Effects of different natural products in patients with non-alcoholic fatty liver disease-A network meta-analysis of randomized controlled trials.

Due to a scarcity of appropriate therapeutic approaches capable of ameliorating or eliminating non-alcoholic fatty liver disease (NAFLD), many researchers have come to focus on natural products based on traditional medicine that can be utilized to successfully treat NAFLD. In this study, we aimed to evaluate the effects exerted by seven natural products (curcumin, silymarin, resveratrol, artichoke leaf extract, berberine, catechins, and naringenin) on patients with NAFLD. For this purpose, PubMed, Embase, Cochrane Library, and Web of Science, were searched for randomized controlled trials (RCTs) exclusively. The selected studies were evaluated for methodological quality via the Cochrane bias risk assessment tool, and data analysis software was used to analyze the data accordingly. The RCTs from the earliest available date until September 2022 were collected. This process resulted in 37 RCTs with a total sample size of 2509 patients being included. The results of the network meta-analysis showed that artichoke leaf extract confers a relative advantage in reducing the aspartate aminotransferase (AST) levels (SUCRA: 99.1%), alanine aminotransferase (ALT) levels (SUCRA: 88.2%) and low-density lipoprotein cholesterol (LDL-C) levels (SUCRA: 88.9%). Naringenin conferred an advantage in reducing triglyceride (TG) levels (SUCRA: 97.3%), total cholesterol (TC) levels (SUCRA: 73.9%), and improving high-density lipoprotein cholesterol (HDL-C) levels (SUCRA: 74.9%). High-density catechins significantly reduced body mass index (BMI) levels (SUCRA: 98.5%) compared with the placebo. The Ranking Plot of the Network indicated that artichoke leaf extract and naringenin performed better than the other natural products in facilitating patient recovery. Therefore, we propose that artichoke leaf extract and naringenin may exert a better therapeutic effect on NAFLD. This study may help guide clinicians and lead to further detailed studies.

[Research progress of traditional Chinese medicine in regulating autophagy for intervening in diabetic cardiomyopathy].

Diabetic cardiomyopathy(DCM) is a chronic complication of diabetes mellitus that leads to cardiac damage in the later stages of the disease, and its pathogenesis is complex, involving metabolic disorders brought about by a variety of aberrant alterations such as endoplasmic reticulum stress, oxidative stress, inflammation, and apoptosis, defects in cardiomyocyte Ca~(2+) transporter, and myocardial fibrosis. Currently, there is a lack of specific diagnosis and treatment in the clinic. Autophagy is a highly conserved scavenging mechanism that removes proteins, damaged organelles or foreign contaminants and converts them into energy and amino acids to maintain the stability of the intracellular environment. Inhibition of autophagy can cause harmful metabolites to accumulate in the cell, while over-activation of autophagy can disrupt normal cellular structures and cause cell death. Prolonged high glucose levels disrupt cardiomyocyte autophagy levels and exacerbate the development of DCM. The protective or detrimental effects of autophagy on cells ring true with the traditional Chinese medicine theory of healthy Qi and pathogenic Qi. Autophagy in the physiological state of the removal of intracellular substances and the generation of substances beneficial to the survival of cells is the inhibition of pathogenic Qi to help the performance of healthy Qi, so the organism is healthy. In the early stages of the disease, when autophagy is impaired and incapable of removing waste substances, pathogenic Qi is prevalent; In the later stages of the disease, excessive activation of autophagy can destroy normal cells, leading to a weakening of healthy Qi. Traditional Chinese medicine has the advantage of targeting multiple sites and pathways. Studies in recent years have confirmed that traditional Chinese medicine monomers or formulas can target autophagy, promote the restoration of autophagy levels, maintain mitochondrial and endoplasmic reticulum homeostasis, and reduce oxidative stress, endoplasmic reticulum stress, inflammation, and apoptosis in order to prevent and control DCM. This study provides a review of the relationship between autophagy and DCM and the intervention of traditional Chinese medicine in autophagy for the treatment of DCM, with a view to providing new clinical ideas and methods for the treatment of DCM with traditional Chinese medicine.

[Diosgenin alleviates NAFLD induced by a high-fat diet in rats via mTOR/SREBP-1c/HSP60/MCAD/SCAD signaling pathway].

