The temporal protein signature analyses of developing human deciduous molar tooth germ.

The tooth serves as an exemplary model for developmental studies, encompassing epithelial-mesenchymal transition and cell differentiation. The essential factors and pathways identified in tooth development will help understand the natural development process and the malformations of mineralized tissues such as skeleton. The time-dependent proteomic changes were investigated through the proteomics of healthy human molars during embryonic stages, ranging from the cap-to-early bell stage. A comprehensive analysis revealed 713 differentially expressed proteins (DEPs) exhibiting five distinct temporal expression patterns. Through the application of weighted gene co-expression network analysis (WGCNA), 24 potential driver proteins of tooth development were screened, including CHID1, RAP1GDS1, HAPLN3, AKAP12, WLS, GSS, DDAH1, CLSTN1, AFM, RBP1, AGO1, SET, HMGB2, HMGB1, ANP32A, SPON1, FREM1, C8B, PRPS2, FCHO2, PPP1R12A, GPALPP1, U2AF2, and RCC2. Then, the proteomics and transcriptomics expression patterns of these proteins were further compared, complemented by single-cell RNA-sequencing (scRNA-seq). In summary, this study not only offers a wealth of information regarding the molecular intricacies of human embryonic epithelial and mesenchymal cell differentiation but also serves as an invaluable resource for future mechanistic inquiries into tooth development.

Temperature-sensitive hydrogel releasing pectolinarin facilitate scarless wound healing.

The dressing that promotes scarless healing is essential for both normal function and aesthetics after a wound. With a deeper understanding of the mechanisms involved in scar formation during the wound healing process, the ideal dressing becomes clearer and more promising. For instance, the yes-associated transcriptional regulator (YAP) has been extensively studied as a key gene involved in regulating scar formation. However, there has been limited attention given to pectolinarin, a natural flavonoid that may exhibit strong binding affinity to YAP, in the context of scarless healing. In this study, we successfully developed a temperature-sensitive Pluronic@F-127 hydrogel as a platform for delivering pectolinarin to promote scarless wound healing. The bioactive pectolinarin was released from the hydrogel, effectively enhancing endothelial cell migration, proliferation and the expression of angiogenesis-related genes. Additionally, a concentration of 20 µg/mL of pectolinarin demonstrated remarkable antioxidant ability, capable of counteracting the detrimental effects of reactive oxygen species (ROS). Our results from rat wound healing models demonstrated that the hydrogel accelerated wound healing, promoting re-epithelialization and facilitating skin appendage regeneration. Furthermore, we discovered that a concentration of 50 µg/mL of pectolinarin incorporated to the hydrogel exhibited the most favourable outcomes in terms of promoting wound healing and minimizing scar formation. Overall, our study highlights that the significant potential of locally released pectolinarin might substantially inhibit YAP and promoting scarless wound healing.

Photochemical Mechanisms of Hydroxyquinoline Benzimidazole: Insights from Electronic Structure Calculations and Nonadiabatic Dynamics Simulations.

Excited-state intramolecular double proton transfer (ESIDPT) has received much attention because of its widespread existence in the life reactions of living organisms, and materials with this property are significant for their special luminescent properties. In this work, the complete active space self-consistent field (CASSCF) and OM2/multireference configuration interaction (OM2/MRCI) methods have been employed to study the static electronic structure calculations of the photochemistry and the possibility of ESIDPT process of hydroxyquinoline benzimidazole (HQB) molecule, along with the nonadiabatic dynamics simulations. The computational results show that the HQB molecule is relaxed to the S1-ENOL minimum after being excited to the Franck-Condon point in the S1 state. Subsequently, during the nonadiabatic deactivation process, the OH···N proton transfer and the twisting of benzimidazole occur before arriving at the single proton transfer conical intersection S1S0-KETO. Finally, the system can either return to the initial ground-state structure S0-ENOL or to the single proton transfer ground-state structure S0-KETO, both of which have almost the same probability. The dynamics simulations also show that no double proton transfer occurs. The excited-state lifetime of HQB is fitted to 1.1 ps, and only 64% of the dynamic trajectories return to the ground state within the 2.0 ps simulation time. We hope the detailed reaction mechanism of the HQB molecule will provide new insights into similar systems.

