Design, synthesis, and biological evaluation of novel 8-substituted quercetin derivatives targeting the ß­catenin/B-cell lymphoma 9 interaction.

The ß-catenin/B-cell lymphoma 9 (BCL9) protein-protein interaction (PPI) is a potential target for aberrantly active Wnt/ß-catenin signaling which actively participates in initiating and progressing of many cancers. Herein, we discovered novel 8-substituted quercetin derivatives with potential inhibitory activities targeting ß-catenin/BCL9 PPI. Among all the derivatives, compound B4 displayed the most promising PPI inhibitory activity with an IC50 value of 2.25 µM in a competitive fluorescence polarization assay and a KD value of 1.44 µM for the ß-catenin protein. Furthermore, B4 selectively inhibited the growth of colorectal cancer (CRC) cells, suppressed the transactivation of Wnt signaling, and downregulated the expression of oncogenic Wnt target gene. Especially, B4 showed potent anti-CRC activity in vivo with the tumor growth inhibition (TGI) of 75.99 % and regulated the tumor immune microenvironment.

Nonalcoholic fatty liver disease is an independent risk factor for ischemic stroke after revascularization in patients with Moyamoya disease: a prospective cohort study.

BACKGROUND: The study aimed to investigate the association between nonalcoholic fatty liver disease (NAFLD) and ischemic stroke events after revascularization in patients with Moyamoya disease (MMD). METHODS: This study prospectively enrolled 275 MMD patients from September 2020 to December 2021. Patients with alcoholism and other liver diseases were excluded. NAFLD was confirmed by CT imaging or abdominal ultrasonography. Stroke events and modified Rankin Scale (mRS) scores at the latest follow-up were compared between the two groups. RESULTS: A total of 275 patients were enrolled in the study, among which 65 were diagnosed with NAFLD. Univariate logistic regression analysis showed that NAFLD (P = 0.029) was related to stroke events. Multivariate logistic regression analysis showed that NAFLD is a predictor of postoperative stroke in MMD patients (OR = 27.145, 95% CI = 2.031-362.81, P = 0.013). Kaplan-Meier analysis showed that compared with MMD patients with NAFLD, patients in the control group had a longer stroke-free time (P = 0.004). Univariate Cox analysis showed that NAFLD (P = 0.016) was associated with ischemic stroke during follow-up in patients with MMD. Multivariate Cox analysis showed that NAFLD was an independent risk factor for stroke in patients with MMD (HR = 10.815, 95% CI = 1.259-92.881, P = 0.030). Furthermore, fewer patients in the NAFLD group had good neurologic status (mRS score ≤ 2) than the control group (P = 0.005). CONCLUSION: NAFLD was an independent risk factor for stroke in patients with MMD after revascularization and worse neurological function outcomes.

IDEAL-IQ combined with intravoxel incoherent motion diffusion-weighted imaging for quantitative diagnosis of osteoporosis.

BACKGROUND: Osteoporosis (OP) is a common chronic metabolic bone disease characterized by decreased bone mineral content and microstructural damage, leading to increased fracture risk. Traditional methods for measuring bone density have limitations in accurately distinguishing vertebral bodies and are influenced by vertebral degeneration and surrounding tissues. Therefore, novel methods are needed to quantitatively assess changes in bone density and improve the accurate diagnosis of OP. METHODS: This study aimed to explore the applicative value of the iterative decomposition of water and fat with echo asymmetry and least-squares estimation-iron (IDEAL-IQ) sequence combined with intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) for the diagnosis of osteoporosis. Data from 135 patients undergoing dual-energy X-ray absorptiometry (DXA), IDEAL-IQ, and IVIM-DWI were prospectively collected and analyzed. Various parameters obtained from IVIM-DWI and IDEAL-IQ sequences were compared, and their diagnostic efficacy was evaluated. RESULTS: Statistically significant differences were observed among the three groups for FF, R2*, f, D, DDC values, and BMD values. FF and f values exhibited negative correlations with BMD values, with r=-0.313 and - 0.274, respectively, while R2*, D, and DDC values showed positive correlations with BMD values, with r = 0.327, 0.532, and 0.390, respectively. Among these parameters, D demonstrated the highest diagnostic efficacy for osteoporosis (AUC = 0.826), followed by FF (AUC = 0.713). D* exhibited the lowest diagnostic performance for distinguishing the osteoporosis group from the other two groups. Only D showed a significant difference between genders. The AUCs for IDEAL-IQ, IVIM-DWI, and their combination were 0.74, 0.89, and 0.90, respectively. CONCLUSIONS: IDEAL-IQ combined with IVIM-DWI provides valuable information for the diagnosis of osteoporosis and offers evidence for clinical decisions. The superior diagnostic performance of IVIM-DWI, particularly the D value, suggests its potential as a more sensitive and accurate method for diagnosing osteoporosis compared to IDEAL-IQ. These findings underscore the importance of integrating advanced imaging techniques into clinical practice for improved osteoporosis management and highlight the need for further research to explore the full clinical implications of these imaging modalities.

