Integrative clinical and preclinical studies identify FerroTerminator1 as a potent therapeutic drug for MASH.

The complex etiological factors associated with metabolic dysfunction-associated fatty liver disease (MAFLD), including perturbed iron homeostasis, and the unclear nature by which they contribute to disease progression have resulted in a limited number of effective therapeutic interventions. Here, we report that patients with metabolic dysfunction-associated steatohepatitis (MASH), a pathological subtype of MAFLD, exhibit excess hepatic iron and that it has a strong positive correlation with disease progression. FerroTerminator1 (FOT1) effectively reverses liver injury across multiple MASH models without notable toxic side effects compared with clinically approved iron chelators. Mechanistically, our multi-omics analyses reveal that FOT1 concurrently inhibits hepatic iron accumulation and c-Myc-Acsl4-triggered ferroptosis in various MASH models. Furthermore, MAFLD cohort studies suggest that serum ferritin levels might serve as a predictive biomarker for FOT1-based therapy in MASH. These findings provide compelling evidence to support FOT1 as a promising novel therapeutic option for all stages of MAFLD and for future clinical trials.

Fight or flee, a vital choice for Clostridioides difficile.

Clostridioides difficile is a leading cause of healthcare-associated infections, causing billions of economic losses every year. Its symptoms range from mild diarrhea to life-threatening damage to the colon. Transmission and recurrence of C. difficile infection (CDI) are mediated by the metabolically dormant spores, while the virulence of C. difficile is mainly due to the two large clostridial toxins, TcdA and TcdB. Producing toxins or forming spores are two different strategies for C. difficile to cope with harsh environmental conditions. It is of great significance to understand the molecular mechanisms for C. difficile to skew to either of the cellular processes. Here, we summarize the current understanding of the regulation and connections between toxin production and sporulation in C. difficile and further discuss the potential solutions for yet-to-be-answered questions.

Influence of Supercritical CO2 Fracturing Fluid on the Permeability of Shale Reservoir and Mechanism Analysis.

Reduction of the reservoir permeability during supercritical CO2 fracturing caused significant reservoir damage, which directly affects the crude oil recovery rate. This investigation explored a novel thickener for supercritical CO2 fracturing fluid, this CO2 thickener not only effectively improves the viscosity and rheological properties of CO2 fracturing fluid but also contributes to reduce reservoir damage and improve permeability. The research results indicated that the synthesized CO2 thickener (3 wt %) can increase the apparent viscosity of supercritical CO2 fracturing fluid to 7 mPa·s, and a 9% matrix permeability damage rate and a 0.5 mD permeability decrease value are shown in a 3% CO2 fracturing fluid. However, 3 wt % of commercial CO2 thickener only increases the apparent viscosity of supercritical CO2 fracturing fluid to 3 mPa·s, while the reservoir damage rate increases to 13%. Two thickeners exhibit completely different damage capabilities to the reservoir, and the synthesized CO2 thickener shows excellent characteristics of reducing reservoir permeability and is also conducive to protecting shale reservoirs. Furthermore, supercritical CO2 fracturing fluid containing synthetic thickeners has better temperature and shear resistance compared with commercial thickeners. This may be because the synthesized thickener and the micro grid formed by supercritical CO2 reduce the adsorption in shale crevices, but a large amount of commercial thickeners can adsorb on the surface of shale.

Signs of front-line healthcare professionals' information anxiety during the COVID-19 pandemic: Grounded theory study in a Wuhan hospital.

