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Abstract Circulating tumor cells (CTCs) shed from primary tumors must overcome the cytotoxicity of immune cells, particularly natural killer (NK) cells, to cause metastasis. The tumor microenvironment (TME) protects tumor cells from the cytotoxicity of immune cells, which is partially executed by cancer‐associated mesenchymal stromal cells (MSCs). However, the mechanisms by which MSCs influence the NK resistance of CTCs remain poorly understood. This study demonstrates that MSCs enhance the NK resistance of cancer cells in a gap junction‐dependent manner, thereby promoting the survival and metastatic seeding of CTCs in immunocompromised mice. Tumor cells crosstalk with MSCs through an intercellular cGAS‐cGAMP‐STING signaling loop, leading to increased production of interferon‐β (IFNβ) by MSCs. IFNβ reversely enhances the type I IFN (IFN‐I) signaling in tumor cells and hence the expression of human leukocyte antigen class I (HLA‐I) on the cell surface, protecting the tumor cells from NK cytotoxicity. Disruption of this loop reverses NK sensitivity in tumor cells and decreases tumor metastasis. Moreover, there are positive correlations between IFN‐I signaling, HLA‐I expression, and NK tolerance in human tumor samples. Thus, the NK‐resistant signaling loop between tumor cells and MSCs may serve as a novel therapeutic target.

The development of water‐soluble aggregation‐induced emission luminogens (AIEgens) emitting in the near‐infrared (NIR) window holds promise for efficient biomedical applications. Nevertheless, synthesizing water‐soluble counterparts of NIR AIEgens presents difficulties due to their intrinsic hydrophobic properties. To address this issue, researchers have developed various molecular design strategies to improve the water solubility of NIR AIEgens. The integration of hydrophilic groups and targeting moieties is a crucial aspect of achieving precise phototheranostics. Here, diverse approaches to attain water‐soluble NIR AIEgens for biomedical applications are presented, and three commonly used strategies that involve decorating NIR AIEgens with positively or negatively charged groups, hydrophilic chains, and bioactive moieties are elaborated. These rational design strategies are believed to provide solutions for enhancing the water solubility and biological performance of NIR AIEgens in a single action. The remaining challenges and opportunities in this field are also discussed. The aim is to provide new insights into the design of water‐soluble NIR AIEgens and inspire more researchers to make significant contributions to this promising research area.

Abstract The development of optical organic nanoparticles (NPs) is desirable and widely studied. However, most organic dyes are water-insoluble such that the derivatization and modification of these dyes are difficult. Herein, we demonstrated a simple platform for the fabrication of organic NPs designed with emissive properties by loading ten different organic dyes (molar masses of 479.1–1081.7 g/mol) into water-soluble polymer nanosponges composed of poly(styrene-alt-maleic acid) (PSMA). The result showed a substantial improvement over the loading of commercial dyes (3.7–50% loading) while preventing their spontaneous aggregation in aqueous solutions. This packaging strategy includes our newly synthesized organic dyes (> 85% loading) designed for OPVs (242), DSSCs (YI-1, YI-3, YI-8), and OLEDs (ADF-1–3, and DTDPTID) applications. These low-cytotoxicity organic NPs exhibited tunable fluorescence from visible to near-infrared (NIR) emission for cellular imaging and biological tracking in vivo. Moreover, PSMA NPs loaded with designed NIR-dyes were fabricated, and photodynamic therapy with these dye-loaded PSMA NPs for the photolysis of cancer cells was achieved when coupled with 808 nm laser excitation. Indeed, our work demonstrates a facile approach for increasing the biocompatibility and stability of organic dyes by loading them into water-soluble polymer-based carriers, providing a new perspective of organic optoelectronic materials in biomedical theranostic applications.

