HGF facilitates methylation of MEG3, potentially implicated in vemurafenib resistance in melanoma.

BACKGROUND: Melanoma, a frequently encountered cutaneous malignancy characterized by a poor prognosis, persists in presenting formidable challenges despite the advancement in molecularly targeted drugs designed to improve survival rates significantly. Unfortunately, as more therapeutic choices have developed over time, the gradual emergence of drug resistance has become a notable impediment to the effectiveness of these therapeutic interventions. The hepatocyte growth factor (HGF)/c-met signaling pathway has attracted considerable attention, associated with drug resistance stemming from multiple potential mutations within the c-met gene. The activation of the HGF/c-met pathway operates in an autocrine manner in melanoma. Notably, a key player in the regulatory orchestration of HGF/c-met activation is the long non-coding RNA MEG3. METHODS: Melanoma tissues were collected to measure MEG3 expression. In vitro validation was performed on MEG3 to prove its oncogenic roles. Bioinformatic analyses were conducted on the TCGA database to build the MEG3-related score. The immune characteristics and mutation features of the MEG3-related score were explored. RESULTS: We revealed a negative correlation between HGF and MEG3. In melanoma cells, HGF inhibited MEG3 expression by augmenting the methylation of the MEG3 promoter. Significantly, MEG3 exhibits a suppressive impact on the proliferation and migration of melanoma cells, concurrently inhibiting c-met expression. Moreover, a predictive model centered around MEG3 demonstrates notable efficacy in forecasting critical prognostic indicators, immunological profiles, and mutation statuses among melanoma patients. CONCLUSIONS: The present study highlights the potential of MEG3 as a pivotal regulator of c-met, establishing it as a promising candidate for targeted drug development in the ongoing pursuit of effective therapeutic interventions.

Ivermectin as a potential therapeutic strategy for glioma.

Ivermectin (IVM), a semi-synthetic macrolide parasiticide, has demonstrated considerable effectiveness in combating internal and external parasites, particularly nematodes and arthropods. Its remarkable ability to control parasites has earned it significant recognition, culminating in Satoshi Omura and William C. Campbell's receipt of the 2015 Nobel Prize in Physiology or Medicine for their contributions to the development of IVM. In recent years, investigations have revealed that IVM possesses antitumor properties. It can suppress the growth of various cancer cells, including glioma, through a multitude of mechanisms such as selective targeting of tumor-specific proteins, inducing programmed cell death, and modulation of tumor-related signaling pathways. Hence, IVM holds tremendous potential as a novel anticancer drug. This review seeks to provide an overview of the underlying mechanisms that enable IVM's capacity to suppress glioma. Furthermore, it aims to elucidate the challenges and prospects associated with utilizing IVM as a new anticancer agent.

A new method to estimate the histological stage of primary biliary cholangitis.

OBJECTIVE: To analyze the diagnostic efficacy of the periportal hypoechoic band (PHB) in the histological stage of patients with primary biliary cholangitis (PBC). METHODS: We prospectively included 77 cases of PBC pathologically or clinically confirmed, and high-frequency ultrasound (HFUS) measurements of the PHB were performed in all included patients. Ludwig staging system of histopathology was used as the gold standard. RESULTS: The width of the PHB was positively correlated with histological staging (r = 0.844, p < 0.001). By area under the receiving operating characteristic curve (AUROC), the best cutoff value for PHB for advanced stage (≥ stage 3) was 2.4 mm (AUROC: 0.934; 95%CI: 0.841-0.981) and 0.93 for sensitivity, and 0.91 for specificity, the concordance rates of PHB vs. liver biopsy was 90.3%. The correct rate for early-stage PBC was 87.9% and for the progressive stage was 93.1%. After multi-factor regression analysis, the PHB (OR = 1.331, CI = 1.105-1.603, p = 0.003) and total bilirubin (OR = 1.156, CI = 1.041-1.285, p = 0.007) were independent influencing factors for progressive PBC. CONCLUSIONS: Measurement of the PHB to assess advanced PBC is a simple and effective method. This method may complement current methods for the histological staging assessment of patients with PBC. REGISTRATION: Clinical trial registration: ChiCTR 2000032053, 2020/04/19. CLINICAL RELEVANCE STATEMENT: The measurement of periportal hypoechoic band (PHB) provides a simple and easy assessment of the degree of disease progression in patients with PBC and provides an important clinical reference in predicting the histological staging of PBC from an ultrasound perspective. KEY POINTS: • The PHB is correlated with histological staging in the patient with PBC. • The area under the ROC curves of PHB for detecting advanced stage (≥ stage 3) were 0.934 and 0.93 for sensitivity, and 0.91 for specificity, the concordance rates of PHB vs. liver biopsy was 90.3%. The application of PHB can better assess the advanced PBC. • Measurement of the PHB to assess advanced PBC is a simple and effective method that can significantly reduce the need for liver biopsy.

