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ObjectiveTo study the migration rule of melamine and formaldehyde under acidic conditions in bamboo fiber-melamine resin （BM） tableware， discuss the main factors affecting the migration level and safety risks， and provide suggestions for the safety management of such products.MethodsA total of 14 brands of BM tableware （including baby and infant tableware） with clear identification of bamboo fiber in the market were collected. Ethanol （10%， V/V）and acetic acid （4%， V/V）were selected， and the tableware were soaked in according to GB 5009.156—2016， and then conduct migration tests under acidic conditions according to the national food safety standards GB 31604.15—2016 and GB 31604.48—2016.ResultsWhen BM tableware was exposed to 4% （V/V） acetic acid， the migration level of melamine and formaldehyde was much higher than that of 10% （V/V） ethanol. For a single sample， the migration trend of melamine and formaldehyde was positively correlated， and long-term repeated exposure to more acidic food may have caused a higher chance of excessive migration. With increased frequency of use， the migration level of melamine and formaldehyde increased gradually， which was more obvious in the products with higher bamboo fiber addition.ConclusionThe migration rules of melamine and formaldehyde in BM tableware were basically the same after long term repeated use. The migration level of melamine better reflected the decomposition of resin. BM tableware had a higher chance of excessive migration when repeatedly contacting acidic food for a long time， especially for infant products. The guidance on labels and consumer education should be strengthened and the use of non-conforming raw materials should be eliminated to promote the development of the industry within safety standards.

Background: Acute myeloid leukaemia (AML) comprises a group of heterogeneous and aggressive haematological malignancies with unsatisfactory prognoses and limited treatment options. Treatments targeting B-cell lymphoma-2 (BCL-2) with venetoclax have been approved for patients with AML, and venetoclax-based drug combinations are becoming the standard of care for older patients unfit for intensive chemotherapy. However, the therapeutic duration of either single or combination strategies is limited, and the development of resistance seems inevitable. Therefore, more effective combination regimens are urgently needed. Methods: The efficacy of combination therapy with NL101, a SAHA-bendamustine hybrid, and venetoclax was evaluated in preclinical models of AML including established cell lines, primary blasts from patients, and animal models. RNA-sequencing and immunoblotting were used to explore the underlying mechanism. Results: NL101 significantly potentiated the activity of venetoclax in AML cell lines, as evidenced by the enhanced decrease in viability and induction of apoptosis. Mechanistically, the addition of NL101 to venetoclax decreased the stability of the antiapoptotic protein myeloid cell leukaemia-1 (MCL-1) by inhibiting ERK, thereby facilitating the release of BIM and triggering mitochondrial apoptosis. Moreover, the strong synergy between NL101 and venetoclax also relied on the downregulation of c-Myc via PI3K/Akt/GSK3β signalling. The combination of NL101 and venetoclax synergistically eliminated primary blasts from 10 AML patients and reduced the leukaemia burden in an MV4-11 cell-derived xenograft model. Conclusions: Our results encourage the pursuit of clinical trials of combined treatment with NL101 and venetoclax and provide a novel venetoclax-incorporating therapeutic strategy for AML. [ABSTRACT FROM AUTHOR]

Due to natural sedimentation and artificial filling, slopes exhibit heterogeneity in the form of multi-layer soils, namely, layered slopes. Compared with homogenous slopes, the failure mechanism of layered slopes is more complex owing to the different shear strengths of each soil layer. Therefore, it is of great importance to gain insight into the stability of layered slopes. In this study, the upper bound theorem of limit analysis incorporated with a pseudo-static approach is utilized to investigate the seismic stability of two kinds of two-layered slopes: one with a stiff lower soil layer and the other with a weak lower soil layer. Three failure patterns, namely face failure, toe failure and base failure, are taken into account. A depth coefficient (Δ) is introduced to describe the distribution of two soil layers. The layer-wise summation method is adopted to calculate the safety factor and yield acceleration coefficient more conveniently. Based on Newmark's method, the earthquake-induced horizontal displacement is estimated. The calculated results are validated by comparisons with published literature and the numerical method in terms of safety factor, critical failure surface and yield acceleration coefficient. The results show that the depth coefficient has a significant influence on the failure mechanism of two-layered slopes by determining whether the stability of upper-layered soil is dominant in the overall slope stability or not. Inaccurately identifying the failure patterns will overestimate the seismic performance of two-layered slopes in the aspects of safety factor and yield acceleration coefficient, leading to an underestimation of earthquake-induced horizontal displacement. [ABSTRACT FROM AUTHOR]

