ZNL0325, a Pyrazolopyrimidine-Based Covalent Probe, Demonstrates an Alternative Binding Mode for Kinases.

The pyrazolopyrimidine (PP) heterocycle is a versatile and widely deployed core scaffold for the development of kinase inhibitors. Typically, a 4-amino-substituted pyrazolopyrimidine binds in the ATP-binding pocket in a conformation analogous to the 6-aminopurine of ATP. Here, we report the discovery of ZNL0325 which exhibits a flipped binding mode where the C3 position is oriented toward the ribose binding pocket. ZNL0325 and its analogues feature an acrylamide side chain at the C3 position which is capable of forming a covalent bond with multiple kinases that possess a cysteine at the αD-1 position including BTK, EGFR, BLK, and JAK3. These findings suggest that the ability to form a covalent bond can override the preferred noncovalent binding conformation of the heterocyclic core and provides an opportunity to create structurally distinct covalent kinase inhibitors.

Efficient Oxidative Decomposition of Jet-Fuel exo-Tetrahydrodicyclopentadiene (JP-10) by Aluminum Nanoparticles in a Catalytic Microreactor: An Online Vacuum Ultraviolet Photoionization Study.

The oxidation of gas-phase exo-tetrahydrodicyclopentadiene (JP-10, C10H16) over aluminum nanoparticles (AlNP) has been explored between a temperature range of 300 and 1250 K with a novel chemical microreactor. The results are compared with those obtained from chemical microreactor studies of helium-seeded JP-10 and of helium-oxygen-seeded JP-10 without AlNP to gauge the effects of molecular oxygen and AlNP, respectively. Vacuum ultraviolet (VUV) photoionization mass spectrometry reveals that oxidative decomposition of JP-10 in the presence of AlNP is lowered by 350 and 200 K with and without AlNP, respectively, in comparison with pyrolysis of the fuel. Overall, 63 nascent gas-phase products are identified through photoionization efficiency (PIE) curves; these can be categorized as oxygenated molecules and their radicals as well as closed-shell hydrocarbons along with hydrocarbon radicals. Quantitative branching ratios of the products reveal diminishing yields of oxidized species and enhanced branching ratios of hydrocarbon species with the increase in temperature. While in the low-temperature regime (300-1000 K), AlNP solely acts as an efficient heat transfer medium, in the higher-temperature regime (1000-1250 K), chemical reactivity is triggered, facilitating the primary decomposition of the parent JP-10 molecule. This enhanced reactivity of AlNP could plausibly be linked to the exposed reactive surface of the aluminum (Al) core generated upon the rupture of the alumina shell material above the melting point of the metal (Al).

Genome-Wide CRISPR Screens Identify Multiple Synthetic Lethal Targets That Enhance KRASG12C Inhibitor Efficacy.

Non-small lung cancers (NSCLC) frequently (∼30%) harbor KRAS driver mutations, half of which are KRASG12C. KRAS-mutant NSCLC with comutated STK11 and/or KEAP1 is particularly refractory to conventional, targeted, and immune therapy. Development of KRASG12C inhibitors (G12Ci) provided a major therapeutic advance, but resistance still limits their efficacy. To identify genes whose deletion augments efficacy of the G12Cis adagrasib (MRTX-849) or adagrasib plus TNO155 (SHP2i), we performed genome-wide CRISPR/Cas9 screens on KRAS/STK11-mutant NSCLC lines. Recurrent, potentially targetable, synthetic lethal (SL) genes were identified, including serine-threonine kinases, tRNA-modifying and proteoglycan synthesis enzymes, and YAP/TAZ/TEAD pathway components. Several SL genes were confirmed by siRNA/shRNA experiments, and the YAP/TAZ/TEAD pathway was extensively validated in vitro and in mice. Mechanistic studies showed that G12Ci treatment induced gene expression of RHO paralogs and activators, increased RHOA activation, and evoked ROCK-dependent nuclear translocation of YAP. Mice and patients with acquired G12Ci- or G12Ci/SHP2i-resistant tumors showed strong overlap with SL pathways, arguing for the relevance of the screen results. These findings provide a landscape of potential targets for future combination strategies, some of which can be tested rapidly in the clinic. SIGNIFICANCE: Identification of synthetic lethal genes with KRASG12C using genome-wide CRISPR/Cas9 screening and credentialing of the ability of TEAD inhibition to enhance KRASG12C efficacy provides a roadmap for combination strategies. See related commentary by Johnson and Haigis, p. 4005.

