Corrigendum: Plastic biodegradation by in vitro environmental microorganisms and in vivo gut microorganisms of insects.

[This corrects the article DOI: 10.3389/fmicb.2022.1001750.].

Chromosome-level genome assembly of a cliff plant Taihangia rupestris var. ciliata provides insights into its adaptation and demographic history.

BACKGROUND: Cliffs are recognized as one of the most challenging environments for plants, characterized by harsh conditions such as drought, infertile soil, and steep terrain. However, they surprisingly host ancient and diverse plant communities and play a crucial role in protecting biodiversity. The Taihang Mountains, which act as a natural boundary in eastern China, support a rich variety of plant species, including many unique to cliff habitats. However, it is little known how cliff plants adapt to harsh habitats and the demographic history in this region. RESULTS: To better understand the demographic history and adaptation of cliff plants in this area, we analyzed the chromosome-level genome of a representative cliff plant, T. rupestris var. ciliata, which has a genome size of 769.5 Mb, with a scaffold N50 of 104.92 Mb. The rapid expansion of transposable elements may have contributed to the increasing genome and its ability to adapt to unique and challenging cliff habitats. Comparative analysis of the genome evolution between Taihangia and non-cliff plants in Rosaceae revealed a significant expansion of gene families associated with oxidative phosphorylation, which is likely a response to the abiotic stresses faced by cliff plants. This expansion may explain the long-term adaptation of Taihangia to harsh cliff environments. The effective population size of the two varieties has continuously decreased due to climatic fluctuations during the Quaternary period. Furthermore, significant differences in gene expression between the two varieties may explain the varied leaf phenotypes and adaptations to harsh conditions in different natural distributions. CONCLUSION: Our study highlights the extraordinary adaptation of T. rupestris var. ciliata, shedding light on the evolution of cliff plants worldwide.

Toxicological Research on Nano and Microplastics in Environmental Pollution: Current Advances and Future Directions.

This review explains the sources of nanoplastics (NPs) and microplastics (MPs), their release, fate, and associated health risks in the aquatic environment. In the 21st century, scientists are grappling with a major challenge posed by MPs and NPs. The global production of plastic has skyrocketed from 1.5 million tons in the 1950s to an astonishing 390.7 million tons in 2021. This pervasive presence of these materials in our environment has spurred scientific inquiry into their potentially harmful effects on living organisms. Studies have revealed that while MPs, with their larger surface area, are capable of absorbing contaminants and pathogens from the surroundings, NPs can easily be transferred through the food chain. As a result, living organisms may ingest them and accumulate them within their bodies. Due to their minuscule size, NPs are particularly difficult to isolate and quantify. Furthermore, exposure to both NPs and MPs has been linked to various adverse health effects in aquatic species, including neurological impairments, disruption of lipid and energy metabolism, and increased susceptibility to cytotoxicity, oxidative stress, inflammation, and reactive oxygen species (ROS) production. It is alarming to note that MPs have even been detected in commercial fish, highlighting the severity of this issue. There are also challenges associated with elucidating the toxicological effects of NPs and MPs, which are discussed in detail in this review. In conclusion, plastic pollution is a pressing issue that governments should tackle by ensuring proper implementation of rules and regulations at national and provincial levels to reduce its health risks.

Probiotics mitigate kidney damage after exposure to Sri Lanka's local groundwater from chronic kidney disease with uncertain etiology (CKDu) prevalent area in zebrafish.

Groundwater in Sri Lanka, contaminated with environmental toxins, is suspected to potentially induce chronic kidney disease of uncertain etiology (CKDu) in humans. This study aims to elucidate the potential mitigating effects of probiotics on kidney damage induced by exposure to this local groundwater (LW) in zebrafish. We used zebrafish as a model organism and exposed them to local groundwater to evaluate the risk of CKDu. Probiotics were then added at a concentration of 108 colony-forming units per milliliter (CFU/mL). Our findings revealed that exposure to local groundwater resulted in abnormalities, such as tail deletion and spinal curvature in zebrafish larvae. However, the addition of probiotics mitigated these effects, improving the hatching rate, heart rate, length, weight, deformity rate, survival rate, and abnormal behavior of zebrafish. It also positively influenced the differential expression levels of kidney development and immunity-related genes (dync2h1, foxj1, pkd2, gata3, slc20a1, il1ß, and lyso). Furthermore, exposure to LW decreased both the diversity and abundance of microbiota in zebrafish larvae. However, treatment with probiotics, such as L. plantarum and L. rhamnosus partially restored the disrupted gut microbiota and significantly impacted the cellular process pathways of the microbial community, as determined by KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis. In conclusion, this study highlights the risks associated with Sri Lanka's local groundwater from a CKDu prevalent area and confirms the beneficial effects of different probiotics. These findings may provide new insights into bacterial function in host kidney health.

