From pollution to solutions: Insights into the sources, transport and management of plastic debris in pristine and urban rivers.

River systems are important recipients of environmental plastic pollution and have become key pathways for the transfer of mismanaged waste from the land to the ocean. Understanding the sources and fate of plastic debris, including plastic litter (>5 mm) and microplastics (MPs) (<5 mm), entering different riverine systems is essential to mitigate the ongoing environmental plastic pollution crisis. We comprehensively investigated the plastic pollution in the catchments of two rivers in the Yangtze River basin: an urban river, the Suzhou section of the Beijing-Hangzhou Grand Canal (SZ); and a pristine rural river, the Jingmen section of the Hanjiang River (JM). The abundance of plastic pollutants in SZ was significantly higher than in JM: 0.430 ± 0.450 items/m3 and 0.003 ± 0.003 items/m3 of plastic litter in the water; 23.47 ± 25.53 n/m3 and 2.78 ± 1.55 n/m3 MPs in the water; and 218.82 ± 77.40 items/kg and 5.30 ± 1.99 items/kg of MPs in the sediment, respectively. Plastic litter and MPs were closely correlated in abundance and polymer composition. Overall, the polymer type, shape and color of MPs were dominant by polypropylene (42.5%), fragment (60.4%) and transparent (40.0%), respectively. Source tracing analysis revealed that packaging, shipping, and wastewater were the primary sources of plastic pollutants. The mantel analysis indicated that socio-economic and geospatial factors play crucial roles in driving the hotspot formation of plastic pollution in river networks. The composition of the MP communities differed significantly between the sediments and the overlying water. The urban riverbed sediments had a more pronounced pollutant 'sink' effect compared with the pristine rivers. These findings suggested that the modification of natural streams during urbanization may influence the transport and fate of plastic pollutants in them. Our results offer pivotal insights into effective preventive measures.

Design of Multifunctional Mesosphere-Ionosphere Sounding System and Preliminary Results.

This paper describes a novel sounding system for which the functions of the medium frequency (MF) radar and the ionosonde are integrated on the same hardware platform and antenna structure, namely the middle atmosphere-ionosphere (MAI) system. Unlike the common MF radar, MAI system adopts the pseudo-random (PRN) phase-coded modulation technology, which breaks the limitation of the traditional monopulse mode. Through the pulse compression, only a small peak power is needed to achieve the signal-to-noise ratio (SNR) requirement. The excellent anti-jamming performance is also very suitable for the ionospheric sounding. One transmitting and six receiving modes are adopted for the MF sounding. While neglecting the structure of the T/R switches, the coupling interference between the transmitter and the receiver may also be avoided. Moreover, by employing a miniaturized antenna array composed of progressive-wave antennas for the MF receiving and ionospheric sounding, the MAI system takes account of the requirements of the inversion algorithms of MF radar and the large bandwidth need for the ionospheric sounding concurrently. Such an antenna structure can also greatly simplify the system structure and minimize the difficulty of deployment. The experiments verified the availability of the system scheme and its engineering application significance. Through further analysis of the sounding data, the wind field of the mesosphere, the electron density of D layer and electron density profile from layers E to F were obtained at the identical location. The capability of MAI system can play an important role in studying the interaction and coupling mechanism between the mesosphere and ionosphere.

A Novel Ionospheric Sounding Network Based on Complete Complementary Code and Its Application.

In this paper, complete complementary code (CCC) sequences are applied to a High Frequency (HF) ionospheric sounding network. Ionosondes distributed at multiple locations use the mutually orthogonal CCC sequences to conduct vertical soundings synchronously. At the same time, thanks to the omnidirectional antennas, every station can receive the oblique echoes transmitted from the others. Due to the orthogonality between the code sequences, both vertical and oblique ionograms can be simultaneously obtained and completely separated. Through this method, the sounding efficiency can be enhanced, and the inversion difficulty can be reduced. Further, by using the data assimilation method, vertical and oblique sounding results can be combined to obtain a wide range of regional ionospheric characteristics. To verify the performance of this kind of sounding network, validation experiments are implemented to demonstrate that vertical and oblique ionograms can be obtained independently at the same time and inverted separately and that the maps of foF2 parameters obtained by using the data assimilation method provide more details than single vertical or oblique sounding.

