Gut microbial metabolites in MASLD: Implications of mitochondrial dysfunction in the pathogenesis and treatment.

With an increasing prevalence, metabolic dysfunction-associated steatotic liver disease (MASLD) has become a major global health problem. MASLD is well-known as a multifactorial disease. Mitochondrial dysfunction and alterations in the gut bacteria are 2 vital events in MASLD. Recent studies have highlighted the cross-talk between microbiota and mitochondria, and mitochondria are recognized as pivotal targets of the gut microbiota to modulate the host's physiological state. Mitochondrial dysfunction plays a vital role in MASLD and is associated with multiple pathological changes, including hepatocyte steatosis, oxidative stress, inflammation, and fibrosis. Metabolites are crucial mediators of the gut microbiota that influence extraintestinal organs. Additionally, regulation of the composition of gut bacteria may serve as a promising therapeutic strategy for MASLD. This study reviewed the potential roles of several common metabolites in MASLD, emphasizing their impact on mitochondrial function. Finally, we discuss the current treatments for MASLD, including probiotics, prebiotics, antibiotics, and fecal microbiota transplantation. These methods concentrate on restoring the gut microbiota to promote host health.

Flexible ureteroscopic incision and drainage or laparoscopic unroofing for the parapelvic renal cysts: A systematic review and meta­analysis.

The aim of the present study was to compare flexible ureteroscopy and laparoscopy in the treatment of peripelvic renal cysts, so as to determine the best treatment method for patients with peripelvic renal cysts. A systematic search of the PubMed, EMBASE, Cochrane Library, CONAHL, Clinicaltrials.gov, Google Scholar, CNKI and WanFang DATA databases was conducted for articles published over 22 years (December 1980-December 2022) using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. By searching the database, a total of 594 studies were found, of which eight were analyzed as evidence. A total of 394 patients were included in the present study. Of these, 193 were treated laparoscopically and 201 were treated by flexible ureteroscopy. In terms of analysis results, radiation reexamination after laparoscopic therapy had a higher success rate. Ureteroscopy has advantages in the time spent in the operation, the amount of blood lost during the operation, the time to recover the anal exhaust after the operation and the length of postoperative hospital stay. There were no significant difference in postoperative recurrence or complications between the two surgical methods. After comprehensive analysis, it was considered that flexible ureteroscopy has more advantages in the treatment of peripelvic renal cyst, which is mainly manifested in the duration of operation, the total amount of blood loss during operation, the interval of recovery of anal exhaust after operation and the total length of postoperative hospital stay. It is worth further exploration and promotion.

Unexpected increase of sulfate concentrations and potential impact on CH4 budgets in freshwater lakes.

The continuous increase in sulfate (SO42-) concentrations discharged by anthropogenic activities lacks insights into their dynamics and potential impact on CH4 budgets in freshwater lakes. Here we conducted a field investigation in the lakes along the highly developed Yangtze River basin, China, additionally, we analyzed long-term data (1950-2020) from Lake Taihu, a typical eutrophic lake worldwide. We observed a gradual increase in SO42- concentrations up to 100 mg/L, which showed a positive correlation with the trophic state of the lakes. The annual variations indicated that eutrophication intensified the fluctuation of SO42- concentrations. A random forest model was applied to assess the impact of SO42- concentrations on CH4 emissions, revealing a significant negative effect. Synchronously, a series of microcosms with added SO42- were established to simulate cyanobacteria decomposition processes and explore the coupling mechanism between sulfate reduction and CH4 production. The results showed a strong negative correlation between CH4 concentrations and initial SO42- levels (R2 = 0.83), indicating that higher initial SO42- concentrations led to lower final CH4 concentrations. This was attributed to the competition for cyanobacteria-supplied substrates between sulfate reduction bacteria (SRB) and methane production archaea (MPA). Our study highlights the importance of considering the unexpectedly increasing SO42- concentrations in eutrophic lakes when estimating global CH4 emission budgets.

Comparative study of urea-15N fate in pure bamboo and bamboo-broadleaf mixed forests.

