Artemisitene shows superiority over artemisinin in preventing Schistosoma japonica-induced liver disease.

BACKGROUND: Artemisinin (ART) analogs, such as dihydroartemisinin, arteether, artemether, and artesunate, all featuring an endoperoxide bridge, have demonstrated efficacy against schistosomiasis. Artemisitene (ATT), which contains an additional α, ß-unsaturated carbonyl structure, has shown enhanced biological activities. This study aims to evaluate the anti-schistosomaiasis japonica activity of ATT and compare it with ART. METHODS: We assessed liver inflammation and fibrosis in mice using hematoxylin and eosin staining and Sirius red staining, respectively. RNA sequencing analyzed transcriptomics in female and male Schistosoma japonicum (S. japonicum) adult worms and mice livers, with cytokine profiling and flow cytometry to study immune responses under ART or ATT treatment. RESULTS: ATT exhibits a marked reduction in female S. japonicum adult worms and egg numbers, damaging the adult worms' surface. It also influences the transcription of genes related to cellular anatomical structures. Notably, ATT treatment resulted in significant reductions in liver granuloma size and collagen area, alongside lowering serum levels of glutamic pyruvic and glutamic oxaloacetic transaminase more effectively than ART. Both ART and ATT markedly decreased neutrophil frequency in the liver and elevated eosinophil counts. However, only ATT treatment significantly reduced the M1/M2 and Th1/Th2 indices, indicating a pronounced shift in immune response profiles. ATT-affected host immunity correlated with the extent of liver fibrosis and the count of single males more strongly than ART. CONCLUSION: ATT, as a novel preventive strategy for schistosomiasis japonica in mice, significantly outperforms ART.

Evaluation of protective immune response of immersion inactivated vaccine against Singapore grouper iridovirus.

Singapore grouper iridovirus (SGIV) always causes high transmission efficiency and mortality in the larval and juvenile stages of grouper in aquaculture industry. Although inactivated virus and recombinant DNA vaccines administered via intraperitoneal injection have shown efficacy in protection against SGIV, their potential applications in field testing were limited due to the vaccine delivery methods. Here, we developed an immersion vaccine containing inactivated virus and Montanide IMS 1312 adjuvant (IMS 1312) and evaluated its protective efficacy against SGIV infection. Compared to the PBS group, fish vaccinated with immersion inactivated vaccine with or without IMS 1312 were significantly protected against SGIV, with a relative percent survival (RPS) of 57.69 % and 38.47 %, respectively. Furthermore, the transcripts of viral core genes were reduced, and the histopathological severity caused by SGIV were relatively mild in multiple tissues of the IMS + V group. The immersion vaccine activated the AKP and ACP activities and increased the mRNA levels of IFN and inflammation-associated genes. The transcriptome analysis showed that a total of 731 and 492 genes were significantly regulated in the spleen and kidney from the IMS + V group compared to the PBS group, respectively. Among them, 129 DEGs were co-regulated, and enriched in the KEGG pathways related to immune and cell proliferation, including MAPK signaling, JAK-STAT signaling and PI3K-Akt signaling pathways. Similarly, the DEGs specially regulated in the kidney and spleen upon vaccine immunization were significantly enriched in the KEGG pathways related to interferon and inflammation response. Together, our results elucidated that the immersion vaccine of inactivated SGIV with IMS 1312 induced a protective immune response of grouper against SGIV.

Association between lymphatic abnormalities in the neck and thorax in primary chylopericardium and surgical outcomes evaluated by non-enhanced magnetic resonance (MR) lymphangiography.

