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Shuangyan Tian,1 Juan Li,1 Qi Tao,2,3 Yawen Zhao,1 Zhufen Lv,4 Fan Yang,1 Haoyun Duan,5 Yanzhong Chen,4 Qingjun Zhou,5 Dongzhi Hou1 1Guangdong Engineering and Technology Research Center of Topical Precise Drug Delivery System, College of Pharmacy, Department of Pharmaceutics, Guangdong Pharmaceutical University, 2CAS Key Laboratory of Mineralogy and Metallogeny, 3Guangdong Provincial Key Laboratory of Mineral Physics and Materials, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, 4Guangdong Provincial Key Laboratory of Advanced Drug Delivery Systems, Guangdong Pharmaceutical University, Guangzhou, 5State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, China Background: Glaucoma is a serious eye disease that can lead to loss of vision. Unfortunately, effective treatments are limited by poor bioavailability of antiglaucoma medicine due to short residence time on the preocular surface. Materials and methods: To solve this, we successfully prepared novel controlled-release ion-exchange microparticles to deliver betaxolol hydrochloride (BH). Montmorillonite/BH complex (Mt-BH) was prepared by acidification-intercalation, and this complex was encapsulated in microspheres (Mt-BH encapsulated microspheres [BMEMs]) by oil-in-oil emulsion–solvent evaporation method. The BH loaded into ion-exchange Mt was 47.45%±0.54%. After the encapsulation of Mt-BH into Eudragit microspheres, the encapsulation efficiency of BH into Eudragit microspheres was 94.35%±1.01% and BH loaded into Eudragit microspheres was 14.31%±0.47%. Results: Both Fourier transform infrared spectra and X-ray diffraction patterns indicated that BH was successfully intercalated into acid-Mt to form Mt-BH and then Mt-BH was encapsulated into Eudragit microspheres to obtain BMEMs. Interestingly, in vitro release duration of the prepared BMEMs was extended to 12 hours, which is longer than both of the BH solution (2.5 hours) and the conventional BH microspheres (5 hours). Moreover, BMEM exhibited lower toxicity than that of BH solution as shown by the results of cytotoxicity tests, chorioallantoic membrane-trypan blue staining, and Draize rabbit eye test. In addition, both in vivo and in vitro preocular retention capacity study of BMEMs showed a prolonged retention time. The pharmacodynamics showed that BMEMs could extend the drug duration of action. Conclusion: The developed BMEMs have the potential to be further applied as ocular drug delivery systems for the treatment of glaucoma. Keywords: glaucoma, montmorillonite, controlled release, betaxolol hydrochloride, preocular retention, microspheres

Introduction: This study utilized a injectable curcumin (Cur)-infused calcium phosphate silicate cement (CPSC) for addressing defects caused by bone cancer, and evaluated its promoting bone regeneration and exerting cytotoxic effects on osteosarcoma cells., Methods: The material's physicochemical properties, biocompatibility with osteoblasts, and cytotoxicity toward osteosarcoma cells were rigorously analyzed., Results: The findings demonstrate that CPSC-Cur signicantly prolongs the setting time, which can be optimized by adding silanized cellulose nanober (CNF-SH) to achieve a balance between workability and mechanical strength. Biological assessments reveal a pronounced cytotoxic effect on osteosarcoma cells while maintaining minimal toxicity toward pre-osteoblasts, highlighting CPSC-Cur's potential as a promising material for repairing bone defects following cancer removal., Conclusion: This study lays the groundwork for future investigations into CPSC-Cur's in vivo efficacy and its role in the clinical treatment of bone cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Lu, Meng, Zhou, Wu, Gong and Wu.)

The Cyphotheca-Plagiopetalum-Sporoxeia clade (Sonerileae, Melastomataceae) comprises Cyphotheca Diels, Plagiopetalum Rehder, Sporoxeia W.W.Sm., and some species of the highly polyphyletic Phyllagathis Blume, as well as some undescribed species, which requires taxonomic revision at the generic level. In this study, we expanded taxon sampling of the CPS clade and reconstructed phylogenetic relationships using genomic SNPs and whole plastomes assembled from genome resequencing data. We recognized six subclades in the CPS clade and observed strong cytonuclear incongruences within and among subclades. Gene tree simulation and Patterson's D-statistic indicated that the conflicting phylogenetic signals were mainly caused by incomplete lineage sorting and hybridization/introgression. Molecular and morphological divergence among species of the CPS clade were evaluated using principal component analysis. Genomic SNP data clearly separated the six subclades, whereas the boundaries of some subclades were obscure in the plots of morphological data. Through reconstruction of morphological characteristics, we found a high level of homoplasy for some characters but also identified potential synapomorphies for the lineages. Based on the results, a revised generic classification is proposed for the CPS clade. Specifically, we expand Cyphotheca, Plagiopetalum, and Sporoxeia to include additional species, and establish three new genera, namely Chiehchenii, Neophyllagathis, and Sporocyphoxeia. A description and a list of species are provided for each of the six genera. Four new species are described., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Inc. All rights reserved.)

The diversity observed in canine breed phenotypes, together with their risk for heritabily disorders of relevance to dogs and humans, makes the species an ideal subject for studies aimed at understanding the genetic basis of complex traits and human biomedical models. Dog10K is an ongoing international collaboration that aims to uncover the genetic basis of phenotypic diversity, disease, behavior, and domestication history of dogs. To best present and make the extensive data accessible and user friendly, we have established the Dog10K (http://dog10k.kiz.ac.cn/) database, a comprehensive-omics resource summarizing multiple types of data. This database integrates single nucleotide variants (SNVs) from 1987 canine genomes, de-novo mutations (DNMs) from 43 dog breeds with >40× sequence, RNA-seq data of 105057 single nuclei from hippocampus, 74067 single cells from leukocytes and 30 blood samples from published canid studies. We provide clear visualization, statistics, browse, searching, and downloading functions for all data. We have integrated three analysis tools, Selscan, LiftOver and AgeConversion, to aid researchers in custom exploration of the comprehensive-omics data. The Dog10K database will serve as a foundational platform for analyzing, presenting and utilizing canine multi-omics data., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Understanding how life history shapes genetic diversity is a fundamental issue in evolutionary biology, with important consequences for conservation. However, we still have an incomplete picture of the impact of life history on genome-wide patterns of diversity, especially in long-lived semelparous plants. Puya raimondii is a high-altitude semelparous species from the Andes that flowers at 40-100 years of age. We sequenced the whole genome and estimated the nucleotide diversity of 200 individuals sampled from nine populations. Coalescent-based approaches were then used to infer past population dynamics. Finally, these results were compared with results obtained for the iteroparous species, Puya macrura. The nine populations of P. raimondii were highly divergent, highly inbred, and carried an exceptionally high genetic load. They are genetically depauperate, although, locally in the genome, balancing selection contributed to the maintenance of genetic polymorphism. While both P. raimondii and P. macrura went through a severe bottleneck during the Pleistocene, P. raimondii did not recover from it and continuously declined, while P. macrura managed to bounce back. Our results demonstrate the importance of life history, in particular generation time and reproductive strategy, in affecting population dynamics and genomic variation, and illustrate the genetic fragility of long-lived semelparous plants., (© 2024 The Author(s). New Phytologist © 2024 New Phytologist Foundation.)