Objectives: Bamboo is a globally significant plant with ecological, environmental, and economic bene-fits. Choosing suitable native tree species for mixed planting in bamboo forests is an effective measure for achieving both ecological and economic benefits of bamboo forests. However, little is currently known about the impact of bamboo forests on nitrogen cycling and utilization efficiency after mixing with other tree species. Therefore, our study aims to compare the nitrogen cycling in pure bamboo forests with that in mixed forests. Methods: Through field experiments, we investigated pure Qiongzhuea tumidinoda forests and Q. tumidinoda-Phellodendron chinense mixed forests, and utilized 15N tracing technology to explore the fertilization effects and fate of urea-15N in different forest stands. Results: The results demonstrated the following: 1) in both forest stands, bamboo culms account for the highest biomass percentage (42.99%-51.86%), while the leaves exhibited the highest nitrogen concentration and total nitrogen uptake (39.25%-44.52%/29.51%-33.21%, respectively) Additionally, the average nitrogen uptake rate of one-year-old bamboo is higher (0.25 mg kg-1 a-1) compared to other age groups. 2) the urea-15N absorption in mixed forests (1066.51-1141.61 g ha-1, including 949.65-1000.07 g ha-1 for bamboo and 116.86-141.54 g ha-1 for trees) was significantly higher than that in pure forests (663.93-727.62 g ha-1, P<0.05). Additionally, the 15N recovery efficiency of culms, branches, leaves, stumps, and stump roots in mixed forests was significantly higher than that in pure forests, with increases of 43.14%, 69.09%, 36.84%, 51.63%, 69.18%, 34.60%, and 26.89%, respectively. 3) the recovery efficiency of urea-15N in mixed forests (45.81%, comprising 40.43% for bamboo and 5.38% for trees) and the residual urea-15N recovery rate in the 0-60 cm soil layer (23.46%) are significantly higher compared to those in pure forests (28.61%/18.89%). This could be attributed to the nitrogen losses in mixed forests (30.73%, including losses from ammonia volatilization, runoff, leaching, and nitrification-denitrification) being significantly lower than those in pure forests (52.50%). Conclusion: These findings suggest that compared to pure bamboo forests, bamboo in mixed forests exhibits higher nitrogen recovery efficiency, particularly with one-year-old bamboo playing a crucial role.

Advances in Bioinspired Artificial System Enabling Biomarker-Driven Therapy.

Bioinspired molecular engineering strategies have emerged as powerful tools that significantly enhance the development of novel therapeutics, improving efficacy, specificity, and safety in disease treatment. Recent advancements have focused on identifying and utilizing disease-associated biomarkers to optimize drug activity and address challenges inherent in traditional therapeutics, such as frequent drug administrations, poor patient adherence, and increased risk of adverse effects. In this review, we provide a comprehensive overview of the latest developments in bioinspired artificial systems (BAS) that use molecular engineering to tailor therapeutic responses to drugs in the presence of disease-specific biomarkers. We examine the transition from open-loop systems, which rely on external cues, to closed-loop feedback systems capable of autonomous self-regulation in response to disease-associated biomarkers. We detail various BAS modalities designed to achieve biomarker-driven therapy, including activatable prodrug molecules, smart drug delivery platforms, autonomous artificial cells, and synthetic receptor-based cell therapies, elucidating their operational principles and practical in vivo applications. Finally, we discuss the current challenges and future perspectives in the advancement of BAS-enabled technology and envision that ongoing advancements toward more programmable and customizable BAS-based therapeutics will significantly enhance precision medicine.

Mercury supply limits methylmercury production in paddy soils.

The neurotoxic methylmercury (MeHg) is a product of inorganic mercury (IHg) after microbial transformation. Yet it remains unclear whether microbial activity or IHg supply dominates Hg methylation in paddies, hotspots of MeHg formation. Here, we quantified the response of MeHg production to changes in microbial activity and Hg supply using 63 paddy soils under the common scenario of straw amendment, a globally prevalent agricultural practice. We demonstrate that the IHg supply is the limiting factor for Hg methylation in paddies. This is because IHg supply is generally low in soils and can largely be facilitated (by 336-747 %) by straw amendment. The generally high activities of sulfate-reducing bacteria (SRB) do not limit Hg methylation, even though SRB have been validated as the predominant microbial Hg methylators in paddies in this study. These findings caution against the mobilization of legacy Hg triggered by human activities and climate change, resulting in increased MeHg production and the subsequent flux of this potent neurotoxin to our dining tables.

