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Background: Evaluating antibiotics most commonly associated with pseudomembranous colitis (PMC) based on the real-world data is of great significance., Research Design and Methods: We used the data from FAERS to evaluate the potential association between antibiotics and PMC by disproportionality analyzes., Results: Eighty-one antibiotics which met the three algorithms simultaneously were enrolled. There were 1683 reports of PMC associated with the enrolled antibiotics. In the top 24 antibiotics, cefoxitin, streptomycin, fosfomycin, and micafungin had a high risk of PMC, but there were few reports in the literature., Conclusions: This study was of great significance for healthcare professionals to realize the potential PMC risks of antibiotics.

Lactobacillus delbrueckii subsp. bulgaricus ( L. bulgaricus ) is one of the most commonly employed Lactobacillus in the food industry. Exopolysaccharides (EPS) of Lactobacillus , which are known to exhibit probiotic properties, are secondary metabolites produced during the growth of Lactobacillus . This study identified the structure of the EPS produced by L. bulgaricus 1.0207 and investigated the mitigation of L. bulgaricus 1.0207 EPS on H 2 O 2 -induced oxidative stress in IPEC-J2 cells. L. bulgaricus 1.0207 EPS consisted of glucose and galactose and possessed a molecular weight of 4.06 × 10 4 Da. L. bulgaricus 1.0207 EPS exhibited notable scavenging capacity against DPPH, hydroxyl radicals, superoxide anions, and ABTS radicals. Additionally, L. bulgaricus 1.0207 EPS enhanced cell proliferation, reduced intracellular reactive oxygen species (ROS) accumulation, increased activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and total antioxidant capacity (T-AOC) elevated the relative expression of CAT, SOD, HO-1, NQO1, ZO-1, and Occludin genes. Moreover, L. bulgaricus 1.0207 EPS improved the expression of Nrf2, p Nrf2, p Nrf2/Nrf2, and Bcl-2 proteins, while decreasing the expression of Keap1, Caspase3, and Bax proteins, with the best effect at a concentration of 100 μg/mL. L. bulgaricus 1.0207 EPS mitigated H 2 O 2 -induced oxidative stress injury in IPEC-J2 cells by activating the Keap1/Nrf2 pathway. Meanwhile, L. bulgaricus 1.0207 EPS exhibited the potential to decrease apoptosis and restore the integrity of the gut barrier. The findings establish a theoretical foundation for the development and application of L.bulgaricus 1.0207 and its EPS.

The purpose of this study was to examine how individual openness to experience influences humor production and to explore the underlying psychological mechanisms of this relationship, specifically focusing on cognitive flexibility (the cognitive path) and ambiguity tolerance (the motivational path). To comprehensively evaluate individuals' humor production ability, Study 1 employed a subjective self-report questionnaire on sense of humor, while Study 2 used an objective humor dialogue generation task. The results of Study 1 indicated that openness to experience did not directly impact sense of humor; instead, the relationship between openness to experience and sense of humor was fully mediated by cognitive flexibility. In Study 2, findings showed that openness to experience positively predicted humor production ability, with ambiguity tolerance partially mediating this effect. These results suggest that individuals with higher levels of openness to experience have a greater capacity for generating humorous perspectives. Moreover, the study identified two psychological pathways-cognition and motivation-in the process of generating funny ideas. The specific pathway influenced by the measurement method used for humor production further highlights the importance of both cognitive flexibility and ambiguity tolerance in understanding how openness to experience contributes to humor production., (© 2024 The Author(s). PsyCh Journal published by Institute of Psychology, Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.)

Background: This study aimed to assess the association between drug-induced liver injury (DILI) and antibody-drug conjugates (ADCs) by comprehensively evaluating spontaneous reports submitted to the Food and Drug Administration Adverse Event Reporting System (FAERS) database from 2004Q1 to 2022Q3., Research Design and Methods: All DILI cases with ADCs as primary suspected drugs were extracted from the FAERS database from 2004Q1 to 2022Q3 using OpenVigil 2.1. The reporting odds ratio (ROR) and the proportional reporting ratio (PRR) for reporting the association between different drugs and DILI risk were calculated., Results: A total of 504 DILI cases were attributed to ADCs during the study period. Patients with ADCs-related DILI ( n  = 504) had a mean age of 56.2 ± 18.4 years, with 167 cases not reporting patients' age. Females and males comprised 42.5% and 44.0% of the cases, respectively, while there was no information on gender in 13.5% of the cases. The DILI signals were detected in trastuzumab emtansine, enfortumab vedotin, brentuximab vedotin, polatuzumab vedotin, gemtuzumab ozogamicin, inotuzumab ozogamicin, and trastuzumab deruxtecan., Conclusions: The FAERS data mining suggested an association between DILI and some ADCs. Further studies are warranted to unraveling the underlying mechanisms and taking preventive measures for ADCs-related DILI.

Introduction: Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are first-line treatments for hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer. With their increasing clinical use, infection-related adverse events (AEs) associated with CDK4/6 inhibitors have been widely reported in recent years. This study aimed to analyze the occurrence of infections associated with the CDK4/6 inhibitors (palbociclib, ribociclib and abemaciclib) based on the real-world data from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database., Methods: Data were extracted from the FAERS database between 2015Q1 and 2022Q3. The clinical characteristics of patients with primary suspected infection-related AEs were analyzed. A disproportionality analysis was performed to investigate the potential association between AEs and CDK4/6 inhibitors. The influencing factors were evaluated using Pearson's chi-square test., Results: Reports of infection-related AEs associated with ribociclib accounted for 8.58% of the total reports of AEs associated with ribociclib, followed by palbociclib (2.72%) and abemaciclib (1.24%). Ribociclib (67.65%) was associated with more serious outcome events than palbociclib (30%) or abemaciclib (48.08%). The sex and age were not associated with outcome severity. Disproportionality analysis showed that fourteen, sixteen and two infection-related preferred terms were detected for palbociclib, ribociclib and abemaciclib, respectively., Conclusion: Infection-related AEs were highly associated with three CDK4/6 inhibitors, especially palbociclib and ribociclib, based on the real-world data from the FAERS database. However, further causality assessment is required., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Tang, Song, Sun and Zhang.)

Background: Netherton syndrome, a rare autosomal recessive genetic disease, lacks effective treatment options. This article presents a novel case of successful Upadacitinib therapy in a 14-year-old boy with Netherton syndrome., Case Presentation: A 14-year-old male with a lifelong history of dry skin, erythema, scaling, itching, and notable body odor was evaluated. These symptoms, accompanied by irregular hair growth and delayed development, prompted an initial diagnosis of atopic dermatitis at a local hospital. Treatment with antihistamines, moisturizers, and topical corticosteroids failed to alleviate systemic manifestations of red patches and persistent itching. Seeking further evaluation, the patient was presented to our center. Upon examination, the characteristics of "bamboo hair" and "golf tee sign" were observed microscopically in the patient's hair. Whole exome sequencing identified a paternally inherited mutation in the SPINK5 gene, confirming Netherton syndrome. No mutations were found in the mother. Despite initial positive responses to Secukinumab and Dupilumab, therapeutic efficacy waned over time., Results and Conclusions: Initiation of Upadacitinib at a daily dose of 15 mg yielded significant therapeutic benefits within a short timeframe. This study marks the first documented use of Upadacitinib in pediatric Netherton syndrome treatment. This case highlights the efficacy of Upadacitinib in treating Netherton syndrome, particularly in pediatric patients. Further studies are warranted to elucidate its long-term effects and optimal dosing regimens.