This study aims to observe the effects of diosgenin on the expression of mammalian target of rapamycin(mTOR), sterol regulatory element-binding protein-1c(SREBP-1c), heat shock protein 60(HSP60), medium-chain acyl-CoA dehydrogenase(MCAD), and short-chain acyl-CoA dehydrogenase(SCAD) in the liver tissue of the rat model of non-alcoholic fatty liver disease(NAFLD) and explore the mechanism of diosgenin in alleviating NAFLD. Forty male SD rats were randomized into five groups: a control group, a model group, low-(150 mg·kg~(-1)·d~(-1)) and high-dose(300 mg·kg~(-1)·d~(-1)) diosgenin groups, and a simvastatin(4 mg·kg~(-1)·d~(-1)) group. The rats in the control group were fed with a normal diet, while those in the other four groups were fed with a high-fat diet. After feeding for 8 weeks, the body weight of rats in the high-fat diet groups increased significantly. After that, the rats were administrated with the corresponding dose of diosgenin or simvastatin by gavage every day for 8 weeks. The levels of triglyceride(TG), total cholesterol(TC), alanine transaminase(ALT), and aspartate transaminase(AST) in the serum were determined by the biochemical method. The levels of TG and TC in the liver were measured by the enzyme method. Oil-red O staining was employed to detect the lipid accumulation, and hematoxylin-eosin(HE) staining to detect the pathological changes in the liver tissue. The mRNA and protein levels of mTOR, SREBP-1c, HSP60, MCAD, and SCAD in the liver tissue of rats were determined by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR) and Western blot, respectively. Compared with the control group, the model group showed increased body weight, food uptake, liver index, TG, TC, ALT, and AST levels in the serum, TG and TC levels in the liver, lipid deposition in the liver, obvious hepatic steatosis, up-regulated mRNA and protein expression levels of mTOR and SREBP-1c, and down-regulated mRNA and protein expression levels of HSP60, MCAD, and SCAD. Compared with the model group, the rats in each treatment group showed obviously decreased body weight, food uptake, liver index, TG, TC, ALT, and AST levels in the serum, TG and TC levels in the liver, lessened lipid deposition in the liver, ameliorated hepatic steatosis, down-regulated mRNA and protein le-vels of mTOR and SREBP-1c, and up-regulated mRNA and protein levels of HSP60, MCAD, and SCAD. The high-dose diosgenin outperformed the low-dose diosgenin and simvastatin. Diosgenin may prevent and treat NAFLD by inhibiting the expression of mTOR and SREBP-1c and promoting the expression of HSP60, MCAD, and SCAD to reduce lipid synthesis, improving mitochondrial function, and promoting fatty acid ß oxidation in the liver.

CPEB4 promotes cell migration and invasion via upregulating Vimentin expression in breast cancer.

Cytoplasmic polyadenylation element binding protein 4 (CPEB4) is a member of CPEB family which is overexpressed in variety of cancers. However, the biological role and regulatory mechanism of CPEB4 in cancers remain unknown. Here, we first investigate the role of CPEB4 in breast cancer progression and metastasis. The expression of CPEB4 is elevated in breast cancer tissues compared with adjacent normal tissues. Furthermore, high expression levels of CPEB4 is associated with tumor metastasis in breast cancer patients. Ectopic expression of CPEB4 dramatically promotes EMT, migration and invasion of breast cancer cells, while silencing CPEB4 expression significantly reduces these events. Mechanically, overexpression of CPEB4 upregulates Vimentin expression and silencing Vimentin expression blocks CPEB4-induced migration and invasion of breast cancer cells. These results implicate the potential role of CPEB4 and Vimentin in breast cancer metastasis, which is further confirmed by the finding that there is a physical interaction between the two proteins. Altogether, our results provide a novel insight into CPEB4 in regulating breast cancer progression and metastasis.

Capsaicin Protects Against Oxidative Insults and Alleviates Behavioral Deficits in Rats with 6-OHDA-Induced Parkinson's Disease via Activation of TRPV1.

