The involvement of keratinocytes in pruritus of chronic inflammatory dermatosis.

Frequent itching and incessant scratching are commonly observed in various chronic inflammatory skin conditions, including atopic dermatitis and psoriasis. The persistent and prolonged nature of pruritus can worsen one's quality of life. Keratinocytes (KCs), the predominant cells of the epidermis, have been confirmed to interact with sensory neurons and immune cells and be involved in chronic skin inflammatory diseases associated with pruritus. Initially, KCs and sensory neurons form a unique synapse-like connection within the epidermis, serving as the structural foundation for their interaction. Additionally, several receptors, including toll-like receptors and protease-activated receptor 2, expressed on KCs, become activated in an inflammatory milieu. On the one hand, activated KCs are sources of pro-inflammatory cytokines and neurotrophic factors, such as adenosine triphosphate, thymic stromal lymphopoietin, and nerve growth factor, which directly or indirectly participate in stimulating sensory neurons, thereby contributing to the itch sensations. On the other hand, KCs also function as primary transducers alongside intraepidermal nerve endings, directly initiating pruritic responses. This review summarizes the current literature and highlights the critical role of KCs in the development and persistence of chronic itch in inflammatory skin disorders.

Triggers for the onset and recurrence of psoriasis: a review and update.

Psoriasis is an immune-mediated inflammatory skin disease, involving a complex interplay between genetic and environmental factors. Previous studies have demonstrated that genetic factors play a major role in the pathogenesis of psoriasis. However, non-genetic factors are also necessary to trigger the onset and recurrence of psoriasis in genetically predisposed individuals, which include infections, microbiota dysbiosis of the skin and gut, dysregulated lipid metabolism, dysregulated sex hormones, and mental illness. Psoriasis can also be induced by other environmental triggers, such as skin trauma, unhealthy lifestyles, and medications. Understanding how these triggers play a role in the onset and recurrence of psoriasis provides insights into psoriasis pathogenesis, as well as better clinical administration. In this review, we summarize the triggers for the onset and recurrence of psoriasis and update the current evidence on the underlying mechanism of how these factors elicit the disease. Video Abstract.

Systemic lupus erythematosus combined with Wilson's disease: a case report and literature review.

BACKGROUND: Systemic lupus erythematosus (SLE) and Wilson's disease (WD) are both systemic diseases that can affect multiple organs in the body. The coexistence of SLE and WD is rarely encountered in clinical practice, making it challenging to diagnose. CASE REPORT: We present the case of a 9-year-old girl who initially presented with proteinuria, haematuria, pancytopenia, hypocomplementemia, and positivity for multiple autoantibodies. She was diagnosed with SLE, and her blood biochemistry showed elevated liver enzymes at the time of diagnosis. Despite effective control of her symptoms, her liver enzymes remained elevated during regular follow-up. Laboratory tests revealed decreased serum copper and ceruloplasmin levels, along with elevated urinary copper. Liver biopsy revealed chronic active hepatitis, moderate inflammation, moderate-severe fibrosis, and a trend towards local cirrhosis. Genetic sequencing revealed compound heterozygous mutations in the ATP7B gene, confirming the diagnosis of SLE with WD. The girl received treatment with a high-zinc/low-copper diet, but her liver function did not improve. Upon recommendation following multidisciplinary consultation, she underwent liver transplantation. Unfortunately, she passed away on the fourth day after the surgery. CONCLUSIONS: SLE and WD are diseases that involve multiple systems and organs in the body, and SLE complicated with WD is rarely encountered in the clinic; therefore, it is easy to misdiagnose. Because penicillamine can induce lupus, it is not recommended. Liver transplantation is indicated for patients with liver disease who do not respond to medical treatment with WD. However, further research is needed to determine the optimal timing of liver transplantation for patients with SLE complicated with WD.

Clinical features and genetic analysis of 15 Chinese children with dent disease.

