Pleiotropy of positive selection in ancient ACE2 suggests an alternative hypothesis for bat-specific adaptations to host coronaviruses.

Angiotensin-convertingenzyme 2 (ACE2) has dual functions, regulating cardiovascular physiology and serving as the receptor for coronaviruses. Bats, the only true flying mammals and natural viral reservoirs, have evolved positive alterations in traits related to both functions of ACE2. This suggests significant evolutionary changes in ACE2 during bat evolution. To test this hypothesis, we examine the selection pressure in ACE2 along the ancestral branch of all bats (AncBat-ACE2), where powered flight and bat-coronavirus coevolution occurred, and detect a positive selection signature. To assess the functional effects of positive selection, we resurrect AncBat-ACE2 and its mutant (AncBat-ACE2-mut) created by replacing the positively selected sites. Compared to AncBat-ACE2-mut, AncBat-ACE2 exhibits stronger enzymatic activity, enhances mice's performance in exercise fatigue, and shows lower affinity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our findings indicate the functional pleiotropy of positive selection in the ancient ACE2 of bats, providing an alternative hypothesis for the evolutionary origin of bats' defense against coronaviruses.

ABSCISIC ACID-INSENSITIVE 5-KIP-RELATED PROTEIN 1-SHOOT MERISTEMLESS modulates reproductive development of Arabidopsis.

Soil (or plant) water deficit accelerates plant reproduction. However, the underpinning molecular mechanisms remain unknown. By modulating cell division/number, ABSCISIC ACID-INSENSITIVE 5 (ABI5), a key bZIP (basic (region) leucine zippers) transcription factor, regulates both seed development and abiotic stress responses. The KIP-RELATED PROTEIN (KRP) cyclin-dependent kinases (CDKs) play an essential role in controlling cell division, and SHOOT MERISTEMLESS (STM) plays a key role in the specification of flower meristem identity. Here, our findings show that abscisic acid (ABA) signaling and/or metabolism in adjust reproductive outputs (such as rosette leaf number and open flower number) under water-deficient conditions in Arabidopsis (Arabidopsis thaliana) plants. Reproductive outputs increased under water-sufficient conditions but decreased under water-deficient conditions in the ABA signaling/metabolism mutants abscisic acid2-1 (aba2-1), aba2-11, abscisic acid insensitive3-1 (abi3-1), abi4-1, abi5-7, and abi5-8. Further, under water-deficient conditions, ABA induced-ABI5 directly bound to the promoter of KRP1, which encodes a CDK that plays an essential role in controlling cell division, and this binding subsequently activated KRP1 expression. In turn, KRP1 physically interacted with STM, which functions in the specification of flower meristem identity, promoting STM degradation. We further demonstrate that reproductive outputs are adjusted by the ABI5-KRP1-STM molecular module under water-deficient conditions. Together, our findings reveal the molecular mechanism by which ABA signaling and/or metabolism regulate reproductive development under water-deficient conditions. These findings provide insights that may help guide crop yield improvement under water deficiency.

Electronic and Transport Properties of InSe/PtTe2 van der Waals Heterostructure.

Two-dimensional (2D) InSe and PtTe2 have drawn extensive attention due to their intriguing properties. However, the InSe monolayer is an indirect bandgap semiconductor with a low hole mobility. van der Waals (vdW) heterostructures produce interesting electronic and optoelectronic properties beyond the existing 2D materials and endow totally new device functions. Herein, we theoretically investigated the electronic structures, transport behaviors, and electric field tuning effects of the InSe/PtTe2 vdW heterostructures. The calculated results show that the direct bandgap type-II vdW heterostructures can be realized by regulating the stacking configurations of heterostructures. By applying an external electric field, the band alignment and bandgap of the heterostructures can also be flexibly modulated. Particularly, the hole mobility of the heterostructures is improved by 2 orders of magnitude to ∼103 cm2 V-1 s-1, which overcomes the intrinsic disadvantage of the InSe monolayer. The InSe/PtTe2 vdW heterostructures have great potential applications in developing novel optoelectronic devices.

Angiotensin II type-2 receptor signaling facilitates liver injury repair and regeneration via inactivation of Hippo pathway.

