China's health silk road construction during the COVID-19 pandemic.

China has been contributing to new approaches to global governance. The Health Silk Road (HSR), a significant component of the Belt and Road Initiative (BRI), was proposed by China in 2016. This paper claims that HSR is a new institution introduced alongside the existing WHO-led multilateral health system, and its relationship with the existing system can be described as layering. Having explored the new development of HSR during COVID-19, this paper further argues that while HSR has its unique strength in making contributions to global health governance and economic recovery, it faces a prominent issue of securitisation in the context of China-U.S. strategic competition, suspicion of the quality of medical products and sectoral fragmentation.

Laboratory study of Se speciation in the sediment and oligochaete Lumbriculus variegatus from an aquatic environment.

Sediments are the major sink for selenium (Se) in aquatic environments. Se speciation in sediments is crucial for its bioavailability and toxicity in benthos, but this is relatively understudied. In this study, the background levels of Se in the river sediments, fish flakes, and Lumbriculus variegatus were also detected. Then, the dynamic changes of selenium speciation and concentrations in sediments were investigated after adding selenite (Se(IV)) and seleno-L-methionine (Se-Met) in the sediments for 90 and 7 days, and the accumulation and depuration of Se(IV) and Se-Met for 7 days in the oligochaete L. variegatus were also explored. Without the presence of worms, the levels of Se(IV) in the sediments were relatively stable within 7 days but showed a decreasing trend during the 90 days of aging. In contrast, Se-Met in the sediments showed a sharp decrease within 3 days of aging. The LC50-96 h values of Se(IV) and Se-Met in L. variegatus were 372.6 and 9.4 µg/g, respectively. Interestingly, the dominant Se species in Se(IV)- or Se-Met-treated L. variegatus was Se-Met, whose level was increased with time in 7 days of exposure. Se was barely depurated from L. variegatus during the 8 days of the depuration period. This study has provided indispensable data on the levels of total Se in the abiotic and biotic matrices and the biodynamics of Se in a representative benthos, which could better understand the ecological risk of Se to the freshwater benthic communities.

Altered life history traits and transcripts of molting- and reproduction-related genes by cadmium in Daphnia magna.

Cadmium (Cd) is a non-essential element and can be toxic to aquatic organisms at low concentrations. Despite its well-known toxicity to Daphnia magna, the effects of Cd on physiological parameters (heart rate and thoracic limb activity) and molting- and reproduction-related genes are relatively understudied. In this study, D. magna were exposed to 0 (control), 25, 50 and 75 µg L-1 of Cd for 7 d and 21 d to determine the toxicity of Cd. The results showed that the Cd body burden in D. magna was significantly increased with elevated Cd concentrations, up to 13.4 µg Cd/g dry weight (dw) after exposure to 75 µg L-1 for 21 d. After 21 d of exposure, the body length and body weight of D. magna were significantly decreased in all Cd treatments compared to the control. The heart rate and thoracic limb activity were reduced by 4.3-11.7 and 5.0-10.3%, respectively. The levels of malondialdehyde (MDA) were increased by ~24-37% and the activity of catalase (CAT) was inhibited by ~50% compared to the control. The reproductive parameters (i.e., size of the first brood, the total number of offspring per female and the number of offspring per brood) were remarkably reduced, causing adverse effects on the population dynamics. In addition, the transcripts of genes (cyp314, cyp18a1, ecra, usp, hr3, cut, cht and cht3) related to the molting of D. magna were altered, whereas the transcripts of genes (vtg1, vtg2 and vmo1) related to reproduction were down-regulated. This study helps better understand the effects of Cd at different biological levels.

Aloperine protects human retinal pigment epithelial cells against hydrogen peroxide-induced oxidative stress and apoptosis through activation of Nrf2/HO-1 pathway.