Sulfonamides (SAs) exposure causes neurobehavioral toxicity at environmentally relevant concentrations (ERCs) in early development of zebrafish.

Antibiotics, due to their stability and persistence in the environment, can have chronic impacts on various ecosystems and organisms. However, the molecular mechanisms underlying antibiotic toxicity at environmental concentrations, particularly the neurotoxic effects of sulfonamides (SAs), remain poorly understood. In this study, we assessed the neurotoxicity of six SAs including the sulfadiazine (SD), sulfathiazole (ST), sulfamethoxazole (SMX), sulfisoxazole (SIZ), sulfapyridine (SPD), and sulfadimethoxine (SDM) by exposing zebrafish to environmentally relevant concentrations (ERCs). The SAs exhibited concentration-dependent effects on zebrafish behavior, including spontaneous movement, heartbeat, survival rate, and body metrics, ultimately leading to depressive-like symptoms and sublethal toxicity during early life stages. Notably, even the lowest SA concentration (0.05 µg/L) induced neurotoxicity and behavioral impairment in zebrafish. We observed a dose-dependent increase in melancholy behavior as indicated by increased resting time and decreased motor activity in zebrafish larvae. Following exposure to SAs from 4 to 120 h post-fertilization (hpf), key genes involved in folate synthesis [sepiapterin reductase a (spra), phenylalanine hydroxylase (pah), tyrosine hydroxylase (th), and tryptophan hydroxylase 1 (tryptophan 5-monooxygenase) a tryptophan hydroxylase (tph1a)] and carbonic anhydrase (CA) metabolism [carbonic anhydrase II (ca2), carbonic anhydrase IV a (ca4a), carbonic anhydrase VII (ca7), and carbonic anhydrase XIV (ca14)] were significantly downregulated or inhibited at different concentrations. Our findings demonstrate that acute exposure to six SAs at environmentally relevant concentrations induces developmental and neurotoxic effects in zebrafish, impacting folate synthesis pathways and CA metabolism. These results provide valuable insights into the potential role of antibiotics in depressive disorders and neuroregulatory pathways.

Bacteriophage-based techniques for elucidating the function of zebrafish gut microbiota.

Bacteriophages (or phages) are unique viruses that can specifically infect bacteria. Since their discovery by Twort and d'Herelle, phages with bacterial specificity have played important roles in microbial regulation. The intestinal microbiota and host health are intimately linked with nutrient, metabolism, development, and immunity aspects. However, the mechanism of interactions between the composition of the microbiota and their functions in maintaining host health still needs to be further explored. To address the lack of methodology and functions of intestinal microbiota in the host, we first proposed that, with the regulations of special intestinal microbiota and applications of germ-free (GF) zebrafish model, phages would be used to infect and reduce/eliminate the defined gut bacteria in the conventionally raised (CR) zebrafish and compared with the GF zebrafish colonized with defined bacterial strains. Thus, this review highlighted the background and roles of phages and their functional characteristics, and we also summarized the phage-specific infection of target microorganisms, methods to improve the phage specificity, and their regulation within the zebrafish model and gut microbial functional study. Moreover, the primary protocol of phage therapy to control the intestinal microbiota in zebrafish models from larvae to adults was recommended including phage screening from natural sources, identification of host ranges, and experimental design in the animal. A well understanding of the interaction and mechanism between phages and gut bacteria in the host can potentially provide powerful strategies or techniques for preventing bacteria-related human diseases by precisely regulating in vitro and in vivo, which will provide novel insights for phages' application and combined research in the future. KEY POINTS: • Zebrafish models for clarifying the microbial and phages' functions were discussed • Phages infect host bacteria with exquisite specificity and efficacy • Phages can reduce/eliminate the defined gut bacteria to clarify their function.