Gas-phase formation of the resonantly stabilized 1-indenyl (C9H7•) radical in the interstellar medium.

The 1-indenyl (C9H7•) radical, a prototype aromatic and resonantly stabilized free radical carrying a six- and a five-membered ring, has emerged as a fundamental molecular building block of nonplanar polycyclic aromatic hydrocarbons (PAHs) and carbonaceous nanostructures in deep space and combustion systems. However, the underlying formation mechanisms have remained elusive. Here, we reveal an unconventional low-temperature gas-phase formation of 1-indenyl via barrierless ring annulation involving reactions of atomic carbon [C(3P)] with styrene (C6H5C2H3) and propargyl (C3H3•) with phenyl (C6H5•). Macroscopic environments like molecular clouds act as natural low-temperature laboratories, where rapid molecular mass growth to 1-indenyl and subsequently complex PAHs involving vinyl side-chained aromatics and aryl radicals can occur. These reactions may account for the formation of PAHs and their derivatives in the interstellar medium and carbonaceous chondrites and could close the gap of timescales of their production and destruction in our carbonaceous universe.

Proteomics-Based Discovery of First-in-Class Chemical Probes for Programmed Cell Death Protein 2 (PDCD2).

Chemical probes are essential tools for understanding biological systems and for credentialing potential biomedical targets. Programmed cell death 2 (PDCD2) is a member of the B-cell lymphoma 2 (Bcl-2) family of proteins, which are critical regulators of apoptosis. Here we report the discovery and characterization of 10 e, a first-in-class small molecule degrader of PDCD2. We discovered this PDCD2 degrader by serendipity using a chemical proteomics approach, in contrast to the conventional approach for making bivalent degraders starting from a known binding ligand targeting the protein of interest. Using 10 e as a pharmacological probe, we demonstrate that PDCD2 functions as a critical regulator of cell growth by modulating the progression of the cell cycle in T lymphoblasts. Our work provides a useful pharmacological probe for investigating PDCD2 function and highlights the use of chemical proteomics to discover selective small molecule degraders of unanticipated targets.

Unconventional gas-phase preparation of the prototype polycyclic aromatic hydrocarbon naphthalene (C10H8) via the reaction of benzyl (C7H7) and propargyl (C3H3) radicals coupled with hydrogen-atom assisted isomerization.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in the interstellar medium and in meteorites such as Murchison and Allende and signify the missing link between resonantly stabilized free radicals and carbonaceous nanoparticles (soot particles, interstellar grains). However, the predicted lifetime of interstellar PAHs of some 108 years imply that PAHs should not exist in extraterrestrial environments suggesting that key mechanisms of their formation are elusive. Exploiting a microchemical reactor and coupling these data with computational fluid dynamics (CFD) simulations and kinetic modeling, we reveal through an isomer selective product detection that the reaction of the resonantly stabilized benzyl and the propargyl radicals synthesizes the simplest representative of PAHs - the 10π Hückel aromatic naphthalene (C10H8) molecule - via the novel Propargyl Addition-BenzAnnulation (PABA) mechanism. The gas-phase preparation of naphthalene affords a versatile concept of the reaction of combustion and astronomically abundant propargyl radicals with aromatic radicals carrying the radical center at the methylene moiety as a previously passed over source of aromatics in high temperature environments thus bringing us closer to an understanding of the aromatic universe we live in.

Structure-Based Design of Y-Shaped Covalent TEAD Inhibitors.

Transcriptional enhanced associate domain (TEAD) proteins together with their transcriptional coactivator yes-associated protein (YAP) and transcriptional coactivator with the PDZ-binding motif (TAZ) are important transcription factors and cofactors that regulate gene expression in the Hippo pathway. In mammals, the TEAD families have four homologues: TEAD1 (TEF-1), TEAD2 (TEF-4), TEAD3 (TEF-5), and TEAD4 (TEF-3). Aberrant expression and hyperactivation of TEAD/YAP signaling have been implicated in a variety of malignancies. Recently, TEADs were recognized as being palmitoylated in cells, and the lipophilic palmitate pocket has been successfully targeted by both covalent and noncovalent ligands. In this report, we present the medicinal chemistry effort to develop MYF-03-176 (compound 22) as a selective, cysteine-covalent TEAD inhibitor. MYF-03-176 (compound 22) significantly inhibits TEAD-regulated gene expression and proliferation of the cell lines with TEAD dependence including those derived from mesothelioma and liposarcoma.

