Go for gold: As‐prepared insulin–Au nanoclusters (NCs) show intense red fluorescence, excellent biocompatibility, and preservation of natural insulin bioactivity in lowering the blood‐glucose level. ...Their versatility in applications is demonstrated by fluorescence imaging, X‐ray computed tomography, and insulin–inhibitor interactions (see picture; IDE=insulin‐degrading enzyme).
This study investigates whether geopolitical risks influence Chinese firms' cash holdings. We find that firms tend to hoard more cash as a precautionary measure when faced with geopolitical risk. ...Moreover, firms that are financially constrained maintain cash reserves as buffer against geopolitical risk. Finally, firms in manufacturing-related industries tend to save more cash and protect themselves from risk spillover as China's manufacturing sector has slowed down with the current China–United States trade war. Our research notes that policymakers and investors can pay more attention to the effect of geopolitical risk on enterprises' cash reserves.
•Firms tend to hoard more cash as a precautionary measure when faced with geopolitical risk.•Firms that are financially constrained maintain cash reserves as buffer against geopolitical risk.•Firms in manufacturing-related industries tend to save more cash and protect themselves.
MicroRNAs (miRNAs), i.e. small non-coding RNA molecules (~22 nt), can bind to one or more target sites on a gene transcript to negatively regulate protein expression, subsequently controlling many ...cellular mechanisms. A current and curated collection of miRNA-target interactions (MTIs) with experimental support is essential to thoroughly elucidating miRNA functions under different conditions and in different species. As a database, miRTarBase has accumulated more than 3500 MTIs by manually surveying pertinent literature after data mining of the text systematically to filter research articles related to functional studies of miRNAs. Generally, the collected MTIs are validated experimentally by reporter assays, western blot, or microarray experiments with overexpression or knockdown of miRNAs. miRTarBase curates 3576 experimentally verified MTIs between 657 miRNAs and 2297 target genes among 17 species. miRTarBase contains the largest amount of validated MTIs by comparing with other similar, previously developed databases. The MTIs collected in the miRTarBase can also provide a large amount of positive samples to develop computational methods capable of identifying miRNA-target interactions. miRTarBase is now available on http://miRTarBase.mbc.nctu.edu.tw/, and is updated frequently by continuously surveying research articles.
We survey progress in the 3D cross-point phase-change memory (PCM) field over recent years, starting from the choice of 3D-capable access devices to candidate Ovonic threshold switching (OTS) ...materials, particularly with high cycling endurance and good thermal stability. First, we discuss 3D integration challenges faced when combining OTS and PCM. Then, we review the operation scheme of the OTS+PCM cross-point devices as well as the criteria that an OTS access device needs to meet (e.g. Vth and IOFF) to successfully operate true cross-point array. We also review arsenic (As) and non-As-based OTS materials and discuss their properties as well as those of phase-change materials, focusing in particular on fast switching speed and long endurance compounds, which are among those proposed for storage-class memory (SCM). Finally, we briefly survey recent work on OTS integrated with PCM in stackable devices for SCM application.