Application of Biphase Complete Complementary Code for Ionospheric Sounding.

This paper illustrates the processes carried out for the application of biphase complete complementary code (CCC) for ionospheric sounding to address the coherent interference problem in multi-station ionospheric sounding. An algorithm to generate the biphase CCC is described, and the detailed process of waveform construction and signal processing is presented. Characteristics of the autocorrelation and cross-correlation are analyzed through simulations, and the technical feasibility of the application of CCC is explored. Experiments of ionospheric sounding with the CCC are also implemented to verify performance. Results demonstrate that the CCC performs well in multi-station ionospheric sounding, and is capable of eliminating the coherent interference in the network of ionosondes, compared to the conventional complementary code.

Wuhan Ionospheric Oblique Backscattering Sounding System and Its Applications-A Review.

For decades, high-frequency (HF) radar has played an important role in sensing the Earth's environment. Advances in radar technology are providing opportunities to significantly improve the performance of HF radar, and to introduce more applications. This paper presents a low-power, small-size, and multifunctional HF radar developed by the Ionospheric Laboratory of Wuhan University, referred to as the Wuhan Ionospheric Oblique Backscattering Sounding System (WIOBSS). Progress in the development of this radar is described in detail, including the basic principles of operation, the system configuration, the sounding waveforms, and the signal and data processing methods. Furthermore, its various remote sensing applications are briefly reviewed to show the good performance of this radar. Finally, some suggested solutions are given for further improvement of its performance.

Interaction of CARD14, SENP1 and VEGFA polymorphisms on susceptibility to high altitude polycythemia in the Han Chinese population at the Qinghai-Tibetan Plateau.

High altitude polycythemia (HAPC) is a serious public health problem among Han Chinese immigrants to the Qinghai-Tibetan Plateau. This study aims to explore the genetic basis of HAPC in the Han Chinese population. 484 male subjects (234 patients and 250 controls) were enrolled in this study. Genotyping was performed for polymorphisms of I/D in ACE, C1772T and G1790A in exon 12 of HIF-1α, rs2567206 in CYP1B1, rs726354 in SENP1, rs3025033 in VEGFA, rs7251432 in HAMP, rs2075800 in HSPA1L and rs8065364 in CARD14. Gene-gene interaction was assessed by multifactor dimensionality reduction. A significant association was seen between CARD14 polymorphism rs8065364 and risk of HAPC development in male Han Chinese, and the C allele of rs8065364 was a risk factor (odds ratio (OR)=1.59, 95% confidence interval (95% CI)=1.21-2.08). Gene-gene interaction analysis indicated that a synergistic relationship existed between rs3025033 and rs8065364 (1.00%), rs3025033 and rs726354 (0.18%), and rs726354 and rs8065364 (0.17%). The combination of rs8065364 in CARD14, rs3025033 in VEGFA and rs726354 in SENP1 was the best model to predict HAPC development in this study (testing accuracy=0.6183, p=0.0010, cross-validated consistency=10/10). Genetic interactions of SNPs in CARD14, SENP1 and VEGFA might represent a functional mechanism in the pathogenesis of HAPC.

Chronic mountain sickness in Chinese Han males who migrated to the Qinghai-Tibetan plateau: application and evaluation of diagnostic criteria for chronic mountain sickness.

