Recurrent myocardial injury in a de novo SON mutation ZTTK syndrome patient: a case report.

BACKGROUND: Zhu-Tokita-Takenouchi-Kim syndrome (ZTTK syndrome) is a severe multi-systemic developmental disorder, caused by variants in the SON gene. A patient diagnosed with ZTTK syndrome who carried a de novo SON mutation and exhibited recurrent myocardial injury was described in this case. CASE PRESENTATION: A 7-year-old girl was admitted to the Cardiology Department of Beijing Children's Hospital in November 2019 due to myocardial injury following respiratory infection. She displayed elevated myocardial enzymes and severe T-wave changes on electrocardiogram. Over the past three years, she had experienced myocardial injury on three occasions. Additionally, she exhibited intellectual disability, congenital amblyopia, and dysmorphic facial features. Genetic analysis revealed a de novo heterozygous mutation c.3852_3856delGGTAT in the SON gene, which was confirmed by Sanger sequencing of her parents. She received anti-infection treatment and was administered metoprolol orally. Her condition was stable at the time of discharge. Over a 42-month follow-up period at the outpatient clinic, she complained intermittent fatigue and palpitation. CONCLUSIONS: The identified SON mutation, which plays a crucial role in heart development and mitochondrial function, may be associated with an increased susceptibility to myocardial injury or cardiomyopathy. This case report contributes novel insights into this rare condition and suggests the expansion of the ZTTK syndrome phenotype.

Clinical analysis of sixty-nine children with anomalous aortic origin of the coronary artery.

We aimed to analyse the clinical characteristics of children with different types of anomalous aortic origin of the coronary artery (AAOCA) at different ages, and to discuss the factors related to myocardial ischaemia. In this retrospective study, we included 69 children diagnosed with AAOCA using CT coronary angiography; we classified the participants based on the type of AAOCA, age, and high-risk anatomy. The clinical characteristics of the different AAOCA types and age groups were compared, and the correlation between manifestations and high-risk anatomy was analysed. Anomalous origin of the left coronary artery from the right coronary artery sinus, anomalous origin of the right coronary artery from the left coronary artery sinus, and a coronary artery origin without coronary sinuses was found in 10 (14.5%), 57 (82.6%), 2 (2.9%) patients, respectively. There were no significant differences in sex, clinical manifestations, percentage of positive myocardial injury markers, electrocardiogram, transthoracic echocardiography, or proportion of high-risk anatomy among the groups with different AAOCA types. According to age group, the proportion of asymptomatic infants and pre-schoolers was the highest (p < 0.001). Forty-three patients (62.3%) had high-risk anatomy and were more likely to present with severe symptoms and cardiac syncope (p < 0.05).   Conclusion: There were no significant differences in the proportions of high-risk anatomy and clinical characteristics among children with different AAOCA types. We found a relation between the severity of AAOCA clinical symptoms and anatomical risk. What is Known: • Clinical symptoms in children with AAOCA are varied and the results of routine cardiological examinations lack specificity. • High-risk anatomical features, exercise, cardiac symptoms, and ALCA are risk factors for the occurrence of SCD in patients with AAOCA. What is New: • Compared the clinical characteristics of different types of AAOCA and ages. • Analysed the correlation between symptoms and high-risk anatomical features.

Laser-triggered intelligent drug delivery and anti-cancer photodynamic therapy using platelets as the vehicle.

In our previous study, target drug delivery and treatment of malignant tumors have been achieved by using platelets as carriers loading nano-chemotherapeutic agents (ND-DOX). However, drug release from ND-DOX-loaded platelets is dependent on negative platelet activation by tumor cells, whose activation is not significant enough for the resulting drug release to take an effective anti-tumor effect. Exploring strategies to proactively manipulate the controlled release of drug-laden platelets is imperative. The present study innovatively revealed that photodynamic action can activate platelets in a spatiotemporally controlled manner. Consequently, based on the previous study, platelets were used to load iron oxide-polyglycerol-doxorubicin-chlorin e6 composites (IO-PG-DOX-Ce6), wherein the laser-triggered drug release ability and anti-tumor capability were demonstrated. The findings suggested that IO-PG-DOX-Ce6 could be stably loaded by platelets in high volume without any decrease in viability. Importantly and interestingly, drug-loaded platelets were significantly activated by laser irradiation, characterized by intracellular ROS accumulation and up-regulation of CD62p. Additionally, scanning electron microscopy (SEM) and hydrated particle size results also showed a significant aggregation response of laser irradiated-drug-loaded platelets. Further transmission electron microscopy (TEM) measurements indicated that the activated platelets released extracellularly their cargo drug after laser exposure, which could be taken up by co-cultured tumor cells. Finally, the co-culture model of drug-loaded platelets and tumor cells proved that laser-triggered delivery system of platelets could effectively damage the DNA and promote apoptosis of tumor cells. Overall, the present study discovers a drug-loaded platelets delivery using photodynamic effect, enabling laser-controlled intelligent drug delivery and anti-tumor therapy, which provides a novel and feasible approach for clinical application of cytopharmaceuticals.

