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Background and purpose: N-Myc down stream-regulated gene 2 (NDRG2) is a new type of tumor suppressor gene, which plays an important role in cell proliferation and apoptosis. The chemotherapy resistance of bladder cancer is the main cause for the failure of clinical treatment; therefore, this study aimed to clarify the expression of NDRG2 and its potential role in the pathogenesis of cisplatin (CDDP) resistance in bladder cancer cells. Methods: Bladder cancer T24 cells were continuously passaged by increasing the CDDP concentration for 6 months to obtain CDDP-resistant T24/CR cell lines. Lentiviral transfection was used to achieve high expression of NDRG2 in T24/CR. Cell viability was measured by MTT, apoptosis and transwell invasion assay were performed. The effect of NDRG2 overexpression on T24 cell resistance to CDDP was compared. Bcl-2-siRNA transient transfection was used to knock down the expression of NDRG2 in T24 cells, and then the expression in different groups was detected by Western blot. Real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) was used to detect the expression level of NDRG2 mRNA. Results: The expression level of NDRG2 was significantly down-regulated in CDDP-resistant bladder cancer cells. Exogenous overexpression of NDRG2 enhanced the sensitivity to CDDP and inhibited the viability and invasion of bladder cancer cells in the presence of CDDP. Knockdown of NDRG2 expression had no significant effect on the expression of Bcl-2. Knockdown of Bcl-2 could effectively eliminate the effect of low NDRG2 expression on the viability and apoptosis of bladder cancer cells, and could restore the sensitivity to CDDP in bladder cancer cells. Conclusion: The unbalance of NDRG2/Bcl-2 maybe the key mechanism of CDDP resistance in advanced bladder cancer. Enhanced expression of NDRG2 might be used as a candidate for the treatment of CDDP-resistant or refractory bladder cancer.

This article explores the impact mechanism of different types of environmental regulations on corporate green technology innovation (GTI). The research focuses on analyzing three types of environmental regulations: command based environmental regulation (ER1), market-oriented environmental regulation (ER2), and voluntary environmental regulation (ER3), and how they affect corporate GTI. This study selected enterprise GTI as the dependent variable and measured it by the number of applications for green invention patents and green utility model patents. The independent variables are the three types of environmental regulations mentioned above. According to data from Chinese A-share listed companies. Using benchmark regression models to analyze the impact of different environmental regulations on GTI, and constructing a moderating effect model to study the role of corporate R&D investment and government support in the process of environmental regulations affecting GTI. The results indicate that (1) ER1, ER2, and ER3 can all promote enterprise GTI, and the three environmental regulatory methods have a better synergistic effect. (2) R&D investment has a positive correlation with the relationship between ER2 and GTI, and a negative correlation with ER 3 and ER 1. (3) There are differences in the GTI performance of enterprises in different regions, ownership nature, factor density, and industry types under the influence of environmental regulations. (4) The impact of environmental regulatory policies on corporate GTI is mainly short-term. This study provides a new perspective on how environmental regulations affect corporate GTI, especially in the context of developing countries like China. The research findings emphasize the role of different types of environmental regulations in incentivizing corporate GTI, while also pointing out factors that governments need to consider when formulating environmental policies, such as regional differences and corporate characteristics, which are of great significance for promoting green development of enterprises and achieving broader sustainable development goals. [ABSTRACT FROM AUTHOR]