Development of a Covalent Inhibitor of c-Jun N-Terminal Protein Kinase (JNK) 2/3 with Selectivity over JNK1.

The c-Jun N-terminal kinases (JNKs) are members of the mitogen-activated protein kinase (MAPK) family, which includes JNK1-JNK3. Interestingly, JNK1 and JNK2 show opposing functions, with JNK2 activity favoring cell survival and JNK1 stimulating apoptosis. Isoform-selective small molecule inhibitors of JNK1 or JNK2 would be useful as pharmacological probes but have been difficult to develop due to the similarity of their ATP binding pockets. Here, we describe the discovery of a covalent inhibitor YL5084, the first such inhibitor that displays selectivity for JNK2 over JNK1. We demonstrated that YL5084 forms a covalent bond with Cys116 of JNK2, exhibits a 20-fold higher Kinact/KI compared to that of JNK1, and engages JNK2 in cells. However, YL5084 exhibited JNK2-independent antiproliferative effects in multiple myeloma cells, suggesting the existence of additional targets relevant in this context. Thus, although not fully optimized, YL5084 represents a useful chemical starting point for the future development of JNK2-selective chemical probes.

Exotic Reaction Dynamics in the Gas-Phase Preparation of Anthracene (C14H10) via Spiroaromatic Radical Transients in the Indenyl-Cyclopentadienyl Radical-Radical Reaction.

The gas-phase reaction between the 1-indenyl (C9H7•) radical and the cyclopentadienyl (C5H5•) radical has been investigated for the first time using synchrotron-based mass spectrometry coupled with a pyrolytic reactor. Soft photoionization with tunable vacuum ultraviolet photons afforded for the isomer-selective identification of the production of phenanthrene, anthracene, and benzofulvalene (C14H10). The classical theory prevalent in the literature proposing that radicals combine only at their specific radical centers is challenged by our discovery of an unusual reaction pathway that involves a barrierless combination of a resonantly stabilized hydrocarbon radical with an aromatic radical at the carbon atom adjacent to the traditional C1 radical center; this unconventional addition is followed by substantial isomerization into phenanthrene and anthracene via a category of exotic spiroaromatic intermediates. This result leads to a deeper understanding of the evolution of the cosmic carbon budget and provides new methodologies for the bottom-up synthesis of unique spiroaromatics that may be relevant for the synthesis of more complex aromatic carbon skeletons in deep space.

Unconventional Pathway in the Gas-Phase Synthesis of 9H-Fluorene (C13 H10 ) via the Radical-Radical Reaction of Benzyl (C7 H7 ) with Phenyl (C6 H5 ).

The simplest polycyclic aromatic hydrocarbon (PAH) carrying a five-membered ring-9H-fluorene (C13 H10 )-is produced isomer-specifically in the gas phase by reacting benzyl (C7 H7 ⋅) with phenyl (C6 H5 ⋅) radicals in a pyrolytic reactor coupled with single photon ionization mass spectrometry. The unconventional mechanism of reaction is supported by theoretical calculations, which first produces diphenylmethane and unexpected 1-(6-methylenecyclohexa-2,4-dienyl)benzene intermediates (C13 H12 ) accessed via addition of the phenyl radical to the ortho position of the benzyl radical. These findings offer convincing evidence for molecular mass growth processes defying conventional wisdom that radical-radical reactions are initiated through recombination at their radical centers. The structure of 9H-fluorene acts as a molecular building block for complex curved nanostructures like fullerenes and nanobowls providing fundamental insights into the hydrocarbon evolution in high temperature settings.

Covalent disruptor of YAP-TEAD association suppresses defective Hippo signaling.

