OBJECTIVES: To fabricate an injectable composite microsphere hydrogel reinforced with silk fibroin/hyaluronic acid microspheres, achieving synergistic enhance-ment of mechanical robustness and biofunctionality. METHODS: Methacrylated hyaluronic acid (HAMA) and thiolated silk fibroin (TSF) were synthesized. Monodisperse microspheres generated via microfluidics were UV-cured (420 nm) through thiol-ene click reaction. These microspheres were embedded in a TSF/HAMA matrix to form photo-cured composites. The grafting rate of TSF and HAMA was characterized by H1-NMR; particle size distribution of microsphere hydrogels in soybean oil was observed by optical microscopy; gel point of composite microsphere hydrogels was determined by advanced extensional rheometer; microscopic morphology of microsphere hydrogels was observed by scanning electron microscopy; elemental distribution of microsphere hydrogels was detected by X-ray energy dispersive spectroscopy; tunability of composite microsphere hydrogels was observed by inverted confocal microscopy; mechanical properties of composite microsphere hydrogels were tested by compression testing; swelling ratio, degradation rate and water retention rate of composite microsphere hydrogels were measured by gravimetric method. Cytotoxicity of the composite microsphere hydrogels was determined by Calcein-AM/propidium iodide dual staining and CCK-8 assay; cell migration capability was observed by scratch assay. RESULTS: The grafting rates of HAMA and TSF was 48.03% and 17.99%, respectively. Microsphere hydrogels with particle sizes of (43.3±1.2), (78.1±3.0), and (130.8±1.9) μm were prepared. The gel time of the composite microsphere hydrogels was 48-115s. The laser confocal imaging confirmed dynamic regulation characteristics of the composite microsphere hydrogels. The compressive strength of the composite microsphere hydrogels reached 22.7 kPa and maintained structural integrity at 40% strain after 20 compression cycles. The composite microsphere hydrogels exhibited differential deswelling behaviors in simulated physiological environments, and reducing microsphere particle size could significantly enhance its stability under moist conditions. The degradation rate of the composite microsphere hydrogels was (49.1±0.9)% after 200 h, and water retention rate was maintained at 40%-60% after 96 h. Biocompatibility assays confirmed >95% cell viability and unimpaired cell migration abilities. CONCLUSIONS The TSF/HAMA composite microsphere hydrogel developed in this study has characteristics of rapid fabrication, adjustable mechanical properties, enhanced environmental stability and excellent biocom-patibility, thus providing a new material solution for tissue repair and regenerative medicine.
Fibroins/chemistry* ; Hydrogels/chemistry* ; Microspheres ; Hyaluronic Acid/chemistry* ; Humans

Somatostatin receptor 1 (SSTR1) is a crucial therapeutic target for various neuroendocrine and oncological disorders. Current SSTR1-targeted treatments, including the first-generation somatostatin analog lanreotide (Lan) and the second-generation analog pasireotide (Pas), show promise but encounter challenges related to selectivity and efficacy. This study presents high-resolution cryo-electron microscopy structures of SSTR1 complexed with Lan or Pas, revealing the distinct mechanisms of ligand-binding and activation. These structures illustrate unique conformational changes in the SSTR1 orthosteric pocket induced by each ligand, which are critical for receptor activation and ligand selectivity. Combined with the biochemical assays and molecular dynamics simulations, our results provide a comparative analysis of binding characteristics within the SSTR family, highlighting subtle differences in SSTR1 activation by Lan and Pas. These insights pave the way for designing next-generation therapies with enhanced efficacy and reduced side effects through improved receptor subtype selectivity.

Objective:To analyze the clinical characteristics and management strategy of carotid web (CW)-related stroke and improve the understanding of CW.Methods:The clinical data of 6 patients with CW-related stroke treated at Xuanwu Hospital, Capital Medical University, from January 2018 to September 2022 were retrospectively analyzed. Relevant data included clinical manifestations, bronchial magnetic resonance imaging (MRI), CT angiography (CTA)/digital subtraction angiography (DSA), carotid ultrasonography, and transcranial color-coded Doppler sonography (TCCD). Treatments and follow-ups were also reported.Results:All 6 patients were middle-aged or young, without traditional risk factors for cerebrovascular disease. The male-to-female ratio was 2∶4. All patients had recurrent strokes, with a score of 2-4 on the National Institutes of Health Stroke Scale at the time of onset. Head MRI showed 5 patients with cerebral infarction in the middle cerebral artery supply area; 1 patient had no intracranial infarction. No significant stenosis of the vessels at the site of the CW was observed in any of the 6 patients. Four patients had ipsilateral stenosis or occlusion of the middle cerebral artery, 1 patient had microembolic signals in the middle cerebral artery, and 1 patient had no significant abnormalities in the intracranial artery. All 6 patients were initially diagnosed by ultrasound. Diagnoses were confirmed by CTA/DSA in 5 cases; the other patient did not show any significant abnormalities. All 6 patients underwent a carotid endarterectomy after a pathological examination to confirm the diagnosis. Postoperatively, regular antiplatelet aggregation and statin lipid-lowering therapies were administered. A follow-up of 0.5 to 5.2 years showed no stroke recurrence in any patient.Conclusions:CW-related stroke is a rare cause of cryptogenic stroke and has a high recurrence rate. For stroke patients who do not have traditional risk factors for cerebrovascular disease while repeatedly experiencing embolic events of the internal carotid artery system, attention should be paid to the combination of the carotid and cerebral arteries, and comprehensive hemodynamic characteristics should be checked for the presence of a CW. Carotid artery ultrasound and TCCD combined with other imaging methods can improve the detection rate of a CW. Simple antiplatelet aggregation therapy cannot effectively prevent stroke recurrence. For patients with confirmed CW-related cerebral infarction, surgical resection can be performed, and the treatment effect can be evaluated using ultrasonography.