(1) Background: Humor stands out as the most dynamic and innovative aspect of human intelligence. Drawing on the cognitive parallels between humor and creativity, this study explored the EEG alpha frequency band activity patterns during humor generation by comparing the process of generating humorous and creative ideas. (2) Methods: Thirty-six participants were randomly assigned to either the humor generation group or the creative generation group, and the dependent variable was the neural oscillation in both low-frequency and high-frequency alpha during the early, middle, and late stages of both humor and creative generation. (3) Results: In the early stages, both humor and creative generation exhibited significantly higher power in low-frequency alpha and high-frequency alpha in the temporal region compared to the middle and late stages. In the middle and late stages, the low-frequency alpha oscillation in the frontal region for humor generation was significantly higher than that for creative generation. (4) Conclusions: Humor and creative generation share similar neural activation patterns in the early stages, involving the activation and retrieval of long-term memory information based on contextual cues. The differences between the two primarily manifest in the middle and late stages, where the selection of humorous ideas requires inhibiting not only irrelevant or ordinary ideas, akin to creative generation but also novel yet non-humorous ideas. This study sheds light on the neurocognitive mechanisms of humor generation and provides insights into the cognitive parallels and distinctions between humor generation and creative generation.

Introduction: Triazole antifungal agents are widely used to treat and prevent systemic mycoses. With wide clinical use, the number of reported adverse events has gradually increased. The aim of this study was to analyze the cardiac disorders associated with TAAs (fluconazole, voriconazole, itraconazole, posaconazole and isavuconazole) based on data from the US Food and Drug Administration Adverse Event Reporting System FDA Adverse Event Reporting System., Methods: Data were extracted from the FAERS database between the first quarter of 2004 and third quarter of 2022. The clinical characteristics in TAA-associated cardiac AE reports were analyzed. Disproportionality analysis was performed to evaluate the potential association between AEs and TAAs using the reporting odds ratio (ROR) and proportional reporting ratio (PRR)., Results: Among 10,178,522 AE reports, 1719 reports were TAA-associated cardiac AEs as primary suspect drug. Most reports were related to fluconazole (38.34%), voriconazole (28.56%) and itraconazole (26.76%). Itraconazole (N = 195, 42.39%) and isavuconazole (N = 2, 14.29%) had fewer serious outcome events than three other drugs including fluconazole, voriconazole, and posaconazole. 13, 11, 26, 5 and 1 signals were detected for fluconazole, voriconazole, itraconazole, posaconazole and isavuconazole, respectively. The number of new signals unrecorded in the drug label was 9, 2, 13, 2 and 0 for fluconazole, voriconazole, itraconazole, posaconazole and isavuconazole, respectively., Conclusion: Isavuconazole might be the safest of the five TAAs for cardiac AEs. TAA-associated cardiac disorders may result in serious adverse outcomes. Therefore, in addition to AEs on the drug label, we should pay attention to new AEs unrecorded on the drug label during the clinical use of TAAs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Xu, Yu, Sun and Zhang.)

Background: Antibody-drug conjugates (ADCs) are a relatively new class of anticancer agents that use monoclonal antibodies to specifically recognize tumour cell surface antigens. However, off-target effects may lead to severe adverse events. This study evaluated the neurotoxicity of ADCs using the FDA Adverse Event Reporting System (FAERS) database. Research design and methods: Data were extracted from the FAERS database for 2004 Q1 to 2022 Q4. We analysed the clinical characteristics of ADC-related neurological adverse events (AEs). We used the reporting odds ratio (ROR) and proportional reporting ratio (PRR) for the disproportionality analysis to evaluate the potential association between AEs and ADCs. Results: A total of 562 cases of neurological AEs were attributed to ADCs. The median age was 65 years old [(Min; Max) = 3; 92]. Neurotoxic signals were detected in patients receiving brentuximab vedotin, enfortumab vedotin, polatuzumab vedotin, trastuzumab emtansine, gemtuzumab ozogamicin, inotuzumab ozogamicin, and trastuzumab deruxtecan. The payloads of brentuximab vedotin, enfortumab vedotin, polatuzumab vedotin, and trastuzumab emtansine were microtubule polymerization inhibitors, which are more likely to develop neurotoxicity. We also found that brentuximab vedotin- and gemtuzumab ozogamicin-related neurological AEs were more likely to result in serious outcomes. The eight most common ADC-related nervous system AE signals were peripheral neuropathy [ROR (95% CI) = 16.98 (14.94-19.30), PRR (95% CI) = 16.0 (14.21-18.09)], cerebral haemorrhage [ROR (95% CI) = 9.45 (7.01-12.73), PRR (95% CI) = 9.32 (6.95-12.50)], peripheral sensory neuropathy [ROR (95% CI) = 47.87 (33.13-69.19), PRR (95% CI) = 47.43 (32.93-68.30)], polyneuropathy [ROR (95% CI) = 26.01 (18.61-36.33), PRR (95% CI) = 25.75 (18.50-35.86)], encephalopathy [ROR (95% CI) = 5.16 (3.32-8.01), PRR (95% CI) = 5.14 (3.32-7.96)], progressive multifocal leukoencephalopathy [ROR (95% CI) = 22.67 (14.05-36.58), PRR (95% CI) = 22.52 (14.01-36.21)], taste disorder [ROR (95% CI) = 26.09 (15.92-42.76), PRR (95% CI) = 25.78 (15.83-42.00)], and guillain barrier syndrome [ROR (95% CI) = 17.844 (10.11-31.51), PRR (95% CI) = 17.79 (10.09-31.35)]. The mortality rate appeared to be relatively high concomitantly with AEs in the central nervous system. Conclusion: ADCs may increase the risk of neurotoxicity in cancer patients, leading to serious mortality. With the widespread application of newly launched ADC drugs, combining the FAERS data with other data sources is crucial for monitoring the neurotoxicity of ADCs. Further studies on the potential mechanisms and preventive measures for ADC-related neurotoxicity are necessary., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tang, Sun, Liu, Wu and Ding.)

Context: Ginkgo biloba Linn (Ginkgoaceae) [leaves extract (GBE)] is authorized for the treatment of sudden hearing loss (SHL); however, its clinical feasibility in SHL has not been thoroughly investigated., Objective: To evaluate the efficacy and safety of adjuvant GBE in the treatment of SHL., Materials and Methods: We used PubMed, EMBASE, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang, Chinese Scientific Journal Database, China Biomedical Database for literature research, starting from inception to 30 June 2022. The key terms: Ginkgo biloba extract, Sudden Sensorineural Deafness. This meta-analysis contained randomized controlled trials that compared the safety and efficacy of the combination of GBE and general treatments (GT) with GT alone for SHL. The extracted data were analyzed using Revman5.4 software with risk ratio (RR), 95% confidence intervals (CI) and mean difference (MD)., Results: Our meta-analysis included 27 articles with a total of 2623 patients. The results revealed that the effects of GBE adjuvant therapy was superior than GT (total effective rate: RR = 1.22, 95% CI: 1.18-1.26, p  < 0.00001), the pure tone hearing threshold ( MD  = 12.29, 95% CI: 11.74-12.85, p  < 0.00001) and hemorheology indexes (whole blood high shear viscosity: MD  = 1.46, 95% CI: 0.47-2.44, p  = 0.004) after treatment were significantly improved compared to non-treatment, while there was no significant difference as for hematocrit (red blood cells) ( MD  = 4.15, 95% CI: -7.15-15.45, p  = 0.47)., Conclusion: The efficacy of GBE + GT for the treatment of SHL may be more promising than GT alone.

