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Background: Alpha‑fetoprotein-producing gastric cancer (AFPGC) is a rare type of gastric cancer with a high rate of metastasis and poor prognosis. Despite substantial progress in the treatment of many solid tumors, there are no reports of the safety and effectiveness of immune checkpoint inhibitors in combination with antiangiogenesis agents for AFPGC patients who have proficient mismatch repair. Case presentation: We describe a 69-year-old man who was diagnosed with metastatic AFPGC. After progression to chemotherapy resistance, tislelizumab combined with apatinib was administered, although the patient's gastroscopic pathology showed proficient mismatch repair. After three cycles of therapy, partial remission (reduced by 56%) was obtained, and the quality of life improved significantly. Surprisingly, after more than 1 year of continuous application of the combination treatment regimen, both the primary and metastatic tumors in this patient eventually disappeared, which obtained complete remission without surgery. The patient has had a progression-free survival of more than 24 months and is still continuing to benefit. Conclusions: This case is the first example of effective treatment of AFPGC with tislelizumab combined with apatinib. The outcomes of this case suggest a highly effective and tolerable therapeutic strategy for microsatellite-stabilized AFPGC. [ABSTRACT FROM AUTHOR]

The battery electric vehicle (BEV) industry, commanding over half of the global market share in China, has garnered significant attention in response to escalating concerns about climate change. NCM (LiNi x Co y Mn z O 2) batteries, prized for their high energy density, are pivotal in this industry. However, their production relies on critical metals, posing environmental challenges. Recycling processes aim to address this issue by recovering critical metals from end-of-life batteries. The industry is updating from NCM 111 to NCM 811 batteries to enhance energy density and reduce costs, but the key factors influencing the material flows and environmental impacts remain uncertain. This paper aims to identify the key factors contributing to the potential differences in material flows and environmental impacts introduced by the NCM battery upgrading in China. Following the new energy vehicle sales projections in China until 2035, a dynamic material flow analysis was employed to calculate material demands, recovered amounts, and substitution rates for various upgrading scenarios. The study reveals that the majority of retired batteries until 2035 were sold between 2022 and 2029. Material substitution rates prove to be more sensitive to the upgrading scenario than the lifetime and growth rate of BEVs. Faster NCM 811 penetration results in over 2.5 times more saved cobalt demand compared to additional nickel demand. A life cycle assessment of NCM batteries reveals a 39% lower global warming impact for NCM 811 compared to NCM 111, highlighting environmental benefits from increased energy density and reduced cobalt consumption. The energy density improvement contributed 85%, while the alteration in material composition contributed 15% to the global warming reduction in NCM 811. Recycling emerges as a crucial strategy in mitigating environmental impacts across all categories, particularly addressing eutrophication, previously deemed challenging due to the difficulty in recovering Li 2 CO 3. [ABSTRACT FROM AUTHOR]

Fluoride, a ubiquitous environmental compound, carries significant health risks at excessive levels. This study investigated the reproductive toxicity of fluoride exposure during puberty in mice, focusing on its impact on testicular development, spermatogenesis, and underlying mechanisms. The results showed that fluoride exposure during puberty impaired testicular structure, induced germ cell apoptosis, and reduced sperm counts in mice. Additionally, the SOD activity and GSH content were significantly decreased, while MDA content was significantly elevated in the NaF group. Immunohistochemistry showed an increase in the number of cells positive for GRP78, a key ER stress marker. Moreover, qRT-PCR and Western blot analyses confirmed the upregulation of both Grp7 8 mRNA and protein expression, as well as increased mRNA expression of other ER stress-associated genes (Grp94 , chop , Atf6 , Atf4, and Xbp1) and enhanced protein expression of phosphorylated PERK, IRE1α, eIF2α, JNK, XBP-1, ATF-6α, ATF-4, and CHOP. In conclusion, our findings demonstrate that fluoride exposure during puberty impairs testicular structure, induces germ cell apoptosis, and reduces sperm counts in mice. ER stress may participate in testicular cell apoptosis, and contribute to the testicular damage and decreased sperm counts induced by fluoride. Fluoride exposure during puberty induces testicular germ cell apoptosis, impairs testicular structure, and reduces sperm count in mice. ER stress may participate in testicular cell apoptosis via activating JNK and CHOP, ultimately contributing to testicular damage and decreased sperm counts in mice caused by fluoride exposure during puberty. [Display omitted] • Fluoride exposure during puberty impairs testis development in mice. • Fluoride exposure during puberty decreases sperm counts in mice. • Fluoride triggers testicular germ cells apoptosis in mice. • ER stress involves in fluoride-induced testicular germ cells apoptosis. [ABSTRACT FROM AUTHOR]