Gene expression analyses of GH/IGF axis in triploid crucian carp with growth heterosis.

Hybridization and polyploid breeding are the main approaches used to obtain new aquaculture varieties. Allotriploid crucian carp (3n) with rapid growth performance was generated by mating red crucian carp (RCC) with allotetraploids (4n). Fish growth is controlled by the growth hormone (GH)/insulin-like growth factor (IGF) axis. In the present study, we examined the expression characteristics of GH/IGF axis genes in hybrids F1, 4n, 3n, RCC and common carp (CC). The results showed that GHRa, GHRb, IGF1, IGF2, and IGF-1Ra were highly expressed in 3n compared with RCC and CC, whereas IGF3 was undetectable in the liver in RCC, CC and 3n. GHRa and GHRb had low expression in the 4n group. In hybrid F1, GHRa expression was low, whereas GHRb was highly expressed compared to the levels in RCC and CC. Moreover, in hybrid F1, the expression of IGF3 was higher, and the expression of IGF1 and IGF2 was lower than that in the RCC and CC, whereas the expression of IGF-1Ra was similar to that in RCC and CC. For the IGFBP genes, IGFBP1 had higher expression in 3n compared than that in RCC and CC, while other IGFBP genes were not high expressed in 3n. Among the genes detected in this study, 11 genes were nonadditively expressed in 3n, with 5 genes in the transgressive upregulation model. We proposed that the 11 nonadditive expression of GH/IGF axis genes is related to growth heterosis in 3n. This evidence provides new insights into hybridization and polyploid breeding from the perspective of hormone regulation.

Soil Geobacteraceae are the key predictors of neurotoxic methylmercury bioaccumulation in rice.

Contamination of rice by the potent neurotoxin methylmercury (MeHg) originates from microbe-mediated Hg methylation in soils. However, the high diversity of Hg methylating microorganisms in soils hinders the prediction of MeHg formation and challenges the mitigation of MeHg bioaccumulation via regulating soil microbiomes. Here we explored the roles of various cropland microbial communities in MeHg formation in the potentials leading to MeHg accumulation in rice and reveal that Geobacteraceae are the key predictors of MeHg bioaccumulation in paddy soil systems. We characterized Hg methylating microorganisms from 67 cropland ecosystems across 3,600 latitudinal kilometres. The simulations of a rice-paddy biogeochemical model show that MeHg accumulation in rice is 1.3-1.7-fold more sensitive to changes in the relative abundance of Geobacteraceae compared to Hg input, which is recognized as the primary parameter in controlling MeHg exposure. These findings open up a window to predict MeHg formation and accumulation in human food webs, enabling more efficient mitigation of risks to human health through regulations of key soil microbiomes.

Transcriptome analysis of the Nile tilapia (Oreochromis niloticus) reveals altered expression of immune genes by cadmium.

Nile tilapia (Oreochromis niloticus) is a worldwide farmed fish and has been widely used for the study on comparative immunology in teleosts. It is well known that cadmium (Cd) can cause a variety of adverse effects in fish. However, data on the effects of Cd in fish liver and the defensive mechanisms of these effects using transcriptome approach are relatively scarce to date. In this study, by using an RNA sequencing approach, the gene expression profiling was performed in livers of tilapia exposed to 0 (control), 50, 100, and 200 µg/L of Cd for 2 months. The results showed that exposure to 50 µg/L Cd altered the expressions of 911 genes, while exposure to 100 and 200 µg/L Cd resulted in 4318 and 3737 differentially expressed genes compared to the control. Weighted correlation network analysis (WGCNA) and gene ontology (GO) analysis identified a 14-gene network linked to the immune system development. Further, in a fuzzy analysis, the GO term immune system development was enriched in cluster 3, and gene expression decreased with increasing Cd levels in a concentration-dependent manner. The qPCR and RNA-seq results identified 4 genes, i.e., dnmt3bb.1, sf3b1, SMARCAL1, and zap70, as convenient potential biological indicators for detecting waterborne Cd. The present results help systematically understand the effects of Cd on the hepatic transcriptome in tilapia.