Summary: In the late 19th century, scientists began to study the photophysical differences between chromophores in the solution and aggregate states, which breed the recognition of the prototypical processes of aggregation-caused quenching and aggregation-induced emission (AIE). In particular, the conceptual discovery of the AIE phenomenon has spawned the innovation of luminogenic materials with high emission in the aggregate state based on their unique working principle termed the restriction of intramolecular motion. As AIE luminogens have been practically fabricated into AIE dots for bioimaging, further improvement of their brightness is needed although this is technically challenging. In this review, we surveyed the recent advances in strategic molecular engineering of highly emissive AIE dots, including nanoscale crystallization and matrix-assisted rigidification. We hope that this timely summary can deepen the understanding about the root cause of the high emission of AIE dots and provide inspiration to the rational design of functional aggregates.

Abstract Efficient red emissive carbon dots (CDs) in aqueous solutions are very scarce for high performance bioimaging applications. In this work, we report a one-step solvothermal treatment to synthesize pure red emissive CDs (FA-CDs) from citric acid and urea in formic acid without complicated purification procedures. Photoluminescence quantum yield (PLQY) of 43.4% was observed in their dimethyl sulfoxide solutions. High PLQY up to 21.9% in aqueous solutions was achieved in their bovine serum albumin (BSA) composites (FA-CDs@BSA) with significantly enhanced multi-photon fluorescence. The strong surface electron-withdrawing structure of FA-CDs caused by the high content of C = O groups contributes for their pure red emission. Owing to the significantly enhanced single and multi-photon red fluorescence and enlarged particle sizes after composing with BSA, in vivo tumor imaging and two-photon fluorescence imaging of blood vessels in mouse ear have been realized via intravenous injection of FA-CDs@BSA aqueous solutions.

Conventional techniques for in vitro cancer drug screening require labor-intensive formalin fixation, paraffin embedding, and dye staining of tumor tissues at fixed endpoints. This way of assessment discards the valuable pharmacodynamic information in live cells over time. Here, we found endogenous lipofuscin-like autofluorescence acutely accumulated in the cell death process. Its unique red autofluorescence could report the apoptosis without labeling and continuously monitor the treatment responses in 3D tumor-culture models. Lifetime imaging of lipofuscin-like red autofluorescence could further distinguish necrosis from apoptosis of cells. Moreover, this endogenous fluorescent marker could visualize the apoptosis in live zebrafish embryos during development. Overall, this study validates that lipofuscin-like autofluorophore is a generic cell death marker. Its characteristic autofluorescence could label-free predict the efficacy of anti-cancer drugs in organoids or animal models.

Objective: With the rapid growth of high-speed deep-tissue imaging in biomedical research, there is an urgent need to develop a robust and effective denoising method to retain morphological features for further texture analysis and segmentation. Conventional denoising filters and models can easily suppress the perturbative noise in high-contrast images; however, for low photon budget multiphoton images, a high detector gain will not only boost the signals but also bring significant background noise. In such a stochastic resonance imaging regime, subthreshold signals may be detectable with the help of noise, meaning that a denoising filter capable of removing noise without sacrificing important cellular features, such as cell boundaries, is desirable. Method: We propose a convolutional neural network-based denoising autoencoder method — a fully convolutional deep denoising autoencoder (DDAE) — to improve the quality of three-photon fluorescence (3PF) and third-harmonic generation (THG) microscopy images. Results: The average of 200 acquired images of a given location served as the low-noise answer for the DDAE training. Compared with other conventional denoising methods, our DDAE model shows a better signal-to-noise ratio (28.86 and 21.66 for 3PF and THG, respectively), structural similarity (0.89 and 0.70 for 3PF and THG, respectively), and preservation of the nuclear or cellular boundaries (F1-score of 0.662 and 0.736 for 3PF and THG, respectively). It shows that DDAE is a better trade-off approach between structural similarity and preserving signal regions. Conclusions: The results of this study validate the effectiveness of the DDAE system in boundary-preserved image denoising. Clinical Impact: The proposed deep denoising system can enhance the quality of microscopic images and effectively support clinical evaluation and assessment.