Summary Background Major adjuvant treatments for pancreatic adenocarcinoma include fluorouracil, gemcitabine, chemoradiation, and chemoradiation plus fluorouracil or gemcitabine. Since the optimum ...regimen remains inconclusive, we aimed to compare these treatments in terms of overall survival after tumour resection and in terms of grade 3–4 toxic effects with a systematic review and random-effects Bayesian network meta-analysis. Methods We searched PubMed, trial registries, and related reviews and abstracts for randomised controlled trials comparing the above five treatments with each other or observation alone before April 30, 2013. We estimated relative hazard ratios (HRs) for death and relative odds ratios (ORs) for toxic effects among different therapies by combining HRs for death and survival durations and ORs for toxic effects of included trials. We assessed the effects of prognostic factors on survival benefits of adjuvant therapies with meta-regression. Findings Ten eligible articles reporting nine trials were included. Compared with observation, the HRs for death were 0·62 (95% credible interval 0·42–0·88) for fluorouracil, 0·68 (0·44–1·07) for gemcitabine, 0·91 (0·55–1·46) for chemoradiation, 0·54 (0·15–1·80) for chemoradiation plus fluorouracil, and 0·44 (0·10–1·81) for chemoradiation plus gemcitabine. The proportion of patients with positive lymph nodes was inversely associated with the survival benefit of adjuvant treatments. After adjustment for this factor, fluorouracil (HR 0·65, 0·49–0·84) and gemcitabine (0·59, 0·41–0·83) improved survival compared with observation, whereas chemoradiation resulted in worse survival than fluorouracil (1·69, 1·12–2·54) or gemcitabine (1·86, 1·04–3·23). Chemoradiation plus gemcitabine was ranked the most toxic, with significantly higher haematological toxic effects than second-ranked chemoradiation plus fluorouracil (OR 13·33, 1·01–169·36). Interpretation Chemotherapy with fluorouracil or gemcitabine is the optimum adjuvant treatment for pancreatic adenocarcinoma and reduces mortality after surgery by about a third. Chemoradiation plus chemotherapy is less effective in prolonging survival and is more toxic than chemotherapy. Funding None.
The as-prepared cobalt oxide (assigned as CoO
x
) was fabricated by precipitation–oxidation from aqueous cobalt nitrate solution using sodium hydroxide and oxidation with hydrogen peroxide. Another ...series of pure cobalt oxides was refined by the decomposition of CoO
x
in a nitrogen environment at temperatures of 280, 450 and 950
°C (D-280, D-450 and D-950, respectively). Phase transformation, structural properties and red-ox properties were characterized by thermogravimetry-mass spectrometry (TG-MS), X-ray diffraction (XRD), infrared spectroscopy (IR), Raman spectroscopy and temperature-programmed decomposition/reduction (TPD/TPR). Analysis of the thermal behavior on CoO
x
revealed that a series of pure cobalt oxide with particle sizes of 10–20
nm could be obtained easily. The results demonstrated that the refined samples D-280, D-450 and D-950 were CoO(OH), Co
3O
4 and CoO, respectively.
MicroRNA-122 (miR-122), which accounts for 70% of the liver's total miRNAs, plays a pivotal role in the liver. However, its intrinsic physiological roles remain largely undetermined. We demonstrated ...that mice lacking the gene encoding miR-122a (Mir122a) are viable but develop temporally controlled steatohepatitis, fibrosis, and hepatocellular carcinoma (HCC). These mice exhibited a striking disparity in HCC incidence based on sex, with a male-to-female ratio of 3.9:1, which recapitulates the disease incidence in humans. Impaired expression of microsomal triglyceride transfer protein (MTTP) contributed to steatosis, which was reversed by in vivo restoration of Mttp expression. We found that hepatic fibrosis onset can be partially attributed to the action of a miR-122a target, the Klf6 transcript. In addition, Mir122a(-/-) livers exhibited disruptions in a range of pathways, many of which closely resemble the disruptions found in human HCC. Importantly, the reexpression of miR-122a reduced disease manifestation and tumor incidence in Mir122a(-/-) mice. This study demonstrates that mice with a targeted deletion of the Mir122a gene possess several key phenotypes of human liver diseases, which provides a rationale for the development of a unique therapy for the treatment of chronic liver disease and HCC.