Research suggests that physical cleansing leads individuals to perceive themselves as morally purer, thereby influencing their moral activities, but findings are inconsistent. Some researchers have found that individuals act more morally after physical cleansing, whereas others have observed the reverse effect. Building on embodied cognition theory, which holds that cognition is developed from physical experience and that this experience in turn guides their responses, we hypothesized that physical cleansing would have a general impact on individuals' moral activities by highlighting themselves. In contrast to previous research, we did not expect that physical cleansing would directly make people more (im)moral. Two experiments were conducted to test our hypotheses. In experiment 1, participants who had bathed showed reduced susceptibility to external moral priming (morality-related descriptions of themselves) than did control participants. Experiment 2 showed that physical cleansing (but not the control condition) amplified the interplay among participants' moral activities, depending on the order of immoral behavior and intention measurement. Taken together, these results suggest that physical cleansing strengthens the connection between individuals' morality and bodily experiences, weakening the effect of external priming (experiment 1) and enhancing the influence of moral activities performed by themselves (experiment 2). Although further research is required to provide direct evidence for these findings, our study contributes to the integration of inconsistencies in previous findings by suggesting a new perspective for the understanding of the embodied effect of physical cleansing., Competing Interests: Declaration of competing interest The authors declared no potential conflicts of interest with respect to the research, authorship, and publication of this article., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Aim: To evaluate the effects of antiglaucoma eye drops on corneal nerves by in vivo confocal microscopy (IVCM)., Methods: This study comprised 79 patients diagnosed with glaucoma and 16 healthy control individuals. Among the glaucoma patients, 54 were treated with medication, while 25 remained untreated. Central corneal images were evaluated by IVCM, and then ACCMetrics was used to calculate the following parameters: corneal nerve fiber density (CNFD), branch density (CNBD), fiber length (CNFL), total branch density (CTBD), fiber area (CNFA), fiber width (CNFW), and fractal dimension (CNFrD). The correlation between IVCM parameters and drugs was evaluated using non-parametric measurements of Spearman's rank correlation coefficient., Results: The CNFD was reduced in glaucoma groups compared to healthy subjects ( P <0.01). Patients using anti-glaucoma medications exhibited poorer confocal parameters compared to untreated patients. As the number of medications and usage count increased, CNFD, CNBD, CNFL, CTBD, CNFA, and CNFrD experienced a decline, while CNFW increased (all P <0.01). For the brinzolamide-therapy group, there was a significant decrease in CNFD and CNFL compared to the other monotherapy groups ( P <0.001). In the absence of medication, CNFD in males was lower than that in females ( P <0.05). Among patients under medication therapy, CNFD remained consistent between males and females., Conclusion: Antiglaucoma eye drops affect the microstructure of corneal nerves. IVCM and ACCMetrics are useful tools that could be used to evaluate the corneal nerve changes., Competing Interests: Conflicts of Interest: Zhu XY, None; Ge QS, None; Li ZY, None; Zhou LF, None; Bu QW, None; Su Y, None; Wang XJ, None; Zhou QJ, None; Pan XJ, None; Hu D, None., (International Journal of Ophthalmology Press.)

Introduction: Aeromonas spp. are ubiquitous inhabitants of ecosystems, and many species are opportunistically pathogenic to humans and animals. Multidrug-resistant (MDR) Aeromonas species have been widely detected in hospitals, urban rivers, livestock, and aquatic animals., Results: In this study, we identified two Aeromonas isolates, namely Aeromonas veronii 0728Q8Av and Aeromonas caviae 1029Y16Ac, from coastal waters in Zhejiang, China. Both isolates exhibited typical biochemical characteristics and conferred MDR to 11 kinds of antibiotics, remaining susceptible to ceftazidime. Whole-genome sequencing revealed that both isolates harbored multiple antibiotic resistance genes (ARGs) and several mobile genetic elements (MGEs) on the chromosomes, each containing a resistance genomic island (GI), a typical class 1 integron, a transposon, and various insertion sequences (ISs). Most ARGs were situated within the multiple resistance GI, which contained a class 1 integron and a transposon in both Aeromonas isolates. Furthermore, a chromosomal mcr-3.16 gene was identified in A. veronii 0728Q8Av, while a chromosomal mcr-3.3 was found in A. caviae 1029Y16Ac. Both mcr-3 variants were not located within but were distanced from the multidrug resistance GI on the chromosome, flanking by multiple ISs. In addition, a mcr-3-like was found adjacent to mcr-3.16 to form a tandem mcr-3.16 - mcr-3-like - dgkA structure; yet, Escherichia coli carrying the recombinants of mcr-3-like did not exhibit resistance to colistin. And an incomplete mcr-3-like was found adjacent to mcr-3.3 in A. caviae 1029Y16Ac, suggesting the possibility that mcr-3 variants originated from Aeromonas species. In vivo bacterial pathogenicity test indicated that A. veronii 0728Q8Av exhibited moderate pathogenicity towards infected ayu, while A. caviae 1029Y16Ac was non-virulent., Discussion: Thus, both Aeromonas species deserve further attention regarding their antimicrobial resistance and pathogenicity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Chen, Chen, Zhou, Shang, Tang, Xu, Duan, Jin, Xu, Yan and Chen.)

Background: The relationship between plaque psoriasis and both MASLD and lean MASLD has not been sufficiently explored in the current literature., Method: This retrospective and observational study was carried out from January 2021 to January 2023 at The First Affiliated Hospital of Zhejiang Chinese Medical University. Patients diagnosed with plaque psoriasis and a control group consisting of individuals undergoing routine physical examinations were enrolled. The incidence of MASLD and lean MASLD among these groups was compared. Additionally, patients with plaque psoriasis were divided into those with MASLD, those with lean MASLD, and a control group with only psoriasis for a serological comparative analysis., Results: The incidence of MASLD in the observation group and the control group was 43.67% (69/158) and 22.15% (35/158), respectively ( p  < 0.01). Furthermore, the incidence of lean MASLD within the observation group and the control group was 10.76% (17/158) and 4.43% (7/158), respectively ( p  < 0.01). After controlling for potential confounding variables, plaque psoriasis was identified as an independent risk factor for MASLD with an odds ratio of 1.88 (95% cl: 1.10-3.21). In terms of serological comparison, compared to the simple psoriasis group, we observed a significant elevation in the tumor marker CYFRA21-1 levels in both groups compared to the control group with simple psoriasis ( p  < 0.01). Moreover, the MASLD group exhibited elevated levels of inflammatory markers and psoriasis score, whereas these effects were mitigated in the lean MASLD group., Conclusion: The prevalence of MASLD and lean MASLD is higher among patients with psoriasis. Those suffering from psoriasis along with MASLD show increased psoriasis scores and inflammatory markers compared to those without metabolic disorders. MASLD likely worsens psoriasis conditions, indicating the necessity of targeted health education for affected individuals to reduce the risk of MASLD, this education should include guidelines on exercise and diet. In serological assessments, elevated levels of cytokeratin 19 fragment (CYFRA21-1) were noted in both MASLD and lean MASLD groups, implying a potential synergistic role between psoriasis and MASLD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lin, Shi, Yu, Ma, Pan, Dou, Zhou and Cao.)

Double perovskites (DPs) have attracted attention in the field of luminescence due to their inherent broadband emission of self-trapping excitons. In this work, we choose [(CH 3 ) 3 NCH 2 CHCH 2 ] + and [CH 3 CHOHCH 2 NH 2 ] + as organic cations to synthesize two new organic-inorganic hybrid DPs, [(CH 3 ) 3 NCH 2 CHCH 2 ] 2 KInCl 6 ( 1 ) and [CH 3 CHOHCH 2 NH 2 ] 2 KInCl 6 ( 2 ). The [KCl 6 ] 3- and [InCl 6 ] 3- octahedra are interchangeably connected by sharing two opposite faces, forming a one-dimensional coordination chain. Each K atom coordinates with six chlorine atoms in 1 , while it coordinates with two oxygen atoms in addition to the six chlorine atoms in 2 . The coordination between ions K and O in compound 2 may have significantly reduced its luminescence. As a result, compound 1 shows bright-yellow light with a quantum yield of more than 90%, while 2 shows weak blue light with a quantum yield of only 0.98%. In addition, different from no phase transition found in 2 , 1 undergoes a reversible phase transition at 324/307 K in the heating-cooling cycle. Through structural and spectral analysis and density functional theory calculation, we conclude that the larger degree of [InCl 6 ] 3- octahedral distortion and the larger anion distance (In···In) also cause the PLQY of compound 1 to be higher than that of compound 2 .