Remote programming for subthalamic deep brain stimulation in Parkinson's disease.

Introduction: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is effective for the treatment of Parkinson's disease (PD). Moreover, remote programming is widely used in Mainland China. This necessitates evaluating the ability of remote programming to achieve the ideal postoperative effect. Therefore, we aimed to retrospectively evaluate the effects of different programming modes on the effectiveness of STN-DBS 12 months postoperatively in patients with PD. Methods: Clinical data were collected retrospectively, before and 12 months after surgery, in 83 patients with PD. Based on the programming modes voluntarily selected by the patients during 12 months postoperatively, they were divided into three groups, namely remote programming alone, hospital programming alone, and hospital + remote programming. We compared the programming data and the effects of different programming methods on STN-DBS-related improvements 12 months postoperatively among these groups. Furthermore, we analyzed STN-DBS-related improvements at 12 months postoperatively in 76 patients. Results: The effectiveness of STN-DBS was not influenced by the three programming modes. The postoperative Movement Disorder Society Unified Parkinson's Disease Rating Scale scores did not reveal statistically significant differences between the remote alone and hospital alone programming groups, except for motor examination. The postoperative decline in the levodopa equivalent daily dose was most apparent in the hospital programming alone group. The programming frequency of the hospital + remote programming group was considerably higher than that of the remaining groups. Seventy-six patients with PD displayed good STN-DBS surgical efficacy. Conclusion: Programming modes do not influence the short-term efficacy of STN-DBS, and remote programming can yield a satisfactory surgical effect.

[Characteristics of Eukaryotic Phytoplankton Community Structure and Its Relationship with Environmental Factors in Danjiangkou Reservoir].

Eukaryotic phytoplankton play crucial roles in ecosystem processes, and understanding their community composition and abundance is of great importance to protect the balance of aquatic ecosystems. Danjiangkou Reservoir is a canyon lake in central China that acts as the water source of the Mid-route of South-to-North Water Diversion Project. In this study, the composition of planktonic microeukaryotes from water samples with a depth ranging from 0.5 to 20 m in Danjiangkou Reservoir were investigated using high-throughput 18S rDNA gene sequencing. The environmental factors including pH, water temperature (WT), nitrate (NO3--N), ammonia (NH4+-N), total nitrogen (TN), conductivity (Cond.), water depth, and dissolved oxygen (DO) in the reservoir areas were measured, and their correlations with the abundance and diversity of eukaryotic phytoplankton were analyzed. The results of high-throughput sequencing showed that a total of 68 genera of phytoplankton belonging to 12 phyla were detected, and the phytoplankton communities were mainly composed of Dinophyceae, Bacillariophyta, and Chlorophyta. In particular, significant differences in the diversity of phytoplankton communities on a vertical distribution were found. The diversity and abundance of the phytoplankton communities in Songgang (SG), Tumen (TM), and Dangzikou (DZK) decreased with the increase in water depth, and the relationship between phytoplankton and water depth in other sampling sites was not obvious. The results of RDA showed that NO3--N, water depth, DO, pH, and WT could influence the vertical distribution of the phytoplankton community in the Danjiangkou Reservoir. Among these phytoplankton types, Dinophyceae was negatively correlated with NO3--N and water depth and positively correlated with other environmental factors. Meanwhile, Bacillariophyta was positively correlated with NO3--N and water depth and negatively correlated with other environmental factors. In addition, Chlorophyta was negatively correlated with WT, pH, and DO and not significantly correlated with water depth.

Ophthalmologic problems correlates with cognitive impairment in patients with Parkinson's disease.

