Identification of A Novel Variant of Filamin A Destroying the Attraction Between Benzene Rings and Sulfhydryl in Developmental Dysplasia of the Hip.

Developmental dysplasia of the hip (DDH), characterized by acetabular deformity that manifests from loose ligaments to complete dislocation of the hip, can cause notable pain and dysfunction and lead to hip dislocation, secondary fractures, scoliosis, and osteoarthritis of hip. Variants in FLNA may produce a spectrum of malformations in multiple organs, especially the skeleton. This study aimed to identify the genetic etiologies of DDH patients and provide genetic testing information for further diagnosis and treatment of DDH. We recruited a Chinese woman with DDH and her family members. Whole-exome sequencing was used to identify the patient's genetic etiologies. Protein models were used to analyze the pathogenic mechanism of the identified variants. A novel variant (c.3493T>G, p.C1165G) of FLNA was detected. The structural models of the mutant FLNA protein indicated that the variant would lose its sulfhydryl side chain and destroy the attraction between benzene rings and sulfhydryl. We reported a novel variant (c.3493T>G, p.C1165G) of FLNA in a Chinese woman with DDH. Our research outcome enriches the gene pool for hip dysplasia and emphasizes the pathogenicity of sulfhydryl side chain disruption in FLNA.

The application of infrared thermography technology in flap: A perspective from bibliometric and visual analysis.

The application of infrared thermography technology (IRT) in flap has become a major focus of research, as it provides a non-invasive, real-time, and quantitative approach for monitoring flap perfusion. In this regard, we conducted a comprehensive visualization and scientometric analysis to systematically summarize and discuss the current state of research in this field. We systematically reviewed publications on the application of IRT in flap procedures from 1999 to 2022, using the Web of Science Core Collection (WoSCC). Through scientometric analysis, we examined annual trends, affiliations, countries, journals, authors, and their relationships, providing insights into current hotspots and future developments in this area. We analysed 522 English studies and found a steady increase in annual publications. The United States and Germany had the highest publication rates, with Beth Israel Deaconess Medical Center and Shanghai Jiaotong University being leading institutions. Notably, Lee BT and Alex Keller emerged as influential authors in this field. Compared to existing techniques, infrared-based technology offers significant advantages for non-invasive monitoring of flap perfusion, including simplicity of operation and objective results. Future trends should focus on interdisciplinary collaborations to develop new infrared devices and achieve intelligent image processing, enabling broader application in various clinical scenarios. This bibliometric study summarizes the progress and landscape of research on 'the Application of infrared thermography technology in flap' over the past two decades, providing valuable insights and serving as a reliable reference to drive further advancements and spark researchers' interest in this field.

The research landscape on vascularized composite allografts: a bibliometric analysis (2002-2021).

OBJECTIVE: Vascularized composite allografts (VCAs) refer to the transplantation of multiple types of tissues during plastic and reconstructive surgery. Several publications have emerged in the field of VCA. However, there are no bibliometric studies on this topic. The aim was to multidimensionally analyze the knowledge base and hotspots in this subject. METHODS: We retrieved all publications related to VCA from the Web of Science Core Collection (WoSCC), published from 2002 to 2021. Next, scientometric analysis of different items was performed using various bibliometrics software to explore knowledge base, research hotspots, and advancement trends in this field. RESULTS: We included a total of 3,190 English articles from 2002 to 2021. The number of publications increased steadily annually. The United States produced the highest number of publications, followed by China. Most publications were from Harvard University, followed by Johns Hopkins University. The most authoritative academic journal was Plastic and Reconstructive Surgery. Transplantation occupied the first rank of co-cited journal list. Maria Z Siemionow may have the highest influence in the VCA field with the highest number of citations (n = 88) and co-cited references (n = 1252). Clinical studies on different allografts, immunosuppression, and tissue engineering were both the knowledge base and recent topics in VCA research. CONCLUSIONS: The first bibliometric study comprehensively summarized the trends and development of VCA research with steady growth over the past two decades. Currently, the most active topics are the clinical application of multiple allografts, immunosuppression strategies/therapies, and translation of tissue engineering to clinical practice.

R97 at "Handlebar" Binding Mode in Active Pocket Plays an Important Role in Fe(II)/α-Ketoglutaric Acid-Dependent Dioxygenase cis-P3H-Mediated Selective Synthesis of (2S,3R)-3-Hydroxypipecolic Acid.