Abstract Carbon dots (CDs) have attracted significant interest as one of the most emerging photoluminescence (PL) nanomaterials. However, the realization of CDs with dominant near‐infrared (NIR) absorption/emission peaks in aqueous solution remains a great challenge. Herein, CDs with both main NIR absorption bands at 720 nm and NIR emission bands at 745 nm in an aqueous solution are fabricated for the first time by fusing large conjugated perylene derivatives under solvothermal treatment. With post‐surface engineering, the polyethyleneimine modified CDs (PEI‐CDs) exhibit enhanced PL quantum yields (PLQY) up to 8.3% and 18.8% in bovine serum albumin aqueous and DMF solutions, which is the highest PLQY of CDs in NIR region under NIR excitation. Density functional theory calculations support the strategy of fusing large conjugated perylene derivatives to achieve NIR emissions from CDs. Compared to the commercial NIR dye Indocyanine green, PEI‐CDs exhibit excellent photostability and much lower cost. Furthermore, the obtained PEI‐CDs illustrate the advantages of remarkable two‐photon NIR angiography and in vivo NIR fluorescence bioimaging. This work demonstrates a promising strategy of fusing large conjugated molecules for preparing CDs with strong NIR absorption/emission to promote their bioimaging applications.

Remarkable advancement has been made in the application of nanoparticles (NPs) for cancer therapy. Although NPs have been favorably delivered into tumors by taking advantage of the enhanced permeation and retention (EPR) effect, several physiological barriers present within tumors tend to restrict the diffusion of NPs. To overcome this, one of the strategies is to design NPs that can reach lower size limits to improve tumor penetration without being rapidly cleared out by the body. Several attempts have been made to achieve this, such as selecting appropriate nanocarriers and modifying surface properties. While many studies focus on the optimal design of NPs, the influence of mouse strains on the effectiveness of NPs remains unknown. Therefore, this study aimed to assess whether the vascular permeability of NPs near the lower size limit differs among mouse strains. We found that the vessel permeability of dextran NPs was size-dependent and dextran NPs with a size below 15 nm exhibited leakage from postcapillary venules in all strains. Most importantly, the leakage rate of 8-nm fluorescein isothiocyanate dextran was significantly higher in the BALB/c mouse strain than in other strains. This strain dependence was not observed in slightly positive TRITC-dextran with comparable sizes. Our results indicate that the influence on mouse strains needs to be taken into account for the evaluation of NPs near the lower size limit.

Macrophages play pivotal roles in the maintenance of tissue homeostasis. However, the reactivation of macrophages toward proinflammatory states correlates with a plethora of inflammatory diseases, including atherosclerosis, obesity, neurodegeneration, and bone marrow (BM) failure syndromes. The lack of methods to reveal macrophage phenotype and function in vivo impedes the translational research of these diseases. Here, we found that proinflammatory macrophages accumulate intracellular lipid droplets (LDs) relative to resting or noninflammatory macrophages both in vitro and in vivo, indicating that LD accumulation serves as a structural biomarker for macrophage phenotyping. To realize the staining and imaging of macrophage LDs in vivo, we developed a fluorescent fatty acid analog-loaded poly(lactic-co-glycolic acid) nanoparticle to label macrophages in mice with high efficiency and specificity. Using these novel nanoparticles, we achieved in situ functional identification of single macrophages in BM, liver, lung, and adipose tissues under conditions of acute or chronic inflammation. Moreover, with this intravital imaging platform, we further realized in vivo phenotyping of individual macrophages in the calvarial BM of mice under systemic inflammation. In conclusion, we established an efficient in vivo LD labeling and imaging system for single macrophage phenotyping, which will aid in the development of diagnostics and therapeutic monitoring. Moreover, this method also provides new avenues for the study of lipid trafficking and dynamics in vivo.