Bike-sharing offers a convenient and sustainable mode of transportation. Numerous studies have investigated the influence of temporal variations in the natural environment on cycling, as well as the impact of physical street characteristics like networks and infrastructures. However, few studies integrated and compared the effects of natural environment and street visual quality on cycling in the spatial dimension. As a case study, we focused on the impact of these two factors on Citi Bike system on weekdays and weekends in New York City, while accounting for sociodemographic and functional factors. This study employed machine learning and multiscale geographically weighted regression models at both station and neighborhood scales for a comprehensive analysis of their relationships. The results reveal that the natural environment factors, particularly visibility, are more important factors associated with bike-sharing use. Among the visual quality factors, motorized traffic has a negative impact on both weekday and weekend cycling. When considering geographical location, sky openness exhibits an unfavorable influence on weekday cycling in specific areas. By combining natural environment and visual quality factors, our study promotes optimal resource allocation and the development of bike-friendly cities. • A comprehensive analysis combined the effects of the natural environment and visual quality on bike-sharing. • Bike-sharing usage was predicted based on machine learning and geospatial modeling across two spatial units. • Contrary to simple expectations, visibility has the most significant negative impact on cycling. • Sky and car pixel in Street View images affects cycling, varying regionally and between weekdays and weekends. [ABSTRACT FROM AUTHOR]

Abstract Chromatin spatial organization is essential for transcriptional modulation and stabilization. The pattern of DNA distal interplay form the multiple topological associating domains (TADs), and further assemble the functional compartmentalization with open and expression-active chromatin ("A" compartments) or closed and expression-inactive chromatin ("B" compartments) in genome, whose boundaries were defined by the high enrichment of CCCTC-binding factor (CTCF). Nevertheless, As a potential therapeutic strategy, changing the local chromatin architecture via adding or removing the CTCF binding sites in situ to regulate the transcription activity of genes within one TAD in cancer cells is poorly explored. In present study, we observed that the metallothionein (MT) family were all remarkably decreased in HCC of TCGA database, and MT genes family were located within a TAD of 1.2 Mb at 16q13 in order, and CTCF binding sites were distributed at the both sites of MT gene clusters. Furthermore, CRISPR/Cas9 was employed to destroy the CTCF binding sites at the vicinity of the MT family in human liver hepatocellular carcinoma (HCC) cell lines Huh-7 and HepG2. And the presence of up-regulated transcription of MTs were observed in Huh-7 and HepG2 cells compared to normal liver CRL-12461 cells. Moreover, the presence of the varying DNA interplay as well as H3K4me3 and H3K9me3 modification on different MT genes were observed after CTCF binding domain destruction compared to the control using chromosome conformation capture (3C) and chromatin immunoprecipitation (ChIP). Our results determined a potential way to regulate the transcription of a series of genes via changing the local genomic organization for diseases treatment. Highlights • CTCF controls the transcription activity of metallothionein family. • CTCF binding sites affect the local chromatin organization. • Editing CTCF binding sites by CRISPR/Cas9 is a way for cancer treatment. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) is essential in regulation of cancer cell and cancer stem cells (CSCs) behaviour. Linc00662 is a newly identified human lung cancer related lncRNA. In this study, we aimed to explore the function of Linc00662 in human lung cancer. The expression level of Linc00662 was analysed by quantitative real-time PCR. Cell metastasis and invasive ability were detected by transwell and scratch wound healing assays. The stemness of CSCs was shown by tumorsphere formation assay and flow cytometry. The interaction between Linc00662 and Lin28 was confirmed by RNA immunoprecipitation and RNA pulldown assay. Overexpression of Linc00662 promoted the poor prognosis of lung cancer. Cell invasion, metastasis and CSCs stemness in H1299 and A549 could be influenced by Linc00662. Linc00662 had direct interaction with Lin28, and the Linc00662 function was dependent on Lin28. We demonstrate that overexpression of Linc00662 enhances lung cancer cell metastasis and CSC stemness by interacting with Lin28 in human lung cancer, which could be utilized as a potential diagnostic and therapeutic target for lung cancer patients. [ABSTRACT FROM AUTHOR]