Leukemia-initiating cells (LICs) are regarded as the origin of leukemia relapse and therapeutic resistance. Identifying direct stemness determinants that fuel LIC self-renewal is critical for developing targeted approaches. Here, we show that the RNA-editing enzyme ADAR1 is a crucial stemness factor that promotes LIC self-renewal by attenuating aberrant double-stranded RNA (dsRNA) sensing. Elevated adenosine-to-inosine editing is a common attribute of relapsed T cell acute lymphoblastic leukemia (T-ALL) regardless of molecular subtype. Consequently, knockdown of ADAR1 severely inhibits LIC self-renewal capacity and prolongs survival in T-ALL patient-derived xenograft models. Mechanistically, ADAR1 directs hyper-editing of immunogenic dsRNA to avoid detection by the innate immune sensor melanoma differentiation-associated protein 5 (MDA5). Moreover, we uncover that the cell-intrinsic level of MDA5 dictates the dependency on the ADAR1-MDA5 axis in T-ALL. Collectively, our results show that ADAR1 functions as a self-renewal factor that limits the sensing of endogenous dsRNA. Thus, targeting ADAR1 presents an effective therapeutic strategy for eliminating T-ALL LICs., Competing Interests: Declaration of interests C.J. has served as an advisor for AbbVie, Bristol-Myers Squibb, and Celgene; was a co-founder of Impact Biomedicines and is a co-founder of Aspera Biomedicines; and received royalties from Forty Seven, Inc., and the Jamieson laboratory received unrestricted research grant funding from Janssen, Inc., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Micropterus salmoides rhabdovirus (MSRV) is one of the main pathogens of largemouth bass, leading to serious economic losses. The G protein, as the only envelope protein present on the surface of MSRV virion, contains immune-related antigenic determinants, thereby becoming the primary target for the design of MSRV vaccines. Here, we displayed the G protein on the surface of yeast cells (named EBY100/pYD1-G) and conducted a preliminary assessment of the protective efficacy of the recombinant yeast vaccine. Upon oral vaccination, a robust immune response was observed in systemic and mucosal tissue. Remarkably, following the MSRV challenge, the relative percent survival of EBY100/pYD1-G treated largemouth bass significantly increased to 66.7 %. In addition, oral administration inhibited viral replication and alleviated the pathological symptoms of MSRV-infected largemouth bass. These results suggest that EBY100/pYD1-G could be used as a potential oral vaccine against MSRV infection., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Zoonotic parasites pose significant health risks globally. In the present study, we combined a microfluidic chip with loop-mediated isothermal amplification (on-chip LAMP) to detect five zoonotic parasites: Toxoplasma gondii , Cryptosporidium parvum , Cryptosporidium hominis , Clonorchis sinensis , and Taenia solium . This method enabled the simultaneous parallel analysis of five genetic markers from a maximum of four samples per chip. The on-chip LAMP assay was conducted in a highly automated format via the addition (by pipetting) of each sample in a single operation. The reaction was performed in volumes as low as 5 μL at a temperature of 65°C for 60 min, achieving limits of detection ranging from 10 -2 to 10 -3  pg./μL of recombinant plasmid DNA. All the time-to-positive values were less than 40 min, and almost all the coefficients of variation were less than 10%, even when using limit of detection concentrations for multiple pathogens, indicating robust reproducibility among replicates. The clinical sensitivity and specificity for detecting 135 field samples were 98.08 and 97.59%, respectively, compared with traditional biological methods, indicating good applicability in the detection of field samples. This on-chip LAMP assay allows for low reagent consumption, ease of operation, and multiple analyses of samples and genetic targets, and is applicable for on-site detection and the routine monitoring of multiple zoonotic parasites., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Lou, Duan, Zhou, Xu, Chen, Chen, Xu, Du and Chen.)

Based on the simulation of the fluid-structure interaction response, the cause of an overturning of a gantry crane induced by a downburst in Shenzhen is studied in this paper. According to the results, (1) Vicroy's downburst model could establish the steady-state wind field of the downburst more reasonably when there was only low-level wind speed observation data, and its simulation results were close to the two-dimensional downburst numerical simulation results; (2) Compared with the normal exponential vertical profile of wind speed, the disturbance caused by the front girder of the double-girder gantry crane structure under the downburst wind field was more severe, which increases the probability of the gantry crane overturning. (3) The downwind displacement of the main girder of the gantry crane under the condition of downburst is far greater than that under the normal condition. At the same time, under the condition of downburst, the pressure difference on the surface of the gantry crane was greater, and the distribution of the support reaction force was more uneven, resulting in a stronger overturning tendency of the gantry crane. (4) Under the condition of downburst, the overturning moment and the shearing force borne by the foundation of gantry crane exceeded the critical value to maintain the stability of the gantry crane by the gravity, resulting in the overturning of the gantry crane., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Ltd.)

White spot disease, caused by the parasitic ciliate Ichthyophthirius multifiliis , is a significant threat to the freshwater fish farming industry worldwide, resulting in massive mortality and economic losses. Eliminating the free-swimming theronts from the culture environment is considered crucial for the control of I. multifiliis infection. It is well-documented that planktonic ciliates are valuable food resources for macro-zooplankton in aquatic ecosystems. In this study, we developed a fluorescence labeling method for alive theronts and found that cyclopoid copepods Thermocyclops taihokuensis , Mesocyclops spp., Macrocyclops sp., and Paracyclopina sp. present predation on the theronts in co-culture experiments. Laboratory challenge tests further confirmed that the presence of zooplankton in the culture water body significantly reduced the infection of I. multifiliis in goldfish ( p < 0.01). Results from this study revealed that cyclopoid copepods have the potential to be used as biological control agents against white spot disease in aquaculture.

Leukemia initiating cells (LICs) are regarded as the origin of leukemia relapse and therapeutic resistance. Identifying direct stemness determinants that fuel LIC self-renewal is critical for developing targeted approaches to eliminate LICs and prevent relapse. Here, we show that the RNA editing enzyme ADAR1 is a crucial stemness factor that promotes LIC self-renewal by attenuating aberrant double-stranded RNA (dsRNA) sensing. Elevated adenosine-to-inosine (A-to-I) editing is a common attribute of relapsed T-ALL regardless of molecular subtypes. Consequently, knockdown of ADAR1 severely inhibits LIC self-renewal capacity and prolongs survival in T-ALL PDX models. Mechanistically, ADAR1 directs hyper-editing of immunogenic dsRNA and retains unedited nuclear dsRNA to avoid detection by the innate immune sensor MDA5. Moreover, we uncovered that the cell intrinsic level of MDA5 dictates the dependency on ADAR1-MDA5 axis in T-ALL. Collectively, our results show that ADAR1 functions as a self-renewal factor that limits the sensing of endogenous dsRNA. Thus, targeting ADAR1 presents a safe and effective therapeutic strategy for eliminating T-ALL LICs., Competing Interests: DECLARATION OF INTERESTS C.H.M.J. has served as an advisor for AbbVie, Bristol-Myers Squibb and Celgene; was a co-founder of Impact Biomedicines and is a co-founder of Aspera Biomedicines; received royalties from Forty Seven Inc. and the Jamieson laboratory received unrestricted research grant funding from Janssen Inc. All other authors declare no competing financial interests.

