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BACKGROUND: To identify the cut-off values for the number of metastatic lymph nodes (nMLN) and lymph node ratio (LNR) that can predict outcomes in patients with FIGO 2018 IIICp cervical cancer (CC). METHODS: Patients with CC who underwent radical hysterectomy with pelvic lymphadenectomy were identified for a propensity score-matched (PSM) cohort study. A receiver operating characteristic (ROC) curve analysis was performed to determine the critical nMLN and LNR values. Five-year overall survival (OS) and disease-free survival (DFS) rates were compared using Kaplan-Meier and Cox proportional hazard regression analyses. RESULTS: This study included 3,135 CC patients with stage FIGO 2018 IIICp from 47 Chinese hospitals between 2004 and 2018. Based on ROC curve analysis, the cut-off values for nMLN and LNR were 3.5 and 0.11, respectively. The final cohort consisted of nMLN ≤ 3 (n = 2,378) and nMLN > 3 (n = 757) groups and LNR ≤ 0.11 (n = 1,748) and LNR > 0.11 (n = 1,387) groups. Significant differences were found in survival between the nMLN ≤ 3 vs the nMLN > 3 (post-PSM, OS: 76.8% vs 67.9%, P = 0.003; hazard ratio [HR]: 1.411, 95% confidence interval [CI]: 1.108-1.798, P = 0.005; DFS: 65.5% vs 55.3%, P < 0.001; HR: 1.428, 95% CI: 1.175-1.735, P < 0.001), and the LNR ≤ 0.11 and LNR > 0.11 (post-PSM, OS: 82.5% vs 76.9%, P = 0.010; HR: 1.407, 95% CI: 1.103-1.794, P = 0.006; DFS: 72.8% vs 65.1%, P = 0.002; HR: 1.347, 95% CI: 1.110-1.633, P = 0.002) groups. CONCLUSIONS: This study found that nMLN > 3 and LNR > 0.11 were associated with poor prognosis in CC patients.

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Small cell lung cancer (SCLC) is an aggressive malignancy with a high propensity for brain metastases (BM). Limited-stage SCLC (LS-SCLC) can be effectively treated with chemoradiotherapy and prophylactic cranial irradiation (PCI) to enhance patient outcomes. The aim of the present study was to assess the risk factors and prognostic significance of brain metastases (BM) in patients with limited-stage small cell lung cancer (LS-SCLC) who attained complete remission (CR) or partial remission (PR) following combined chemoradiotherapy and subsequent prophylactic cranial irradiation (PCI). Data for 290 patients diagnosed with LS-SCLC and treated at Chengde Central Hospital and Hebei Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine (Chengde, China), who achieved CR or PR and underwent PCI between 2015 and 2023, were retrospectively analyzed. BM rates and overall survival (OS) were estimated using the Kaplan-Meier method, whilst differences were assessed using the log-rank test. Risk factors affecting BM and OS were assessed using univariate and multivariate Cox regression analyses. The overall incidence of BM after PCI was 16.6% (48/290), with annual rates of 1.4, 6.6 and 12.8% at 1, 2 and 3 years, respectively. Multivariate Cox regression analysis identified an initial tumor size of >5 cm [hazard ratio (HR)=15.031; 95% confidence interval (CI): 5.610-40.270; P<0.001] as a significant independent risk factor for BM following PCI. The median OS was 28.8 months and the 5-year OS rate was 27.9%. The median OS for patients with and without BM at 27.55 and 32.5 months, respectively, and the corresponding 5-year OS rates were 8.3 and 31.8%, respectively (P=0.001). Median OS rates for stages I, II and III were 61.15, 48.5 and 28.4 months, respectively, with 5-year OS rates of 62.5, 47.1 and 21.6%, respectively (P<0.001). Further multivariate Cox regression analysis indicated that BM (HR=1.934; 95% CI: 1.358-2.764; P<0.001) and clinical stage (HR=1.741; 95% CI: 1.102-2.750; P=0.018; P=0.022) were significant independent risk factors associated with patient OS. In conclusion, a tumor size of >5 cm is a significant risk factor for BM following PCI in patients with LS-SCLS achieving CR or PR through radiotherapy and chemotherapy. Furthermore, BM and clinical staging independently influence OS.

