Bifidobacterium longum suppresses colorectal cancer through the modulation of intestinal microbes and immune function.

Colorectal cancer (CRC), one of the most common malignancies in the world, urgently requires more treatment strategies. Although there has been much research on probiotics, limited research has been done in treating cancer. The purpose of this study was to investigate the role of Bifidobacterium longum (B. longum) in the prevention and treatment of CRC. Through Cell Counting Kit-8 and Colony Formation Assays, 8 h and a B. longum count of 1 × 108 CFU/ml were chosen as the best cocultivation conditions with CRC cells. The role of B. longum in inhibiting the progression of CRC cells was verified by a series of functional and immunofluorescence assays. For instance, in vivo assays have verified that B. longum could alleviate CRC progression. In addition, according to the results of in vivo assays and clinical statistical analysis, B. longum could reduce diarrhea symptoms. Mechanistically, by 16S and RNA sequencing, it was found that B. longum could affect the development of CRC by regulating the composition of gut microbes and enhancing immune function. The B. longum might inhibit the occurrence and development of CRC and relieve diarrhea symptoms by regulating intestinal microbes and immune function.

Revealing chemical release from plastic debris in animals' digestive systems using nontarget and suspect screening and simulating digestive fluids.

Plastic debris in the environment are not only pollutants but may also be important sources of a variety of contaminants. This work simulated kinetics and potential of chemical leaching from plastic debris in animals' digestive systems by incubating polyvinyl chloride (PVC) cord particles in artificial digestive fluids combined with nontarget and suspect screening based on UHPLC-Orbitrap HRMS. Impacts of particle size, aging, and digestive fluid were investigated to elucidate mechanisms of chemical leaching. Thousands of chemical features were screened in the leachates of PVC cord particles in the artificial digestive fluids, among which >60% were unknown. Bisphenol A (BPA) and bis(2-ethylhexyl) phthalate (DEHP) were the dominant identified CL1 compounds. Finer size and aging of the PVC particles and prolonged incubation time enhanced chemical release, resulting in greater numbers, higher levels, and more complexity in components of the released chemicals. The gastrointestinal fluid was more favorable for chemical leaching than the gastric fluid, with greater numbers and higher levels. Hundreds to thousands of chemical features were screened and filtered in the leachates of consumer plastic products, including food contact products (FCPs) in the artificial bird gastrointestinal fluid. In addition to BPA and DEHP, several novel bisphenol analogues were identified in the leachate of at least one FCP. The results revealed that once plastic debris are ingested by animals, hundreds to thousands of chemicals may be released into animals' digestive tracts in hours, posing potential synergistic risks of plastic debris and chemicals to plastic-ingesting animals. Future research should pay more attentions to identification, ecotoxicities, and environmental fate of vast amounts of unknown chemicals potentially released from plastics in order to gain full pictures of plastic pollution in the environment.

Nutrient composition and functional constituents of daylily from different producing areas based on widely targeted metabolomics.

Daylily is a functional food with high nutritional value in China. Datong (DT) in Shanxi Province is one of the four main production areas of daylily. Therefore, Linfen (LF), Lvliang (LL), and Yangquan (YQ) in Shanxi Province have also introduced daylily from DT. However, geographical and climatic conditions and producing patterns cause variations in the daylily quality. In the present study, we found that the nutrient composition of daylilies from different producing areas of Shanxi Province varied. The key environmental factors affecting the nutrition of daylily in different regions were altitude and temperature. The widely targeted metabolomics results showed that 1642 metabolites were found in daylily. The differential metabolites between DT and YQ, LL and LF were 557, 667, and 359, respectively. Notably, 9 metabolic pathways and 59 metabolite markers were associated with daylily from different areas. This study provides a theoretical basis for the quality maintenance and health efficacy research of daylily.

TMEM65 promotes gastric tumorigenesis by targeting YWHAZ to activate PI3K-Akt-mTOR pathway and is a therapeutic target.