To summarize the clinical diagnosis and treatment process and genetic test results and characteristics of one child with Angelman syndrome (AS) complicated with oculocutaneous albinism type 2 (OCA2), and to review the literature. "Angelman syndrome" "P gene" and "Oculocutaneous albinism type 2" were used as keywords to search at CNKI, Wanfang, and PubMed databases (from creation to December 2019). Then all the patients were analyzed. The patient in this study was a girl aged 1 year. After birth, she was found to present as white body, yellow hair, and nystagmus. She could raise her head at the age of 2 months and turn over at the age of 7 months. The head circumference was 42 cm and she could not sit alone or speak at present. Trio-based exome sequencing revealed that the patient carried a homozygous mutation of c.168del (p.Gln58ArgfsTer44) in the P gene, and her father was heterozygous and her mother was wild-type. The detection of copy number variation showed deletion on the maternal chromosome at 15q11.2-13.1 region (P gene located in this region) in the patient. Until December 2019, a total of 4 cases in the 4 literature had been reported. Adding our case here, the 5 cases were summarized and found that all the cases showed white skin, golden hair, and shallow iris after birth. Comprehensive developmental delay was found around 6 months of age after birth, and the language remained undeveloped in 2 cases till follow-up into childhood. Seizures occurred in 4 patients. Two cases had ataxia. All the 5 cases had acquired microcephaly. Two cases had a family history of albinism. Electroencephalogram monitoring was completed in 3 cases and the results were abnormal. Genetic tests showed that all the 5 cases had deletion on maternal chromosome at 15q11-13 region. Four cases carried mutation of P gene on paternal chromosome. And 1 case was clinically diagnosed as OCA2 without P gene test. AS combined with OCA2 is relatively rare. OCA2 is easily diagnosed based on the obvious clinical manifestations after birth. When combined with clinical manifestations such as neurodevelopmental delay, it might indicate the possibility of AS that is hardly diagnosed clinically at an early stage. Genetic tests can reveal the cross-genetic phenomenon of AS and OCA2 and the complex of them can be eventually diagnosed.

In recent years, with the further understanding of medical circles on diabetic ocular complications, the ocular surface abnormalities of diabetes has drawn increasing concerns. Nearly 50% of diabetic patients suffer from dry eye symptoms. The main manifestations of diabetes related dry eye were abnormal lacrimal secretion, poor lacrimal stability, decreased corneal sensitivity, persistent corneal epithelial defect and even corneal ulcer, which were mainly related to the changes of structure and function of lacrimal gland, the decrease of goblet cells in conjunctiva, the abnormality of meibomian gland function and the degeneration of corneal nerve caused by diabetes. In this paper, we summarized and analyzed the recent research progress on the effect of diabetes on lacrimal film, corneal innervation and lacrimal gland innervation, and the correlation between oxidative stress, advanced glycation end products and diabetes-related dry eye, to explore the pathogenesis of diabetes-related dry eye and to provide reference for clinical diagnosis, treatment and research.

Preeclampsia, a progressive disease involving multiple systems, afflicts pregnancy specifically. It contributes to severe maternal and perinatal morbidity and mortality. It has been reported that preeclampsia initiates from a mismatch between the utero-placental supply and demand, which subsequently triggers the release of placental syncytiotrophoblast stress-derived factors and an imbalance of proangiogenic/antiangiogenic factors, eventually causing maternal systemic endothelial lesions and systemic inflammatory response. Currently, treatments available for preeclampsia are very limited in number. Hence, prediction and prevention carry special significance. Herein, we reviewed the current understanding of preeclampsia, especially findings on the prediction and prevention of preeclampsia published within the past 5 years. We discussed the Fetal Medicine Foundation (FMF) screening model based on placental growth factor (PlGF) and the effects of aspirin, calcium, exercise, and termination of pregnancy in preventing preeclampsia. The efficacy and safety of other new preventive measures still need further validation., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

A simple food chain (plant, insect pests, and predatory arthropods) in an agro-ecosystem was set up here as a model system to elucidate the potential effect of transgenic Bacillus thuringiensis (Bt) cotton on non-target organisms. The system included transgenic/non-transgenic cotton, neonate larvae of three herbivorous insects ( Spodoptera exigua , Helicoverpa armigera , and S . litura ), and predatory lacewing larvae ( Chrysopa spp.), which represent the first, second, and third trophic levels, respectively. The results showed that transgenic treatments and different densities of prey had significant effects on both body-weight gain of neonate herbivorous larvae and the number of prey captured by lacewing larvae, respectively. It was found that Bt toxin could persist at the third trophic level in lacewing larvae. The diet mixture bioassay showed that body-weight gain of lacewing larvae was significantly affected by various treatments, especially at lower concentrations of plant-expressed Bt toxin in the diet mixture, which caused significant decreases in body-weight gain. In contrast, synthetic Bt toxin at higher concentrations in the diet did not show this effect. Thus, we inferred that Bt toxin indirectly affected the growth of the lacewings and the lacewings may not be susceptible to Bt toxin or are able to metabolize it.

Sonerileae is a diverse Melastomataceae lineage comprising ca. 1000 species in 44 genera, with >70% of genera and species distributed in Asia. Asian Sonerileae are taxonomically intractable with obscure generic circumscriptions. The backbone phylogeny of this group remains poorly resolved, possibly due to complexity caused by rapid species radiation in early and middle Miocene, which hampers further systematic study. Here, we used genome resequencing data to reconstruct the phylogeny of Asian Sonerileae. Three parallel datasets, viz. single-copy ortholog (SCO), genomic SNPs, and whole plastome, were assembled from genome resequencing data of 205 species for this purpose. Based on these genome-scale data, we provided the first well resolved phylogeny of Asian Sonerileae, with 34 major clades identified and 74% of the interclade relationships consistently resolved by both SCO and genomic data. Meanwhile, widespread phylogenetic discordance was detected among SCO gene trees as well as species trees reconstructed using different tree estimation methods (concatenation/site-based coalescent method/summary method) or different datasets (SCO/genomic/plastome). We explored sources of discordance using multiple approaches and found that the observed discordance in Asian Sonerileae was mainly caused by a combination of biased distribution of missing data, random noise from uninformative genes, incomplete lineage sorting, and hybridization/introgression. Exploration of these sources can enable us to generate hypotheses for future testing, which is the first step towards understanding the evolution of Asian Sonerileae. We also detected high levels of homoplasy for some characters traditionally used in taxonomy, which explains current chaotic generic delimitations. The backbone phylogeny of Asian Sonerileae revealed in this study offers a solid basis for future taxonomic revision at the generic level., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The process of domestication has led to dramatic differences in behavioral traits between domestic dogs and gray wolves. Whole-genome research found that a class of putative positively selected genes were related to various aspects of learning and memory, such as long-term potentiation and long-term depression. In this study, we constructed a single-nucleus transcriptomic atlas of the dog hippocampus to illustrate its cell types, cell lineage and molecular features. Using the transcriptomes of 105 057 nuclei from the hippocampus of a Beagle dog, we identified 26 cell clusters and a putative trajectory of oligodendrocyte development. Comparative analysis revealed a significant convergence between dog differentially expressed genes (DEGs) and putative positively selected genes (PSGs). Forty putative PSGs were DEGs in glutamatergic neurons, especially in Cluster 14, which is related to the regulation of nervous system development. In summary, this study provides a blueprint to understand the cellular mechanism of dog domestication., (© The Author(s) 2022. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)