Lactobacillus paracasei AH2 isolated from Chinese sourdough alleviated gluten-induced food allergy through modulating gut microbiota and promoting short-chain fatty acid accumulation in a BALB/c mouse model.

BACKGROUND: A large number of people worldwide suffer from gluten-induced food allergy. As investigated in our previous research, Lactobacillus paracasei AH2 isolated from traditionally homemade sourdough in Anhui province of China showed the potential to reduce the immune reactivity of wheat protein by in vitro evaluation. However, whether L. paracasei AH2 has a role in alleviating wheat allergy in an in vivo model and its underlying mechanisms have not been elucidated. RESULTS: In this study, the alleviative effects of L. paracasei AH2 on gluten-induced allergic response were evaluated. Compared with a gluten-allergic mouse, L. paracasei AH2 suppressed anaphylaxis symptoms, gluten-specific immunoglobulin E, histamine and interleukin-4. Moreover, L. paracasei AH2 attenuated splenomegaly and induced Th1 or Treg cell differentiation to modulate the Th1/Th2 immune balance toward Th1 polarization. Short-chain fatty acid (SCFA) levels were enhanced after L. paracasei AH2 supplementation, contributing to allergy relief as well as reducing the pH of colonic contents. The α and ß diversities of the gut microbiota were modulated by L. paracasei AH2 with increased relative abundance of Lacticaseibacillus and SCFA producers (Faecalibaculum, Alloprevotella and Bacteroides genera), as well as decreased unfavorable Lachnospiraceae_NK4A136_group and Alistipes. Additionally, L. paracasei AH2 protected the intestinal barrier function by upregulating tight junctions and improved the antioxidant activities in serum. CONCLUSION: Our findings indicate that L. paracasei AH2 could act as a potential probiotic for relieving wheat allergy by modulating the gut microbiota and elevating SCFA levels. © 2023 Society of Chemical Industry.

Targeting Cyclophilin A and CD147 to Inhibit Replication of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and SARS-CoV-2-Induced Inflammation.

Identification and development of effective therapeutics for coronavirus disease 2019 (COVID-19) are still urgently needed. The CD147-spike interaction is involved in the severe acute respiratory syndrome coronavirus (SARS-CoV)-2 invasion process in addition to angiotensin-converting enzyme 2 (ACE2). Cyclophilin A (CyPA), the extracellular ligand of CD147, has been found to play a role in the infection and replication of coronaviruses. In this study, our results show that CyPA inhibitors such as cyclosporine A (CsA) and STG-175 can suppress the intracellular replication of SARS-CoV-2 by inhibiting the binding of CyPA to the SARS-CoV-2 nucleocapsid C-terminal domain (N-CTD), and the IC50 is 0.23 µM and 0.17 µM, respectively. Due to high homology, CsA also had inhibitory effects on SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), and the IC50 is 3.2 µM and 2.8 µM, respectively. Finally, we generated a formulation of phosphatidylserine (PS)-liposome-CsA for pulmonary drug delivery. These findings provide a scientific basis for identifying CyPA as a potential drug target for the treatment of COVID-19 as well as for the development of broad-spectrum inhibitors for coronavirus via targeting CyPA. Highlights: 1) SARS-CoV-2 infects cells via the binding of its S protein and CD147; 2) binding of SARS-CoV-2 N protein and CyPA is essential for viral replication; 3) CD147 and CyPA are potential therapeutic targets for SARS-CoV-2; and 4) CsA is a potential therapeutic strategy by interrupting CD147/CyPA interactions. SIGNIFICANCE STATEMENT: New severe acute respiratory syndrome coronavirus (SARS-CoV)-2 variants and other pathogenic coronaviruses (CoVs) are continually emerging, and new broad-spectrum anti-CoV therapy is urgently needed. We found that binding sites of cyclophilin A/cyclosporin A (CyPA/CsA) overlap with CyPA/N-CTD (nucleocapsid C-terminal domain), which shows the potential to target CyPA during SARS-CoV-2 infection. Here, we provide new evidence for targeting CyPA in the treatment of coronavirus disease 2019 (COVID-19) as well as the potential of developing CyPA inhibitors for broad-spectrum inhibition of CoVs.