Increasing evidence suggests that capsaicin may play a role in modulating neuronal function and controlling motor behavior. However, the underlying mechanism is still unclear and the activation of transient receptor potential vanilloid 1 (TRPV1) might be involved in. This study investigated the potential neuroprotective role of capsaicin in a rat model of 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease (PD). Capsaicin was treated intraperitoneally for the 6-OHDA induced PD rats and the locomotor activity and abnormal involuntary movements were found alleviated. Besides, brain oxidative stress (lipid peroxidation, superoxide dismutase and catalase) was also assessed, and oxidative insults were investigated relieved. Both the expression of tyrosine hydroxylase and TRPV1 were increased in the striatal and substantia nigra areas of 6-OHDA induced rats after the treatment of capsaicin by the semi-quantitative analysis of Western Blot. And the immunostaining of substantia nigra further suggested that capsaicin might protect against dopaminergic neuronal loss. Our results showed that TRPV1 might be a novel therapeutic target for PD.

Discovery of novel benzotriazole ultraviolet stabilizers in surface water.

The comprehensive understanding of the occurrence of benzotriazole UV stabilizers (BZT-UVs) in environmental surface water is imperative due to their widespread application and potential aquatic toxicity. We conducted an analysis of 13 traditional BZT-UVs in surface water samples collected from Taihu Lake (TL, n = 23) and Qiantang River (QR, n = 22) in China. The results revealed that 5­chloro-2-(3,5-di-tertbutyl-2-hydroxyphenyl)-benzotriazole (UV-327) was consistently the predominant BZT-UV in water samples from TL (mean 16 ng/L; detection frequency 96 %) and QR (14 ng/L; 91 %). Furthermore, we developed a characteristic fragment ion-based strategy to screen and identify unknown BZT-UVs in collected surface water, utilizing a high-resolution mass spectrometer. A total of seven novel BZT-UVs were discovered in water samples, and their chemical structures were proposed. Four of these novel BZT-UVs were further confirmed with standards provided by industrial manufacturers. Semi-quantitative analysis revealed that among discovered novel BZT-UVs, 2-(2­hydroxy-3­tert­butyl­5-methylphenyl)-benzotriazole was consistently the predominant novel BZT-UV in TL (mean 4.1 ng/L, detection frequency 70 %) and QR (2.8 ng/L, 77 %) water. In TL water, the second predominant novel BZT-UV was 2-(3-allyl-2­hydroxy-5-methylphenyl)-2H-benzotriazole (mean 3.9 ng/L,

Idebenone ameliorates statin-induced myotoxicity in atherosclerotic ApoE-/- mice by reducing oxidative stress and improving mitochondrial function.

Statins are the first line of choice for the treatment for atherosclerosis, but their use can cause myotoxicity, a common side effect that may require dosage reduction or discontinuation. The exact mechanism of statin-induced myotoxicity is unknown. Previous research has demonstrated that the combination of idebenone and statin yielded superior anti-atherosclerotic outcomes. Here, we investigated the mechanism of statin-induced myotoxicity in atherosclerotic ApoE-/- mice and whether idebenone could counteract it. After administering simvastatin to ApoE-/- mice, we observed a reduction in plaque formation as well as a decrease in their exercise capacity. We observed elevated levels of lactic acid and creatine kinase, along with a reduction in the cross-sectional area of muscle fibers, an increased presence of ragged red fibers, heightened mitochondrial crista lysis, impaired mitochondrial complex activity, and decreased levels of CoQ9 and CoQ10. Two-photon fluorescence imaging revealed elevated H2O2 levels in the quadriceps, indicating increased oxidative stress. Proteomic analysis indicated that simvastatin inhibited the tricarboxylic acid cycle. Idebenone treatment not only further reduced plaque formation but also ameliorated the impaired exercise capacity caused by simvastatin. Our study represents the inaugural comprehensive investigation into the mechanisms underlying statin-induced myotoxicity. We have demonstrated that statins inhibit CoQ synthesis, impair mitochondrial complex functionality, and elevate oxidative stress, ultimately resulting in myotoxic effects. Furthermore, our research marks the pioneering identification of idebenone's capability to mitigate statin-induced myotoxicity by attenuating oxidative stress, thereby safeguarding mitochondrial complex functionality. The synergistic use of idebenone and statin not only enhances the effectiveness against atherosclerosis but also mitigates statin-induced myotoxicity.