Here, the high fluorescent silicon-doped carbon quantum dots (Si-CQDs) were prepared by a facile and one-pot hydrothermal assay using 3-aminopropyltrimethoxysilane as the carbon and silicon source. The prepared Si-CQDs exhibit favorable water-soluble, high-temperature resistance, acid resistance, alkali resistance, high ionic strength resistance, high photostability, film-forming ability and solid-state fluorescence. Compared to other Si-CQDs that have been reported, the prepared Si-CQDs show unique up-conversion fluorescence. Furthermore, it is found that berberine hydrochloride (BH) can effectively quench the down- and up-conversion fluorescence of the Si-CQDs, making it can be used as a highly sensitive and specific probe for BH dual-mode sensing. Meanwhile, the linear range of down-conversion fluorescence detection for BH is 0.5-30.0 µmol/L with a limit of detection (LOD) of 50 nmol/L, and the linear range of up-conversion fluorescence assay for BH is 0-25.0 µmol/L. The mechanism of down-conversion fluorescence quenching by BH was investigated through a series of studies. The results show the quenching mechanism is the inner filter effect (IFE). Moreover, this proposed strategy has been well used to analyze BH in urine samples with satisfactory results., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Vertebrate evolution was accompanied by two rounds of whole-genome duplication followed by functional divergence in terms of regulatory circuits and gene expression patterns. As a basal and slow-evolving chordate species, amphioxus is an ideal paradigm for exploring the origin and evolution of vertebrates. Single-cell sequencing has been widely used to construct the developmental cell atlas of several representative species of vertebrates (human, mouse, zebrafish, and frog) and tunicates (sea squirts). Here, we perform single-nucleus RNA sequencing (snRNA-seq) and single-cell assay for transposase accessible chromatin sequencing (scATAC-seq) for different stages of amphioxus (covering embryogenesis and adult tissues). With the datasets generated, we constructed a developmental tree for amphioxus cell fate commitment and lineage specification and characterize the underlying key regulators and genetic regulatory networks. The data are publicly available on the online platform AmphioxusAtlas., Competing Interests: Declaration of interests These authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Hong Kong oyster (Crassostrea hongkongensis) is one of the main species of economic shellfish cultivated in the coastal areas of southern China. The cultivation of this shellfish may be adversely impacted by Vibrio parahaemolyticus, a harmful pathogenic bacterium for many mariculture species, as it usually exists on the surface of Hong Kong oysters. Although previous studies have discovered that oysters rely on non-specific immune system to fight pathogen invasion, the genes corresponding to the complex immune system against Vibrio is still not fully elucidated. Therefore, we conducted a transcriptome analysis on the gill from Hong Kong oysters at two time points (i.e., 12 h and 24 h after V. parahaemolyticus or PBS challenge) to identify potential immune genes against V. parahaemolyticus infection. A total of 61779 unigenes with the average length of 1221 bp were obtained, and the annotation information of 39917 unigenes were obtained from Nr, SwissProt, KEGG and COG/KOG. After a pairwise comparison between V. parahaemolyticus or PBS challenge at the two time points, three groups of differentially expressed genes induced by V. parahaemolyticus were captured and analyzed. GO and KEGG analyses showed that multiple immune-related genes played an important role in pathogen infection, including HSP70, PCDP3 and TLR4. Furthermore, genes annotation indicated that LITAF, TNFSF10, Duox2 and big defensin family are also involved in immune regulation. Our study provides a reference for further exploration the molecular mechanism that defenses the pathogen infection regarding the identified immune-related genes in Hong Kong oysters., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Lysine-specific demethylase 5A (KDM5A, also named RBP2 or JARID1A) is a demethylase that can remove methyl groups from histones H3K4me1/2/3. It is aberrantly expressed in many cancers, where it impedes differentiation and contributes to cancer cell proliferation, cell metastasis and invasiveness, drug resistance, and is associated with poor prognosis. Pharmacological inhibition of KDM5A has been reported to significantly attenuate tumor progression in vitro and in vivo in a range of solid tumors and acute myeloid leukemia. This review will present the structural aspects of KDM5A, its role in carcinogenesis, a comparison of currently available approaches for screening KDM5A inhibitors, a classification of KDM5A inhibitors, and its potential as a drug target in cancer therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Background: Robotic-assisted thoracic surgery (RATS) has been widely used in the treatment of lung cancer. The perioperative outcomes of right upper lobectomy (RUL) using RATS and video-assisted thoracic surgery (VATS) were retrospectively investigated and compared. We aimed to summarize a single-center experience of RATS and 4-port unidirectional VATS in RUL, and to discuss the safety and the essentials of the surgery., Methods: We retrospectively analyzed the 685 with non-small cell lung cancer (NSCLC) patients who underwent minimally invasive RUL in our center by the same surgical group from January 2015 to December 2019. Both RATS and VATS were performed with three ports with utility incision. The 685 participants were divided into RATS (335 cases) and VATS (350 cases) groups according to surgical method. Baseline characteristics and perioperative outcomes including dissected lymph nodes, postoperative duration of drainage, postoperative hospital stay, and incidence of postoperative complications were compared between the groups., Results: In the 685 patients enrolled, the baseline characteristics were comparable, and no postoperative 30-day mortality or intraoperative blood transfusion were observed. Compared with VATS, RATS had less surgical duration (90.22±12.16 vs. 92.68±12.26 min, P<0.001), less length of stay (4.71±1.37 vs. 5.26±1.56 days, P<0.001), and decreased postoperative duration of drainage (3.49±1.15 vs. 4.09±1.57 days, P<0.001). No significant difference was observed in the lymph nodes dissection, blood loss, conversion rate and morbidities. The cost of RATS was much higher than VATS (85,329.41±12,893.44 vs. 68,733.43±14,781.32 CNY, P<0.001)., Conclusions: Robot assisted RUL had similar perioperative outcomes compared to VATS RUL lobectomy using similar three port with utility incision technique. The advantages of RATS included finer dissection of lymph node, relatively less operation time, earlier chest tube removal and discharge., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/tlcr-21-960). MPK reports royalty from Medtronic; consulting fee from Medtronic, Intuitive Surgical, Veran/Olympus and AstraZeneca. REM reports that he is a speaker of Intuitive Surgical. The other authors have no conflicts of interest to declare., (2021 Translational Lung Cancer Research. All rights reserved.)

Aim: To evaluate the midterm outcomes of penetrating keratoplasty (PK) following allogeneic cultivated limbal epithelial transplantation (CLET) for bilateral total limbal stem cell deficiency (LSCD)., Methods: Ten patients (10 eyes) with bilateral LSCD were enrolled in this prospective noncomparative case series study. Each participant underwent PK approximately 6mo after a CLET. Topical tacrolimus, topical and systemic steroids, and oral ciclosporin were administered postoperatively. Best-corrected visual acuity (BCVA), intraocular pressure (IOP), ocular surface grading scores (OSS), corneal graft epithelial rehabilitation, persistent epithelial defect (PED), immunological rejection, and graft survival rate were assessed., Results: The time interval between PK and allogeneic CLET was 6.90±1.29 (6-10)mo. BCVA improved from 2.46±0.32 logMAR preoperatively to 0.77±0.55 logMAR post-PK ( P <0.001). Kaplan-Meier analysis of mean graft survival revealed graft survival rates of 100% at 12 and 24mo and 80.0% at 36mo. PEDs appeared in 5 eyes at different periods post-PK, and graft rejection occurred in 4 eyes. The total OSS decreased from 12.4±4.4 before allogeneic CLET to 1.4±1.51 after PK., Conclusion: A sequential therapy design of PK following allogeneic CLET can maintain a stable ocular surface with improved BCVA despite the relatively high graft rejection rate., (International Journal of Ophthalmology Press.)

Aim: To evaluate the efficacy of recombinant human nerve growth factor-loaded amniotic membrane (rhNGF-AM) on corneal epithelial and nerve regeneration in rabbit model., Methods: Freshly prepared human amniotic membrane (AM) were immersed into PBS buffer containing 100 or 500 µg/mL rhNGF for 15, 30, and 60min at 4°C. The in vitro release kinetics of rhNGF was measured with ELISA. For in vivo evaluation, the AM were immersed with 500 µg/mL rhNGF for 30min. Fifty-seven rabbits were selected to establish corneal epithelial defect model. In addition to the 19 rabbits in control group, 38 rabbits received AM transplantation with or without rhNGF after the removal of central epithelium. Corneal epithelial defect area, sub-epithelial nerve fiber density, corneal sensitivity, rhNGF contents in resident AM and corneas were measured after the surgery., Results: rhNGF was sustained release from the AM within 14d in vitro , with the positive correlation with initial immersion concentration. The immersion of AM in 500 µg/mL rhNGF for 30min achieved the most stable release within 14d. After transplantation in rabbit cornea, a high concentration of rhNGF in resident rhNGF-AM and cornea was maintained within 8d. Corneal epithelial healing, nerve fiber regeneration and the recovery of corneal sensitivity were significantly accelerated after the rhNGF-AM transplantation when compared to simple AM transplantation (all P <0.05)., Conclusion: Simple immersion of AM achieves the sustained release of rhNGF, and promotes corneal epithelial wound healing and nerve regeneration, as well as the recovery of corneal sensitivity in rabbit., (International Journal of Ophthalmology Press.)