A 56-year-old female was admitted to Department of Gastroenterology at Peking Union Medical College Hospital with diarrhea for seven months, and abnormal liver function for six months. She had a history of type 1 diabetes. The main clinical manifestations were recurrent fatty diarrhea and abnormal liver function, accompanied by abdominal and retroperitoneal lymphadenopathy, elevated CA19-9 and CEA. Progressive impairment of hepatic synthetic function and shrinkage of liver developed in a short period of time. The pathology of liver biopsy suggested that nodular regeneration of hepatocytes was followed by hyperplasia of thin bile ducts after submassive necrosis. Intestinal mucosa biopsies were performed twice. The pathology showed that the intestinal villi were completely blunt, accompanied with crypt hyperplasia. Goblet cells disappeared with reduced mucin. Paneth cells were barely seen without intraepithelial infiltration of lymphocytes. Rifaximin was not effective, while glucocorticoids improved clinical situation. The diagnosis of autoimmune enteropathy was finally confirmed by multidisciplinary team including departments of gastroenterology, pathology, endocrinology, hematology, infectious diseases, and rheumatology. With the administration of glucocorticoid and sirolimus, diarrhea relieved and liver function returned to normal.

Objective:To investigate the correlation between depression risk and the test time for dual-task timed up-and-go(TUG)test in the elderly.Methods:A total of 193 elderly volunteers aged 60 years and over who lived in the Nanjing community of Jiangsu Province were recruited.The Geriatric Depression Scale(GDS)was used to screen for geriatric depression.The single-task TUG(TUG-single), TUG with additional operational tasks(TUG-manual)and TUG with additional cognitive tasks(TUG-cognitive)were tested in all subjects.The differences in test times taken to complete TUG-single, TUG-manual and TUG-cognitive tests were analyzed by ANOVA.The correlation of GDS scores with test time for TUG-single, TUG-manual, TUG-cognitive was analyzed by using Pearson's correlation.Results:The average test times for TUG-cognitive and TUG-manual tests were longer than that for TUG-single test( P<0.0001). The higher the GDS score, the longer the TUG-single test time, with a significantly positive correlation between GDS and the test time for TUG-single( r=0.2261, P=0.0016). Similarly, GDS score showed significantly positive correlations with the test time for TUG-manual( r=0.2359, P=0.0010)and the TUG-cognitive test time( r=0.1946, P=0.0067). Conclusions:The increase of depression risk is significantly and positively correlated with the prolongation of the TUG test time in the elderly.The TUG test can be used to assess the functional mobility in elderly patients with depression.

Psoriasis is a chronic,non-infective inflammatory dermatosis characterized by erythemas covered with scales.Psoriasis is considered as a systemic disease,and several studies have confirmed that it is associated with many other diseases,such as cardiovascular diseases,obesity,diabetes mellitus type Ⅱ,dyslipidemia,nonalcoholic fatty liver disease,anxiety disorder,depression and inflammatory bowel disease.The occurrence and development of psoriasis is closely related to the immune response,and the immune dysfunction of T lymphocytes induced by the infiltration and activation of inflammatory cells has been confirmed as the key step in the pathogenesis of psoriasis.Various kinds of cytokines in the local microenvironment can promote the activation and proliferation of T lymphocytes,and regulate the differentiation of T lymphocytes into different subsets,which take an important part in the occurrence of psoriasis.In recent years,researchers have found that local microbes also play an important role in this process.Thus,this review summarizes the progress in the roles of human skin and gut microbiota in psoriasis.