Copy number alterations are crucial for the development of gastric cancer (GC). Here, we identified Transmembrane Protein 65 (TMEM65) amplification by genomic hybridization microarray to profile copy-number variations in GC. TMEM65 mRNA level was significantly up-regulated in GC compared to adjacent normal tissues, and was positively associated with TMEM65 amplification. High TMEM65 expression or DNA copy number predicts poor prognosis (P < 0.05) in GC. Furtherly, GC patients with TMEM65 amplification (n = 129) or overexpression (n = 78) significantly associated with shortened survival. Ectopic expression of TMEM65 significantly promoted cell proliferation, cell cycle progression and cell migration/invasion ability, but inhibited apoptosis (all P < 0.05). Conversely, silencing of TMEM65 in GC cells showed opposite abilities on cell function in vitro and suppressed tumor growth and lung metastasis in vivo (all P < 0.01). Moreover, TMEM65 depletion by VNP-encapsulated TMEM65-siRNA significantly suppressed tumor growth in subcutaneous xenograft model. Mechanistically, TMEM65 exerted oncogenic effects through activating PI3K-Akt-mTOR signaling pathway, as evidenced of increased expression of key regulators (p-Akt, p-GSK-3ß, p-mTOR) by Western blot. YWHAZ (Tyrosine 3-Monooxygenase/Tryptophan 5-Monooxygenase) was identified as a direct downstream effector of TMEM65. Direct binding of TMEM65 with YWHAZ in the cytoplasm inhibited ubiquitin-mediated degradation of YWHAZ. Moreover, oncogenic effect of TMEM65 was partly dependent on YWHAZ. In conclusion, TMEM65 promotes gastric tumorigenesis by activating PI3K-Akt-mTOR signaling via cooperating with YWHAZ. TMEM65 overexpression may serve as an independent new biomarker and is a therapeutic target in GC.

High Soluble Fiber Promotes Colorectal Tumorigenesis Through Modulating Gut Microbiota and Metabolites in Mice.

BACKGROUND & AIMS: Dietary fibers are mainly fermented by the gut microbiota, but their roles in colorectal cancer (CRC) are largely unclear. Here, we investigated the associations of different fibers with colorectal tumorigenesis in mice. METHODS: Apcmin/+ mice and C57BL/6 mice with azoxymethane (AOM) injection were used as CRC mouse models. Mice were fed with mixed high-fiber diet (20% soluble fiber and 20% insoluble fiber), high-inulin diet, high-guar gum diet, high-cellulose diet, or diets with different inulin dose. Germ-free mice were used for validation. Fecal microbiota and metabolites were profiled by shotgun metagenomic sequencing and liquid chromatography-mass spectrometry, respectively. RESULTS: Mixed high-fiber diet promoted colorectal tumorigenesis with increased tumor number and tumor load in AOM-treated and Apcmin/+ mice. Antibiotics use abolished the pro-tumorigenic effect of mixed high-fiber diet, while transplanting stools from mice fed with mixed high-fiber diet accelerated tumor growth in AOM-treated germ-free mice. We therefore characterized the contribution of soluble and insoluble fiber in CRC separately. Our results revealed that soluble fiber inulin or guar gum, but not insoluble fiber cellulose, promoted colorectal tumorigenesis in AOM-treated and Apcmin/+ mice. Soluble fiber induced gut dysbiosis with Bacteroides uniformis enrichment and Bifidobacterium pseudolongum depletion, accompanied by increased fecal butyrate and serum bile acids and decreased inosine. We also identified a positive correlation between inulin dosage and colorectal tumorigenesis. Moreover, transplanting stools from mice fed with high-inulin diet increased colonic cell proliferation and oncogene expressions in germ-free mice. CONCLUSION: High-dose soluble but not insoluble fiber potentiates colorectal tumorigenesis in a dose-dependent manner by dysregulating gut microbiota and metabolites in mice.

Comparative analysis of flavonoid metabolites from different parts of Hemerocallis citrina.