Age-adjusted Charlson comorbidity index is associated with the risk of osteoporosis in older fall-prone men: a retrospective cohort study.

BACKGROUND: There is growing evidence linking the age-adjusted Charlson comorbidity index (aCCI), an assessment tool for multimorbidity, to fragility fracture and fracture-related postoperative complications. However, the role of multimorbidity in osteoporosis has not yet been thoroughly evaluated. We aimed to investigate the association between aCCI and the risk of osteoporosis in older adults at moderate to high risk of falling. METHODS: A total of 947 men were included from January 2015 to August 2022 in a hospital in Beijing, China. The aCCI was calculated by counting age and each comorbidity according to their weighted scores, and the participants were stratified into two groups by aCCI: low (aCCI < 5), and high (aCCI ≥5). The Kaplan Meier method was used to assess the cumulative incidence of osteoporosis by different levels of aCCI. The Cox proportional hazards regression model was used to estimate the association of aCCI with the risk of osteoporosis. Receiver operating characteristic (ROC) curve was adapted to assess the performance for aCCI in osteoporosis screening. RESULTS: At baseline, the mean age of all patients was 75.7 years, the mean BMI was 24.8 kg/m2, and 531 (56.1%) patients had high aCCI while 416 (43.9%) were having low aCCI. During a median follow-up of 6.6 years, 296 participants developed osteoporosis. Kaplan-Meier survival curves showed that participants with high aCCI had significantly higher cumulative incidence of osteoporosis compared with those had low aCCI (log-rank test: P < 0.001). When aCCI was examined as a continuous variable, the multivariable-adjusted model showed that the osteoporosis risk increased by 12.1% (HR = 1.121, 95% CI 1.041-1.206, P = 0.002) as aCCI increased by one unit. When aCCI was changed to a categorical variable, the multivariable-adjusted hazard ratios associated with different levels of aCCI [low (reference group) and high] were 1.00 and 1.557 (95% CI 1.223-1.983) for osteoporosis (P <  0.001), respectively. The aCCI (cutoff ≥5) revealed an area under ROC curve (AUC) of 0.566 (95%CI 0.527-0.605, P = 0.001) in identifying osteoporosis in older fall-prone men, with sensitivity of 64.9% and specificity of 47.9%. CONCLUSIONS: The current study indicated an association of higher aCCI with an increased risk of osteoporosis among older fall-prone men, supporting the possibility of aCCI as a marker of long-term skeletal-related adverse clinical outcomes.

Anion-Reinforced Solvation Structure Enables Stable Operation of Ether-Based Electrolyte in High-Voltage Potassium Metal Batteries.

Electrolytes with anion-dominated solvation are promising candidates to achieve dendrite-free and high-voltage potassium metal batteries. However, it's challenging to form anion-reinforced solvates at low salt concentrations. Herein, we construct an anion-reinforced solvation structure at a moderate concentration of 1.5 M with weakly coordinated cosolvent ethylene glycol dibutyl ether. The unique solvation structure accelerates the desolvation of K+, strengthens the oxidative stability to 4.94 V and facilitates the formation of inorganic-rich and stable electrode-electrolyte interface. These enable stable plating/stripping of K metal anode over 2200 h, high capacity retention of 83.0 % after 150 cycles with a high cut-off voltage of 4.5 V in K0.67MnO2//K cells, and even 91.5 % after 30 cycles under 4.7 V. This work provides insight into weakly coordinated cosolvent and opens new avenues for designing ether-based high-voltage electrolytes.