The Hippo signaling pathway is a kinase cascade that plays an important role in organ size control. As the main effectors of the Hippo pathway, transcription coactivators Yap1/Wwtr1 are regulated by the upstream kinase Stk3. Recent studies in mammals have implicated the Hippo pathway in kidney development and kidney diseases. To further illustrate its roles in vertebrate kidney, we generated a series of zebrafish mutants targeting stk3, yap1 and wwtr1 genes. The stk3−/− mutant exhibited edema, formation of glomerular cysts and pronephric tubule dilation during the larval stage. Interestingly, disruption of wwtr1, but not yap1, significantly alleviated the renal phenotypes of the stk3−/− mutant, and overexpression of Wwtr1 with the CMV promoter also induced pronephric phenotypes, similar to those of the stk3−/− mutant, during larval stage. Notably, adult fish with Wwtr1 overexpression developed phenotypes similar to those of human polycystic kidney disease (PKD). Overall, our analyses revealed roles of Stk3 and Wwtr1 in renal cyst formation. Using a pharmacological approach, we further demonstrated that Stk3-deficient zebrafish could serve as a PKD model for drug development.

Abstract The encapsulation and/or surface modification can stabilize and protect the phosphorescence bio‐probes but impede their intravenous delivery across biological barriers. Here, a new class of biocompatible rhenium (ReI) diimine carbonyl complexes is developed, which can efficaciously permeate normal vessel walls and then functionalize the extravascular collagen matrixes as in situ oxygen sensor. Without protective agents, ReI‐diimine complex already exhibits excellent emission yield (34%, λem = 583 nm) and large two‐photon absorption cross‐sections (σ2 = 300 GM @ 800 nm) in water (pH 7.4). After extravasation, remarkably, the collagen‐bound probes further enhanced their excitation efficiency by increasing the deoxygenated lifetime from 4.0 to 7.5 µs, paving a way to visualize tumor hypoxia and tissue ischemia in vivo. The post‐extravasation functionalization of extracellular matrixes demonstrates a new methodology for biomaterial‐empowered phosphorescence sensing and imaging.

A considerable amount of early breast tumors grown at a depth over 2 cm in breast tissues. With high near-infrared absorption of iron-platinum (FePt) nanoparticles, we achieved few centimeters deep photoacoustic (PA) imaging for the diagnosis of breast tumors. The imaging depth can extend over 5 cm in chicken breast tissues at the low laser energy density of 20 mJ/cm2 (≤ ANSI safety limit). After anti-VEGFR conjugation and the tail-vein injection, we validated their targeting on tumor sites by the confocal microscopy and PA imaging. Using a home-made whole-body in vivo PA imaging, we found that the nanoparticles were rapidly cleared away from the site of the tumor and majorly metabolized through the liver. These results validated the clinical potential of the FePt nanoparticles in the low-toxicity PA theragnosis of early breast cancer and showed the capacity of our whole-body PA imaging technique on monitoring the dynamic biodistribution of nanoparticles in the living body.

Photodynamic therapy (PDT) provides a potential therapeutic approach for killing malignant cell/solid tumors, but currently approved photosensitizers (PSs) are generally excited by visible light, limiting the penetration depth in tissues. It is necessary to develop a near-infrared (NIR) responsive photodynamic platform, providing maximum tissue penetration. Here, we present a gold nanopeanut platform exhibiting dual functions of NIR PDT and two-photon luminescence imaging. The nanopeanut with a size less than 100 nm exhibits two distinct NIR surface plasmon absorption bands at approximately 1110 and 1300 nm. To perform PDT, we conjugated commercial toluidine blue O (TBO) PS on the surface of the nanopeanuts. With spectral overlap, the 1230-nm femtosecond Cr: forsterite laser can excite the surface plasmons of nanopeanuts, transfer energy to TBO, and generate singlet oxygen to kill cells. Moreover, the plasmon resonance-enhanced two-photon luminescence of nanopeanuts can be used to map their delivery in vivo. These results demonstrate that the PS-conjugated gold nanopeanut is an effective theranostic system for NIR PDT.