Age-related macular degeneration (AMD) is a complex multifactorial disease associated with the dysfunction of retinal pigment epithelium (RPE). Aloperine is a quinolizidine alkaloid that has been proven to possess broad pharmacological activities. However, the effects of aloperine on AMD remain unclear. In the present study, we used hydrogen peroxide (H2O2) to induce oxidative injury in human RPE cells (ARPE-19 cells). ARPE-19 cells were pretreated with different concentrations of aloperine for 2 h, followed by H2O2 exposure. Cell cytotoxicity was determined using lactate dehydrogenase (LDH) release assay. Cell viability was measured using Cell Counting Kit-8 (CCK-8) assay. The reactive oxygen species (ROS) generation, malondialdehyde (MDA) level, superoxide dismutase (SOD) activity and glutathione peroxidase (GSH-PX) activity were detected to reflect oxidative status. Western blot was performed to detect the expressions of bcl-2, bax, nuclear factor-erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1). The activity of caspase-3 was also assessed to indicate cell apoptosis. In addition, ARPE-19 cells were transfected with siNrf2 to knock down Nrf2. Our results showed that pretreatment with aloperine elevated the reduced cell viability of H2O2-induced ARPE-19 cells in a dose-dependent manner. Aloperine greatly decreased the production of ROS and MDA, and increased the activities of SOD and GSH-PX in H2O2-stimulated ARPE-19 cells. H2O2-caused a decrease in bcl-2 expression and increases in bax expression and caspase-3 activity were mitigated by aloperine. Moreover, aloperine treatment enhanced the expression levels of Nrf2 in nuclear fraction and the HO-1 expression in lysates. Knockdown of Nrf2 reversed the protective effects of aloperine on H2O2-induced ARPE-19 cells. In conclusion, these findings demonstrated that aloperine protected ARPE-19 cells from H2O2-induced oxidative stress and apoptosis in part via activating the Nrf2/HO-1 signaling pathway. The findings suggested a therapeutic potential of aloperine for the treatment of ADM.

Cyclophosphamide affects eye development and locomotion in zebrafish (Danio rerio).

Cyclophosphamide (CP) is a broad-spectrum anticancer drug and has been frequently detected in aquatic environments due to its incomplete removal by wastewater treatment facilities and slow degradation in waters. Its toxicity in fish remains largely unknown. In this study, zebrafish eggs <4 h post fertilization (hpf) were exposed to CP at the concentrations from 0.5 to 50.0 µg/L until 168 hpf, and its toxicity was evaluated by biochemical, transcriptomic, and behavioral approaches. The results showed that malformation and mortality rates increased with CP concentrations. The 7-day malformation EC50 and mortality (LC30) by CP were calculated to be 86.8 µg/L and 7.5 mg/L, respectively. Inhibited startle response (light to dark) (a minimal of 19%) and reduced swimming velocity (a minimal of 30%) were observed in the CP-exposed larvae. The thicknesses of retinal ganglion layer, inner plexiform layer, and inner nuclear layer in the retina were increased after exposure to CP. Meanwhile, exposure to CP increased karyorrhexis and karyolysis in the liver tissue. Transcriptomic analysis identified 607 differentially expressed genes (DEGs) (159 up-regulated and 448 down-regulated). A significant reduction in the transcripts of sgk1 (the FoxO pathway), jun (the MAPK pathway), and diabloa (apoptosis pathway) were observed in the CP-treated larvae. This study has demonstrated that low concentrations of CP cause malformation, reduced swimming capacity, histopathological alterations in the retina and liver tissues, and interference on transcriptional expressions of key genes associated with different pathways. The ecological risk of CP and other anticancer drugs to aquatic organisms merits future investigation.

Dietary Seleno-l-methionine Alters the Microbial Communities and Causes Damage in the Gastrointestinal Tract of Japanese Medaka Oryzias latipes.

Excess dietary seleno-l-methionine (Se-Met) induces various adverse effects in fish inhabiting the Se-contaminated environments. However, there is an extreme paucity of data on the effects of excess dietary Se-Met on the microbiota in the gastrointestinal (GI) tract in fish. In this study, Japanese medaka Oryzias latipes (three months old) were fed the Se-Met enriched diets at environmentally relevant concentrations: 2.90 (Control: (C), 6.69 (L), 11.89 (M), and 27.05 (H) µg Se/g dw) for 60 d. Histopathological, high throughput sequencing, and biochemical approaches were used to investigate the alterations in histology and microbial communities of the GI tract, enzymatic activity, and transcripts of closely related genes. The results showed that the fish weight was reduced at ∼13% from the L and H treatments. Decreased height and thickness of villus in the GI tract were observed in the H treatment. Meanwhile, the level of D-lactate and activity of diamine oxidase (DAO), protease, and lipase were inhibited in the H treatment. The transcripts of the genes related to the inflammation (i.e., IL-1ß and IL-8) were elevated, while those of the genes related to the intestinal barrier (i.e., cdh1, ZO-1, ocln, and cldn7) were inhibited in the H treatment. In addition, alpha diversity at the genus level was higher in the L treatment than the control, and the composition of the microbial community was altered by dietary Se-Met. Furthermore, 5 genera (Rhodobacter, Cloacibacterium, Bdellovibrio, Shinella, and Aeromonas) exhibited the largest variation in abundance among treatments. This study has demonstrated that excess dietary Se-Met inhibits growth, causes hispathological damage to the GI tract, and alters the composition of the microbial community in Oryzias latipes.

