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ObjectiveWe investigated the mutational landscape of mammalian target of rapamycin (mTOR) signalling cascade in hepatocellular carcinomas (HCCs) with chronic HBV background, aiming to evaluate and delineate mutation-dependent mechanism of mTOR hyperactivation in hepatocarcinogenesis.DesignWe performed next-generation sequencing on human HCC samples and cell line panel. Systematic mutational screening of mTOR pathway-related genes was undertaken and mutant genes were evaluated based on their recurrence. Protein expressions of tuberous sclerosis complex (TSC)1, TSC2 and pRPS6 were assessed by immunohistochemistry in human HCC samples. Rapamycin sensitivity was estimated by colony-formation assay in HCC cell lines and the treatment was further tested using our patient-derived tumour xenograft (PDTX) models.ResultsWe identified and confirmed multiple mTOR components as recurrently mutated in HBV-associated HCCs. Of significance, we detected frequent (16.2%, n=18/111) mutations of TSC1 and TSC2 genes in the HCC samples. The spectrum of TSC1/2 mutations likely disrupts the endogenous gene functions in suppressing the downstream mTOR activity through different mechanisms and leads to more aggressive tumour behaviour. Mutational disruption of TSC1 and TSC2 was also observed in HCC cell lines and our PDTX models. TSC-mutant cells exhibited reduced colony-forming ability on rapamycin treatment. With the use of biologically relevant TSC2-mutant PDTXs, we demonstrated the therapeutic benefits of the hypersensitivity towards rapamycin treatment.ConclusionsTaken together, our findings suggest the significance of previously undocumented mutation-dependent mTOR hyperactivation and frequent TSC1/2 mutations in HBV-associated HCCs. They define a molecular subset of HCC having genetic aberrations in mTOR signalling, with potential significance of effective specific drug therapy.

Spinal muscular atrophy (SMA) is the most common genetic motoneuron degenerative disorder, but the mechanism(s) of motoneuron degeneration is unclear. We previously generated SMA model mice, which genotypically and phenotypically mimicked human SMA patients, by a combination of knockout and transgenic techniques. Here, we used these SMA model mice to decipher the apoptotic mechanism(s) involved in SMA motoneuron degeneration. We found a significant increase in proapoptotic Bax expression in the spinal cords of SMA mice in comparison with their wild-type littermates. After crossing SMA mice with Bax knockout mice, we produced in vivo evidence indicating that Bax protein plays an important role in the degeneration of SMA spinal motoneurons. Progeny Bax-deficient SMA mice showed milder disease severity, longer life spans, and significant increases in spinal motoneuron densities compared to SMA littermates with wild-type Bax genes. Our results strongly suggest that suppression of Bax-involved apoptosis has the potential for amelioration of SMA.

Spinal muscular atrophy (SMA) is the most common genetic motoneuron degenerative disorder, but the mechanism(s) of motoneuron death is unclear. Previously, a direct interaction between tumor-suppressive TP53 protein and the SMA determinant gene product, survival motor neuron protein, was identified and therefore it has been suggested that a mechanism of TP53-dependent apoptosis plays an important role in motoneuron degeneration in SMA. We used our SMA model mice, generated by a combination of knockout and transgenic techniques, to decipher the role of TP53 protein in the motoneuron degeneration in SMA. We detected a significant increase of Trp53 expression in the spinal cord of SMA-like mice compared to their normal littermates. After crossing SMA-like mice with Trp53 knockout mice, the progeny Trp53-deficient SMA-like mice did not show milder disease severity or longer lifespan compared to SMA littermates with wild-type Trp53 genes. Our studies provide in vivo evidence indicating that Trp53-dependent apoptosis does not play a crucial role in motoneuron degeneration in SMA-like mice.