AIM: Being front-line healthcare professionals is associated with possible severe information anxiety during the COVID-19 pandemic. Investigating signs of information anxiety is the first and key step of its targeted medical intervention. This study aims to explore the signs of front-line healthcare professionals' information anxiety during the COVID-19 pandemic. DESIGN: This study is qualitative research. Grounded theory was used to classify information anxiety signs of front-line healthcare professionals. METHODS: Twenty-four front-line healthcare professionals from a general hospital with over 5000 beds in Wuhan were recruited to participate in semi-structured interviews. According to the frequency and frequency variation of signs appearing in interviews, the trends of signs during the virus encounter, lockdown, flattening and second wave were compared. Based on the interviews, those signs that were conceptually related to each other were extracted to construct a conceptual model. RESULTS: Psychological signs (emotion, worry, doubt, caution, hope), physical signs (insomnia, inattention, memory loss, appetite decreased) and behavioural signs (panic buying of goods, be at a loss, pay attention to relevant information, change habits) could be generalized from 13 subcategories of information anxiety signs. Psychological signs were the most in every period of the pandemic. Furthermore, psychological signs decreased significantly during lockdown, while behavioural and physical signs increased. Finally, severe psychological and behavioural signs were associated with physical signs.

Upper limb motor assessment for stroke with force, muscle activation and interhemispheric balance indices based on sEMG and fNIRS.

Introduction: Upper limb rehabilitation assessment plays a pivotal role in the recovery process of stroke patients. The current clinical assessment tools often rely on subjective judgments of healthcare professionals. Some existing research studies have utilized physiological signals for quantitative assessments. However, most studies used single index to assess the motor functions of upper limb. The fusion of surface electromyography (sEMG) and functional near-infrared spectroscopy (fNIRS) presents an innovative approach, offering simultaneous insights into the central and peripheral nervous systems. Methods: We concurrently collected sEMG signals and brain hemodynamic signals during bilateral elbow flexion in 15 stroke patients with subacute and chronic stages and 15 healthy control subjects. The sEMG signals were analyzed to obtain muscle synergy based indexes including synergy stability index (SSI), closeness of individual vector (CV) and closeness of time profile (CT). The fNIRS signals were calculated to extract laterality index (LI). Results: The primary findings were that CV, SSI and LI in posterior motor cortex (PMC) and primary motor cortex (M1) on the affected hemisphere of stroke patients were significantly lower than those in the control group (p < 0.05). Moreover, CV, SSI and LI in PMC were also significantly different between affected and unaffected upper limb movements (p < 0.05). Furthermore, a linear regression model was used to predict the value of the Fugl-Meyer score of upper limb (FMul) (R2 = 0.860, p < 0.001). Discussion: This study established a linear regression model using force, CV, and LI features to predict FMul scale values, which suggests that the combination of force, sEMG and fNIRS hold promise as a novel method for assessing stroke rehabilitation.

The role of interleukin-20 in liver disease: Functions, mechanisms and clinical applications.

Liver disease is a severe public health concern worldwide. There is a close relationship between the liver and cytokines, and liver inflammation from a variety of causes leads to the release and activation of cytokines. The functions of cytokines are complex and variable, and are closely related to their cellular origin, target molecules and mode of action. Interleukin (IL)-20 has been studied as a pro-inflammatory cytokine that is expressed and regulated in some diseases. Furthermore, accumulating evidences has shown that IL-20 is highly expressed in clinical samples from patients with liver disease, promoting the production of pro-inflammatory molecules involved in liver disease progression, and antagonists of IL-20 can effectively inhibit liver injury and produce protective effects. This review highlights the potential of targeting IL-20 in liver diseases, elucidates the potential mechanisms of IL-20 inducing liver injury, and suggests multiple viable strategies to mitigate the pro-inflammatory response to IL-20. Genomic CRISPR/Cas9-based screens may be a feasible way to further explore the signaling pathways and regulation of IL-20 in liver diseases. Nanovector systems targeting IL-20 offer new possibilities for the treatment and prevention of liver diseases.

Identification of a hemorrhagic determinant in Clostridioides difficile TcdA and Paeniclostridium sordellii TcsH.