Background: Although RET‐tyrosine kinase inhibitors (RET‐TKIs) are the preferred first‐line therapy for advanced RET‐arranged NSCLC, most patients cannot afford them. In this population, bevacizumab, immunotherapy, and chemotherapy are the most commonly used regimens. However, the optimal scheme beyond RET‐TKIs has not been defined in the first‐line setting. Methods: This retrospective study included 86 stage IV NSCLC patients harboring RET rearrangement from six cancer centers between May 2017 and October 2022. RET‐TKIs, chemotherapy, or one of the combination therapies (including immune checkpoint inhibitor (ICI) combined with chemotherapy (I + C), bevacizumab combined with chemotherapy (B + C), ICI and bevacizumab combined with chemotherapy (I + B + C)), were used as the first‐line therapeutics. The clinical outcomes and safety were evaluated. Results: Fourteen of the 86 patients received RET‐TKIs, 57 received combination therapies, and 15 received chemotherapy alone. Their medium PFS (mPFS) were 16.92 months (95% CI: 5.9–27.9 months), 8.7 months (95% CI: 6.5–11.0 months), and 5.55 months (95% CI: 2.4–8.7 months) respectively. Among all the combination schemes, B + C (p = 0.007) or I + B + C (p = 0.025) gave beneficial PFS compared with chemotherapy, while I + C treatment (p = 0.169) generated comparable PFS with chemotherapy. In addition, I + B + C treatment had a numerically longer mPFS (12.21 months) compared with B + C (8.74 months) or I + C (7.89 months) schemes. In terms of safety, I + B + C treatment led to the highest frequency of hematological toxicity (50%) and vomiting (75%), but no ≥G3 adverse effect was observed. Conclusions: I + B + C might be a preferred option beyond RET‐TKIs in the first‐line therapy of RET‐arranged NSCLC. Combination with Bevacizumab rather than with ICIs offered favorable survival compared with chemotherapy alone. [ABSTRACT FROM AUTHOR]

The estuarine planktonic copepods have a wide geographical distribution and commendable tolerance to various kinds of contaminants. The primary aim of the present study was to contrast the impacts of model POPs (TBBPA and HBCD) on three common estuarine planktonic copepods (Oithona similis, Acartia pacifica and Pseudodiaptomus inopinus) and establish a protocol for the assessment of acute toxicity of marine organic pollutants. We first quantified the 96h-LC50 (0.566, 0.04 and 0.257 mg/L of TBBPA to the three subjects above respectively and 0.314 mg/L of HBCD to P. inopinus; all reported concentrations are nominal values). In the sub-lethal toxicity tests, it was turned out that the effects of copepods exposed to TBBPA could product different influences on the energy ingestion and metabolism. Different type of pollutions, meanwhile, could also bring varying degree effect on the target copepods. In general, the indicators (the rate of oxygen consumption, ammonia excretion, food ingestion and filtration) in higher concentration groups showed marked significant difference compared with controls as well a dose-effect relationship. The study also extended the research on the joint toxicity of TBBPA and HBCD based on the survival rate of P.inopinus. Whether 1:1 concentration or 1:1 toxic level, the research showed synergy effect relative to single exposure conditions. The result indicated that current single ecological testing used for environmental protection activities may underestimate the risk for copepods. It was also demonstrated that short-term sub-lethal experiment could be a standard to evaluate the sensitivity of copepods to POPs. [ABSTRACT FROM AUTHOR]