OBJECTIVE:  The clinical characteristics, genetic mutation spectrum, treatment strategies and prognoses of 15 children with Dent disease were retrospectively analyzed to improve pediatricians' awareness of and attention to this disease. METHODS:  We analyzed the clinical and laboratory data of 15 Chinese children with Dent disease who were diagnosed and treated at our hospital between January 2017 and May 2023 and evaluated the expression of the CLCN5 and OCRL1 genes. RESULTS:  All 15 patients were male and complained of proteinuria, and the incidence of low-molecular-weight proteinuria (LMWP) was 100.0% in both Dent disease 1 (DD1) and Dent disease 2 (DD2) patients. The incidence of hypercalciuria was 58.3% (7/12) and 66.7% (2/3) in DD1 and DD2 patients, respectively. Nephrocalcinosis and nephrolithiasis were found in 16.7% (2/12) and 8.3% (1/12) of DD1 patients, respectively. Renal biopsy revealed focal segmental glomerulosclerosis (FSGS) in 1 patient, minimal change lesion in 5 patients, and small focal acute tubular injury in 1 patient. A total of 11 mutations in the CLCN5 gene were detected, including 3 missense mutations (25.0%, c.1756C > T, c.1166T > G, and c.1618G > A), 5 frameshift mutations (41.7%, c.407delT, c.1702_c.1703insC, c.137delC, c.665_666delGGinsC, and c.2200delG), and 3 nonsense mutations (25.0%, c.776G > A, c.1609C > T, and c.1152G > A). There was no significant difference in age or clinical phenotype among patients with different mutation types (p > 0.05). All three mutations in the OCRL1 gene were missense mutations (c.1477C > T, c.952C > T, and c.198A > G). CONCLUSION:  Pediatric Dent disease is often misdiagnosed. Protein electrophoresis and genetic testing can help to provide an early and correct diagnosis.

A novel mutation of the RPGRIP1L gene in a Chinese boy with Joubert syndrome with oculorenal involvement.

BACKGROUND: Joubert syndrome (JS) is a rare genetically heterogeneous primary ciliopathy characterized by a pathognomonic cerebellar and brainstem malformation, the "molar tooth sign", and variable organ involvement (such as eye, kidney, liver, and skeleton). Here, we present a case of JS in a Chinese boy. CASE PRESENTATION: An 11-year-old Chinese boy presented with neonatal asphyxiation and hypoxia, strabismus, subsequent developmental delay, ataxia and end-stage kidney disease (ESKD). Routine blood tests showed severe anemia, increasing blood urea nitrogen and creatinine, elevated parathyroid hormone, hypocalcemia, hypokalemia and metabolic acidosis. Urine tests showed mild proteinuria. Ultrasound showed two small kidneys. Brain magnetic resonance imaging (MRI) showed dysplasia of the cerebellar vermis and extension of the upper cerebellar feet with the "molar tooth sign". Genetic analysis showed novel compound heterozygous mutations in the RPGRIP1L gene [p.L447fs*7(p.Leu447fsTer7) and p.G908V (p.Gly908Val)]. CONCLUSION: In the present study, we identified novel compound heterozygous mutations in the RPGRIP1L gene in a Chinese boy. The clinical and genetic findings of this study will expand the understanding of JS.

Clinical features of children with anti-CFH autoantibody-associated hemolytic uremic syndrome: a report of 8 cases.

OBJECTIVE: To explore the clinical characteristics, treatment protocol and prognosis of children with anti-complement factor H (CFH) autoantibody (Ab)-associated hemolytic uremic syndrome (HUS). METHODS: Clinical data of 8 patients with anti-CFH Ab-associated HUS who were admitted to Shandong Provincial Hospital from January 2011 to December 2020 were collected retrospectively. RESULTS: The age at disease onset ranged between 5.83 and 13.5 years, with a male: female ratio of 1.67:1. The time of onset was distributed from May to June and November to December. Digestive and upper respiratory tract infections were common prodromal infections. Positivity for anti-CFH Ab and reduced C3 levels were observed among all patients. Heterozygous mutation of the CHFR5 gene (c.669del A) and homozygous loss of the CFHR1 gene [loss2(EXON:2-6)] were found in two patients. All patients received early treatment with plasma exchange and corticosteroid therapy. Six patients were given immunosuppressive agents (cyclophosphamide and/or mycophenolate mofetil) for persistent proteinuria. The follow-up period was 12-114 months. Four of 8 patients achieved complete remission, 3 achieved partial remission, and 1 died. Relapse occurred in two patients. CONCLUSION: Children with anti-CFH Ab-associated HUS were mainly school-aged and predominantly male, with onset times of summer and winter. Digestive and upper respiratory tract infections were common prodromal infections. Plasma exchange combined with methylprednisolone pulse therapy in the acute phase and cyclophosphamide or mycophenolate mofetil treatment for maintenance can be utilized in children with anti-CFH Ab-associated HUS if eculizumab is not available.