Recent Progress of Three-dimensionally Ordered Macroporous (3DOM) Materials in Photocatalytic Applications: A Review.

In recent years, three-dimensionally ordered macroporous (3DOM) materials have attracted tremendous interest in the field of photocatalysis due to the periodic spatial structure and unique physicochemical properties of 3DOM catalysts. In this review, the fundamentals and principles of 3DOM photocatalysts are briefly introduced, including the overview of 3DOM materials, the photocatalytic principles based on 3DOM materials, and the advantages of 3DOM materials in photocatalysis. The preparation methods of 3DOM materials are also presented. The structure and properties of 3DOM materials and their effects on photocatalytic performance are briefly summarized. More importantly, 3DOM materials, as a supported catalyst, are extensively employed to combine with various common materials, including metal nanoparticles, metal oxides, metal sulfides, and carbon materials, to enhance photocatalytic performance. Finally, the prospects and challenges for the development of 3DOM materials in the field of photocatalysis are presented.

Recent Advances and Perspectives of Core-Shell Nanostructured Materials for Photocatalytic CO2 Reduction.

Photocatalytic CO2 conversion into solar fuels is a promising technology to alleviate CO2 emissions and energy crises. The development of core-shell structured photocatalysts brings many benefits to the photocatalytic CO2 reduction process, such as high conversion efficiency, sufficient product selectivity, and endurable catalyst stability. Core-shell nanostructured materials with excellent physicochemical features take an irreplaceable position in the field of photocatalytic CO2 reduction. In this review, the recent development of core-shell materials applied for photocatalytic reduction of CO2 is introduced . First, the basic principle of photocatalytic CO2 reduction is introduced. In detail, the classification and synthesis techniques of core-shell catalysts are discussed. Furthermore, it is also emphasized that the excellent properties of the core-shell structure can greatly improve the activity, selectivity, and stability in the process of photocatalytic CO2 reduction. Hopefully, this paper can provide a favorable reference for the preparation of efficient photocatalysts for CO2 reduction.

Identification and validation of DNA methylation-driven gene PCDHB4 as a novel tumor suppressor for glioblastoma diagnosis and prognosis.

Aberrant DNA methylation is a critical regulator of gene expression in the development and progression of glioblastoma (GBM). However, the impact of methylation-driven gene PCDHB4 changes on GBM occurrence and progression remains unclear. Therefore, this study aimed to identify the PCDHB4 gene for early diagnosis and prognostic evaluation and clarify its functional role in GBM. Methylation-driven gene PCDHB4 was selected for GBM using the multi-omics integration method based on publicly available data sets. The diagnostic capabilities of PCDHB4 methylation and 5-hydroxymethylcytosines were validated in tissue and blood cell-free DNA (cfDNA) samples, respectively. Combined survival analysis of PCDHB4 methylation and immune infiltration cells evaluated the prognostic predictive performance of GBM patients. We identified that the PCDHB4 gene achieved high discriminative capabilities for GBM and normal tissues with an area under the curve value of 0.941. PCDHB4 hypermethylation was observed in cfDNA blood samples from GBM patients. Compared with GBM patients with PCDHB4 hypermethylation level, patients with PCDHB4 hypomethylation level had significantly poorer overall survival (p = 0.035). In addition, GBM patients with PCDHB4 hypermethylation and high infiltration of CD4+ T cell activation level had a favorable survival (p = 0.026). Moreover, we demonstrated that mRNA expression of PCDHB4 was downregulated in GBM tissues and upregulated in GBM cell lines with PCDHB4 demethylation, and PCDHB4 overexpression inhibited GBM cell proliferation and migration. In summary, we discovered a novel methylation-driven gene PCDHB4 for the diagnosis and prognosis of GBM and demonstrated that PCDHB4 is a tumor suppressor in vitro experiments.

Evaluation and comparison of immune responses induced by two Mpox mRNA vaccine candidates in mice.