Diabetic neuropathy is a common complication of diabetes. Its incidence among diabetic patients is more than 50%, and its ocular manifestations include diabetic retinopathy and diabetic corneal neuropathy. By using confocal microscopy, diabetic neuropathy in the cornea has been found to occur earlier than other parts of the body, which helps for early diagnosis, risk assessment and treatment options for diabetic peripheral neuropathy. The repair and treatment of nerve damage in diabetic corneal neuropathy has been frequently studied. This review focuses on the research progress of diabetic corneal neuropathy in recent years, and discusses the research findings on corneal nerve injury, anatomical and functional changes, and mechanism of injury and repair. (Chin J Ophthalmol, 2021, 57: 630-636) .

Objective: To investigate the prevention and treatment status of venous thromboembolism (VTE) of pregnant women in general hospitals and specialized hospitals in China. Methods: This study was a cross-sectional survey about VTE prevention and treatment in 112 hospitals across China from January 1st to December 31st, 2019, including general information, resource accessibility, hospital system and strategy. According to the characteristics, the hospitals were divided into general hospital group (70 hospitals) and specialized hospital group (42 hospitals). The basic information, VTE diagnosis and treatment resources, prevention systems and the preference of the VTE risk assessment form of the two groups were compared. Logistic regression was used to analyze the proportion of VTE incidence and related factors in the two groups of hospitals. Results: (1) The median annual delivery volume of the general hospital group was significantly lower than that of the specialized hospital group (3 428 vs 9 969 cases, P <0.01), the diagnostic accessibility of CT pulmonary angiography (CTPA) was significantly higher than that of the specialized hospital [92.9% (65/70) vs 59.5% (25/42), P <0.01], and the proportion of obstetric VTE risk assessment was significantly higher than that of the specialized hospital group [85.7% (60/70) vs 66.7% (28/42), P =0.017]. (2) Among the 88 hospitals using the VTE risk assessment sheet, the utilization rate of the evaluation sheet recommended by the obstetric VTE guideline in specialized hospitals (78.6%, 22/28) was higher than that of general hospitals (48.3%, 29/60), and the difference was statistically significant ( P =0.007). (3) The proportion of VTE incidence in general hospital group was 0.126% (360/286 517), and the proportion of VTE incidence in specialized hospital group was 0.032% (154/484 111). Logistic regression analysis showed that the OR value of the specialized hospital group was 0.253 (95% CI : 0.209-0.305) and the difference was statistically significant ( P <0.01) compared with the general hospital group. After adjusting the hospital level, B-ultrasonography and CTPA accessibility, whether to establish a risk assessment and obstetric VTE system, the proportion of VTE incidence in specialized hospitals was still lower than that in general hospitals ( OR =0.307, 95% CI : 0.251-0.376, P <0.01). Conclusions: General hospitals have higher access to resources for diagnosing VTE than specialized hospitals, and the VTE evaluation system is better implemented. The utilization rate of the obstetric VTE guidelines in specialized hospitals is higher than that of general hospitals.

We herein report the long-term effect of valgus intertrochanteric osteotomy for nonunion after femoral neck fracture. In this report, we describe our experience using valgus intertrochanteric osteotomy to treat nonunion after femoral neck fracture in a 20-year-old woman. The patient was discharged from the hospital 10 days after the operation, the internal fixation device was removed 1 year after the operation, and the patient was then followed up for 18 years. Valgus intertrochanteric osteotomy can effectively treat nonunion after adductive femoral neck fracture.

Rapid and user-friendly diagnostic tests are necessary for early diagnosis and immediate detection of diseases, particularly for on-site screening of pathogenic microorganisms in aquaculture. In this study, we developed a dual-sample microfluidic chip integrated with a real-time fluorogenic loop-mediated isothermal amplification assay (dual-sample on-chip LAMP) to simultaneously detect 10 pathogenic microorganisms, that is Aeromonas hydrophila, Edwardsiella tarda, Vibrio harveyi, V. alginolyticus, V. anguillarum, V. parahaemolyticus, V. vulnificus, infectious hypodermal and haematopoietic necrosis virus, infectious spleen and kidney necrosis virus, and white spot syndrome virus. This on-chip LAMP provided a nearly automated protocol that can analyse two samples simultaneously, and the tests achieved limits of detection (LOD) ranging from 10 0 to 10 -1  pg/μl for genomic DNA of tested bacteria and 10 -4 to 10 -5  pg/μl for recombinant plasmid DNA of tested viruses, with run times averaging less than 30 min. The coefficient of variation for the time-to-positive value was less than 10%, reflecting a robust reproducibility. The clinical sensitivity and specificity were 93.52% and 85.53%, respectively, compared to conventional microbiological or clinical methods. The on-chip LAMP assay provides an effective dual-sample and multiple pathogen analysis, and thus would be applicable to on-site detection and routine monitoring of multiple pathogens in aquaculture., (© 2020 John Wiley & Sons Ltd.)

Endothelial cells adopt tissue-specific characteristics to instruct organ development and regeneration 1,2 . This adaptability is lost in cultured adult endothelial cells, which do not vascularize tissues in an organotypic manner. Here, we show that transient reactivation of the embryonic-restricted ETS variant transcription factor 2 (ETV2) 3 in mature human endothelial cells cultured in a serum-free three-dimensional matrix composed of a mixture of laminin, entactin and type-IV collagen (LEC matrix) 'resets' these endothelial cells to adaptable, vasculogenic cells, which form perfusable and plastic vascular plexi. Through chromatin remodelling, ETV2 induces tubulogenic pathways, including the activation of RAP1, which promotes the formation of durable lumens 4,5 . In three-dimensional matrices-which do not have the constraints of bioprinted scaffolds-the 'reset' vascular endothelial cells (R-VECs) self-assemble into stable, multilayered and branching vascular networks within scalable microfluidic chambers, which are capable of transporting human blood. In vivo, R-VECs implanted subcutaneously in mice self-organize into durable pericyte-coated vessels that functionally anastomose to the host circulation and exhibit long-lasting patterning, with no evidence of malformations or angiomas. R-VECs directly interact with cells within three-dimensional co-cultured organoids, removing the need for the restrictive synthetic semipermeable membranes that are required for organ-on-chip systems, therefore providing a physiological platform for vascularization, which we call 'Organ-On-VascularNet'. R-VECs enable perfusion of glucose-responsive insulin-secreting human pancreatic islets, vascularize decellularized rat intestines and arborize healthy or cancerous human colon organoids. Using single-cell RNA sequencing and epigenetic profiling, we demonstrate that R-VECs establish an adaptive vascular niche that differentially adjusts and conforms to organoids and tumoroids in a tissue-specific manner. Our Organ-On-VascularNet model will permit metabolic, immunological and physiochemical studies and screens to decipher the crosstalk between organotypic endothelial cells and parenchymal cells for identification of determinants of endothelial cell heterogeneity, and could lead to advances in therapeutic organ repair and tumour targeting.

Introduction: A meningeal hemangiopericytoma (MHPC) is an aggressive tumor characterized by a high rate of local recurrence and late distant metastasis. The objective of this study was to share our experience with the treatment of a MHPC and how to distinguish this tumor from a meningioma., Patient Concerns: A 62-year-old woman presented with symptoms of hypomnesia, hyperopia, and double vision for 1 month. Complete tumor excision was performed 6 years before. A biopsy sample was diagnosed as an atypical meningioma., Diagnosis: MHPC with late delayed hepatic metastasis., Intervention: Hepatic resection was performed initially, followed by secondary neurosurgery for complete excision of the bilateral frontal lesion 1 month later., Outcome: Based on the tumor pathology and consensus of oncologic surgeons, radiation therapy was initiated. Adjuvant therapy was well-tolerated and the patient remained recurrence-free at 6 months after surgery., Conclusion: Here, we report a case of local brain tumor recurrence and multiple hepatic metastases from a MHPC. Craniotomy combined with radical metastasectomy may be useful in such cases. Detailed immunohistochemical staining is helpful to distinguish a MHPC from a meningioma. Long-term follow-up is recommended.