Climate change and population growth are increasing the frequency of flooding and drought, resulting in conflict over water resources. Social impact assessments (SIA) of the allocation and management of water resources provide a way of reducing and resolving such conflicts. This article first explores the nature of SIA for water environments through an inductive analysis of the cases mentioned in more than 30 papers. Next, it identifies important advantages of SIA over integrated water resources management (IWRM) practices and indicates that while IWRM solves water-related issues to improve social well-being, it cannot entirely grasp the overall social impact of planned interventions. Following this, it analyzes the water environment governance structures in Taiwan, using questionnaire responses from water environment management professionals to discuss challenges of effectively implementing water environment SIA. The questionnaire covers 26 detailed tasks of SIA advocated by Vanclay et al. This research is the first to have evaluated the difficulty of the tasks. The survey results can be used as a reference for the implementation of SIA in other regions. The results show that (1) the water environment SIA is indeed necessary; (2) Taiwan’s water environment professionals need to improve from their current lack of understanding of SIA; (3) it is difficult to implement the water environment SIA; (4) it is necessary for SIA to clarify and integrate the authorities and responsibilities of relevant government departments; (5) the professionals believe the myth of quantification of SIA; and (6) water environment SIA must be integrated with the existing IWRM. Finally, we emphasize the need to integrate SIA and IWRM in a mutually complementary way, and illuminate the need for an integrated SIA framework for water environment management.

With improvements in data quality and technology, the statistical downscaling data of General Circulation Models (GCMs) for climate change impact assessment have been refined from monthly data to daily data, which has greatly promoted the data application level. However, there are differences between GCM downscaling daily data and rainfall station data. If GCM data are directly used for hydrology and water resources assessment, the differences in total amount and rainfall intensity will be revealed and may affect the estimates of the total amount of water resources and water supply capacity. This research proposes a two-stage bias correction method for GCM data and establishes a mechanism for converting grid data to station data. Five GCMs were selected from 33 GCMs, which were ranked by rainfall simulation performance from a baseline period in Taiwan. The watershed of the Zengwen Reservoir in southern Taiwan was selected as the study area for comparison of the three different bias correction methods. The results reveal that the method with the wet-day threshold optimized by objective function with observation rainfall wet days had the best result. Error was greatly reduced in the hydrology model simulation with two-stage bias correction. The results show that the two-stage bias correction method proposed in this study can be used as an advanced method of data pre-processing in climate change impact assessment, which could improve the quality and broaden the extent of GCM daily data. Additionally, GCM ranking can be used by researchers in climate change assessment to understand the suitability of each GCM in Taiwan.

Abstract In this letter, we treat a rod-shaped virus as a free homogenous nanorod and identify its confined acoustic vibration modes that can cause strong resonant microwave absorption through electric dipolar excitation with a core-shell charge distribution. They are found to be the n = 4N-2 modes of the longitudinal modes of the nanorods, where N is an integer starting from 1 and n is the mode order quantum number. This study was confirmed by measuring the microwave absorption spectra of white spot syndrome virus (WSSV), which is a rod-shaped virus. This is also the first study to identify the “dipolar-like” mode in a rod-shaped nano-object. Our study is not only an important step to achieve rapid and sensitive detection of rod-shaped viruses based on their microwave spectroscopic features and a non-contact method to measure the Young’s modulus of rod-shaped viruses, but also is critical to formulate an efficient epidemic prevention strategy to deactivate viruses with the structure-resonant microwaves.