The epidemic of Mpox virus (MPXV) from May 2022 was once declared as a Public Health Emergency of International Concern by the World Health Organization. Vaccines play an important role in prevention of infectious diseases, and mRNA vaccine technology was proved to be a safe and effective platform with successful application in defense of coronavirus disease 2019. In this study, based on A29L, M1R, A35R, and B6R of MPXV, we developed two MPXV mRNA vaccine candidates, designated as MPXfus and MPXmix. The MPXfus was one-component, in which these four antigen proteins were linked in tandem by flexible linker and encoded by an individual mRNA as a fusion protein. The MPXmix was multicomponent containing four mRNA, and each mRNA encoded one antigen protein respectively. Mice were immunized with equal quality of MPXfus or MPXmix, delivered by lipid nanoparticles for evaluation and comparison of the immune responses induced by these two MPXV vaccine candidates. Results of immune response analyses indicated that both MPXfus and MPXmix could elicit high-level of antigen-specific antibodies and robust cellular immune response in mice. Moreover, results of virus neutralization assays suggested that sera from MPXfus- or MPXmix-immunized mice possessed high neutralizing activities against vaccinia virus. In addition, titers of antigen-specific antibody, levels of cellular immune response, and activities of neutralizing antibody against vaccinia virus induced by MPXfus and MPXmix presented no significant difference. In summary, this study provides valuable insights for further clinical development of one-component and multicomponent mRNA vaccine candidates for the prevention of MPXV and other orthomyxoviruses.

Dynamics of parainfluenza virus among hospitalized children with acute respiratory tract infection under two-child policy and COVID-19 pandemic in Hubei Province, China, 2014-2022.

To analyze changes in the detection of parainfluenza virus (PIV) in children hospitalized with acute respiratory tract infection (ARTI) during 2014-2022 in Hubei Province, and explore the impact of the universal two-child policy and the public health measures against COVID-19 epidemic on the prevalence of PIV in China. The study was conducted at the Maternal and Child Health Hospital of Hubei Province. Children aged <18 years with ARTI admitted from January 2014 to June 2022 were enrolled. The infection of PIV was confirmed by the direct immunofluorescence method in nasopharyngeal specimens. Adjusted logistic regression models were used to analyze the influence of the universal two-child policy implementation and public health measurements against COVID-19 on PIV detection. Totally 75 128 inpatients meeting the criteria were enrolled in this study from January 2014 to June 2022 with an overall PIV positive rate of 5.5%. The epidemic seasons of PIV prevalence lagged substantially in 2020. A statistically significant higher positive rate of PIV was observed in 2017-2019 compared to that in 2014-2015 (6.12% vs 2.89%, risk ratio = 2.12, p < 0.001) after the implementation of the universal two-child policy in 2016. A steep decline occurred in PIV positive rate during the COVID-19 epidemic in 2020 (0.92% vs 6.92%, p < 0.001) and it rebounded during the regular epidemic prevention and control period in 2021-2022 (6.35%, p = 0.104). In Hubei Province, the implementation of the universal two-child policy might have led to an increase of PIV prevalence, and public health measures during the COVID-19 epidemic might have influenced the fluctuation in PIV detection since 2020.

Epidemiological change of influenza virus in hospitalized children with acute respiratory tract infection during 2014-2022 in Hubei Province, China.