BACKGROUND: Hemerocallis citrina Baroni is a traditional medical and edible plant. It is rich in flavonoid compounds, which are a kind of important bioactive components with various health benefits and pharmaceutical value. However, the flavonoid metabolomics profile and the comparison of flavonoid compounds from different parts of H. citrina is scarce. RESULTS: In this study, flavonoid metabolites were investigated from roots, stems, leaves and flowers of H. citrina. A total of 364 flavonoid metabolites were identified by UPLC-MS/MS based widely targeted metabolomics, and the four plant parts showed huge differences at flavonoid metabolic level. Compared to roots, 185, 234, and 119 metabolites accounted for upregulated differential flavonoid metabolites (DFMs) in stems, leaves, and flowers, respectively. Compared to stems, 168 and 29 flavonoid metabolites accounted for upregulated DFMs in leaves and flowers, respectively. Compared to leaves, only 29 flavonoid metabolites accounted for upregulated DFMs in flowers. A number of 35 common flavonoid metabolites were observed among six comparison groups, and each comparison group had its unique differential metabolites. The most abundant flavonoid metabolites in the four parts are flavonols and flavones, followed by flavanones, chalcones, flavanols, flavanonols, anthocyanidins, tannin, and proanthocyanidins. 6,7,8-Tetrahydroxy-5-methoxyflavone, 7,8,3',4'-tetrahydroxyflavone, 1-Hydroxy-2,3,8-trimethoxyxanthone, Farrerol-7-O-glucoside, 3',7-dihydroxy-4'-methoxyflavone, 3,3'-O-Dimethylellagic Acid, 5-Hydroxy-6,7-dimethoxyflavone, Nepetin (5,7,3',4'-Tetrahydroxy-6-methoxyflavone), (2s)-4,8,10-trihydroxy-2-methoxy-1 h,2 h-furo[3,2-a]xanthen-11-one are dominant in roots. Isorhamnetin-3-O-(6''-malonyl)glucoside-7-O-rhamnoside, 7-Benzyloxy-5-hydroxy-3',4'-methylenedioxyflavonoid, 3-Hydroxyphloretin-4'-O-glucoside are dominant in stems. Chrysoeriol-7-O-glucoside, Epicatechin glucoside, Kaempferol-3-O-rhamnoside (Afzelin)(Kaempferin)*, Azaleatin (5-O-Methylquercetin), Chrysoeriol-5-O-glucoside, Nepetin-7-O-glucoside(Nepitrin), 3,5,7,2'-Tetrahydroxyflavone; Datiscetin, Procyanidin B2*, Procyanidin B3*, Procyanidin B1, Isorhamnetin-3-O-(6''-acetylglucoside) are dominant in leaves. kaempferol-3-p-coumaroyldiglucoside, Delphinidin-3-O-sophoroside-5-O-glucoside, Limocitrin-3-O-sophoroside, Kaempferol-3-O-rutinoside(Nicotiflorin), Luteolin-7-O-(6''-malonyl)glucoside-5-O-rhamnoside are dominant in flowers. CONCLUSION: There was significant difference in flavonoid metabolites among different parts of H. citrina. Leaves had relative higher metabolites contents than other parts. This study provided biological and chemical evidence for the different uses of various plant parts of H. citrina, and these informations are important theoretical basis for the food industry, and medical treatment.

Inhibitory activity of flavonoids fraction from Astragalus membranaceus Fisch. ex Bunge stems and leaves on Bacillus cereus and its separation and purification.

Introduction: Astragalus membranaceus Fisch. ex Bunge is a traditional botanical drug with antibacterial, antioxidant, antiviral, and other biological activities. In the process of industrialization of A. membranaceus, most of the aboveground stems and leaves are discarded without resource utilization except for a small amount of low-value applications such as composting. This study explored the antibacterial activity of A. membranaceus stem and leaf extracts to evaluate its potential as a feed antibiotic substitute. Materials and methods: The antibacterial activity of the flavonoid, saponin, and polysaccharide fractions in A. membranaceus stems and leaves was evaluated by the disk diffusion method. The inhibitory activity of the flavonoid fraction from A. membranaceus stems and leaves on B. cereus was explored from the aspects of the growth curve, cell wall, cell membrane, biofilm, bacterial protein, and virulence factors. On this basis, the flavonoid fraction in A. membranaceus stems and leaves were isolated and purified by column chromatography to determine the main antibacterial components. Results: The flavonoid fraction in A. membranaceus stems and leaves had significant inhibitory activity against B. cereus, and the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were 1.5625 and 6.25 mg/mL, respectively. A. membranaceus stem and leaf flavonoid fraction can induce death of B. cereus in many ways, such as inhibiting growth, destroying cell wall and cell membrane integrity, inhibiting biofilm formation, inhibiting bacterial protein synthesis, and downregulating virulence factor expression. In addition, it was clear that the main flavonoid with antibacterial activity in A. membranaceus stems and leaves was isoliquiritigenin. Molecular docking showed that isoliquiritigenin could form a hydrogen bonding force with FtsZ. Conclusion: A. membranaceus stem and leaf flavonoid fractions had significant inhibitory activity against B. cereus, and the main chemical composition was isoliquiritigenin.