Background: Chylopericardium refers to the accumulation of chylous fluid in the pericardial cavity. Non-enhanced magnetic resonance lymphangiography (MRL) can show neck and thoracic lymphatic abnormalities in the primary chylopericardium. It is not clear whether there is a relationship between neck and thoracic lymphatic abnormalities in primary chylopericardium and thoracic duct terminal release surgery. This study aimed to explore the correlation between the severity of neck and thoracic lymphatic abnormalities observed in non-enhanced MRL and the surgical outcomes in primary chylopericardium. Methods: This is a retrospective cohort study. A retrospective analysis was conducted on fifty-six patients diagnosed with primary chylopericardium between January 2016 and December 2021, all of whom underwent thoracic duct terminal release surgery. Ultrasonography, chest computed tomography (CT) and non-enhanced MRL were performed prior to the surgical intervention. Patients were categorized into four types based on the severity of neck and thoracic lymphatic abnormalities observed in the non-enhanced MRL. Clinical and laboratory examinations and surgical outcomes were compared across different types using χ 2-test or Fisher's exact test, t-test, and Kruskal-Wallis H-test. Additionally, independent factors influencing surgical outcomes were analyzed. Results: Among primary chylopericardium cases (n=56), 22 (39.2%) were classified as type I or II, 17 (30.4%) as type III, and 17 (30.4%) as type IV. Surgical outcomes were more favorable for type I or II patients than those with type III or IV, accompanied by a reduction in postoperative primary chylopericardium volume (P=0.002). Postoperative chest CT scans indicated that type I or II patients had fewer instances of large grid shadows, small grid shadows, and bronchovascular bundle thickening compared to preoperative scans (P=0.001, P=0.02, P=0.03). Age and bronchomediastinal trunk dilation emerged as independent factors influencing surgical outcomes [odds ratio (OR) 0.03, 95% confidence interval (CI): 0.003-0.220, P=0.001; OR 11.10, 95% CI: 1.70-72.39, P=0.01, respectively]. Conclusions: A more severe degree of neck and thoracic lymphatic abnormalities is associated with worse surgical outcomes. Moreover, age and bronchomediastinal trunk dilatation are independent predictors of surgical outcomes. Preoperative utilization of non-enhanced MRL for severity of lymphatic abnormalities classification in primary chylopericardium patients offers a noninvasive means of assessing surgical risk.

Diagnostic value of combined CT lymphangiography and 99Tcm-DX lymphoscintigraphy in primary chylopericardium.

OBJECTIVE: To investigate the diagnostic value of combined 99Tcm-DX lymphoscintigraphy and CT lymphangiography (CTL) in primary chylopericardium. METHODS: Fifty-five patients diagnosed with primary chylopericardium clinically were retrospectively analyzed. 99Tcm-DX lymphoscintigraphy and CTL were performed in all patients. Primary chylopericardium was classified into three types, according to the 99Tcm-DX lymphoscintigraphy results. The evaluation indexes of CTL include: (1) abnormal contrast distribution in the neck, (2) abnormal contrast distribution in the chest, (3) dilated thoracic duct was defined as when the widest diameter of thoracic duct was > 3 mm, (4) abnormal contrast distribution in abdominal. CTL characteristics were analyzed between different groups, and P < 0.05 was considered a statistically significant difference. RESULTS: Primary chylopericardium showed 12 patients with type I, 14 patients with type II, and 22 patients with type III. The incidence of abnormal contrast distribution in the posterior mediastinum was greater in type I than type III (P = 0.003). The incidence of abnormal contrast distribution in the pericardial and aortopulmonary windows, type I was greater than type III (P = 0.008). And the incidence of abnormal distribution of contrast agent in the bilateral cervical or subclavian region was greater in type II than type III (P = 0.002). CONCLUSION: The combined application of the 99Tcm-DX lymphoscintigraphy and CTL is of great value for the localized and qualitative diagnosis of primary chylopericardium and explore the pathogenesis of lesions.

91-month follow-up of solitary punctate chorioretinitis in a Chinese patient.

