles of 52.93â (1) and 85.21â (1)°, respectively, with the chloro-phenyl and tolyl rings. The crystal packing is stabilized by π-π [centroid-to-centroid distance 3.830â (2)â Å, interplanar distance 3.705â Å, slippage 0.968â Å]; C-Hâ¯πâ¯tolyl ring inter-actions are also present.
ABSTRACT
When an efficient automated coating machine is used to process layer-by-layer (LBL) deposited nanofibrous mats, it causes an obvious planar effect on the surface of the mats, which can be eliminated through ultimate immersion. During this process, chitosan (CS) - rectorite (REC) intercalated composite films are built on the surface of cellulose acetate (CA) nanofibrous mats by a coating machine. Then, the immersion process is utilized to allow positively charged CS or CS-REC intercalated composites to uniformly assemble on the surface of negatively charged CA nanofibers. An investigation into the morphology of the resultant scaffolds confirms that the uniquely small pore size, high specific surface area and typically three-dimensional (3D) structure of nanofibrous mats remain present. The results of Fourier transform infrared (FT-IR) and X-ray photoelectron spectroscopy (XPS) indicate that it is feasible to assemble nanofibrous mats using a coating machine. The intercalated structure of CS-REC is confirmed by the results of small-angle X-ray diffraction (SAXRD) and wide-angle X-ray diffraction (WAXRD). The results of the cell experiment and antibacterial test demonstrate that the addition of REC not only has little impact on the cytocompatibility of the mats but also enhances their ability to inhibit bacteria.
Subject(s)
Aluminum Silicates/pharmacology , Anti-Bacterial Agents/chemistry , Cellulose/analogs & derivatives , Chitosan/chemistry , Minerals/pharmacology , Nanofibers/chemistry , Aluminum Silicates/chemistry , Anti-Bacterial Agents/pharmacology , Automation, Laboratory , Cellulose/chemistry , Colony Count, Microbial , Escherichia coli/drug effects , Escherichia coli/growth & development , Membranes, Artificial , Minerals/chemistry , Nanofibers/ultrastructure , Staphylococcus aureus/drug effects , Staphylococcus aureus/growth & development , Static Electricity , Surface PropertiesABSTRACT
Determination of the degree of acetylation of chitosan by UV spectrophotometry using dual standards is investigated. The UV absorbance of a pure chitosan solution is contributed additively by the N-acetylglucosamine and glucosamine residues; the absorbance divided by the total molar concentration of the residues (A/c(t)) is linearly related to the degree of acetylation (DA). Using acetyl glucosamine and glucosamine hydrochloride as standards in 0.1M hydrochloric acid solution, the equation obtained by linear regression is A/c(t)=3.3615 DA+0.0218, R(2)=0.9958. The DA of the analytical sample (m milligram of chitosan in V liters solution) can be calculated by.
Subject(s)
Chitosan/chemistry , Spectrophotometry, Ultraviolet/methods , Acetylation , Animals , Brachyura , Reference StandardsABSTRACT
Quaternized carboxymethyl chitosan (QCM-chitosan) and organic rectorite (OREC) immobilized nanofibrous mats are fabricated via layer-by-layer (LBL) technique in a self-assembly manner. The negatively charged cellulose nanofibrous mats hydrolyzed from electrospun cellulose acetate (CEL) mats are alternately modified with the positively charged QCM-chitosan and OREC intercalated composites and the negatively charged sodium alginate (ALG) via LBL technique. The morphology and antibacterial activity of the resultant mats are studied by changing the number of deposition bilayers, the compositions of dipping solutions and outermost layer. X-ray photoelectron spectroscopy results imply that QCM-chitosan and OREC are coated on cellulose mats. Besides, wide angle X-ray diffraction and small angle X-ray diffraction are applied to investigate the crystalline of the composite mats and the interlayer distance of OREC, respectively. The antibacterial activity of the mats increases with the incorporation of OREC into LBL films.
Subject(s)
Alginates/chemistry , Aluminum Silicates/chemistry , Anti-Bacterial Agents/chemistry , Chitosan/analogs & derivatives , Minerals/chemistry , Nanofibers/chemistry , Anti-Bacterial Agents/pharmacology , Chitosan/chemistry , Escherichia coli/drug effects , Polymerization , Staphylococcus aureus/drug effectsABSTRACT
The composite nanoparticles (NPs) consisted of quaternized chitosan (QC)/bovine serum albumin (BSA)/rectorite (REC) were prepared successfully just by adding BSA solution into QC-REC nanocomposites solution via electrostatic interactions. The average diameter of NPs increased with the accretion of REC, which was demonstrated with dynamic laser scattering (DLS) and transmission electron microscopy (TEM). The results of small angle X-ray diffraction (SAXRD) and selected area electron diffraction (SAED) demonstrated that the intercalated structure of REC was enlarged with the addition of REC. Besides, it can was proved that the interaction had occurred between QC and REC in NPs with fourier transform infrared (FT-IR) and X-ray photoelectron spectroscopy (XPS). In addition, doxorubicin (DOX) was used to investigate the entrapment efficiency and release pattern in NPs. It turned out to be that the addition of REC could increase the encapsulation efficiency (EE) and loading capacity (LC). The results also exhibited that the drug release in simulated gastric fluid reduced apparently with the addition of REC, which could ensure more DOX released in intestines.