Exploring new avenues of health protection: plant-derived nanovesicles reshape microbial communities.

Symbiotic microbial communities are crucial for human health, and dysbiosis is associated with various diseases. Plant-derived nanovesicles (PDNVs) have a lipid bilayer structure and contain lipids, metabolites, proteins, and RNA. They offer unique advantages in regulating microbial community homeostasis and treating diseases related to dysbiosis compared to traditional drugs. On the one hand, lipids on PDNVs serve as the primary substances that mediate specific recognition and uptake by bacteria. On the other hand, due to the multifactorial nature of PDNVs, they have the potential to enhance growth and survival of beneficial bacterial while simultaneously reducing the pathogenicity of harmful bacteria. In addition, PDNVs have the capacity to modulate bacterial metabolism, thus facilitating the establishment of a harmonious microbial equilibrium and promoting stability within the microbiota. These remarkable attributes make PDNVs a promising therapeutic approach for various conditions, including periodontitis, inflammatory bowel disease, and skin infection diseases. However, challenges such as consistency, isolation methods, and storage need to be addressed before clinical application. This review aims to explore the value of PDNVs in regulating microbial community homeostasis and provide recommendations for their use as novel therapeutic agents for health protection.

Non-adiabatic dynamics simulations of the S1 excited-state relaxation of diacetyl phenylenediamine.

The small molecule built around the benzene ring, diacetyl phenylenediamine (DAPA), has attracted much attention due to its synthesis accessibility, large Stokes shift, etc. However, its meta structure m-DAPA does not fluoresce. In a previous investigation, it was found that such a property is due to the fact that it undergoes an energy-reasonable double proton transfer conical intersection during the deactivation of the S1 excited-state, then returns to the ground state by a nonradiative relaxation process eventually. However, our static electronic structure calculations and non-adiabatic dynamics analysis results indicate that only one reasonable non-adiabatic deactivation channel exists: after being excited to the S1 state, m-DAPA undergoes an ultrafast and barrierless ESIPT process and reaches the single-proton-transfer conical intersection. Subsequently, the system either returns to the keto-form S0 state minimum with proton reversion or returns to the single-proton-transfer S0 minimum after undergoing a slight twist of the acetyl group. The dynamics results show that the S1 excited-state lifetime of m-DAPA is 139 fs. In other words, we propose an efficient single-proton-transfer non-adiabatic deactivation channel of m-DAPA that is different from previous work, which can provide important mechanistic information of similar fluorescent materials.

Excited-state relaxation mechanisms of 2,2'-(1-phenyl-1H-1,2,4-triazole-3,5-diyl)diphenol: single- or double-proton transfer?

Triazole compounds are important organic systems with excellent electronic properties, which have diagnostic potential in the fields of organic electronics and organic photovoltaics. The important photophysical nature of these systems is the transformation between the enol and keto forms after excited-state proton transfer. In this study, the IR vibrational spectrum, ESIPT mechanism, and excited-state decay dynamics of 2,2'-(1-phenyl-1H-1,2,4-triazole-3,5-diyl)diphenol (ExPh) were explored using electronic structure calculations and non-adiabatic dynamics simulations. Two S1/S0 conical intersections with distinct proton transfer (ESIPT-I and ESIPT-II) involved were obtained. The associated two-dimensional S1 minimum-energy potential energy surface indicated that the dynamical roles of these two S1/S0 conical intersections in the S1 excited-state decay were quite different. The ESIPT-I reaction was more favorable to occur than the ESIPT-II process. Our dynamics simulations supported this hypothesis with the whole trajectories decaying to the ground state via the S1S0-1 conical intersection, which involved the ESIPT-I process. The ESIPT-Involved efficient deactivation pathway could be partially responsible for the decrease in fluorescence emission. These results and ESIPT mechanisms are helpful for understanding the decay pathways of similar systems.

Utilizing nanozymes for combating COVID-19: advancements in diagnostics, treatments, and preventative measures.