BACKGROUND: Solitary Punctate Chorioretinitis (SPC) is a recently identified form of punctate inner choroidopathy (PIC) characterized by a single lesion in the fovea of the macula. Previous studies with a maximum follow-up of 48 months were insufficient. Our review uncovered a case sustained for 91 months. CASE PRESENTATION: A 28-year-old young woman experienced with sudden visual loss in her right eye. Comprehensive examinations, including assessment of best-corrected visual acuity (BCVA), slit-lamp biomicroscopy, noncontact tonometry, fundus fluorescein angiography (FFA), fundus autofluorescence (FAF), optical coherence tomography angiography (OCTA), perimetry, and microperimetry, were conducted. Over 91 months, the lesion slightly enlarged, remained yellow-white and punctate, and stayed in the central macula of the posterior pole. OCT images depicted subsidence in the inner nuclear layer (INL), the outer plexiform layer (OPL), photoreceptor layer, and disruption of the external limiting membrane (ELM), ellipsoid zone, and retinal pigment epithelium (RPE)/Bruch's membrane complex. Retinal herniation, focal choroidal excavation (FCE), and abnormal vessels in the choriocapillaris were noted. At the slab of the choriocapillaris, OCTA demonstrated that the lesion resembled a linear vascular structure, distinct from the structure of normal choriocapillaris. This confirmed the lesion as an abnormal vascular formation. FAF revealed a punctate hypo-autofluorescence lesion and abnormal hyper-autofluorescence near the optic disc and macula. FFA demonstrated a punctate hyper-fluorescent lesion inferotemporal to the fovea. The vascular structure remained stable without fluid exudation on OCT images, hence anti-vascular endothelial growth factor (anti-VEGF) treatment was not administered. Visual acuity improved from counting fingers to 0.07 in 52 days, reached 0.6 after 15 months, remained at 0.6 from 56 to 80 months, and returned to 0.8 after 91 months, although accompanied by local scotomas. The lesion pattern slightly enlarged without scarring. CONCLUSIONS: Throughout long-term follow-up, we had long suspected the presence of choroidal neovascularization (CNV) and found the FCE in the last visit. Eventually, we concluded that SPC could potentially constitute a distinct subtype of PIC. The patient received no treatment, and vision recovered to 0.8. If CNV is suspected in SPC, anti-VEGF treatment may not be necessary without activity on OCT, but close monitoring is essential.

Anti-pulmonary fibrosis activity analysis of methyl rosmarinate obtained from Salvia castanea Diels f. tomentosa Stib. using a scalable process.

Pulmonary fibrosis is a progressive, irreversible, chronic interstitial lung disease associated with high morbidity and mortality rates. Current clinical drugs, while effective, do not reverse or cure pulmonary fibrosis and have major side effects, there are urgent needs to develop new anti-pulmonary fibrosis medicine, and corresponding industrially scalable process as well. Salvia castanea Diels f. tomentosa Stib., a unique herb in Nyingchi, Xizang, China, is a variant of S. castanea. and its main active ingredient is rosmarinic acid (RA), which can be used to prepare methyl rosmarinate (MR) with greater drug potential. This study presented an industrially scalable process for the preparation of MR, which includes steps such as polyamide resin chromatography, crystallization and esterification, using S. castanea Diels f. tomentosa Stib. as the starting material and the structure of the product was verified by NMR technology. The anti-pulmonary fibrosis effects of MR were further investigated in vivo and in vitro. Results showed that this process can easily obtain high-purity RA and MR, and MR attenuated bleomycin-induced pulmonary fibrosis in mice. In vitro, MR could effectively inhibit TGF-ß1-induced proliferation and migration of mouse fibroblasts L929 cells, promote cell apoptosis, and decrease extracellular matrix accumulation thereby suppressing progressive pulmonary fibrosis. The anti-fibrosis effect of MR was stronger than that of the prodrug RA. Further study confirmed that MR could retard pulmonary fibrosis by down-regulating the phosphorylation of the TGF-ß1/Smad and MAPK signaling pathways. These results suggest that MR has potential therapeutic implications for pulmonary fibrosis, and the establishment of this scalable preparation technology ensures the development of MR as a new anti-pulmonary fibrosis medicine.

Research Progress on the Mechanism of the Antitumor Effects of Cannabidiol.

Cannabidiol (CBD), a non-psychoactive ingredient extracted from the hemp plant, has shown therapeutic effects in a variety of diseases, including anxiety, nervous system disorders, inflammation, and tumors. CBD can exert its antitumor effect by regulating the cell cycle, inducing tumor cell apoptosis and autophagy, and inhibiting tumor cell invasion, migration, and angiogenesis. This article reviews the proposed antitumor mechanisms of CBD, aiming to provide references for the clinical treatment of tumor diseases and the rational use of CBD.

Lymphatic plastic bronchitis and primary chylothorax: A study based on computed tomography lymphangiography.