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With the prosperity of the development of carbon nanorings, certain topologically or functionally unique units-embedded carbon nanorings have sprung up in the past decade. Herein, we report the facile and efficient synthesis of three cyclooctatetraene-embedded carbon nanorings (COTCNRs) that contain three (COTCNR1 and COTCNR2) and four (COTCNR3) COT units in a one-pot Yamamoto coupling. These nanorings feature hoop-shaped segments of Gyroid (G-), Diamond (D-), and Primitive (P-) type carbon schwarzites. The conformations of the trimeric nanorings COTCNR1 and COTCNR2 are shape-persistent, whereas the tetrameric COTCNR3 possesses a flexible carbon skeleton which undergoes conformational changes upon forming host-guest complexes with fullerenes (C60 and C70), whose co-crystals may potentially serve as fullerene-based semiconducting supramolecular wires with electrical conductivities on the order of 10-7 S cm-1 (for C60⊂COTCNR3) and 10-8 S cm-1 (for C70⊂COTCNR3) under ambient conditions. This research not only describes highly efficient one-step syntheses of three cyclooctatetraene-embedded carbon nanorings which feature hoop-shaped segments of distinctive topological carbon schwarzites, but also demonstrates the potential application in electronics of the one-dimensional fullerene arrays secured by COTCNR3.

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Apart from single hemostasis, antibacterial and other functionalities are also desirable for hemostatic materials to meet clinical needs. Cationic materials have attracted great interest for antibacterial/hemostatic applications, and it is still desirable to explore rational structure design to address the challenges in balanced hemostatic/antibacterial/biocompatible properties. In this work, a series of cationic microspheres (QMS) were prepared by the facile surface modification of microporous starch microspheres with a cationic tannic acid derivate, the coating contents of which were adopted for the first optimization of surface structure and property. Thermoresponsive gels with embedded QMS (F-QMS) were further prepared by mixing a neutral thermosensitive polymer and QMS for second structure/function optimization through different QMS and loading contents. In vitro and in vivo results confirmed that the coating content plays a crucial role in the hemostatic/antibacterial/biocompatible properties of QMS, but varied coating contents of QMS only lead to a classical imperfect performance of cationic materials. Inspiringly, the F-QMS-4 gel with an optimal loading content of QMS4 (with the highest coating content) achieved a superior balanced in vitro hemostatic/antibacterial/biocompatible properties, the mechanism of which was revealed as the second regulation of cell-material/protein-material interactions. Moreover, the optimal F-QMS-4 gel exhibited a high hemostatic performance in a femoral artery injury model accompanied by the easy on-demand removal for wound healing endowed by the thermoresponsive transformation. The present work offers a promising approach for the rational design and facile preparation of cationic materials with balanced hemostatic/antibacterial/biocompatible properties.

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Objective: To investigate the value of pretreatment inflammatory-nutritional biomarkers in predicting the pathological response of locally advanced rectal cancer (LARC) after neoadjuvant chemotherapy (nCT). Methods: This retrospective study included eligible participants who underwent nCT followed by radical surgery. Pretreatment inflammatory nutritional biomarkers were calculated within one week prior to nCT. Correlations between biomarkers and pathological responses were analyzed. The cut-off values of the pretreatment biomarkers for predicting non-response were determined using receiver operating characteristic (ROC) curve analysis. The inflammation-nutrition score was calculated using the lymphocyte level, neutrophil-to-lymphocyte ratio (NLR), and prognostic nutritional index (PNI). Results: A total of 235 patients were retrospectively recruited between January 2017 and September 2022. Lower lymphocyte levels, lymphocyte monocyte ratio (LMR), and PNI, and higher NLR and platelet-to-lymphocyte ratio (PLR) were observed in patients without response. Multivariate logistic regression analysis revealed that NLR could independently predict non-response to nCT in patients with LARC. The sensitivity and specificity of the inflammation-nutrition score for predicting nonresponse were 71.2% and 61.7%, respectively. Conclusion: The pretreatment inflammation-nutrition score is a practical parameter for predicting non-response to nCT in patients with LARC. Patients with high scores were more likely to respond poorly to nCT.