The emergence of human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses significant challenges to global public health. Despite the extensive efforts of researchers worldwide, there remains considerable opportunities for improvement in timely diagnosis, specific treatment, and effective vaccines for SARS-CoV-2. This is due, in part, to the large number of asymptomatic carriers, rapid virus mutations, inconsistent confinement policies, untimely diagnosis and limited clear treatment plans. The emerging of nanozymes offers a promising approach for combating SARS-CoV-2 due to their stable physicochemical properties and high surface areas, which enable easier and multiple nano-bio interactions in vivo. Nanozymes inspire the development of sensitive and economic nanosensors for rapid detection, facilitate the development of specific medicines with minimal side effects for targeted therapy, trigger defensive mechanisms in the form of vaccines, and eliminate SARS-CoV-2 in the environment for prevention. In this review, we briefly present the limitations of existing countermeasures against coronavirus disease 2019 (COVID-19). We then reviewed the applications of nanozyme-based platforms in the fields of diagnostics, therapeutics and the prevention in COVID-19. Finally, we propose opportunities and challenges for the further development of nanozyme-based platforms for COVID-19. We expect that our review will provide valuable insights into the new emerging and re-emerging infectious pandemic from the perspective of nanozymes.

Plant-derived nanovesicles: harnessing nature's power for tissue protection and repair.

Tissue damage and aging lead to dysfunction, disfigurement, and trauma, posing significant global challenges. Creating a regenerative microenvironment to resist external stimuli and induce stem cell differentiation is essential. Plant-derived nanovesicles (PDNVs) are naturally bioactive lipid bilayer nanovesicles that contain proteins, lipids, ribonucleic acid, and metabolites. They have shown potential in promoting cell growth, migration, and differentiation into various types of tissues. With immunomodulatory, microbiota regulatory, antioxidant, and anti-aging bioactivities, PDNVs are valuable in resisting external stimuli and facilitating tissue repair. The unique structure of PDNVs provides an optimal platform for drug encapsulation, and surface modifications enhance their stability and specificity. Moreover, by employing synergistic administration strategies, PDNVs can maximize their therapeutic potential. This review summarized the progress and prospects of PDNVs as regenerative tools, provided insights into their selection for repair activities based on existing studies, considered the key challenge for clinical application, and anticipated their continued prominent role in the field of biomedicine.

Trunk rot of Juglans regia caused by Myrmaecium fulvopruinatum in China.