The evaluation of wildlife tourism benefits is one of the key considerations in planning proper management measures and promoting mutually beneficial coexistence of wildlife tourism and wildlife resources. This key consideration is also important for Black-Faced Spoonbills (Platalea minor), which are at risk of extinction. To understand the value of Black-Faced Spoonbill wildlife tourism, this study adopted choice experiments to investigate tourists’ preferences and willingness to pay (WTP) for recreational environmental resources in the Black-Faced Spoonbill Reserve in Taiwan. The total WTP price indicates that the promotion of tourism activities in the Black Faced Spoonbill Reserve and the proper maintenance of tourist and recreation facilities will increase the WTP value for tourists, increases the opportunity costs of using the Reserve’s land for other purposes, and reduces the possibility of developing the Reserve.Keywords: Biodiversity; recreational quality; development; bird-watching.

Macrophages are an important component of host defense and inflammation and play a pivotal role in immune regulation, tissue remodeling, and metabolic regulation. Since macrophages are ubiquitous in human bodies and have versatile physiological functions, they are involved in virtually every disease, including cancer, diabetes, multiple sclerosis, and atherosclerosis. Molecular biological and histological methods have provided critical information on macrophage biology. However, many in vivo dynamic behaviors of macrophages are poorly understood and yet to be discovered. A better understanding of macrophage functions and dynamics in pathogenesis will open new opportunities for better diagnosis, prognostic assessment, and therapeutic intervention. In this article, we will review the advances in macrophage tracking and analysis with in vivo optical imaging in the context of different diseases. Moreover, this review will cover the challenges and solutions for optical imaging techniques during macrophage intravital imaging.

Osteocytes are the most abundant cell in the bone, and have multiple functions including mechanosensing and regulation of bone remodeling activities. Since osteocytes are embedded in the bone matrix, their inaccessibility makes in vivo studies problematic. Therefore, a non-invasive technique with high spatial resolution is desired. The purpose of this study is to investigate the use of third harmonic generation (THG) microscopy as a noninvasive technique for high-resolution imaging of the lacunar-canalicular network (LCN) in live mice. By performing THG imaging in combination with two- and three-photon fluorescence microscopy, we show that THG signal is produced from the bone-interstitial fluid boundary of the lacuna, while the interstitial fluid-osteocyte cell boundary shows a weaker THG signal. Canaliculi are also readily visualized by THG imaging, with canaliculi oriented at small angles relative to the optical axis exhibiting stronger signal intensity compared to those oriented perpendicular to the optical axis (parallel to the image plane). By measuring forward- versus epi-detected THG signals in thinned versus thick bone samples ex vivo, we found that the epi-collected THG from the LCN of intact bone contains a superposition of backward-directed and backscattered forward-THG. As an example of a biological application, THG was used as a label-free imaging technique to study structural variations in the LCN of live mice deficient in both histone deacetylase 4 and 5 (HDAC4, HDAC5). Three-dimensional analyses were performed and revealed statistically significant differences between the HDAC4/5 double knockout and wild type mice in the number of osteocytes per volume and the number of canaliculi per lacunar surface area. These changes in osteocyte density and dendritic projections occurred without differences in lacunar size. This study demonstrates that THG microscopy imaging of the LCN in live mice enables quantitative analysis of osteocytes in animal models without the use of dyes or physical sectioning.

Extreme uneven spatial and temporal distributions of rainfall pose the risk of water shortage to the industries in Taiwan, particularly during dry seasons, which may be worsen under climate change. This study aims to develop adaptation actions for an industrial company to reduce the risk of droughts. The Formosa Plastics Corporation (FPC) in Chuoshui River watershed is selected as a study case and an integrated risk assessment tool of water resources TaiWAP is used. The water shortage of FPC is mainly in the dry seasons because the water rights of public and agricultural uses are prioritized over industrial use. The considered adaptation options including water reuse, a desalination plant, smart agricultural water management, and rainwater harvesting. The results show that the waste-water reuse and sea-water desalination are the most effective adaptation options, which reduces the water shortage risks 33–44% per day in the return period of ten years. The results are generalized for the reference of other studies. The risk assessment and adaptation measure identification of the company require regional information. Moreover, some adaptation measures that the company implements help reduce the water shortage of the region and are consequently beneficial to the company, e.g., smart agricultural water management.