Association of serum bisphenols, parabens, and triclosan concentrations with Sjögren Syndrome in the Hangzhou, China population.

Exposure to endocrine-disrupting chemicals (EDCs) has been linked to various immune deficiency disorders, including autoimmune diseases like Sjögren Syndrome (SjS). However, the detrimental effects of exposure to EDCs, including bisphenols, parabens, and triclosan (TCS), on SjS have been inadequately documented. Thus, we conducted a cross-sectional study that included both healthy individuals (controls) and patients with SjS (cases). We assessed serum concentrations of bisphenol A (BPA), bisphenol S (BPS), methyl parabens (MeP), ethyl parabens (EtP), and TCS. The relationship between the five EDCs levels and the risk of SjS was also explored. Additionally, we conducted an in-depth analysis of the collective influence of these EDCs mixtures on SjS, employing a weighted quantile sum regression model. Out of the five EDCs analyzed, EtP displayed the highest mean concentration (2.80 ng/mL), followed by BPA (2.66 ng/mL) and MeP (1.99 ng/mL), with TCS registering the lowest level (0.36 ng/mL). Notably, BPS exposure was significantly positively associated with the risk of being diagnosed with SjS (with an odds ratio [OR] of 1.17, p = 0.042). No statistically significant associations with SjS were observed for BPA, MeP, EtP, and TCS (p > 0.05). And we did not observe any significant effects of the EDCs mixture on SjS. To the best of our knowledge, this study is the first to suggest that BPS may potentially increase the risk of SjS. Although no significant effects were observed between other EDCs and SjS risk, we cannot disregard the potential harm of EDCs due to their non-monotonic dose response.

Diosgenin attenuates metabolic-associated fatty liver disease through the hepatic NLRP3 inflammasome-dependent signaling pathway.

Metabolic-associated fatty liver disease (MAFLD) is one of the most common liver diseases worldwide; however, its pathogenesis and treatment methods have not been perfected. NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) is a promising therapeutic target for MAFLD. Diosgenin (DG) is a natural compound that was identified in a traditional Chinese herbal medicine, which has pharmacological effects, such as anti-inflammatory, antioxidant, hepatoprotective, and hypolipidemic activities. In this study, we examined the effects and molecular mechanisms of DG on MAFLD in vitro and in vivo. We established a rat model by administering a high-fat diet (HFD). We also generated an in vitro MAFLD model by treating HepG2 cells with free fatty acids (FFAs). The results indicated that DG attenuated lipid accumulation and liver injury in both in vitro and in vivo models. DG downregulated the expression of NLRP3, apoptosis-associated speckle-like protein (ASC), cysteinyl aspartate specific proteinase-1 (caspase-1), gasdermin D (GSDMD), GSDMD-n, and interleukin-1ß (IL-1ß). In addition, we silenced and overexpressed NLRP3 in vitro to determine the effects of DG on antiMAFLD. Silencing NLRP3 enhanced the effect of DG on the treatment of MAFLD, whereas NLRP3 overexpression reversed its beneficial effects. Taken together, the results show that DG has a favorable effect on attenuating MAFLD through the hepatic NLRP3 inflammasome-dependent signaling pathway. DG represents a natural NLRP3 inhibitor for the MAFLD treatment.

Diosgenin attenuates nonalcoholic hepatic steatosis through the hepatic SIRT1/PGC-1α pathway.

The prevalence of nonalcoholic fatty liver disease (NAFLD) has been increasing worldwide in recent years, causing severe economic and social burdens. Therefore, the lack of currently approved drugs for anti-NAFLD has gradually gained attention. SIRT1, as a member of the sirtuins family, is now the most widely studied in the pathophysiology of many metabolic diseases, and has great potential for preventing and treating NAFLD. Natural products such as Diosgenin (DG) have the potential to be developed as clinical drugs for the treatment of NAFLD due to their excellent multi-target therapeutic effects. In this study, we found that DG can activate the SIRT1/PGC-1α pathway and upregulate the expression of its downstream targets nuclear respiratory factor 1 (NRF1), complex IV (COX IV), mitofusin-2 (MFN2), and PPARα (perox-isome proliferator-activated receptor α) in SD rats induced by high-fat diet (HFD) and HepG2 cells caused by free fatty acids (FFAs, sodium oleate: sodium palmitate = 2:1). Conversely, the levels of dynamin-related protein 1 (DRP1) and inflammatory factors, including NF-κB p65, IL6, and TNFα, were downregulated both in vitro and in vivo. This improved mitochondrial dysfunction, fatty acid oxidation (FAO), lipid accumulation, steatosis, oxidative stress, and hepatocyte inflammation. Subsequently, we applied SIRT1 inhibitor EX527 and SIRT1 agonist SRT1720 to confirm further the necessity of activating SIRT1 for DG to exert therapeutic effects on NAFLD. In summary, these results further demonstrate the potential therapeutic role of DG as a SIRT1 natural agonist for NAFLD. (Graphical Abstracts).