Histone methyltransferase Dot1L recruits O-GlcNAc transferase to target chromatin sites to regulate histone O-GlcNAcylation.

O-GlcNAc transferase (OGT) is the distinctive enzyme responsible for catalyzing O-GlcNAc addition to the serine or threonine residues of thousands of cytoplasmic and nuclear proteins involved in such basic cellular processes as DNA damage repair, RNA splicing, and transcription preinitiation and initiation complex assembly. However, the molecular mechanism by which OGT regulates gene transcription remains elusive. Using proximity labeling-based mass spectrometry, here, we searched for functional partners of OGT and identified interacting protein Dot1L, a conserved and unique histone methyltransferase known to mediate histone H3 Lys79 methylation, which is required for gene transcription, DNA damage repair, cell proliferation, and embryo development. Although this specific interaction with OGT does not regulate the enzymatic activity of Dot1L, we show that it does facilitate OGT-dependent histone O-GlcNAcylation. Moreover, we demonstrate that OGT associates with Dot1L at transcription start sites and that depleting Dot1L decreases OGT associated with chromatin globally. Notably, we also show that downregulation of Dot1L reduces the levels of histone H2B S112 O-GlcNAcylation and histone H2B K120 ubiquitination in vivo, which are associated with gene transcription regulation. Taken together, these results reveal that O-GlcNAcylation of chromatin is dependent on Dot1L.

Anchoring Polar Organic Molecules in Defective Ammonium Vanadate for High-Performance Flexible Aqueous Zinc-Ion Battery.

Ammonium vanadate (NVO) often has unsatisfactory electrochemical performance due to the irreversible removal of NH4 + during the reaction. Herein, layered DMF-NVO nanoflake arrays (NFAs) grown on highly conductive carbon cloth (CC) are employed as the binder-free cathode (DMF-NVO NFAs/CC), which produces an enlarged interlayer spacing of 12.6 Å (against 9.5 Å for NH4 V4 O10 ) by effective N, N-dimethylformamide (DMF) intercalation. Furthermore, the strong attraction of highly polar carbonyl and ammonium ions in DMF can stabilize the lattice structure, and low-polar alkyl groups can interact with the weak electrostatic generated by Zn2+ , which allows Zn2+ to be freely intercalated. The DMF-NVO NFAs/CC//Zn battery exhibits an impressive high capacity of 536 mAh g-1 at 0.5 A g-1 , excellent rate capability, and cycling performance. The results of density functional theory simulation demonstrate that the intercalation of DMF can significantly reduce the band gap and the diffusion barrier of Zn2+ , and can also accommodate more Zn2+ . The assembled flexible aqueous rechargeable zinc ion batteries (FARZIBs) exhibit outstanding energy density and power density, up to 436 Wh kg-1 at 400 W kg-1 , and still remains 180 Wh kg-1 at 4000 W kg-1 . This work can provide a reference for the design of cathode materials for high-performance FARZIBs.

Research Progress in Heterologous Crocin Production.

Crocin is one of the most valuable components of the Chinese medicinal plant Crocus sativus and is widely used in the food, cosmetics, and pharmaceutical industries. Traditional planting of C. sativus is unable to fulfill the increasing demand for crocin in the global market, however, such that researchers have turned their attention to the heterologous production of crocin in a variety of hosts. At present, there are reports of successful heterologous production of crocin in Escherichia coli, Saccharomyces cerevisiae, microalgae, and plants that do not naturally produce crocin. Of these, the microalga Dunaliella salina, which produces high levels of ß-carotene, the substrate for crocin biosynthesis, is worthy of attention. This article describes the biosynthesis of crocin, compares the features of each heterologous host, and clarifies the requirements for efficient production of crocin in microalgae.