Ghrelin promotes cardiomyocyte differentiation of adipose tissue­derived mesenchymal stem cells by DDX17­mediated regulation of the SFRP4/Wnt/ß­catenin axis.

Adipose tissue­derived mesenchymal stem cells (ADMSCs) differentiate into cardiomyocytes and may be an ideal cell source for myocardial regenerative medicine. Ghrelin is a gastric­secreted peptide hormone involved in the multilineage differentiation of MSCs. To the best of our knowledge, however, the role and potential downstream regulatory mechanism of ghrelin in cardiomyocyte differentiation of ADMSCs is still unknown. The mRNA and protein levels were measured by reverse transcription­quantitative PCR and western blotting. Immunofluorescence staining was used to show the expression and cellular localization of cardiomyocyte markers and ß­catenin. RNA sequencing was used to explore the differentially expressed genes (DEGs) that regulated by ghrelin. The present study found that ghrelin promoted cardiomyocyte differentiation of ADMSCs in a concentration­dependent manner, as shown by increased levels of cardiomyocyte markers GATA binding protein 4, α­myosin heavy chain (α­MHC), ISL LIM homeobox 1, NK2 homeobox 5 and troponin T2, cardiac type. Ghrelin increased ß­catenin accumulation in nucleus and decreased the protein expression of secreted frizzled­related protein 4 (SFRP4), an inhibitor of Wnt signaling. RNA sequencing was used to determine the DEGs regulated by ghrelin. Functional enrichment showed that DEGs were more enriched in cardiomyocyte differentiation­associated terms and Wnt pathways. Dead­box helicase 17 (DDX17), an upregulated DEG, showed enhanced mRNA and protein expression levels following ghrelin addition. Overexpression of DDX17 promoted protein expression of cardiac­specific markers and ß­catenin and enhanced the fluorescence intensity of α­MHC and ß­catenin. DDX17 upregulation inhibited protein expression of SFRP4. Rescue assay confirmed that the addition of SFRP4 partially reversed ghrelin­enhanced protein levels of cardiac­specific markers and the fluorescence intensity of α­MHC. In conclusion, ghrelin promoted cardiomyocyte differentiation of ADMSCs by DDX17­mediated regulation of the SFRP4/Wnt/ß­catenin axis.

Double-network hydrogel enhanced by SS31-loaded mesoporous polydopamine nanoparticles: Symphonic collaboration of near-infrared photothermal antibacterial effect and mitochondrial maintenance for full-thickness wound healing in diabetes mellitus.

Diabetic wound healing has become a serious healthcare challenge. The high-glucose environment leads to persistent bacterial infection and mitochondrial dysfunction, resulting in chronic inflammation, abnormal vascular function, and tissue necrosis. To solve these issues, we developed a double-network hydrogel, constructed with pluronic F127 diacrylate (F127DA) and hyaluronic acid methacrylate (HAMA), and enhanced by SS31-loaded mesoporous polydopamine nanoparticles (MPDA NPs). As components, SS31, a mitochondria-targeted peptide, maintains mitochondrial function, reduces mitochondrial reactive oxygen species (ROS) and thus regulates macrophage polarization, as well as promoting cell proliferation and migration, while MPDA NPs not only scavenge ROS and exert an anti-bacterial effect by photothermal treatment under near-infrared light irradiation, but also control release of SS31 in response to ROS. This F127DA/HAMA-MPDA@SS31 (FH-M@S) hydrogel has characteristics of adhesion, superior biocompatibility and mechanical properties which can adapt to irregular wounds at different body sites and provide sustained release of MPDA@SS31 (M@S) NPs. In addition, in a diabetic rat full thickness skin defect model, the FH-M@S hydrogel promoted macrophage M2 polarization, collagen deposition, neovascularization and wound healing. Therefore, the FH-M@S hydrogel exhibits promising therapeutic potential for skin regeneration.