Trehalose attenuates renal ischemia-reperfusion injury by enhancing autophagy and inhibiting oxidative stress and inflammation.

Renal ischemia-reperfusion (IR) injury is one of the most common acute kidney injuries, but there is still a lack of effective treatment in the clinical setting. Trehalose (Tre), a natural disaccharide, has been demonstrated to protect against oxidative stress, inflammation, and apoptosis. However, whether it could protect against IR-induced renal injury needs to be investigated. In an in vivo experiment, C57BL/6J mice were pretreated with or without Tre (2 g/kg) through a daily single intraperitoneal injection from 3 days before renal IR surgery. Renal function, apoptosis, oxidative stress, and inflammation were analyzed to evaluate kidney injury. In an in vitro experiment, mouse proximal tubular cells were treated with or without Tre under a hypoxia/reoxygenation condition. Western blot analysis, autophagy flux detection, and apoptosis assay were performed to evaluate the level of autophagy and antiapoptotic effect of Tre. The in vivo results showed that the renal damage induced by IR was ameliorated by Tre treatment, as renal histology and renal function were improved and the enhanced protein levels of kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin were blocked. Moreover, autophagy was activated by Tre pretreatment along with inhibition of the IR injury-induced apoptosis, oxidative stress, and inflammation. The in vitro results showed that Tre treatment activated autophagy and protected against hypoxia/reoxygenation-induced tubular cell apoptosis and oxidative stress. Our results demonstrated that Tre protects against IR-induced renal injury, possibly by enhancing autophagy and blocking oxidative stress, inflammation, and apoptosis, suggesting its potential use for the clinical treatment of renal IR injury.

Hierarchical sequence labeling for extracting BEL statements from biomedical literature.

BACKGROUND: Extracting relations between bio-entities from biomedical literature is often a challenging task and also an essential step towards biomedical knowledge expansion. The BioCreative community has organized a shared task to evaluate the robustness of the causal relationship extraction algorithms in Biological Expression Language (BEL) from biomedical literature. METHOD: We first map the sentence-level BEL statements in the BC-V training corpus to the corresponding text segments, thus generating hierarchically tagged training instances. A hierarchical sequence labeling model was afterwards induced from these training instances and applied to the test sentences in order to construct the BEL statements. RESULTS: The experimental results on extracting BEL statements from BioCreative V Track 4 test corpus show that our method achieves promising performance with an overall F-measure of 31.6%. Furthermore, it has the potential to be enhanced by adopting more advanced machine learning approaches. CONCLUSION: We propose a framework for hierarchical relation extraction using hierarchical sequence labeling on the instance-level training corpus derived from the original sentence-level corpus via word alignment. Its main advantage is that we can make full use of the original training corpus to induce the sequence labelers and then apply them to the test corpus.

The effect of process parameters and microstructural changes on a new convenience food - quick-frozen paste-coated mushrooms (Agaricus bisporus).

The technology of quick-freezing paste-coated mushrooms (Agaricus bisporus) was studied and optimized. The best microwave pretreatment condition for 1 cm slices, regarding color protection, was 5.4 W/g, for 55, 55-60 and 60 s for mushrooms with 3, 4 and 5 cm diameter caps respectively. For a batch of paste (668.2-1034.6 g), the process parameters considered were oil content (46.6-63.4 g), water content (381-562.6 g) and flour content (166-334 g) with a constant additional content of 30 g starch, 9 g baking powder, 2.6 g carrageenan, 30 g salt and 3 g pepper. These parameters were investigated using response surface methodology (RSM) with a central composite design. The optimal levels of the major paste components were 300 g flour, 432.5 g water and 50 g oil. The freezing time and sensory acceptability for paste-coated Agaricus bisporus(PCAB) under the optimized conditions were 7.49 min and 6.2 respectively. The freezing curves of PCAB were established at different temperatures and the freezing rates were calculated to find the freezing characteristics. In addition, the cell structure of PCAB, frozen at -75 °C, the lowest freezing temperature, and studied using transmission electron microscopy, was similar in quality to that of fresh Agaricus bisporus. The results suggested that Agaricus bisporus can be quick-frozen with a paste coating to produce an acceptable and nutritious convenience food.