Tissue regeneration capacity declines with aging in association with heightened oxidative stress. Expression of the oxidant-generating enzyme, NADPH oxidase 4 (Nox4), is elevated in aged mice with diminished capacity for fibrosis resolution. Bromodomain-containing protein 4 (Brd4) is a member of the bromodomain and extraterminal (BET) family of proteins that function as epigenetic "readers" of acetylated lysine groups on histones. In this study, we explored the role of Brd4 and its interaction with the p300 acetyltransferase in the regulation of Nox4 and the in vivo efficacy of a BET inhibitor to reverse established age-associated lung fibrosis. BET inhibition interferes with the association of Brd4, p300, and acetylated histone H4K16 with the Nox4 promoter in lung fibroblasts stimulated with the profibrotic cytokine, TGF-β1. A number of BET inhibitors, including I-BET-762, JQ1, and OTX015, downregulate Nox4 gene expression and activity. Aged mice with established and persistent lung fibrosis recover capacity for fibrosis resolution with OTX015 treatment. This study implicates epigenetic regulation of Nox4 by Brd4 and p300 and supports BET/Brd4 inhibition as an effective strategy for the treatment of age-related fibrotic lung disease.

Bredia hispida (Sonerileae, Melastomataceae), a species occurring in southeastern Sichuan, China, is newly described based on morphological and molecular data. The generic placement of B. hispida is well supported by phylogenetic analysis and morphological characters, including basally cordate, hairy leaf blade, cymose inflorescence, basally gibbous anthers and enlarged ovary crown enclosing an inverted frustum-shaped depression. Both molecular and morphological divergence showed that B. hispida is well separated from its close relatives, justifying its recognition as a distinct species. The new species resembles B. repens , B. changii and B. guidongensis in the prostrate habit and isomorphic stamens but differs markedly in the unequal opposed leaves, the 2-4 mm long, stout bristles on the adaxial surface of leaf blade and acuminate leaf apex. Bredia hispida co-occurs with B. esquirolii in the wild. No morphologically putative hybrids between them were observed despite their overlap in flowering season. The isolating mechanism remains unclear, pending further investigation., (Jin-Hong Dai, Qiu-Jie Zhou, Ren-Chao Zhou, Ying Liu.)

This article was published ahead of print on the official website of Chinese Journal of Ophthalmolog on Apirl 22,2020. Objective: Angiotensin converting enzyme 2 (ACE2) and Transmembrane serine protease 2 (TMPRSS2) are the key proteins for 2019-nCoV entry into host cells. To evaluate the potential infection risk of 2019-nCoV on ocular surface, we compared ACE2 and TMPRSS2 expression among different eye tissues. Methods: Experimental study. Thirty mice were assigned to male, female, aged, diabetic and non-diabetic groups, with 6 mice in each group. Real-time PCR was performed to quantify ACE2 and TMPRSS2 gene expression in conjunctiva, cornea, lacrimal gland, iris, lens, retina, lung, heart, kidney, and liver from male mice. Immunohistochemistry staining was applied to visualize the distribution of the two proteins in different mice tissues, and in human corneal and conjunctival sections. Published transcriptome datasets were extracted to generate the expression comparasion of ACE2 and TMPRSS2 between human conjunctival and corneal tissues, and results were analyzed using Mann-Whitney U test. Female mice, aged mice, STZ-induced diabetic mice, diabetic group control mice were also subjected to ACE2 expression analysis. Results were analyzed using Student's t -test. Results: The expression of ACE2 and TMPRSS2 genes were the highest in conjunctiva among all the six mice eye tissues explored. The expression of these two genes in conjunctiva were lower than that in kidney and lung. ACE2 and TMPRSS2 shared similar expression pattern with the staining concentrated in corneal epithelium, conjunctival epithelium and lacrimal gland serous cells. The expression levels of ACE2 showed gender difference. Female mice had lower ACE2 in conjunctiva and cornea than male mice, with the expression levels being only 43% ( t =3.269, P =0.031) and 63% ( t =4.080, P =0.015) of that in the male conjunctiva and cornea, respectively. Diabetic mice expressed more ACE2 in conjunctiva (1.21-fold, P >0.05) and lacrimal gland (1.10-fold, P >0.05) compared with the control group. No significant difference on ACE2 expression was found between the aged and young adult mice. The expression level of human conjunctiva ACE2 and TMPRSS2 were significantly higher than that in the cornea ( P =0.007), with 5.74-fold and 12.84-fold higher in the conjunctiva than in the corneal epithelium cells, which resembled the situation in mice. Conclusion: The observation of high-level ACE2 and TMPRSS2 expression in conjunctiva among the 6 eye tissues examined suggests that conjunctiva serves as an infection target tissue of 2019-nCoV. (Chin J Ophthalmol, 2020, 56:438-446) .

Background: Local infiltration analgesia (LIA) has become popular in postoperative pain relief after total hip arthroplasty (THA) or total knee arthroplasty (TKA). The aim of this meta-analysis was to compare the efficacy and safety of LIA with intrathecal morphine and epidural analgesia after THA and TKA., Methods: A systematic article search was performed from PubMed, Embase, and Web of Science databases, up to February 21, 2019. The main outcomes included visual analog scale for assessment of pain, morphine equivalent consumption, length of hospital stay, and adverse events. The data were calculated using weight mean difference (WMD) or risk ratio (RR) with 95% confidence intervals (95% CIs)., Results: Eleven studies with a total of 707 patients met the inclusion criteria and were included in this meta-analysis. LIA provided better pain control than other 2 techniques at 24-hour (WMD = 10.61, 95% CI: 3.36-17.87; P = .004), 48-hour (WMD = 16.0, 95% CI: 8.87-23.13; P < .001), and 72-hour (WMD = 11.31, 95% CI: 3.78-18.83; P < .001). Moreover, LIA had similar morphine consumption and duration of hospital stay with intrathecal morphine and epidural analgesia. There was significantly lower incidence of adverse events with LIA than with the other 2 techniques., Conclusion: LIA provided better postoperative pain control and less adverse events than intrathecal morphine and epidural analgesia after THA and TKA.

This article was published ahead of print on the official website of Chinese Jounal of Ophthalmology on February 19, 2020. The prevention and treatment of coronavirus disease 2019 (COVID-2019) has reached the critical stage in China. Ocular surface represents a possible route for infection. Based on the previous studies and our own research, we summarize the potential transmission route and clinical symptoms of COVID-2019 in the eye, as well as the further prevention and research, with the expectation of contributing to the development in the field of infectious eye disease in China. (Chin J Ophthalmol, 2020, 56:250-252) .

Interleukin-34 (IL-34) is a novel cytokine that plays an important role in innate immunity and inflammatory processes by binding to the colony-stimulating factor-1 receptor (CSF-1R). However, information on the function of IL-34 in fish remains limited. In the present study, we identified an IL-34 homolog from mudskippers ( Boleophthalmus pectinirostris ). In silico analysis showed that the mudskipper IL-34 (BpIL-34) was similar to other known IL-34 variants in sequence and structure and was most closely related to an orange-spotted grouper ( Epinephelus coioides ) homolog. BpIL-34 transcripts were constitutively expressed in various tissues, with the highest level of expression found in the brain. Edwardsiella tarda infection significantly up-regulated the mRNA expression of BpIL-34 in the mudskipper tissues. The recombinant mature BpIL-34 peptide (rBpIL-34) was purified and used to produce anti-rBpIL-34 IgG. Western blot analysis combined with PNGase F digestion revealed that native BpIL-34 in monocytes/macrophages (MOs/MФs) was N-glycosylated. In vitro , rBpIL-34 treatment enhanced the phagocytotic and bactericidal activity of mudskipper MOs/MФs, as well as the mRNA expression of pro-inflammatory cytokines like tumor necrosis factor α ( BpTNF-α ) and BpIL-1β in these cells. Furthermore, the knockdown of mudskipper CSF-1R1 ( BpCSF-1R1 ), but not mudskipper BpCSF-1R2 , significantly inhibited the rBpIL-34-mediated enhanced effect on MO/MФ function. In conclusion, our results indicate that mudskipper BpIL-34 modulates the functions of MOs/MФs via BpCSF-1R1.

