Antibiotics and antibiotic resistance genes in global lakes:A review and meta-analysis

Lakes are an important source of freshwater, containing nearly 90% of the liquid surface fresh water worldwide. Long retention times in lakes mean pollutants from discharges slowly circulate around the lakes and may lead to high ecological risk for ecosystem and human health. In recent decades, antibiotics and antibiotic resistance genes (ARGs) have been regarded as emerging pollutants. The occurrence and distribution of antibiotics and ARGs in global freshwater lakes are summarized to show the pollution level of antibiotics and ARGs and to identify some of the potential risks to ecosystem and human health. Fifty-seven antibiotics were reported at least once in the studied lakes. Our meta-analysis shows that sulfamethoxazole, sulfamerazine, sulfameter, tetracycline, oxytetracycline, erythromycin, and roxithromycin were found at high concentrations in both lake water and lake sediment. There is no significant difference in the concentration of sulfonamides in lake water from China and that from other countries worldwide; however, there was a significant difference in quinolones. Erythromycin had the lowest predicted hazardous concentration for 5% of the species (HC5) and the highest ecological risk in lakes. There was no significant difference in the concentration of sulfonamide resistance genes (sul1 and sul2) in lake water and river water. There is surprisingly limited research on the role of aquatic biota in propagation of ARGs in freshwater lakes. As an environment that is susceptible to cumulative build-up of pollutants, lakes provide an important environment to study the fate of antibiotics and transport of ARGs with a broad range of niches including bacterial community, aquatic plants and animals

Purification and Characterization of a New Alginate Lyase from Marine Bacterium Vibrio sp. SY08

Unsaturated alginate disaccharides (UADs), enzymatically derived from the degradation of alginate polymers, are considered powerful antioxidants. In this study, a new high UAD-producing alginate lyase, AlySY08, has been purified from the marine bacterium Vibrio sp. SY08. AlySY08, with a molecular weight of about 33 kDa and a specific activity of 1070.2 U/mg, showed the highest activity at 40 °C in phosphate buffer at pH 7.6. The enzyme was stable over a broad pH range (6.0–9.0) and retained about 75% activity after incubation at 40 °C for 2 h. Moreover, the enzyme was active in the absence of salt ions and its activity was enhanced by the addition of NaCl and KCl. AlySY08 resulted in an endo-type alginate lyase that degrades both polyM and polyG blocks, yielding UADs as the main product (81.4% of total products). All these features made AlySY08 a promising candidate for industrial applications in the production of antioxidants from alginate polysaccharides

Extracellular Vesicle Directed Exogenous Ion Channel Transport for Precise Manipulation of Biological Events

A larger number of human diseases are related to dysregulation or loss of cellular functions. Effective restoration of the missing or defective cellular functions is highly desirable for fundamental research and therapeutic applications. Inspired by the fantastic feature of cell-derived extracellular vesicles (EVs) that can transport various bioactive molecules between cells, herein, we developed a simple and efficient strategy based on EVs for transferring ion channels to recipient cells, thereby conferring specific biological function to the target cells and regulating the biological events. The constructed channel rhodopsin 2 (ChR2)-loaded EV (EV-ChR2) system can mediate the anchor of light-responsive ion channel ChR2 on the plasma membrane of recipient cells through membrane fusion. Upon blue light irradiation, the ion channel ChR2 was activated and opened, thus permitting the rapid flux of cation ions (e.g., calcium ion) across the plasma membrane of recipient cells. Moreover, the increased Ca²⁺ in the cytosol could effectively activate Ca²⁺-dependent transcription factors, further triggering the calcium signaling pathway. This strategy can be extended to modulate other cellular processes and provides a novel insight on the manipulation of biological events

Synthesis of Core-shell Lanthanide-doped Upconversion Nanocrystals for Cellular Applications

Lanthanide-doped upconversion nanocrystals (UCNs) have attracted much attention in recent years based on their promising and controllable optical properties, which allow for the absorption of near-infrared (NIR) light and can subsequently convert it into multiplexed emissions that span over a broad range of regions from the UV to the visible to the NIR. This article presents detailed experimental procedures for high-temperature co-precipitation synthesis of core-shell UCNs that incorporate different lanthanide ions into nanocrystals for efficiently converting deep-tissue penetrable NIR excitation (808 nm) into a strong blue emission at 480 nm. By controlling the surface modification with biocompatible polymer (polyacrylic acid, PAA), the as-prepared UCNs acquires great solubility in buffer solutions. The hydrophilic nanocrystals are further functionalized with specific ligands (dibenzyl cyclooctyne, DBCO) for localization on the cell membrane. Upon NIR light (808 nm) irradiation, the upconverted blue emission can effectively activate the light-gated channel protein on the cell membrane and specifically regulate the cation (e.g., Ca2+) influx in the cytoplasm. This protocol provides a feasible methodology for the synthesis of core-shell lanthanide-doped UCNs and subsequent biocompatible surface modification for further cellular applications.Published versio

Nighttime Sleep Awakening Frequency and Its Consistency Predict Future Academic Performance in College Students