Walnut (Juglans regia) is a deciduous tree of the Juglandaceae family, widely cultivated in China, and provides value in a variety of ways, including the usage of the wood and nuts, and offers substantial economic, social, and environmental advantages (Wang et al, 2017). Nevertheless, a fungal disease of causing walnut trunk rot was observed in approximately 30% of 50 counted ten-year-old J. regia in Chongzhou City (30°33'34″N, 103°38'35″E, 513 m), Sichuan Province, China, and this disease has greatly delete healthy growth of walnut. The infected bark exhibited purple necrotic lesions, and the sick parts were surrounded by water-soaked plaques. From 10 trunks of the 10 diseased trees, 20 isolated fungal colonies were the same. The ascospores placed in 60 mm plates were almost entirely covered with mycelium within 8 days, colonies on the PDA changed from initial pale to white, ad then turned yellowish to light orange or rosy to yellow-brown (25℃, 90% relative humidity, 12-h photoperiod). On the host, Ectostromata were immersed to erumpent, globose to subglobose, purple and brown, and measured 0.6 - 4.5 × 0.3 - 2.8 mm (x̄ = 2.6 × 1.6 mm, n = 40); Ascomata were flask-shaped to subglobose, dark brown, and measured 0.1 - 0.6 × 0.1 - 0.4 mm (x̄ = 0.35 × 0.25 mm, n = 40); Asci were numerous, cylindrical to subclavate, contained 8 uniseriate ascospores, and measured 80 - 150 × 10 - 20 µm (x̄ = 115 × 15 µm, n = 40), and Ascospores were ellipsoid, 2-celled, dark brown to black, plump or attenuated towards, apices with 1 large drop per cell, and measured 14 - 20 × 6.5 - 9 µm (x̄ = 17 × 7.8 µm, n = 40). These morphological characteristics are consistent with the species Myrmaecium fulvopruinatum (Berk.) Jaklitsch & Voglmayr (Jaklitsch et al. 2015). The genomic DNA of a representative isolate SICAUCC 22-0148 was extracted. The ITS, LSU region, tef1-α, rpb2 genes region were amplified using the primer pairs ITS1/ITS4 primers (White et al. 1990), LR0R/LR5 (Moncalvo et al. 1995), EF1-688F/986R (Alves et al. 2008), fRPB2-5f/fRPB2-7cr (Liu et al. 1999), respectively. The sequences were deposited in NCBI with accession numbers ON287043 (ITS), ON287044 (LSU), ON315870 (tef1-α), and ON315871 (rpb2), rspectively, which showed 99.8, 99.8, 98.1, and 98.5% identities with M. fulvopruinatum CBS 139057 holotype (accession numbers KP687858, KP687858, KP688027, and KP687933 respectively). Based on the analyses of phylogenies and morphologies, the isolates were identified as M. fulvopruinatum. The pathogenicity of SICAUCC 22-0148 was tested by inoculating surface-sterilized trunk wounds of four-year-old trees of J. regia with a mycelial plug (Desai et al. 2019). Sterile PDA plugs were used as controls. Wounds were covered with a film, to ensure humidity and prevent contamination. Each inoculation was repeated twice and included two plants, control and inoculated. A month later, the symptoms observed on inoculated trunks were similar to those in the wild, and M. fulvopruinatum was re-isolated from the inoculated trunk, confirming Koch's postulates. Previous research has reported M. fulvopruinatum as an important fungal species that cause canker delete symptoms on Chinese sweet chestnut in China (Jiang et al. 2018). We carried the taxonomy work of the fungi that caused trunk rot on walnut, and this is the first time that M. fulvopruinatum has been linked to walnut trunk rot on J. regia. Trunk rot of walnut will not only cause weakening of trees, but also affect the yield and quality of walnuts, bringing huge economic losses. This study was supported by the Sichuan Science and Technology Program under Grant 2022NSFSC1011. References: Alves, A., et al. 2008. Fungal Diversity 28:1-13. Desai, D.D., et al. 2019. International Journal of Economic Plants 6:147-149. Jaklitsch., W.M., et al. 2015. Fungal Diversity 73(1):159-202. Jiang, N., et al. 2018. Mycosphere 9(6):1268-1289. Liu, Y.L., et al. 1999. Mol Biol Evol 16:1799-1808. Moncalvo, J.M., et al. 1995. Mycologia 87:223-238. Wang, Q.H., et al. 2017. Australasian Plant Pathology 46:585-595. White, T.J., et al. 1990. Page 315 in: PCR Protocols: A Guide to Methods and Applications. Academic Press, San Diego, CA.

Excited-state photochemistry dynamics of 2-(1-naphthyl) phenol: electronic structure calculations and non-adiabatic dynamics simulations.

The excited-state proton transfer processes and the formation mechanism of quinone methide of (1-naphthyl)phenol were investigated by combining static electronic structure calculations and non-adiabatic dynamics simulations in vacuum. The results indicated the existence of two minimum energy structures (S0-ENOL-1 and S0-ENOL-2) in the ground and excited states, which correspond to two ESIPT pathways. Upon excitation of S0-ENOL-1 to the bright S1 state, the system relaxes to the S1 minimum quickly in the enol region, for which two decay pathways have been described. The first is a barrierless ESIPT-1 process that generates keto species. Afterwards, the system encounters a keto conical intersection, which funnels the system to the ground state. The generated keto species, in the S0 state, either regenerated the starting material via ground-state proton transfer or yielded the keto product at the end of the simulations. In the other pathway, the system de-excites from the S1 state to the S0 state via one enol-type conical intersection. The dynamics simulations showed that 58.8% of trajectories experience keto-type conical intersection and the rest undergo enol-type conical intersection. Besides the ESIPT-1 process, a new-type ESIPT (ESIPT-2), which was not observed experimentally, was found with the irradiation of S0-ENOL-2. The ESIPT-2 process occurs after overcoming a small barrier (0.9 kcal mol-1) and yields a distinct quinone methide. Our simulation results also showed that the S1 lifetime of S0-ENOL-1 (S0-ENOL-2) would be 437 (617) fs in the gas phase. These results provide detailed and important mechanistic insights into the systems in which ESPT to carbon atoms occurs.

Excited-State Deactivation Mechanism of 3,5-bis(2-hydroxyphenyl)-1H-1,2,4-triazole: Electronic Structure Calculations and Nonadiabatic Dynamics Simulations.