The angiotensin II type 2 receptor (AT2R) is a well-established component of the renin-angiotensin system and is known to counteract classical activation of this system and protect against organ damage. Pharmacological activation of the AT2R has significant therapeutic benefits, including vasodilation, natriuresis, anti-inflammatory activity, and improved insulin sensitivity. However, the precise biological functions of the AT2R in maintaining homeostasis in liver tissue remain largely unexplored. In this study, we found that the AT2R facilitates liver repair and regeneration following acute injury by deactivating Hippo signaling and that interleukin-6 transcriptionally upregulates expression of the AT2R in hepatocytes through STAT3 acting as a transcription activator binding to promoter regions of the AT2R. Subsequently, elevated AT2R levels activate downstream signaling via heterotrimeric G protein Gα12/13-coupled signals to induce Yap activity, thereby contributing to repair and regeneration processes in the liver. Conversely, a deficiency in the AT2R attenuates regeneration of the liver while increasing susceptibility to acetaminophen-induced liver injury. Administration of an AT2R agonist significantly enhances the repair and regeneration capacity of injured liver tissue. Our findings suggest that the AT2R acts as an upstream regulator in the Hippo pathway and is a potential target in the treatment of liver damage.

AXIN1/MYC Axis Mediated the Osimertinib Resistance in EGFR Mutant Non-Small Cell Lung Cancer Cells.

Osimertinib, a promising and approved third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is a standard strategy for EGFR-mutant non-small cell lung cancer (NSCLC) patients. However, developed resistance is unavoidable, which reduces its long-term effectiveness. In this study, RNA sequencing was performed to analyze differentially expressed genes (DEGs). The PrognoScan database and Gene Expression Profiling Interactive Analysis (GEPIA) were used to identify the key genes for clinical prognosis and gene correlation respectively. Protein expression was determined by western blot analysis. Cell viability assay and Ki67 staining were used to evaluate the effect of osimertinib on tumor cells. Finally, we screened out two hub genes, myelocytomatosis oncogene (Myc) and axis inhibition protein 1 (Axin1), upregulated in three osimertinib-resistant cell lines through RNA sequencing and bioinformatics analysis. Next, cell experiment confirmed that expression of C-MYC and AXIN1 were elevated in different EGFR mutant NSCLC cell lines with acquired resistance to osimertinib, compared with their corresponding parental cell lines. Furthermore, we demonstrated that AXIN1 upregulated the expression of C-MYC and mediated the acquired resistance of EGFR mutant NSCLC cells to osimertinib in vitro. In conclusion, AXIN1 affected the sensitivity of EGFR mutant NSCLC to osimertinib via regulating C-MYC expression in vitro. Targeting AXIN1/MYC signaling may be a potential new strategy for overcoming acquired resistance to osimertinib.

Real-Time Detection of Unauthorized Unmanned Aerial Vehicles Using SEB-YOLOv8s.

Aiming at real-time detection of UAVs, small UAV targets are easily missed and difficult to detect in complex backgrounds. To maintain high detection performance while reducing memory and computational costs, this paper proposes the SEB-YOLOv8s detection method. Firstly, the YOLOv8 network structure is reconstructed using SPD-Conv to reduce the computational burden and accelerate the processing speed while retaining more shallow features of small targets. Secondly, we design the AttC2f module and replace the C2f module in the backbone of YOLOv8s with it, enhancing the model's ability to obtain accurate information and enriching the extracted relevant information. Finally, Bi-Level Routing Attention is introduced to optimize the Neck part of the network, reducing the model's attention to interfering information and filtering it out. The experimental results show that the mAP50 of the proposed method reaches 90.5% and the accuracy reaches 95.9%, which are improvements of 2.2% and 1.9%, respectively, compared with the original model. The mAP50-95 is improved by 2.7%, and the model's occupied memory size only increases by 2.5 MB, effectively achieving high-accuracy real-time detection with low memory consumption.

Wafer-Scale Single Crystal Hexagonal Boron Nitride Layers Grown by Submicron-Spacing Vapor Deposition.