The Role of JAK/STAT Signaling Pathway and Its Downstream Influencing Factors in the Treatment of Atherosclerosis.

Atherosclerosis is now widely considered to be a chronic inflammatory disease, with increasing evidence suggesting that lipid alone is not the main factor contributing to its development. Rather, atherosclerotic plaques contain a significant amount of inflammatory cells, characterized by the accumulation of monocytes and lymphocytes on the vessel wall. This suggests that inflammation may play a crucial role in the occurrence and progression of atherosclerosis. As research deepens, other pathological factors have also been found to influence the development of the disease. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway is a recently discovered target of inflammation that has gained attention in recent years. Numerous studies have provided evidence for the causal role of this pathway in atherosclerosis, and its downstream signaling factors play a significant role in this process. This brief review aims to explore the crucial role of the JAK/STAT pathway and its representative downstream signaling factors in the development of atherosclerosis. It provides a new theoretical basis for clinically affecting the development of atherosclerosis by interfering with the JAK/STAT signaling pathway.

Mechanism of Action and Related Natural Regulators of Nrf2 in Nonalcoholic Fatty Liver Disease.

With the acceleration of people's pace of life, non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in the world, which greatly threatens people's health and safety. Therefore, there is still an urgent need for higher-quality research and treatment in this area. Nuclear factor Red-2-related factor 2 (Nrf2), as a key transcription factor in the regulation of oxidative stress, plays an important role in inducing the body's antioxidant response. Although there are no approved drugs targeting Nrf2 to treat NAFLD so far, it is still of great significance to target Nrf2 to alleviate NAFLD. In recent years, studies have reported that many natural products treat NAFLD by acting on Nrf2 or Nrf2 pathways. This article reviews the role of Nrf2 in the pathogenesis of NAFLD and summarizes the currently reported natural products targeting Nrf2 or Nrf2 pathway for the treatment of NAFLD, which provides new ideas for the development of new NAFLD-related drugs.

Targeting autophagy with natural products as a potential therapeutic approach for diabetic microangiopathy.

As the quality of life improves, the incidence of diabetes mellitus and its microvascular complications (DMC) continues to increase, posing a threat to people's health and wellbeing. Given the limitations of existing treatment, there is an urgent need for novel approaches to prevent and treat DMC. Autophagy, a pivotal mechanism governing metabolic regulation in organisms, facilitates the removal of dysfunctional proteins and organelles, thereby sustaining cellular homeostasis and energy generation. Anomalous states in pancreatic ß-cells, podocytes, Müller cells, cardiomyocytes, and Schwann cells in DMC are closely linked to autophagic dysregulation. Natural products have the property of being multi-targeted and can affect autophagy and hence DMC progression in terms of nutrient perception, oxidative stress, endoplasmic reticulum stress, inflammation, and apoptosis. This review consolidates recent advancements in understanding DMC pathogenesis via autophagy and proposes novel perspectives on treating DMC by either stimulating or inhibiting autophagy using natural products.

Large-scale genomic rearrangements boost SCRaMbLE in Saccharomyces cerevisiae.