3,5-bis(2-Hydroxyphenyl)-1H-1,2,4-triazole (bis-HPTA) has attracted wide attention due to the important application in the detection of microorganisms and insecticidal activity. However, the mechanisms of excited-state intramolecular proton transfer (ESIPT) process and decay pathways are still a matter of debate. In this work, we have comprehensively investigated the photodynamics of bis-HPTA by executing combined electronic structure calculations and nonadiabatic surface-hopping dynamics simulations. Based on the computed electronic structure and dynamics information, we propose two nonadiabatic deactivation channels that efficiently populate the ground state from the Franck-Condon region. In the first one, after being excited to the bright S1 state, bis-HPTA molecule undergoes an ultrafast and barrierless ESIPT-1 process. Then, the system encounters with an energetically accessible S1/S0 conical intersection (CI), which funnels the system to the ground state speedily. Afterward, the keto species either arrives at the keto product or return to its enol species via a ground-state proton transfer in the S0 state. In the other excited-state decay channel, the S1 system hops to the ground state through a different CI, which involves the ESIPT-2 process. In our dynamics simulations, about 79.6% of the trajectories decay to the S0 state via the first CI, while the remaining ones employ the second conical intersection. The results of dynamics simulations also demonstrated that the lifetime of the S1 state is estimated as 315 fs. The present work will give elaborating mechanistic information of similar compounds in various environments.

Nanoengineering facilitating the target mission: targeted extracellular vesicles delivery systems design.

Precision medicine has put forward the proposition of "precision targeting" for modern drug delivery systems. Inspired by techniques from biology, pharmaceutical sciences, and nanoengineering, numerous targeted drug delivery systems have been developed in recent decades. But the large-scale applications of these systems are limited due to unsatisfactory targeting efficiency, cytotoxicity, easy removability, and instability. As such, the natural endogenous cargo delivery vehicle-extracellular vesicles (EVs)-have sparked significant interest for its unique inherent targeting properties, biocompatibility, transmembrane ability, and circulatory stability. The membranes of EVs are enriched for receptors or ligands that interact with target cells, which endows them with inherent targeting mission. However, most of the natural therapeutic EVs face the fate of being cleared by macrophages, resulting in off-target. Therefore, the specificity of natural EVs delivery systems urgently needs to be further improved. In this review, we comprehensively summarize the inherent homing mechanisms of EVs and the effects of the donor cell source and administration route on targeting specificity. We then go over nanoengineering techniques that modify EVs for improving specific targeting, such as source cell alteration and modification of EVs surface. We also highlight the auxiliary strategies to enhance specificity by changing the external environment, such as magnetic and photothermal. Furthermore, contemporary issues such as the lack of a gold standard for assessing targeting efficiency are discussed. This review will provide new insights into the development of precision medicine delivery systems.

miRTarBase 2020: updates to the experimentally validated microRNA-target interaction database.

MicroRNAs (miRNAs) are small non-coding RNAs (typically consisting of 18-25 nucleotides) that negatively control expression of target genes at the post-transcriptional level. Owing to the biological significance of miRNAs, miRTarBase was developed to provide comprehensive information on experimentally validated miRNA-target interactions (MTIs). To date, the database has accumulated >13,404 validated MTIs from 11,021 articles from manual curations. In this update, a text-mining system was incorporated to enhance the recognition of MTI-related articles by adopting a scoring system. In addition, a variety of biological databases were integrated to provide information on the regulatory network of miRNAs and its expression in blood. Not only targets of miRNAs but also regulators of miRNAs are provided to users for investigating the up- and downstream regulations of miRNAs. Moreover, the number of MTIs with high-throughput experimental evidence increased remarkably (validated by CLIP-seq technology). In conclusion, these improvements promote the miRTarBase as one of the most comprehensively annotated and experimentally validated miRNA-target interaction databases. The updated version of miRTarBase is now available at http://miRTarBase.cuhk.edu.cn/.

Factors determining the myopia control effect of an orthokeratology lens: A two-year multi-level model.