Simple Summary: Chub mackerel is an economic fishery species that is key in transferring energy from zooplankton to large-bodied carnivores through the local food webs. Understanding the ecological conversion efficiency of this species is important for ecosystem-based fishery. However, the ecological conversion efficiency cannot be accurately determined in the laboratory. In this study, an in situ enrichment method was designed to simulate the wild conditions and used for the determination of ecological conversion efficiency of chub mackerel. Additionally, the method described in this study provided insights into the determination of other wild fishes that are difficult to sample in situ and domesticate in the laboratory. Understanding the ecological conversion efficiency of a fish species can be used to estimate the potential impact of the marine food web and accordingly provides scientific advice to ecosystem-based fishery management. However, only laboratory experiments may limit the accuracy of determining this index. In this study, food ingestion and ecological conversion efficiency of wild chub mackerel (Somber japonicus), a typical marine pelagic fish, were determined with gastric evacuation method in laboratory and in situ enriched simulation conditions. Additionally, the effect of temperature and body weight on ecological conversion efficiency was further estimated based on the 2D interpolation method. The results showed that, at 25.1 °C, the ecological conversion efficiency determined in-lab (35.31%) was significantly higher than in situ (23.85%). Moreover, the interpolation model estimated that with an increase in temperature (10–27 °C), the ecological conversion efficiency initially decreased, followed by an increase when the temperature reached 18 °C, but the ecological conversion efficiency generally decreased against the body weight at each temperature. The findings of this study enhanced the understanding of the energy budget of chub mackerel and also provided an efficient method for the determination of wild fishes that are difficult to sample in situ and domesticate in the laboratory. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI), especially moderate or severe TBI, is one of the most devastating injuries to the nervous system, as the existing therapies for neurological defect repair have difficulty achieving satisfactory results. Neural stem cells (NSCs) therapy is a potentially effective treatment option, especially after specific genetic modifications and when used in combination with biomimetic biological scaffolds. In this study, tussah silk fibroin (TSF) scaffolds with interconnected nanofibrous structures were fabricated using a top-down method. We constructed the apelin-overexpressing NSCs that were cocultured with a TSF nanofiber scaffold (TSFNS) that simulated the extracellular matrix in vitro. To verify the therapeutic efficacy of engineered NSCs in vivo, we constructed TBI models and randomized the C57BL/6 mice into three groups: a control group, an NSC-ctrl group (transplantation of NSCs integrated on TSFNS), and an NSC-apelin group (transplantation of apelin-overexpressing NSCs integrated on TSFNS). The neurological functions of the model mice were evaluated in stages. Specimens were obtained 24 days after transplantation for immunohistochemistry, immunofluorescence, and western blot experiments, and statistical analysis was performed. The results showed that the combination of the TSFNS and apelin overexpression guided extension and elevated the proliferation and differentiation of NSCs both in vivo and in vitro. Moreover, the transplantation of TSFNS-NSCs-Apelin reduced lesion volume, enhanced angiogenesis, inhibited neuronal apoptosis, reduced blood-brain barrier damage, and mitigated neuroinflammation. In summary, TSFNS-NSC-Apelin therapy could build a microenvironment that is more conducive to neural repair to promote the recovery of injured neurological function. [ABSTRACT FROM AUTHOR]

Engineered extracellular vesicles (EVs) are considered excellent delivery vehicles for a variety of therapeutic agents, including nucleic acids, proteins, drugs, and nanomaterials. Recently, several studies have indicated that clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR‐associated 9 (Cas9) delivered by EVs enable efficient DNA editing. However, an RNA editing tool delivered by EVs is still unavailable. Here, a signal peptide‐optimized and EVs‐delivered guide RNA (gRNA) and CRISPR/CasRx (Cas13d) system capable of rapidly inhibiting the expression of targeted genes with quick catabolism after performing their functions is developed. EVs with CRISPR/CasRx and tandem gRNAs targeting pivotal cytokines are further packed whose levels increase substantially over the course of acute inflammatory diseases and find that these engineered EVs inhibit macrophage activation in vitro. More importantly, this system attenuates lipopolysaccharide (LPS)‐triggered acute lung injury and sepsis in the acute phase, mitigating organ damage and improving the prognosis in vivo. In summary, a potent tool is provided for short‐acting RNA editing, which could be a powerful therapeutic platform for the treatment of acute diseases. [ABSTRACT FROM AUTHOR]