PURPOSE: Influenza virus (IFV) causes acute respiratory tract infection (ARTI) and leads to high morbidity and mortality annually. This study explored the epidemiological change of IFV after the implementation of the universal two-child policy and evaluated the impact of coronavirus disease 2019 (COVID-19) pandemic on the detection of IFV. METHODS: Hospitalized children under 18 years with ARTI were recruited from Hubei Maternal and Child Healthcare Hospital of Hubei Province from January 2014 to June 2022. The positive rates of IFV were compared among different periods by the implementation of the universal two-child policy and public health measures against COVID-19 pandemic. RESULTS: Among 75,128 hospitalized children with ARTI, the positive rate of IFV was 1.98% (1486/75128, 95% CI 1.88-2.01). Children aged 6-17 years had the highest positive rate of IFV (166/5504, 3.02%, 95% CI 2.58-3.50). The positive rate of IFV dropped to the lowest in 2015, then increased constantly and peaked in 2019. After the universal two-child policy implementation, the positive rate of IFV among all the hospitalized children increased from 0.40% during 2014-2015 to 2.70% during 2017-2019 (RR 6.72, 95% CI 4.94-9.13, P < 0.001), particularly children under one year shown a violent increasing trend from 0.20 to 2.01% (RR 10.26, 95% CI 5.47-19.23, P < 0.001). During the initial outbreak of COVID-19, the positive rate of IFV decreased sharply compared to that before COVID-19 (0.35% vs. 3.37%, RR 0.10, 95% CI 0.04-0.28, P < 0.001), and then rebounded to 0.91%, lower than the level before COVID-19 (RR 0.26, 95% CI 0.20-0.36, P < 0.001). CONCLUSION: IFV epidemiological pattern has changed after the implementation of the universal two-child policy. More attention should be emphasized to comprehend the health benefits generated by COVID-19 restrictions on IFV transmission in future.

Ultrasound imaging findings in primary biliary cholangitis.

BACKGROUND: Our study aimed to analyze the characteristics of ultrasound images corresponding to each histological stage of primary biliary cholangitis (PBC). METHODS: We prospectively analyzed 75 confirmed cases of PBC and used liver biopsy as the gold standard to determine the disease stage. RESULTS: The typical ultrasound images of patients with PBC were characterized by a thickening of the portal vein wall (PVW) and periportal hypoechoic band (PHB) width with increasing histological stages, and significant increases in the left hepatic lobe diameter (LHLD) in stage II (by 64.0%) and stage III (by 69.2%). PHB width (r = 0.857, p < 0.001), PVW thickness (r = 0.488, p < 0.001), and spleen area (r = 0.8774, p < 0.001) were positively correlated with the histological stage. Significant changes were noted in the liver surface, echo texture, and edge between different stages. The areas under the receiver operating characteristic curve of composite indicators were 0.965 for predicting progressive PBC(≥ stage 2), and 0.926 for predicting advanced PBC(≥ stage 3). CONCLUSIONS: The ultrasound imaging characteristics of patients with PBC varied according to the histological staging. LHLD, PVW thickness, and PHB width were significantly correlated with the histological stage. A combination of high- and low-frequency ultrasound imaging can provide relevant cues regarding the degree of PBC progression and important clinical reference values. The application of all the ultrasound image findings as the composite indicators can better predict progressive and advanced PBC, providing important clinical reference values.

Identification and characterization of two SERPINC1 mutations causing congenital antithrombin deficiency.

BACKGROUND: Antithrombin (AT) is the main physiological anticoagulant involved in hemostasis. Hereditary AT deficiency is a rare autosomal dominant thrombotic disease mainly caused by mutations in SERPINC1, which was usually manifested as venous thrombosis and pulmonary embolism. In this study, we analyzed the clinical characteristics and screened for mutant genes in two pedigrees with hereditary AT deficiency, and the functional effects of the pathogenic mutations were evaluated. METHODS: Candidate gene variants were analyzed by next-generation sequencing to screen pathogenic mutations in probands, followed by segregation analysis in families by Sanger sequencing. Mutant and wild-type plasmids were constructed and transfected into HEK293T cells to observe protein expression and cellular localization of SERPINC1. The structure and function of the mutations were analyzed by bioinformatic analyses. RESULTS: The proband of pedigree A with AT deficiency carried a heterozygous frameshift mutation c.1377delC (p.Asn460Thrfs*20) in SERPINC1 (NM000488.3), a 1377C base deletion in exon 7 resulting in a backward shift of the open reading frame, with termination after translation of 20 residues, and a different residue sequence translated after the frameshift. Bioinformatics analysis suggests that the missing amino acid sequence caused by the frameshift mutation might disrupt the disulfide bond between Cys279 and Cys462 and affect the structural function of the protein. This newly discovered variant is not currently included in the ClinVar and HGMD databases. p.Arg229* resulted in a premature stop codon in exon 4, and bioinformatics analysis suggests that the truncated protein structure lost its domain of interaction with factor IX (Ala414 site) after the deletion of nonsense mutations. However, considering the AT truncation protein resulting from the p.Arg229* variant loss a great proportion of the molecule, we speculate the variant may affect two functional domains HBS and RCL and lack of the corresponding function. The thrombophilia and decreased-AT-activity phenotypes of the two pedigrees were separated from their genetic variants. After lentiviral plasmid transfection into HEK293T cells, the expression level of AT protein decreased in the constructed c.1377delC mutant cells compared to that in the wild-type, which was not only reduced in c.685C > T mutant cells but also showed a significant band at 35 kDa, suggesting a truncated protein. Immunofluorescence localization showed no significant differences in protein localization before and after the mutation. CONCLUSIONS: The p.Asn460Thrfs*20 and p.Arg229* variants of SERPINC1 were responsible for the two hereditary AT deficiency pedigrees, which led to AT deficiency by different mechanisms. The p.Asn460Thrfs*20 variant is reported for the first time.