Dry heating affects the multi-structures, physicochemical properties, and in vitro digestibility of blue highland barley starch.

As a physical method for starch modification, dry heating treatment (DHT) at high temperatures (150 and 180°C, respectively) was applied to blue highland barley (BH) starch with different durations (2 and 4 h). The effects on its multi-structures, physicochemical properties, and in vitro digestibility were investigated. The results showed that DHT had changed the morphology of BH starch, and the diffraction pattern remained an "A"-type crystalline structure. However, with an extension of DHT temperature and time, the amylose content, gelatinization temperature, enthalpy value, swelling power, and pasting viscosity of modified starches decreased, while the light transmittance, solubility, and water and oil absorption capacities increased. Additionally, compared with native starch, the content of rapidly digestible starch in modified samples increased after DHT, whereas those of slowly digestible starch and RS decreased. Based on these results, the conclusion could be drawn that DHT is an effective and green way to transform multi-structures, physicochemical properties, and in vitro digestibility of BH starch. This fundamental information might be meaningful to enrich the theoretical basis of physical modification on BH starch and extend the applications of BH in the food industry.

[Application of absorbable anchor combined with Kirschner wire in reconstruction of extension function of old mallet finger].

Objective: To investigate the feasibility and effectiveness of absorbable anchor combined with Kirschner wire fixation in the reconstruction of extension function of old mallet finger. Methods: Between January 2020 and January 2022, 23 cases of old mallet fingers were treated. There were 17 males and 6 females with an average age of 42 years (range, 18-70 years). The cause of injury included sports impact injury in 12 cases, sprain in 9 cases, and previous cut injury in 2 cases. The affected finger included index finger in 4 cases, middle finger in 5 cases, ring finger in 9 cases, and little finger in 5 cases. There were 18 patients of tendinous mallet fingers (Doyle type Ⅰ), 5 patients were only small bone fragments avulsion (Wehbe type ⅠA). The time from injury to operation was 45-120 days, with an average of 67 days. The patients were treated with Kirschner wire to fix the distal interphalangeal joint in a mild back extension position after joint release. The insertion of extensor tendon was reconstructed and fixed with absorbable anchors. After 6 weeks, the Kirschner wire was removed, and the patients started joint flexion and extension training. Results: The postoperative follow-up ranged from 4 to 24 months (mean, 9 months). The wounds healed by first intention without complications such as skin necrosis, wound infection, and nail deformity. The distal interphalangeal joint was not stiff, the joint space was good, and there was no complication such as pain and osteoarthritis. At last follow-up, according to Crawford function evaluation standard, 12 cases were excellent, 9 cases were good, 2 cases were fair, and the good and excellent rate was 91.3%. Conclusion: Absorbable anchor combined with Kirschner wire fixation can be used to reconstruct the extension function of old mallet finger, which has the advantages of simple operation and less complications.

Freeze-dried powder of daylily bud improves bromocriptine-induced lactation disorder in rats via JAK2/STAT5 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Milk deficiency is a prevalent problem in the world. Daylily (Hemerocallis citrina Borani), called the Chinese mother flower, is a traditional vegetable and is believed to possess a galactagogue effect in China. Flavonoids and phenols are considered as the active ingredients of daylily to promote lactation and improve depression. AIM OF THE STUDY: The aim of this study was to investigate the prolactin effects of freeze-dried powder of flower buds of H. citrina Baroni in rat and its action mechanisms. MATERIALS AND METHODS: The chemical constituents of flower buds of H. citrina Baroni treated by different drying techniques were analyzed by ultrahigh pressure liquid chromatography-mass spectrometry. Sprague-Dawley (SD) rat model induced by bromocriptine was used to evaluate the effect of freeze-dried powder of daylily buds on promoting lactation. Network pharmacology method, ELISA, qPCR, and Western blot were used to clarify the action mechanisms. RESULTS: We detected 657 compounds in daylily buds. The relative contents of total flavonoids and phenols in freeze-dried samples were higher than those in dried ones. Bromocriptine, as a dopamine receptor agonist, can significantly inhibit prolactin in rats. Daylily buds can restore the levels of prolactin, progesterone and estradiol depressed by bromocriptine, effectively improve the milk production of the rat, and promote the repair of rat mammary gland tissue. We analyzed the relationship between the chemical components of daylily buds and the genes related to lactation with network pharmacology method, revealing that flavonoids and phenols may be the active components that promoted milk production via JAK2/STAT5 pathway, which was confirmed by the results of qPCR and Western blot. Daylily buds can increase the mRNA expression of PRLR, CSN2, LALBA and FASN and the protein expression of PRLR, JAK2 and STAT5. CONCLUSION: Daylily buds can improve the insufficient lactation of rats induced by bromocriptine through PRLR/JAK2/STAT5 pathway, and the freeze-dried processing method may better retain the active components of flavonoids and phenols that promote milk in daylily.