The transcription factor TEAD, together with its coactivator YAP/TAZ, is a key transcriptional modulator of the Hippo pathway. Activation of TEAD transcription by YAP has been implicated in a number of malignancies, and this complex represents a promising target for drug discovery. However, both YAP and its extensive binding interfaces to TEAD have been difficult to address using small molecules, mainly due to a lack of druggable pockets. TEAD is post-translationally modified by palmitoylation that targets a conserved cysteine at a central pocket, which provides an opportunity to develop cysteine-directed covalent small molecules for TEAD inhibition. Here, we employed covalent fragment screening approach followed by structure-based design to develop an irreversible TEAD inhibitor MYF-03-69. Using a range of in vitro and cell-based assays we demonstrated that through a covalent binding with TEAD palmitate pocket, MYF-03-69 disrupts YAP-TEAD association, suppresses TEAD transcriptional activity and inhibits cell growth of Hippo signaling defective malignant pleural mesothelioma (MPM). Further, a cell viability screening with a panel of 903 cancer cell lines indicated a high correlation between TEAD-YAP dependency and the sensitivity to MYF-03-69. Transcription profiling identified the upregulation of proapoptotic BMF gene in cancer cells that are sensitive to TEAD inhibition. Further optimization of MYF-03-69 led to an in vivo compatible compound MYF-03-176, which shows strong antitumor efficacy in MPM mouse xenograft model via oral administration. Taken together, we disclosed a story of the development of covalent TEAD inhibitors and its high therapeutic potential for clinic treatment for the cancers that are driven by TEAD-YAP alteration.

Gas-phase synthesis of racemic helicenes and their potential role in the enantiomeric enrichment of sugars and amino acids in meteorites.

The molecular origins of homochirality on Earth is not understood well, particularly how enantiomerically enriched molecules of astrobiological significance like sugars and amino acids might have been synthesized on icy grains in space preceding their delivery to Earth. Polycyclic aromatic hydrocarbons (PAHs) identified in carbonaceous chondrites could have been processed in molecular clouds by circularly polarized light prior to the depletion of enantiomerically enriched helicenes onto carbonaceous grains resulting in chiral islands. However, the fundamental low temperature reaction mechanisms leading to racemic helicenes are still unknown. Here, by exploiting synchrotron based molecular beam photoionization mass spectrometry combined with electronic structure calculations, we provide compelling testimony on barrierless, low temperature pathways leading to racemates of [5] and [6]helicene. Astrochemical modeling advocates that gas-phase reactions in molecular clouds lead to racemates of helicenes suggesting a pathway for future astronomical observation and providing a fundamental understanding for the origin of homochirality on early Earth.

Urinary incontinence as a possible signal of neuromuscular toxicity during immune checkpoint inhibitor treatment: Case report and retrospective pharmacovigilance study.

Background: Immune checkpoint inhibitors (ICIs) are associated with different immune-related adverse events (irAEs), but there is limited evidence regarding the association between urinary incontinence and ICIs. Methods: We described the case of a patient experiencing urinary incontinence who later experienced a series of irAEs such as myocarditis, myositis, and neurologic diseases while on ICI treatment in our hospital. In addition, we queried the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) from the third quarter of 2010 to the third quarter of 2020 to perform a retrospective study to characterize the clinical features of urinary incontinence associated with ICIs. Result: In the FAERS study, 59 cases of ICI-related urinary incontinence were retrieved, and approximately 32.2% of the cases were fatal. Combination therapy with nervous system drugs and age >80 years old were the significant risk factors for fatal outcomes. Among these cases of ICI-related urinary incontinence, 40.7% (n = 24) occurred concomitantly with other adverse events, especially, neurological (fifteen cases), cardiovascular (seven cases), musculoskeletal (six cases), and urological disorders (five cases). Five cases had an overlapping syndrome similar to our case report, including one case of myasthenia gravis with myocarditis and another of myasthenic syndrome with polymyositis. Conclusion: ICI-related urinary incontinence might be a signal of fatal neuromuscular irAEs, especially when it occurs concomitantly with ICI-associated neuromuscular-cardiovascular syndrome. Clinicians should be aware of the occurrence of urinary incontinence to identify potentially lethal irAEs in the early phase.

Neuroendoscopic-assisted versus mini-open craniotomy for hypertensive intracerebral hemorrhage: a retrospective analysis.