Objective: Visual impairment is a common non-motor symptom (NMS) in patients with Parkinson's disease (PD) and its implications for cognitive impairment remain controversial. We wished to survey the prevalence of visual impairment in Chinese Parkinson's patients based on the Visual Impairment in Parkinson's Disease Questionnaire (VIPD-Q), identify the pathogens that lead to visual impairment, and develop a predictive model for cognitive impairment risk in Parkinson's based on ophthalmic parameters. Methods: A total of 205 patients with Parkinson's disease and 200 age-matched controls completed the VIPD-Q and underwent neuro-ophthalmologic examinations, including ocular fundus photography and optical coherence tomography. We conducted nomogram analysis and the predictive model was summarized using the multivariate logistic and LASSO regression and verified via bootstrap validation. Results: One or more ophthalmologic symptoms were present in 57% of patients with Parkinson's disease, compared with 14% of the controls (χ2-test; p < 0.001). The visual impairment questionnaire showed good sensitivity and specificity (area under the curve [AUC] = 0.918, p < 0.001) and a strong correlation with MoCA scores (Pearson r = -0.4652, p < 0.001). Comparing visual impairment scores between pre- and post-deep brain stimulation groups showed that DBS improved visual function (U-test, p < 0.001). The thickness of the retinal nerve fiber layer and vessel percentage area predicted cognitive impairment in PD. Interpretation: The study findings provide novel mechanistic insights into visual impairment and cognitive decline in Parkinson's disease. The results inform an effective tool for predicting cognitive deterioration in Parkinson's based on ophthalmic parameters.

Exposure to Sri Lanka's local groundwater in a CKDu prevalent area causes kidney damage in zebrafish.

How local groundwater induces chronic kidney disease of unknown etiology (CKDu) in Sri Lanka is still elusive. This study aims to elucidate the impacts of Sri Lanka's local groundwater in a CKDu prevalent area and reveal the possible pathogenic mechanism of CKDu using zebrafish models. The drinking water from the local underground well in Vavuniya was sampled and the water quality parameters including Na+, Mg2+, K+, Ca2+, Cl-, NO3-, SO42-, and F- were analyzed. Then, local groundwater exposure to zebrafish larvae and 293T cells was performed, and water with high hardness and fluoride was prepared as parallel groups. Our result showed that exposure to Sri Lanka's local groundwater caused developmental toxicity, kidney damage, and pronephric duct obstruction as well as abnormal behavior in zebrafish. Similar results were also found after exposure to water with high hardness and fluoride in zebrafish. Further, the expression levels of marker genes related to renal development and functions (foxj1a, dync2h1, pkd2, gata3, and slc20a1) were significantly altered, which is also confirmed in the 293T cells. Taken together, those results indicated that Sri Lanka's local groundwater in a CKDu prevalent area could cause kidney damage, implying that high water hardness and fluorine might be the inducible environmental factors for the etiological cause of CKDu.

Genetic polymorphisms of 66 InDel loci in the Chinese Han population.

Insertion/deletion polymorphism (InDel) genetic markers refer to insertion or deletion of DNA fragments into genomic DNA, which have advantages in the identification of degraded samples. In this study, we independently screened 66 highly polymorphic InDel markers from the dbSNP database to establish a multiplex PCR system for forensic DNA identification using next-generation sequencing system (66-plex InDels). We assessed the population genetic data among 251 Chinese Han population using this system and evaluated their potential forensic application. The results showed that all 66 InDel loci conformed to the Hardy-Weinberg equilibrium (P>0.000 758), and all the pairwise InDel loci were in linkage equilibrium after Bonferroni correction. The mean observed heterozygosity (Ho) was 0.482, the mean expected heterozygosity (He) was 0.483,the mean discrimination power (DP) was 0.612, the mean polymorphism information content (PIC) was 0.365, the total discrimination power (TDP) reached 0.999 999 999 999 999 999 999 999 999 428 18. The cumulative power of exclusion for 66 InDel loci was 0.999 739 in duo cases (CPEduo) and was 0.999 999 999 417 in trios cases (CPEtrio). The results show that the 66 InDel loci have high genetic polymorphisms in the Chinese Han population and can be used independently for forensic DNA identification and paternity testing.

Plastic biodegradation by in vitro environmental microorganisms and in vivo gut microorganisms of insects.