PURPOSE: A multi-level model was used to analyse factors, including environmental factors, affecting the controlling effect of orthokeratology on myopia progression. METHODS: A 2-year prospective study was conducted in the West China Hospital, Sichuan University. Age, sex, height, baseline spherical equivalent refraction, choroidal thickness, axial length and other biometric ocular parameters were collected. Additionally, data on the following environmental factors were obtained: near-work distance and time, sleep time and time spent outdoors. After the baseline measurements, participants were followed up every 3 months for 2 years of lens wear. The primary outcome measure was axial length elongation over 2 years of orthokeratology. All variables were included in a univariate, three-level analysis model with inclusion in the final multivariate multi-level model if statistically significant. RESULTS: Thirty-three participants (average age 9.73 ± 1.55 years) were included in this study. During the 2-year period of lens wearing, binocular changes in axial length increased significantly from the ninth month and continued until the end of the follow-up. Changes in axial length after 2 years of lens wearing were 0.44 ± 0.30 mm and 0.37 ± 0.26 mm in the right and left eyes, respectively (both p < 0.001). Based on the 2-year multi-level model, age, sex, baseline spherical equivalent refraction, flatter keratometry meridian and near-work time influence the effect of orthokeratology. CONCLUSIONS: This is the first study to use a multi-level model to analyse factors, including environmental factors, that affect myopia control using orthokeratology. These results showed that younger age, being female, having lower myopia at baseline, a steeper flattest keratometry meridian and no more than 5 h of near work per day were associated with better myopia control effect using orthokeratology over a 2-year treatment period.

Trunk canker of Juglans sigillata caused by Lasiodiplodia pseudotheobromae in China.

Iron walnut (Juglans sigillata Dode) is a temperate deciduous tree indigenous to China. It is mainly distributed in southwestern China, and valued for its wood and nuts (Feng et al. 2018). In September 2020, symptoms of canker on J. sigillata were observed in an orchard measuring 2 hectares located in Chongzhou City, Sichuan Province (31°5' 25″N, 105°27'36″E, 365 m altitude). Twenty percent of plants showed canker symptoms during the 50 surveyed plants. The infected trunk showed necrotic lesions with black pycnidia, that led to necrosis of branches and death of the whole plant in severe cases (Fig. 1). Six specimens from different diseased plants were collected for pathogen isolation and morphological observation. Pure cultures were obtained from single conidium on potato-dextrose agar (PDA) media according to the method described by Chomnunti (Chomnunti et al. 2014). Colonies grew fast and reached 3 cm after 5 days. The aerial mycelium was abundant, which was initially white and then grayish. Conidiomata on the host were measured 160-280 µm × 140-190 µm (average: 220 × 165 µm, n = 20), stromatic, uniloculate, dark brown to black, immersed, and erumpent when mature. Pycnidial walls 32-58 µm wide, were composed of 5-7 layers of brown to dark brown cells. Conidia were hyaline, and ellipsoidal with rounded apex and base, widest at the middle, thick-walled, and unicellular, with a size 21.5-31 µm × 11.5-15.7 µm (average: 27 × 13.5 µm, n = 50). Morphological characteristics fit the description of Lasiodiplodia pseudotheobromae A.J.L. Phillips, A. Alves & Crous (Aives et al. 2008). The internal transcribed spacers (ITS), 18S small subunit rRNA (SSU), 28S large subunit rDNA (LSU), translation elongation factor 1-alpha (tef1-α), and beta-tubulin (tub2) were amplified by polymerase chain reaction and sequenced with primers ITS1/ITS4, NS1/NS4, LR0R/LR5, EF1-728F/EF1-986R and Bt2a/Bt2b, respectively (Li et al. 2018). The sequences of the representative isolate (SICAUCC 22-0079) were deposited in NCBI with accession numbers ON090365 (ITS), ON090406 (SSU), ON090418 (LSU), ON112377 (tef1-α), and ON112378 (tub2), respectively. Nucleotide blast showed 100% similarity of all the analyzed and NCBI submitted isolates with L. pseudotheobromae (CBS116459; holotype) (accession numbers EF622077, EU673199, EU673256, EF622057, EU673111). Phylogenetic analyses based on a combined dataset showed 100% bootstrap support values in a clade with L. pseudotheobromae complexes (Fig. 2). Based on morphological and molecular analyses, the fungal pathogen was identified as L. pseudotheobromae. To conduct Koch's postulates, four 2-year-old healthy plants of J. sigillata were inoculated with 10 µL spore suspension (105 conidia/mL) onto the wounded sites via sterile pin. As control, four healthy plants were treated with sterile distilled water. The inoculated and untreated plants were placed in a growth chamber at 25°C with relative humidity >90% and 12-h photoperiod. Trunk canker symptoms appeared on inoculated plants after 15-20 days, and the pathogen was re-isolated and the controls were symptomless, confirming Koch's postulates. L. pseudotheobromae is widely distributed in various plants all over the world, usually as a pathogen associated with damping-off, wilt, die-back, root rot, collar rot, witches' brooms, or fruit rots (Zhao et al. 2010). To our knowledge, this is the first report of trunk canker on J. sigillata caused by L. pseudotheobromae in China. Trunk canker caused by L. pseudotheobromae is becoming a potential threat to walnut production, and some necessary measures for integrated management should be made.