OBJECTIVE: To compare outcomes in neuroendoscopic-assisted vs mini-open craniotomy for hypertensive intracerebral hemorrhage (HICH), so as to provide reasonable surgical treatment. METHODS: Clinical data of 184 patients with HICH in the hospital from January 2019 to May 2021 were analyzed retrospectively. The patients were divided into mini-open craniotomy group and neuroendoscopic-assisted group. The operation time, hematoma clearance rate, intraoperative blood loss, neurological function recovery, and postoperative mortality of the two groups were compared by retrospective analysis. RESULTS: The operation time and intraoperative blood loss in the mini-open craniotomy group were more than those in the neuroendoscopic-assisted group, but there was no significant difference between the two groups. There was no significant difference in hematoma clearance rate between the two groups, but for the rugby hematoma, the hematoma clearance rate in the neuroendoscopic-assisted group was higher than in the mini-open craniotomy group, the difference was statistically significant. Within 1 month after the operation, there was no significant difference in mortality between the two groups. 6 months after the operation, there was no significant difference in the recovery of neurological function between the two groups. CONCLUSION: Neuroendoscopic-assisted and mini-open craniotomy for the treatment of HICH has the advantages of minimal trauma with good effects, and its main reason for short operation time, reduced bleeding, and high hematoma clearance rate. Although the two surgical methods can improve the survival rate of patients, they do not change the prognosis of patients. Therefore, the choice of surgical methods should be adopted based on the patient's clinical manifestations, hematoma volume, hematoma type, and the experience of the surgeon.

Formation of Benzene and Naphthalene through Cyclopentadienyl-Mediated Radical-Radical Reactions.

Resonantly stabilized free radicals (RSFRs) have been contemplated as fundamental molecular building blocks and reactive intermediates in molecular mass growth processes leading to polycyclic aromatic hydrocarbons (PAHs) and carbonaceous nanoparticles on Earth and in deep space. By combining molecular beams and computational fluid dynamics simulations, we provide compelling evidence on the formation of benzene via the cyclopentadienyl-methyl reaction and of naphthalene through the cyclopentadienyl self-reaction, respectively. These systems offer benchmarks for the conversion of a five-membered ring to the 6π-aromatic (benzene) and the generation of the simplest 10π-PAH (naphthalene) at elevated temperatures. These results uncover molecular mass growth processes from the "bottom up" via RSFRs in high temperature circumstellar environments and combustion systems expanding our fundamental knowledge of the organic, hydrocarbon chemistry in our universe.

Development of PDE6D and CK1α Degraders through Chemical Derivatization of FPFT-2216.

Immunomodulatory drugs are a class of drugs approved for the treatment of multiple myeloma. These compounds exert their clinical effects by inducing interactions between the CRL4CRBN E3 ubiquitin ligase and a C2H2 zinc finger degron motif, resulting in degradation of degron-containing targets. However, although many cellular proteins feature the degron motif, only a subset of those are degradable via this strategy. Here, we demonstrated that FPFT-2216, a previously reported "molecular glue" compound, degrades PDE6D, in addition to IKZF1, IKZF3, and CK1α. We used FPFT-2216 as a starting point for a focused medicinal chemistry campaign and developed TMX-4100 and TMX-4116, which exhibit greater selectivity for degrading PDE6D and CK1α, respectively. We also showed that the region in PDE6D that interacts with the FPFT-2216 derivatives is not the previously pursued prenyl-binding pocket. Moreover, we found that PDE6D depletion by FPFT-2216 does not impede the growth of KRASG12C-dependent MIA PaCa-2 cells, highlighting the challenges of drugging PDE6D-KRAS. Taken together, the approach we described here represents a general scheme to rapidly develop selective degraders by reprogramming E3 ubiquitin ligase substrate specificity.

Analysis of the Influence of the Breaking Radiation Magnetic Field of a 10 kV Intelligent Circuit Breaker on an Electronic Transformer.

The development of the smart grid requires the distribution switch to not be limited to the original breaking function. More functional requirements lead to more complex switch structures, especially the intelligent processing unit on the secondary side. A technology called primary and secondary integration optimizes the structure of the switch, which greatly increases the intelligence level of the switch, but also has disadvantages. The secondary intelligent unit is arranged close to the primary high-voltage electromagnetic environment, and the distribution switch is prone to failure due to electromagnetic interference. In order to explore the influence of electromagnetic interference on it, a transient electromagnetic interference simulation test platform was built for a 10 kV intelligent distribution switch based on the principle of spherical gap arc discharge, and the interference signal of the intelligent distribution switch was measured; the law of the spatial magnetic field near the electronic transformer is mainly studied in this paper. The shielding effectiveness of the distribution terminal of the switch was analyzed, and the interference of the power line of the sensor merging unit circuit board was calculated. The results show that the electronic transformer may have serious faults under continuous strong transient electromagnetic interference. The electromagnetic transient simulation test system studied in this paper can evaluate the anti strong electromagnetic interference ability of the electronic transformer.