The direct growth of wafer-scale single crystal two-dimensional (2D) hexagonal boron nitride (h-BN) layer with a controllable thickness is highly desirable for 2D-material-based device applications. Here, for the first time, a facile submicron-spacing vapor deposition (SSVD) method is reported to achieve 2-inch single crystal h-BN layers with controllable thickness from monolayer to tens of nanometers on the dielectric sapphire substrates using a boron film as the solid source. In the SSVD growth, the boron film is fully covered by the same-sized sapphire substrate with a submicron spacing, leading to an efficient vapor diffusion transport. The epitaxial h-BN layer exhibits extremely high crystalline quality, as demonstrated by both a sharp Raman E2g vibration mode (12 cm-1 ) and a narrow X-ray rocking curve (0.10°). Furthermore, a deep ultraviolet photodetector and a ZrS2 /h-BN heterostructure fabricated from the h-BN layer demonstrate its fascinating properties and potential applications. This facile method to synthesize wafer-scale single crystal h-BN layers with controllable thickness paves the way to future 2D semiconductor-based electronics and optoelectronics.

Necroptosis-related subtypes are associated with bronchiectasis in pulmonary non-tuberculous mycobacteria-infected patients: a perspective based on transcriptomic analysis.

The aim of this study was to explore the potential mechanisms responsible for the different manifestations of bronchiectasis in patients with pulmonary non-tuberculous mycobacteria (pNTM) infection. We found that the necroptosis level increased significantly after NTM infection. Further, the 31 pNTM-infected patients were classified into two subtypes based on necroptosis-related genes (NRGs) by unsupervised cluster analysis. After that, we compared the differences in clinical parameters, immune cell infiltration, and gene expression between the two subtypes. We observed that the high-necroptosis subtype possessed higher CT scores for bronchiectasis extent (P = 0.008) and severity (P = 0.023). And, more neutrophil infiltration in the high-necroptosis subtype was demonstrated both by the CIBERSORT algorithm and by blood neutrophil count (P = 0.001). Next, 688 differentially expressed genes (DEGs) between two subtypes were identified. To explore the portion in DEGs that might contribute to bronchiectasis, we intersected the DEGs with two gene modules. These two gene modules were identified as the most associated with CT scores for bronchiectasis extent and severity by weighted gene co-expression network analysis (WGCNA). Ninety-three intersection genes were obtained. Finally, 7 hub genes including ACSL1, ANXA3, DYSF, HK3, SLC11A1, STX11, and TLR4 were further screened out by machine learning algorithms and protein-protein interaction network analysis. These results suggested that the differential levels of necroptosis in pNTM patients might lead to differential extent and severity of bronchiectasis on radiographic imaging. This process might be associated with neutrophil infiltration and the involvement of seven hub genes.

A hybrid type Ia supernova with an early flash triggered by helium-shell detonation.

Type Ia supernovae arise from the thermonuclear explosion of white-dwarf stars that have cores of carbon and oxygen. The uniformity of their light curves makes these supernovae powerful cosmological distance indicators, but there have long been debates about exactly how their explosion is triggered and what kind of companion stars are involved. For example, the recent detection of the early ultraviolet pulse of a peculiar, subluminous type Ia supernova has been claimed as evidence for an interaction between a red-giant or a main-sequence companion and ejecta from a white-dwarf explosion. Here we report observations of a prominent but red optical flash that appears about half a day after the explosion of a type Ia supernova. This supernova shows hybrid features of different supernova subclasses, namely a light curve that is typical of normal-brightness supernovae, but with strong titanium absorption, which is commonly seen in the spectra of subluminous ones. We argue that this early flash does not occur through previously suggested mechanisms such as the companion-ejecta interaction. Instead, our simulations show that it could occur through detonation of a thin helium shell either on a near-Chandrasekhar-mass white dwarf, or on a sub-Chandrasekhar-mass white dwarf merging with a less-massive white dwarf. Our finding provides evidence that one branch of previously proposed explosion models-the helium-ignition branch-does exist in nature, and that such a model may account for the explosions of white dwarfs in a mass range wider than previously supposed.

Assessment of post-COVID-19 fatigue among female survivors 2 years after hospital discharge: a nested case-control study.