Zinc-dependent histone deacetylases (HDACs) play a critical role in transcriptional repression and gene silencing, and are among the most attractive targets for the development of new therapeutics against cancer and various other diseases. Two HDAC inhibitors have been approved by FDA as anti-cancer drugs: one is SAHA whose hydroxamate is directly bound to zinc, the other is FK228 whose active form may use thiol as the zinc binding group. In spite of extensive studies, it remains to be ambiguous regarding how thiol and hydroxamate are bound to the zinc active site of HDACs. In this work, our computational approaches center on Born-Oppenheimer ab initio quantum mechanical/molecular mechanical (QM/MM) molecular dynamics with umbrella sampling, which allow for modeling of the zinc active site with reasonable accuracy while properly including dynamics and effects of protein environment. Meanwhile, an improved short-long effective function (SLEF2) to describe non-bonded interactions between zinc and other atoms has been employed in initial MM equilibrations. Our ab initio QM/MM MD simulations have confirmed that hydroxamate is neutral when it is bound to HDAC8, and found that thiol is deprotonated when directly bound to zinc in the HDAC active site. By comparing thiol and hydroxamate, our results elucidated the differences in their binding environment in the HDAC active sites, and emphasized the importance of the linker design to achieve more specific binding toward class IIa HDACs. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The relationship between cancer and iron metabolism has received more attention, but there is less research on nutritional support to improve the nutritional and inflammatory status of cancer patients by regulating iron metabolism. A survey was conducted involving 90 patients with lung cancer. The control group was given routine hospitalization diet and the oral nutrition supplement (ONS) group was given oral nutrient solution on the basis of routine hospitalization diet. It lasted for 2 weeks. The changes of iron metabolism, nutritional status, and inflammatory indicators of the two groups were compared. After 2 weeks of intervention, the levels of ALB and PA in the ONS group were increased than that in the control group (P <.05), the inflammation was significantly decreased in the ONS group (P <.05), and the levels of Hb, SI, and TIBC in the ONS group were higher than that in the control group, while the SF was significantly reduced (P <.05). ONS could improve iron metabolism, nutritional status, and inflammatory levels. We speculate that the decrease in inflammation may be due to the changes of iron metabolism, thereby improving nutritional status. It may become a new target for tumor treatment. [ABSTRACT FROM AUTHOR]

[Display omitted] • Highly enantioselectivities synthesis of spiropyrazolones. • Spiro[pyrazolone-pyrrolidinethiones] were synthetized under mild conditions. • The asymmetric Michael addition of 4-isothiocyanato pyrazolones with ethyl β -benzoylacrylates. The cascade Michael addition/cyclization reaction of 4-isothiocyanato pyrazolones with ethyl β -benzoylacrylates has been explored by asymmetric organocatalysis, delivering spiro[pyrazolone-pyrrolidinethione] cores bearing three contiguous stereogenic centers in excellent enantioselectivities (up to 95% ee) with excellent yields (up to 91%). This process exhibited broad substrate scope and the advantages of simple operation. A plausible mechanism for this reaction was proposed. [ABSTRACT FROM AUTHOR]

Epithelial protein lost in neoplasm (EPLIN) has been implicated as a suppressor of cancer progression. The current study explored EPLIN expression in clinical gastric cancer and its association with chemotherapy resistance. EPLIN transcript expression, in conjunction with patient clinicopathological information and responsiveness to neoadjuvant chemotherapy (NAC), was explored in two gastric cancer cohorts collected from the Beijing Cancer Hospital. Kaplan-Meier survival analysis was undertaken to explore EPLIN association with patient survival. Reduced EPLIN expression was associated with significant or near significant reductions of overall, disease-free, first progression or post-progression survival in the larger host cohort and Kaplan Meier plotter datasets. In the larger cohort EPLIN expression was significantly higher in the combined T1 + T2 gastric cancer group compared to the T3 + T4 group and identified to be an independent prognostic factor of disease-free survival and overall survival by multivariate analysis. In the smaller, NAC cohort, EPLIN expression was found to be significantly lower in tumour tissues than in paratumour tissues. EPLIN expression was significantly associated with responsiveness to chemotherapy which contributes to overall survival. Together, EPLIN appears to be a prognostic factor and may be associated with patient sensitivity to NAC. [ABSTRACT FROM AUTHOR]