The N6-methyladenine DNA demethylase ALKBH1 promotes gastric carcinogenesis by disrupting NRF1 binding capacity.

DNA N6-methyladenine (6mA) is an epigenetic modification that regulates various biological processes. Here, we show that gastric cancer (GC) cells and tumors display a marked reduction in 6mA levels compared with normal gastric tissues and cells. 6mA is abundant in the surrounding transcription start sites and occurs at consensus motifs. Among the 6mA regulators, ALKBH1, a demethylase, is significantly overexpressed in GC tissues compared with adjacent normal tissues. Moreover, high ALKBH1 expression is associated with poor survival of patients with GC. ALKBH1 knockout in mice impairs chemically induced gastric carcinogenesis. Mechanistically, ALKBH1 mediates DNA 6mA demethylation to repress gene expression. In particular, the 6mA sites are enriched in NRF1 binding sequences and targeted for demethylation by ALKBH1. ALKBH1-induced 6mA demethylation inhibits NRF1-driven transcription of downstream targets, including multiple genes involved in the AMP-activated protein kinase (AMPK) signaling pathway. Accordingly, ALKBH1 suppresses AMPK signaling, causing a metabolic shift toward the Warburg effect, which facilitates tumorigenesis.

Comparison of the generation of α-glucosidase inhibitory peptides derived from prolamins of raw and cooked foxtail millet: In vitro activity, de novo sequencing, and in silico docking.

Foxtail millet prolamin has been demonstrated to have anti-diabetic effects. In this study, we compared the generation of anti-α-glucosidase peptides derived from prolamins of raw and cooked foxtail millet (PRFM and PCFM). PRFM and PCFM hydrolysates (PRFMH and PCFMH) both exhibited α-glucosidase inhibitory activity. After ultrafiltration according to molecular weight (Mw), the fraction with Mw < 3 kDa in PCFMH (PCFMH<3) showed higher α-glucosidase inhibitory activity than that in PRFMH (PRFMH<3). The composition of α-glucosidase inhibitory peptides identified by de novo sequencing in PCFMH<3 and PRFMH<3 was compared by virtual screening, combining biological activity, net charge, grand average of hydropathicity (GRAVY), and key hydrophobic amino acids (Met, Pro, Phe, and Leu). We found that the proportion of peptides with excellent α-glucosidase binding force in PCFMH<3 was higher than in PRFMH<3. Overall, cooking may positively affect the generation of peptides that perform well in inhibiting α-glucosidase derived from foxtail millet prolamin.

Chinese version of the auditory verbal learning test: normative study and clinical applications in Chinese-speaking population in Shijiazhuang city.

OBJECTIVE: The purposes were to establish standardized values for the Auditory Verbal Learning Test (AVLT) in the communities of Shijiazhuang city (China), with particular focus on the influences of age, education and sex, and to detect the discriminant validity data of the AVLT in patients with acute ischemic stroke (AIS). METHODS: 406 Chinese-speaking subjects (age: 50-84 years old) from Shijiazhuang city, were brought into this study. Using linear regression analyses, standardized values were developed for three variables of interest, including scores on short-term memory (sum of AVLT trials 1-3), delayed recall (AVLT trial 4), and an index representing recognition memory corrected for false-positive identifications (AVLT trial 5). 177 patients with AIS were included to probe the discriminant validity of the AVLT. RESULTS: The linear regression analysis showed statistically significant effect of age and sex on all trials of the AVLT. Years of education contributed significantly to trial 1-3 and trial 4 but not trial 5. Based on the results obtained, trail 1-3 and trail 4 of AVLT norms were stratified by age (3 strata), education (2 strata), and sex (2 strata). Trail 5 norms were stratified by age (3 strata) and sex (2 strata). Moreover, AIS groups performed significantly worse on most AVLT trials than matched cognitively healthy controls. CONCLUSIONS: Normative data stratified by age, education and sex for the Chinese-speaking community-residents in Shijiazhuang was presented for use in research and clinical settings. The AVLT measures adequately differentiated between the cognitive performance (especially memory decline) of healthy adults and patients with AIS.