Association of RNF213 Variants With Periventricular Anastomosis in Moyamoya Disease.

BACKGROUND: The pathogenic mechanisms of periventricular anastomosis (PA) in moyamoya disease remain unknown. Here, we aimed to describe the angiographic profiles of PA and their relationships with really interesting new gene (RING) finger protein 213 (RNF213) genotypes. METHODS: We conducted a retrospective cohort study of moyamoya disease patients consecutively recruited between June 2019 and January 2021 in Beijing Tiantan Hospital, Capital Medical University, China. C-terminal region of RNF213 was sequenced. Angiographic characteristics of PA vessels (lenticulostriate artery, thalamotuberal artery, thalamoperforating artery, anterior choroidal artery, and posterior choroidal artery) were compared between different groups of RNF213 genotypes. The dilatation and extension of PA vessels were measured by using PA score (positive, score 1-5; negative, score 0). Multivariate regression analysis was conducted to assess variables associated with PA score. In addition, gene expression of RNF213 in human brain regions was evaluated from the Allen Human Brain Atlas. RESULTS: Among 260 patients (484 hemispheres), 71.2% carried no RNF213 rare and novel variants, 20.0% carried p.R4810K heterozygotes, and 8.8% carried other rare and novel variants. PA scores in patients with p.R4810K and other rare and novel variants were significantly higher than in wild-type patients (P<0.001). Age (odds ratio [OR], 0.958 [95% CI, 0.942-0.974]; P<0.001), platelet count (OR, 0.996 [95% CI, 0.992-0.999]; P=0.027), p.R4810K variant (OR, 2.653 [95% CI, 1.514-4.649]; P=0.001), other rare and novel variants (OR, 3.197 [95% CI, 1.012-10.094]; P=0.048), Suzuki stage ≥4 (OR, 1.941 [95% CI, 1.138-3.309]; P=0.015), and posterior cerebral artery involvement (OR, 1.827 [95% CI, 1.020-3.271]; P=0.043) were significantly correlated with PA score. High expression of RNF213 was detected in the periventricular area. CONCLUSIONS: RNF213 variants were confirmed to be associated with PA in moyamoya disease. Individuals with RNF213 p.R4810K heterozygotes and other C-terminal region rare variants exhibited different angiographic phenotypes, compared with wild-type patients.

Soft 2D Covalent Organic Framework with Compacted Honeycomb Topology.

In this contribution, we report the synthesis of an imine-based soft 2D covalent organic framework (S-COF) with compacted honeycomb topology via inveterately selecting a helically folded ditopic flexible linker and a trigonal building block. In contrast to various topological structures of rigid monomer-based COFs (R-COFs) reported so far, owing to the presence of flexible skeleton S-COF can spontaneously form a compacted and nonporous topological structure via intramolecular π stacking of presupposed honeycomb-like topology. Such S-COFs with a compacted honeycomb topology have neither been proposed theoretically nor been achieved experimentally. The compacted topological structure of 2D S-COF was clearly characterized by transmission electron microscopy (TEM), atomic force microscopy (AFM), powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), Fourier-transform infrared spectroscopy (FT-IR), and circular dichroism (CD) measurements. This study opens a new window to the development of S-COFs and will significantly expand the scope of COF materials.

TiO2/activated carbon synthesized by microwave-assisted heating for tetracycline photodegradation.