Inhibition of α-amylase digestion by a Lonicera caerulea berry polyphenol starch complex revealed via multi-spectroscopic and molecular dynamics analyses.

Polyphenol-starch complexes exhibit synergistic and beneficial effects on both polyphenols and resistant starches. This study evaluates the inhibitory effects and mechanisms of α-amylase on a Lonicera caerulea berry polyphenol-wheat starch (LPWS) complex following high hydrostatic pressure treatments of 400 MPa for 30 min and 600 MPa for 30 min. The IC50 values for α-amylase inhibition by the complex were 3.61 ± 0.10 mg/mL and 3.42 ± 0.08 mg/mL at a 10 % (w/w) polyphenol content. This interaction was further supported by Fourier-transform infrared spectroscopy and circular dichroism, which confirmed that the alpha helix component of the secondary structure of α-amylase was reduced due to the complex. Multifluorescence spectroscopy revealed that the complex induces changes in the microenvironment of fluorophores surrounding the α-amylase active site. Molecular dynamics simulations and molecular docking revealed that the active site of amylose within the complex becomes enveloped in polyphenol clusters. This wrapping effect reduced the hydrogen bonds between amylose and α-amylase, decreasing from 16 groups to just one group. In summary, the LPWS complex represents a low-digestible carbohydrate food source, thus laying the groundwork for the research and development of functional foods aimed at postprandial hypoglycemic effects.

Effects of dynamic high-pressure microfluidization treatment on the structural, physicochemical, and digestive properties of wheat starch-Lonicera caerulea berry polyphenol complex.

Polyphenol complexes can improve the physicochemical and functional properties of starch. In this study, a wheat starch-Lonicera caerulea berry polyphenol complex (WS-LCBP) was prepared using dynamic high-pressure microfluidization (DHPM). The effects of different DHPM pressures (150 and 250 MPa), number of cycles (1 and 3), and LCBP content (0 %, 6 %, 8 %, and 10 %) on the multiscale structure, physicochemical properties, and in vitro digestibility of WS-LCBP were examined. After a single 250 MPa DHPM cycle, Average particle size and water separation rate of WS were reduced by 42.40 % and 16.67 %, the freeze-thaw stability was significantly improved (P < 0.05), and the resistant starch (RS) content 68.67 % was significantly increased (P < 0.05). WS-LCBP has a V-shaped starch structure, which hinders gelatinization and increases enthalpy. The RS content of the WS-LCBP ranged from 72.46 % to 89.09 %, which was significantly higher (P < 0.05) than that of wheat starch subjected to a single 150 MPa DHPM cycle (36.31 %). Three 250 MPa DHPM cycles were beneficial for the formation of WS-LCBP. However, excessive DHPM treatment pressure and frequency reduced the recombination rate of LCBP and wheat starch. This study provides reference data for the industrial production of nutritionally functional wheat-resistant starch using green technologies.

A mechanistic study of chestnut starch retrogradation and its effects on in vitro starch digestion.

Starch retrogradation is a mechanism that is associated with the quality of starch-based food products. A thorough understanding of chestnut starch retrogradation behavior plays an important role in maintaining the quality of chestnut foods during processing and storage. In this study, we investigated the effects of storage time on the structural properties and in vitro digestibility of gelatinized chestnut starch by using X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, and solid-state 13C nuclear magnetic resonance (NMR). The results showed that the long-range crystallinity and short-range molecular order of retrograded chestnut starch first rapidly increased from 3 h to 3 d and then decreased from 3 d to 7 d, followed by a slight increase from 7 d to 14 d with retrogradation. With the extension of storage time at 4 °C, there were generally obvious increases in single and double helical structures, which were stacked into long-term ordered structure, resulting in increased enthalpy changes as detected by differential scanning calorimetry spectroscopy (DSC) and reduction of the digestion rate of retrograded chestnut starch. Overall, this study may provide important implications for manipulating and improving the quality of chestnut foods.

Soluble Dietary Fiber of Hawthorn Relieves Constipation Induced by Loperamide Hydrochloride by Improving Intestinal Flora and Inflammation, Thereby Regulating the Aquaporin Ion Pathway in Mice.