What is the context?1. Platelets were applied to load IO-PG-DOX-Ce6, wherein the laser-triggered drug release and anti-tumor effect were investigated in vitro.2. The findings indicated that IO-PG-DOX-Ce6 could be stably loaded by platelets in high volume without any decrease in viability, which may attribute to the activation of autophagy in platelets.3. IO-PG-DOX-Ce6-loaded platelets could be significantly activated by laser irradiation (690 nm).4. Activated platelets released extracellularly their cargo drug after laser exposure, which could be taken up by co-cultured tumor cells5. The co-culture model of drug-loaded platelets and tumor cells proved that the laser-triggered delivery system of platelets could effectively damage the DNA and promote apoptosis of tumor cells.What is new?1. Platelets could be utilized as the vehicle to load photosensitizer-loaded-nano-drug.2. Photodynamic action can activate platelets in a spatiotemporally controlled manner, which could be a tool to regulate the activation of platelets.3. The laser-triggered activation of drug-loaded platelets allows for target release of cargo.4. The limitation of the current research is that only in vitro experiments were carried out to demonstrate our conclusions.What is impact?The present work provides a novel and feasible approach for the clinical application of cytopharmaceuticals.

A nanoreactor boosts chemodynamic therapy and ferroptosis for synergistic cancer therapy using molecular amplifier dihydroartemisinin.

BACKGROUND: Chemodynamic therapy (CDT) relying on intracellular iron ions and H2O2 is a promising therapeutic strategy due to its tumor selectivity, which is limited by the not enough metal ions or H2O2 supply of tumor microenvironment. Herein, we presented an efficient CDT strategy based on Chinese herbal monomer-dihydroartemisinin (DHA) as a substitute for the H2O2 and recruiter of iron ions to amplify greatly the reactive oxygen species (ROS) generation for synergetic CDT-ferroptosis therapy. RESULTS: The DHA@MIL-101 nanoreactor was prepared and characterized firstly. This nanoreactor degraded under the acid tumor microenvironment, thereby releasing DHA and iron ions. Subsequent experiments demonstrated DHA@MIL-101 significantly increased intracellular iron ions through collapsed nanoreactor and recruitment effect of DHA, further generating ROS thereupon. Meanwhile, ROS production introduced ferroptosis by depleting glutathione (GSH), inactivating glutathione peroxidase 4 (GPX4), leading to lipid peroxide (LPO) accumulation. Furthermore, DHA also acted as an efficient ferroptosis molecular amplifier by direct inhibiting GPX4. The resulting ROS and LPO caused DNA and mitochondria damage to induce apoptosis of malignant cells. Finally, in vivo outcomes evidenced that DHA@MIL-101 nanoreactor exhibited prominent anti-cancer efficacy with minimal systemic toxicity. CONCLUSION: In summary, DHA@MIL-101 nanoreactor boosts CDT and ferroptosis for synergistic cancer therapy by molecular amplifier DHA. This work provides a novel and effective approach for synergistic CDT-ferroptosis with Chinese herbal monomer-DHA and Nanomedicine.

Recent developments in less known and multi-resistant fungal opportunists.

Fungal infections have increased in recent years due to host factors, such as oncohaematological and transplant-related disorders, immunosuppressive therapy, and AIDS. Additionally, molecular and proteomic facilities have become available to identify previously unrecognizable opportunists. For these reasons, reports on less-known and recalcitrant mycoses, such as those caused by black fungi, hyaline filamentous fungi, coelomycetes, Mucorales, and non-Candida yeasts have emerged. In this review, novel taxonomy in these groups, which often are multi-resistant to one or several classes of antifungals, is discussed. Clinical presentations, diagnosis and current treatment of some major groups are summarised.