Luminescent materials with aggregation-induced emission (AIE) have attracted extensive attentions for their strong emission in aggregated states. Although all kinds of AIE luminogens have been recently developed, it is difficult to realize full-color AIE which is popular for the various applications in optoelectronic fields. Herein, a class of diphenylfumaronitrile core-based dyes emitting in a wide region from near ultraviolet (382 nm) to near-infrared (682 nm) have been synthesized and well characterized. It is found that the emission wavelength of the dyes severely depends on the peripheral substituent, including electron-withdrawing trifluoromethyl (1), methyl (2), electron-pushing methoxyl (3), and bulky aromatic amine (7 – 9), and that the substituting location imposes great effect on the emission intensity of multiple-substituted dyes (4 – 6). Compound 4 with two methyl substituting at 3,4-position gives a ultrahigh quantum yield of 93% for unique packing structure. 1 – 3 and 7 can be used in explosive detecting and data storage for their emission sensitive to picric acid and external stimuli, respectively. When 4 and 8 applied in white-light-emitting diodes (WLEDs), a pure white emission can be obtained with 90 of CRI and (0.32, 0.32) of CIE. Image 1 • A series of diphenylfumaronitrile dyes with different substituent were synthesized. • Emissive wavelength can be adjusted from near ultraviolet to near-infrared regions. • Dye 4 with two methyl at 3,4-position shows highly efficient emission (Φ f = 93%). • The dyes were successfully applied in explosive detecting and rewritable data recording. • Pure white emission from WLED can be obtained with 90 of CRI and (0.32, 0.32) of CIE. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor 2 mRNA-binding protein 3 (IMP3) and vascular endothelial growth factor-A (VEGF-A) may play important roles in the process of tumor progression and tumor angiogenesis. The aim of the present study was to examine the co-expression of IMP3 and VEGF-A in primary human non-small cell lung cancer (NSCLC), to investigate the association between these two expression levels and determine the clinicopathological implications, including changes to microvessel density (MVD), and to assess the prognostic value of co-expression. Using immunohistochemical staining, the expression of IMP3, VEGF-A and CD34 expression was detected in 128 primary NSCLC tissue samples. According to the expression of IMP3 and VEGF-A, the cases were divided into four groups. Next, the clinicopathological features, MVD and survival time were investigated across the different groups. The immunohistochemical analyses demonstrated that there was a significant correlation between IMP3 and VEGF-A expression in NSCLC (r=0.181; P=0.041). Co-expression of IMP3 and VEGF-A was significantly associated with larger primary tumor size (P=0.016), poorer differentiation (P=0.014), more advanced Tumor-Node-Metastasis stage (P=0.012), increased MVD (P=0.004) and positive lymph node metastasis (P=0.002). Survival analysis demonstrated that cases with IMP3 and VEGF-A double-positive staining were significantly associated with lower survival rates compared with cases with double-negative staining (P=0.039). In the early NSCLC (I–IIa) subgroup, the mean survival time of the double-positive staining group was significantly shorter compared with that of the double-negative staining group (P=0.015). Co-expression of IMP3 and VEGF-A was associated with angiogenesis and a poorer prognosis in NSCLC, and may therefore play a critical role in NSCLC progression. [ABSTRACT FROM AUTHOR]

We intended to clarify the role of sphingosine kinase 1 (SPHK1) in gastric cancer (GC) using both in vitro and in vivo assays. The study was designed to identify novel therapeutic targets for GC treatment. Differential analysis was utilized to dissect two gene expression omnibus series (GSE49515 and GSE79973) microarray data form Gene Expression Omnibus (GEO) (https://www.ncbi.nlm.nih.gov/geo/) dataset. MRNA and protein expressions were determined by quantitative polymerase chain reaction and Western blot, respectively. GC cell growth was measured by MTT assays and verified by in vivo analysis. Cell cycle and cell apoptosis were detected via flow cytometer observation. Cell migration and invasion were assessed by wound healing assays and Transwell assays. The targeting relationship between miRNA and SPHK1/S1PR1 was identified via dual‐luciferase assay. Twenty‐four common differentially expressed genes were screened out from two gene expression omnibus series (GSE49515 and GSE79973), among which SPHK1 was chosen for its higher fold change. We found elevated SPHK1 expression in GC tissues and cells, along with an increased concentration of SPHK1‐generated sphingosine‐1‐phosphate (S1P) in both GC serum and tissue. SPHK1 knockdown significantly suppressed cell proliferation, migration, and invasion of MKN1 and KATO3 cells. It also blocked cell cycle and induced apoptosis in MKN1 and KATO3 cells. Silencing of SPHK1 also refrained tumor growth and inhibited S1P level. MiR‐330‐3p directly targeted SPHK1 and S1PR1. Overexpressed miR‐330‐3p in MKN1 cells repressed SPHK1 and S1PR1 expressions like their chemical inhibitors‐SPHK1 inhibitors (FTY720) and S1PR1 inhibitors (VPC23019), and acted anti‐tumor both in vitro and in vivo. Our study provides evidence that SPHK1 was promotive for GC tumor growth and cell biological behaviors, and that miR‐330‐3p targeted 3′‐UTR of SPHK1 and inhibited its expression. SPHK1 was expected to become a new molecular marker and miR‐330‐3p a novel therapeutic target for GC. © 2018 IUBMB Life, 70(11):1164–1176, 2018 [ABSTRACT FROM AUTHOR]