A furfural residue-derived activated carbon (AC) supported black-TiO2 photocatalyst was successfully prepared by ultrasonic-assisted sol-gel treatment (USG) and solvothermal treatment (ST) combined with microwave-assisted heating (MH). The prepared composites were characterized and evaluated based on the degradation of tetracycline hydrochloride (TC) under ultraviolet (UV) illumination. The average TiO2 nanoparticle size of the as-synthesized catalysts was between 9 and 11 nm. The bandgap of TiO2-USGM was 1.6 eV, much lower than that of other reference catalysts. Organic carbon and AC in the catalyst play positive roles in reducing the band gap (e.g. 1.6∼2.6 eV) and improving visible-light absorption. The oxygen vacancies are responsible for UV-visible absorption. Adding AC into black TiO2 resulted in a lower degree of recombination of photogenerated electrons. Mott-Schottky plots showed that AC-containing TiO2@AC-STM reduced the value of conduction band value from -0.59 eV to -0.24 eV, which is beneficial to photogenerated electrons. Compared with TiO2, the Ti-O-C and Ti-C- in TiO2@AC remarkably improved the adsorption and catalytic efficiency of TC. In a near-neutral pH environment, TiO2@AC-STM and TiO2@AC-USGM exhibited high removal efficiencies (88.0% and 75.7%, respectively) and degradation rates (0.0418 and 0.0302 µmol/g/s, respectively) at a catalyst load of 0.25 g/L. Notably, the catalyst can be effectively used over a wide range of pH (6-9). The solution pH after treatment was close to neutral, which is advantageous for wastewater treatment. The activation energies were found to be approximately 3.47 kJ/mol. The thermodynamic parameters showed that the photodegradation process was non-spontaneous and endothermic. Based on the trapping experiments, O2⋅- was mainly responsible for TC photodegradation over TiO2@AC-STM, followed by h+. The TC degradation pathways and catalyst stability were also investigated. Biomass-derived carbon-supported catalysts have great potential for waste biomass utilization as green, and low-cost catalysts.

Direct Measurements of Turbulence in the Upper Western Pacific North Equatorial Current over a 25-h Period.

Measurements of the turbulent kinetic energy dissipation rate (ε) were conducted by a free-fall microstructure profiler in the western Pacific North Equatorial Current (WPNEC) during a continuous period of 25 h, from the sea surface to about 160 m depth. In the mixed layer (ML), ε values were typically on the order of 10-8∼10-7 W kg-1, and an obvious diurnal cycle existed in the upper 40 m of the surface mixing layer. Below the ML, ε was reduced to 10-9∼10-8 W kg-1 with some patches of high ε reaching 10-7.5 W kg-1. The barrier layer was identified in the nighttime with a maximum thickness of 20 m, and it was eroded by the advection of freshwater within the lower part of the isothermal layers associated with an anticyclonic eddy in the afternoon. A simple scaling relevant to shear (S2) instability and stratification (N2) that can predict turbulent dissipation rates in the transition layer, between the well-mixed layer and the thermocline below, was obtained through the scaling ε∼S-0.40N0.20. Besides turbulence, double-diffusive processes also contributed to the vertical mixing levels in the upper WPNEC.

Electrochromic Metamaterials of Metal-Dielectric Stacks for Multicolor Displays with High Color Purity.

Inorganic electrochromic (EC) materials with vibrant multicolor change that are compatible with large-scale processing have been at the forefront of EC technology and are crucial in a wide range of applications, such as displays and camouflage. However, limited strategies are available to realize such inorganic materials, and challenges such as low color purity are yet to be overcome. Here, we demonstrate multilayered metal-dielectric metamaterials (MMDMs) as a new family of inorganics-based EC materials to achieve dynamic alternation among multicolors with high contrast and high color purity, which are structurally realized by significantly enhancing the confinement of the incident light in specific optical frequencies. This multilayer structure renders high reflectivity (75%), high quality factor (7.4), and a full width at half-maximum of 60 nm before coloration and presents a color gamut at least 40% wider than that of previously reported metamaterials after coloration, indicating good color quality.

RORγt agonist synergizes with CTLA-4 antibody to inhibit tumor growth through inhibition of Treg cells via TGF-ß signaling in cancer.

To date, the overall response rate to checkpoint blockade remains unsatisfactory, partially due to the limited understanding of the tumor immune microenvironment. The retinoic acid-related orphan receptor γt (RORγt) is the key transcription factor of T helper cell 17 (Th17) cells and plays an essential role in tumor immunity. In this study, we used JG-1, a potent and selective small-molecule RORγt agonist to evaluate the therapeutic potential and mechanism of action of targeting RORγt in tumor immunity. JG-1 promotes Th17 cells differentiation and inhibition of regulatory T (Treg) cells differentiation. JG-1 demonstrates robust tumor growth inhibition in multiple syngeneic models and shows a synergic effect with the Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) antibody. In tumors, JG-1 not only promotes Th17 cells differentiation and increases C-C Motif Chemokine Receptor 6 (CCR6)- Chemokine (C-C motif) ligand 20 (CCL20) expression, but also inhibits both the expression of transforming growth factor-ß1 (TGF-ß1) and the differentiation and infiltration of Treg cells. In summary, JG-1 is a lead compound showing a potent activity in vitro and robust tumor growth inhibition in vivo with synergetic effects with anti-CTLA-4.