Efficient Delivery of Chlorin e6 by Polyglycerol-Coated Iron Oxide Nanoparticles with Conjugated Doxorubicin for Enhanced Photodynamic Therapy of Melanoma.

Chlorin e6 (Ce6) is a promising photosensitizer for tumor photodynamic therapy (PDT). However, the efficacy of Ce6 PDT is limited by Ce6's poor water solubility, rapid blood clearance, and inadequate accumulation in the tumor tissue. This problem is tackled in this work, wherein functionalized superparamagnetic iron oxide nanoparticles (IO-NPs) were used as carriers to deliver Ce6 to melanoma. The IO-NPs were coated with polyglycerol (PG) to afford good aqueous solubility. The chemotherapeutic agent doxorubicin (DOX) was attached to the PG coating via the hydrazone bond to afford affinity to the cell membrane and thereby promote the cell uptake. The hydrophobic nature of DOX also induced the aggregation of IO-NPs to form nanoclusters. Ce6 was then loaded onto the IO nanoclusters through physical adsorption and coordination with surface iron atoms, yielding the final composites IO-PG-DOX-Ce6. In vitro experiments showed that IO-PG-DOX-Ce6 markedly increased Ce6 uptake in mouse melanoma cells, leading to much-enhanced photocytotoxicity characterized by intensified reactive oxygen species production, loss of viability, DNA damage, and stimulation of tumor cell immunogenicity. In vivo experiments corroborated the in vitro findings and demonstrated prolonged blood clearance of IO-PG-DOX-Ce6. Importantly, IO-PG-DOX-Ce6 markedly increased the Ce6 distribution and retention in mouse subcutaneous melanoma grafts and significantly improved the efficacy of Ce6-mediated PDT. No apparent vital organ damage was observed at the same time. In conclusion, the IO-PG-DOX NPs provide a simple and safe delivery platform for efficient tumor enrichment of Ce6, thereby enhancing antimelanoma PDT.

Phylogeny of Graphostromatacea with two new species (Biscogniauxia glaucae sp. nov. and Graphostroma guizhouensis sp. nov.) and new record of Camillea broomeana isolated in China.

In the process of studying the diversity of Xylariales in China, three species owning characteristics of Graphostromataceae were observed in China. Morphology of the described species with illustrations and their phylogeny based on regions of internal transcribed spacers (ITS), the second-largest subunit of the RNA polymerase II (RPB2), ß-tubulin (TUB2) and α-actin (ACT) are provided. Two new species and one new record from China are identified. Morphologically, Biscogniauxia glaucae sp. nov. differs from B. atropunctata var. maritima, B. citriformis var. macrospora, B. fuscella and B. mediterranea by its stromata with raised margins, clear outlines, punctate ostioles openings and ascospores which are equilateral with broadly rounded ends, a straight spore-length germ slit on the more concave side, lacking appendages and sheathes. Graphostroma guizhouensis is identified as a new species based on the multi-gene phylogenetic tree. Camillea broomeana with scanning electron microscope description of ascospores is illustrated as a new record from China. Cryptostroma is proposed in Graphostromataceae based on molecular data. Vivantia is accepted in Graphostromataceae based on its morphological characteristics and Nodulisporiurn anamorphs which are similar to those of Biscogniauxia.

Two New Isoprenoid Flavonoids from Sophora flavescens with Antioxidant and Cytotoxic Activities.

Sophora flavescens is a regularly used traditional Chinese medicine. In an attempt to discover adequate active agents, the isoprenoid flavonoids from S. flavescens were further investigated. In this work, two new compounds (1-2, kurarinol A-B) together with 26 known ones (3-28) were isolated and elucidated on the basis of extensive NMR, UV and MS analyses. Furthermore, the antioxidant activity of all constituents was assessed through ABTS, PTIO and DPPH methodologies and also were evaluated for cytotoxic activity by three tumor cell lines (HepG2, A549 and MCF7) and one human normal cell line (LO2 cells). As a result, a multitude of components revealed significant inhibitory activity. In particular, compound 1-2 (kurarinol A-B), two new flavanonols derivatives, exhibited the most potent ABTS inhibitory activity with IC50 of 1.21 µg/mL and 1.81 µg/mL, respectively. Meanwhile, the new compound 1 demonstrated remarkable cytotoxicity against three cancer cells lines with IC50 values ranging from 7.50-10.55 µM but showed little effect on the normal cell. The two new isoprenoid flavonoids could be promising antioxidant and anti-tumor nature agents.

