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The world's 1.4 million lakes (>= 10 ha) provide many ecosystem services that are essential for human well-being; however, only if their health status is good. Here, we reviewed common lake health issues and classified them using a simple human health-based approach to outline that lakes are living systems that are in need of oxygen, clean water and a balanced energy and nutrient supply. The main reason for adopting some of the human health terminology for the lake health classification is to increase the awareness and understanding of global lake health issues. We show that lakes are exposed to various anthropogenic stressors which can result in many lake health issues, ranging from thermal, circulatory, respiratory, nutritional and metabolic issues to infections and poisoning. Of particular concern for human well-being is the widespread lake drying, which is a severe circulatory issue with many cascading effects on lake health. We estimated that similar to 115,000 lakes evaporate twice as much water as they gain from direct precipitation, making them vulnerable to potential drying if inflowing waters follow the drying trend, putting more than 153 million people at risk who live in close vicinity to those lakes. Where lake health issues remain untreated, essential ecosystem services will decline or even vanish, posing a threat to the well-being of millions of people. We recommend coordinated multisectoral and multidisciplinary prevention and treatment strategies, which need to include a follow-up of the progress and an assessment of the resilience of lakes to intensifying threats. Priority should be given to implementing sewage water treatment, mitigating climate change, counteracting introductions of non-native species to lakes and decreasing uncontrolled anthropogenic releases of chemicals into the hydro-, bio-, and atmosphere. Lakes around the world come in an array of sizes, shapes and colors, each telling a unique story of geological history and environment

Earth's lakes at northern latitudes are mostly ice-covered in winter. When lake water freezes, some organic matter dissolved in the water is excluded from the ice. We performed complementary field sampling and laboratory freeze-up experiments to explore how freeze-up may impact the partitioning and composition of dissolved organic matter (DOM) in boreal lakes. We found that 16.2 ± 4.7% of dissolved organic carbon (DOC) was retained in the overlying ice, 81.3 ± 5.7% of DOC was expelled to underlying unfrozen water, and 1.3 ± 0.7% was expelled as flocs. During ice formation, nitrogen (TDN, total dissolved nitrogen), ions (specific conductance), and oxidized and aromatic DOM were preferentially expelled to the underlying water column. The apparent retention factor DOCIce: DOCBefore decreased from clearwater to brownwater lakes, that is, with increasing allochthonous DOC lost from lake ice, indicating that DOM exclusion from the ice cover will become more prevalent as lakes experience browning.

Lakes are hotspots for global carbon cycling, yet few studies have explored how rainstorms alter the flux, composition, and bio-lability of dissolved organic matter (DOM) in inflowing rivers using high-frequency monitoring. We conducted extensive campaigns in the watershed of Lake Taihu and made daily observations for three years in its two largest inflowing tributaries, River Dapu and River Yincun. We found higher DOC, bio-labile DOC (BDOC), and specific UV absorbance (SUVA(254)) levels in the northwestern inflowing regions compared with the remaining lake regions. DOC and BDOC increased during rainstorms in River Dapu, and DOC declined due to local dilution and BDOC increased during rainstorms in River Yincun. We found that rainstorms resulted in increased DOM absorbance a(350), SUVA(254), and humification index (HIX) and enhanced percentages of humic-like fluorescent components, %polycyclic condensed aromatic and %polyphenolic compounds as revealed from ultrahigh-resolution mass spectrometry (FT-ICR MS), while spectral slope (S275-295) and the percentages of protein-like C1 and C3 declined during rainstorms compared with other seasons. This can be explained by a combined flushing of catchment soil organic matter and household effluents. The annual inflows of DOC and BDOC to Lake Taihu were 1.15 +/- 0.18 x 10(4) t C yr(-1) and 0.23 +/- 0.06 x 104 t C yr(-1) from River Dapu and 2.92 +/- 0.42 x 103 t C yr(-1) and 0.53 +/- 0.07 x 10(3) t C yr(-1) from River Yincun, respectively, and the fluxes of DOC and BDOC from both rivers increased during rainstorms. We found an elevated frequency of heavy rainfall and rainstorms in the lake watershed during the past six decades. We conclude that an elevated input of terrestrial organic-rich DOM with concurrent high aromaticity and high bio-lability from inflowing rivers is likely to occur in a future wetter climate.