Due to the growing industry and industrialization of many urban communities, one of the dangers that threaten human life is long‐term exposure to heavy metals such as lead. Lead contamination can have a detrimental effect on fertility. On the other hand, the combination of ginger and zinc supplements can be a powerful sexual enhancer. Despite extensive studies on the effect of ginger and zinc on reproduction, the effects of the combination of ginger and zinc supplement on lead‐induced reproductive dysfunction are not fully understood. Sixty‐four adult male rats were allocated into control, lead acetate (10 mg/kg), ginger (250 mg/kg), ginger–lead group, zinc (120 mg/kg) group, zinc–lead group, ginger–zinc group and ginger–zinc–lead group. The drugs were administrated by gavage for 4 weeks. The concentration of LH, FSH, testosterone, TNF‐α, IL‐1β, antioxidant enzyme activity, MDA, spermatogenesis, and sperm parameters were measured. The expression of NF‐kB, Nrf2, Bcl2, BAX, and Cas‐3 was evaluated. The histopathological assessment was also detected. Lead significantly could induce inflammation, apoptosis, and oxidative damage in testis tissue, and decrease hormonal levels, spermatogenesis, and sperm parameters compared to the control group (p < 0.05). While in reverse manner ginger, zinc, and their combination significantly improved all of them compared to the lead group (p < 0.05). These results were also supported by histological findings. It can be concluded that ginger, zinc, and their combination could prevent lead‐induced reproductive dysfunction by inhibiting apoptosis mediated by oxidative damage and inflammation and improve reproductive performance. [ABSTRACT FROM AUTHOR]

Polystyrene nanoparticles (PS-NPs) are organic pollutants that are widely detected in the environment and organisms, posing potential threats to both ecosystems and human health. PS-NPs have been proven to penetrate the blood–brain barrier and increase the incidence of neurodegenerative diseases. However, information relating to the pathogenic molecular mechanism is still unclear. This study investigated the neurotoxicity and regulatory mechanisms of PS-NPs in human neuroblastoma SHSY-5Y cells. The results show that PS-NPs caused obvious mitochondrial damages, as evidenced by inhibited cell proliferation, increased lactate dehydrogenase release, stimulated oxidative stress responses, elevated Ca2+ level and apoptosis, and reduced mitochondrial membrane potential and adenosine triphosphate levels. The increased release of cytochrome c and the overexpression of apoptosis-related proteins apoptotic protease activating factor-1 (Apaf-1), cysteinyl aspartate specific proteinase-3 (caspase-3), and caspase-9 indicate the activation of the mitochondrial apoptosis pathway. In addition, the upregulation of autophagy markers light chain 3-II (LC3-II), Beclin-1, and autophagy-related protein (Atg) 5/12/16L suggests that PS-NPs could promote autophagy in SHSY-5Y cells. The RNA interference of Beclin-1 confirms the regulatory role of autophagy in PS-NP-induced neurotoxicity. The administration of antioxidant N-acetylcysteine (NAC) significantly attenuated the cytotoxicity and autophagy activation induced by PS-NP exposure. Generally, PS-NPs could induce neurotoxicity in SHSY-5Y cells via autophagy activation and mitochondria dysfunction, which was modulated by mitochondrial oxidative stress. Mitochondrial damages caused by oxidative stress could potentially be involved in the pathological mechanisms for PS-NP-induced neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate two modes of Rigiscan for predicting tadalafil response, and to identify which Rigiscan variables are the most efficient at making these predictions. Methods: All patients received at least two rounds of nocturnal penile tumescence and rigidity (NPTR) testing and/or audiovisual sexual stimulation (AVSS), then completed the International Index of Erectile Function-5 (IIEF-5) questionnaire, followed by oral 5 mg tadalafil daily for 4 weeks. After a 4-week washout period, all respondents underwent an the IIEF-5 questionnaire again. ED patients were then categorized into tadalafil responders and tadalafil non-responders, who were then further divided into cured patients and uncured patients. Results: When predicting tadalafil responders, the area under the curve (AUC) of NPTR was superior to that of AVSS (0.68~0.84 VS 0.69~0.73), and the predicted optimal cut-off values were DOEE60≥17.75 min in NPTR, compared to other parameters regardless of AVSS or NPTR (P<0.05). When predicting which patients would be cured, the AUC of AVSS was superior to NPTR parameters (0.77~0.81 vs 0.61~0.76), and the determined best diagnostic cut-off values were DOEE≥4.125min in AVSS, compared to other parameters regardless of AVSS or NPTR (P < 0.05). Conclusion: Rigiscan was able to predict the efficacy of daily tadalafil accurately and efficiently. Its diagnostic value was at maximum when DOEE60 ≥17.75 min of NPTR in tadalafil responders and DOEE ≥ 4.125 min of AVSS in cured patients. [ABSTRACT FROM AUTHOR]