BACKGROUND: Chronic mountain sickness (CMS), originally characterized by excess hemoglobin (Hb), is currently diagnosed using score-based diagnostic criteria combined with excessive erythrocytosis and clinical symptoms. However, the current criteria have limited applicability. We applied these criteria to 1,029 Chinese Han males migrated to and have been stayed at the Qinghai-Tibet plateau (3,700-5,000 m) for 2-96 months to investigate the prevalence of CMS and its correlations with Hb concentration, altitude, and the length of residence. METHODS: Subjects were screened for CMS using the latest approved diagnostic criteria combined with excessive erythrocytosis and clinical symptoms. Hb concentrations were measured, and a cut-off point was determined with k-means clustering. Predisposing factors were evaluated with binary logistic analysis and curve fitting analysis. RESULTS: (1) The prevalence of CMS at the Qinghai-Tibetan plateau was 17.8% (183/1029 subjects, with CMS score ≥ 6, and Hb ≥ 210 g/L), which is higher than that previously reported. (2) While individuals were identified into two Hb clusters with a cut-off point of 200 g/L, in the low-Hb cluster (Hb < 200 g/L), the oxygen saturation remained stable as the Hb increased; in the high-Hb cluster (Hb ≥ 200 g/L), the oxygen saturation decreased as the Hb increased. (3) Two critical factors associated with CMS development were residence at an altitude of 4,500 m and a 60-month length of residence. CONCLUSIONS: Our presenting scoring system is more sensitive than previous diagnostic criteria and favors early screening and treatment of patients with CMS. Our finding suggests that an adjusted Hb threshold of 200 g/L (instead of 210 g/L) is more adaptable in Han individuals at all altitudes. The weight of Hb level should score ≥ 6 points using the CMS scoring system because of the pathophysiologic role of excessive erythrocytosis in patients with CMS. In addition, our data suggest the importance of early screening of CMS via regular medical examinations within the first 60 months of residence at high altitudes, especially >4500 m.

An EPAS1 haplotype is associated with high altitude polycythemia in male Han Chinese at the Qinghai-Tibetan plateau.

BACKGROUND: Hemoglobin concentration at high altitude is considered an important marker of high altitude adaptation, and native Tibetans in the Qinghai-Tibetan plateau show lower hemoglobin concentrations than Han people who have emigrated from plains areas. Genetic studies revealed that EPAS1 plays a key role in high altitude adaptation and is associated with the low hemoglobin concentration in Tibetans. Three single nucleotide polymorphisms (rs13419896, rs4953354, rs1868092) of noncoding regions in EPAS1 exhibited significantly different allele frequencies in the Tibetan and Han populations and were associated with low hemoglobin concentrations in Tibetans. METHODS: To explore the hereditary basis of high altitude polycythemia (HAPC) and investigate the association between EPAS1 and HAPC in the Han population, these 3 single nucleotide polymorphisms were assessed in 318 male Han Chinese HAPC patients and 316 control subjects. Genotyping was performed by high resolution melting curve analysis. RESULTS: The G-G-G haplotype of rs13419896, rs4953354, and rs1868092 was significantly more frequent in HAPC patients than in control subjects, whereas no differences in the allele or genotype frequencies of the 3 single nucleotide polymorphisms were found between HAPC patients and control subjects. Moreover, genotypes of rs1868092 (AA) and rs4953354 (GG) that were not observed in the Chinese Han in the Beijing population were found at frequencies of 1.6% and 0.9%, respectively, in our study population of HAPC patients and control subjects. CONCLUSIONS: Carriers of this EPAS1 haplotype (G-G-G, rs13419896, rs4953354, and rs1868092) may have a higher risk for HAPC. These results may contribute to a better understanding of the pathogenesis of HAPC in the Han population.

Biofiltration of toluene and ethyl acetate mixture by a fungal-bacterial biofilter: Performance and community structure analysis.