Understanding the Effects of China's Agro-Environmental Policies on Rural Households' Labor and Land Allocation with a Spatially Explicit Agent-Based Model.

Understanding household labor and land allocation decisions under agro-environmental policies is challenging due to complex human-environment interactions. Here, we develop a spatially explicit agent-based model based on spatial and socioeconomic data to simulate households' land and labor allocation decisions and investigate the impacts of two forest restoration and conservation programs and one agricultural subsidy program in rural China. Simulation outputs reveal that the forest restoration program accelerates labor out-migration and cropland shrink, while the forest conservation program promotes livelihood diversification via increasing non-farm employment. Meanwhile, the agricultural subsidy program keeps labor for cultivation on land parcels with good quality, but appears less effective for preventing marginal croplands from being abandoned. The policy effects on labor allocation substantially differ between rules based on bounded rational and empirical knowledge of defining household decisions, particularly on sending labor out-migrants and engaging in local off-farm jobs. Land use patterns show that the extent to which households pursue economic benefits through shrinking cultivated land is generally greater under bounded rationality than empirical knowledge. Findings demonstrate nonlinear social-ecological impacts of the agro-environmental policies through time, which can deviate from expectations due to complex interplays between households and land. This study also suggests that the spatial agent-based model can represent adaptive decision-making and interactions of human agents and their interactions in dynamic social and physical environments.

Study on metastasis inhibition of Kejinyan decoction on lung cancer by affecting tumor microenvironment.

BACKGROUND: Kejinyan decoction, as an experienced formula of Zhou Zhongying (the Master of Traditional Chinese Medicine) has been widely used in clinic for lung cancer treatment in China, while the anti-lung cancer mechanism of it is still remained to be elucidated. Herein, our basic study found that the survival of lung cancer xenograft mice was significantly prolonged after intragastrically administered high dose of Kejinyan decoction (3.8 g per kg BW) for 15 days. More importantly, we found that Kejinyan decoction inhibited the metastasis of lung cancer cells in vivo. Thus in this study, we aim to elucidate the anti-metastasis effects of Kejinyan decoction. METHODS: RNA-Seq was used to find out the gene regulation of Kejinyan decoction on the mice, flow cytometry assay was used to detect the immunocytes in the spleen, ELISA assay was used to detect the inflammatory factors in the serum and spleen, and immunofluorescence assay was used to detect the level of immune cells and the expression of glycol-metabolism related enzymes in situ. Also, we established a lung cancer orthotopic xenograft tumor model to assess the influence of Kejinyan decoction on the metastatic ability of lung cancer cells in vivo. RESULTS: GO analysis of gene sequencing of tumor tissue samples showed that Kejinyan decoction regulated immune response. Further flow cytometry analysis of splenic lymphocyte showed that Kejinyan decoction upregulated M1 macrophages and downregulated M2 macrophages, while the total level of macrophages changed little, which was verified by detection of CD68, F4/80, CD206, and CD86 in tumor tissue section. Moreover, detection of inflammatory cytokines showed that Kejinyan decoction downregulated TNF-α, IFN-γ, IL-6, as well as IL-4, IL-13 in tumor microenvironment. Further studies also showed that Kejinyan decoction had little effect on tumor hypoxia, but downregulated glycolysis in tumor tissues. More importantly, we found that Kejinyan decoction inhibited the metastasis of lung cancer cells in vivo. CONCLUSION: Our findings conclude that Kejinyan decoction inhibited lung cancer cell metastasis through affecting macrophage polarization and energy reprogramming.

Vulcaniibacterium gelatinicum sp. nov., a moderately thermophilic bacterium isolated from a hot spring.