CB2R agonist GW405833 alleviates acute liver failure in mice via inhibiting HIF-1α-mediated reprogramming of glycometabolism and macrophage proliferation.

The inflammatory responses involving infiltration and activation of liver macrophages play a vital role in acute liver failure (ALF). In the liver of ALF mice, cannabinoid receptor 2 (CB2R) is significantly upregulated on macrophages, while CB2R agonist GW405833 (GW) could protect against cell death in acute liver damage. In this study, we investigated the molecular mechanisms underlying the protective effects of GW against ALF in vivo and in vitro from a perspective of macrophage glycometabolism. Mice were pretreated with GW (10 mg/kg, i.p.), then were injected with D-GalN (750 mg/kg, i.p.) and LPS (10 mg/kg, i.p.) to induce ALF. We verified the protective effects of GW pretreatment in ALF mice. Furthermore, GW pretreatment significantly reduced liver macrophage infiltration and M1 polarization, and inhibited the release of inflammatory factors TNF-α and IL-1ß in ALF mice. These protective effects were eliminated by CB2R antagonist SR144528 or in CB2R-/- ALF mice. We used LPS-stimulated RAW264.7 cells as an in vitro M1 macrophage-centered model of inflammatory response, and demonstrated that pretreatment with GW (10 µM) significantly reduced glucose metabolism by inhibiting glycolysis, which inhibited LPS-induced macrophage proliferation and inflammatory cytokines release. We verified these results in a stable CB2R-/- RAW264.7 cell line. Moreover, we found that GW significantly inhibited the expression of hypoxia inducible factor 1α (HIF-1α). Using a stable HIF-1α-/- RAW264.7 cell line, we confirmed that GW reduced the release of inflammatory cytokines from macrophages and inhibited glycolysis by downregulating HIF-1α expression. In conclusion, activation of CB2Rs inhibits the proliferation of hepatic macrophages and release of inflammatory factors in ALF mice through downregulating HIF-1α to inhibit glycolysis.

Contrast-enhanced Ultrasound Combined With Elastography for the Evaluation of Muscle-invasive Bladder Cancer in Rats.

OBJECTIVES: By comparing with the control group, we evaluated the usefulness of contrast-enhanced ultrasound (CEUS) combined with elastography for the assessment of muscle invasion by bladder cancer (MIBC) in a Sprague-Dawley (SD) rat model. METHODS: In the experimental group, 40 SD rats developed in situ bladder cancer (BLCA) in response to N-methyl-N-nitrosourea treatment, whereas 40 SD rats were included in the control group for comparison. We compared PI, Emean , microvessel density (MVD), and collagen fiber content (CFC) between the two groups. In the experimental group, Bland-Altman test was used to assess the relationships between various parameters. The largest Youden value was used as the cut-off point, and binomial logistic regression analysis was performed to analyze the PI and Emean . Receiver operating characteristic (ROC) curve analysis was performed to determine the diagnostic power of parameters, individually and in combination. RESULTS: The PI, Emean , MVD, and CFC were significantly lower in the control group than in the experimental group (P < .05). The PI, Emean , MVD, and CFC were significantly higher for MIBC than for non-muscle-invasive bladder cancer (P < .05). There were significant correlations between PI and MVD, and between Emean and CFC. The diagnostic efficiency analysis showed PI had the highest sensitivity, CFC had the highest specificity, and PI + Emean had the highest diagnostic efficacy. CONCLUSION: CEUS and elastography can distinguish lesions from normal tissue. PI, MVD, Emean , and CFC were useful for the detection of BLCA myometrial invasion. The comprehensive utilization of PI and Emean improved diagnostic accuracy and have clinical application.