The inhibitory effect of hydrophilic volatile organic compounds (VOCs) on hydrophobic VOCs removal was found to be efficiently reduced by the fungal-bacterial biofilters (F&B-BFs) developed in the present study. Overall, the toluene and ethyl acetate mixture removal efficiencies (REs) and elimination capacities (ECs) of F&B-BFs were superior to those of bacterial biofilters (B-BFs). The REs for toluene and ethyl acetate were 32.5 ± 0.8 % and 74.6 ± 1.0 %, respectively, for F&B-BFs, in comparison to 8.0 ± 0.3 % and 60 ± 1.3 % for B-BFs. The ECs for toluene and ethyl acetate were 13.0 g m-3 h-1 and 149.2 g m-3 h-1, respectively, for the F&B-BF, compared to 3.2 g m-3 h-1 and 119.6 g m-3 h-1 for the B-BFs. This was achieved at a constant empty bed residence time (EBRT) of 45 s. F&B-BFs exhibited a superior mineralization efficiencies (MEs) compared to B-BFs for a VOC mixture of toluene and ethyl acetate (≈36.1 % vs ~ 29.6 %). This is attributed to the direct capture of VOCs by the presence of fungi, increased the contact time between VOCs and VOCs-degrading bacteria, and even distribution of VOCs-degrading bacteria in the F&B-BFs. Moreover, compared with B-BFs, the coupling effect of genus Pseudomonas degradation, and unclassified_f_Herpotrichiellaceae and unclassified_p_Ascomycota adsorption of F&B-BF resulted in a reduction in the impact of the presence of hydrophilic VOCs on the removal of hydrophobic VOCs, thereby enhancing the biofiltration performance of mixtures of hydrophilic and hydrophobic VOCs.

Improving Parental Health Literacy in Primary Caregivers of 0- to 3-Year-Old Children Through a WeChat Official Account: Cluster Randomized Controlled Trial.

Background: Parental health literacy is important to children's health and development, especially in the first 3 years. However, few studies have explored effective intervention strategies to improve parental literacy. Objective: This study aimed to determine the effects of a WeChat official account (WOA)-based intervention on parental health literacy of primary caregivers of children aged 0-3 years. Methods: This cluster randomized controlled trial enrolled 1332 caregiver-child dyads from all 13 community health centers (CHCs) in Minhang District, Shanghai, China, between April 2020 and April 2021. Participants in intervention CHCs received purposefully designed videos via a WOA, which automatically recorded the times of watching for each participant, supplemented with reading materials from other trusted web-based sources. The contents of the videos were constructed in accordance with the comprehensive parental health literacy model of WHO (World Health Organization)/Europe (WHO/Europe). Participants in control CHCs received printed materials similar to the intervention group. All the participants were followed up for 9 months. Both groups could access routine child health services as usual during follow-up. The primary outcome was parental health literacy measured by a validated instrument, the Chinese Parental Health Literacy Questionnaire (CPHLQ) of children aged 0-3 years. Secondary outcomes included parenting behaviors and children's health outcomes. We used the generalized linear mixed model (GLMM) for data analyses and performed different subgroup analyses. The ß coefficient, risk ratio (RR), and their 95% CI were used to assess the intervention's effect. Results: After the 9-month intervention, 69.4% (518/746) of caregivers had watched at least 1 video. Participants in the intervention group had higher CPHLQ total scores (ß=2.51, 95% CI 0.12-4.91) and higher psychological scores (ß=1.63, 95% CI 0.16-3.10) than those in the control group. The intervention group also reported a higher rate of exclusive breastfeeding (EBF) at 6 months (38.9% vs 23.44%; RR 1.90, 95% CI 1.07-3.38) and a higher awareness rate of vitamin D supplementation for infants younger than 6 months (76.7% vs 70.5%; RR 1.39, 95% CI 1.06-1.82). No significant effects were detected for the physical score on the CPHLQ, breastfeeding rate, routine checkup rate, and children's health outcomes. Furthermore, despite slight subgroup differences in the intervention's effects on the total CPHLQ score and EBF rate, no interaction effect was observed between these subgroup factors and intervention factors. Conclusions: Using a WHO literacy model-based health intervention through a WOA has the potential of improving parental health literacy and EBF rates at 6 months. However, innovative strategies and evidence-based content are required to engage more participants and achieve better intervention outcomes.