[Dynamic Changes of Dissolved Organic Matter Derived from Algal Decomposition and the Environmental Effects in Eutrophic Lakes].

The global occurrences of lake eutrophication have led to algal bloom and the subsequent algal decomposition, releasing high amounts of algae-derived dissolved organic matter (DOM) into the lake water. Algae-derived DOM could regulate the quantity and composition of DOM in lake water and further impact the biogeochemical cycles of multiple elements. In this study, the dynamic changes in the quantity and quality of DOM during algal decomposition under different eutrophic scenarios (e.g., from oligotrophication to severe eutrophication) were monitored, and the corresponding environmental effects (e.g., microbial responses and greenhouse gas emissions) caused by algal decomposition were further explored. The results showed that algal decomposition significantly increased the DOM levels, bioavailability, and intensities of fluorescent components in the water. The total DOM levels gradually decreased, whereas the average molecular weight increased along the decomposition process. Furthermore, unsaturated hydrocarbon and aliphatic compounds were preferentially utilized by microorganisms during algal decomposition, and some refractory molecules (e.g., lignin, condensed hydrocarbons, and tannin with high O/C values) were synchronously generated, as evidenced by the results from ultra-high-resolution mass spectrometry. The dominant bacterial species during algal decomposition shifted from Proteobacteria (46%) to Bacteroidetes (42%). In addition, algae addition resulted in 1.2-5 times the emissions of CO2 and CH4 from water, and the emission rates could be well predicted by the optical index of a254 in water. This study provides comprehensive perspectives for understanding the environmental behaviors of aquatic DOM and further paves the ways for the mitigation of lake eutrophication.

Piezo channels in the intestinal tract.

The intestine is the largest mechanosensitive organ in the human body whose epithelial cells, smooth muscle cells, neurons and enteroendocrine cells must sense and respond to various mechanical stimuli such as motility, distension, stretch and shear to regulate physiological processes including digestion, absorption, secretion, motility and immunity. Piezo channels are a newly discovered class of mechanosensitive ion channels consisting of two subtypes, Piezo1 and Piezo2. Piezo channels are widely expressed in the intestine and are involved in physiological and pathological processes. The present review summarizes the current research progress on the expression, function and regulation of Piezo channels in the intestine, with the aim of providing a reference for the future development of therapeutic strategies targeting Piezo channels.

Methylmercury photodegradation in paddy water: An overlooked process mitigating methylmercury risks.

Photodegradation is critical to reduce the potent neurotoxic methylmercury (MeHg) in water and its subsequent accumulation along food chains. However, this process has been largely ignored in rice paddies, which are hotspots of MeHg production and receive about a quarter of the world's developed freshwater resources. Here, we reported that significant MeHg photodegradation, primarily mediated by hydroxyl radicals, occurs in the overlying water during rice growth. By incorporating field-measured light interception into a rice paddy biogeochemistry model, as well as photodegradation rates obtained from 42 paddy soils stretching ∼3500 km across China, we estimated that photodegradation reduced MeHg concentrations in paddy water and rice by 82 % and 11 %, respectively. Without photodegradation, paddy water could be a significant MeHg source for downstream ecosystems, with an annual export of 178 - 856 kg MeHg to downstream waters in China, the largest rice producer. These findings suggest that photodegradation in paddy water is critical for preventing greater quantities of MeHg entering human food webs.

Using blood transcriptome analysis for Alzheimer's disease diagnosis and patient stratification.