Comparison of Ultrasound and CT Imaging for the Diagnosis of Coronavirus Disease and Influenza A Pneumonia.

OBJECTIVE: The outbreak of coronavirus disease (COVID-19) coincided with the season of influenza A pneumonia, a common respiratory infectious disease. Therefore, this study compared ultrasonography and computed tomography (CT) for the diagnosis of the two diseases. METHODS: Patients with COVID-19 or influenza A infection hospitalized at our hospital were included. The patients were examined by ultrasonography every day. The CT examination results within 1 day before and after the day of the highest ultrasonography score were selected as the controls. The similarities and differences between the ultrasonography and CT results in the two groups were compared. RESULTS: There was no difference between the ultrasonography and CT scores (P = .307) for COVID-19, while there was a difference between ultrasonography and CT scores for influenza A pneumonia (P = .024). The ultrasonography score for COVID-19 was higher than that for influenza A pneumonia (P = .000), but there was no difference between the CT scores (P = .830). For both diseases, there was no difference in ultrasonography and CT scores between the left and right lungs; there were differences between the CT scores of the upper and middle lobes, as well as between the upper and lower lobes of the lungs; however, there was no difference between the lower and middle lobes of the lungs. CONCLUSION: Ultrasonography is equivalent to the gold standard CT for diagnosing and monitoring the progression of COVID-19. Because of its convenience, ultrasonography has important application value. Furthermore, the diagnostic value of ultrasonography for COVID-19 is higher than that for influenza A pneumonia.

Artificial Intelligence-Based Psoriasis Severity Assessment: Real-world Study and Application.

BACKGROUND: Psoriasis is one of the most frequent inflammatory skin conditions and could be treated via tele-dermatology, provided that the current lack of reliable tools for objective severity assessments is overcome. Psoriasis Area and Severity Index (PASI) has a prominent level of subjectivity and is rarely used in real practice, although it is the most widely accepted metric for measuring psoriasis severity currently. OBJECTIVE: This study aimed to develop an image-artificial intelligence (AI)-based validated system for severity assessment with the explicit intention of facilitating long-term management of patients with psoriasis. METHODS: A deep learning system was trained to estimate the PASI score by using 14,096 images from 2367 patients with psoriasis. We used 1962 patients from January 2015 to April 2021 to train the model and the other 405 patients from May 2021 to July 2021 to validate it. A multiview feature enhancement block was designed to combine vision features from different perspectives to better simulate the visual diagnostic method in clinical practice. A classification header along with a regression header was simultaneously applied to generate PASI scores, and an extra cross-teacher header after these 2 headers was designed to revise their output. The mean average error (MAE) was used as the metric to evaluate the accuracy of the predicted PASI score. By making the model minimize the MAE value, the model becomes closer to the target value. Then, the proposed model was compared with 43 experienced dermatologists. Finally, the proposed model was deployed into an app named SkinTeller on the WeChat platform. RESULTS: The proposed image-AI-based PASI-estimating model outperformed the average performance of 43 experienced dermatologists with a 33.2% performance gain in the overall PASI score. The model achieved the smallest MAE of 2.05 at 3 input images by the ablation experiment. In other words, for the task of psoriasis severity assessment, the severity score predicted by our model was close to the PASI score diagnosed by experienced dermatologists. The SkinTeller app has been used 3369 times for PASI scoring in 1497 patients from 18 hospitals, and its excellent performance was confirmed by a feedback survey of 43 dermatologist users. CONCLUSIONS: An image-AI-based psoriasis severity assessment model has been proposed to automatically calculate PASI scores in an efficient, objective, and accurate manner. The SkinTeller app may be a promising alternative for dermatologists' accurate assessment in the real world and chronic disease self-management in patients with psoriasis.