BACKGROUND: Fatigue is a common symptom of long COVID syndrome. Compared to male survivors, females have a higher incidence of post-COVID fatigue. Therefore, long-term follow-up is necessary to understand which groups of females are more vulnerable to post-COVID fatigue. METHODS: This is a nested case-control study of female COVID-19 survivors who were discharged from two designated hospitals in Wuhan, China in 2020, and received 2-year follow-up from March 1 to April 6, 2022. All patients completed the Checklist Individual Strength-subscale subjective fatigue (CIS-fatigue), a chronic obstructive pulmonary disease (COPD) assessment test (CAT), and the Hospital Anxiety and Depression Scale (HADS; including the HADS-Anxiety [HADS-A] and the HADS-Depression [HADS-D]). Individuals with CIS-fatigue scores of 27 or higher were classified as cases. The risk factors for fatigue was analysed with multivariable logistic regression analysis. RESULTS: A total of 899 female COVID-19 survivors were enrolled for analysis, including 47 cases and 852 controls. Compared with controls, cases had higher CAT, HADS-A and HADS-D scores, and showed a higher prevalence of symptoms, including anxiety (cases vs. controls, 44.7% vs. 4.0%, p < 0.001), chest tightness (21.2% vs. 2.3%, p < 0.001), dyspnoea (19.1% vs. 0.8%, p < 0.001) and so on. In multivariable logistic regression analysis, age (OR, 1.03; 95% CI, 1.01-1.06; p = 0.02) and cerebrovascular disease (OR, 11.32; 95% CI, 2.87-43.00; p < 0.001) were risk factors for fatigue. Fatigue had a statistically significant moderate correlation with depression (r = 0.44, p < 0.001), but not with CAT ≥ 10. CONCLUSION: Female COVID-19 patients who had cerebrovascular disease and older age have higher risk of fatigue. Patients with fatigue have higher CAT scores, and are more likely to have concurrent depression.

Development and validation of an HPLC coupled with tandem mass spectrometry method for the determination of HSK7653, a novel super long-acting dipeptidyl peptidase-4 inhibitor, in human plasma and urine and its application to a pharmacokinetic study.

HSK7653 is a novel super long-acting dipeptidyl peptidase-4 inhibitor, which is promising for the treatment of type 2 diabetes mellitus with the twice-monthly dosing regimen. In this article, a robust and sensitive HPLC coupled with tandem mass spectrometry method for determining the concentration of HSK7653 in human plasma and urine was developed and validated for the first time. Plasma and urine samples were prepared by protein precipitation. After that, the extracts were analyzed using an LC-20A HPLC system coupled with API 4000 tandem MS equipped with an electrospray ionization source in positive mode. Separation was obtained using an XBridge Phenyl column (2.1 × 50 mm, 3.5 µm) with a gradient elution of acetonitrile and water containing 0.1% formic acid and 5% acetonitrile at room temperature. This bioanalysis method has been fully validated and the results showed good sensitivity and specificity. In brief, the standard curves were linear over the concentration range of 2.00-2000 ng/ml for plasma and 20.0-20,000 ng/ml for urine, respectively. In addition, the precisions of inter- and intra-run of HSK7653 were less than 12.7% and the accuracies were -3.3% to 6.3% for both plasma and urine. Finally, this method was successfully applied to explore the pharmacokinetic characteristics of HSK7653 in Chinese healthy volunteers in a first-in-human study.

A multivariate model based on gadoxetic acid-enhanced MRI using Li-RADS v2018 and other imaging features for preoperative prediction of dual­phenotype hepatocellular carcinoma.

OBJECTIVE: To investigate the diagnostic value of liver imaging reporting and data system (LI-RADS) v2018 and other imaging features in dual-phenotype hepatocellular carcinoma (DPHCC), establish a prediagnostic model based on gadoxetic acid-enhanced MRI, and explore the prognostic significance after surgery of the DPHCC. MATERIALS AND METHODS: Preoperative enhanced MRI findings and the clinical and pathological data of patients with surgically confirmed HCC were analysed retrospectively. Image analysis was based on LI-RADS v2018 and other image features. Univariate analysis was used to screen for predictive factors of DPHCC, and multivariate logistic regression analysis was used to determine the predictive factors. A regression diagnostic model was established. Receiver operating characteristic (ROC) curve analysis was used to determine the critical value, area under curve (AUC), and the corresponding 95% confidence interval (95% CI). The diagnostic performance was verified by fivefold cross-validation. Cox regression analysis was used to determine the prognostic factors associated with early recurrence after surgical resection. RESULTS: In total, 158 patients were included, of whom 79 had DPHCC and 79 had non-DPHCC. Multivariate analysis showed that rim arterial phase hyperenhancement (Rim APHE) and targetoid restriction were independent risk factors for DPHCC (P < 0.05). The AUC (95% CI) of the model was 0.862 (0.807-0.918), sensitivity was 81.01%, and specificity was 89.874%. Cox regression analysis showed that DPHCC, microvascular invasion, tumour diameter, and an increase of alpha-fetoprotein were independent factors for recurrence. CONCLUSION: Rim APHE and targetoid restriction were sensitive imaging features of DPHCC before surgery, and the identification of DPHCC has important prognostic significance for early recurrence.