Dietary Seleno-l-Methionine Causes Alterations in Neurotransmitters, Ultrastructure of the Brain, and Behaviors in Zebrafish (Danio rerio).

Elevated concentrations of dietary selenium (Se) cause abnormalities and extirpation of fish inhabiting in Se-contaminated environments. However, its effect on fish behavior and the underlying mechanisms remain largely unknown. In this study, two-month-old zebrafish (Danio rerio) was fed seleno-l-methionine (Se-Met) at environmentally relevant concentrations (i.e., control (2.61), low (5.43), medium (12.16), and high (34.61) µg Se/g dry weight (dw), respectively, corresponding to the C, L, M, and H treatments) for 60 days. Targeted metabolomics, histopathological, and targeted transcriptional endpoints were compared to behavioral metrics to evaluate the effects of dietary exposure to Se-Met . The results showed that the levels of total Se and malondialdehyde in fish brains were increased in a dose-dependent pattern. Meanwhile, mitochondrial damages and decreased activities of the mitochondria respiratory chain complexes were observed in the neurons at the M and H treatments. In addition, dietary Se-Met affected neurotransmitters, metabolites, and transcripts of the genes associated with the dopamine, serotonin, gamma-aminobutyric acid, acetylcholine, and histamine signaling pathways in zebrafish brains at the H treatments. The total swimming distance and duration in the Novel Arm were lowered in fish from the H treatment. This study has demonstrated that dietary Se-Met affects the ultrastructure of the zebrafish brain, neurotransmitters, and associated fish behaviors and may help enhance adverse outcome pathways for neurotransmitter-behavior key events in zebrafish.

Anticancer drugs in the aquatic ecosystem: Environmental occurrence, ecotoxicological effect and risk assessment.

Anticancer drugs are a group of therapeutic agents used to enhance cell death in targeted cell types of neoplasia. Because of frequent use and eventual discharge, they have been often detected in wastewater from pharmaceutical factories and hospitals, domestic wastewater, and surface waters. The occurrence of these drugs in aquatic ecosystems and their effects on aquatic organisms have been poorly characterized. This review focuses on the global occurrence of major classes of anticancer drugs in water and sediments of freshwater ecosystems and their ecotoxicological effects at different biological levels. While the availability of data is fairly limited, concentrations of most anticancer drugs range from < 2 ng/L to 762 µg/L in receiving water, while levels in sediments and sludge vary from 0.25 to 42.5 µg/kg. Their detection frequencies were 58%, 52% (78%) and 59% in hospital wastewater, wastewater treatment plant effluents (influents) and surface water, respectively. Predicted log Kow values of vincristine, imatinib mesylate and tamoxifen are higher than 3 and have estimated half-lives>60 d in waters using quantitative structure-activity relationship models, indicating high potential for persistence and bioaccumulation. Based on a species sensitivity distribution evaluation of 9 compounds, crustaceans are most sensitive to anticancer drugs. The most hazardous compound is cisplatin which has a hazard concentration at the 5th percentile. For Daphnia magna, the acute toxicities of major classes of anticancer drugs are ranked as platinum complexes > endocrine therapy agents > antibiotics > antimetabolite agents > alkylating agents. Using hazard quotient analysis based primarily on the lowest observed effect concentrations (LOECs), cyclophosphamide, cisplatin, 5-fluorouracil, imatinib mesylate, bicalutamide, etoposide and paclitaxel have the highest hazard for aquatic organisms. Further research is needed to identify appropriate chronic endpoints for risk assessment thresholds as well as to better understand the mechanisms of action and the potential multigenerational toxicity, and trophic transfer in ecosystems.