Dietary fiber can be fermented and utilized by gut microbiota to reshape the gut microbiota, thereby alleviating constipation. This experiment mainly studied the physicochemical functions of hawthorn soluble dietary fiber (HSDF)and its effect and mechanism in alleviating constipation in mice. Forty-five mice were divided into blank control group C, model group M, positive control HS group, low-dose LHSDF group (1 g/kg/bw), and high-dose HHSDF group (2 g/kg/bw). The mice were modeled at a dose of 10 mg/kg/bw of loperamide hydrochloride for 7 days, while the remaining groups were orally administered an equal amount of distilled water and test samples. After continuous gavage for 45 days we performed a bowel movement test, and then continued gavage for 7 days and performed a small intestine propulsion test and indicator testing. The results showed that HSDF is mainly composed of galacturonic acid, belonging to the type I crystal structure, with a loose surface resembling a snowflake, a small molecular weight, and strong water-holding and antioxidant abilities. Animal experiments showed that compared with group M, HSDF significantly upregulated AQP3 and AQP8 by 52.67% and 164.54%, respectively, and downregulated AQP9 protein expression by 45.88%, thereby promoting intestinal peristalsis. It can also alleviate constipation by increasing the levels of excitatory hormones such as MTL, GAS, and SP in the gastrointestinal tract, and reducing the levels of inhibitory hormones such as SS, NO, and MDA. In addition, HSDF can reduce the levels of inflammatory factors such as IL-6 and PL-1 ß, increase the content of various short-chain fatty acids, alleviate intestinal inflammation, maintain intestinal integrity, and promote defecation. It can also promote the growth of probiotics such as Bacteroides, inhibit the growth of harmful bacteria such as Bifidobacterium and Lactobacillus, and alter the diversity of gut microbiota.

Chestnut Shell Polyphenols Inhibit the Growth of Three Food-Spoilage Bacteria by Regulating Key Enzymes of Metabolism.

The microbial contamination of food poses a threat to human health. Chestnut shells, which are byproducts of chestnut processing, contain polyphenols that exert various physiological effects, and thus have the potential to be used in food preservation. This study investigates the bacteriostatic effect and mechanism(s) of the action of chestnut shell polyphenols (CSPs) on three food-spoilage bacteria, namely Bacillus subtilis, Pseudomonas fragi, and Escherichia coli. To this end, the effect of CSPs on the ultrastructure of each bacterium was determined using scanning electron microscopy and transmission electron microscopy. Moreover, gene expression was analyzed using RT-qPCR. Subsequent molecular docking analysis was employed to elucidate the mechanism of action employed by CSPs via the inhibition of key enzymes. Ultrastructure analysis showed that CSPs damaged the bacterial cell wall and increased permeability. At 0.313 mg/mL, CSPs significantly increased the activity of alkaline phosphatase and lactate dehydrogenase, as well as protein leakage (p < 0.05), whereas the activity of the tricarboxylic acid (TCA) cycle enzymes, isocitrate dehydrogenase and α-ketoglutarate dehydrogenase, were inhibited (p < 0.05). The expression levels of the TCA-related genes gltA, icd, sucA, atpA, citA, odhA, IS178_RS16090, and IS178_RS16290 are also significantly downregulated by CSP treatment (p < 0.05). Moreover, CSPs inhibit respiration and energy metabolism, including ATPase activity and adenosine triphosphate (ATP) synthesis (p < 0.05). Molecular docking determined that proanthocyanidins B1 and C1, the main components of CSPs, are responsible for the antibacterial activity. Therefore, as natural antibacterial substances, CSPs have considerable potential for development and application as natural food preservatives.

Umbelliferone attenuates cisplatin-induced acute kidney injury by inhibiting oxidative stress and inflammation via NRF2.