[Difference in Brain Age Between Alzheimer's Disease and Mild Cognitive Impairment].

Objective To investigate the brain age differences between Alzheimer's disease(AD)and mild cognitive impairment(MCI)patients,and further explore the correlations between brain age gap(BAG)and clinical features.Methods The clinical data and radiologic findings of 132 probable AD and AD-derived MCI patients diagnosed at Beijing Tiantan Hospital,Capital Medical University from December 2018 to July 2021 were retrospectively analyzed.According to the diagnostic criteria for AD and MCI,the patients were assigned into AD and MCI groups.In addition,156 volunteers without neurological diseases and other severe diseases were recruited as the control group.The general data,Montreal cognitive assessment(MoCA)score,and mini-mental state examination(MMSE)score were compared among the three groups.The deep learning-based brain age prediction model was employed to calculate the BAGs of the three groups.Spearman correlation analysis was conducted to explore the correlations between BAG and clinical features.Results The 132 patients included 106 patients in the AD group and 26 patients in the MCI group.The MoCA and MMSE scores followed an ascending trend of AD group

[Protective effect of melatonin against oxygen-induced retinopathy: a study based on the HMGB1/NF-κB/NLRP3 axis]. / 基于HMGB1/NF-κB/NLRP3è½´æŽ¢è®¨è¤ªé»‘ç´ å¯¹æ°§è¯±å¯¼è§†ç½‘è†œç— å˜çš„ä¿æŠ¤ä½œç”¨.

OBJECTIVES: To study the protective effect of melatonin (Mel) against oxygen-induced retinopathy (OIR) in neonatal mice and the role of the HMGB1/NF-κB/NLRP3 axis. METHODS: Neonatal C57BL/6J mice, aged 7 days, were randomly divided into a control group, a model group (OIR group), and a Mel treatment group (OIR+Mel group), with 9 mice in each group. The hyperoxia induction method was used to establish a model of OIR. Hematoxylin and eosin staining and retinal flat-mount preparation were used to observe retinal structure and neovascularization. Immunofluorescent staining was used to measure the expression of proteins and inflammatory factors associated with the HMGB1/NF-κB/NLRP3 axis and lymphocyte antigen 6G. Colorimetry was used to measure the activity of myeloperoxidase. RESULTS: The OIR group had destruction of retinal structure with a large perfusion-free area and neovascularization, while the OIR+Mel group had improvement in destruction of retinal structure with reductions in neovascularization and perfusion-free area. Compared with the control group, the OIR group had significant increases in the expression of proteins and inflammatory factors associated with the HMGB1/NF-κB/NLRP3 axis, the expression of lymphocyte antigen 6G, and the activity of myeloperoxidase (P<0.05). Compared with the OIR group, the OIR+Mel group had significant reductions in the above indices (P<0.05). Compared with the control group, the OIR group had significant reductions in the expression of melatonin receptors in the retina (P<0.05). Compared with the OIR group, the OIR+Mel group had significant increases in the expression of melatonin receptors (P<0.05). CONCLUSIONS: Mel can alleviate OIR-induced retinal damage in neonatal mice by inhibiting the HMGB1/NF-κB/NLRP3 axis and may exert an effect through the melatonin receptor pathway.

Quantitative Assessment of Arsenite-Induced Perturbation of Ubiquitinated Proteome.

Arsenic contamination in food and groundwater constitutes a public health concern for more than 200 million people worldwide. Individuals chronically exposed to arsenic through drinking and ingestion exhibit a higher risk of developing cancers and cardiovascular diseases. Nevertheless, the underlying mechanisms of arsenic toxicity are not fully understood. Arsenite is known to bind to and deactivate RING finger E3 ubiquitin ligases; thus, we reason that a systematic interrogation about how arsenite exposure modulates global protein ubiquitination may reveal novel molecular targets for arsenic toxicity. By employing liquid chromatography-tandem mass spectrometry, in combination with stable isotope labeling by amino acids in cell culture (SILAC) and immunoprecipitation of di-glycine-conjugated lysine-containing tryptic peptides, we assessed the alterations in protein ubiquitination in GM00637 human skin fibroblast cells upon arsenite exposure at the entire proteome level. We observed that arsenite exposure led to altered ubiquitination of many proteins, where the alterations in a large majority of ubiquitination events are negatively correlated with changes in expression of the corresponding proteins, suggesting their modulation by the ubiquitin-proteasomal pathway. Moreover, we observed that arsenite exposure confers diminished ubiquitination of a rate-limiting enzyme in cholesterol biosynthesis, HMGCR, at Lys248. We also revealed that TRC8 is the major E3 ubiquitin ligase for HMGCR ubiquitination in HEK293T cells, and the arsenite-induced diminution of HMGCR ubiquitination is abrogated upon genetic depletion of TRC8. In summary, we systematically characterized arsenite-induced perturbations in a ubiquitinated proteome in human cells and found that the arsenite-elicited attenuation of HMGCR ubiquitination in HEK293T cells involves TRC8.