Polo-like kinase 1 (PLK1) is an attractive therapeutic target for the treatment of tumors, as it is an essential cell-cycle regulator frequently overexpressed in tumor tissues. PLK1 can promote tumor invasion and metastasis, and is often associated with poor prognosis in cancer patients. However, no PLK1 inhibitor has been granted marketing approval until now. Therefore, more potentially promising PLK1 inhibitors need to be investigated. In this study, a series of novel inhibitors targeting PLK1 was designed and optimized derived from a new scaffold. After synthesis and characterization, we obtained the structure-activity relationship and led to the discovery of the most promising compound 30e for PLK1. The antiproliferative activity against HCT116 cells (IC 50  = 5 nM versus 45 nM for onvansertib) and the cellular permeability and efflux ratio were significantly improved (P appA→B  = 2.03 versus 0.345 and efflux ratio = 1.65 versus 94.7 for 30e and onvansertib, respectively). Further in vivo studies indicated that 30e had favorable antitumor activity with 116.2% tumor growth inhibition (TGI) in comparison with TGI of 43.0% for onvansertib. Furthermore, 30e improved volume of tumor tissue distribution in mice as compared to onvansertib. This initial study on 30e holds promise for further development of an antitumor agent., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jing Lu reports financial support was provided by National Natural Science Foundation of China. Jing Lu reports financial support was provided by Natural Science Foundation of Shandong Province. Jianzhao Zhang reports financial support was provided by Initial Scientific Research Fund of Yantai University. Hui Lei has patent pending to Luye Pharma Group Ltd. No., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The abnormal upregulation of programmed death ligand-1 (PD-L1) on tumor cells impedes T-cell mediated cytotoxicity through PD-1 engagement, and further exploring the mechanisms regulation of PD-L1 in cancers may enhance the clinical efficacy of PD-L1 blockade. Here, using single-guide RNAs (sgRNAs) screening system, we identify ubiquitin-specific processing protease 2 (USP2) as a novel regulator of PD-L1 stabilization for tumor immune evasion. USP2 directly interacts with and increases PD-L1 abundance in colorectal and prostate cancer cells. Our results show that Thr288, Arg292 and Asp293 at USP2 control its binding to PD-L1 through deconjugating the K48-linked polyubiquitination at lysine 270 of PD-L1. Depletion of USP2 causes endoplasmic reticulum (ER)-associated degradation of PD-L1, thus attenuates PD-L1/PD-1 interaction and sensitizes cancer cells to T cell-mediated killing. Meanwhile, USP2 ablation-induced PD-L1 clearance enhances antitumor immunity in mice via increasing CD8 + T cells infiltration and reducing immunosuppressive infiltration of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs), whereas PD-L1 overexpression reverses the tumor growth suppression by USP2 silencing. USP2-depletion combination with anti-PD-1 also exhibits a synergistic anti-tumor effect. Furthermore, analysis of clinical tissue samples indicates that USP2 is positively associated with PD-L1 expression in cancer. Collectively, our data reveal a crucial role of USP2 for controlling PD-L1 stabilization in tumor cells, and highlight USP2 as a potential therapeutic target for cancer immunotherapy., (© 2023. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.)

Background: Research on Jinshuibao (JSB) for chronic renal failure (CRF) is limited, its clinical efficacy on CRF has not been evaluated. Our aim is to systematically evaluate the efficacy of JSB for the treatment of CRF in Chinese patients, and to provide evidence-based medical advice for clinical practice., Methods: Randomized controlled trials (RCTs) which compared JSB combined with conventional treatment (CT) with CT alone in CRF were searched in 8 databases including PubMed, EMBASE, Cochrane Library, Web of science, China Biology Medicine disc, Wanfang, Chinese Scientific Journal Database (VIP) and China National Knowledge Infrastructure form inception to March 31, 2023. RevMan5.4 statistical software was used for meta-analysis., Results: 17 trials involving 1431 cases were identified for meta-analysis. The results showed that total effective rate (relative risk [RR] = 1.25, 95% confidence internal [CI]: 1.17-1.34, P < .00001), creatinine clearance rate (Ccr) (MD = -8.63, 95% CI: -12.42 to -4.84, P < .00001), albumin (Alb) (MD = -2.88, 95% CI: -4.85 to -0.92, P = .004) and hemoglobin (Hb) (MD = -5.88, 95% CI: -7.42 to -4.34, P < .00001) in JSB plus CT were significantly higher than those in CT; while blood urea nitrogen (BUN) (MD = 2.03, 95% CI: 1.27-2.80, P < .00001), serum creatinine (Scr) (MD = 48.23, 95% CI: 31.96-64.49, P < .00001), 24-hour urine protein (24hpro) (MD = 0.19, 95% CI: 0.06-0.31, P = .003), uric acid (UA) (MD = 76.36, 95% CI: 12.40-140.31, P = .02), tumor necrosis factor-α (TNF-α) (MD = 10.74, 95% CI: 5.04-16.45, P = .0002), interleukin-6 (IL-6) (MD = 5.07,95% CI: 1.21-8.92, P = .01), high-sensitivity C-reactive protein (hs-CRP) (MD = 3.74, 95% CI: 0.96-6.52, P = .008) in JSB plus CT were significantly lower than those in CT., Conclusion: Combining JSB with CT has a good effect on the treatment of CRF in Chinese people. High-quality RCTs are needed to further confirm the results., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Humor is a lubricant of interpersonal relationships and is regarded as an important quality of individual creativity. Previous studies have mainly focused on passive humor appreciation and comprehension but ignored active humor generation, especially the cognitive process of humor generation. Based on the hypothesis that humor generation is similar to creative cognition, this study used humorous two-part allegorical sayings to explore whether humor generation involves the cognitive processes of the activation and inhibition of information. The experiment manipulated the duration (5/10 s) of the presentation of the first part of humorous two-part allegorical sayings, which are called "yinyu," and the type of subthreshold probe words (humorous probe words/usual probe words). The results showed that the interaction between the duration of the presentation of yinyu and the type of subthreshold probe words was significant; the correct number of humorous probe words reported was significantly lower than that of usual probe words when the yinyu was presented for 5 s, which reflected the widespread activation of information. The correct number of humorous probe words reported was significantly higher than that of usual probe words when the yinyu was presented for 10 s, which suggested the inhibition of non-humorous information. This study revealed the dynamic cognitive processes of humor generation and verified possible cognitive similarities between humor generation and creative cognition., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Immune checkpoint therapies (ICT) have achieved unprecedented efficacy in multiple cancer treatments, but are still limited by low clinical response rates. Identification of immunogenic cell death (ICD)-inducing drugs that can induce tumor cell immunogenicity and reprogram the tumor microenvironment is an attractive approach to enhance antitumor immunity. In the present study, Raddeanin A (RA), an oleanane class triterpenoid saponin isolated from Anemone raddeana Regel, is uncovered as a potent ICD inducer through an ICD reporter assay combined with a T cell activation assay. RA significantly increases high-mobility group box 1 release in tumor cells and promotes dendritic cell (DC) maturation and CD8 + T cell activation for tumor control. Mechanistically, RA directly binds to transactive responsive DNA-binding protein 43 (TDP-43) and induces TDP-43 localization to mitochondria and mtDNA leakage, leading to cyclic GMP-AMP synthase/stimulator of interferon gene-dependent upregulation of nuclear factor κB and type I interferon signaling, thereby potentiating the DC-mediated antigen cross-presentation and T cell activation. Moreover, combining RA with anti-programmed death 1 antibody effectively enhances the efficacy of ICT in animals. These findings highlight the importance of TDP-43 in ICD drug-induced antitumor immunity and reveal a potential chemo-immunotherapeutic role of RA in enhancing the efficacy of cancer immunotherapy., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

The second-generation mammalian target of rapamycin (mTOR) inhibitor PP242 has demonstrated limited success in some rapamycin-insensitive tumours. We examined the therapeutic potential of combining PP242 with adenosine 50- monophosphate-activated protein kinase (AMPK) activator metformin, using a panel of colorectal carcinoma (CRC) cell lines. We found that the PP242 and metformin combination enhanced the suppression of CRC cell proliferation, colony formation, and cancer cell apoptosis induction. The effect of this combination was observed on AMPK phosphorylation. Western blotting showed that PP242 inhibited mTORC1 activation, as indicated by the reduced expression of its major substrate p-S6K1 and the partially reduced phosphorylation of eIF4E-binding protein 1 (4E-BP1). The inhibition of mTORC2-mediated AKT phosphorylation at Ser 473 (AKT Ser473) was transient and occurred in the first few hours of PP242 treatment; metformin exposure decreased the PP242 activity, counteracting AKT activation. We further demonstrated that this was related to direct AMPK-mediated phosphorylation of IRS-1 at Ser789. Thus, the combination of PP242 and metformin completely blocked the activity of both mTORC1 and mTORC2 kinase. This study suggests that this combination could be a more effective strategy for the treatment of CRC.