Traditional plastics, such as polyethylene (PE), polystyrene (PS), polypropylene (PP), polyvinyl chloride (PVC), polyethylene terephthalate (PET), polyurethane (PUR), and other plastic polymers, are difficult to degrade and are gradually accumulated in the environment to cause a serious environmental problem, which is urgently needed to develop novel treatments or control technology. The biodegradation of plastics has gained great attention due to the advantages of green and safe characteristics. Microorganisms play a vital role in the biodegradation of plastics, including environmental microbes (in vitro) and gut microbes of insects (in vivo). Microbial degradation in environmental conditions in vitro is extremely slow for major plastics at degradation rates on the basis of a month or even a year time, but recent discoveries show that the fast biodegradation of specific plastics, such as PS, PE, and PUR, in some invertebrates, especially insects, could be enhanced at rates on basis of hours; the biodegradation in insects is likely to be gut microbial-dependent or synergetic bioreactions in animal digestive systems. This review comprehensively summarizes the latest 7-year (2016-2022) publications on plastic biodegradation by insects and microorganisms, elucidates the mechanism of plastic degradation in insects and environmental microbes, and highlights the cutting-edge perspectives for the potential applications of plastic biodegradation.

Impact of Subthalamic Deep Brain Stimulation on Hyposmia in Patients With Parkinson's Disease Is Influenced by Constipation and Dysbiosis of Microbiota.

Background: Non-motor symptoms in PD usually arise at very early stage and vary during the whole disease progression. Deep brain stimulation (DBS) is considered as a highly efficient treatment option for PD's motor function. However, the effect of DBS on NMS, especially hyposmia, has not been fully understood and the deep connection between different NMS such as hyposmia and constipation is still unknown. Objective: The objective of this study was to evaluate the therapeutic effect of DBS on hyposmia in PD patients with or without constipation and find potential factors which might influence the efficacy. Methods: A retrospective analysis of 65 PD patients accepted STN-DBS operation in Qilu Hospital during 2019-2020 were conducted to evaluate the exact therapeutic effect of DBS on hyposmia in PD. Sub-group analyses about the relationship between hyposmia and constipation were carried out. Analysis of flora in nasal mucosa was also conducted to evaluate the abundance and variety in different PD groups. Results: Our study showed that DBS had clearly improved olfactory function in Parkinson patients (P = 0.012) and subgroup analysis found that PD patients with constipation have lower olfactory function scores (25.27 ± 3.44 vs. 33.90 ± 6.633, p = 0.014) and worse improvement after DBS operation (ΔTDI 12.11 ± 3.2 vs. 8.78 ± 2.91, p = 0.0072). Analysis of flora indicated the obvious discrepancy on olfactory function scores and degree of improvement might be related to the abundance and dysbiosis of microbiota. Conclusion: In summary, this article presents a study on PD with hyposmia and constipation after DBS operation, explored the relationship between different NMS and offer a potential explanation on why PD patients with constipation usually have worse olfactory function for the less abundance and variety of microbiota.

Role of germ-free animal models in understanding interactions of gut microbiota to host and environmental health: A special reference to zebrafish.

Numerous pieces of evidence documented the importance of gut microbiota in regulating human health and evaluating the toxicity of environmental pollutants, which are closely related to the host health in various aspects, including nutrition, energy translation, metabolism, pathogen resistance, and immune function. A variety of environmental factors can disrupt gut microbiota and their functions, and inevitably cause immune diseases, obesity and diabetes. However, deciphering the inner mechanisms involved in the functional interaction of gut microbes with host health is still needed extensive investigations. This review focused on the essential roles of intestinal microbes in host-related diseases and highlighted the development and applications of germ-free (GF) animal models, mainly zebrafish. Moreover, the generation, immunity characters, advantages and challenges of GF zebrafish models were also summarized. Importantly, the composition and isolation of zebrafish gut bacteria for further application and toxicity evaluation of aquatic environmental pollutants were also discussed. In conclusion, GF zebrafish play irreplaceable roles in understanding the potential functions and responses of customized microbiota towards human and environmental health implications.

Gut bacteria Vibrio sp. and Aeromonas sp. trigger the expression levels of proinflammatory cytokine: First evidence from the germ-free zebrafish.