Fixed dosing of kukoamine B in sepsis patients: Results from population pharmacokinetic modelling and simulation.

AIMS: To assess the appropriateness of the body weight or fixed dosing regimen, a population pharmacokinetic (PopPK) model of kukoamine B has been built in sepsis patients. METHODS: Plasma concentrations of kukoamine B and the covariates information were taken from 30 sepsis patients assigned into 0.06 mg/kg, 0.12 mg/kg and 0.24 mg/kg groups in a Phase IIa clinical trial. The PopPK model was built using a nonlinear mixed-effect (NLME) modelling approach. Based on the final model, PK profiles were respectively simulated 500 times applying the body weight and renal function information of 12 sepsis patients from the 0.24 mg/kg group on the body weight or the fixed dosing regimen. For each dosing regimen, PK profiles of 6000 virtual patients were obtained. Statistical analyses for Cmax and Cmin were performed. If the biases of Cmax and Cmin can all meet the criteria of ±15%, the fixed dosing regimen can substitute for the body weight dosing regimen. RESULTS: The PopPK model was successfully developed using the NLME approach. A bi-compartmental model was selected as the basic model. Renal function was identified as a statistically significant covariate of systemic clearance with the objective function value (OFV) decreasing 8.6, resulting in a 5.2% decrease in inter-individual variability (IIV) of systemic clearance. Body weight was not identified as a statistically significant covariate. Simulation results demonstrated two methods had a bias of 8.1% for Cmax , and 8.6% for Cmin . Furthermore, PK variability was lower on the fixed dosing regimen than the body weight regimen. CONCLUSIONS: Based on the simulation results, a fixed dosing regimen was recommended in the subsequent clinical trials.

Angiotensin II Type 2 Receptor Modulates Synovial Macrophage Polarization by Inhibiting GRK2 Membrane Translocation in a Rat Model of Collagen-Induced Arthritis.

The chronic inflammatory autoimmune disease rheumatoid arthritis (RA) is characterized by an infiltration of activated proinflammatory immune cells into the joint that is accompanied by an overproduction of various mediators, leading to destruction of cartilage and bone erosion. Angiotensin II type 2 receptor (AT2R) is involved in antioxidative, anti-inflammatory, and antifibrotic responses. Synovial macrophages (SMs) are a type of tissue macrophages that are derived from bone marrow cells. SMs plays a central role in synovial regional immunization, which is significantly increased in both collagen-induced mice with arthritis mice and RA patients. AT2R activation caused a reversal of the polarization of SMs in the joint from the proinflammatory M1 SM to the tolerogenic, benign M2 SM. In consequence, this switch resulted in an attenuated form of the joint pathology in a rat model of collagen-induced arthritis. These results were mechanistically linked to the observation that GRK2 was translocated into cytoplasm, and ERK1/2 and NF-κB activation were inhibited. These findings open the way to a new therapeutic approach using an activation of AT2R to subvert joint inflammation in RA.

An exploration of optimal time and safety of 595-nm pulsed dye laser for the treatment of early superficial infantile hemangioma.