Mechanisms of Action of Potentilla discolor Bunge in Type 2 Diabetes Mellitus Based on Network Pharmacology and Experimental Verification in Drosophila.

Purpose: Type 2 diabetes mellitus (T2DM) is associated with reduced insulin uptake and glucose metabolic capacity. Potentilla discolor Bunge (PDB) has been used to treat T2DM; however, the fundamental biological mechanisms remain unclear. This study aimed to understand the active ingredients, potential targets, and underlying mechanisms through which PDB treats T2DM. Methods: Components and action targets were predicted using network pharmacology and molecular docking analyses. PDB extracts were prepared and validated through pharmacological intervention in a Cg>InRK1409A diabetes Drosophila model. Network pharmacology and molecular docking analyses were used to identify the key components and core targets of PDB in the treatment of T2DM, which were subsequently verified in animal experiments. Results: Network pharmacology analysis revealed five effective compounds made up of 107 T2DM-related therapeutic targets and seven protein-protein interaction network core molecules. Molecular docking results showed that quercetin has a strong preference for interleukin-1 beta (IL1B), IL6, RAC-alpha serine/threonine-protein kinase 1 (AKT1), and cellular tumor antigen p53; kaempferol exhibited superior binding to tumor necrosis factor and AKT1; ß-sitosterol demonstrated pronounced binding to Caspase-3 (CASP3). High-performance liquid chromatography data quantified quercetin, kaempferol, and ß-sitosterol at proportions of 0.030%, 0.025%, and 0.076%, respectively. The animal experiments revealed that PDB had no effect on the development, viability, or fertility of Drosophila and it ameliorated glycolipid metabolism disorders in the diabetes Cg>InRK1409A fly. Furthermore, PDB improved the body size and weight of Drosophila, suggesting its potential to alleviate insulin resistance. Moreover, PDB improved Akt phosphorylation and suppressed CASP3 activity to improve insulin resistance in Drosophila with T2DM. Conclusion: Our findings suggest that PDB ameliorates diabetes metabolism disorders in the fly model by enhancing Akt activity and suppressing CASP3 expression. This will facilitate the development of key drug targets and a potential therapeutic strategy for the clinical treatment of T2DM and related metabolic diseases.

Design and Evaluation of 3-Phenyloxetane Derivative Agonists of the Glucagon-Like Peptide-1 Receptor.

Various small molecule GLP1R agonists have been developed and tested for treating type 2 diabetes (T2DM) and obesity. However, many of these new compounds have drawbacks, such as potential hERG inhibition, lower activity compared to natural GLP-1, limited oral bioavailability in cynomolgus monkeys, and short duration of action. Recently, a new category of 3-phenyloxetane derivative GLP1R agonists with enhanced hERG inhibition has been discovered. Using an AIDD/CADD method, compound 14 (DD202-114) was identified as a potent and selective GLP1R agonist, which was chosen as a preclinical candidate (PCC). Compound 14 demonstrates full agonistic efficacy in promoting cAMP accumulation and possesses favorable drug-like characteristics compared to the clinical drug candidate Danuglipron. Additionally, in hGLP-1R knock-in mice, compound 14 displayed a sustained pharmacological effect, effectively reducing blood glucose levels and food intake. These findings suggest that compound 14 holds promise as a future treatment option for T2DM and obesity, offering improved properties.

Microfiber Hotspots' Association with Ships in a Remote Port before and during Covid-19.