Gut microbiota plays a central part in the regulation of multiple host metabolic pathways, such as homeostasis, immunostasis, mucosa permeability, and even brain development. Though, slight known about the function of an individual gut bacterium in zebrafish. In this study, germ-free (GF) and conventionally reared (CV) zebrafish models utilized for studying the role of gut bacteria Vibrio sp. and Aeromonas sp. After the analysis of gut microbial profile in zebrafish male and female at three-month age, Proteobacteria and Fusobacteria dominated the main composition of zebrafish intestinal microflora. However, the relative richness of them was different base on gender variance. Aeromonas sp. and Vibrio sp. belonging to Proteobacteria phylum of bacteria were isolated from zebrafish gut, and their potential capacities to trigger innate immunity were investigated. In gut microbiota absence, the expression levels of the innate immunity genes in the GF group were not significantly changed compared to the CV group. After exposure to Aeromonas sp. and Vibrio sp., the expression levels of myd88, TLRs-, and inflammation-related genes were increased in both GF and CV groups, except tlr2 and NLRs-related genes. However, the expression level of NF-κB and JNK/AP-1 pathway genes were all decreased after exposure to Aeromonas sp. and Vibrio sp. in both GF and CV groups. Interestingly, inflammation-related genes (tnfa, tnfb, and il1ß) were activated in the CV group, and there were not significantly changed in the GF group, indicating that other bacteria were indispensable for Aeromonas sp. or Vibrio sp. to activate the inflammation response. Taken together, this is the first study of gut bacteria Vibrio sp. and Aeromonas sp. prompting the innate immune response using the GF and CV zebrafish model.

Acute and chronic effects of polystyrene microplastics on brine shrimp: First evidence highlighting the molecular mechanism through transcriptome analysis.

Microplastics contamination is one of the leading environmental catastrophes for the marine ecosystem, but the molecular toxicity mechanism of those microplastics remains elusive. This study aims to determine the acute and chronic toxicity after exposure to polystyrene microplastics in brine shrimp with various concentrations. Our results demonstrated that acute exposure to polystyrene microplastics induced no significant effects on the survival of brine shrimp. Interestingly, the concentration-dependent increase in both bioaccumulation and the generation of reactive oxygen species (ROS) was observed after acute and chronic exposure. Moreover, the histopathology analysis revealed the deformation of epithelial cells in the midgut region after both acute exposures at 100 mg/L and chronic exposure at 1 mg/L to polystyrene microplastics. To elucidate the underlying mechanisms of microplastics-mediated toxicity, the transcriptome analysis was performed after chronic exposure, and the result showed 721 differentially expressed genes (DEGs) associated with 156 known KEGG pathways. 292 DEGs genes were significantly upregulated and 429 genes were significantly downregulated. The transcriptome analysis further revealed the DEGs related pathways. Taken together, this study not only highlighted the negative effects but also provided detailed sequencing data from transcriptome profiling to enhance our understanding of the molecular toxicity of polystyrene microplastics in brine shrimp.

Effect of LRRK2 G2385R Variant on Subthalamic Deep Brain Stimulation Efficacy in Parkinson's Disease in a Han Chinese Population.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for advanced Parkinson's disease (PD). The G2385R variant of LRRK2 is a risk factor for PD in Han Chinese individuals. We retrospectively compared the clinical outcomes of STN-DBS surgery between PD Han Chinese G2385R variant carriers and non-carriers. Fifty-seven PD patients with bilateral STN-DBS were enrolled, including 8 G2385R+ variant carriers (G2385R+ group) and 49 non-carriers (G2385R- group). Clinical data included Unified Parkinson's Disease Rating Scale (UPDRS) parts I to IV, levodopa equivalent daily dose (LEDD), Mini-Mental State Examination Scale (MMSE) score, and Hamilton Depression Rating Scale (HAMD) score measured prior to DBS and 12 months post-DBS. DBS settings were also recorded. All PD patients benefited from STN-DBS surgery. There were no statistical differences between the two groups in terms of motor function, daily living activities, and LEDD reductions at 12 months post-DBS. The rigidity of the post-surgical G2385R+ group was significantly improved compared with that of the G2385R- group (P = 0.045). Post-surgical voltage in the G2385R+ group was significantly higher than that in the G2385R- group (P = 0.033). STN-DBS outcomes were not influenced by the LRRK2 G2385R variant in Han Chinese patients.

Prognostic and Clinic Pathological Value of Cx43 Expression in Glioma: A Meta-Analysis.