The present study aimed to determine the taxonomic positions of strains designated R-5-52-3T, R-5-33-5-1-2, R-5-48-2 and R-5-51-4 isolated from hot spring water samples. Cells of these strains were Gram-stain-negative, non-motile and rod-shaped. The strains shared highest 16S rRNA gene sequence similarity with Vulcaniibacterium thermophilum KCTC 32020T (95.1%). Growth occurred at 28-55 °C, at pH 6-8 and with up to 3 % (w/v) NaCl. DNA fingerprinting, biochemical, phylogenetic and 16S rRNA gene sequence analyses suggested that R-5-52-3T, R-5-33-5-1-2, R-5-48-2 and R-5-51-4 were different strains but belonged to the same species. Hence, R-5-52-3T was chosen for further analysis and R-5-33-5-1-2, R-5-48-2 and R-5-51-4 were considered as additional strains of this species. R-5-52-3T possessed Q-8 as the only quinone and iso-C15:0, iso-C11:0, C16 : 0 and iso-C17 : 0 as major fatty acids. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, unidentified polar lipids and two unidentified phospholipids. The genomic G+C content was 71.6 mol%. Heat shock proteins (e.g. Hsp20, GroEL, DnaK and Clp ATPases) were noted in the R-5-52-3T genome, which could suggest its protection in the hot spring environment. Pan-genome analysis showed the number of singleton gene clusters among Vulcaniibacterium members varied. Average nucleotide identity (ANI) values between R-5-52-3T, Vulcaniibacterium tengchongense YIM 77520T and V. thermophilum KCTC 32020T were 80.1-85.8 %, which were below the cut-off level (95-96 %) recommended as the ANI criterion for interspecies identity. Thus, based on the above results, strain R-5-52-3T represents a novel species of the genus Vulcaniibacterium, for which the name Vulcaniibacterium gelatinicum sp. nov. is proposed. The type strain is R-5-52-3T (=KCTC 72061T=CGMCC 1.16678T).

Pseudomonas Saliphila sp. nov., a Bacterium Isolated from Oil-Well Production Water in Qinghai Oilfield of China.

Strain 16W4-4-3 T was isolated from the oil-well production water in Qinghai Oilfield, China. Cells were Gram-stain-negative, rod-shaped, catalase- and oxidase-positive, facultatively anaerobic and motile by single polar flagellum. The 16S rRNA gene sequences of strain 16W4-4-3 T showed the highest similarities with Pseudomonas profundi M5T (98.8%), P. pelagia CL-AP6T (98.0%), P. salina XCD-X85T (97.7%), and P. sabulinigri J64T (97.5%). The phylogenetic trees based on multilocus sequence analyses with concatenating 16S rRNA, gyrB, rpoD and rpoB genes suggested that this strain should be affiliated to the genus Pseudomonas but remotely related from other species. In addition, whole genome analyses revealed that the digital DNA-DNA hybridization values and average nucleotide identities of strain 16W4-4-3 T against its close relatives were all below 28.8% and 86.5%, respectively. Furthermore, the isolate had totally different whole cell protein profile as compared to those of other species. Major fatty acids were summed feature 8 (C18:1ω7c and/or C18:1ω6c), C16:0, summed feature 3 (C16:1ω7c and/or C16:1ω6c) and C17:0cyclo. Major isoprenoid quinone was ubiquinone (Q-9), and major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, and phosphatidylethanolamine. The DNA G + C content was 58.5 mol%. Therefore, phenotypic, phylogenetic, genomic, chemotaxonomic, and proteomic traits showed that the isolate represented a novel species of the genus Pseudomonas, the name Pseudomonas saliphila sp. nov. is proposed. Type strain is 16W4-4-3 T (= CGMCC 1.13350 T = KCTC 72619 T).

Toll-like receptor 2 deficiency promotes the generation of alloreactive Th17 cells after cardiac transplantation in mice.

The emergence of alloreactive Th17 cells that mediate allograft rejection has provided an impetus to understand the factors affecting the generation of Th17 cells in allograft transplantation. How toll-like receptor 2 (TLR2) signalling regulates the generation of Th17 cells upon alloantigen stimuli remains unclear. In this study, we used a mouse model of cardiac allograft transplantation to investigate whether TLR2 signalling influences the development of Th17 cells. Here, we demonstrate that the TLR2-deficient recipient mice show high Th17 cells, both in spleens and allografts, as well as higher infiltrating inflammatory leukocytes in cardiac allografts compared to wild-type control recipient mice. mRNA expression of IL-17, IL-6, TNF-α, CCR6 and CCL20 within the allografts is markedly increased in TLR2-deficient recipient mice compared to wild-type recipient mice. In addition, TLR2 deficiency leads to upregulation of Signal transducer and activator of transcription 3 (STAT3) phosphorylation in both spleens and allografts. In an in vitro experiment, a mixed lymphocyte reaction was assessed, which further confirmed that TLR2 deficiency leads to a significant increase in the generation of Th17 cells compared with wild-type controls. Furthermore, IL-6 secreted by the dendritic cells of TLR2-deficient mice contributes to driving the generation of these Th17 cells. These results suggest that TLR2 signalling is important in regulating the development of Th17 cells after cardiac allograft transplantation.