Paeniclostridium sordellii hemorrhagic toxin (TcsH) and Clostridioides difficile toxin A (TcdA) are two major members of the large clostridial toxin (LCT) family. These two toxins share ~87% similarity and are known to cause severe hemorrhagic pathology in animals. Yet, the pathogenesis of their hemorrhagic toxicity has been mysterious for decades. Here, we examined the liver injury after systemic exposure to different LCTs and found that only TcsH and TcdA induce overt hepatic hemorrhage. By investigating the chimeric and truncated toxins, we demonstrated that the enzymatic domain of TcsH alone is not sufficient to determine its potent hepatic hemorrhagic toxicity in mice. Likewise, the combined repetitive oligopeptide (CROP) domain of TcsH/TcdA alone also failed to explain their strong hemorrhagic activity in mice. Lastly, we showed that disrupting the first two short repeats of CROPs in TcsH and TcdA impaired hemorrhagic toxicity without causing overt changes in cytotoxicity and lethality. These findings lead to a deeper understanding of toxin-induced hemorrhage and the pathogenesis of LCTs and could be insightful in developing therapeutic avenues against clostridial infections. IMPORTANCE: Paeniclostridium sordellii and Clostridioides difficile infections often cause hemorrhage in the affected tissues and organs, which is mainly attributed to their hemorrhagic toxins, TcsH and TcdA. In this study, we demonstrate that TcsH and TcdA, but not other related toxins. including Clostridioides difficile toxin B and TcsL, induce severe hepatic hemorrhage in mice. We further determine that a small region in TcsH and TcdA is critical for the hemorrhagic toxicity but not cytotoxicity or lethality of these toxins. Based on these results, we propose that the hemorrhagic toxicity of TcsH and TcdA is due to an uncharacterized mechanism, such as the presence of an unknown receptor, and future studies to identify the interactive host factors are warranted.

Pore structure characterization and its influence on aqueous phase trapping damage in tight gas sandstone reservoirs.

Aqueous phase trapping (APT), which is one of the most prominent damages, seriously restricts the natural gas production in tight gas sandstone with low permeability. Pore size and microscopic pore structures are the most important factors to determine the water blocking damage. In this paper, 9 core samples from tight gas sandstone with various physical properties were employed, and the pore size distribution (PSD) of the core samples were investigated by high pressure mercury intrusion tests (HPMI). Results showed that the porosity of core samples ranges from 5.68% to 13.7%, and the permeability ranges from 0.00456 to 7.86 mD, which is a typical tight reservoir with strong heterogeneity. According to the HPMI capillary curve, the cores can be divided into two types: Type I and Type II, and the pore sizes of type I are larger than that of type II. Fractal distributions were obtained using HPMI data to further determine the pore structure characteristics of tight reservoirs. The pore structures of tight sandstones display the multifractal fractal feature: D1 corresponding to macro-pores, and D2 corresponding to fractal dimension of micro-pores. Furthermore, APT damage was determined by the permeability recovery ratios (Kr) after gas flooding tests. The correlation of Kr and PSD and fractal dimensions were jointly analyzed in tight gas sandstone. Although positive correlations between pore size parameters and the permeability recovery ratios were observed with relatively weak correlations, for those core samples with very close permeability, pore size parameters (both permeability and PSD) is inadequate in clarifying this damage. The fractal dimension can well describe the complexity and heterogeneity of flow channels in pores, which can become the determining factor to distinguish the flow capacity of tight sandstone. The D2 for samples of type I and type II exhibited a good negative relation with Kr with a correlation coefficient of 0.9878 and 0.7723, respectively. The significance of this finding is that for tight gas sandstone, fractal dimensions, especially the small pore fractal dimension (D2), can be used to predict the possible APT damage very well.

Multi-scale 3D-CRU for EEG emotion recognition.