Background: China's two-child policy has led to a trend of aging in pregnancy which was associated with adverse outcomes. This study aimed to identify the clinically cutoff maternal age for adverse obstetric outcomes in China., Methods: This secondary analysis of a multicenter retrospective cohort study included data of childbearing women from 39 hospitals collected in urban China during 2011 to 2012. Logistic regression was used to assess the adjusted odds ratios (aOR) of adverse outcomes in different age groups in comparison to women aged 20 to 24 years. The adjustments included the location of the hospital, educational level, and residence status. Clinically cutoff age was defined as the age above which the aOR continuously become both statistically (P < 0.05) and clinically (aOR > 2) significant., Results: Overall, 108,059 women were recruited. In primiparae, clinically cutoff maternal ages for gestational diabetes (aOR: 2.136, 95% confidence interval [CI]: 1.856-2.458, P < 0.001), placenta previa (aOR: 2.400, 95% CI: 1.863-3.090, P < 0.001), cesarean section (aOR: 2.511, 95% CI: 2.341-2.694, P < 0.001), hypertensive disorder (aOR: 2.122, 95% CI: 1.753-2.569, P < 0.001), post-partum hemorrhage (aOR: 2.129, 95% CI: 1.334-3.397, P < 0.001), and low birth weight (aOR: 2.174, 95% CI: 1.615-2.927, P < 0.001) were 27, 31, 33, 37, 41, and 41 years, respectively. In multiparae, clinically cutoff ages for gestational diabetes (aOR: 2.977, 95%CI: 1.808-4.904, P < 0.001), hypertensive disorder (aOR: 2.555, 95% CI: 1.836-3.554, P < 0.001), cesarean section (aOR: 2.224, 95% CI: 1.952-2.534, P < 0.001), post-partum hemorrhage (aOR: 2.140, 95% CI: 1.472-3.110, P < 0.001), placenta previa (aOR: 2.272, 95% CI: 1.375-3.756, P < 0.001), macrosomia (aOR: 2.215, 95% CI: 1.552-3.161, P < 0.001), and neonatal asphyxia (aOR: 2.132, 95% CI: 1.461-3.110, P < 0.001) were 29, 31, 33, 35, 35, 41, and 41 years, respectively., Conclusions: Early cutoff ages for gestational diabetes and cesarean section highlight a reasonable childbearing age in urban China. The various optimized cutoff ages for different adverse pregnancy outcomes should be carefully considered in childbearing women.

β-defensin is a cationic host defense peptide actively participating in host innate immune response against pathogens. In teleost fish, β-defensin exhibits a diversity in genotypes and functions. Herein, a β-defensin homolog (PaBD) was identified from ayu, Plecoglossus altivelis, showing multiple tissues' upregulation against Vibrio anguillarum challenge. In vivo experiments revealed that intraperitoneal injection of chemically synthesized mature PaBD (mPaBD) increased the survival rate of V. anguillarum-infected ayu, accompanied by reduced bacterial load and decreased tissue mRNA levels of tumor necrosis factor α (PaTNF-α) and interleukin 1β (PaIL-1β). However, in vitro, mPaBD showed weak bactericidal activity against V. anguillarum. Interestingly, mPaBD enhanced phagocytosis, intracellular bacterial killing, and respiratory burst of ayu monocytes/macrophages (MO/MΦ). Moreover, it inhibited mRNA levels of PaIL-1β and PaTNF-α in MO/MФ upon V. anguillarum infection. In conclusion, PaBD protects ayu against V. anguillarum challenge not only through its direct antibacterial ability, but also through its immunomodulation in MO/MΦ., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The aim of this study was to measure the urate volume within tophus and bone erosion volume using dual-energy computed tomography in patients with tophaceous gout. Furthermore, our study aims to quantitatively analyze the relationship between monosodium urate (MSU) crystal deposition and bone erosion according to the anatomic location of urate deposition.Seventy-seven subjects with chronic gout were positively identified for the presence of urate deposition. Only 27 subjects identified for the presence of urate in contact with bone erosion were included in this study. The urate volumes and associated erosion volumes were measured. The relationships between urate within tophus and bone erosion were separately analyzed according to the anatomic location of urate deposition.Twenty-seven subjects were all male (100%) with a median (interquartile range, IQR) age of 52 (45-61) years. From all the subjects, 103 tophi depositions were identified in contact with bone erosion, including 58/103 tophi that contained an intraosseous component and 45/103 nonintraosseous tophi. Tophi containing intraosseous components were larger than nonintraosseous tophi (urate volume: median [IQR] 45.64 [4.79-250.89] mm vs 19.32 [6.97-46.71] mm, P = .035) and caused greater bone erosion (erosion volume: 249.03 [147.08-845.33] mm vs 69.07 [32.88-111.24] mm, P < .001). Almost all erosion volumes were larger than urate volumes in nonperiarticular tophi, in contrast to most erosion volumes, which were less than urate volumes in the tophi that contained a periarticular component (odds ratio, 95% confidence interval: 74.00, 14.70-372.60; P < .001). Urate volume and erosion volume demonstrated positive correlations in intraosseous tophi, intraosseous-intra-articular-periarticular tophi, and intraosseous-intra-articular tophi (rs = 0.761, rs = 0.695, rs = 0.629, respectively, P < .05).MSU crystal deposition shows a promoting effect on the development of bone erosions in varying degrees, associated with the location of MSU crystals deposited in the joints. The intraosseous tophi contribute the most to bone erosions, followed by intra-articular tophi, and periarticular tophi.

Bredia (Melastomataceae) is an Asian genus that extends from central and southern mainland China to Taiwan and the Ryukyu islands. Molecular phylogenetic analyses reveal that the type of Bredia is nested in a clade of 20 species, while Tashiroea , a genus previously synonymized in Bredia , falls in another distantly related clade of 10 species. Our morphological survey shows that the two clades can be distinguished by several diagnostic features including leaf indumentum, texture, leaf surface sculpture under SEM, presence/absence of yellowish uniseriate trichomes, and capsule morphology. Based on molecular and morphological evidence, Bredia is recircumscribed and Tashiroea is resurrected. Description and a list of species are provided for the two genera with the description of a new species, T.villosa .

Fordiophytonjinpingense (Melastomataceae; Sonerileae), a species occurring in south-eastern Yunnan, China, is described as new, based on morphological and molecular data. Phylogenetic analyses, based on nrITS sequence data, showed that, except F.breviscapum , all species sampled in Fordiophyton formed a strongly supported clade in which two geographical lineages were recovered. The generic placement of F.jinpingense is well supported by phylogenetic analyses and a character combination of 4-merous flowers, distinctly dimorphic stamens and the connectives basally not calcarate. Molecular divergence and morphological evidence indicate that F.jinpingense is well separated from other members of the genus, thus justifying its recognition as a distinct species. Fordiophytonjinpingense is phylogenetically closest to F.repens , but differs markedly from the latter in stem morphology (short, obtusely 4-sided vs. long, 4-angular), habit (erect vs. creeping), leaf size (6-16.5 × 4.5-13 cm vs. 4-7.5 × 4-6.5 cm) and flower number per inflorescence (5-13 vs. 3-6).