Simultaneous quantitative analysis of phosphocreatine, creatine and creatinine in plasma of children by HPLC-MS/MS method: Application to a pharmacokinetic study in children with viral myocarditis.

A simple and rapid HPLC-MS/MS method was developed and validated for simultaneous measurement of phosphocreatine and its metabolites creatine and creatinine in children's plasma. A 50 µL aliquot of plasma was prepared by protein precipitation with acetonitrile-water (1000 µL, 1:1, v/v) followed by separation on a Hypersil Gold C18 column (35°C) with gradient mobile phase consisting of 2 mm ammonium acetate aqueous solution (pH 10) and methanol at a flow rate of 0.3 mL/min and analyzed by mass spectrometry in both positive (phosphocreatine) and negative (creatine and creatinine) ion multiple reaction monitoring mode. Good linearity (r > 0.99) was obtained for the three analytes. The intra-day and inter-day values of CV were <5.46% (-13.09% ≤ RE ≤ 2.57%). The average recoveries of the three analytes were 70.9-97.5%. No obvious impact was found for the quantitation of three analytes in normal, hemolyzed and hyperlipemic plasma. In the end, this method was successfully applied to a pharmacokinetic study of phosphocreatine in children (six cases) with viral myocarditis of children after intravenous infusion of 2 g of the test drug. The pharmacokinetc parameters of phosphocreatine/creatine were as follows: t1/2 0.24/0.83 h, Tmax 0.49/0.55 h, Cmax 47.34/59.29 µg/mL, AUClast 17.07/59.63 h µg/mL, AUCinf 17.16/79.01 h µg/mL and MRT 0.29/0.67 h.

Value of Raw Rhubarb Solution in the Precaution of Post-endoscopic Retrograde Cholangiopancreatography Pancreatitis in Patients with High-Risk Factors: A Predictive Random Compared Research in One Center.

BACKGROUND AND AIMS: Post-ERCP pancreatitis and hyperamylasemia are common complications of endoscopic retrograde cholangiopancreatography (ERCP), especially in high-risk patients. The aim of this study is to evaluate whether a raw rhubarb solution can reduce the incidence of PEP and post-ERCP hyperamylasemia. METHODS: From October 2012 to October 2013, 2100 patients received ERCP in our Endoscopic Center. Five hundred patients with high-risk factors were enrolled randomly into the raw rhubarb group (RG, 250 cases drank a raw rhubarb soak solution per 3 h until defecation after ERCP) and the control group (CG, 250 cases drank water after ERCP) in the study. The serum amylase concentration was measured. The abdominal pain, purge time and symptoms of patients were observed in the two groups. RESULTS: There were no differences in patient demographics, medical history, ERCP procedure, and patient- and procedure-related high-risk factors between the two groups. PEP incidence was 2% (5/250) in the RG group, which was lower than that in the CG group (7.6%, 19/250) (P < 0.01). The rate of post-ERCP hyperamylasemia was 5.2% (13/250) and 16.8% (42/250) in the RG group and CG group, respectively. The incidence of hyperamylasemia in the RG group was significantly lower than that in the CG group (P < 0.01). The incidence of abdominal pain 24 h after ERCP in the RG group was lower than that in the CG group (P < 0.01). No side effects were observed for raw rhubarb solution. CONCLUSIONS: A raw rhubarb solution is safe and effective in preventing the incidence of PEP and hyperamylasemia in high-risk patients.

CircTHSD4 promotes the malignancy and docetaxel (DTX) resistance in prostate cancer by regulating miR-203/HMGA2 axis.