The Eastern Route of the South-to-North Water Diversion Project (SNWDP-ER) is a large scale multi-decade infrastructure project aiming to divert substantial amounts of water (approximate to 45 billion m3 yr-1) to alleviate water shortage in comparatively arid regions of northern China. The project has ramifications for hydrological con-nectivity and biogeochemical cycling of dissolved organic matter (DOM) in regional lakes affected by the project. We carried out an extensive field sampling campaign along the SNWDP-ER in different hydrological seasons of 2018 and monthly observations in Lake Hongze and Lake Luoma from April 2018 to June 2021. We found the lakes connecting to the SNWDP-ER had higher mean DOC, specific UV absorbance, higher ratio of humic-like to protein-like fluorophores (Humic : Protein), and shallower spectral slope (S275-295) in the wet season compared to the wet-to-dry transition, and dry seasons. The southern lakes and Yangtze River had lower DOC concen-tration, bioavailable DOC (BDOC), and higher DOM aromaticity compared to the northern two downstream lakes. Ultrahigh-resolution mass spectrometry (FT-ICR MS) revealed higher relative abundance of CHO-containing and aromatic compounds in the Yangtze River and the southern three upstream lakes compared to the northern two lakes. The data from Lake Hongze and Lake Luoma, studied in different hydrological seasons, suggest that water delivery had high consistency in DOM composition and BDOC over the season. We conclude that positioning along the watercourse and seasonally variable hydrological conditions play an important role in influencing the DOM composition and bioavailability of key lakes connecting to the SNWDP-ER. Our results indicated that the water diversion project delivers water with low DOC concentration and higher aromaticity and thus is of higher quality since it has higher DOM removal potential during drinking water treatment.

Xin Yu,1,* Lijun Xu,2,* Yongqiang Zhou,3 Xiaorong Zhou,4 Lei Yang,2 Yan Zhou1 1Department of Orthodontics and Periodontology, Affiliated Nantong Stomatological Hospital of Nantong University, Nantong, People’s Republic of China; 2Department of Clinical Biobank & Institute of Oncology, Affiliated Hospital of Nantong University & Medical School of Nantong University, Nantong, People’s Republic of China; 3Department of Oral and Maxillofacial Surgery, Affiliated Nantong Stomatological Hospital of Nantong University, Nantong, People’s Republic of China; 4Department of Immunology, School of Medicine, Nantong University, Nantong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan Zhou, Affiliated Nantong Stomatological Hospital of Nantong University, Nantong, 226001, People’s Republic of China, Tel +86 513-89898899, Fax +86 513-89898890, Email ntyaner@126.com Lei Yang, Affiliated Hospital of Nantong University & Medical School of Nantong University, Nantong, 226001, People’s Republic of China, Tel +86 513-85052806, Email yang-lei@ntu.edu.cnBackground: Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy with a high mortality rate and poor prognosis. The exploration and understanding of biomarkers will help to further improve the diagnosis and treatment of OSCC.Methods: Tumor tissue samples from 319 OSCC patients were retrospectively collected, along with their clinical information. In combination with bioinformatics tools and multiplex immunohistochemistry (mIHC) analyses, we evaluated NUP62CL protein expression and its relationship to tumor-infiltrating immune cells (TIICs) and immune checkpoints in the tumor microenvironment (TME), as well as its association with clinical features and prognosis of OSCC.Results: We identified high-NUP62CL expression in OSCC tissues, and high-NUP62CL protein expression was associated with large tumor size, advanced clinical

Lakes receive and actively process terrestrial dissolved organic matter (DOM) and play an important role in the global carbon cycle. Urbanization results in elevated inputs of nonpoint-source DOM to headwater streams. Retention of water in lakes allows time for alteration and transformation of the chemical composition of DOM by microbes and UV radiation. Yet, it remains unclear how anthropogenic and natural drivers impact the composition and biolability of DOM in non-pristine lakes. We used optical spectroscopy, Fourier transform ion cyclotron mass spectrometry, stable isotopic measurements, and laboratory bioincubations to investigate the chemical composition and biolability of DOM across two large data sets of lakes associated with a large gradient of urbanization in lowland Eastern China, encompassing a total of 99 lakes. We found that increased urban land use, gross domestic products, and population density in the catchment were associated with an elevated trophic level index, higher chlorophyll-a, higher bacterial abundance, and a higher amount of organic carbon with proportionally higher contribution of aliphatic and peptide-like DOM fractions, which can be highly biolabile. Catchment areas, water depth, lake area: catchment area, gross primary productivity, delta O-18-H2O, and bacterial abundance, however, had comparatively little linkage with DOM composition and biolability. Urban land use is currently intensifying in many developing countries, and our results anticipate an increase in the level of biolabile aliphatic DOM from nonpoint sources and accelerated carbon cycling in lake ecosystems in such regions.

We compiled a nationwide dataset of carbon dioxide (CO2) efflux from 1405 measurements, and found that lakes, reservoirs, and rivers emit a total of 61.9 ± 55.3 TgC as CO2 each year, corresponding to 6.3% of the annual total national CO2 emission in 2020. Our analysis showed that the presence of anthropogenic disturbances in catchments strongly influences the emission of CO2 from these waters in the non-pristine areas, masking the catchment productivity effect on the emission of CO2. Our results highlight the need for adjusting climate change models for taking into account anthropogenic effects on CO2 emissions from inland waters.