Synthetic Chromosome Rearrangement and Modification by LoxP-mediated Evolution (SCRaMbLE) is a promising tool to study genomic rearrangements. However, the potential of SCRaMbLE to study genomic rearrangements is currently hindered, because a strain containing all 16 synthetic chromosomes is not yet available. Here, we construct SparLox83R, a yeast strain containing 83 loxPsym sites distributed across all 16 chromosomes. SCRaMbLE of SparLox83R produces versatile genome-wide genomic rearrangements, including inter-chromosomal events. Moreover, when combined with synthetic chromosomes, SCRaMbLE of hetero-diploids with SparLox83R leads to increased diversity of genomic rearrangements and relatively faster evolution of traits compared to hetero-diploids only with wild-type chromosomes. Analysis of the SCRaMbLEd strain with increased tolerance to nocodazole demonstrates that genomic rearrangements can perturb the transcriptome and 3D genome structure and consequently impact phenotypes. In summary, a genome with sparsely distributed loxPsym sites can serve as a powerful tool for studying the consequence of genomic rearrangements and accelerating strain engineering in Saccharomyces cerevisiae.

Designing a synthetic moss genome using GenoDesigner.

The de novo synthesis of genomes has made unprecedented progress and achieved milestones, particularly in bacteria and yeast. However, the process of synthesizing a multicellular plant genome has not progressed at the same pace, due to the complexity of multicellular plant genomes, technical difficulties associated with large genome size and structure, and the intricacies of gene regulation and expression in plants. Here we outline the bottom-up design principles for the de novo synthesis of the Physcomitrium patens (that is, earthmoss) genome. To facilitate international collaboration and accessibility, we have developed and launched a public online design platform called GenoDesigner. This platform offers an intuitive graphical interface enabling users to efficiently manipulate extensive genome sequences, even up to the gigabase level. This tool is poised to greatly expedite the synthesis of the P. patens genome, offering an essential reference and roadmap for the synthesis of plant genomes.

Environmentally relevant exposure to cotinine induces neurobehavioral toxicity in zebrafish (Danio rerio): A study using neurobehavioral and metabolomic approaches.

As an important psychoactive substance, cotinine is ubiquitous in aquatic environment and poses a threat to aquatic organisms. However, the mechanism of its adverse health impacts remains unclear. We evaluated the effects of cotinine exposure at environmentally relevant concentrations on the development and locomotor behavior of zebrafish (Danio rerio) larvae using neurotransmitters and whole endogenous metabolism. Mild developmental toxicity and significant neurobehavior disorder, such as spontaneous movement (1-1000 µg/L), 48 hpf tactile response (50, 100, and 1000 µg/L), and 144 hpf swimming speed (1, 10, 100, 500, and 1000 µg/L), were observed in zebrafish. Exposure to cotinine led to significant alterations in 11 neurotransmitters, including homogentisic acid, serotonin, glutamic acid and aspartic acid, etc. 298 metabolites were identified and two pathways - linoleic acid metabolism and taurine and hypotaurine metabolism - were delineated. In addition, amino acid neurotransmitters were significantly correlated with metabolites such as arachidonic acid as well as its derivatives, steroidal compounds, and amino acids. Serotonin demonstrates a noteworthy correlation with 31 out of 40 differentially expressed neurotransmitters, encompassing lipids, amino acids, and other compounds. These novel findings contribute to a comprehensive understanding of the ecological risks associated with cotinine contamination in surface waters.

Identification of key factors affecting neonicotinoid residues in crops and risk of dietary exposure.

Neonicotinoids, widely used on farmland, are ubiquitous in food; however, their distribution among various crops and associated exposure risks at the provincial level in China remain unclear. We collected 19 types of crop samples (fruits, vegetables, and tea) from farmland in nine prefectural cities in Zhejiang Province, China. We analyzed nine commonly used neonicotinoids in the edible portions of these crops. A notable detection rate (42.1 %-82.9 %) and high residual neonicotinoid concentrations (278 ± 357 ng/g) were observed. Tea exhibited the highest residue, followed by fruits, and vegetables showed the lowest (P < 0.05). Neonicotinoid ratios in crops to soil (R_C/S) and soil to water (R_S/W) were defined to discern insecticide distribution across different environments. Increased water solubility leads to increased migration of neonicotinoids (R_S/W) from agricultural soils to water through runoff, thereby increasing the relative contribution of nitenpyram and dinotefuran in water. In comparison with other studied compounds, all crops demonstrated the strongest soil uptake of thiamethoxam, denoted by the highest R_C/S value. Elevated R_C/S values in tea, pickled cabbage, and celery suggest increased susceptibility of these crops to neonicotinoid absorption from the soil (P < 0.05). Estimated dietary intake for teenagers, adults and elders was 8.9 ± 0.5, 8.9 ± 0.6, and 8.8 ± 0.3 µg/kg/d, respectively, below the reference dose (57 µg/kg/d). Teenagers, compared to adults and elders, exhibited significantly higher neonicotinoid exposure through fruit consumption, emphasizing the need for increased attention to neonicotinoid exposure among vulnerable populations.