Purpose: We explored the adverse drug reaction signals of drug-induced neutropenia (DIN) and drug-induced agranulocytosis (DIA) in hospitalized patients and evaluated the novelty of these correlations., Method: A two-step method was established to identify the relationship between drugs and DIN or DIA using 5-year electronic medical records (EMRs) obtained from 242 000 patients at Qilu Hospital of Shandong University. First, the drugs suspected to induce DIN or DIA were selected. The associations between suspected drugs and DIN or DIA were evaluated by a retrospective cohort study using unconditional logistic regression analysis and multiple linear regression model., Results: Twelve suspected drugs (vancomycin, meropenem, voriconazole, acyclovir, ganciclovir, fluconazole, oseltamivir, linezolid, compound borax solution, palonosetron, polyene phosphatidylcholine, and sulfamethoxazole) were associated with DIN, and six suspected drugs (vancomycin, voriconazole, acyclovir, ganciclovir, fluconazole, and oseltamivir) were associated with DIA. The multivariate linear regression model revealed that nine drugs (vancomycin, meropenem, voriconazole, ganciclovir, fluconazole, oseltamivir, compound borax solution, palonosetron, and polyene phosphatidylcholine) and four drugs (vancomycin, voriconazole, ganciclovir, and fluconazole) were found to be associated with DIN and DIA, respectively. While logistic regression analysis revealed that palonosetron and ganciclovir were associated with DIN and DIA, respectively., Conclusion: Palonosetron and ganciclovir were found to be correlated with drug-induced granulocytopenia. The results of this study provide an early warning of drug safety signals for drug-induced granulocytopenia, facilitating a quick and appropriate response for clinicians., (© 2022 John Wiley & Sons Ltd.)

The plate-like iron-rich intermetallic phases in recycled aluminum alloys significantly deteriorate the mechanical properties. In this paper, the effects of mechanical vibration on the microstructure and properties of the Al-7Si-3Fe alloy were systematically investigated. Simultaneously, the modification mechanism of the iron-rich phase was also discussed. The results indicated that the mechanical vibration was effective in refining the α-Al phase and modifying the iron-rich phase during solidification. The forcing convection and a high heat transfer inside the melt to the mold interface caused by mechanical vibration inhibited the quasi-peritectic reaction: L + α-Al 8 Fe 2 Si → (Al) + β-Al 5 FeSi and eutectic reaction: L → (Al) + β-Al 5 FeSi + Si. Thus, the plate-like β-Al 5 FeSi phases in traditional gravity-casting were replaced by the polygonal bulk-like α-Al 8 Fe 2 Si. As a result, the ultimate tensile strength and elongation were increased to 220 MPa and 2.6%, respectively.

Menaquinone-7 (MK-7) is an important vitamin K 2 , synthesized from the menaquinone parent ring and seven isoprene side chains. Presently, the synthesis of MK-7 stimulated by environmental stress primarily focuses on oxygen stress, while the effect of alkali stress is rarely studied. Therefore, this study researched the effects of alkali stress on the fermentation performance and gene expression of Bacillus subtilis natto . The organism's growth characteristics, biomass, sporogenesis, MK-7 biosynthesis, and gene expression were analyzed. After a pH 8.5 stress adaptation treatment for 0.5 h and subsequent fermentation at pH 8.5, which promoted the growth of the strain and inhibited the spore formation rate. In addition, biomass was significantly increased ( P < 0.05). The conversion rate of glycerol to MK-7 was 1.68 times higher than that of the control group, and the yield of MK-7 increased to 2.10 times. Transcriptomic analysis showed that the MK-7 high-yielding strain had enhanced carbon source utilization, increased glycerol and pyruvate metabolism, enhanced the Embden-Meyerhof pathway (EMP), tricarboxylic acid (TCA) circulation flux, and terpenoid biosynthesis pathway, and promoted the accumulation of acetyl-CoA, the side-chain precursor of isoprene. At the same time, the up-regulation of transketolase increased the metabolic flux of the pentose phosphate (HMP) pathway, which was conducive to the accumulation of D-erythrose 4-phosphate, the precursor of the menadione parent ring. This study's results contribute to a better understanding of the effects of environmental stress on MK-7 fermentation by Bacillus subtilis natto and the molecular regulatory mechanism of MK-7 biosynthesis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Shang, Zhang, Sun, Zhang, Liu, Li, Li and Du.)

Background: Cracked teeth may cause various clinical symptoms depending on the extension depth of the crack and the subsequent bacterial infections. However, techniques to reliably determine the extension depths of cracks in teeth before treatment are lacking. The aim of this study was to develop a new technique based on contrast-enhanced cone beam computed tomography (CBCT) to improve the accuracy of crack depth evaluation in vitro., Methods: We developed an in vitro artificial simulation model of cracked teeth. Pre-experimental CBCT (pre-CBCT), and micro-computed tomography (micro-CT) were first performed for all cracked teeth (n = 31). Contrast-enhanced CBCT was then performed by infiltrating the crack with ioversol under vacuum conditions. The sensitivities of pre-CBCT and contrast-enhanced CBCT for the diagnosis of cracked teeth were calculated. According to the K-means clusters, crack depths measured by micro-CT were changed into categorical variables. Bland-Altman plot and the intraclass correlation coefficient (ICC) were used to analyze the consistency of the crack depths between the pre-CBCT and contrast-enhanced CBCT, as well as the ICC between the contrast-enhanced CBCT and micro-CT. Receiver operating characteristic (ROC) curves were generated to assess the ability for predicting crack depth in the differential diagnosis using pre-CBCT and contrast-enhanced CBCT. Restricted cubic splines were also used to model the non-linear relationship between the crack depths of contrast-enhanced CBCT and micro-CT., Results: The sensitivities of pre-CBCT and contrast-enhanced CBCT were 48.4%, and 67.7%, respectively. The ICC value of crack depth as measured by pre-CBCT and contrast-enhanced CBCT was 0.847 (95% confidence interval [CI] 0.380-0.960; P < 0.001). The areas under ROC curves (AUC) of pre-CBCT and contrast-enhanced CBCT were different: the AUC of pre-CBCT was 0.958 (P = 0.000, 95% CI 0.843-1.074), and the AUC of contrast-enhanced CBCT was 0.979 (P = 0.000, 95% CI 0.921-1.037), and the difference was not statistically significant (Z = - 0.707, P = 0.480). The ICC value of crack depth as measured by contrast-enhanced CBCT and micro-CT was 0.753 (95% CI 0.248-0.911; P < 0.001)., Conclusion: Contrast-enhanced CBCT under vacuum conditions with a contrast medium can significantly improve the crack detection rate of cracked teeth; however, it cannot measure the crack depths accurately., (© 2022. The Author(s).)