BACKGROUND: This study presents an evaluation of the computed tomography lymphangiography (CTL) features of lymphatic plastic bronchitis (PB) and primary chylothorax to improve the diagnostic accuracy for these two diseases. AIM: To improve the diagnosis of lymphatic PB or primary chylothorax, a retrospective analysis of the clinical features and CTL characteristics of 71 patients diagnosed with lymphatic PB or primary chylothorax was performed. METHODS: The clinical and CTL data of 71 patients (20 with lymphatic PB, 41 with primary chylothorax, and 10 with lymphatic PB with primary chylothorax) were collected retrospectively. CTL was performed in all patients. The clinical manifestations, CTL findings, and conventional chest CT findings of the three groups of patients were compared. The chi-square test or Fisher's exact test was used to compare the differences among the three groups. A difference was considered to be statistically significant when P < 0.05. RESULTS: (1) The percentages of abnormal contrast medium deposits on CTL in the three groups were as follows: Thoracic duct outlet in 14 (70.0%), 33 (80.5%) and 8 (80.0%) patients; peritracheal region in 18 (90.0%), 15 (36.6%) and 8 (80.0%) patients; pleura in 6 (30.0%), 33 (80.5%) and 9 (90.0%) patients; pericardium in 6 (30.0%), 6 (14.6%) and 4 (40.0%) patients; and hilum in 16 (80.0%), 11 (26.8%) and 7 (70.0%) patients; and (2) the abnormalities on conventional chest CT in the three groups were as follows: Ground-glass opacity in 19 (95.0%), 18 (43.9%) and 8 (80.0%) patients; atelectasis in 4 (20.0%), 26 (63.4%) and 7 (70.0%) patients; interlobular septal thickening in 12 (60.0%), 11 (26.8%) and 3 (30.0%) patients; bronchovascular bundle thickening in 14 (70.0%), 6 (14.6%) and 4 (40.0%) patients; localized mediastinal changes in 14 (70.0%), 14 (34.1%), and 7 (70.0%) patients; diffuse mediastinal changes in 6 (30.0%), 5 (12.2%), and 3 (30.0%) patients; cystic lesions in the axilla in 2 (10.0%), 6 (14.6%), and 2 (20.0%) patients; and cystic lesions in the chest wall in 0 (0%), 2 (4.9%), and 2 (4.9%) patients. CONCLUSION: CTL is well suited to clarify the characteristics of lymphatic PB and primary chylothorax. This method is an excellent tool for diagnosing these two diseases.

Understanding Chromium Slag Recycling with Sintering-Ironmaking Processes: Influence of Cr2O3 on the Sinter Microstructure and Mechanical Properties of the Silico-Ferrite of Calcium and Aluminum (SFCA).

Chromium slag is a solid waste of chromium salt production, which contains highly toxic Cr(VI) and significant amounts of valuable metals, such as Fe and Cr. Recycling chromium slag as a raw sintering material in sintering-ironmaking processes can simultaneously reduce toxic Cr(VI) and recover valuable metals. A micro-sintering experiment, compressive strength test, microhardness test, and first-principles calculation are performed to investigate the influence of Cr2O3 on the sintering microstructure and mechanical properties of the silico-ferrite of calcium and aluminum (SFCA) in order to understand the basis of the sintering process with chromium slag addition. The results show that the microstructure of SFCA changes from blocky to interwoven, with further increasing Cr2O3 content from 0 wt% to 3 wt%, and transforms to blocky with Cr2O3 content increasing to 5 wt%. Cr2O3 reacts with Fe2O3 to form (Fe1-xCrx)2O3 (0 ≤ x ≤ 1), which participates in forming SFCA. With the increase in Cr doping concentrations, the hardness of SFCA first decreases and then increases, and the toughness increases. When Cr2O3 content increases from 0 wt% to 3 wt%, the SFCA microhardness decreases and the compressive strength of the sintered sample increases. Further increasing Cr2O3 contents to 5 wt%, the SFCA microhardness increases, and the compressive strength of sintered sample decreases.

The value of the dermal rim sign on nonenhanced magnetic resonance imaging for predicting dermal backflow in patients with primary lower extremity lymphedema.