Pipecolic acid (Pip) and its derivative hydroxypipecolic acids, such as (2S,3R)-3-hydroxypipecolic acid (cis-3-L-HyPip), are components of many natural and synthetic bioactive molecules. Fe(II)/α-ketoglutaric acid (Fe(II)/2-OG)-dependent dioxygenases can catalyze the hydroxylation of pipecolic acid. However, the available enzymes with desired activity and selectivity are limited. Herein, we compare the possible candidates in the Fe(II)/2-OG-dependent dioxygenase family, and cis-P3H is selected for potentially catalyzing selective hydroxylation of L-Pip. cis-P3H was further engineered to increase its catalytic efficiency toward L-Pip. By analyzing the structural confirmation and residue composition in substrate-binding pocket, a "handlebar" mode of molecular interactions is proposed. Using molecular docking, virtual mutation analysis, and dynamic simulations, R97, E112, L57, and G282 were identified as the key residues for subsequent site-directed saturation mutagenesis of cis-P3H. Consequently, the variant R97M showed an increased catalytic efficiency toward L-Pip. In this study, the kcat/Km value of the positive mutant R97M was about 1.83-fold that of the wild type. The mutation R97M would break the salt bridge between R97 and L-Pip and weaken the positive-positive interaction between R97 and R95. Therefore, the force on the amino and carboxyl groups of L-Pip was lightly balanced, allowing the molecule to be stabilized in the active pocket. These results provide a potential way of improving cis-P3H catalytic activity through rational protein engineering.

Current Researches on Nanodrug Delivery Systems in Bladder Cancer Intravesical Chemotherapy.

Bladder cancer is one of the most common malignant tumors in urinary system. Intravesical chemotherapy is a common adjuvant therapy after transurethral resection of bladder tumors. However, it has several disadvantages such as low drug penetration rate, short residence time, unsustainable action and inability to release slowly, thus new drug delivery and new modalities in delivery carriers need to be continuously explored. Nano-drug delivery system is a novel way in treatment for bladder cancer that can increase the absorption rate and prolong the duration of drug, as well as sustain the action by controlling drug release. Currently, nano-drug delivery carriers mainly included liposomes, polymers, and inorganic materials. In this paper, we reveal current researches in nano-drug delivery system in bladder cancer intravesical chemotherapy by describing the applications and defects of liposomes, polymers and inorganic material nanocarriers, and provide a basis for the improvement of intravesical chemotherapy drugs in bladder cancer.

Sensitive Electrochemiluminescence Biosensor Based on the Target Trigger Difference of the Electrostatic Interaction between an ECL Reporter and the Electrode Surface.

The discrepancy of the electrostatic interaction of negatively charged signal molecules to long and short DNA strands of the modified electrode surface has been used for the first time to the develop an electrochemiluminescence (ECL) biosensor for human papillomavirus 16 (HPV 16) DNA detection. The short single-stranded capture probe (CP) was modified first on the surface of the gold electrode, which only has a small amount of negative charge. The electrostatic interaction between the negatively charged tris(2,2'-bipyridyl) ruthenium(II) chloride hexahydrate-doped SiO2 nanoparticles (Ru@SiO2 NPs) and CP is weak, hence Ru@SiO2 NPs easily diffuse to the surface of the electrode to generate a strong ECL signal. Hybrid chain reaction (HCR) amplification products (long strand dsDNA) were prepared in homogeneous solution in advance. When the target was present, the dsDNA can be connected on the electrode surface and cause the enhancement of the negative charge on the electrode surface. Owing to electrostatic interaction and steric hindrance, Ru@SiO2 NPs are difficult to diffuse to the electrode surface, resulting in a significantly reduced ECL signal. The decrease of ECL signal is linearly correlated with the logarithm of the HPV concentration under optimal conditions, with the detection range being 0.1 fM -5 pM with a limit of 1.41 aM. This innovative methodology expands the application of electrostatic interaction in ECL sensing, but can also easily develop biosensors for detecting other targets by changing the DNA sequence used in this strategy.

Facile Transformations of a Binuclear Cp*Co(II) Diamidonaphthalene Complex to Mixed-Valent Co(II)Co(III), Co(III)(µ-H)Co(III), and Co(III)(µ-OH)Co(III) Derivatives.