It is essential to develop cost-effective rechargeable metal-air batteries, with high activity, stability, and efficiency, that use non-precious metals (NPMs)-based cathodic oxygen reduction reaction (ORR) catalysts. Here, by using earth-abundant corncob (CC) as the carbon source, Co(OH) 2 , NaH 2 PO 4 , and melamine as the precursors, and KOH as the chemical activator, CoNP@bio-C-a is obtained and comparative studies are carried out with three other types of CC-derived carbon-based catalytic materials, namely, bio-C, CoP@bio-C, and CoNP@bio-C. Depending mainly on the formation of Co 2 O 3 /Co 2 N 0.67 active sites (as p-n heterojunctions) and N, P, O-containing functional groups, the resultant CoNP@bio-C-a catalyst exhibits best electrocatalytic activity among the four types of catalysts; via a 4-electron pathway, it has good stability and good methanol tolerance. In addition, its unique honeycomb-like porous structure, high graphitization degree, and abundant oxygen-containing groups contribute to its excellent ORR activity. This study provides insights for exploring the application of heteroatom-doped biomass-derived carbon catalysts., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The electronic and transport properties of fluorographane (C 2 HF) nanoribbons, i.e. , bare (B-C 2 HF) and hydrogen-passivated (H-C 2 HF) C 2 HF nanoribbons, are extensively investigated using first-principles calculations. The results indicate that edge states are present in all the B-C 2 HF nanoribbons, which are not allowed in the H-C 2 HF nanoribbons regardless of the directions. The spin splitting phenomenon of band structure only appears in the zigzag direction. This behavior mainly originates from the dehydrogenation operation, which leads to sp 2 hybridization at the edge. The H-C 2 HF nanoribbons are semiconductors with wide band gaps. However, the band gap of B-C 2 HF nanoribbons is significantly reduced. Remarkably, the phase transition can be induced by the changes in the magnetic coupling at the nanoribbon edges. In addition, the B-C 2 HF nanoribbons along the zigzag direction show optimal conductivity, which is consistent with the band structures. Furthermore, a perfect spin filtering controller can be achieved by changing the magnetization direction of the edge C atoms. These results may serve as a useful reference for the application of C 2 HF nanoribbons in spintronic devices., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Valsa mali is the causative agent of apple tree valsa canker, which causes significant losses in apple production. It produces various toxic compounds that kill plant cells, facilitating infection. Among these, protocatechuic acid exhibits the highest phytotoxic activity. However, those genes involved in toxin production have not been studied. In this study we identified four hydroxybenzoate hydroxylase genes (VmHbh1, VmHbh2, VmHbh3, and VmHbh4) from the transcriptome of V. mali. The VmHbh protein had high enzymatic activities of hydroxybenzoate hydroxylase, which could convert 4-hydroxybenzoate to protocatechuic acid. These four VmHbh genes all had highly elevated transcript levels during the V. mali infection process, especially VmHbh1 and VmHbh4, with 26.0- and 53.4-fold increases, respectively. Mutants of the four genes were generated to study whether VmHbhs are required for V. mali pathogenicity. Of the four genes, the VmHbh1 and VmHbh4 deletion mutants considerably attenuated V. mali virulence in apple leaves and in twigs, coupled with much reduced toxin levels. The VmHbh2 and VmHbh3 deletion mutants promoted the transcript levels of the other VmHbhs, suggesting functional redundancies of VmHbhs in V. mali virulence. The results provide insights into the functions of VmHbhs in the production of protocatechuic acid by V. mali during its infection of apple trees., (© 2021 The Authors. Molecular Plant Pathology published by British Society for Plant Pathology and John Wiley & Sons Ltd.)

BACKGROUND This study aimed to compare the size and location of the traditional and conservative endodontic access cavities of the right maxillary first molar teeth, projected on the occlusal surface using cone-beam computed tomography (CBCT), to obtain an ideal access cavity. MATERIAL AND METHODS Five hundred CBCT images of the right maxillary first molars, including 198 males and 302 females, were retrospectively evaluated using KaVo eXam Vision software. First, a rectangular coordinate system was established. The coordinates of 4 pulp horns and 3 root canal orifices, which projected on the occlusal surface, were marked on it. Two different access cavities were then created by connecting these points: (1) traditional endodontic access cavity (TEC) required removal of the entire roof of the pulp chamber to establish a straight-line access to the root canal system; (2) conservative endodontic access cavity (CEC) was formed by connecting the projection of each root canal orifice on the occlusal. Data were analyzed using Kruskal-Wallis and Pearson's correlation tests at a 5% significance level. RESULTS The area of TEC was approximately 9.61 mm2 for males and 8.91 mm² for females. The area of CEC was approximately 3.4 mm² for males and 3.16 mm² for females. The projections of all pulp horns and root canal orifices were in or near the central area of nine-rectangle-grid. CONCLUSIONS Compared with the traditional access cavity, creating a conservative access cavity was less invasive. Meanwhile, the access cavity should be limited to the central or near the central area of nine-rectangle-grid.

The apple tree canker is caused by Valsa mali , which produces major pathogenic factors involving multiple cell wall-degrading enzymes (CWDEs) and toxins. The β-glucosidases are among the main CWDEs, and thus, they play important roles in the virulence of necrotrophic pathogens. However, the specific roles of β-glucosidases in the virulence of V. mlai remain largely unknown. In this study, we identified a β-glucosidase gene, V mGlu2 , which was upregulated during the V. mali infection. We found that VmGlu2 protein had high enzyme activity of β-glucosidase using p-nitrophenyl-β-D-glucopyranoside (pNPG) as a substrate, while the VmGlu2 could convert phloridzin to phloretin with the release of glucose. The deletion and overexpression of VmGlu2 showed no effect on vegetative growth, but gene deletion mutants of V. mlai showed significantly reduced pycnidia formation. The gene deletion mutants had lower β-glucosidase activities and toxin levels as compared to the wild-type strain. Therefore, these mutants showed a reduced virulence. Moreover, the overexpression of VmGlu2 did not affect toxin levels, but it significantly enhanced β-glucosidase activities, which resulted in an increased pathogenicity. Thus, we conclude that VmGlu2 is required for the full virulence of V. mali . These results provide valuable evidence to the complex role of CWDEs in the fungal pathogenicity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Huang, Yu, Sun, Saleem, Li, Li and Wang.)

Background: According to the diagnosis criteria of the American Association of Endodontists (AAE), sensitive responses to cold and/or heat tests of suspected teeth compared with those of control teeth can be used for the diagnosis of pulpitis, but the role of electric pulp test (EPT) is not mentioned. It is believed that EPT has some limitations in determining the vitality of the pulp. The aim of this study was to explore the association between the difference in EPT values and the differential diagnoses of reversible pulpitis (RP) and symptomatic irreversible pulpitis (SIRP) caused by dental caries., Methods: A total of 203 cases with pulpitis caused by dental caries were included. A diagnosis of pulpitis was made on the basis of the diagnostic criteria of AAE. Patient demographic and clinical examination data were collected. The EPT values of the suspected teeth and control teeth were measured, and the differences between them were calculated. The correlation between the difference in the EPT values and diagnosis of pulpitis was analyzed using univariate and multivariate logistic regression., Results: In the 203 cases (78 males and 125 females; 115 cases of RP, 88 cases of SIRP; 9 anterior teeth, 59 premolars, and 135 molars), the mean patient age was 34.04 ± 13.02 (standard deviation) years. The unadjusted (crude) model, model 1 (adjusted for age), model 2 (adjusted for age and sex), and model 3 (adjusted for age, sex, and tooth type) were established for the statistical analyses. In model 3 [odds ratio (OR) = 1.025; 95% confidence interval (CI) 1.002-1.050; P = 0.035], the difference in EPT values between RP and SIRP was statistically significant. However, the areas under the curve of predictive probability of the crude model, model 1, model 2, and model 3 were 0.565, 0.570, 0.585, and 0.617, respectively, showing that the model accuracy was low. The P-value for the trend in differences between the EPT values as a categorical variable showed that the differences in the EPT values, comparing RP and SIRP, were not statistically significant., Conclusions: Based on the present data, the difference in EPT values was not sufficient to differentiate RP from SIRP., (© 2021. The Author(s).)

The present study tests the precariousness of manhood and the impact of precarious manhood on aggression. In total, 50 undergraduates (25 girls, 25 boys) participated in this experiment. It was found that the male participants used more verbs in the "A man should&#95;&#95;" sentence string than in the "One woman should&#95;&#95;" sentence string, and similar language patterns were found even after controlling for gender stereotypes. Individuals were found to more often attribute the individual behavior caused by cultural scripts to external situational factors; that is, if individuals agreed that another male's aggression was due to threatened manhood, this behavior was seen to be because of the male cultural script and was due to external circumstances. To test this view, a total of 56 college students participated in this experiment. In total, 25 college students (11 males, 14 females) took part in the attribution evaluation of two male fighters, and 31 college students (15 males, 16 females) participated in the attribution evaluation of two female fighters. It was found that the male participants believed that other male physical aggression that threatened their manhood was induced by situational factors rather than the internal characteristics of the attacker. The differences between the female participants were not significant, indicating that it was part of the male cultural script for men (rather than women) to defend or restore precarious manhood through aggression.