Objective To investigate clinical manifestations and histopathological features of cutaneous metastasis of malignant visceral tumors,to improve diagnosis of cutaneous metastasis of malignant visceral tumors.Methods A total of 50 patients with cutaneous metastasis of malignant visceral tumors were enrolled from Shanghai Skin Disease Hospital between January 2012 and June 2018,and the features of the skin lesions,source of tumors,histological and immunohistochemical features were retrospectively analyzed.Results There were 24 males and 26 females among the 50 patients,with an average age of 67.0 years (range,28-93 years).The average duration from the notice of cutaneous metastasis of malignant visceral tumors to the first clinic visit was 4.4 months (range,2 weeks-13 months).Cutaneous metastasis of malignant visceral tumors mostly occurred on the chest (16 cases),followed by the lower limbs (7 cases),the head and neck (5 cases),the back (5 cases),the abdomen (4 cases),the external genitalia (4 cases) and the upper limbs (3 cases).Cutaneous metastasis of malignant visceral tumors simultaneously or successively occurred on multiple sites in 6 cases.The most common skin lesion was solitary lump (35 cases,70％),followed by multiple papules and nodules (13 cases,26％),infiltrative plaques (1 case,2％) and non-infiltrative erythema (1 case,2％).The most common types of primary cancers were breast cancer (11 cases,22％),lung cancer (9 cases,18％) and gastric cancer (6 cases,12％),and the most common histological types were adenocarcinoma (32 cases,64％) and squamous cell carcinoma (8 cases,16％).Conclusions Cutaneous metastasis of malignant visceral tumors mostly occur in the elderly and on the chest.The most common skin lesion was solitary lump.Breast carcinoma,lung cancer and gastric cancer are the most common primary tumors,and adenocarcinoma and squamous cell carcinoma are the most common histological types.

ATP-sensitive potassium channels (K) are energy sensors on the plasma membrane. By sensing the intracellular ADP/ATP ratio of β-cells, pancreatic K channels control insulin release and regulate metabolism at the whole body level. They are implicated in many metabolic disorders and diseases and are therefore important drug targets. Here, we present three structures of pancreatic K channels solved by cryo-electron microscopy (cryo-EM), at resolutions ranging from 4.1 to 4.5 Å. These structures depict the binding site of the antidiabetic drug glibenclamide, indicate how Kir6.2 (inward-rectifying potassium channel 6.2) N-terminus participates in the coupling between the peripheral SUR1 (sulfonylurea receptor 1) subunit and the central Kir6.2 channel, reveal the binding mode of activating nucleotides, and suggest the mechanism of how Mg-ADP binding on nucleotide binding domains (NBDs) drives a conformational change of the SUR1 subunit.
Adenosine Triphosphate ; metabolism ; Amino Acid Sequence ; Animals ; Binding Sites ; Cryoelectron Microscopy ; Ligands ; Mesocricetus ; Mice ; Models, Molecular ; Nucleotides ; metabolism ; Pancreas ; metabolism ; Potassium Channels, Inwardly Rectifying ; chemistry ; metabolism ; Protein Binding ; Protein Multimerization ; Protein Structure, Quaternary ; Protein Subunits ; chemistry ; metabolism ; Sf9 Cells ; Spodoptera ; Sulfonylurea Receptors ; chemistry ; metabolism

Stable isotope coded derivatization (ICD) is an isotope labeling technique for specific functional groups of the target analytes through chemical derivatization.ICD combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) enables systematically analyzing the biomolecules with the same labeling reaction characteristic.ICD technique can effectively solve the limited sensitivity in complex bio-matrices analysis and unavailability of isotope internal standards in quantitative analysis.In recent years, ICD technique has been widely used in metabolomics research field.Based on this background, the ICD technique and the design of ICD reagents are briefly described in this review.The recent advances in ICD reagents for carboxyl, amino, carbonyl, thiol and hydroxyl groups and their applications in the analysis of small molecule metabolites in bio-matrices with LC-MS/MS are reviewed.

Objective To analyze the correlation of characteristics of carotid artery structure and the incidence of residual stenosis after carotid artery stent (CAS) placement and its influencing factors using color Doppler flow imaging (CDFI).Methods Five hundred and ninety-six cases from January 2013 to December 2015 who underwent CAS (600 pieces of stent) were included in this study.All patients were examined by CDFI within 1 month before and 1 week after carotid artery stenting.The incidence of residual stenosis was analysed.The correlation of residual stenosis and the characteristics of carotid artery lesions and atherosclerotic plaque before stenting were analyzed respectively.Results There was positive correlation between the incidence rates of residual stenosis and irregularly shaped plaque (odd ratios,9.02;95% confidence interval,5.21-15.59,P<0.05),the plaques with calcification in the surface(odd ratios,2.55;95% confidence interval,1.45-4.49,P<0.05),the residual diameter of carotid stenosis less than 1.0 mm(odd ratios,1.61;95% confidence interval,1.06-2.45,P<0.05),which were the independent risk factors for influencing residual stenosis after CAS.Conclusions Choosing a more adaptable stent based on the characteristics of carotid artery lesions and atherosclerotic plaque by CDFI before stenting may be useful for the patients to get best result of revascularization.The rate of residual stenosis may be decreased.