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Aiming at the construction of novel soft actuators through the amplified motions of molecular machines at the nanoscale, the design and synthesis of a new family of photoresponsive rotaxane-branched dendrimers through an efficient controllable divergent approach was successfully realized for the first time. In the third-generation rotaxane-branched dendrimers, up to 21 azobenzene-based rotaxane units located at each branch, thus making them the first successful synthesis of light-control integrated artificial molecular machines. Notably, upon alternative irradiation with UV and visible light, photoisomerization of the azobenzene stoppers leads to the collective and amplified motions of the precisely arranged rotaxane units, resulting in controllable and reversible dimension modulation of the integrating photoresponsive rotaxane-branched dendrimers in solution. Moreover, novel macroscopic soft actuators were further constructed based on these photoresponsive rotaxane-branched dendrimers, which revealed fast shape transformation behaviors with an actuating speed up to 21.2 ± 0.2° s-1 upon ultraviolet irradiation. More importantly, the resultant soft actuators could produce mechanical work upon light control that has been further successfully employed for weight-lifting and cargo transporting, thus laying the foundation toward the construction of novel smart materials that can perform programmed events.

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Inhibition of NLRP3 inflammasome activation produces potent therapeutic effects in a wide array of inflammatory diseases. Bergapten (BeG), a furocoumarin phytohormone present in many herbal medicines and fruits, exibits anti-inflammatory activity. In this study we characterized the therapeutic potential of BeG against bacterial infection and inflammation-related disorders, and elucidated the underlying mechanisms. We showed that pre-treatment with BeG (20 µM) effectively inhibited NLRP3 inflammasome activation in both lipopolysaccharides (LPS)-primed J774A.1 cells and bone marrow-derived macrophages (BMDMs), evidenced by attenuated cleaved caspase-1 and mature IL-1ß release, as well as reduced ASC speck formation and subsequent gasdermin D (GSDMD)-mediated pyroptosis. Transcriptome analysis revealed that BeG regulated the expression of genes involved in mitochondrial and reactive oxygen species (ROS) metabolism in BMDMs. Moreover, BeG treatment reversed the diminished mitochondrial activity and ROS production after NLRP3 activation, and elevated the expression of LC3-II and enhanced the co-localization of LC3 with mitochondria. Treatment with 3-methyladenine (3-MA, 5 mM) reversed the inhibitory effects of BeG on IL-1ß, cleaved caspase-1 and LDH release, GSDMD-N formation as well as ROS production. In mouse model of Escherichia coli-induced sepsis and mouse model of Citrobacter rodentium-induced intestinal inflammation, pre-treatment with BeG (50 mg/kg) significantly ameliorated tissue inflammation and injury. In conclusion, BeG inhibits NLRP3 inflammasome activation and pyroptosis by promoting mitophagy and maintaining mitochondrial homeostasis. These results suggest BeG as a promising drug candidate for the treatment of bacterial infection and inflammation-related disorders.