Olecranon osteotomy approach for Dubberley type Ⅲ coronal fractures of the distal humerus / 中国骨伤

OBJECTIVE@#To retrospectively analyze the clinical efficacy of olecranon osteotomy approach in the treatment of Dubberley type Ⅲ coronal fractures of the distal humerus and summarize the treatment experience.@*METHODS@#From January 2016 to June 2020, 17 patients (5 males and 12 females) with Dubberley type Ⅲ coronal fractures of the distal humerus were treated by olecranon osteotomy approach. The age ranged from 37 to78 years old with an average of (58.5±12.9) years old. According to Dubberley classification, there were 5 cases of type Ⅲ A and 12 cases of type Ⅲ B. The curative effect was evaluated using the Borberg-Morrey elbow function score. The flexion, extension and rotation range of motion of the elbow joint, complications and postoperative imaging evaluation were recorded.@*RESULTS@#All the 17 patients got bony union. The follow-up time ranged from 12 to 33 months with an average of (15.6±5.6) months. There was 1 case of ischemic necrosis of capitulum humeri, 2 cases of traumatic arthritis and 1 case of heterotopic ossification, 1 case of malunion of fracture. The range of motion was (114.80±19.50) °. The Broberg-Morrey score was 85.3±8.2, excellent in 5 cases, good in 9 cases, fair in 3 cases and poor in 0 case.@*CONCLUSION@#Through olecranon osteotomy approach, the articular surface of distal humerus could be fully exposed, and the operation is convenient. Anatomical reduction and rigid fixation of the articular surface of distal humerus are the key factors for the succesful outcome.

Multi-residue determination of bisphenol analogues in organism tissues by ultra-high performance liquid chromatography-tandem mass spectrometry.

A reliable and sensitive analyzing method was developed and validated for determination of 13 novel bisphenol analogues (BPs) along with bisphenol A (BPA) in organism tissues. The complex organism tissues were treated by ultrasonic-assisted extraction using acetonitrile/formic acid (99:1, v/v), followed by successive purification using enhanced matrix removal-lipid sorbents and primary secondary amine sorbents. The BPs were finally determined by ultra-high performance liquid chromatography-tandem mass spectrometry after derivatization using pyridine-3-sulfonyl chloride. Satisfactory recoveries of 75 - 118% were obtained for the BPs, with good repeatability (RSD < 20%). Matrix interferences were efficiently diminished. The method quantification limits (MQLs) reached 0.003 - 0.1 ng g-1 dry weight (dw). The validated method was successfully applied to a preliminary investigation of the BPs in wild marine organisms collected from the nearshore waters along the coast of Guangdong, China. Besides BPA, novel BPs such as bisphenol F, bisphenol AF, and tetrabromobisphenol A were also detected at < MDL - 15.5 ng g-1 dw. This work laid a strong basis for further in-depth research on bioaccumulation of the novel BPs in the environment.

Vitamin D receptor (VDR) contributes to the development of hypercalciuria by sensitizing VDR target genes to vitamin D in a genetic hypercalciuric stone-forming (GHS) rat model.