Although the relationship between sleep and academic performance has been extensively examined, how sleep predicts future academic performance (e.g., 2–3 years) remains to be further investigated. Using wearable smartwatches and a self-report questionnaire, we tracked sleep activities of 45 college students over a period of approximately half a month to see whether their sleep activities predicted their academic performance, which was estimated by grade point average (GPA). Results showed that both nighttime sleep awakening frequency and its consistency in the tracking period were not significantly correlated with the GPA for the courses taken in the sleep tracking semester (current GPA). However, both nighttime sleep awakening frequency and its consistency inversely predicted the GPA for the rest of the courses taken after that semester (future GPA). Moreover, students with more difficulty staying awake throughout the day obtained lower current and future GPAs, and students with higher inconsistency of sleep quality obtained lower future GPA. Together, these findings highlight the importance of nighttime sleep awakening frequency and consistency in predicting future academic performance, and emphasize the necessity of assessing the consistency of sleep measures in future studies

Near-infrared light-mediated rare-earth nanocrystals: recent advances in improving photon conversion and alleviating the thermal effect

With the rapid development of nanotechnology, the unique rare-earth lanthanide-doped upconversion nanocrystals (UCNs), which can convert tissue-penetrable near-infrared (NIR) photonic irradiation into ultraviolet, visible, and NIR emissions, have a significant potential in bioimaging, diagnosis, and therapy, as well as in photovoltaic systems and optical data storage. Despite the promising achievements made in the past decade, critical challenges associated with low upconversion efficiencies and the overheating effect induced by NIR laser-irradiation still remain in the biomedical fields. In high demand are more well-defined material design and unique structural modifications that are capable of solving these technical concerns and promoting such promising NIR light-mediated upconversion nanocrystals for their further application in the medical sciences. Recent advances in upconversion nanomaterials have witnessed a tremendous development towards enhancing their photon conversion efficiency, which provides great opportunities in expanding the potential of the UCNs in bioimaging diagnosis and anticancer therapy. Hence, this review is mainly focused on summarizing the fundamental principles and strategies that improve upconversion luminescence and the approaches to reduce the local thermal effect on the basis of a rational design of UCNs. In addition, the future perspectives in the development of UCNs for biomedical applications are also proposed.Published versio

Enhanced cellular ablation by attenuating hypoxia status and reprogramming tumor-associated macrophages via NIR light-responsive upconversion nanocrystals

Near-infrared (NIR) light-mediated photodynamic therapy (PDT), especially based on lanthanide-doped upconversion nanocrystals (UCNs), have been extensively investigated as a promising strategy for effective cellular ablation owing to their unique optical properties to convert NIR light excitation into multiple short-wavelength emissions. Despite the deep tissue penetration of NIR light in living systems, the therapeutic efficiency is greatly restricted by insufficient oxygen supply in hypoxic tumor microenvironment. Moreover, the coexistent tumor-associated macrophages (TAMs) play critical roles in tumor recurrence during the post-PDT period. Herein, we developed a unique photosensitizer-loaded UCNs nanoconjugate (PUN) by integrating manganese dioxide (MnO2) nanosheets and hyaluronic acid (HA) biopolymer to improve NIR light-mediated PDT efficacy through attenuating hypoxia status and synergistically reprogramming TAMs populations. After the reaction with overproduced H2O2 in acidic tumor microenvironment, the MnO2 nanosheets were degraded for the production of massive oxygen to greatly enhance the oxygen-dependent PDT efficiency upon 808 nm NIR light irradiation. More importantly, the bioinspired polymer HA could effectively reprogram the polarization of pro-tumor M2-type TAMs to anti-tumor M1-type macrophages to prevent tumor relapse after PDT treatment. Such promising results provided the great opportunities to achieve enhanced cellular ablation upon NIR light-mediated PDT treatment by attenuating hypoxic tumor microenvironment, and thus facilitated the rational design of new generations of nanoplatforms toward immunotherapy to inhibit tumor recurrence during post-PDT period

The Long Non-Coding RNA RHPN1-AS1 Promotes Uveal Melanoma Progression

Increasing evidence suggests that aberrant long non-coding RNAs (lncRNAs) are significantly correlated with the pathogenesis, development and metastasis of cancers. RHPN1 antisense RNA 1 (RHPN1-AS1) is a 2030-bp transcript originating from human chromosome 8q24. However, the role of RHPN1-AS1 in uveal melanoma (UM) remains to be clarified. In this study, we aimed to elucidate the molecular function of RHPN1-AS1 in UM. The RNA levels of RHPN1-AS1 in UM cell lines were examined using the quantitative real-time polymerase chain reaction (qRT-PCR). Short interfering RNAs (siRNAs) were designed to quench RHPN1-AS1 expression, and UM cells stably expressing short hairpin (sh) RHPN1-AS1 were established. Next, the cell proliferation and migration abilities were determined using a colony formation assay and a transwell migration/invasion assay. A tumor xenograft model in nude mice was established to confirm the function of RHPN1-AS1 in vivo. RHPN1-AS1 was significantly upregulated in a number of UM cell lines compared with the normal human retinal pigment epithelium (RPE) cell line. RHPN1-AS1 knockdown significantly inhibited UM cell proliferation and migration in vitro and in vivo. Our data suggest that RHPN1-AS1 could be an oncoRNA in UM, which may serve as a candidate prognostic biomarker and target for new therapies in malignant UM