Water resources management has become more challenging in Taiwan due to rapid socio-economic development and the complications of climate change. This study developed a systematic procedure for assessing water resources vulnerability and resilience with an integrated tool, TaiWAP, including climate change scenarios, a weather generator, a hydrological model, and system dynamic models. Five assessment indicators, including two for vulnerability, two for resilience, and one for availability were used to quantify changes in water resources and improvements after implementing adaption measures. Each indicator was presented with 3 grades, namely low, medium, and high. Water resources vulnerability and resilience for Tainan City in southern Taiwan were evaluated. Insufficient water supply facilities capacity is the major weakness causing low resilience. Water resources allocation flexibility is limited by substantial agricultural water demands. A total of 9 adaption measures and combinations of measures were assessed. Desalination plant implementation can steadily supply public water to lessen system failure duration. Although agricultural water conservation and fallow land can greatly reduce water demand, fallow compensation is a potential cost. When food security is considered, reducing irrigation leakage will be a better adaption measure to both water and agriculture stakeholders. Both agriculture water conservation and cropping systems adjustment have cross-spatial flexibilities. The combination of desalination, reservoirs and public water conservation provide the most beneficial effects in reducing climate change impact.

Hydrological assessment is critical to the successful implementation of adaption measures. In this study, projections of seven global circulation models (GCMs) associated with high and medium–low Representative Concentration Pathways (RCP 8.5 and RCP 4.5) for the period 2021–2040 and 2081–2100 were adopted to assess changes on runoffs in the Gilgel Abbay watershed, the upper Blue Nile basin. A weather generator was employed to generate daily temperature and precipitation to drive a hydrological model for impact assessment. Despite the projected magnitude of changes varied among different GCMs and RCPs, increasing runoffs in wet-season and decreasing in dry-season are observed in both periods, mainly attributed to the change in projected precipitation. Such changes are profound in cases of RCP 8.5 with respect to those of RCP 4.5 and in cases of 2081–2100 with respect to those of 2021–2040. Although the increasing runoffs would provide greater inflow to Lake Tana, the increase of precipitation in wet-season would imply a higher possibility of flash floods. On the other hand, decrease runoffs in dry-season further intensify existing shortage of irrigation water demand. These changes will have deleterious consequences on the economic wellbeing of the country and require successful implementation of adaption measures to reduce vulnerability.

Climate change and variability have significant influences on hydrological cycles and the availability of water in the Horn of Africa. Projections of six General Circulation Models (GCMs) in association with high (A2) and low (B1) emission scenarios were adopted in this study from the Special Report on Emission Scenarios (SRES) for the period 2020 - 2039 to assess the impacts of climate changes on the Gilgel Abbay and Gumara watershed hydrology, the upper Blue Nile basin, Ethiopia. The GCMs selected were screened in accordance with baseline climate statistics of study areas. A weather generator was employed to generate daily temperature and precipitation to drive the General Water Loading Function (GWLF) hydrological model for simulating runoffs. Projected changes in temperature differences and precipitation ratios relative to the baseline were analyzed to explain the variations in evapotranspiration and the influences on runoff. Despite the fact that the projected magnitude varies among GCMs, increasing runoff in both wet and dry seasons was observed for both watersheds, attributable mainly to the increase in precipitation projected by most GCMs. In contrast to the great increases in runoff, variations in evapotranspiration are less significant. The projected runoff in both watersheds implies increased potential for promoting agricultural irrigation in the dry season. Furthermore, it would allow greater inflow to Lake Tana, the largest contributor to the Ethiopian Renaissance Dam on the Blue Nile. Therefore, concerned local, state, and federal government organizations shall be prepared to harness opportunities from the projected increase in runoff.