Gap junctional intercellular communication (GJIC) composed of connexin proteins is considered vital to cancer onset and progression since 50 years ago based on Lowenstein and Kano's works, however altered expression of connexins is still a lesser known "hallmark" of cancer. Although many studies support the hypothesis that connexins are tumor suppressors, recent evidence indicates that, in some tumor types including glioma, they may play contradictory role in some specific stages of tumor progression. We thus conduct a meta-analysis to evaluate the prognostic role of Cx43 in glioma for the unanswered questions that whether Cx43 is a beneficial or insalubrity factor for glioma. Eight studies with 1,706 patients were included for meta-analysis. The results showed that Cx43 expression was a clearly negative factor with tumor grades (I 2 = 34%, P < 0.001) and beneficial for OS (n = 3, HR 2.62, 95%CI 1.47-4.68; P = 0.001). Subgroup analysis also found that Cx43 had different expression in Asian young patients vs. other groups. In conclusion, this article summarize the prognostic value of Cx43 and offer a clinical evidence for the notion that Cx43 is generally a tumor suppressor and beneficial for the patients' survival time.

Prioritizing selected PPCPs on the basis of environmental and toxicogenetic concerns: A toxicity estimation to confirmation approach.

Pharmaceuticals and personal care products (PPCPs), the pollutants of emerging concerns, present potential risks to the ecological environment. This study focused on the prioritization of widely used selected PPCPs belonging to two categories:personal care products (PCPs) and non-steroidal anti-inflammatory drugs (NSAIDs). We predicted the toxicogenetic endpoints of PPCPs and then confirmed them using experimental approaches. Our results revealed a significant similarity in the findings obtained through both approaches, indicating NSAIDs with relatively high environmental impacts and in vitro/vivo toxicity. Experimental approach revealed that musk xylene (MX) from PCPs and DIC from NSAIDs as individual chemicals of priority concern showed elevated environmental impacts and significantly induced pi3k-akt-mTOR in vitro. Similarly, propyl paraben (PP) from PCPs and diclofenac (DIC) from NSAIDs caused significant cytotoxicity and DNA damage in vitro. Moreover, PP and MX from the PCPs group and naproxen (NAP) and DIC from the NSAIDs group induced developmental toxicity and perturbations to phases I, II, and III detoxification pathways in vivo. In addition, MX and DIC as priority PPCPs inhibited hematopoiesis and hepatogenesis in vivo. Apart from the specific effects, PPCPs can be ranked as: MX > PP > methylparaben (MP) for PCPs, and DIC > NAP > ibuprofen (IBU) for NSAIDs, regarding their toxic and environmental concerns.

Mechanistic toxicity of DEHP at environmentally relevant concentrations (ERCs) and ecological risk assessment in the Three Gorges Reservoir Area, China.

Di-(2-ethylhexyl) phthalate (DEHP) associated in vitro/vivo toxicity at current environmentally relevant concentration (ERC) with attendant ecological risks in the Three Gorges Reservoir Area (TGRA) is still elusive. Responding to this challenge, a novel integrated study based on analytical and biological assays was designed to elucidate the underlying mechanisms for toxicity of DEHP and its ecological risks at ERC. In this study, GC-MS analysis showed that the highest environmental concentration of DEHP in the TGRA surface water was nearly double that of WHO and USEPA standards. Both distribution and ecological risk decreased from the upper to middle and lower reaches of the TGRA. In vitro toxicity was assessed by cell viability and DNA damage assays: DEHP exposure at ERCs (100-800 µg/L) caused significant reduction in cell viability and elevated DNA damage. Further, DEHP exposure above 400 µg/L resulted in enhanced migration behavior of cancer cells. For in vivo toxicity assessment, short term acute exposure (7 d, 400 µg/L) apparently activated the PI3K-AKT-mTOR pathway, and chronic low-level exposure (3 months, 10-33 µg/L) suppressed the hypothalamus pituitary thyroid (HPT) axis pathway in zebrafish. In addition, acute low-level exposure (5 d, 33-400 µg/L) to DEHP increased aryl hydrocarbon receptor (AhR) activity in Tg(cyp1a:gfp) zebrafish in a concentration-dependent manner. In short, DEHP at ERC has extended potential to induce diverse in vitro and in vivo toxicity at concentrations that also cause impairment of biochemical function in aquatic species of the TGRA.