Human idiopathic hypercalciuria (IH) is the most common cause of calcium oxalate nephrolithiasis with perturbed calcium metabolism with increased bone resorption and decreased renal calcium reabsorption, which can be phenotype-copied in the genetic hypercalciuric stone-forming (GHS) rat model. We previously demonstrated that high VDR expression plays important roles in the development of hypercalciuria in the GHS rats. However, the underlying mechanism through which VDR impact hypercalciuria development remains to be fully understood. Here, we sought to determine how VDR regulated its target genes that are implicated in calcium homeostasis and potentially hypercalciuria. We found that VDR expression in the GHS rats was elevated in the calcium transporting tissues, as well as in the thymus and prostate, but not in lung, brain, heart, liver and spleen, when compared with control SD rats. Snail expression in the GHS rats was significantly downregulated in kidney, intestine, thymus and testis. Intraperitoneal injection of 1,25(OH)2D3 significantly upregulated the expression of renal calcium sensing receptor (CaSR), intestinal calcium transporters transient receptor potential vanilloid type 6 (TRPV6), and VDR in GHS rats, compared with that in control SD rats. ChIP assays revealed that VDR specifically bound to the proximal promoters of target genes, followed by histone H3 hyperacetylation or hypermethylation. Collectively, our results suggest that elevated VDR expression may contribute to the development of hypercalciuria by sensitizing VDR target genes to 1,25(OH)2D3 through histone modifications at their promoter regions in a genetic hypercalciuric stone-forming (GHS) rat model.

Defective UiO-66-NH2 Functionalized with Stable Superoxide Radicals toward Electrocatalytic Nitrogen Reduction with High Faradaic Efficiency.

The electrocatalytic nitrogen reduction reaction (NRR) to NH3 is limited by low Faradaic efficiency (FE). Herein, defective UiO-66-NH2 functionalized with quite stable superoxide radicals (O2•) is developed as a highly active NRR catalyst. The experimental and computational results show that one linker per Zr6 node is missed and two Zr atoms are exposed in the defective UiO-66-NH2. One of the two exposed Zr atoms can stably adsorb O2•, and thus, a Zr-OO• site forms during the preparations without light excitation or postoxidation, while the other Zr atom is activated as an active site. The synergistic effects of the two Zr sites in the defective UiO-66-NH2 suppress hydrogen and hydrazine evolutions considerably. They are as follows: (i) due to repulsion of the proton on the active Zr site and stabilization of the proton on the Zr-OO• site, the active Zr site is unfavorable for the adsorption of the proton with a high energy barrier, which is the HER rate-determining step (RDS); (ii) under the assistance of the OO• of the Zr-OO• site, the first hydrogenation step of *N2 (i.e., NRR RDS) on the active Zr site is promoted; and (iii) relying on the assistance of the OO• of the Zr-OO• site, the continuous hydrogenation of *NH2NH2 to produce NH3 on the active Zr site is spontaneously exothermic, whereas its desorption to hydrazine is blocked. Accordingly, an extremely high FE of ∼85.21% has been realized along with a high yield rate of NH3 (∼52.81 µg h-1 mgcat-1). To the best of our knowledge, it is the highest FE that has been achieved in recent years. Radical scavenging treatment of the defective UiO-66-NH2 and detailed investigations of two categories of control samples further verify the favorable effects of the O2• that closely correlates with the missed linkers on the performance of the NRR to NH3. This work opens a new way toward highly efficient NRR catalysts, i.e., stable radical-activating defective metal-organic frameworks.

Glucocorticoid-induced expansion of classical monocytes contributes to bone loss.

Classical monocytes are commonly involved in the innate inflammatory response and are the progenitors of osteoclasts. Excess endogenous glucocorticoids (GCs) can increase the levels of classical monocytes in blood and bone marrow. The role of this cell population in high-dose exogenous GC-induced osteoporosis (GIOP) remains to be elucidated. In this study, GIOP was established in rats and mice by daily methylprednisolone injection, and monocyte subsets were analyzed by flow cytometry. We demonstrated that classical monocytes accumulate in bone marrow during GIOP. Similarly, the monocyte proportion among bone marrow nucleated cells was also increased in patients with steroid treatment history. We sorted classical monocytes and analyzed their transcriptional profile in response to GCs by RNA sequencing. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that classical monocytes isolated from GC-treated rats exhibited osteoclast differentiation potential. Deletion of classical monocytes by clodronate liposome treatment prevented GIOP via inhibition of osteoclastogenesis and restoration of CD31HiendomucinHi vessels. Regarding the molecular mechanism, classical monocytes express high levels of glucocorticoid receptors. In vitro treatment with GCs increased both the percentage and absolute number of monocytes and promoted their proliferation. In summary, classical monocytes mediated GC-induced bone loss and are a potential target for therapeutic intervention in GIOP treatment.