Formononetin improves the inflammatory response and bone destruction in knee joint lesions by regulating the NF-kB and MAPK signaling pathways.

Formononetin (FMN) is a phytoestrogen that belongs to the isoflavone family. It has antioxidant and anti-inflammatory effects, as well as, many other biological activities. Existing evidence has aroused interest in its ability to protect against osteoarthritis (OA) and promote bone remodeling. To date, research on this topic has not been thorough and many issues remain controversial. Therefore, the purpose of our study was to explore the protective effect of FMN against knee injury and clarify the possible molecular mechanisms. We found that FMN inhibited osteoclast formation induced by receptor activator of NF-κB ligand (RANKL). Inhibition of the phosphorylation and nuclear translocation of p65 in the NF-κB signaling pathway plays a role in this effect. Similarly, during the inflammatory response of primary knee cartilage cells activated by IL-1ß, FMN inhibited the NF-κB signaling pathway and the phosphorylation of the ERK and JNK proteins in the MAPK signaling pathway to suppress the inflammatory response. In addition, in vivo experiments showed that both low- and high-dose FMN had a clear protective effect against knee injury in the DMM (destabilization of the medial meniscus) model, and the therapeutic effect of high-dose FMN was stronger. In conclusion, these studies provide evidence of the protective effect of FMN against knee injury.

A Lysosome-Targeting Self-Condensation Prodrug-Nanoplatform System for Addressing Drug Resistance of Cancer.

Lysosome-targeting self-assembling prodrugs had emerged as an attractive approach to overcome the acquisition of resistance to chemotherapeutics by inhibiting lysosomal sequestration. Taking advantage of lysosomal acidification induced intracellular hydrolytic condensation, we developed a lysosomal-targeting self-condensation prodrug-nanoplatform (LTSPN) system for overcoming lysosome-mediated drug resistance. Briefly, the designed hydroxycamptothecine (HCPT)-silane conjugates self-assembled into silane-based nanoparticles, which were taken up into lysosomes by tumor cells. Subsequently, the integrity of the lysosomal membrane was destructed because of the acid-triggered release of alcohol, wherein the nanoparticles self-condensed into silicon particles outside the lysosome through intracellular hydrolytic condensation. Significantly, the LTSPN system reduced the half-maximal inhibitory concentration (IC50) of HCPT by approximately 4 times. Furthermore, the LTSPN system realized improved control of large established tumors and reduced regrowth of residual tumors in several drug-resistant tumor models. Our findings suggested that target destructing the integrity of the lysosomal membrane may improve the therapeutic effects of chemotherapeutics, providing a potent treatment strategy for malignancies.

Comparative Analyses of Chloroplast Genome Provide Effective Molecular Markers for Species and Cultivar Identification in Bougainvillea.

Bougainvillea is popular in ornamental horticulture for its colorful bracts and excellent adaptability, but the complex genetic relationship among this genus is fuzzy due to limited genomic data. To reveal more genomic resources of Bougainvillea, we sequenced and assembled the complete chloroplast (cp) genome sequences of Bougainvillea spectabilis 'Splendens'. The cp genome size was 154,869 bp in length, containing 86 protein-coding genes, 38 tRNAs, and eight rRNAs. Cp genome comparison across 12 Bougainvillea species (B. spectabilis, B. glabra, B. peruviana, B. arborea, B. praecox, B. stipitata, B. campanulata, B. berberidifolia, B. infesta, B. modesta, B. spinosa, and B. pachyphylla) revealed five mutational hotspots. Phylogenetic analysis suggested that B. spectabilis published previously and B. glabra clustered into one subclade as two distinct groups, sister to the subclade of B. spectabilis 'Splendens'. We considered the phylogeny relationships between B. spectabilis and B. glabra to be controversial. Based on two hypervariable regions and three common plastid regions, we developed five molecular markers for species identification in Bougainvillea and applied them to classify 53 ornamental Bougainvillea cultivars. This study provides a valuable genetic resource for Bougainvillea breeding and offers effective molecular markers to distinguish the representative ornamental species of Bougainvillea.