Finite element analysis of the kinematic coupling effect of the joints around talus when Ponseti manipulation.

BACKGROUND: Little information was obtained from the published papers about the kinematic coupling effect between tarsal bones during Ponseti manipulation. The aim was to explore the kinematic coupling effect of the joints around talus, to investigate the kinematic rhythm and coupling relationship of tarsal joints; to clarify the pulling effect on medial ligament of the ankle during the process of Ponseti manipulation. METHODS: The model of foot and ankle was reconstructed from the Chinese digital human girl No.1 (CDH-G1) image database. Finite element analysis was applied to explore the kinematic coupling effect of the joints around talus. The distal tibia and fibula bone and the head of talus were fixed in all six degrees of freedom; outward pressure was added to the first metatarsal head to simulate the Ponseti manipulation. Kinematic coupling of each tarsal joint was investigated using the method of whole model splitting, and medial ligament pulling of the ankle was studied by designing the model of medial ligament deletion during the Ponseti manipulation. RESULTS: All the tarsal joints produced significant displacement in kinematic coupling effect, and the talus itself produced great displacement in the joint of ankle. Quantitative analysis revealed that the maximum displacement was found in the joints of talonavicular (12.01mm), cuneonavicular (10.50mm), calcaneocuboid (7.97mm), and subtalar(6.99mm).The kinematic coupling rhythm between talus and navicular, talus and calcaneus, calcaneus and cuboid, navicular and cuneiform 1 were 1:12, 1:7, 1:2 and 1:1.6. The results of ligaments pulling showed that the maximum displacement was presented in the ligaments of tibionavicular (mean 27.99mm), talonavicular (21.03mm), and calcaneonavicular (19.18 mm). CONCLUSIONS: All the tarsal joints around talus were involved in the process of Ponseti manipulation, and the strongest kinematic coupling effect was found in the joints of talonavicular, subtalar, calcaneocuboid, and cuneonavicular. The ligaments of tibionavicular, talonavicular, and calcaneonavicular were stretched greatly. It was suggested that the method of Ponseti management was a complex deformity correction processes involved all the tarsal joints. The present study contributed to better understanding the principle of Ponseti manipulation and the pathoanatomy of clubfoot. Also, the importance of cuneonavicular joint should be stressed in clinical practice.

Dieback and Leaf Spot in Box Elder (Acer negundo) Caused by Exserohilum rostratum.

Leaf spot and dieback were observed on box elder (Acer negundo) grown in a nursery in Tai'an city, Shandong Province, China, in 2019, with a disease incidence of 86%. The incidences of Exserohilum rostratum isolation were 75% from the shoots and 66.6% from the leaves of field-infected plants. Isolates were identified at the species level on the basis of morphological characteristics and through phylogenetic analysis of concatenated partial sequences of the internal transcribed spacer (ITS) region and cam, gapdh, tef1, rpb2, tub2, and his genes from the Exserohilum isolates. The effects of temperature on the mycelial growth of the Exserohilum rostratum isolates were also characterized. In greenhouse tests, seedlings inoculated with the pathogen exhibited systemic symptoms similar to those observed in the field. In pathogenicity experiments on shoots, wounded seedlings were observed to be blighted, suggesting that leaf spot and dieback may develop into more severe blight or dieback when high winds, sudden temperature decreases, or insect infestations occur. To our knowledge, this is the first report of dieback and leaf spot caused by E. rostratum on a species of A. negundo.

Anatomic characteristics of the knee influence the risk of suffering an isolated meniscal injury and the risk factors differ between women and men.