Background: With the development of communication technology, the public is paying increasing attention to whether electromagnetic radiation is harmful to health. Mobile phone communication has entered the 5G era, and there are almost no reports on electromagnetic radiation at 2650 MHz. Therefore, it is necessary to evaluate the risk of adverse effects of 5G mobile phone EMR exposure on the human brain. Methods: Male animals were continuously exposed to 2650 MHz‐EMR for 28 days with a whole‐body averaged specific absorption rate (WBSAR) of 2.06 W/kg for 4 h per day. Mouse behavior was assessed using the open‐field test (OFT), elevated‐plus maze (EPM), and tail suspension test (TST). The Morris water maze (MWM), HE staining, and TUNEL staining were used to evaluate the spatial memory ability and pathological morphology of hippocampal dentate gyrus cells. Additionally, the expression levels of brain‐derived neurotrophic factor (BDNF), aminobutyric acid (GABA), and glucocorticoid (GR) in the hippocampus were detected by western blotting and immunohistochemistry, while the corticosterone (CORT) level in serum was detected by ELISA. Results: In the OFT, the total distance traveled, central distance traveled, and residence time significantly decreased in the EMR exposure group (p <.05). In EPM, the percentage of the number of times to open the arm and the percentage of time to open the arm significantly decreased in the EMR exposure group. However, in the TST, the two groups had no significant difference in the 4‐min immobility time. In the MWM, the escape latency of the EMR exposure group was shorter than that of the control group, with no significant difference. Furthermore, CORT levels in serum were significantly increased in the EMR exposure group (p <.05), while the expression of BDNF and GR proteins in the hippocampus was reduced (p <.05), but there was no significant difference in GABA expression. Conclusions: Our results indicate that exposure to 2650 MHz‐EMR (WBSAR: 2.06 W/kg, 28 days, 4 h per day) had no significant effect on the spatial memory ability of mice (in comparison to little effect). The exposure may be associated with anxiety‐like behavior in mice but not related to depression‐like behavior in mice. [ABSTRACT FROM AUTHOR]

[Display omitted] • A multifunctional PDMS-modulated WPU coating with liquid-repellence is developed employing dual-crosslinking strategy. • The coating exhibits outstanding anti-smudge and self-cleaning performances. • The coating possesses exceptional anti-corrosion properties safeguarding the substrate against erosion. • The coating shows excellent mechanical robustness in various external impact tests. The inferior anti-smudge properties and compromised anti-corrosion performance of waterborne polyurethanes (WPUs) stem from the presence of abundant hydrophilic groups in their polymer networks. Despite various hydrophobic segments have been introduced in WPU skeleton to lower the impacts of hydrophilic groups, the limited migration capability of hydrophobic segments in waterborne matrix often result in unsatisfactory performance. Herein, we fabricate a multifunctional PDMS-modulated WPU coating employing sorbitan monooleate (SP), a renewable bio-derived polyol, as an internal crosslink agent, and hexamethoxymethylmelamine (HMMM) as a post-crosslink agent to fully eliminate the polar hydrophilic groups in the molecular linkages and further enhance the crosslink density of the coating. It is found that the coating exhibits exceptional anti-graffiti and self-cleaning effects when subjected to tests involving oil-based and water-based pens and inks, as well as common household liquids like milk, coffee, cooking oil, ethanol, n-hexadecane, etc. Such anti-smudge coating could readily remove carbon powder-like dust with water, ensuring a clean surface, and also possess a certain level of resistance to fingerprint smudges. Apart from excellent mechanical robustness and impressed durability after 500 cycles of writing erase tests, the coating also remains intact and has anti-smudge properties when folded or bent. For chemical resistance, the coating can resist at least 18 h of acid, alkali, and salt intrusion without being damaged. Moreover, the sufficient crosslink density imparts the coating with good thermal stability and outstanding anti-corrosion performance in extremely corrosive environments. This research presents a facile and effective approach for developing stain and corrosion-resistant PDMS-modulated waterborne polyurethane materials with high protective reliability and long lifespan through the dual-crosslinking strategy. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is a common pollutant with reproductive toxicity. Our previous study revealed that Cd triggered spermatogonia ferroptosis. However, the underlying mechanisms remain unclear. Nuclear receptor coactivator 4 (NCOA4) mediates ferritinophagy and specific degradation of ferritin through lysosomes, resulting in the release of ferrous ions. Excessive autophagy can lead to ferroptosis. This study investigated the role of autophagy in Cd-triggered ferroptosis using GC-1 spermatogonial (spg) cells which exposed to CdCl 2 (5 μM, 10 μM, or 20 μM) for 24 without/with CQ. The cells which transfected with Ncoa4-siRNA were used to explore the role of NCOA4-mediated ferritinophagy in Cd-triggered ferroptosis. The results revealed that Cd caused mitochondrial swelling, rupture of cristae, and vacuolar-like changes. The Cd-treated cells exhibited more autophagosomes. Simultaneously, Cd increased intracellular iron, reactive oxygen species, and malondialdehyde concentrations while decreasing glutathione content and Superoxide Dismutase-2 activity. Moreover, Cd upregulated mRNA levels of ferritinophagy-associated genes (Ncoa4, Lc3b and Fth1), as well as enhanced protein expression of NCOA4, LC3B, and FTH1. While Cd decreased the mRNA and protein expression of p62/SQSTM1. These results showed that Cd caused ferritinophagy and ferroptosis. The use of chloroquine to inhibit autophagy ameliorated Cd-induced iron overload and ferroptosis. Moreover, Ncoa4 knockdown in spermatogonia significantly reduced intracellular iron concentration and alleviated Cd-triggered ferroptosis. In conclusion, our findings demonstrate that Cd activates the ferritinophagy pathway mediated by NCOA4, resulting in iron accumulation through ferritin degradation. This causes oxidative stress, ultimately initiating ferroptosis in spermatogonia. Our results may provide new perspectives and potential strategies for preventing and treating Cd-induced reproductive toxicity. [Display omitted] • Cd causes iron overload and triggers ferroptosis in spermatogonia. • Cd induces ferritinophagy in spermatogonia. • CQ antagonizes against Cd-caused iron overload in spermatogonia. • NCOA4-mediated ferritinophagy participates in Cd-triggered ferroptosis. [ABSTRACT FROM AUTHOR]