Large reservoirs are hotspots for carbon emissions, and the continued input and decomposition of terrestrial dissolved organic matter (DOM) from upstream catchments is an important source of carbon emissions. Rainstorm events can cause a surge in DOM input; however, periodic sampling often fails to fully capture the impact of these discrete rainstorm events on carbon emissions. We conducted a set of frequent observations prior to and following a rainstorm event in a major reservoir Lake Qiandao (China; 580 km(2)) from June to July 2021 to investigate how rainstorms alter water chemistry and CO2 and CH4 emissions. We found that the mean CO2 efflux (FCO2) (13.2 +/- 9.3 mmol m(-)(2) d(-1)) and CH4 efflux (FCH4) (0.12 +/- 0.02 mmol m(-2) d(-1)) in the postrainstorm campaign were significantly higher than those in the prerainstorm campaign (-3.8 +/- 3.0 and +0.06 +/- 0.02 mmol m(-)(2) d(-)(1), respectively). FCO2 and FCH4 increased with increasing nitrogen and phosphorus levels, elevated DOM absorption (a(350)), specific UV absorbance SUVA(254), and terrestrial humic-like fluorescence. Furthermore, FCO2 and FCH4 decreased with increasing chlorophyll-a (Chl-a), dissolved oxygen (DO), and pH. A five-day laboratory anoxic bioincubation experiment further revealed a depletion of terrestrial-DOM concurrent with increased CO2 and CH4 production. We conclude that rainstorms boost the emission of CO2 and CH4 fueled by the surge and decomposition of fresh terrestrially derived biolabile DOM in this and likely many other reservoir's major inflowing river mouths.

Eutrophication affects bacterial communities by fueling them with nutrients and carbon sources. While the influence of physicochemical conditions on bacterial communities is well studied, little is known about how dissolved organic matter (DOM) quality affects bacterial interspecific interactions and community composition with increasing eutrophication. Here, we examined the relative importance of physicochemical conditions and chromophoric DOM (CDOM) composition for bacterial community variation across trophic gradients using 109 samples data collected in 33 lakes of the Yangtze-Huaihe River basin. We found a notable increase of bacterial abundance, elevated modularity of co-occurrence networks, and decreased habitat niche breadths from mesotrophic sites to hyper-eutrophic sites, suggesting changes in co-occurrence patterns with eutrophication. Variation partitioning revealed that the proportion purely explained by CDOM composition was higher at the moderate- and hyper-eutrophic sites than at the mesotrophic sites. Moreover, the module structures of the networks correlated significantly with CDOM composition at the eutrophic sites but not at the mesotrophic sites. The significant negative correlation between community-level habitat niche breadths and the intensities of the protein-like components at the moderate- and hyper-eutrophic sites indicates a strong association between biolabile protein-like compounds and habitat specialists in nutrient and substrate enriched lake systems. Our results suggest that consideration of DOM composition can strengthen the identification of links between environmental factors and bacterial community composition and interspecific interactions, especially under resource-rich conditions.

Large rivers are the main arteries for transportation of carbon to the ocean; yet, how hydrology and anthropogenic disturbances may change the composition and export of dissolved organic matter along large river continuums is largely unknown. The Yangtze River has a watershed area of 1.80 x 10(6) km(2). It originates from the Qinghai-Tibet Plateau and flows 6300 km eastward through the center of China. We collected samples (n = 271) along the river continuum and analyzed weekly samples at the most downstream situated gauging station in 2017-2018 and gathered long-term (2006-2018) water quality data. We found higher gross domestic product, population density, and urban and agricultural land use downstream than upstream of the Three Gorges Dam, coinciding with higher dissolved organic carbon (DOC), UV absorption (a(254)), specific ultraviolet absorbance (SUVA(254)), parallel factor analysis-derived C1-C5, aliphatic compounds, and lower a(250):a(365) and spectral slope (S275-295). Chemical oxygen demand, humic-like C1-C2 and C6, and protein-like C4 and C7 increased, while dissolved oxygen and ammonium decreased with increasing discharge at most of the sites studied, including the intensively monitored downstream site. The annual DOC fluxes were ca. 1.5-1.8 Tg yr(-1), and 12-18% was biodegradable in a 28-d bio-incubation. Our results highlight that urbanization and stormwater periods enhanced the export of both terrestrial organic-rich substances and household effluents from nearshore residential areas. Our study emphasizes the continued need to protect the Yangtze River watershed as increased organic carbon loading or altered composition and bio-lability may change the ecosystem function and carbon cycling.