PURPOSE: To analyse the relationship between multiple anatomic characteristics of the knee (tibia and femur) and isolated meniscal injury in women and men. METHODS: Forty-seven patients with isolated medial meniscal injuries, 62 patients with isolated lateral meniscal injuries, and 70 control subjects were included. Medial posterior tibial slope (MTS), lateral posterior tibial slope (LTS), medial tibial plateau depth (MTD), coronal tibial slope (CTS), femoral notch width (NW), femoral condylar width (FCW), intercondylar notch depth (ND), femoral notch width index (NWI), intercondylar notch shape index (NSI), and cruciate ligaments tensity (CLT) were measured from magnetic resonance images. Anatomic characteristics differing between groups were compared, and risk factors for isolated meniscal injury were identified by multivariate forward stepwise logistic regression for men and women separately. RESULTS: Risk factors for an isolated medial meniscal injury were a steeper MTS and a lowered MTD in men, and a steeper MTS and an increased NWI in women. Risk factors for isolated lateral meniscal injury were a steeper LTS and an increased NW in men, and a steeper LTS and a lowered ND in women. Risk factors for both medial and lateral meniscal injuries were a higher CTS, an increased NWI, and a looser CLT in men, and a higher CTS, an increased NSI, and a looser CLT in women. CONCLUSION: The anatomic characteristics of the tibial plateau, femur, and cruciate ligaments influence the risk of suffering isolated meniscal injury, and the risk factors differ between men and women. This study provides a reference for developing identification criteria for those at risk of isolated meniscal injury. LEVEL OF EVIDENCE: III.

Differentiating novel coronavirus pneumonia from general pneumonia based on machine learning.

BACKGROUND: Chest CT screening as supplementary means is crucial in diagnosing novel coronavirus pneumonia (COVID-19) with high sensitivity and popularity. Machine learning was adept in discovering intricate structures from CT images and achieved expert-level performance in medical image analysis. METHODS: An integrated machine learning framework on chest CT images for differentiating COVID-19 from general pneumonia (GP) was developed and validated. Seventy-three confirmed COVID-19 cases were consecutively enrolled together with 27 confirmed general pneumonia patients from Ruian People's Hospital, from January 2020 to March 2020. To accurately classify COVID-19, region of interest (ROI) delineation was implemented based on ground-glass opacities (GGOs) before feature extraction. Then, 34 statistical texture features of COVID-19 and GP ROI images were extracted, including 13 gray-level co-occurrence matrix (GLCM) features, 15 gray-level-gradient co-occurrence matrix (GLGCM) features and 6 histogram features. High-dimensional features impact the classification performance. Thus, ReliefF algorithm was leveraged to select features. The relevance of each feature was the average weights calculated by ReliefF in n times. Features with relevance larger than the empirically set threshold T were selected. After feature selection, the optimal feature set along with 4 other selected feature combinations for comparison were applied to the ensemble of bagged tree (EBT) and four other machine learning classifiers including support vector machine (SVM), logistic regression (LR), decision tree (DT), and K-nearest neighbor with Minkowski distance equal weight (KNN) using tenfold cross-validation. RESULTS AND CONCLUSIONS: The classification accuracy (ACC), sensitivity (SEN), specificity (SPE) of our proposed method yield 94.16%, 88.62% and 100.00%, respectively. The area under the receiver operating characteristic curve (AUC) was 0.99. The experimental results indicate that the EBT algorithm with statistical textural features based on GGOs for differentiating COVID-19 from general pneumonia achieved high transferability, efficiency, specificity, sensitivity, and impressive accuracy, which is beneficial for inexperienced doctors to more accurately diagnose COVID-19 and essential for controlling the spread of the disease.

Low-depth whole genome sequencing reveals copy number variations associated with higher pathologic grading and more aggressive subtypes of lung non-mucinous adenocarcinoma.

OBJECTIVE: Histology grade, subtypes and TNM stage of lung adenocarcinomas are useful predictors of prognosis and survival. The aim of the study was to investigate the relationship between chromosomal instability, morphological subtypes and the grading system used in lung non-mucinous adenocarcinoma (LNMA). METHODS: We developed a whole genome copy number variation (WGCNV) scoring system and applied next generation sequencing to evaluate CNVs present in 91 LNMA tumor samples. RESULTS: Higher histological grades, aggressive subtypes and more advanced TNM staging were associated with an increased WGCNV score, particularly in CNV regions enriched for tumor suppressor genes and oncogenes. In addition, we demonstrate that 24-chromosome CNV profiling can be performed reliably from specific cell types (<100 cells) isolated by sample laser capture microdissection. CONCLUSIONS: Our findings suggest that the WGCNV scoring system we developed may have potential value as an adjunct test for predicting the prognosis of patients diagnosed with LNMA.

Correction: Protein Poly(ADP-ribosyl)ation Regulates Arabidopsis Immune Gene Expression and Defense Responses.

[This corrects the article DOI: 10.1371/journal.pgen.1004936.].