Parkinson's disease (PD) is one of the common long-term degenerative disorders that primarily affect motor systems. Gastrointestinal (GI) symptoms are common in individuals with PD and often present ...before motor symptoms. It has been found that gut dysbiosis to PD pathology is related to the severity of motor and non-motor symptoms in PD. Probiotics have been reported to have the ability to improve the symptoms related to constipation in PD patients. However, the evidence from preclinical or clinical research to verify the beneficial effects of probiotics for the motor functions in PD is still limited. An experimental PD animal model could be helpful in exploring the potential therapeutic strategy using probiotics. In the current study, we examined whether daily and long-term administration of probiotics has neuroprotective effects on nigrostriatal dopamine neurons and whether it can further alleviate the motor dysfunctions in PD mice. Transgenic MitoPark PD mice were chosen for this study and the effects of daily probiotic treatment on gait, beam balance, motor coordination, and the degeneration levels of dopaminergic neurons were identified. From the results, compared with the sham treatment group, we found that the daily administration of probiotics significantly reduced the motor impairments in gait pattern, balance function, and motor coordination. Immunohistochemically, a tyrosine hydroxylase (TH)-positive cell in the substantia nigra was significantly preserved in the probiotic-treated PD mice. These results showed that long-term administration of probiotics has neuroprotective effects on dopamine neurons and further attenuates the deterioration of motor dysfunctions in MitoPark PD mice. Our data further highlighted the promising possibility of the potential use of probiotics, which could be the relevant approach for further application on human PD subjects.
Background and aims
Liver cancer is a detrimental complication in patients with chronic viral hepatitis and alcoholic or nonalcoholic fatty liver disease (NAFLD). However, metabolic risk factors ...underlying NAFLD usually cause substantial differences in their clinical outcomes. Recently, several studies have used a novel definition of metabolic dysfunction-associated fatty liver disease (MAFLD) to reassess patients with NAFLD and pointed out the importance of metabolic risk factors. Since patients with NAFLD, MAFLD, or metabolic syndrome (MetS) have different burden of metabolic risk factors, it is crucial to decipher the risk of developing hepatic complications in these populations.
Methods
Through a longitudinal nationwide cohort study, the risk of liver cancer was investigated in patients with MetS alone, NAFLD alone, overlap NAFLD/MAFLD, and coexisting MetS and NAFLD. The general characteristics, comorbidities, and incidence of liver cancer were also compared.
Results
Intriguingly, patients diagnosed with MetS alone did not have a significant risk of developing HCC compared to control individuals, while patients with NAFLD alone, NAFLD/MAFLD, and coexisting NAFLD and MetS exhibited 6.08-, 5.81-, and 15.33-fold risks of developing HCC, respectively. Apart from metabolic risk factors, renal function status and liver cirrhosis were the independent risk factors for the development of HCC among these groups.
Conclusion
Our data emphasize that metabolic dysfunction has a significant impact on hepatocarcinogenesis in patients with NAFLD. Moreover, coexisting multiple metabolic risk factors would dampen the risk of developing HCC in patients with NAFLD. Closely tracing HCC formation through laboratory examination or imaging is crucial in these patients.
To investigate the incidence and risk factors of hepatitis B virus (HBV) reactivation in HBV surface antigen (HBsAg)
/ HBV core antibody (HBcAb)
patients who underwent rituximab (RTX) therapy for ...rheumatoid arthritis (RA). From January 2000 through December 2017, a total of 134 RA patients with various HBV serostatuses who received RTX at Dalin Tzu Chi Hospital were screened. Finally, 50 HBsAg
/HBcAb
patients were enrolled in this retrospective study. Baseline characteristics, comedications, and the occurrence of HBV reactivation were recorded. Four HBsAg
/HBcAb
RA patients (8%; 4/50) experienced HBV reactivation after treatment with RTX. Hepatitis flare-up occurred in 2 of these 4 patients, with a fatal outcome in one. HBV reactivation occurred approximately 1-4 years after the first dose of RTX and 0.5-1.5 years after the last one. In HBsAg
/HBcAb
patients, HBV reactivation was significantly more common in those who were HBV surface antibody (HBsAb)
at baseline than in those who were HBsAb
(30% vs 4%; p = 0.02). A history of adalimumab use was associated with HBV reactivation (100% vs 39%; p = 0.02). A moderate risk of HBV reactivation was observed in HBsAg
/HBcAb
RA patients receiving RTX therapy. The reactivation may induce acute hepatitis and even death. To reduce the risk of HBV reactivation, regular monitoring of liver function is insufficient; monitoring of viral load and HBsAg or prophylaxis with antiviral therapy should be considered.
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