In this paper, we propose a novel multi-scale 3D-CRU model, with the goal of extracting more discriminative emotion feature from EEG signals. By concurrently exploiting the relative electrode locations and different frequency subbands of EEG signals, a three-dimensional feature representation is reconstructed wherein the Delta (δ) frequency pattern is included. We employ a multi-scale approach, termed 3D-CRU, to concurrently extract frequency and spatial features at varying levels of granularity within each time segment. In the proposed 3D-CRU, we introduce a multi-scale 3D Convolutional Neural Network (3D-CNN) to effectively capture discriminative information embedded within the 3D feature representation. To model the temporal dynamics across consecutive time segments, we incorporate a Gated Recurrent Unit (GRU) module to extract temporal representations from the time series of combined frequency-spatial features. Ultimately, the 3D-CRU model yields a global feature representation, encompassing comprehensive information across time, frequency, and spatial domains. Numerous experimental assessments conducted on publicly available DEAP and SEED databases provide empirical evidence supporting the enhanced performance of our proposed model in the domain of emotion recognition. These findings underscore the efficacy of the features extracted by the proposed multi-scale 3D-GRU model, particularly with the incorporation of the Delta (δ) frequency pattern. Specifically, on the DEAP dataset, the accuracy of Valence and Arousal are 93.12% and 94.31%, respectively, while on the SEED dataset, the accuracy is 92.25%.

Optimizing fluconazole-embedded transfersomal gel for enhanced antifungal activity and compatibility studies.

Fungal infections are of major concern all over the globe, and fluconazole is the most prevalently used drug to treat it. The goal of this research work was to formulate a fluconazole-embedded transfersomal gel for the treatment of fungal infections. A compatibility study between fluconazole and soya lecithin was performed by differential scanning calorimetry (DSC). Transfersomes were formulated by a thin-film hydration technique using soya lecithin and Span 80. A central composite design was adopted to prepare different formulations. Soya lecithin and Span 80 were chosen as independent variables, and the effect of these variables was studied on in vitro drug diffusion. Formulations were evaluated for entrapment efficiency and in vitro drug diffusion. The results of in vitro drug diffusion were analyzed using the analysis of variance (ANOVA) test. Optimized formulation was prepared based on the overlay plot and evaluated by scanning electron microscopy, DSC, vesicle size, polydispersity index (PDI), zeta potential, and in vitro drug diffusion studies. An optimized formulation was loaded into xanthan gum gel base and evaluated for pH, viscosity, in vitro and ex vivo drug diffusion, and antifungal activity. DSC studies revealed compatibility between fluconazole and soya lecithin. Entrapment efficiency and in vitro drug diffusion of various formulations ranged between 89.92% ± 0.20% to 97.28% ± 0.42% and 64% ± 1.56% to 85% ± 2.05%, respectively. A positive correlation was observed between in vitro drug diffusion and Span 80; conversely, a negative correlation was noted with soya lecithin. Entrapment efficiency, particle size, zeta potential, PDI, and drug diffusion of optimized formulation were 95.0% ± 2.2%, 397 ± 2 nm, -38 ± 5 mV, 0.43%, and 81 % ± 2%, respectively. SEM images showed well-distributed spherical-shaped transfersomes. In vitro, ex vivo drug diffusion and antifungal studies were conclusive of better diffusion and enhanced antifungal potential fluconazole in transfersomal formulation.

Glycated Walnut Meal Peptide-Calcium Chelates: Preparation, Characterization, and Stability.

Finding stable and bioavailable calcium supplements is crucial for addressing calcium deficiency. In this study, glycated peptide-calcium chelates (WMPHs-COS-Ca) were prepared from walnut meal protein hydrolysates (WMPHs) and chitosan oligosaccharides (COSs) through the Maillard reaction, and the structural properties and stability of the WMPHs-COS-Ca were characterized. The results showed that WMPHs and COSs exhibited high binding affinities, with a glycation degree of 64.82%. After glycation, Asp, Lys, and Arg decreased by 2.07%, 0.46%, and 1.06%, respectively, which indicated that these three amino acids are involved in the Maillard reaction. In addition, compared with the WMPHs, the emulsifying ability and emulsion stability of the WMPHs-COS increased by 10.16 mg2/g and 52.73 min, respectively, suggesting that WMPHs-COS have better processing characteristics. After chelation with calcium ions, the calcium chelation rate of peptides with molecular weights less than 1 kDa was the highest (64.88%), and the optimized preparation conditions were 5:1 w/w for WMPH-COS/CaCl2s, with a temperature of 50 °C, a chelation time of 50 min, and a pH of 7.0. Scanning electron microscopy showed that the "bridging role" of WMPHs-COS changed to a loose structure. UV-vis spectroscopy and Fourier transform infrared spectrometry results indicated that the amino nitrogen atoms, carboxyl oxygen atoms, and carbon oxygen atoms in WMPHs-COS chelated with calcium ions, forming WMPHs-COS-Ca. Moreover, WMPHs-COS-Ca was relatively stable at high temperatures and under acidic and alkaline environmental and digestion conditions in the gastrointestinal tract, indicating that WMPHs-COS-Ca have a greater degree of bioavailability.