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(1) Background: The early screening strategy for type A acute aortic syndrome (A-AAS) patients has always been challenging. (2) Methods: From September 2020-31 March 2022, 179 consecutive patients with suspected A-AAS were retrospectively reviewed. We assessed the diagnostic value of the use of handheld echocardiographic devices (PHHEs) by emergency medicine (EM) residents either alone or in combination with serum acidic calponin in this patient group. (3) Results: The direct sign of PHHE had a specificity (SP) of 97.7%. The sign of ascending aortic dilatation showed SE = 77.6%, SP = 68.5%, PPV = 48.1% and NPV = 89%. SE, SP, PPV and NPV of a positive PHHE direct sign were 55.6%, 100%, 100% and 71.4% in 19 hypotension/shock patients with suspected A-AAS, respectively. The area under curve (AUC) of acidic calponin combined with an ascending aorta diameter >40 mm was 0.927, with an SE and SP of 83.7% and 89.2%, respectively. These two combined indicators significantly improved the diagnostic efficiency of A-AAS compared with either of them alone (p = 0.017; standard error 0.016, Z value 2.39; p = 0.001, standard error 0.028, Z value 3.29). (4) Conclusion: EM resident-performed PHHE was highly indicative of A-AAS in patients presenting with shock or hypotension. An ascending aorta diameter > 40 mm combined with acidic calponin demonstrated acceptable diagnostic accuracy as a rapid first-line triage tool to identify patients with suspected A-AAS.

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General access to highly valuable seven-membered rings via Büchner-type reaction remains a formidable challenge. Here we report a Cu-catalyzed intermolecular oxidation of alkynes using N-oxides as oxidants, which enables expedient preparation of valuable benzo[6,7]azepino[2,3-b]quinolines and pyridine-based diones. Importantly, in contrast to the well-established gold-catalyzed intermolecular alkyne oxidation, the dissociated pyridine or quinoline partner could be further utilized to construct N-heterocycles in this system and the reaction most likely proceeds by a Büchner-type ring expansion pathway. A mechanistic rationale for this cascade cyclization is supported by DFT calculations.

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In this study, nickel (Ni) was recovered from electroplating sludge in the form of Ni(OH)2 using a bipolar membrane electrodialysis (BMED) system. The results showed that the H+ generated by the bipolar membrane could effectively desorb Ni from the sludge to the solution and the solution pH considerably affected Ni desorption. The desorption process can be described using the first-order kinetic model. The current density and solid/liquid ratio (m/v) considerably affected Ni recovery. Moreover, 100% of Ni was removed from the electroplating sludge and 93.5% of Ni was recovered after 28 h under a current density of 20 mA/cm2, a solid/liquid ratio of 1.0:15 and an electroplating-sludge particle size of 100 mesh. As the number of electroplating compartments increased from one to two and three, the current efficiency for recovering Ni changed from 12.1% to 11.8% and 11.9%, respectively, and the specific energy consumption decreased from 0.064 to 0.048 and 0.039 kW·h/g, respectively. Fourier-transform infrared spectroscopy and Raman spectroscopy showed that the precipitate obtained in this study is similar to commercial Ni(OH)2 and the purity of Ni(OH)2 in the obtained precipitate was 79%. Thus, the results showed that the BMED system is effective for recovering Ni from electroplating sludge.

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BACKGROUND: Purple sweet potato Ipomoea batatas (L.) has long been used as a medicine and a food. It contains various bioactive substances such as polysaccharides, anthocyanins, and flavonoids. Purple sweet potato polysaccharides are known to have anti-oxidant, anti-tumor, and immunomodulatory functions. Nevertheless, studies on the structural characterization of purple sweet potato polysaccharides and their ability to prevent non-alcoholic fatty liver disease (NAFLD) have rarely been reported. RESULTS: A novel polysaccharide (PSPP-A) was extracted and isolated from purple sweet potato, and its structural characteristics and preventive effects on NAFLD were investigated. The results indicated that PSPP-A was composed of l-rhamnose, d-arabinose, d-galactose, d-glucose, and d-glucuronic acid with molar ratios of 1.89:8.45:1.95:1.13:1. Its molecular weight was 2.63 × 103 kDa. Methylation and nuclear magnetic resonance (NMR) analysis indicated that the glycosidic linkages were →3)-α-L-Araf-(1→, α-L-Araf-(1→, →2,4)-α-L-Rhap-(1→, 4-O-Me-ß-D-GlcAp-(1→, →4)-α-D-Glcp-(1→, →4)-ß-D-Galp-(1→, and →6)-ß-D-Galp-(1→. Scanning electron microscopy (SEM) indicated that the structure of PSPP-A was irregular. Subsequently, the protective effect of PSPP-A on NAFLD was investigated. The results indicated that bodyweight, liver index, and triglyceride (TG), total cholesterol (TC), aspartate transaminase (AST), and alanine transaminase (ALT) content were significantly reduced by intervention of purple sweet potato polysaccharide-A (PSPP-A) compared with the - high-fat diet group. Liver histopathological analysis indicated that PSPP-A attenuated irregular hepatocyte patterns and excessive lipid vacuoles. CONCLUSIONS: The novel polysaccharide, PSPP-A, mainly contains arabinose, which has certain preventive effects on NAFLD. This study provides a theoretical basis for further elucidating the hepatoprotective effect of purple sweet potatoes as a functional food. © 2022 Society of Chemical Industry.