Objective: Circular ribose nucleic acids (circRNAs) are implicated in tumor progression and drug resistance of prostate cancer (PCa). The current work explored the function of circ_0005203 (circTHSD4) in the malignancy and docetaxel (DTX) resistance of PCa. Methods: circTHSD4 expression within PCa as well as matched non-carcinoma samples was measured through real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In addition, a subcellular fraction assay was conducted to determine circTHSD4 subcellular localization within PCa cells. In addition, we performed a Western blot (WB) assay to detect high-mobility-group A2 protein (HMGA2) levels. Besides, functional associations of two molecules were investigated through dual luciferase reporter assay. Cell Counting Kit (CCK)-8, colony formation together with Transwell assay was conducted to assess malignant phenotypes of PCa cells, whereas flow cytometry was performed to determine cell apoptosis. Furthermore, a xenograft mouse model was constructed to verify the effect of circTHSD4 on the carcinogenesis of PCa cells. Results: According to RT-qPCR results, circTHSD4 was up-regulated within PCa tissues and cells, which predicted the dismal prognostic outcome of PCa cases. circTHSD4 silencing within PCa cells markedly suppressed cell growth, migration, and colony formation. circTHSD4 silencing remarkably elevated PCa cell apoptosis and carcinogenesis within the xenograft model. Further, circTHSD4 silencing enhanced docetaxel (DTX) sensitivity in PCa cells. Furthermore, we demonstrated that circTHSD4 modulated the malignancy of PCa cells by regulating HMGA2 expression through sponging miR-203. Conclusion: Together, our findings suggest that circTHSD4 overexpression could promote the malignant phenotype and DTX resistance in PCa through the regulation of the miR-203/HMGA2 axis.

Influence of natural organic matter on the aggregation dynamics of biochar colloids derived from various feedstocks.

Abundant biochar colloids (BCs) produced from a wide range of feedstocks, resulting from forest fires, agricultural production, and environmental restoration, exhibit varying aggregation behaviors influenced by feedstock type and natural organic matter. However, the impact of natural organic matter on the colloidal stability of BCs derived from different feedstocks remains poorly understood. In this study, six selected biochars were derived from various feedstocks as follows: sewage sludge (SS), rice husk (RH), oil seed rape straw pellets (OSR), wheat straw pellets (WS), miscanthus straw pellets (MS) and softwood pellets (SW). The colloidal stability of BCs, with the exogenous addition of organic matter, was further determined. The order of critical coagulation concentrations (CCCs) of BCs with the presence of humic acid (HA) was as follows: RH (989.48 mM) < MS (1084.69 mM) < SS (1149.76 mM) < WS (1338.99 mM) < OSR (2402.98 mM) < SW (3151.32 mM). This order was significantly positively correlated with the specific surface area and negatively correlated with the ash content of the bulk biochar. Compared to HA, bovine serum albumin (BSA) more effectively inhibited the aggregation behavior of BCs due to steric hindrance. The initial aggregation rate constant (k) of BCs at 3000 mM NaCl was as follows: MS (0.238 nm/s) > OSR (0.142 nm/s) > WS (0.128 nm/s) > SS (0.126 nm/s) > RH (0.118 nm/s) > SW (0.112 nm/s). The stabilizing effects of BSA on biochar colloids were independent of the physicochemical properties of bulk biochar. In the presence of BSA, a thin layer of protein corona significantly enhanced the stability of biochar colloids, particularly the BCs derived from MS. Our results underscore the importance of considering feedstock resources and natural organic matter type when assessing the aggregation and potential risks of BCs in aquatic systems.

Predicting Kawasaki disease shock syndrome in children.

Background: Kawasaki disease shock syndrome (KDSS) is a critical manifestation of Kawasaki disease (KD). In recent years, a logistic regression prediction model has been widely used to predict the occurrence probability of various diseases. This study aimed to investigate the clinical characteristics of children with KD and develop and validate an individualized logistic regression model for predicting KDSS among children with KD. Methods: The clinical data of children diagnosed with KDSS and hospitalized between January 2021 and December 2023 were retrospectively analyzed. The best predictors were selected by logistic regression and lasso regression analyses. A logistic regression model was built of the training set (n = 162) to predict the occurrence of KDSS. The model prediction was further performed by logistic regression. A receiver operating characteristic curve was used to evaluate the performance of the logistic regression model. We built a nomogram model by visualizing the calibration curve using a 1000 bootstrap resampling program. The model was validated using an independent validation set (n = 68). Results: In the univariate analysis, among the 24 variables that differed significantly between the KDSS and KD groups, further logistic and Lasso regression analyses found that five variables were independently related to KDSS: rash, brain natriuretic peptide, serum Na, serum P, and aspartate aminotransferase. A logistic regression model was established of the training set (area under the receiver operating characteristic curve, 0.979; sensitivity=96.2%; specificity=97.2%). The calibration curve showed good consistency between the predicted values of the logistic regression model and the actual observed values in the training and validation sets. Conclusion: Here we established a feasible and highly accurate logistic regression model to predict the occurrence of KDSS, which will enable its early identification.