Endoplasmic reticulum (ER) stress mediates Cd-caused germ cell apoptosis in testis. The effects of 4-phenylbutyric acid (PBA), a classical chaperone, were investigated on Cd-induced apoptosis in mouse GC-1 spermatogonia cells. The cells were pretreated with PBA before Cd exposure. TUNEL and flow cytometry assays were applied to determine apoptosis. Some key biomarkers of ER stress were analyzed using RT-PCR and western blot. as expected, the apoptotic cells exposed to Cd apparently increased. The mRNA and protein expression levels of GRP78 and ATF6α, were elevated in the Cd groups. Additional experiments displayed that Cd notably increased IRE1α and JNK phosphorylation, and upregulated XBP-1 mRNA and protein expression. Moreover, p-eIF2α and CHOP expressions were clearly elevated in the Cd groups. Interestingly, PBA almost completely inhibited ER stress and protected spermatogonia against apoptosis induced by Cd. PBA alleviated Cd-induced ER stress and spermatogonia apoptosis, and may have the therapeutic role in Cd-induced male reproductive toxicity. • CdCl 2 induced spermatogonia apoptosis in vitro. • CdCl 2 triggered spermatogonia ER stress. • 4-PBA alleviated CdCl 2 -induced spermatogonia apoptosis. [ABSTRACT FROM AUTHOR]

At present, a large number of studies have reported that hydrogen has antioxidant functions and prevents oxidative stress damage. However, it is not clear whether hydrogen can prolong longevity based on these effects. Therefore, we studied and explored the antiaging potential of exogenous hydrogen and its ability to extend longevity using Caenorhabditis elegans (C. elegans) as an animal model. Our results showed that the lifespans of the N2, sod-3 and sod-5 mutant strains were extended by approximately 22.7%, 9.5%, and 8.7%, respectively, after hydrogen treatment, but hydrogen had no effect on the lifespans of the daf-2 and daf-16 mutant strains. Meanwhile, the level of reactive oxygen species (ROS) in the hydrogen treatment group was significantly lower than that in the control group. At the transcript level, the expression of age-1 and let-363 was obviously decreased, while the expression of ins-18 was increased at the same time point (14 d). Compared with the control group, paraquat (PQ) could reduce the lifespan of the N2 and sod-5 mutant strains. Importantly, the longevity of these mutant strains recovered to normal levels when the animals were treated with exogenous hydrogen. According to these results, the lifespan of C. elegans is closely related to oxidative stress and can be significantly prolonged by reducing oxidative stress damage. Taken together, our data showed that hydrogen is a valuable antioxidant that can significantly reduce the body's ROS levels and extend the lifespan of C. elegans. This study also laid a foundation for the subsequent application of hydrogen in antiaging studies. [ABSTRACT FROM AUTHOR]