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The electrical microenvironment plays an important role in bone repair. However, the underlying mechanism by which electrical stimulation (ES) promotes bone regeneration remains unclear, limiting the design of bone microenvironment-specific electroactive materials. Herein, by simple co-incubation in aqueous suspensions at physiological temperatures, biocompatible regenerated silk fibroin (RSF) is found to assemble into nanofibrils with a ß-sheet structure on MXene nanosheets, which has been reported to inhibit the restacking and oxidation of MXene. An electroactive hydrogel based on RSF and bioencapsulated MXene is thus prepared to promote efficient bone regeneration. This MXene/RSF hydrogel also acts as a piezoresistive pressure transducer, which can potentially be utilized to monitor the electrophysiological microenvironment. RNA sequencing is performed to explore the underlying mechanisms, which can activate Ca2+/CALM signaling in favor of the direct osteogenesis process. ES is found to facilitate indirect osteogenesis by promoting the polarization of M2 macrophages, as well as stimulating the neogenesis and migration of endotheliocytes. Consistent improvements in bone regeneration and angiogenesis are observed with MXene/RSF hydrogels under ES in vivo. Collectively, the MXene/RSF hydrogel provides a distinctive and promising strategy for promoting direct osteogenesis, regulating immune microenvironment and neovascularization under ES, leading to re-establish electrical microenvironment for bone regeneration.

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The conversion of dinitrogen to more useful and reactive molecules has been the focus of intense research by chemists. In contrast to reductive N2 fixation, direct oxidation of N2 by O2 to nitric oxide under mild conditions via a thermochemical process is extremely challenging. Herein, we report the first example of N2 and O2 activation and coupling under thermochemical conditions through the remarkable ability of Y2BO+ to react with one N2 and two O2 molecules. Detailed mechanistic studies using mass spectrometry and quantum chemical calculations revealed that the N2 activation by Y2BO+ is facilitated by the double aromatic character of the Y2BON2+ intermediate. Subsequent oxidation with O2 releases NO in a dearomatization process driven by the formation of stronger Y-O bonds over the Y-N bonds. Our findings represent the first example of N2 and O2 activation and coupling under thermochemical conditions at room temperature, providing a novel strategy for small-molecule activation.