Discovery of a subtype-selective, covalent inhibitor against palmitoylation pocket of TEAD3.

The TEA domain (TEAD) family proteins (TEAD1‒4) are essential transcription factors that control cell differentiation and organ size in the Hippo pathway. Although the sequences and structures of TEAD family proteins are highly conserved, each TEAD isoform has unique physiological and pathological functions. Therefore, the development and discovery of subtype selective inhibitors for TEAD protein will provide important chemical probes for the TEAD-related function studies in development and diseases. Here, we identified a novel TEAD1/3 covalent inhibitor (DC-TEADin1072) with biochemical IC50 values of 0.61 ± 0.02 and 0.58 ± 0.12 µmol/L against TEAD1 and TEAD3, respectively. Further chemical optimization based on DC-TEAD in 1072 yielded a selective TEAD3 inhibitor DC-TEAD3in03 with the IC50 value of 0.16 ± 0.03 µmol/L, which shows 100-fold selectivity over other TEAD isoforms in activity-based protein profiling (ABPP) assays. In cells, DC-TEAD3in03 showed selective inhibitory effect on TEAD3 in GAL4-TEAD (1-4) reporter assays with the IC50 value of 1.15 µmol/L. When administered to zebrafish juveniles, experiments showed that DC-TEAD3in03 reduced the growth rate of zebrafish caudal fins, indicating the importance of TEAD3 activity in controlling proportional growth of vertebrate appendages.

A molecular beam and computational study on the barrierless gas phase formation of (iso)quinoline in low temperature extraterrestrial environments.

Despite remarkable progress toward the understanding of the formation pathways leading to polycyclic aromatic hydrocarbons (PAHs) in combustion systems and in deep space, the complex reaction pathways leading to nitrogen-substituted PAHs (NPAHs) at low temperatures of molecular clouds and hydrocarbon-rich, nitrogen-containing atmospheres of planets and their moons like Titan have remained largely obscure. Here, we demonstrate through laboratory experiments and computations that the simplest prototype of NPAHs - quinoline and isoquinoline (C9H7N) - can be synthesized via rapid and de-facto barrier-less reactions involving o-, m- and p-pyridinyl radicals (C5H4N˙) with vinylacetylene (C4H4) under low-temperature conditions.

Knowledge, attitude and practices regarding health self-management among patients with osteogenesis imperfecta in China: an online cross-sectional survey.

OBJECTIVES: Assessing the knowledge, attitude and practices (KAP) regarding health self-management among patients with osteogenesis imperfecta (OI) in China. DESIGN: An online cross-sectional survey. SETTING: A structured questionnaire was distributed online through China-Dolls Center for Rare Disorders (CCRD), a non-governmental charity in China. PARTICIPANTS: Participants were all patients with OI from CCRD. After stratified sampling according to the economic level of residential city, 901 patients were proportionally selected and 869 patients completed the survey (response rate: 96.4%). MAIN OUTCOME MEASURES: Demographic characteristics and KAP information were gathered using a 5-point Likert scale. The score of each dimension of KAP was the sum of the scores of all included items. Χ2 test or Fisher's exact test was used to compare scores of different items. Ordinal regression was employed to determine the significant factors influencing KAP. RESULTS: A total of 802 questionnaires were included for analysis. Male respondents accounted for 57.1%, and 29.1% of respondents were of 26~30 years. More than half (50~60%) of patients knew the main symptoms of OI and the treatment of OI-related complications. Almost 80% of patients showed positive attitude. Nearly 60~70% of the patients were relatively able to take appropriate practice regarding OI management. There was a significant correlation between scores of knowledge and attitude, attitude and practice, as well as knowledge and practice. Patients aged 26~30 years, from urban areas and big cities, had higher KAP scores. Male patients showed better performance in knowledge, and highly educated patients perform better in practice. CONCLUSIONS: Patients with OI did not have sufficient knowledge on disease care and up-to-date caring guidelines, and their practice regarding health self-management also needs to be improved. Gender, age, educational level and economic level of residence can affect the level of KAP for patients, thus developing targeted and tailored programmes for patients with OI is highly recommended.