During monthly water quality monitoring of Norwegian coastal waters, the sea surface waters off Brønnøysund, a remote port in Norway, exhibited an unexpectedly high abundance of microfibers. We further conducted monitoring of microplastics and microfibers from the surface waters off the city before and during the Covid-19 pandemic. Analysis of the microfiber characteristics, which were primarily comprised of cellulosic and polyester fibers, revealed similarities with those found in the global ocean, but at concentrations that were 1-4 orders of magnitude higher, with the maximum concentration reaching 491 n/L (0.34 mg/L). Source apportionment of microfibers using multivariate analyses based on simultaneous water chemistry data showed positive correlations with ships. Contrary to previous assumptions that marine microfibers were derived from land-based sources, our findings revealed that gray water discharge from ships significantly contributed to microfibers in the oceans. The demonstrated causations using path modeling between microfibers, gray water, shipping, and noncargo shipping activities call for urgent research and regulatory actions toward addressing plastic pollution in the UN Decade of Ocean Science.

Salidroside Ameliorates Ischemia/Reperfusion-Induced Human Cardiomyocyte Injury by Inhibiting the Circ_0097682/miR-671-5p/USP46 Pathway.

Salidroside shows an inhibitory effect on myocardial ischemia/reperfusion (I/R) injury; however, the underlying mechanism remains to be explored. The present work analyzes the mechanism that drives salidroside to ameliorate I/R-induced human cardiomyocyte injury. Human cardiomyocytes were subjected to I/R treatment to simulate a myocardial infarction cell model. Cell viability, cell proliferation, and cell apoptosis were analyzed by CCK-8 assay, EdU assay, and flow cytometry analysis, respectively. RNA expression levels of circ_0097682, miR-671-5p, and F-box and ubiquitin-specific peptidase 46 (USP46) were detected by qRT-PCR. Protein expression was measured by Western blotting assay. The levels of IL-6, IL-1ß, and TNF-α in cell supernatant were detected by enzyme-linked immunosorbent assays. Salidroside treatment relieved I/R-induced inhibitory effect on AC16 cell proliferation and promoting effects on cell apoptosis, inflammation, and oxidative stress. Salidroside inhibited circ_0097682 expression in I/R-treated AC16 cells. Salidroside-mediated inhibition of I/R-induced cell injury involved the downregulation of circ_0097682 expression. In addition, circ_0097682 bound to miR-671-5p in AC16 cells, and miR-671-5p inhibitors rescued salidroside pretreatment-mediated effects in I/R-treated AC16 cells. Moreover, miR-671-5p targeted USP46 in AC16 cells, and USP46 introduction partially relieved circ_0097682 depletion or salidroside pretreatment-induced effects in I/R-treated AC16 cells. Salidroside ameliorated I/R-induced AC16 cell injury by inhibiting the circ_0097682/miR-671-5p/USP46 pathway.

Tonifying-Qi-and-Detoxification Decoction attenuated injuries of colon and lung tissues in ulcerative colitis rat model via regulating NF-κB and p38MAPK pathway.

Background: Tonifying-Qi-and-Detoxification Decoction (TQDD) is a Chinese medicine compound. This research probed the possible protective effects of TQDD on injuries of the colon and lung tissues in ulcerative colitis (UC) rat model. Methods: UC rat model was established by colon mucosal tissue sensitization combined with TNBS-ethanol. Ninety-six rats were randomly divided into normal control (NC), model, sulfasalazine (SASP), and TQDD (low, middle, and high dosages) groups. After 4 weeks intervention, all rats were sacrificed. The microstructure of lung tissue was observed using hematoxylin-eosin (HE) staining. Transmission electron microscope (TEM) was utilized to assess the ultrastructure change of alveolar epithelial type II cells (AEC-II). The mRNA expressions of Bax, Caspase 3, nuclear factor kappa B (NF-κB) and NF-κB inhibitor α (IKBα) in tissues were measured via quantitative reverse transcription PCR (qRT-PCR) assay. Western blotting and immunohistochemistry (IHC) were used to test p38MAPK, activating transcription factor 2 (ATF2), c-jun and c-fos expressions in tissues. Results: TQDD alleviated microstructure change of lung tissues, lung cell apoptosis and ultrastructure alterations of AEC-II in UC rat model. Moreover, TQDD suppressed activation of NF-κB pathway in colon and lung tissues. Besides, TQDD inhibited p38MAPK pathway in colon and lung tissues, as well as reduced ATF2, c-jun, and c-fos expressions in colon and lung tissues. Conclusions: This research confirmed the beneficial effect of TQDD on injuries of colon and lung tissues in UC rat model. TQDD attenuated injuries of lung and colon tissues in colon mucosal tissue sensitization combined with TNBS-ethanol-caused UC model via regulating NF-κB and p38MAPK pathways.