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Background: This study assessed the effects of esmolol injection in patients with in-hospital cardiac arrest (IHCA) with refractory ventricular fibrillation (VF)/pulseless ventricular tachycardia (pVT). Methods: From January 2018 to December 2021, 29 patients with IHCA with refractory shockable rhythm were retrospectively reviewed. Esmolol was administered after advanced cardiovascular life support (ACLS)-directed procedures, and outcomes were assessed. Results: Among the 29 cases, the rates of sustained return of spontaneous circulation (ROSC), 24-h ROSC, and 72-h ROSC were 79%, 62%, and 59%, respectively. Of those patients, 59% ultimately survived to discharge. Four patients with cardiac insufficiency died. The duration from CA to esmolol infusion was significantly shorter for patients in the survival group (SG) than for patients in the dead group (DG) (12 min, IQR: 8.5-19.5 vs. 23.5 min, IQR: 14.4-27 min; p = 0.013). Of those patients, 76% (22 of 29) started esmolol administration after the second dose of amiodarone. No significant difference was observed in the survival rate between this group and groups administered an esmolol bolus simultaneously or before the second dose of amiodarone (43% vs. 64%, p = 0.403). Of those patients, 31% (9 of 29) were administered an esmolol bolus for defibrillation attempts ≤ 5, while the remaining 69% of patients received an esmolol injection after the fifth defibrillation attempt. No significant differences were observed in the rates of ≥ 24-h ROSC (67% vs. 60%, p = 0.73), ≥ 72-h ROSC (67% vs. 55%, p = 0.56), and survival to hospital discharge (67% vs. 55%, p = 0.56) between the groups administered an esmolol bolus for defibrillation attempts ≤ 5 and defibrillation attempts > 5. Conclusion: IHCA patients with refractory shockable rhythms receiving esmolol bolus exhibited a high chance of sustained ROSC and survival to hospital discharge. Patients with end-stage heart failure tended to have attenuated benefits from beta-blockers. Further large-scale, prospective studies are necessary to determine the effects of esmolol in patients with IHCA with refractory shockable rhythms.

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PURPOSE: Estrogen receptor 1 (ESR1) XbaI polymorphisms may affect breast cancer susceptibility; however, the results of previously published studies are inconsistent. This meta-analysis aimed to investigate the relationship between ESR1 XbaI polymorphism and breast cancer risk.  Methods: Articles from the PubMed, Embase, Cochrane Library, WoS, Scopus, Wanfang Data, CNKI, CBM and CQVIP databases were systematically searched to determine the association between ESR1 XbaI polymorphism and breast cancer risk. The pooled results were assessed using odds ratios (ORs) and 95% confidence intervals (CIs), followed by subgroup analysis.  Results: Twenty-two studies involving 12,821 cases and 14,739 control subjects were analyzed. The pooled results indicated that ESR1 XbaI polymorphism may decrease risk of breast cancer in AG vs. AA (co-dominant model: OR = 0.88, 95% CI = 0.79-0.97, P = 0.015) and AG + GG vs. AA models (dominant model: OR = 0.89, 95% CI = 0.80-0.98, P = 0.022). Subgroup analysis indicated significant associations between the ESR1 XbaI polymorphism and breast cancer risk were observed in Asian subjects, non-Hardy-Weinberg equilibrium study, post-menopausal status and hospital-based subgroups under the AG vs. AA and AG + GG vs. AA models (all P < 0.05).  Conclusions: Our analysis of pooled data indicated that AG genotype in ESR1 XbaI may be a protective factor for breast cancer patients in some subgroups.

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Chinese yam, as a kind of traditional "medicine and food homologous food" in Asia, could assistance to digestion, nourish the lungs and relieve cough. Some research also suggested that Chinese yam could prevention of hyperglycemia, but the specific mechanism of action was not clear. In this paper, an acidic polysaccharide (CYPB) was isolated from Chinese yam with the molecular weight of 1.55 × 102 kDa. The determination of the monosaccharide composition of CYPB with ion chromatography showed that CYPB was composed of rhamnose, glucose, arabinose, galactose, glucose, xylose and glucuronic acid with the ratio of 6 : 3.73 : 7.31 : 10.95 : 4.56 : 1. The structural analysis indicated that the CYPB contain 1 → 3, 1 → 4, 1 → 2, 1 → 6 and 1 → 3, 6 glycoside bonds. The experimental results of diabetic mice model induced by high-fat diet (HFD) and streptozocin (STZ) indicated that CYPB could improve clinical symptoms and alleviate the glucose tolerance damage symptoms effectively. The underlying mechanism of regulate blood glucose of CYPB may be related to improve the ability of synthesize glycogen, insulin resistance and reduce gluconeogenesis by regulating the expression of InsR, PI3K, Akt and FoxO3, GLUT4 proteins in PI3K/Akt signaling pathway in T2DM mice.