PURPOSE: The dermal rim sign (DRS) on nonenhanced magnetic resonance imaging has been shown to predict dermal backflow (DBF) in patients with secondary upper limb lymphedema. However, whether the DRS has the same effects on primary lower extremity lymphedema (PLEL) has not been clearly reported. Therefore, this study aimed to explore whether the DRS can be used to diagnose DBF on lymphoscintigraphy in patients with PLEL. METHODS: A total of 94 patients who were diagnosed with PLEL were recruited for this retrospective study from January 2022 to December 2023. All the patients were divided into two groups according to the lymphoscintigraphy findings: no DBF and DBF. The magnetic resonance imaging data of the two groups were recorded and statistically compared for the following indicators: range of lymphedema involvement (left, right, whole lower limbs, only thigh, only calf and ankle), signs of lymphedema (notable thickening of skin, parallel line sign, grid sign, honeycomb sign, band sign, lymph lake sign, crescent sign, DRS), and lymphedema measurement (skin thickness, band width). The DRS is characterized by notable thickening of the skin plus the grid sign and/or honeycomb sign, plus the band sign. RESULTS: The following statistically significant differences in the following indicators were found between the two groups (P < .05): notable skin thickening, parallel line sign, grid sign, honeycomb sign, band sign, DRS, skin thickness, and band width. The sensitivity, specificity, and accuracy for predicting for DBF with the DRS was 82%, 64%, and 77%, respectively. CONCLUSIONS: This study confirmed good consistency between the DRS and DBF from the perspective of imaging. This tool is suitable for children, adolescents, and patients with contraindications to lymphoscintigraphy. The DRS has important value in assessing the severity of PLEL. The DRS is suggested for the clinical use of combined surgical treatment of PLEL.

NLRP3 knockout in mice provided protection against Serratia marcescens-induced acute pneumonia by decreasing PD-L1 and PD-1 expression in macrophages.

Antibiotic-resistant Serratia marcescens (Sm) is known to cause bloodstream infections, pneumonia, etc. The nod-like receptor family, pyrin domain-containing 3 (NLRP3), has been implicated in various lung infections. Yet, its role in Sm-induced pneumonia was not well understood. In our study, we discovered that deletion of Nlrp3 in mice significantly improved Sm-induced survival rates, reduced bacterial loads in the lungs, bronchoalveolar lavage fluid (BALF), and bloodstream, and mitigated the severity of acute lung injury (ALI) compared to wild-type (WT) mice. Mechanistically, we observed that 24 h post-Sm infection, NLRP3 inflammasome activation occurred, leading to gasdermin D NH2-terminal (GSDMD-NT)-induced pyroptosis in macrophages and IL-1ß secretion. The NLRP3 or NLRP3 inflammasome influenced the expression PD-L1 and PD-1, as well as the count of PD-L1 or PD-1-expressing macrophages, alveolar macrophages, interstitial macrophages, PD-L1-expressing neutrophils, and the count of macrophage receptors with collagenous structure (MARCO)-expressing macrophages, particularly MARCO+ alveolar macrophages. The frequency of MARCO+ alveolar macrophages, PD-1 expression, particularly PD-1+ interstitial macrophages were negatively or positively correlated with the Sm load, respectively. Additionally, IL-1ß levels in BALF correlated with three features of acute lung injury: histologic score, protein concentration and neutrophil count in BALF. Consequently, our findings suggest that Nlrp3 deletion offers protection agaisnt acute Sm pneumonia in mice by inhibiting inflammasome activation and reducing Sm infection-induced PD-L1/PD-1 or MARCO expression, particularly in macrophages. This highlights potential therapeutic targets for Sm and other gram-negative bacteria-induced acute pneumonia.

Value of the short time inversion recovery sequence of magnetic resonance imaging in the staging of Klippel-Trenaunay syndrome complicated with lymphedema.