Tislelizumab may induce immune-related adverse events, especially adverse skin events. Early detection and timely intervention of cutaneous adverse events are crucial to improve patients' quality of life and reduce the disruption of therapeutic regimens. This study aimed to determine the clinical characteristics of cutaneous adverse reactions to tislelizumab and offer a reference for its rational clinical use. Case reports of cutaneous adverse reactions induced by tislelizumab were collected from the relevant databases (up to 31 March 2023). Patient age, sex, primary disease, medication use, occurrence of adverse skin conditions, treatment, and outcomes were recorded and descriptively analysed. A total of 13 patients were enrolled, including six males and seven females, aged 55–79 years, with a median age of 75 years and a mean age of 70.92 ± 8.84 years. The original disease was lung carcinoma in none patients, cervical carcinoma in two, and urothelial carcinoma and squamous cell carcinoma in one each. The time from the initiation of medication use to the occurrence of cutaneous adverse reactions ranged from 7 to 177 days. Among the 13 patients, 10 showed improvement after drug withdrawal or symptomatic treatment. Two patients died (one died of disease progression and multiorgan failure, one died of acute coronary syndrome), and one patient's adverse skin reactions persisted without treatment. Tislelizumab-related cutaneous adverse reactions mostly occur after several days to months of treatment. In clinical practice, evaluation and monitoring should be strengthened. More attention should be paid to erythema and rashes, which may be signs of serious adverse skin reactions. Early detection and intervention can ensure the safe use of drugs and provide greater clinical benefits to patients. [ABSTRACT FROM AUTHOR]

Myocardial ischemia/reperfusion (I/R) injury is the leading cause of death worldwide. Ginsenoside Rd (GRd) has cardioprotective properties but its efficacy and mechanism of action in myocardial I/R injury have not been clarified. This study investigated GRd as a potent therapeutic agent for myocardial I/R injury. Oxygen-glucose deprivation and reperfusion (OGD/R) and left anterior descending (LAD) coronary artery ligation were used to establish a myocardial I/R injury model in vitro and in vivo. In vivo, GRd significantly reduced the myocardial infarct size and markers of myocardial injury and improved the cardiac function in myocardial I/R injury mice. In vitro, GRd enhanced cell viability and protected the H9c2 rat cardiomyoblast cell line from OGD-induced injury GRd. The network pharmacology analysis predicted 48 potential targets of GRd for the treatment of myocardial I/R injury. GO and KEGG enrichment analysis indicated that the cardioprotective effects of GRd were closely related to inflammation and apoptosis mediated by the PI3K/Akt signaling pathway. Furthermore, GRd alleviated inflammation and cardiomyocyte apoptosis in vivo and inhibited OGD/R-induced apoptosis and inflammation in cardiomyocytes. GRd also increased PI3K and Akt phosphorylation, suggesting activation of the PI3K/Akt pathway, whereas LY294002, a PI3K inhibitor, blocked the GRd-induced inhibition of OGD/R-induced apoptosis and inflammation in H9c2 cells. The therapeutic effect of GRd in vivo and in vitro against myocardial I/R injury was primarily dependent on PI3K/Akt pathway activation to inhibit inflammation and cardiomyocyte apoptosis. This study provides new evidence for the use of GRd as a cardiovascular drug. [ABSTRACT FROM AUTHOR]