Understanding the epidemic of chronic kidney disease of uncertain etiology may be critical for health policies and public health responses. Recent studies have shown that microplastics (MPs) contaminate our food chain and accumulate in the gut, liver, kidney, muscle, and so on. Humans manufacture many plastics-related products. Previous studies have indicated that particles of these products have several effects on the gut and liver. Polystyrene (PS)-MPs (PS-MPs) induce several responses, such as oxidative stress, and affect living organisms. The aim of this study was to investigate the effects of PS-MPs in kidney cells and . PS-MPs were evaluated in human kidney proximal tubular epithelial cells (HK-2 cells) and male C57BL/6 mice. Mitochondrial reactive oxygen species (ROS), endoplasmic reticulum (ER) stress, inflammation, and autophagy were analyzed in kidney cells. , we evaluated biomarkers of kidney function, kidney ultrastructure, muscle mass, and grip strength, and urine protein levels, as well as the accumulation of PS-MPs in the kidney tissue. Uptake of PS-MPs at different concentrations by HK-2 cells resulted in higher levels of mitochondrial ROS and the mitochondrial protein Bad. Cells exposed to PS-MPs had higher ER stress and markers of inflammation. MitoTEMPO, which is a mitochondrial ROS antioxidant, mitigated the higher levels of mitochondrial ROS, Bad, ER stress, and specific autophagy-related proteins seen with PS-MP exposure. Furthermore, cells exposed to PS-MPs had higher protein levels of LC3 and Beclin 1. PS-MPs also had changes in phosphorylation of mitogen-activated protein kinase (MAPK) and protein kinase B (AKT)/mitogen-activated protein kinase (mTOR) signaling pathways. In an study, PS-MPs accumulated and the treated mice had more histopathological lesions in the kidneys and higher levels of ER stress, inflammatory markers, and autophagy-related proteins in the kidneys after PS-MPs treatment by oral gavage. The results suggest that PS-MPs caused mitochondrial dysfunction, ER stress, inflammation, and autophagy in kidney cells and accumulated in HK-2 cells and in the kidneys of mice. These results suggest that long-term PS-MPs exposure may be a risk factor for kidney health. https://doi.org/10.1289/EHP7612.

In recent years, Taiwan’s high-tech chip industry has experienced vigorous growth, with the telecommunications sector being the largest consumer of chips. Since the global outbreak of the pandemic in 2019, the telecommunications industry has played a major role in shaping human life and commercial activities. Moreover, advancements in chip technology are making telecommunications-related Artificial Intelligence (AI) increasingly powerful. Taiwan’s telecommunications AI industry has secured a significant position globally; however, its production processes often generate toxic substances, posing environmental risks. Therefore, companies should emphasize both operational profitability and sustainable development. This study covers a five-year period from 2018 to 2022, using Taiwan’s telecommunications AI industry as the research sample. The main contribution of this study lies in applying the Dynamic Network Directional Distance Function (DN-DDF) to analyze efficiency across four stages: profitability, sustainability, market performance, and overall efficiency. The study aims to enhance technical capabilities and promote rational resource allocation to assist businesses in making decisions that balance profitability with environmental protection, social responsibility, and corporate governance. It also considers market value, which is highly regarded by investors, to improve overall efficiency. Empirical results indicate that the average overall dynamic efficiency is highest at the market stage, followed by the profitability stage, and lowest at the sustainability stage. When dividing the industry into four major segments, branded terminals exhibit the highest average dynamic efficiency, followed by design, manufacturing, assembly, and key semiconductor chips. In contrast, telecommunications companies, being at the most downstream end, show the greatest need for improvement in the future.

Plastic products are inexpensive, convenient, and are have many applications in daily life. We overuse plastic-related products and ineffectively recycle plastic that is difficult to degrade. Plastic debris can be fragmented into smaller pieces by many physical and chemical processes. Plastic debris that is fragmented into microplastics or nanoplastics has unclear effects on organismal systems. Recently, this debris was shown to affect biota and to be gradually spreading through the food chain. In addition, studies have indicated that workers in plastic-related industries develop many kinds of cancer because of chronic exposure to high levels of airborne microplastics. Microplastics and nanoplastics are everywhere now, contaminating our water, air, and food chain. In this review, we introduce a classification of plastic polymers, define microplastics and nanoplastics, identify plastics that contaminate food, describe the damage and diseases caused by microplastics and nanoplastics, and the molecular and cellular mechanisms of this damage and disease as well as solutions for their amelioration. Thus, we expect to contribute to the understanding of the effects of microplastics and nanoplastics on cellular and molecular mechanisms and the ways that the uptake of microplastics and nanoplastics are potentially dangerous to our biota. After understanding the issues, we can focus on how to handle the problems caused by plastic overuse.