A diamido-bridged dicobalt complex supported by a diamidonaphthalene ligand, Cp*2Co2(µ-1,8-C10H8(NH)2) (1), was synthesized, and the reactivity relevant to redox transformations of the Co2N2 core was investigated. It was found that the Co(II)-Co(II) bond allows for protonation by [HPPh3][BF4] resulting in a bridging hydride, [1H]+, with pKa ∼ 7.6 in CH2Cl2. The diamidonaphthalene ligand can stabilize the binuclear system in the Co(II)Co(III) mixed-valent state (1+), which is capable of binding CO to afford [1-CO]+. Surprisingly, the mixed-valent complex also activates H2O to furnish a Co(III)Co(III) hydroxy complex [1-OH]+ accompanied by release of H2. The hydroxy ligand in [1-OH]+ is exchangeable, as demonstrated by 18O-labeling experiments on [1-OH]+ with H218O that led to the heavier isotopolog [1-18OH]+.

Design of an electrochemiluminescence detection system through the regulation of charge density in a microchannel.

Rare electrochemiluminescence (ECL) sensors have been developed based on the direct regulation of ionic current because it is difficult to establish a relationship between ionic current and ECL reporting. Ionic current can be adjusted by the effective radius and charge density of a functionalized microchannel and is frequently adopted to develop electrical sensors. Here, we show a novel ECL sensing platform that combines the microchannel-based electrical sensing technology with an ECL reporting system for the first time. The target regulated the effective radius and charge density of a microchannel which in turn adjusted the ionic transport in it and finally caused the change of ECL reporting of a tris(1,10-phenanthroline)ruthenium(ii)/tripropylamine system. The developed system has already been applied to detect aflatoxin B1 for demonstration. This configuration separated the target sensing and reporting reactions to achieve direct regulation of ECL reporting by ionic current and expanded the application of the ECL detection technology to microanalysis.

Screening and mitigating major threats of regional development to water ecosystems using ecosystem services as endpoints.

Coordinating the coercion of human activities to the ecosystem is a continuous strategic concern. A practical way to conceptualize socioeconomic development and link it to ecosystem response is urgently needed. This study proposed a two-staged method to reveal the threats concealed in socioeconomic development and show the return of water ecosystem services to regulation measures. Eight threat indexes referring to scale, structure and efficiencies of industrial, agriculture and domestic sectors were designed to assess the threats caused by unsustainable development features, while four indexes for evaluating water supply, habitat provision, regulation and quality purification service of ecosystem were set up. For each threat index, the evaluation result is a relative value derived from comparison with a reasonable level. The major threats could be screened out by ranking threat indexes, so that unreasonable development dimension could be identified and subsequent regulation scheme be prepared. On this basis, with the targeted adjustment of socioeconomic development, corresponding improvements in water ecosystem could be expected and quantified. In the case study of Beijing-Tianjin-Hebei District, the most remarkable threats include production inefficiency of the industrial sector and oversized population, of which degrees of deviation from reasonable levels exceed 70%. When all development dimensions were dragged to the suggested levels, the habitat provision and water supply service would witness the largest progress among four services, with the values rising from 0.49 to nearly 1. This method helps discover the critical defect of socioeconomic development in terms of ecosystem response and facilitate the decision maker to establish more sustainable initiatives.

WRF-Chem modeling of particulate matter in the Yangtze River Delta region: Source apportionment and its sensitivity to emission changes.

China has been troubled by high concentrations of fine particulate matter (PM2.5) for many years. Up to now, the pollutant sources are not yet fully understood and the control approach still remains highly uncertain. In this study, four month-long (January, April, July and October in 2015) WRF-Chem simulations with different sensitivity experiments were conducted in the Yangtze River Delta (YRD) region of eastern China. The simulated results were compared with abundant meteorological and air quality observations at 138 stations in 26 YRD cities. Our model well captured magnitudes and variations of the observed PM2.5, with the normal mean biases (NMB) less than ±20% for 19 out of the 26 YRD cities. A series of sensitivity simulations were conducted to quantify the contributions from individual source sectors and from different regions to the PM2.5 in the YRD region. The calculated results show that YRD local source contributed 64% of the regional PM2.5 concentration, while outside transport contributed the rest 36%. Among the local sources, industry activity was the most significant sector in spring (25%), summer (36%) and fall (33%), while residential source was more important in winter (38%). We further conducted scenario simulations to explore the potential impacts of varying degrees of emission controls on PM2.5 reduction. The result demonstrated that regional cooperative control could effectively reduce the PM2.5 level. The proportionate emission controls of 10%, 20%, 30%, 40% and 50% could reduce the regional mean PM2.5 concentrations by 10%, 19%, 28%, 37% and 46%, respectively, and for places with higher ambient concentrations, the mitigation efficiency was more significant. Our study on source apportionment and emission controls can provide useful information on further mitigation actions.