OBJECTIVE: Currently, the focus on limb lymphedema (LE) is on classification and staging. However, few scholars have conducted staging for Klippel-Trenaunay syndrome complicated LE (KTS-LE). This study aimed to investigate the value of the short time inversion recovery sequence of magnetic resonance imaging (MRI) in the staging of KTS-LE. METHODS: Forty-six patients who were diagnosed with KTS-LE were recruited for this retrospective study from July 2011 to November 2022. Referring to the clinical staging standard of lower extremity LE of the International Society of Lymphology in 2020, all patients were divided into three groups: stages I, II, and III. The MRI indicators of the three groups were recorded and statistically compared: LE range (unilateral bilateral, lower limbs, only thighs, only calves and ankles), abnormal parts (skin thickening, abnormal subcutaneous fat signal, abnormal muscle signal, muscle hypertrophy or contraction, abnormal bone signal, hyperostosis), and subcutaneous soft tissue signs (parallel line sign, grid sign, band sign, honeycomb sign, lymph lake sign, crescent sign, and nebula sign). RESULTS: There was a significant difference in the honeycomb sign among the three periods (P = .028). There was a significant difference between stage II and stage I disease (P < .05). There was a significant difference between stage II and stage III disease (P < .05). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the honeycomb sign in diagnosing KTS-LE of stage II were 87.5%, 63.2%, 33.3%, 96.0%, and 67.4%, respectively. In contrast, the other signs were not statistically significant among the three periods. CONCLUSIONS: The short time inversion recovery sequence of MRI is of great value in KTS-LE. The honeycomb sign is an important imaging indicator for the diagnosis of stage II disease. It is necessary to evaluate the severity of edema with MRI for KTS-LE, which is very important for therapeutic options.

MRI-based volume measurement methods for staging primary lower extremity lymphedema: a single-center study of asymmetric volume difference-a diagnostic study.

BACKGROUND: Lower extremity lymphedema (LEL) staging is mainly assessed by systems that solely depend on physical examinations and lack quantitative assessment based on modern imaging. OBJECTIVE: To explore the value of MRI-based asymmetric volume measurements in the clinical staging of primary LEL. METHODS: 92 patients with unilateral primary LEL underwent MRI examinations to determine the volume of the mid-calf (Vcl) calculated using the clinical dermatome method as well as the total volume (Vmri), musculoskeletal volume (VM), and subcutaneous volume (VS) volume of the middle calves. The difference between Vmri (DVmri) and VS (DVS) of the affected and unaffected calves was obtained and defined as the asymmetric volume difference. Meanwhile, the volume of the mid-calf (Vcl) and the difference in volume (DVcl) were calculated using the clinical circumferential method. The relationship between the asymmetric volume difference and clinical staging was then evaluated. Interobserver consistency was assessed through the intraclass correlation coefficient (ICC). Volume comparisons between the three groups were performed using the one-way analysis of variance (ANOVA) or the Kruskal-Wallis test. Spearman's correlation was used to assess volume and clinical stage correlation. The receiver operating characteristic (ROC) curve was used to evaluate the value of asymmetric volume difference for clinical staging. RESULTS: The asymmetric volume difference was statistically significant in stage I compared to stages II and III (p < 0.05). The asymmetric volume difference (DVmri: r = 0.753; DVS: r = 0.759) correlated more with the clinical stage than the affected Vcl (r = 0.581), Vmri (r = 0.628), VS (r = 0.743), and DVcl (r = 0.718). The area under the ROC curve (AUC) for identifying the clinical stage by the asymmetric volume difference was greater than that for the affected Vcl, Vmri, VS, and DVcl, with DVS (AUC = 0.951) having the largest area under the curve to distinguish between stages I and II. CONCLUSION: MRI-based asymmetric volume difference is an adjunctive measure for LEL clinical staging with good reproducibility. DVS could be the best indicator for differentiating between stages I and II of primary LEL.

Case Report: Molecular and microenvironment change upon midostaurin treatment in mast cell leukemia at single-cell level.

Mast cell leukemia is a rare and aggressive disease, predominantly with KIT D816V mutation. With poor response to conventional poly-chemotherapy, mast cell leukemia responded to the midostaurin treatment with a 50% overall response rate (ORR), but complete remission rate is approximately 0%. Therefore, the potential mechanisms of midostaurin resistance and the exact impacts of midostaurin on both gene expression profile and mast cell leukemia microenvironment in vivo are essential for design tailored combination therapy targeting both the tumor cells and the tumor microenvironment. Here we report a 59-year-old male mast cell leukemia patient with KIT F522C mutation treated with midostaurin. Single-cell sequencing of peripheral blood and whole exome sequencing (WES) of bone marrow were performed before and 10 months after midostaurin treatment. In accordance with the clinical response, compared to the pretreatment aberration, the decline of mast cells and increase of T-, NK, B-cells in peripheral blood, and the decrease of the KIT F522C mutation burden in bone marrow were observed. Meanwhile, the emergence of RUNX1 mutation, upregulations of genes expression (RPS27A, RPS6, UBA52, RACK1) on tumor cells, and increased frequencies of T and NK cells with TIGIT, CTLA4, and LAG3 expression were observed after midostaurin treatment, predicting the disease progression of this patient. As far as we know, this is the first case reporting the clinical, immunological, and molecular changes in mast cell leukemia patients before and after midostaurin treatment, illustrating the in vivo mechanisms of midostaurin resistance in mast cell leukemia, providing important clues to develop a sequential option to circumvent tumor progression after targeting oncogene addiction and prolong patients' survival.