When humans are confronted with an epidemic situation or a continuous natural disaster, success depends largely on how critical information is conveyed to as many people as possible, how individuals' emotional experiences of the crisis are elicited, and how their behaviors are directed going forward. Efficient publicity is key to successful epidemic prevention and control. This study explores the role of creative publicity by comparing the influence of creative publicity and general publicity in different periods of the COVID-19 outbreak in China. The effects of creative and general publicity differed across varying periods of the COVID-19 outbreak. Specifically, compared to general publicity, creative publicity had a significant impact on individuals' emotional arousal in the early period of the COVID-19 outbreak while it significantly promoted individuals' emotional arousal, behavioral regulation, and willingness to actively disseminate information in the middle period. In the stable period of the COVID-19 outbreak, creative publicity performed better than general publicity in regulating individuals' behavior. On the other hand, general publicity was more effective than creative publicity in regulating individuals' behavior and actively disseminating information about the epidemic in the early period of the COVID-19 outbreak. In conclusion, creative and general publicity had differing effects in different periods of the COVID-19 outbreak, which may relate to the characteristics of the publicity format and people's psychological conditions in different periods of the COVID-19 outbreak., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Jia, Sun, Zhou, Zhao, Yu, Liu and Wang.)

Apple ring rot caused by Botryosphaeria dothidea is an important disease in China, which leads to serious economic losses during storage. Plant activators are compounds that induce resistance against pathogen infection and are considered as a promising alternative strategy to traditional chemical treatment. In the present study, butylated hydroxytoluene (BHT), a potential plant activator, was evaluated for its induced resistance against B. dothidea in postharvest apple fruits. The physiological and molecular mechanisms involved in induced resistance were also explored. The results showed that BHT treatment could trigger strong resistance in apple fruits against B. dothidea , and the optimum concentration was 200 μmol L -1 by immersion of fruits. BHT treatment significantly increased the activities of four defensive enzymes and alleviated lipid peroxidation by increasing antioxidant enzyme activities. In addition, salicylic acid (SA) content was enhanced by BHT treatment as well as the expression of three SA biosynthesis-related genes ( MdSID2 , MdPAD4 , and MdEDS1 ) and two defense genes ( MdPR1 and MdPR5 ). Our results suggest that BHT-conferred resistance against B. dothidea might be mainly through increasing the activities of defense-related enzymes and activating SA signaling pathway, which may provide an alternative strategy to control apple ring rot in postharvest fruits., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Huang, Sun, Guan, Lian, Li and Wang.)

Apple ring rot, caused by Botryosphaeria dothidea, is one of the important diseases in China. This pathogen infects branches and fruit and also results in fruit decay during storage. Biocontrol agents have been proposed to reduce apple decays during storage and are considered as a promising alternative strategy to traditional chemical treatment. In this study, Meyerozyma guilliermondii Y-1, isolated from healthy grape fruit, was firstly evaluated for its biocontrol efficiency against B. dothidea in postharvest apple fruit, and the possible mechanisms were investigated. The results revealed that M. guilliermondii Y-1 treatment effectively reduced apple ring rot caused by B. dothidea in vivo. The disease incidence and lesion diameter were reduced by 32.22% and 57.51% compared with those of control fruit. Furthermore, the use of filtrate and autoclaved culture of M. guilliermondii Y-1 also showed a certain degree of control efficiency against fruit ring rot. M. guilliermondii Y-1 significantly inhibited the mycelial growth and spore generation of B. dothidea in vitro and exhibited an obvious ability to colonize in apple fruit wounds and surface at 25 °C or 4 °C. In addition, M. guilliermondii Y-1 treatment significantly enhanced the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), phenylalanine ammonialyase (PAL), and polyphenoloxidase (PPO), promoted the total phenolics content, and alleviated lipid peroxidation in apple fruit. As expected, we found that the expression of four pathogenesis-related proteins genes (MdPR1, MdPR5, MdGLU, and MdCHI) was remarkably increased by M. guilliermondii Y-1 treatment. Our data together suggest that M. guilliermondii Y-1 is a potential biocontrol agent against B. dothidea postharvest infection in apple fruit, partially through inhibiting mycelial growth and spore germination of B. dothidea, competing for space and nutrient with pathogen, and inducing resistance in apple fruit by stimulating a series of defense responses., (Copyright © 2020. Published by Elsevier B.V.)

Introduction: The composition and relative abundance of bacterial species change throughout the development of dental caries; however, how these changes relate to clinical symptoms remains elusive. In this study, we explored the relationship between clinical symptoms and specific microorganisms in advanced dentinal caries., Methods: A total of 111 permanent premolars and molars were used to simulate the progression from caries to pulpitis indirectly. Clinical symptoms were evaluated, and teeth were diagnosed according to the diagnostic criteria of the American Association of Endodontics. Samples were collected for 16S ribosomal DNA sequencing. Associations between the microbiota and clinical symptoms/diagnosis and the relationship between alpha diversity and clinical symptoms/diagnosis were evaluated independently by the linear discriminant analysis effect size and Spearman rank correlation analyses., Results: The 16S ribosomal DNA sequences were assigned to 13,852 operational taxonomic units. The linear discriminant analysis effect size and Spearman correlations unveiled negative associations between the relative abundance of Bacteroidia and Gammaproteobacteria and referred pain, Gammaproteobacteria and the electric pulp test response, and Actinomyces and Propionibacterium and diagnosis (r < 0.0, P < .05). Conversely, the relative abundance of Lactobacillus was positively correlated to referred pain, the cold test, the percussion response, and diagnosis (r > 0, P < .05). Lactobillus reuteri, a probiotic bacterium, was more abundant in teeth with referred pain and teeth diagnosed with symptomatic irreversible pulpitis. The Spearman correlation between alpha diversity and clinical symptoms/diagnosis was not significant (P > .05)., Conclusions: Clinical symptoms and diagnosis were significantly associated with specific microorganisms in the most advanced layers of dentinal caries., (Copyright © 2020 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Carbon dots (CDs) synthesized from natural products have drawn numerous attentions due to some unique properties. Here, Prunus cerasifera fruits were used as carbon source to synthesize high luminescent CDs by hydrothermal method. The obtained CDs were characterized by TEM, FTIR and XPS methods, founding the CDs were near-spherical and contained abundant nitrogen element. The CDs aqueous solution exhibited bright blue fluorescence under ultraviolet illumination, with the maximum emission at 450 nm. They could be potentially used as invisible fluorescent ink by written on the paper and irradiated by UV light, due to their fluorescent properties. Moreover, the CDs were found being selectively quenched by Fe 3+ ion. The quench of CDs was linearly related to the concentration of Fe 3+ ion in the range of 0-0.5 mM, meaning they could be developed as fluorescent probe of Fe 3+ ion. At last, the CDs were used for cell imaging, founding they were low toxicity to HepG2 cells and exhibited blue and green fluorescence under a fluorescence microscope. In summary, the CDs prepared from Prunus cerasifera fruits exhibited excellent fluorescence properties, and could be potentially applied in the field of fluorescent ink, Fe 3+ ion detection and cell imaging., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: This study examined the identity of the microbiome of deep dentinal caries and its correlation with the inflammation status of caries-induced pulpitis., Methods: Seventy-five cases were diagnosed based on the American Association of Endodontics's diagnostic criteria and divided into 4 groups: normal pulp with deep caries (NP; n = 13), reversible pulpitis with only cold-evoked pain (CRP; n = 17), reversible pulpitis with both cold/heat-evoked pain (CHRP; n = 24), and symptomatic irreversible pulpitis (SIP; n = 21). Samples were sequenced by 16S rDNA. Alpha and beta diversity were determined. Linear discriminant analysis effect size (LEfSe) analysis was used to detect intergroup differences, and receiver operating characteristic (ROC) curves were generated to assess the role of the caries microbiome in caries-induced pulpitis., Results: The 16S rDNA sequencing yielded 9100 operational taxonomic units. Lactobacillus had the highest relative abundance at the genus level among the 4 groups. There were significant differences in the distribution of the microbiome among the groups. In an alpha diversity analysis, species richness differed between the CRP group and the other groups. In a beta diversity analysis, the distribution of microorganisms in the SIP group was significantly different from those in the other 3 groups. LEfSe analysis indicated substantial differences in the microbiome among the groups, and the areas under the ROC curves (AUC) were all high (AUC: 0.734-0.952)., Conclusions: Characterization of the caries microbiome has the potential to become an auxiliary method for the diagnosis of pulpitis. This finding may prompt new research on diagnostic strategies for caries-induced pulpitis., (Copyright © 2018 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Background: Diagnosing with low-grade gliomas (LGGs) can be a very shocking and stressful experience, a traumatic event potentially leading to the development of posttraumatic stress symptoms (PTSS), and posttraumatic growth (PTG). Understanding how patients cognitively and behaviorally response to their diagnosing is also important to postoperative treatment. Thus, the current study explored the association between PTG and quality of life (QoL) of Chinese patients with LGGs. The moderation effects of coping strategies and PTSS on the relationship between PTG and QoL have been examined as well. Methods: Posttraumatic stress symptoms, Posttraumatic growth, coping strategies, and QoL were measured by using self-report surveys. Three hundred and thirty patients completed surveys approximately 1 month after surgery. We used three multiple regression models and added interaction terms in these models to test the moderation effects of PTSS and coping strategies on the relationship between PTG and QoL. Results: The results of hierarchical multiple regression suggested that PTG significantly predicted QoL, both PTSS and coping strategies moderated the association between PTG and QoL. Specifically, the association between PTG and QoL for patients who have non-significant PTSS is stronger than those who have significant PTSS. Furthermore, as the score of Avoidant Coping increases, the association between PTG and QoL becomes weaker. Conclusion: Posttraumatic growth may help to improve the QoL of LGGs patients, but PTSS and Avoidant Coping impeded the positive effect of PTG on QoL.