Microbe-mediated transformation of dissolved organic matter (DOM) contributes substantially to the carbon dynamics and energy flow of aquatic ecosystems; yet, the temporal dynamics of bacterial communities in response to diverse DOM sources are scarcely known. Here, we supplied four distinct sources of DOM (algae-derived, macrophyte-derived, sewage-derived, and soil-derived) to the same bacterial community to track the effects of these DOM sources on the carbon processing and successional dynamics of bacterial communities. Although by the end of the incubation the proportion of bio-degraded DOM was significantly lower in the soil-derived DOM treatment than for the other sources, rapid initial metabolism of protein-like and aliphatic compounds and increasing aromaticity and humification degree of DOM during the incubation period were observed for all sources. The role of stochastic processes in governing the community assembly decreased substantially from 61.4% on the first day to 16.7% at the end of the incubation. Moreover, stronger deterministic selection and lower temporal turnover rate were observed for the soil-derived than the other DOM sources, indicating stronger environmental filtering by the more aromatic DOM. Significant correlations were also observed between the humification index (HIX) of DOM and bacterial community diversities, co-occurrence patterns, habitat niche breadths, and the contribution of deterministic ecological processes. In addition, we demonstrated that taxa with different abundance patterns all play crucial but different roles in the response to DOM variation. Our results indicate the importance of DOM aromaticity as a predictor of the outcome of different DOM sources on bacterial community dynamics.

Rainstorm events can flush large amounts of terrestrial organic-rich material into lakes that are used for drinking water. To date, few studies have been carried out to investigate how rainstorm events change the molecular composition, bio-lability, and flux of upstream-imported dissolved organic matter (DOM), which can impact the odor and taste of drinking water as well as the efficiency of wastewater treatment. We undertook high-frequency buoy monitoring and point sample collection (n = 495), during high, moderate, and low inflow discharge, in Lake Qiandao, a key drinking water source for about 10 million people. Data from two online fluorescent DOM sensors deployed and field samples collected at the river site, Jiekou, and the lake site, Xiaojinshan, showed that rainstorm events increased the specific UV absorbance (SUVA254), humification index (HIX), humic-like components (C1-C2), and FT-ICR MS derived condensed aromatic and polyphenolic compounds (p < 0.001) and decreased the spectral slope of DOM (S275–295), spectral slope ratio (SR), biological index (BIX), and highly bio-degradable peptide-like and aliphatic substances (p < 0.001). Our results suggest that rainstorm events enhanced the export to the lake of colored, hydrophobic, and aromatic DOM. Upstream-derived dissolved organic carbon (DOC) concentrations decreased (p < 0.001), while DOC bio-availability (BDOC) increased only slightly (p < 0.05) during rainstorm events. The loss rate of DOC in Lake Qiandao is 0.82 × 104 t C yr−1, of which 0.30 × 104 t C yr−1 is highly bio-labile, and higher occurrences of both ≥ 25 mm d − 1 and ≥ 50 mm d − 1 rainfall events are anticipated by linear fittings for this region in the future. The application of in situ fluorescence sensors provides an early warning of DOC surge incidents caused by rainstorm events and may be useful in advising drinking water treatment plant managers of changes in raw water DOM quality and treatability.

Chen Xu,1,2,* Rijin Song,1,* Pei Lu,1,* Jianchun Chen,2 Yongqiang Zhou,2 Gang Shen,2 Minjun Jiang,2 Wei Zhang1 1Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, People’s Republic of China; 2Department of Urology, Affiliated Wujiang Hospital of Nantong Univerisity, Suzhou 215200, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Zhang Email weizhangsir@126.comMinjun Jiang Email 463161688@qq.comIntroduction: Poor cell uptake and incomplete intracellular drug release are the two major challenges for polymeric prodrug-based drug delivery systems (PPDDSs) in cancer treatment.Methods: Herein, a PPDDS with pH-induced surface charge-reversal and reactive oxygen species (ROS) amplification for ROS-triggered self-accelerating drug release was developed, which was formed by encapsulating a ROS generation agent (vitamin K3 (VK3)) in pH/ROS dual-sensitive polymetric prodrug (PEG-b-P(LL-g-TK-PTX)-(LL-g-DMA)) based micelle nanoparticles (denoted as PVD-NPs).Results: The surface charge of the PVD-NPs can change from negative to positive for enhanced cell uptake in response to tumor extracellular acidity pH. After internalization by cancer cells, PVD-NPs demonstrate dual drug release in response to intracellular ROS-rich conditions. In addition, the released VK3 can produce ROS under the catalysis by NAD(P)H:quinone oxidoreductase-1, which facilitates tumor-specific ROS amplification and drug release selectively in cancer cells to enhance chemotherapy.Conclusion: Both in vitro and in vivo experiments demonstrated that the PVD-NPs showed significant antitumor activity in human prostate cancer.Keywords: charge-reversal, dual-responsive, ROS generation, cancer specific chemotherapy