In this study, we investigated the nephroprotective effects of Umbelliferone (UMB) against cisplatin-induced acute kidney injury (AKI). C57BL/6J mice were treated with cisplatin via a single intraperitoneal injection (25 mg/kg) with or without UMB (40 mg/kg/day) by gavage. Renal function, apoptosis, oxidative stress, inflammation, and mitochondrial function were analyzed to evaluate kidney injury. In vitro, human proximal tubule epithelial cells were treated with cisplatin, with or without UMB, for 24 h. Western blotting and immunohistochemistry were performed to explore the mechanisms underlying the nephroprotective effects of UMB. Cisplatin-induced renal dysfunction, including increases in blood urea nitrogen, serum creatinine, and renal tubular injury indices (NGAL and KIM-1), were significantly attenuated by UMB treatment, along with renal phenotypic changes and renal tubular injury, as evidenced by improved renal histology. Moreover, NRF2 was activated by UMB pretreatment, along with the inhibition of oxidative stress and inflammatory response, as evidenced by decreased levels of antioxidant genes and inflammatory cytokines in cisplatin-induced AKI. Our results demonstrate that UMB can protect against cisplatin-induced nephrotoxicity, which is mediated by the NRF2 signaling pathway via antioxidant and anti-inflammatory activities, suggesting the clinical potential of UMB for the treatment of AKI.

Chinese chestnut shell polyphenol extract regulates the JAK2/STAT3 pathway to alleviate high-fat diet-induced, leptin-resistant obesity in mice.

Chinese chestnut shell is a by-product of chestnut food processing and is rich in polyphenols. This study sought to investigate the effect of chestnut shell polyphenol extract (CSP) on weight loss and lipid reduction in a 12-week high-fat diet (HFD)-induced murine obesity model. CSP (300 mg per kg body weight) was administered intragastrically daily. AG490, a JAK2 protein tyrosine kinase inhibitor, was also intraperitoneally injected. The results showed that an HFD induced leptin resistance (LR). Compared to corresponding values in the HFD group, CSP treatment improved blood lipid levels, weight, and leptin levels in obese mice (p < 0.01). Additionally, CSP treatment enhanced enzyme activity by improving total antioxidant capacity, attenuating oxidative stress, and reducing fat droplet accumulation and inflammation in the liver, epididymal, and retroperitoneal adipose tissue. CSP also activated the LEPR-JAK2/STAT3-PTP1B-SOCS-3 signal transduction pathway in hypothalamus tissue and improved LR while regulating the expression of proteins related to lipid metabolism (PPARγ, FAS, and LPL) in white adipose tissue in the retroperitoneal cavity. However, the amelioration of lipid metabolism by CSP was dependent on JAK2. Molecular docking simulation further demonstrated the strong binding affinity of procyanidin C1 (-10.3983297 kcal mol-1) and procyanidin B1 (-9.12686729 kcal mol-1) to the crystal structure of JAK2. These results suggest that CSP may be used to reduce HFD-induced obesity with potential application as a functional food additive.

Hyperoside Prevents Aß42-Induced Neurotoxicity in PC12 Cells and Caenorhabditis elegans.

Traditional Chinese medicines such as hyperoside-rich Acanthopanax senticosus and Crataegus pinnatifida have been confirmed to exhibit anti-oxidative stress properties. Hyperoside, the main ingredient of numerous antioxidant herbs, may have the ability to postpone the onset of neurodegenerative diseases. This study investigates the possible therapeutic mechanism of hyperoside as a natural antioxidant against Alzheimer's disease (AD) in Caenorhabditis elegans and PC12 cells. Specifically, hyperoside reduced reactive oxygen species (ROS) level and Aß42-induced neurotoxicity in C. elegans worms. Meanwhile, hyperoside reduced ROS production and increased mitochondrial membrane potentialin Aß42-induced PC12 cells, which possibly due to the increase of antioxidant enzymes activity and the diminution of malondialdehyde levels. Hoechst 33,342 staining and flow cytometry analysis results suggested that hyperoside reverses cell apoptosis. Network pharmacology predicts potentially relevant hyperoside targets and pathways in AD therapy. As anticipated, hyperoside reversed Aß42-stimulated downregulation of the PI3K/Akt/Nrf2/HO-1. The PI3K inhibitor LY294002 partially abolished the protective capability of hyperoside. The results of molecular docking further indicated that the PI3K/Akt pathways may be involved in the protection of Aß42-induced PC12 cells by hyperoside treatment. The study provides theoretical information for research and development of hyperoside as an antioxidant dietary supplement.

Structural characterization of different starch-fatty acid complexes and their effects on human intestinal microflora.