The Doctrine of the Mean (zhongyong) introduced by Confucianism is not only an aspect of faith, but also a way of thinking for Chinese individuals. Zhongyong includes two thinking forms: eclectic thinking (ET; i.e., "neither-A-nor-B") and integrated thinking (IT; i.e., "both-A-and-B"). Given the inclination of Asian individuals toward situational cognition, this study used questions about situations familiar to Chinese undergraduates to activate either ET or IT. This was done to investigate the effects of the two divergent thinking forms of zhongyong on performance levels on the Remote Associates Test (RAT). Both behavioral and EEG results found that participants in the IT condition demonstrated higher RAT scores than those in the ET condition. The conclusion was that the RAT and priming tasks shared the same neural mechanism. This meant that the priming tasks of IT allowed participants to enter a state of creative preparation in advance, further affecting resolution of the RAT.

Three ruminally fistulated Xuanhan steers weighting 312.5 (±23.85) kg were used to determine the kinetics of ruminal degradation of nutrients using in situ nylon bag technique, and a modified 3-step in vitro procedure was adopted to estimate intestinal digestibility of 16-h rumen undegradable protein (RUP) of maize cob (MC), distillers grains (DG), spent mushroom substrate (SMS), starch residue of sweet potato (SRSP), citrus pulp (CPP), and rice straw (RS). Samples were incubated for 0, 2, 6, 16, 24, 36, 48 and 72 h. Additional samples were incubated for 16 h in the rumen, and the residues from these bags were transferred to the nitrogen-free polyester bags for determination of intestinal digestibility in vitro. The highest DM disappearance at 6-h incubation was in SRSP (P < 0.01), and that at 36, 48, and 72 h was in CPP (P < 0.01). The lowest DM disappearance at 2- and 6-h incubation was in RS and SMS (P < 0.01), and that at 36, 48, and 72 h incubation was in RS, MC, and DG (P < 0.01). The lowest and greatest CP disappearance was in RS and DG, respectively, at all the incubation times (P < 0.01). There was no difference (P > 0.07) on CP disappearance between DG and MC at all the time points except for 16 and 24 h. NDF and ADF disappearance for SRSP was significantly higher (P < 0.01) than other roughages at all the time points except for ADF at 72 h. The lowest NDF and ADF disappearance was in DG at all the time points (P < 0.01) except 2 and 6 h. The effective degradability (ED) of DM was the highest in CPP (P < 0.01) and the lowest in MC and RS (P < 0.01). The highest and lowest ED of CP was in DG and in RS (P < 0.01), respectively. The ED of NDF was the highest in SRSP (P < 0.01), followed by CPP and RS, and the lowest in DG (P < 0.01). The ED of ADF was the highest in SRSP and CPP (P < 0.05), and the lowest in DG (P < 0.01). For MC, DG SMS, SRSP, CPP, and RS, the intestinal digestibility of RUP was 95.28%, 37.23%, 38.72%, 48.06%, 54.49%, and 37.88%, respectively, and the content of intestinal digestible crude protein (IDCP) was 23.65, 83.63, 35.63, 15.03, 25.60, and 12.03 g/kg, respectively. Distillers grain was considered to be of good quality for the greatest content of IDCP. Although not readily degraded in rumen, CP in MC may be digested well in small intestine.

The transport and photoelectric properties of four two-dimensional (2D) silicene/MX 2 (M = Mo, W; X = S, Se) heterostructures have been investigated by employing density functional theory, nonequilibrium Green's function, and Keldysh nonequilibrium Green's function methods. The stabilities of silicene (SiE) are obviously improved after being placed on the MX 2 (M = Mo, W; X = S, Se) substrates. In particular, the conductivities of SiE/MX 2 are enhanced compared with free-standing SiE and MX 2 . Moreover, the conductivities are increased with the group number of X, i.e., in the order of SiE < SiE/MS 2 < SiE/MSe 2 . An evident current oscillation phenomenon is observed in the SiE/WX 2 heterostructures. When a linear light illumination is applied, SiE/MSe 2 shows a stronger photoresponse than SiE/MS 2 . The maximum photoresponse with a value of 9.0 a 0 2 /photon was obtained for SiE/WSe 2 . More importantly, SiE/MS 2 (M = Mo, W) heterostructures are good candidates for application in designing solar cells owing to the well spatial separation of the charge carriers. This work provides some clues for further exploring 2D SiE/MX 2 heterostructures involving tailored photoelectric properties., Competing Interests: The authors declare no competing financial interest.

The electronic, transport, and optoelectronic properties of monolayer black phosphorus (MLBP) are much influenced by grafting PdCl 2 groups, demonstrated here by using density functional theory (DFT) and non-equilibrium Green's function (NEGF) as well as the Keldysh Nonequilibrium Green's Functions (KNEGF) methods. We find that the PdCl 2 groups prefer to locate over the furrow site of MLBP and form a planar quadridentate structure of . The PdCl 2 groups serve as quantum dots by introducing discrete flat levels between the MLBP valence band and the Fermi level ( E f ). The conductivity is much lowered after attaching PdCl 2 quantum dots, due to the fact that the scattering effect of PdCl 2 plays a major role in the process of electron transporting. A threshold voltage is found for the functionalized system with a large density of PdCl 2 quantum dots, a valuable clue for exploring current switches. However, no evident threshold voltage is found for the pure MLBP. Electrons permeate easier through the armchair direction compared with the zigzag either in the pure MLBP or in the functionalized composites. More importantly, grafting PdCl 2 quantum dots is very beneficial for enhancing photoresponse. The values of photoresponse for the modified species are about 20 times higher than the free MLBP. A significant photoresponse anisotropy is observed for both MLBP and n PdCl 2 -BP ( n = 1, 2, and 4), contrary to the conductivity, the zigzag direction shows much stronger photoresponse than the armchair. All of the aforementioned unique properties make these new two-dimensional (2D) MLBP based materials especially attractive for both electronic and optoelectronic devices., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

PTSD (Posttraumatic Stress Disorder) is a common post-disaster psychological condition which research has shown to have comorbidity with depression. To explore the relationship between PTSD and depression further, a cross-sectional study design was adopted. Three years after the Ya'an earthquake, 4137 adolescents (mean age 15.12) who had personally experienced the earthquake were assessed. The study results showed that PTSD significantly predicted future depression, with the effect being partially mediated by the negative life events after the earthquake. Gender was not found to be a significant moderator between PTSD and depression., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives: This article focuses on the effect of road lighting on road safety at accesses to quantitatively analyze the relationship between road lighting and road safety., Methods: An artificial neural network (ANN) was applied in this study. This method is one of the most popular machine learning methods and does not require any predefined assumptions. This method was applied using field data collected from 10 road segments in Nanjing, Jiangsu Province, China., Results: The results show that the impact of road lighting on road safety at accesses is significant. In addition, road lighting has a greater influence when vehicle speeds are higher or the number of lanes is greater. A threshold illuminance was also found, and the results show that the safety level at accesses will become stable when reaching this value., Conclusions: Improved illuminance can decrease the speed variation among vehicles and improve safety levels. In addition, high-grade roads need better illuminance at accesses. A threshold value can also be obtained based on related variables and used to develop scientific guidelines for traffic management organizations.