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In this study, a graphitic carbon nitride (g-C3N4) based ternary catalyst CuO/CuFe2O4/g-C3N4 (CCCN) is successfully prepared thorough calcination method. After confirming the structure and composition of CCCN, the as-synthesized composites are utilized to activate persulfate (PS) for the degradation of organic contaminant. While using tetracycline hydrochloride (TC) as pollutant surrogate, the effects of initial pH, PS and catalyst concentration on the degradation rate are systematically studied. Under the optimized reaction condition, CCCN/PS is able to give 99% degradation extent and 74% chemical oxygen demand removal in assistance of simulated solar light, both of which are apparently greater than that of either CuO/CuFe2O4 and pristine g-C3N4. The great improvement in degradation can be assignable to the effective separation of photoinduced carriers thanks to the integration between CuO/CuFe2O4 and g-C3N4, as well as the increased reaction sites given by the g-C3N4 substrate. Moreover, the scavenging trials imply that the major oxidative matters involved in the decomposition are hydroxyl radicals (•OH), superoxide radicals (•O2-) and photo-induced holes (h+).

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Docosahexaenoic acid (DHA) has been studied for many years owing to its protective effect on the decline in brain function. DHA intake reduces the risk of Alzheimer's disease (AD) and decreases amyloid deposition; however, the underlying molecular mechanism has not been completed elucidated. In this study, the effect of DHA on the cognitive function of amyloid precursor protein (APP)/PS1 in wild-type mice and its related mechanism were investigated. Results from the Morris water maze test showed that DHA improved learning and memory function in mice. Moreover, DHA reduced neuronal damage in mice brains, as determined using Nissl staining. Unsaturated fatty acid levels in the brain of mice increased (p < 0.01) after DHA administration and saturated fatty acid levels decreased (p < 0.01). The deposition of amyloid-beta (Aß) plaques and tau protein neurofibrillary tangles was significantly inhibited. The mechanism of action of DHA was attributed to the upregulation of the expression of ß-secretase (BACE)2, which competed with BACE1 to cleave APP, thus decreasing the production of extracellular Aß fragments (p < 0.01). The expression level of insulin-degrading enzyme was not significantly different. The expression of N-methyl-D-aspartate receptors was further downregulated and the phosphorylation of glycogen synthase kinase-3ß and tau protein was inhibited (p < 0.01). These data indicated that DHA could protect cognitive function in mice by reducing Aß plaque formation and decreasing tau phosphorylation levels.

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In the early stage of osteoarthritis (OA), cartilage degradation in the surface region leads to superficial cartilage defect. However, enhancing the regeneration of cartilage defect remains a great challenge for existing hydrogel technology because of the weak adhesion to wet tissue. In the present study, an injectable mussel-inspired highly adhesive hydrogel with exosomes was investigated for endogenous cell recruitment and cartilage defect regeneration. The hydrogel with high bonding strength to the wet surface was prepared using a crosslinked network of alginate-dopamine, chondroitin sulfate, and regenerated silk fibroin (AD/CS/RSF). Compared with commercial enbucrilate tissue adhesive, the AD/CS/RSF hydrogel provided a comparative lap shear strength of 120 kPa, with a similar gelation time and a higher capacity for maintaining adhesive strength. The AD/CS/RSF/EXO hydrogel with encapsulated exosomes recruited BMSCs migration and inflation, promoted BMSCs proliferation and differentiation. Most importantly, the AD/CS/RSF/EXO hydrogel accelerated cartilage defect regeneration in situ, and extracellular matrix remodeling after injection in rat patellar grooves. The exosomes released by the hydrogels could recruit BMSCs into the hydrogel and neo-cartilage via the chemokine signaling pathway. Our findings reveal an injectable and adhesive hydrogel for superficial cartilage regeneration, which is a promising approach for minimally treating cartilage defect with arthroscopic assistance.