In patients with acute respiratory infections (ARIs), routine diagnostic tests often fail to identify the microbial cause; thus, many ARIs have undetermined etiology. We investigated potential involvement of thermotolerant bacteria in ARIs among patients in Hong Kong, China, by incubating blood agar inoculated with respiratory specimens at 50°C for 5 days. Among 7,257 specimens analyzed, 58 specimens from 57 patients grew thermotolerant bacteria not identified by other methods. We identified Tepidimonas spp. in 42 isolates, 3 of which appear to be a novel Tepidimonas species (tentatively Tepidimonas hongkongensis sp. nov). Genomic analysis revealed various virulence, resistance, and stress-related genomes in the 3 isolates. Tepidimonas spp. bacteria were predominantly isolated from patients with chronic lung disease and malignancies. We also detected T. hongkongensis in hospital water samples but at a lower percentage than in respiratory specimens, suggesting colonization potential. Clinical implications of T. hongkongensis remain unknown; continued surveillance could determine its role in ARIs.

Artificial Intelligence (AI) is increasingly popular, and educators are paying increasing attention to it. For students, learning AI helps them better cope with emerging societal, technological, and environmental challenges. This theory of planned behavior (TPB)-based study developed a survey questionnaire to measure behavioral intention to learn AI (n = 682) among primary school students. The questionnaire was administered online, and it measured responses to five TPB factors. The five factors were (1) self-efficacy in learning AI, (2) AI readiness, (3) perceptions of the use of AI for social good, (4) AI literacy, and (5) behavioral intention. Exploratory factor analysis and a subsequent confirmatory factor analysis were used to validate this five-factor survey. Both analyses indicated satisfactory construct validity. A structural equation model (SEM) was constructed to elucidate the factors' influence on intention to learn AI. According to the SEM, all factors could predict intention to learn AI, whether directly or indirectly. This study provides new insights for researchers and instructors who are promoting AI education in schools.

With the development of economy, people's living standards are improved. The rosewood market continues to grow. But rosewood raw materials can't be certified, the quality of processing can't be identified, and the product price is obviously confused, has become China's three major pain points of rosewood market. To solve this problem becomes a key factor to the future healthy and smooth development of the rosewood industry. This thesis tries to according to Market Transaction Efficiency Theory, Information Asymmetry Theory, and Financial Market Microstructure Theory, analyze the rosewood transaction market under the framework of information asymmetry theory, sort out the sequence of the transaction elements, reconstruct the market organization and reengineer its process, lead elements of the transaction to be a standard transaction product by modern Internet technology, and establish a rosewood trading center for transaction to solve the problem of low efficiency in market. The establishment and operation of

A connection between airway and gut microbiota related to allergen exposure in childhood allergies was not well addressed. We aimed to identify the microbiota alterations in the airway and gut related to mite-specific IgE responses in young children with airway allergies. This study enrolled 60 children, including 38 mite-sensitized children (20 rhinitis and 18 asthma), and 22 non-mite-sensitized healthy controls. Microbiome composition analysis of the throat swab and stool samples was performed using bacterial 16S rRNA sequencing. An integrative analysis of the airway and stool microbial profiling associated with IgE reactions in childhood allergic rhinitis and asthma was examined. The Chao1 and Shannon indices in the airway were significantly lower than those in the stool. Additionally, an inverse association of the airway microbial diversity with house dust mite (HDM) sensitization and allergic airway diseases was noted. Fecal IgE levels were positively correlated with the serum Dermatophagoides pteronyssinus - and Dermatophagoides farinae -specific IgE levels. Airway Leptotrichia spp. related to asthma were strongly correlated with fecal Dorea and Ruminococcus spp., which were inversely associated with fecal IgE levels and risk of allergic rhinitis. Moreover, four airway genera, Campylobacter , Selenomonas , Tannerella , and Atopobium , were negatively correlated with both serum mite-specific and fecal IgE levels. Among them, the airway Selenomonas and Atopobium spp. were positively correlated with stool Blautia and Dorea spp. related to asthma and allergic rhinitis, respectively. In conclusion, airway microbial dysbiosis in response to HDM and its cross-talk with the gut microbial community is related to allergic airway diseases in early childhood.