Rare earth-doped upconversion nanoparticles (UCNPs) have promising potentials in biodetection due to their unique frequency upconverting capability and high detection sensitivity. This paper reports an improved UCNPs-based fluorescence probe for dual-sensing of Aflatoxin B1 (AFB1) and Deoxynivalenol (DON) using a magnetism-induced separation and the specific formation of antibody-targets complex. Herein, the improved UCNPs, which were namely NaYF4:Yb/Ho/Gd and NaYF4:Yb/Tm/Gd, were systematically studied based on the optimization of reaction time, temperature and the concentration of dopant ions with simultaneous phase and size controlled NaYF4 nanoparticles; and the targets were detected using the pattern of competitive combination assay. Under an optimized condition, the advanced fluorescent probes revealed stronger fluorescent properties, broader biological applications and better storage stabilities compared to traditional UCNPs-based ones; and ultrasensitive determinations of AFB1 and DON were achieved under a wide sensing range of 0.001-0.1 ng ml(-1) with the limit of detection (LOD) of 0.001 ng ml(-1). Additionally, the applicability of the improved nanosensor for the detection of mycotoxins was also confirmed in adulterated oil samples., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Rare earth doped upconversion nanoparticles convert near-infrared excitation light into visible emission light. Compared to organic fluorophores and semiconducting nanoparticles, upconversion nanoparticles (UCNPs) offer high photochemical stability, sharp emission bandwidths, and large anti-Stokes shifts. Along with the significant light penetration depth and the absence of autofluorescence in biological samples under infrared excitation, these UCNPs have attracted more and more attention on toxin detection and biological labelling. Herein, the fluorescence probe based on UCNPs was developed for quantifying Aflatoxin B1 (AFB1) in peanut oil. Based on a specific immunity format, the detection limit for AFB1 under optimal conditions was obtained as low as 0.2ng·ml(-1), and in the effective detection range 0.2 to 100ng·ml(-1), good relationship between fluorescence intensity and AFB1 concentration was achieved under the linear ratios up to 0.90. Moreover, to check the feasibility of these probes on AFB1 measurements in peanut oil, recovery tests have been carried out. A good accuracy rating (93.8%) was obtained in this study. Results showed that the nanoparticles can be successfully applied for sensing AFB1 in peanut oil., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Electronic structures and transport properties of prototype MoS2 nanotube (15, 0) nanocables, including undoped PSi@MoS2 and B- and P-doped PSi@MoS2 (where PSi refers to polysilane), are investigated using the density functional theory (DFT) and the non-equilibrium Green's function (NEGF) methods. It is found that transport properties of two-probe systems by sandwiching finite long nanocables between two Au electrodes are basically in agreement with the electronic structures of their corresponding infinitely long systems. Encapsulating undoped and doped PSi nanowires inside the MoS2 nanotubes could not significantly affect the electronic and transport properties. B-doping and P-doping upon PSi play different roles in the electronic and transport properties. B-doping may exert constructive and destructive effects on electron transport depending on its position and applied bias direction, while P-doping displays a negligible effect. In addition, we found that bi-doping by two adjacent B atoms could slightly enhance the conductivity. These results could offer some clues for conducting experiments to achieve nanoelectronic devices with intrinsic transport properties of MoS2 nanotubes.

CD98-mediated β1 and β3 integrins activation can induce Fak phosphorylation which eventually promotes cell survival, proliferation, and migration. We evaluated the expression of CD98, integrin β1, integrin β3 and Fak in 45 cases of matched colorectal cancer (CRC) and liver metastases as well as 35 cases of CRC without liver metastases. There was a gradual increase of the expression of CD98, integrin β1, integrin β3 and Fak as tumor progressed from normal colon to carcinoma to budding tumor cells at the invasive front and to liver metastases. The expression of CD98 and integrin β1 in CRC with liver metastases was significantly higher than that in CRC without liver metastases. Furthermore, for those liver metastases with desmoplastic growth pattern, expression of CD98, integrin β1, integrin β3 and Fak at the metastases center was as strong as that at the metastases periphery. For those liver metastases with pushing or replacement growth patterns, more intense expression of these markers was found at the metastases center than the periphery. Overexpression of CD98, integrin β1, integrin β3 and Fak is associated with the progression and liver metastases of CRC. Overexpression of these markers in liver metastases requires direct contact between tumor cells and the stroma., (Copyright © 2014 Elsevier GmbH. All rights reserved.)

A series of oral prodrugs based on the structure of gemcitabine (2',2'-difluorodeoxycytidine) were synthesised by introducing an amide group at the N4-position of the cytidine ring. A total of 16 compounds were obtained, and their chemical and biological characteristics were evaluated. The half-maximal inhibitory concentrations (IC(50)s) for most of these compounds were higher than that of gemcitabine in vitro. Compounds 5d and 5m, the representative compounds, were examined in terms of their physiological stabilities and pharmacokinetics. Compound 5d showed good stability in PBS and simulated intestinal fluid, and an analysis of its pharmacokinetics in mice suggested that the introduction of an amide group to gemcitabine could greatly improve its bioavailability. Further evaluation of compound 5d in vivo showed that this compound possesses higher activity than gemcitabine against the growth of HepG2 human hepatocellular carcinoma cells and HCT-116 colon adenocarcinoma cells with less toxicity to animals. These results suggest that compound 5d could be further developed as a potential oral anticancer agent for clinical applications in which gemcitabine is currently used., (© 2012 John Wiley & Sons A/S.)

SL-01, an oral gemcitabine derivative, was synthesized by introducing the moiety of 3-(dodecyloxycarbonyl)pyrazine-2-carbonyl at the N4-position on the cytidine ring of gemcitabine. Our goal in this study was to evaluate the efficacy of SL-01 on the growth of human cancers with gemcitabine as control. Experiments were performed on human non-small cell lung cancer NCI-H460 and colon cancer HCT-116 both in vitro and in vivo. In vitro assays, SL-01 significantly inhibited the growth of cancer cells as determined by the 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay. Further studies indicated that SL-01 induced the cancer cells to apoptosis showing chromatin condensation and externalization of phosphatidylserine. In in vivo studies, we evaluated the efficacy of SL-01 in nude mice bearing human cancer xenografts. SL-01 effectively delayed the growth of NCI-H460 and HCT-116 without significant loss of body weight. Molecular analysis indicated that the high efficacy of SL-01 was associated with its ability to induce apoptosis as evidenced by increase of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining cells, activation of caspase-9, caspase-3 and cleaved poly ADP-ribose polymerase (PARP) in tumor tissues. SL-01 also increased Bax/Bcl-2 ratio in cancer cells. These biological activities of SL-01 were more potential than that of gemcitabine. Based on these in vitro and in vivo results, SL-01 is proposed as a potent oral anticancer agent that may supplant the use of gemcitabine in the clinic., (Copyright © 2012 Elsevier Inc. All rights reserved.)