Quantitative evaluation of primary lower extremity lymphedema staging using MRI: a preliminary study.

Background: The staging of primary lower extremity lymphedema (LEL) is difficult yet vital in clinical work, and magnetic resonance imaging (MRI) can be used for quantitative assessment of primary LEL due to its high resolution for soft tissues. In this study, we evaluated the value of MRI-based soft tissue area measurements for staging primary LEL. Methods: A total of 90 consecutive patients with clinically diagnosed primary lower limb lymphoedema from January 2017 to December 2019 in Beijing Shijitan Hospital were enrolled retrospectively. Short time inversion recovery (STIR) sequence was applied to measure the total, muscle, bone, and subcutaneous areas in the upper 1/3 level of the bilateral lower calf. The difference between the affected and unaffected calf regarding the subcutaneous area was obtained, and (subcutaneous area)/(bone area) and (subcutaneous area)/(muscle area) were calculated. According to the International Society of Lymphology (ISL) clinical staging standard established in 2020, all patients were divided into stages I, II, and III, accordingly. Statistical analysis was performed to determine the validity of MRI measurements in staging LEL. Results: There were 33 patients classified as stage I clinically, 44 patients as stage II, and 13 patients as stage III. There were significant differences in total, subcutaneous, the difference in subcutaneous area of limbs, subcutaneous/bone (S/B), and subcutaneous/muscle (S/M) between stage I and II as well as between stage I and III (P<0.001), but not between stage II and III (P=0.706, 0.329, and 0.229, respectively). A positive correlation was detected between the clinical stage and difference in subcutaneous area of limbs (rho =0.752, P<0.001), S/B (rho =0.747, P<0.001), S/M (rho =0.709, P<0.001), and subcutaneous (rho =0.723, P<0.001). For staging primary LEL, receiver operating characteristic (ROC) curves indicated that the difference in subcutaneous area of limbs had the best discrimination ability among parameters [area under the ROC curve (AUC) =0.950; 95% confidence interval (CI): 0.875-0.987; sensitivity: 95.45%; specificity: 84.85%], followed by S/B (AUC =0.930; 95% CI: 0.848-0.975; sensitivity: 77.27%; specificity: 93.94%) and S/M (AUC =0.895; 95% CI: 0.804-0.953; sensitivity: 77.27%; specificity: 90.91%). The ROC curves indicated that subcutaneous area (AUC =0.927; 95% CI: 0.844-0.974; sensitivity: 84.09%, specificity: 90.91%) and total (AUC =0.852; 95% CI: 0.753-0.923; sensitivity: 70.45%; specificity: 90.91%) also had discrimination ability between stage I and II. Conclusions: The measurement of the soft tissue area of the calf may be used as an auxiliary method for staging primary LEL. For patients with unilateral primary LEL, the difference in subcutaneous area of limbs could be a specific indicator to distinguish clinical stage I from II.

Singapore grouper iridovirus VP122 targets grouper STING to evade the interferon immune response.

Singapore grouper iridovirus (SGIV) is a highly pathogenic Iridoviridae that causes hemorrhage and spleen enlargement in grouper. Despite previous genome annotation efforts, many open reading frames (ORFs) in SGIV remain uncharacterized, with largely unknown functions. In this study, we identified the protein encoded by SGIV ORF122, now referred to as VP122. Notably, overexpression of VP122 promoted SGIV replication. Moreover, VP122 exhibited antagonistic effects on the natural antiviral immune response through the cGAS-STING signaling pathway. It specifically inhibited the cGAS-STING-triggered transcription of various immune-related genes, including IFN1, IFN2, ISG15, ISG56, PKR, and TNF-α in GS cells. Additionally, VP122 significantly inhibited the activation of the ISRE promoter mediated by EccGAS and EcSTING but had no effect on EccGAS or EcSTING alone. Immunoprecipitation and Western blotting experiments revealed that VP122 specifically interacts with EcSTING but not EccGAS. Notably, this interaction between VP122 and EcSTING was independent of any specific domain of EcSTING. Furthermore, VP122 inhibited the self-interaction of EcSTING. Interestingly, VP122 did not affect the recruitment of EcTBK1 and EcIRF3 to the EcSTING complex. Collectively, our results demonstrate that SGIV VP122 targets EcSTING to evade the type I interferon immune response, revealing a crucial role for VP122 in modulating the host-virus interaction.