Global Research Trends in Gestational Diabetes Mellitus from 2000 to 2020: A Bibliometric Study.

AIMS: This study analyzed major trends and topics in the field of gestational diabetes mellitus research between 2000 and 2020. METHODS: Studies that investigated gestational diabetes mellitus published between 2000 and 2020 were retrieved from the Web of Science Core Collection database. Data from the identified studies were analyzed using CiteSpace software. RESULTS: A total of 22,713 publications were retrieved, among which 21,722 publications were included in this scientometric analysis. Clustering analysis revealed 13 themes across all fields. Physical activity is an emerging trend. Co-word analysis showed that subject high-frequency keywords were: risk factor, obesity, insulin resistance, prevalence, and association. Centrality indices identified the most influential keywords to be: body mass index, risk factors, gestational weight gain, and obesity. Burst keywords revealed that there were six research frontier subtopics: i) prediction of adverse neonatal outcomes in gestational diabetes mellitus; ii) postpartum period research - blood glucose levels and insulin resistance; iii) meta-analysis - understanding the best evidence in pregnancy gestational diabetes mellitus; iv) gene expression profiles and DNA methylation in gestational diabetes mellitus; v) biomarkers for predicting higher birth and children weights; and vi) discussion on diagnostic criteria for gestational diabetes mellitus classification. CONCLUSION: The number of studies on gestational diabetes mellitus is increasing. For two decades, the United States has been the global leader in the number of published studies. Studies on gestational diabetes mellitus are mainly from developed countries, with a few of them being from developing countries. An emerging field of research aims at elucidating the association between physical activity and gestational diabetes mellitus.

Amniotic fluid metabolomic and lipidomic alterations associated with hemoglobin Bart's diseases.

INTRODUCTION: α-Thalassemia is the most common inherited disease in southern China. The severest form is hemoglobin (Hb) Bart's disease, in which the affected fetuses almost always die in utero or shortly after birth, and the mothers are at high risk for severe morbidity. OBJECTIVE: To investigate the changes in all metabolites in fetuses with Hb Bart's disease and to characterize the metabolomic and lipidomic biomarkers in the development of Hb Bart's fetuses. METHODS: Amniotic fluid (AF) specimens were selected from 34 pregnant women who underwent interventional prenatal diagnosis from June 2017 to June 2018. Gap-PCR analysis was used to diagnose Hb Bart's disease, and untargeted metabolomic and lipidomic analyses were performed. RESULTS: By analyzing AF samples, 935 differential metabolites were selected between Hb Bart's and control fetuses. The metabolites with significant changes mainly involved D-glutamine and D-glutamate metabolism, histidine metabolism, arginine metabolism, beta-alanine metabolism and alanine, aspartate and glutamate metabolism. Further lipidomics analysis revealed 132 differential lipids, mainly involved phosphatidylcholine and triglyceride metabolism. Through the characterized metabolites in AF, a schematic model of Hb Bart's disease was established. CONCLUSION: Glutamate and glutathione metabolism, aspartate metabolism, urea metabolism and triglyceride metabolism were significantly changed in the Hb Bart's group compared to the control group. The characterized biomarkers were mainly involved in oxidative stress reaction, iron overload and liver dysfunction. This finding may help improve the treatment options for α-thalassemia as well as diagnosing phenotype of patients.

A Novel Mutation at HBA1: c.349G>T Causing α-Thalassemia in a Chinese Family.