NUP85 alleviates lipid metabolism and inflammation by regulating PI3K/AKT signaling pathway in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is one of the common causes of chronic liver disease in the world. The problem of NAFLD had become increasingly prominent. However, its pathogenesis is still indistinct. As we all know, NAFLD begins with the accumulation of triglyceride (TG), leading to fatty degeneration, inflammation and other liver tissues damage. Notably, structure of nucleoporin 85 (NUP85) is related to lipid metabolism and inflammation of liver diseases. In this study, the results of researches indicated that NUP85 played a critical role in NAFLD. Firstly, the expression level of NUP85 in methionine-choline-deficient (MCD)-induced mice increased distinctly, as well as the levels of fat disorder and inflammation. On the contrary, knockdown of NUP85 had the opposite effects. In vitro, AML-12 cells were stimulated with 2 mm free fatty acids (FFA) for 24 h. Results also proved that NUP85 significantly increased in model group, and increased lipid accumulation and inflammation level. Besides, NUP85 protein could interact with C-C motif chemokine receptor 2 (CCR2). Furthermore, when NUP85 protein expressed at an extremely low level, the expression level of CCR2 protein also decreased, accompanied with an inhibition of phosphorylation of phosphoinositol-3 kinase (PI3K)-protein kinase B (AKT) signaling pathway. What is more, trans isomer (ISRIB), a targeted inhibitor of NUP85, could alleviate NAFLD. In summary, our findings suggested that NUP85 functions as an important regulator in NAFLD through modulation of CCR2.

Air Pollutants and Mortality Risk in Patients with Aortic Dissection: Evidence from a Clinical Cohort, Single-Cell Sequencing, and Proteomics.

We aimed to evaluate the association between air pollutants and mortality risk in patients with acute aortic dissection (AAD) in a longitudinal cohort and to explore the potential mechanisms of adverse prognosis induced by fine particulate matter (PM2.5). Air pollutants data, including PM2.5, PM10.0, nitrogen dioxide (NO2), carbon monoxide (CO), sulfur dioxide (SO2), and ozone (O3), were collected from official monitoring stations, and multivariable Cox regression models were applied. Single-cell sequencing and proteomics of aortic tissue were conducted to explore the potential mechanisms. In total, 1,267 patients with AAD were included. Exposure to higher concentrations of air pollutants was independently associated with an increased mortality risk. The high-PM2.5 group carried approximately 2 times increased mortality risk. There were linear associations of PM10, NO2, CO, and SO2 exposures with long-term mortality risk. Single-cell sequencing revealed an increase in mast cells in aortic tissue in the high-PM2.5 exposure group. Enrichment analysis of the differentially expressed genes identified the inflammatory response as one of the main pathways, with IL-17 and TNF signaling pathways being among the top pathways. Analysis of proteomics also identified these pathways. This study suggests that exposure to higher PM2.5, PM10, NO2, CO, and SO2 are associated with increased mortality risk in patients with AAD. PM2.5-related activation and degranulation of mast cells may be involved in this process.

Molecular basis of TMPRSS2 recognition by Paeniclostridium sordellii hemorrhagic toxin.