Risk factors and an early predictive model for Kawasaki disease shock syndrome in Chinese children.

BACKGROUND: Kawasaki disease shock syndrome (KDSS), though rare, has increased risk for cardiovascular complications. Early diagnosis is crucial to improve the prognosis of KDSS patients. Our study aimed to identify risk factors and construct a predictive model for KDSS. METHODS: This case-control study was conducted from June, 2015 to July, 2023 in two children's hospitals in China. Children initially diagnosed with KDSS and children with Kawasaki disease (KD) without shock were matched at a ratio of 1:4 by using the propensity score method. Laboratory results obtained prior to shock syndrome and treatment with intravenous immunoglobulin were recorded to predict the onset of KDSS. Univariable logistic regression and forward stepwise logistic regression were used to select significant and independent risk factors associated with KDSS. RESULTS: After matching by age and gender, 73 KDSS and 292 KD patients without shock formed the development dataset; 40 KDSS and 160 KD patients without shock formed the validation dataset. Interleukin-10 (IL-10) > reference value, platelet counts (PLT) < 260 × 109/L, C-reactive protein (CRP) > 80 mg/ml, procalcitonin (PCT) > 1ng/ml, and albumin (Alb) < 35 g/L were independent risk factors for KDSS. The nomogram model including the above five indicators had area under the curves (AUCs) of 0.91(95% CI: 0.87-0.94) and 0.90 (95% CI: 0.71-0.86) in the development and validation datasets, with a specificity and sensitivity of 80% and 86%, 66% and 77%, respectively. Calibration curves showed good predictive accuracy of the nomogram. Decision curve analyses revealed the predictive model has application value. CONCLUSIONS: This study identified IL-10, PLT, CRP, PCT and Alb as risk factors for KDSS. The nomogram model can effectively predict the occurrence of KDSS in Chinese children. It will facilitate pediatricians in early diagnosis, which is essential to the prevention of cardiovascular complications.

Efficacy and safety of intravitreal injection of conbercept for moderate to severe nonproliferative diabetic retinopathy.

Purpose: This study aimed to assess the effectiveness and safety of intravitreal injection of conbercept (IVC) in treating moderate to severe nonproliferative diabetic retinopathy (NPDR), with or without accompanying diabetic macular edema. Methods: In this longitudinal retrospective study, 35 patients (50 eyes) with moderate to severe NPDR and Diabetic Retinopathy Severity Scale (DRSS) scores between 43 and 53 were treated at the Department of Ophthalmology, First Affiliated Hospital of Kunming Medical University, from October 2018 to January 2023. Treatment protocol included three monthly IVC injections followed by a pro re nata (PRN) regimen over a two-year follow-up period. Outcome measures were best-corrected visual acuity (BCVA), intraocular pressure, central macular thickness (CMT), extent of hard exudate (HE), and changes in DRSS scores. DRSS scores before and after treatment were analyzed using the Wilcoxon rank-sum test. Both systemic and ocular adverse events were meticulously documented to ascertain safety. Results: From baseline to the final follow-up, the mean BCVA improved from 0.41 ± 0.39 to 0.23 ± 0.20 logMAR (p<0.05). The mean CMT decreased from 306.22 ± 77.40 to 297.97 ± 88.15 µm (p = 0.385). At 24 months, DRSS scores improved by ≥1 stage in 40 eyes (80%), ≥ 2 stages in 28 eyes (56%), ≥3 stages in 10 eyes (20%), and remained stable in 6 eyes (12%). The DRSS scores at each follow-up interval demonstrated statistically significant improvement from baseline (p<0.05). In 15 of 27 eyes (55.56%) with diabetic macular edema (DME), there was a significant reduction in the mean area of HE from baseline (p<0.05). No serious systemic adverse events were observed. Conclusion: IVC is an effective and safe treatment for moderate to severe NPDR, demonstrating significant improvements in DRSS scores.