Community-based intervention via WeChat official account to improve parental health literacy among primary caregivers of children aged 0 to 3 years: Protocol for a cluster randomized controlled trial.

Background: Parental health literacy is an important determinant of children's health, especially during the critical window of early development in the first 3 years. As the information communication technology develops, health education via social media is widely used to deliver health information. However, few studies have explored the effect of intervention via social media on parental health literacy. Objective: This study aims to determine whether a WeChat official account-based health intervention can improve parental health literacy of primary caregivers of children aged 0 to 3 years in Minhang District, Shanghai, China. Methods: The cluster randomized controlled trial includes all 13 community health centers (CHCs) in Minhang District, Shanghai. We take each CHCs as a cluster in the randomization. The CHCs are randomly allocated to the intervention or the control group through random sequence generation. Ninety primary caregivers of children aged 0 to 2 years will be recruited from each CHC, 1170 in total. Caregivers in the intervention group will be provided with a series of video clips and online reading material links on scientific parenting via a WeChat account. Caregivers in the control group will receive printed educational materials with similar contents to the intervention group. All the participants will access routine child health care and be followed up for 9 months. Online assessment of health literacy will be conducted for both groups before and after the intervention. The primary outcome is the change in the total scores of parental health literacy using a validated instrument. The data of secondary outcomes, such as exclusive breastfeeding in the first 6 months, anthropometric measurements, and disease conditions, will be extracted from routine health care records. Generalized linear mixed model (GLMM) will be used for data analyses. Discussion: Compared with traditional health education, health intervention via WeChat official account could be a feasible and effective solution to improve parental health literacy. Trial registration: This trial is registered with the Chinese Clinical Trial Registry (ChiCTR): (#ChiCTR2000031711) on April 07, 2020.

Analysis of the Anti-Tumour Effect of Xuefu Zhuyu Decoction Based on Network Pharmacology and Experimental Verification in Drosophila.

Background: Tumours are among the most lethal diseases that heavily endanger human health globally. Xuefu Zhuyu Decoction (XFZYD) is a prescription used to treat blood-activating stasis. Although XFZYD has been shown to suppress migration and invasion of tumour cells, the active ingredients, potential targets, and underlying mechanism remain largely elusive. Purpose: To identify the prospective ingredients and major targets of XFZYD against tumours, and evaluate the efficacy and potential molecular mechanisms of XFZYD extract on tumour growth and invasion. Methods: We predicted that XFZYD might act on 80 targets through 128 active components using the network pharmacology analysis method. In addition, we prepared an XFZYD aqueous extract and employed the RasV12/lgl -/- -induced Drosophila tumour model to carry out experimental verification. Results: XFZYD did not exhibit any side effects on development, viability, and fertility. Furthermore, XFZYD significantly impeded tumour size and invasion at moderate concentrations and suppressed the increased phosphorylation of JNK but strongly enhanced the expression of Caspase 3 in the RasV12/lgl -/- model. Finally, the mRNA level of the transcription complex AP-1 component c-FOS was remarkably reduced. In contrast, the transcription of three pro-apoptotic genes was significantly increased when XFZYD was used to treat the tumour model. Conclusion: The study findings suggest that XFZYD may promote tumour cell apoptosis by activating caspase signalling to control primary growth and hinder tumour cell invasion by suppressing JNK/AP-1 signalling activity, thus providing a potential therapeutic strategy for XFZYD in the clinical treatment of cancer and other related diseases.

The evolutionarily conserved arginyltransferase 1 mediates a pVHL-independent oxygen-sensing pathway in mammalian cells.