Hemorrhagic toxin (TcsH) is a major virulence factor produced by Paeniclostridium sordellii, which is a non-negligible threat to women undergoing childbirth or abortions. Recently, Transmembrane Serine Protease 2 (TMPRSS2) was identified as a host receptor of TcsH. Here, we show the cryo-EM structures of the TcsH-TMPRSS2 complex and uncover that TcsH binds to the serine protease domain (SPD) of TMPRSS2 through the CROP unit-VI. This receptor binding mode is unique among LCTs. Five top surface loops of TMPRSS2SPD, which also determine the protease substrate specificity, constitute the structural determinants recognized by TcsH. The binding of TcsH inhibits the proteolytic activity of TMPRSS2, whereas its implication in disease manifestations remains unclear. We further show that mutations selectively disrupting TMPRSS2-binding reduce TcsH toxicity in the intestinal epithelium of the female mice. These findings together shed light on the distinct molecular basis of TcsH-TMPRSS2 interactions, which expands our knowledge of host recognition mechanisms employed by LCTs and provides novel targets for developing therapeutics against P. sordellii infections.

A case of hypertrophic cardiomyopathy with previous aortic valve replacement.

We describe a 45-year-old patient who was diagnosed with hypertrophic obstructive cardiomyopathy (HOCM) after the aortic valve replacement surgery. Enlarged left atria, thickened ventricular septum, left ventricular outflow tract stenosis, moderate mitral regurgitation and mild tricuspid regurgitation in the echocardiography were found. We offered the patient the new minimally invasive treatment modality: percutaneous intra-myocardial septal radiofrequency ablation (PIMSRA). We demonstrate the safety and efficacy with pictures. One month after surgery, the patient recovered well with improved symptoms of chest tightness, and no LVOT obstruction or arrhythmia.

Exploring the Effect of Milk Fat on Fermented Milk Flavor Based on Gas Chromatography-Ion Mobility Spectrometry (GC-IMS) and Multivariate Statistical Analysis.

Milk fat is a premium nutritional health product, yet there is a lack of high-fat dairy products for daily consumption in the current market. This study investigated the influence of different milk fat contents on the physicochemical and textural properties of fermented milk. The research revealed that an increase in milkfat content significantly improved the water-holding capacity, syneresis, color, hardness, springiness, gumminess, and chewiness of fermented milk, while showing minimal changes in pH and total titratable acidity. Response surface analysis indicated that fermented milk with 25% milk fat, 2.5% inoculum, a fermentation time of 16 h, and a fermentation temperature of 30 °C exhibited the highest overall acceptability. Using GC-IMS technology, 36 volatile compounds were identified, with an increase in milk fat content leading to elevated levels of ketone compounds, and 14 compounds were defined as key aroma compounds (ROAV > 1). Electronic nose distinguished samples with different milk fat contents. The results demonstrate that an increase in milk fat content enhances the physicochemical and flavor attributes of fermented milk. This work provides theoretical references for the production and development of high-fat fermented milk.

Effect of succinylation-assisted glycosylation on the structural characteristics, emulsifying, and gel properties of walnut glutenin.

In this study, we examined the effects of various sodium alginate (ALG) concentrations (0.2%-0.8%) on the functional and physicochemical characteristics of succinylated walnut glutenin (GLU-SA). The results showed that acylation decreased the particle size and zeta potential of walnut glutenin (GLU) by 122- and 0.27-fold, respectively. In addition, the protein structure unfolded, providing conditions for glycosylation. After GLU-SA was combined with ALG, the surface hydrophobicity decreased and the net negative charge and disulfide bond content increased. The protein structure was analyzed by FTIR, Endogenous fluorescence spectroscopy, and SEM, and ALG prompted GLU-SA cross-linking to form a stable three-dimensional network structure. The results indicated that dual modification improved the functional properties of the complex, especially its potential protein gel and emulsifying properties. This research provide theoretical support and a technical reference for expanding the application of GLU in the processing of protein and oil products.

Revealing the Development Patterns of the Mandibular Glands of Apis mellifera carnica Based on Transcriptomics and Morphology.