INTRODUCTION: Blood protein biomarkers demonstrate potential for Alzheimer's disease (AD) diagnosis. Limited studies examine the molecular changes in AD blood cells. METHODS: Bulk RNA-sequencing of blood cells was performed on AD patients of Chinese descent (n = 214 and 26 in the discovery and validation cohorts, respectively) with normal controls (n = 208 and 38 in the discovery and validation cohorts, respectively). Weighted gene co-expression network analysis (WGCNA) and deconvolution analysis identified AD-associated gene modules and blood cell types. Regression and unsupervised clustering analysis identified AD-associated genes, gene modules, cell types, and established AD classification models. RESULTS: WGCNA on differentially expressed genes revealed 15 gene modules, with 6 accurately classifying AD (areas under the receiver operating characteristics curve [auROCs] > 0.90). These modules stratified AD patients into subgroups with distinct disease states. Cell-type deconvolution analysis identified specific blood cell types potentially associated with AD pathogenesis. DISCUSSION: This study highlights the potential of blood transcriptome for AD diagnosis, patient stratification, and mechanistic studies. HIGHLIGHTS: We comprehensively analyze the blood transcriptomes of a well-characterized Alzheimer's disease cohort to identify genes, gene modules, pathways, and specific blood cells associated with the disease. Blood transcriptome analysis accurately classifies and stratifies patients with Alzheimer's disease, with some gene modules achieving classification accuracy comparable to that of the plasma ATN biomarkers. Immune-associated pathways and immune cells, such as neutrophils, have potential roles in the pathogenesis and progression of Alzheimer's disease.

Protect the oceans from Japan's radioisotope dumping.

•Dumping of Fukushima's radioactive wastewater raises marine food web concern.•Tritium seems to be the most problematic compound.•Long-lived radioisotopes Biomagnify up to 50,000 folds in marine fish species.•This threatens fragile deep-sea ecosystems requiring immediate action.•Empowered Routine monitoring is crucial to maintain planetary health.

Contamination and Carcinogenic Risks of Lead in Lip Cosmetics in China.

There are growing concerns about elevated lead (Pb) levels in lip cosmetics, yet in China, the largest lip cosmetic market, recent Pb contamination in lip cosmetics and associated Pb exposure remain unclear. Here, we measured Pb levels of 29 popular lip cosmetics in China and conducted the bioaccessibility-corrected carcinogenic risk assessments and sensitivity analysis regarding Pb exposure for consumers using Monte Carlo simulation. The Pb concentrations of collected samples ranged from undetectable (< 0.05 µg/kg) to 0.21 mg/kg, all of which were well below the Pb concentration limit set for cosmetics in China (10 mg/kg). The 50th percentile incremental lifetime cancer risk (ILCR) of Pb in Chinese cosmetics (1.20E-07) was below the acceptable level (1E-06), indicating that the application of lip cosmetics and subsequent Pb exposure does not pose carcinogenic risks to consumers in most cases. The results of this study provide new insights into understanding the Pb risk in lip cosmetics.

Unexpected hydroxyl radical production in brewed tea under sunlight.

Tea is one of the world's most popular and widely consumed beverages. It is a common pastime to enjoy a cup of tea in the sunshine. However, little attention has been given to understanding the possible photochemical reactions occurring beneath the calm surface of brewed tea. Epigallocatechin gallate (EGCG), which is widely used in food and beverages, is the most significant active ingredient found in tea. In this study, we investigated the presence of free radicals in both an aqueous EGCG solution and brewed tea under simulated sunlight conditions. To our surprise, we unexpectedly observed the production of hydroxyl radicals (•OH) in brewed tea. It was found that sunlight irradiation played a critical role in the formation of •OH, independent of the presence of metal ions. Furthermore, we demonstrated that the •OH generated from the EGCG aqueous solution induced cell cytotoxicity and DNA damage in vitro. Considering the crucial role of •OH in various fields, including human health and the environment, it is important to further explore the practical implications of •OH production in brewed tea under sunlight. In summary, our study unveils the unexpected formation of •OH in brewed tea and emphasizes the significance of sunlight-induced reactions. The observed cytotoxic and DNA-damaging effects of •OH emphasize the importance of understanding the potential health consequences associated with tea consumption. Further research in this area will contribute to a better understanding of the broader implications of •OH production in brewed tea under sunlight.