α-Thalassemia (α-thal) is one of the most common genetic diseases in Southern China. Although more than 300 α-thal mutations have been reported in the world, the mutation spectrum is still not comprehensive. In this study, a novel mutation (HBA1: c.349G>T) in a newborn (proband) was first found by next-generation sequencing (NGS). Subsequently, hematological analysis and thalassemia genetic testing were performed for the family members. The results showed that both the proband and her mother were heterozygotes for this novel mutation and presented abnormal hematological indices. Based on the features observed in clinical practice, this novel mutation was considered as a type of α-thal variation.

[Prospective Study on Corneal Safety Evaluation of Children/Adolescents with Low and Moderate Myopia after Long-Term Orthokeratology].

OBJECTIVE: To observe the possible changes in the integrity of the cornea and corneal endothelial cells of children/adolescents with low or moderate myopia after long-term wearing of orthokeratology (ortho-k) lenses, as well as the time when the relevant changes occur, so as to evaluate the safety of long-term wearing of ortho-k lens and to provide a reference for the safety evaluation of subjects wearing ortho-k lenses. METHODS: Subjects were recruited in the Contact Lens Clinic, West China Hospital, Sichuan University for a three-year prospective study. Ortho-k of the same brand was matched for the subjects. The central corneal thickness (CCT), corneal endothelial cell density (ECD), and hexagonal cell ratio (HEX) were measured prior to the wearing of ortho-k lenses and after wearing ortho-k lenses for 1 month, 3 months, 6 months, and every 3 months until 36 months. The results of corneal fluorescence staining were recorded during each follow-up. When corneal staining was observed, the Efron grading standard was used for grading and corresponding treatment was given. RESULTS: A total of 33 (66 eyes) myopic patients were included in the study. 15 cases (46.2%) reported having binocular foreign body sensations and tearing within the first week of wearing the lenses. After the subjects became adapted to wearing the lenses, the symptoms disappeared without intervention. During the follow-up period, 31 cases (93.94%) of binocular corneal staining were observed, of which, 24 cases (72.73%) were graded as G0, receiving no treatment, 5 cases (15.15%) were graded as GⅠ, and 2 cases (6.06%) were graded as GⅡ. Corresponding clinical treatment for corneal staining was given to the GⅠ and GⅡ subjects. This study found that the corneal ECD was inversely proportional to age ( r=－0.380, P=0.002). During the three-year follow-up period, the subjects' left eye ECD decreased from the baseline at 24 months and the right eye ECD decreased from the baseline at 27 months ( P<0.05). The CCT results in the subjects showed that CCT became thinner at 1 month after wearing the lens ( P<0.05), but the follow-up CCT showed a stable trend. CONCLUSION: After three years of long-term follow-up, no serious corneal complications occurred in children/adolescents with moderate and low myopia after long-term wearing of ortho-k lens. The corneal ECD of both eyes started decreasing 24 months after wearing the ortho-k lenses and the CCT decreased 1 month after wearing the lenses.

Bilateral Lateral Rectus Recession for the Treatment of Recurrent Exotropia after Bilateral Medial Rectus Resection.

PURPOSE: To evaluate the efficacy of bilateral lateral rectus muscle recession (BLR) to treat recurrent exotropia after bilateral medial rectus muscle resection (BMR). METHODS: Twenty-four patients who underwent BLR for recurrent exotropia and were followed up for more than 6 months were included in this retrospective study. All of them had prior BMR. The angle of deviation, success rates, near stereopsis, and surgical effect of BLR were evaluated. Surgical success was defined as postoperative deviations ≤10 prism diopters (PD). RESULTS: The overall mean follow-up time after reoperation for patients was 24.13 ± 15.01 months (range 6-60 months). The mean angle of deviation at distance was significantly reduced from -37.75 ± 14.93 PD to +1.50 ± 6.43 PD (p < 0.001). Twenty-two (91.6%) of 24 patients had successful outcomes, 1 (4.2%) had overcorrection, and 1 (4.2%) had undercorrection at the last follow-up. Improved stereopsis after reoperation was observed in 78.3% (18/23) of the patients. The mean surgical effect was 2.78 ± 0.71 PD/mm. CONCLUSION: Based on our results, BLR could be an effective and safe method for treating recurrent exotropia after a moderate to large amount of BMR.