Infantile hemangioma (IH) is the most common benign vascular tumor that occurs in infants and young children. Studies have shown laser therapy to reduce the proliferation of superficial IH and promote its regression, but the optimal timing for treatment has not been determined. Our study explores the timing and safety of 595-nm pulsed dye laser (PDL) treatment for early superficial IH. We retrospectively analyzed 180 cases of superficial IH treated with 595-nm PDL. Data was organized according to patient age at the first visit. Six months after the initial treatment, patients were evaluated using a grade IV classification method, and the clinical curative effect of each group was calculated. The number of laser treatments and the occurrence of adverse reactions were recorded simultaneously. The overall effective and cure rates were 98.3% and 84.4%, respectively, with no significant difference in rates between groups (p > 0.05). There was a statistically significant difference in the number of laser treatments among the age groups (p < 0.05). The average laser frequency: "0-2 months group" < "2-4 months group" < "4-6 months group." The overall incidence of adverse reactions was 11.1%, and 12 (6.7%) cases had short-term adverse reactions, with no statistically significant differences between groups (p > 0.05). Eight cases had long-term adverse reactions. This difference between groups was statistically significant (p < 0.05). Younger children (≤2 months of age) receiving 595-nm PDL treatment for IH require relatively fewer treatment times than other children (>2 months of age), have a shorter course of disease, experience better curative effect, and have fewer sequelae reactions.

Species Diversification of the Coniferous Pathogenic Fungal Genus Coniferiporia (Hymenochaetales, Basidiomycota) in Association with Its Biogeography and Host Plants.

Coniferiporia, belonging to Hymenochaetaceae and now segregated from Phellinidium, is a wood-inhabiting fungal genus with three species, each having a specific geographic distribution and a strong host specificity as a forest pathogen of coniferous trees. In this study, the species diversity of Coniferiporia is further clarified with the aid of a wider sampling and multilocus-based phylogenetic analysis, which reveals a new species Coniferiporia uzbekistanensis. The molecular clock and ancestral geographic origin analyses indicate that the ancestor of Coniferiporia emerged in one of the Pinaceae and Cupressaceae, then jumped to the other plant family originated in eastern Eurasia 17.01 million years ago (Mya; 95% highest posterior density: 9.46 to 25.86 Mya), and later extended its distribution to western North America, Central Asia, and eastern Europe. Coniferiporia sulphurascens speciated on Pinaceae in eastern Eurasia 8.78 Mya (9.46 to 25.86 Mya) and then extended its distribution to western North America and eastern Europe. Coniferiporia qilianensis and C. uzbekistanensis speciated on Juniperus przewalskii in eastern Eurasia 3.67 Mya (0.36 to 8.02 Mya) and on Juniperus polycarpos in Central Asia 4.35 Mya (0.94 to 8.37 Mya), respectively. The speciation event of Coniferiporia weirii occurred 4.45 Mya (0.77 to 9.33 Mya) right after the emergence of its host, the endemic Cupressaceae species Thuja plicata, and soon after, this fungus evolved to also inhabit another endemic Cupressaceae species Calocedrus decurrens. In summary, this study for the first time unambiguously clarified and timed the adaptive evolutionary event of Coniferiporia in association with its biogeography and host plants.

Efficiency comparison with fovea-sparing internal limiting membrane peeling and complete internal limiting membrane peeling for treating myopic traction maculopathy.

PURPOSE: To explore whether the efficacy of fovea-sparing internal limiting membrane peeling (FS-ILMP) is better than that of complete internal limiting membrane peeling (ILMP). METHODS: This retrospective clinical study included 34 cases (34 eyes) with myopic traction maculopathy collected from June 2017 to February 2019. Twenty-three-gauge (23-G) pars plana vitrectomy (23G PPV) was performed on all patients. In the FS-ILMP group, 18 eyes retained the internal limiting membrane (ILM) of about 1 to 1.5 papillary diameter centered on fovea centralis, while in the standard ILMP group, the ILM was completely removed from 16 eyes. The best corrected visual acuity (BCVA), central foveal thickness (CFT), and other indexes were collected before and 6 months after surgery. RESULTS: There was no significant difference in baseline clinical characteristics between the two groups. CFT and BCVA were significantly improved in both FS-ILMP and standard ILMP group, but the postoperative BCVA of the FS-ILMP group was significantly better than that of the standard ILMP group (P < 0.001). Two cases of subretinal effusion in macula were recorded in the FS-ILMP group, and three eyes in the standard ILMP group developed macular holes after surgery. Although both treatments relieved the mechanical traction of macular fovea, the patients in the FS-ILMP group showed better clinical outcomes in various aspects. CONCLUSION: These results improved our understanding of the clinical application of vitrectomy combined with preservation of ILM upon the fovea centralis, which might lay a foundation for in-depth study on the treatment of myopic traction maculopathy.