Subject(s)
Aluminum Silicates/chemistry , Chitosan/chemistry , Drug Carriers/chemistry , Minerals/chemistry , Nanoparticles/chemistry , Serum Albumin, Bovine/chemistry , Antibiotics, Antineoplastic/chemistry , Doxorubicin/chemistry , Drug Liberation , Gastric Juice/chemistry , Green Chemistry Technology , Intestinal Secretions/chemistryABSTRACT
OBJECTIVE: To review the research progress of induced osteogenesis of bone marrow mesenchymal stem cells (BMSCs) transfected by double-gene. METHODS: The recent literature concerning the comparative research of induced osteogenesis of BMSCs transfected by double-gene was extensively reviewed. The characteristics of BMSCs, the advantage and effect of synergistic inductive osteogenesis, the application prospect and problems of BMSCs transfected by double-gene were summarized. RESULTS: The effect of induced osteogenesis concerning BMSCs transfected by double-gene is far superior to single gene transfection and the activity of osteoblast is also significantly increased. The research used in bone tissue engineering experiment also obtain good effect. CONCLUSION: Induced osteogenesis of BMSCs transfected by double-gene is able to make up for the lack of a single gene transfection and has great development prospects in the orthopaedic field.
Subject(s)
Bone Marrow Cells/cytology , Mesenchymal Stem Cells/cytology , Osteogenesis , Transfection/methods , Bone and Bones , Cells, Cultured , Hematopoietic Stem Cells , Humans , Mesenchymal Stem Cells/metabolism , Osteoblasts , Tissue Engineering/methodsABSTRACT
Sequential interpenetrating polymer networks (IPN) hydrogels based on konjac glucomannan (KGM) and poly(methacrylic acid) (PMAA) were prepared by immersion of a solution of methacrylic acid (MAA) monomer with cross-linker N,N'-methylenebisacrylamide (MBAAm) and initiating into a pre-fabricated dried KGM gel. Polymerization and cross-linking of MAA inside the KGM network resulted in a novel biodegradable pH-sensitive IPN hydrogel. The studies on the swelling behavior of IPN hydrogels reveal their sensitive response to environment pH value. It was possible to modulate the degree of swelling of the IPN gels by changing the KGM/PMAA ratio and the cross-linking density of the PMAA component. The KGM component in the IPN can be degraded by ß-glycosidase Mannaway25L. In vitro drug release behavior of IPN hydrogels were investigated under different environments using model drugs 5-fluorouracil. The results suggested that such an IPN hydrogel can be exploited as carrier candidate for colon-specific drug delivery.
Subject(s)
Delayed-Action Preparations/chemistry , Hydrogel, Polyethylene Glycol Dimethacrylate/chemistry , Mannans/chemistry , Polymethacrylic Acids/chemistry , Buffers , Fluorouracil/pharmacology , Hydrogen-Ion Concentration , Kinetics , Molecular Weight , Solutions , Spectroscopy, Fourier Transform InfraredABSTRACT
Proximal symphalangism (SYM1) is an autosomal dominant disorder characterized by ankylosis of the proximal interphalangeal joints and fusion of carpal and tarsal bones. We identified and characterized two five-generation Chinese families with SYM1. The two families share some similarities (e.g., osseous fusion of interphalangeal joints of the 2-4 fingers) with SYM1 families with mutations in the NOG gene or the family with mutation R438L recently reported in the GDF5 gene (encoding a bone morphogenetic protein family member). However, they show some unique features including the absence of cuboid bone, the lack of shortness of the first and fifth metacarpal bones, and manifestation of flat feet. Genome-wide linkage analysis of the two families mapped the disease gene to marker D20S112 with a combined LOD score of 4.32. Mutational analysis revealed a novel E491K mutation in the GDF5 gene in both families. The mutation occurs at a highly conserved residue in the TGF-beta domain of GDF5 and represents the second GDF5 mutation identified for SYM1 to date. The E491K mutation co-segregated with the affected individuals in the two families, and did not exist in unaffected family members or 200 normal controls. These results indicate that defects in GDF5 can cause SYM1 in the Chinese population, and expand the spectrum of clinical phenotypes associated with mutant GDF5.