Dust events frequently occur in Tarim Basin (TB), China. However, research is scarce on the variation characteristics of sand-dust, floating-dust, sand-blowing, and sandstorms in the mountains, oases, and deserts in TB. Therefore, we conducted in-depth studies on the distributions and variations of dust events in TB. The results indicate that dust events tend to increase from south to north. The yearly sand-dust event occurrence rate trend is deserts > oases > mountainous regions. Spring events of sand-dust, floating-dust, sand-blowing, and sandstorms account for 35.9%, 36.0%, 38.5%, and 47.1% and summer events for 33.6%, 33.5%, 43.8%, and 60.3% of the total annual average sand-dust, floating-dust, sand-blowing, and sandstorm days, respectively. From 1961 to 2015, most stations (annual average > 30 stations) showed a downward linear trend in sand-dust, floating-dust, sand-blowing, and sandstorms in TB. All types of sand-dust events in mountains and oases decreased substantially after 1975–1978. In spring and summer, the downward dust trends are the most obvious, which the largest annual average downward linear trend rates of floating-dust, sand-blowing, and sandstorms are − 0.33 d/yr (QM station), − 0.21 d/yr (TGLK station), and − 11 d/yr (KP station), respectively, in spring, and − 0.28 d/yr (QM station), − 0.17 d/yr (TGLK station), and − 0.14 d/yr (KP station), respectively, in summer. It is found that the decreasing and increasing trends of floating-dust are the most frequent among sand-dust events. There are a significant positive correlation between wind speed and relative humidity in mountains and a significant positive correlation between wind speed in oases. [ABSTRACT FROM AUTHOR]

Diffuse large B-cell lymphoma (DLBCL) is among the most aggressive hematological malignancies and patients are commonly treated with combinatorial immunochemotherapies such as R-CHOP. Till now, the prognoses are still variable and unsatisfactory, depending on the molecular subtype and the treatment response. Developing effective and tolerable new agents is always urgently needed, and compounds from a natural source have gained increasing attentions. Wogonin is an active flavonoid extracted from the traditional Chinese herbal medicine Scutellaria baicalensis Georgi and has shown extensive antitumor potentials. However, the therapeutic effect of wogonin on DLBCL remains unknown. Here, we found that treatment with wogonin dose- and time-dependently reduced the viability in a panel of established DLBCL cell lines. The cytotoxicity of wogonin was mediated through apoptosis induction, along with the loss of mitochondrial membrane potential and the downregulation of BCL-2, MCL-1, and BCL-xL. In terms of the mechanism, wogonin inhibited the PI3K and MAPK pathways, as evidenced by the clear decline in the phosphorylation of AKT, GSK3β, S6, ERK, and P38. Furthermore, the combination of wogonin and the BCL-2 inhibitor venetoclax elicited synergistically enhanced killing effect on DLBCL cells regardless of their molecular subtypes. Finally, administration of wogonin significantly impeded the progression of the DLBCL tumor in a xenograft animal model without obvious side effects. Taken together, the present study suggests a promising potential of wogonin in the treatment of DLBCL patients either as monotherapy or an adjuvant for venetoclax-based combinations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The pathophysiological mechanisms involved in fibrotic interstitial lung diseases (FILDs) are akin to those observed in idiopathic pulmonary fibrosis (IPF), implying the potential for shared therapeutic approaches. Pirfenidone exhibits antifibrotic and anti-inflammatory properties, making it the first small-molecule drug approved for treating IPF. Pirfenidone has been utilized in IPF treatment for more than one decade. However, guidelines for progressive pulmonary fibrosis (PPF) treatment suggest that further research and evidence are needed to fully comprehend its efficacy and safety across various PPF subtypes. In recent years, numerous studies have explored the use of pirfenidone in treating non-IPF FILD. Herein, we provide an overview of the latest research data on application of pirfenidone in occupational-related ILD, connective tissue disease-associated ILD, post-coronavirus disease-2019 pulmonary fibrosis, and other conditions. We summarize the level of evidence and highlight challenges associated with using pirfenidone in different FILDs to offer clinical guidance., 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 Han, Liu, Ji, Jin, Jin and Gao.)