The mandibular gland in worker bees synthesizes and secretes the organic acids present in royal jelly, and its development directly affects yield and quality. Therefore, we aimed to analyze the differences in morphology and gene expression in the mandibular glands of Apis mellifera carnica worker bees of different ages (3, 6, 9, 12, and 16 d). We dissected their mandibular glands and performed morphological and transcriptomic analyses to investigate the development of the mandibular gland and the molecular regulatory mechanisms involved in royal jelly secretion. Microscopy revealed that mandibular gland development is likely completed in the early stages. There were no significant differences in the structural morphology or organelles involved in the secretion of royal jelly at different ages. Transcriptomics revealed a total of 1554 differentially expressed genes, which were mainly involved in fat metabolism, lipid transport, and energy metabolism. The extracellular matrix-receptor interaction pathway was significantly enriched and contributed to the royal jelly secretion process. These results elucidate the genetic basis of the role of the mandibular gland in royal jelly secretion in A. mellifera and provide a reference for the genetic improvement of bees with high royal jelly production in the future.

Effects of UV/H2O2 degradation on Moringa oleifera Lam. leaves polysaccharides: Composition, in vitro fermentation and prebiotic properties on gut microorganisms.

Moringa oleifera Lam. leaves are a new raw food material rich in polysaccharides. These polysaccharides exhibit various biological properties, including antioxidant, hypoglycemic and immunoregulatory effects. However, the use of Moringa oleifera Lam. leaves polysaccharides (MOLP) may be limited by their large molecular weight (MW) and presence of numerous impurities, such as pigments. Research has indicated that degraded polysaccharides usually exhibit high biological activity because of changes in physical structure and chemical properties. In this study, we focused on the extraction of a degraded-modified fraction from MOLP using the Ultraviolet/ Hydrogen peroxide (UV/H2O2) method. Specifically, the physicochemical properties and glycosidic bond composition of a particular fraction (UV/H2O2 degraded Moringa oleifera Lam. leaves polysaccharides in 3 h called DMOLP-3) were investigated. In addition, in vitro simulated digestion experiments showed that DMOLP-3 was only partially degraded during gastrointestinal digestion, indicating that DMOLP-3 can be utilised by gut microorganisms. Furthermore, the prebiotic properties of MOLP and DMOLP-3 was studied using an in vitro faecal fermentation model. The results indicated that compared with MOLP, DMOLP-3 led to a decrease in both the colour and MW of the polysaccharides. In addition, this model exhibited enhanced solubility and antioxidant capabilities while also influencing the surface morphology. Moreover, DMOLP-3 can facilitate the proliferation of advantageous microorganisms and enhance the synthesis of short-chain fatty acids (SCFAs). These results provide valuable insights into the utilization of bioactive components in Moringa oleifera Lam. leaves for the intestinal health.

A case report of adolescent myofibrillar myopathy due to a de novo R406W pathogenic variant in desmin with symptoms of "hypertrophic cardiomyopathy".

Objective: Myofibrillar myopathies (MFM) are a group of sporadic and inherited progressive skeletal muscle disorders that can lead to physical disability and premature death. To date, pathogenic variants in different genes are associated with MFM. MFM induced by variants in the Desmin (DES) gene is the most common subtype of MFM. Case presentation: A 15-year-old boy with MFM was described, whose symptoms first presented as cardiac symptoms. Enlarged right and left atria, thickened ventricular septal (IVS) and mild mitral (MR) and tricuspid regurgitation (TR) in the echocardiography were found. Atrial fibrillation, intermittent atrioventricular (AV) block, ST-T changes in the dynamic electrocardiogram (ECG) were shown. Mild myopathic changes in the electromyographic exam were detected. Ultrastructural analysis found slight Z-line changes and a few small myolysis lesions, but no abnormal inclusion bodies. Genetic testing detected a heterozygous missense variant (c.1216C > T) of DES, and 2 rare variants: TNNI3K (c.1102C > G) and PRDM16 (c.3074G > A). The patient's parents didn't show skeletal and cardiac muscle disorders. DNA sequencing analysis showed no variant of DES was carried by them. Thus, we detected a case of MFM caused by de novo DES variant c.1216C > T/p.Arg406Trp with predominantly myocardial alterations.