High plasticity of ribosomal DNA organization in budding yeast.

In eukaryotic genomes, rDNA generally resides as a highly repetitive and dynamic structure, making it difficult to study. Here, a synthetic rDNA array on chromosome III in budding yeast was constructed to serve as the sole source of rRNA. Utilizing the loxPsym site within each rDNA repeat and the Cre recombinase, we were able to reduce the copy number to as few as eight copies. Additionally, we constructed strains with two or three rDNA arrays and found that the presence of multiple arrays did not affect the formation of a single nucleolus. Although alteration of the position and number of rDNA arrays did impact the three-dimensional genome structure, the additional rDNA arrays had no deleterious influence on cell growth or transcriptomes. Overall, this study sheds light on the high plasticity of rDNA organization and opens up opportunities for future rDNA engineering.

Microplastics in Antarctic krill (Euphausia superba) from Antarctic region.

Pollution of microplastics (MPs) has become a potential threat to Antarctic marine ecosystems. However, the occurrence of MPs in Antarctic krill (Euphausia superba), a keystone species in Antarctic ecosystems, remains unclear. In this study, the abundance and characteristics of MPs were examined in Antarctic krill samples (n = 437) collected from two Antarctic regions. MPs were extracted using an alkali digestion method and analyzed using Fourier-transform infrared spectroscopy. The mean abundance of MPs in Antarctic krill samples from the South Shetland Islands (n = 355) and the South Orkney Islands (n = 82) were 0.29 ± 0.14 and 0.20 ± 0.083 items/individual, respectively. >90 % of MPs found in Antarctic krill were < 150 µm in size. Fibers represented 77 % and 87 % of the MPs in Antarctic krill samples from the South Shetland Islands and the South Orkney Islands, respectively. Black, blue, and red were the predominant colors of MPs in Antarctic krill, accounting for 32 %, 22 %, and 21 % of the total MPs, respectively. Seven polymer compositions were identified for the MPs in Antarctic krill, with the predominance of polyethylene (37 % of total MPs), followed by polypropylene (22 %) and polyester (21 %). To our knowledge, this is the first study to investigate the occurrence of MPs in Antarctic krill samples. The results of this study are important for evaluating the risks of MP exposure in Antarctic krill.

Insights into the mechanisms of telbivudine-induced myopathy associated with mitochondrial dysfunction.

As a nucleotide analogue (NA), telbivudine was widely used in the treatment for chronic hepatitis B (CHB) by interfering with reverse transcriptase of hepatitis B virus. However, the use of NAs for hepatitis B treatment has been accompanied by numerous reports highlighting the occurrence of neuromyopathy, particularly in the case of telbivudine. This study aimed to investigate the underlying mechanisms responsible for telbivudine-induced myopathy. We established animal and cell models of telbivudine-induced myopathy using C57BL/6 mice and C2C12 cells, respectively. Our findings revealed that telbivudine significantly reduced mitochondrial DNA (mtDNA) copy number and caused increase of oxidative stress. Telbivudine treatment significantly inhibited mitochondrial complex I and IV expression, impairing the oxidative phosphorylation function of the respiratory chain. Modified Gomori trichrome (MGT) staining of the muscle sections displayed an increase in ragged red fibers (RRFs), indicating abnormal mitochondrial accumulation. In conclusion, our study provides compelling evidence suggesting that telbivudine-induced myopathy is associated with mitochondrial toxicity and impaired energy metabolism. The observed muscle pathology, depletion of mtDNA, elevation of oxidative stress and altered mitochondrial function support the hypothesis that telbivudine disrupts mitochondrial homeostasis, ultimately leading to muscle damage. This may be also a common mechanism for NAs to cause neuromyopathy.