Resistant starch type 5 (RS5), a starch-lipid complex, exhibited potential health benefits in blood glucose and insulin control due to the low digestibility. The effects of the crystalline structure of starch and chain length of fatty acid on the structure, in vitro digestibility, and fermentation ability in RS5 were investigated by compounding (maize, rice, wheat, potato, cassava, lotus, and ginkgo) of different debranched starches with 12-18C fatty acid (lauric, myristic, palmitic, and stearic acids), respectively. The complex showed a V-type structure, formed by lotus and ginkgo debranched starches, and fatty acid exhibited a higher short-range order and crystallinity, and lower in vitro digestibility than others due to the neat interior structure of more linear glucan chains. Furthermore, a fatty acid with 12C (lauric acid)-debranched starches complexes had the highest complex index among all complexes, which might be attributed to the activation energy required for complex formation increased with the lengthening of the lipid carbon chain. Therefore, the lotus starch-lauric acid complex (LS12) exhibited remarkable ability in intestinal flora fermentation to produce short-chain fatty acid (SCFAs), reducing intestinal pH, and creating a favorable environment for beneficial bacteria.

Clinical features and enzyme replacement therapy in 10 children with Fabry disease.

Objective: To summarize the clinical features, diagnosis and enzyme replacement therapy(ERT) of Fabry disease (FD) in children. Methods: The clinical data, laboratory tests, genetic variations and treatment of 10 FD children diagnosed in Shandong Provincial Hospital from September 2020 to June 2022 were retrospectively analyzed. Results: Among the 10 cases from 6 families, 7 patients were boys of 4 to 13 years of age, and 3 were girls of 12 to 15 years of age. There were 7 symptomatic patients, including 6 boys and 1 girl. All 7 patients presented with acral neuralgia. Five patients had little or no sweating. Five patients presented with cutaneous angiokeratoma. Two patients had abdominal pain. One patient developed joint symptoms. Four patients had corneal opacity. One patient had hearing loss; one patient had short stature. One patient had mild proteinuria and 1 patient had dysplasia of the right kidney with decreased eGFR (55.28 ml/min.1.73 m2). The left ventricular mass index was slightly elevated in 1 patient. Three patients had mild obstructive ventilatory dysfunction; a small amount of effusion in the intestinal space of the lower abdomen or mild fatty liver was found in 2 patients. Partial empty sella turcica in 1 patient. A total of 6 GLA gene variants were detected in 10 children, among which C.1059_1061delGAT (p.met353del) was a newly discovered mutation. Five children received ERT, of which 4 were treated with agalsidase beta and 1 was treated with agalsidase alpha. Only 1 patient had anaphylaxis. Lyso-GL-3 levels decreased significantly in the first 3 months of ERT initiation and remained relatively stable thereafter in 3 patients. The Lyso-GL-3 level was decreased, but renal impairment continued to progress in 1 patient treated with agalsidase alpha. Conclusion: The clinical manifestations of FD in childhood are diverse, and it is necessary to make a definite diagnosis by combining family history, enzyme activity, biomarkers, gene testing and other indicators. Pedigree screening and high-risk population screening are helpful for early identification, early diagnosis and early treatment. No serious adverse reactions were found during the short-term treatment with agalsidase alpha and beta.

DNA-dependent protein kinase catalytic subunit (DNA-PKcs) drives chronic kidney disease progression in male mice.

Kidney injury initiates epithelial dedifferentiation and myofibroblast activation during the progression of chronic kidney disease. Herein, we find that the expression of DNA-PKcs is significantly increased in the kidney tissues of both chronic kidney disease patients and male mice induced by unilateral ureteral obstruction and unilateral ischemia-reperfusion injury. In vivo, knockout of DNA-PKcs or treatment with its specific inhibitor NU7441 hampers the development of chronic kidney disease in male mice. In vitro, DNA-PKcs deficiency preserves epithelial cell phenotype and inhibits fibroblast activation induced by transforming growth factor-beta 1. Additionally, our results show that TAF7, as a possible substrate of DNA-PKcs, enhances mTORC1 activation by upregulating RAPTOR expression, which subsequently promotes metabolic reprogramming in injured epithelial cells and myofibroblasts. Taken together, DNA-PKcs can be inhibited to correct metabolic reprogramming via the TAF7/mTORC1 signaling in chronic kidney disease, and serve as a potential target for treating chronic kidney disease.