α-myosin heavy chain lactylation maintains sarcomeric structure and function and alleviates the development of heart failure.

The sarcomeric interaction of α-myosin heavy chain (α-MHC) with Titin is vital for cardiac structure and contraction. However, the mechanism regulating this interaction in normal and failing hearts remains unknown. Lactate is a crucial energy substrate of the heart. Here, we identify that α-MHC undergoes lactylation on lysine 1897 to regulate the interaction of α-MHC with Titin. We observed a reduction of α-MHC K1897 lactylation in mice and patients with heart failure. Loss of K1897 lactylation in α-MHC K1897R knock-in mice reduces α-MHC-Titin interaction and leads to impaired cardiac structure and function. Furthermore, we identified that p300 and Sirtuin 1 act as the acyltransferase and delactylase of α-MHC, respectively. Decreasing lactate production by chemical or genetic manipulation reduces α-MHC lactylation, impairs α-MHC-Titin interaction and worsens heart failure. By contrast, upregulation of the lactate concentration by administering sodium lactate or inhibiting the pivotal lactate transporter in cardiomyocytes can promote α-MHC K1897 lactylation and α-MHC-Titin interaction, thereby alleviating heart failure. In conclusion, α-MHC lactylation is dynamically regulated and an important determinant of overall cardiac structure and function. Excessive lactate efflux and consumption by cardiomyocytes may decrease the intracellular lactate level, which is the main cause of reduced α-MHC K1897 lactylation during myocardial injury. Our study reveals that cardiac metabolism directly modulates the sarcomeric structure and function through lactate-dependent modification of α-MHC.

A mesoporous Al2O3 zincophilic sieve enables ultra-long lifespan of Zn-ion batteries.

The Zn dendrite growth and side reactions hinder the practical application of aqueous Zn-ion batteries. Here, a lactic acid-induced mesoporous Al2O3 (LA-MA) zincophilic sieve was constructed on a Zn anode to resolve these issues. The LA-MA layer with abundant mesoporous ion channels of 3.0 nm can regulate the solvation structure from [Zn2+(H2O)6]SO42- to more highly coordinated [Zn2+(H2O)5OSO32-] and restrain water-induced side reactions. Furthermore, the electrostatic attraction with zincophilic groups (CO, C-O) in the LA-MA layer has a positive effect on reducing the Zn2+ desolvation barrier and accelerating the Zn2+ diffusion. Under the synergism, the LA-MA@Zn symmetric cell exhibits over 5100 h at 0.25 mA cm-2. Impressively, an excellent capacity retention of 94.2% is achieved after 3500 cycles for the CNT/MnO2 cathode.

Spleen tyrosine kinase (SYK) signals are implicated in cardio-cerebrovascular diseases.

Post-translational modifications regulate numerous biochemical reactions and functions through covalent attachment to proteins. Phosphorylation, acetylation and ubiquitination account for over 90% of all reported post-translational modifications. As one of the tyrosine protein kinases, spleen tyrosine kinase (SYK) plays crucial roles in many pathophysiological processes and affects the pathogenesis and progression of various diseases. SYK is expressed in tissues outside the hematopoietic system, especially the heart, and is involved in the progression of various cardio-cerebrovascular diseases, such as atherosclerosis, heart failure, diabetic cardiomyopathy, stroke and others. Knowledge on the role of SYK in the progress of cardio-cerebrovascular diseases is accumulating, and many related mechanisms have been discovered and validated. This review summarizes the role of SYK in the progression of various cardio-cerebrovascular diseases, and aims to provide a theoretical basis for future experimental and clinical research targeting SYK as a therapeutic option for these diseases.