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OBJECTIVE: To compare the early and late predictive values of critical illness score (CIS) and procalcitonin (PCT) in septic patients with blood stream infection (BSI) induced by intra-abdominal infection (IAI), and to identify the value of PCT in etiological diagnosis. METHODS: The clinical data of patients with at least one positive blood culture within 24 hours admission to the emergency department of China-Japan Friendship Hospital from January 2014 to December 2019 and with final diagnosis of IAI induced sepsis were enrolled. Sequential organ failure assessment (SOFA), mortality in emergency department sepsis (MEDS), Logistic organ dysfunction system (LODS), and acute physiology and chronic health evaluation II (APACHE II) scores were calculated based on the parameters on the day of admission. Differences in various indicators among different Gram-stained bacterial infections and among patients with different prognosis at 28 days or 60 days were compared. Receiver operator characteristic curve (ROC curve) was used to analyze the value of PCT in differential etiological diagnosis of IAI induced sepsis caused by single bacterial infection, and the predictive value of CIS and PCT on 28-day and 60-day death of septic patients with BSI induced by IAI. RESULTS: A total of 221 septic patients with IAI caused by single bacterial infection were enrolled. The 28-day mortality was 19.9% (44/221), and the 60-day mortality was 25.8% (57/221). Mortality caused by Gram-positive (G+) bacterial infection of patients was significantly higher than that caused by Gram-negative (G-) bacterial infection (28 days: 34.6% vs. 11.4%, 60 days: 42.0% vs. 16.4%, both P < 0.01). Compared with patients with G+ bacterial infection, the PCT value of patients with G- bacterial infection was higher [µg/L: 4.31 (0.71, 25.71) vs. 1.29 (0.32, 10.83), P < 0.05]. Compared with survival group, the values of CIS and PCT in death group were higher, either in 28 days or in 60 days [death group vs. survival group in 28 days: SOFA score was 6.0 (4.0, 10.0) vs. 3.0 (2.0, 5.0), MEDS score: 11 (9, 14) vs. 6 (6, 9), LODS score: 4.0 (2.0, 6.0) vs. 1.0 (0, 2.0), APACHE II score: 17.0 (15.0, 24.0) vs. 12.0 (8.0, 15.0), PCT (µg/L): 3.48 (1.01, 26.70) vs. 2.45 (0.32, 15.65); death group vs. survival group in 60 days: SOFA score: 6.0 (4.0, 10.0) vs. 3.0 (2.0, 5.0), MEDS score: 9 (6, 14) vs. 6 (6, 9), LODS score: 4.0 (1.0, 5.0) vs. 1.0 (0, 2.0), APACHE II score: 16.5 (12.0, 20.0) vs. 12.0 (8.0, 15.0), PCT (µg/L): 2.67 (0.98, 17.73) vs. 2.22 (0.31, 16.75); all P < 0.05]. ROC curve showed that: (1) the area under ROC curve (AUC) of PCT in the diagnosis of IAI induced sepsis with single bacterial infection was 0.740 [95% confidence interval (95%CI) was 0.648-0.833]. When the optimal cut-off value of PCT was 1.82 µg/L, the sensitivity of diagnosis of G- bacterial infection was 74.0%, and the specificity was 68.2%. When PCT value was higher than 10.92 µg/L, the specificity of diagnosis of G- bacterial infection could reach 81.8%. (2) In the prediction of 28-day and 60-day mortality for septic patients with BSI induced by IAI, the APACHE II score achieved the highest AUC [28 days: 0.791 (95%CI was 0.680-0.902), 60 days: 0.748 (95%CI was 0.645-0.851)]. APACHE II score higher than 14.5 could help to predict 28-day and 60-day mortality for IAI patients with negative predictive values of 94.9% and 88.5%. However, the predictive value of PCT for septic patients with BSI induced by IAI was relatively lower [28-day AUC: 0.610 (95%CI was 0.495-0.725), 60-day AUC: 0.558 (95%CI was 0.450-0.667)]. CONCLUSIONS: PCT is more reliable in the identification of pathogen type among IAI induced sepsis with BSI, while APACHE II score may perform better in predicting early and late mortality.

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