Endometrial cancer (EC), a prevalent gynecologic tumor, is a great threat to women. We aimed to explore miR-142's effects on EC and the relevant mechanisms. Cell proliferation was evaluated with MTT, cell counting, and colony formation assay. MRNA abundances of miR-142 and cyclin D1 (CCND1) were examined with quantitative real-time PCR. CCND1 protein level in cells was analyzed with Western blot. miR-142's downstream target was identified with targetscan and luciferase reporter assay. Nude mice were injected subcutaneously with Ishikawa (ISK) cells transfected with or without miR-142 mimics. Ki-67 and CCND1 expressions in tumors of xenograft mice were analyzed with immunohistochemical assay. miR-142 was expressed at a lower level in human EC tumor samples than matched normal tissues, and its mRNA level in EC patients without metastasis was higher than that in patients with metastatic EC. Additionally, low-level miR-142 was closely linked with the poor prognosis of EC patients. miR-142 restricted ISK and HEC-1A cell proliferation. Targetscan and luciferase reporter assay proved the target relationship between miR-142 and CCND1. Moreover, high-level CCND1 was positively correlated with the poor prognosis of EC patients. Besides, miR-142 mimics restricted tumor growth in ISK xenografted mice, as well as inhibited the expression of Ki67 and CCND1 in excised tumors. miR-142 restricted EC proliferation by targeting CCND1. [ABSTRACT FROM AUTHOR]

Yohimbine is an indole alkaloid from the leaves and bark of the Pausinystalia johimbe tree that has acquired an enviable reputation in treating erectile dysfunction. This report presents four simultaneous severe poisoning/death cases caused by yohimbine. The test samples comprised the venous blood of four middle-aged men (aged 47-65) who were suspected of poisoning; one of the men died due to ineffective rescue. Ethanol concentration determination and toxicological routine screening were performed using gas chromatography with flame ionization detection (GC-FID) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). A specific LC-MS/MS method was developed to quantify yohimbine, which showed concentrations of 459, 249, and 301ng/mL in three poisoned blood samples and concentrations as high as 5631ng/mL in the deceased. Moreover, the deceased's autopsy ruled out death from trauma and previous illness, and no other common toxic components were detected in his blood. Therefore, yohimbine poisoning appears to be the most likely cause of death. As a type of alkaloid that can be employed in the treatment of clinical diseases and additives for supplements, the danger of yohimbine should be of widespread concern in society. [ABSTRACT FROM AUTHOR]

Objective: To investigate the expression of Mitofusin-2 (MFN2) in HCC tissues and its role in the development of HCC. Methods: A total of 107 HCC specimens were collected for tissue microarray analysis and immunohistochemistry (IHC) analysis. The relationship between MFN2 expression and clinical features of patients with HCC was analyzed. Results: Expression level of MFN2 in HCC tissues was 0.92 ± 0.78, significantly lower than that of matched paracancerous liver tissues (1.25 ± 0.75). Patients with low expression of MFN2 had significantly higher rates of cirrhosis than those with high expression of MFN2 (P = 0.049). Kaplan-Meier survival analysis showed that HCC patients with low expression of MFN2 had a worse prognosis in overall survival than HCC patients with high expression of MFN2 (P = 0.027). Patients with high expression of MFN2 had a better prognosis in disease-free survival compared with HCC patients with low expression of MFN2 (P = 0.047). Vascular invasion and MFN2 expression were shown to be prognostic variables for overall survival in patients with HCC. Multivariate analysis showed that vascular invasion (P < 0.001) and MFN2 expression (P = 0.045) were independent prognostic factors for overall survival. Vascular invasion (P < 0.001) and MFN2 expression (P = 0.042) were independent risk factors associated with disease-free survival. Conclusion: Our data revealed that MFN2 expression was decreased in HCC samples. High MFN2 expression was correlated with longer survival times in patients with HCC and served as an independent factor for better outcomes. Our study therefore provides a promising biomarker for the prognostic prediction of HCC and a potential therapeutic target for the disease. [ABSTRACT FROM AUTHOR]