The response to oxygen availability is a fundamental process concerning metabolism and survival/death in all mitochondria-containing eukaryotes. However, the known oxygen-sensing mechanism in mammalian cells depends on pVHL, which is only found among metazoans but not in other species. Here, we present an alternative oxygen-sensing pathway regulated by ATE1, an enzyme ubiquitously conserved in eukaryotes that influences protein degradation by posttranslational arginylation. We report that ATE1 centrally controls the hypoxic response and glycolysis in mammalian cells by preferentially arginylating HIF1α that is hydroxylated by PHD in the presence of oxygen. Furthermore, the degradation of arginylated HIF1α is independent of pVHL E3 ubiquitin ligase but dependent on the UBR family proteins. Bioinformatic analysis of human tumor data reveals that the ATE1/UBR and pVHL pathways jointly regulate oxygen sensing in a transcription-independent manner with different tissue specificities. Phylogenetic analysis suggests that eukaryotic ATE1 likely evolved during mitochondrial domestication, much earlier than pVHL.

Altitude can alter the mtDNA copy number and nDNA integrity in sperm.

OBJECTIVE: Mitochondria are factories for energy production and genetic alterations in mtDNA will directly impact OXPHOS function. The copy number of mtDNA (i.e., the number of mtDNA per spermatozoon) is one of the major mitochondrial genetic features. Besides mtDNA copy number, the change of either mtDNA or nDNA integrity is another important factor causing asthenospermia, or poor sperm motility in infertile men. In this study, we investigated the mtDNA copy number and the integrities of mtDNA and nDNA respectively in semen samples from different donors at 5,300 m altitudes. METHODS: Total DNA was extracted from semen samples from donors in two different altitudes. Quantitative PCR was performed to evaluate the mtDNA copy number. PCR amplification was used to examine the integrity of sperm mtDNA. Flow cytometry was carried out to investigate sperm nDNA integrity. All data were analyzed to show the statistical significance. RESULTS: Sperm mtDNA copy number for those living at high altitude (5,300 m) for one month was significantly higher (P < 0.05) than for those at the lower altitude (1,400 m) or in donors who had been living at the 5,300 m altitude for 1 year. In addition, sperm mtDNA copy numbers were remarkably decreased (P < 0.05) in those who had lived at the greater altitude for 1 year compared to those who had lived there for one month. The ratio of nDNA integrity among the 10,000 sperms at high altitude for one month was significantly lower (P < 0.05) than that at the lower altitude (1,400 m) or at 5,300 m for 1 year, and the ratio of nDNA integrity sperms at high altitude for 1 year was increased, and higher than that for at the lower altitude (P < 0.05). CONCLUSION: High altitude can alter the mtDNA copy number and nDNA integrity in the sperms.

To what extent are we really free from airborne microplastics?

Quality assurance and quality control (QA&QC) procedures are vital for ensuring data reliability, but little is known about the use of such procedures in reducing airborne microplastic (MP) contamination. To address this issue, we tried to determine the efficiency of two common methods (washing and ashing experimental glassware) for removing airborne MPs and identified airborne contamination during MP analytical procedure. The results showed the removal efficiencies of washing and ashing were an average of 88%-98% and 100%, respectively, indicating that both methods could eliminate most of the spiked airborne MPs with no significant difference noted between the two methods. Although rigorous measures were taken to prevent contamination from ambient air, trace amounts of airborne MPs were still detected, which is an issue that has not been adequately investigated in previous studies. All of the procedural contaminants detected in this study were fibrous. Approximately 88% of these fibers were cotton-like (cotton, cellulose, and cellophane) fibers, and 13% of them were plastic. Surprisingly, cotton-like fibers and MPs had a similar size distribution, suggesting that they may have undergone a similar weathering process. In the end, to cope with inevitable airborne contamination, several measures were proposed for further research. Such measures will provide the necessary methodological assistance for accurate quantification of MP pollution in the field.