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Palaeoclimate information on multiple climate variables at different spatiotemporal scales is becoming increasingly important to understand environmental and societal responses to climate change. A lack of high-quality reconstructions of past hydroclimate has recently been identified as a critical research gap. Speleothems, with their precise chronologies, widespread distribution, and ability to record changes in local to regional hydroclimate variability, are an ideal source of such information. Here, we present a new version of the Speleothem Isotopes Synthesis and AnaLysis database (SISALv3), which has been expanded to include trace element ratios and Sr isotopes as additional, hydroclimate-sensitive geochemical proxies. The oxygen and carbon isotope data included in previous versions of the database have been substantially expanded. SISALv3 contains speleothem data from 365 sites from across the globe, including 95 Mg/Ca , 85 Sr/Ca , 52 Ba/Ca , 25 U/Ca , 29 P/Ca , and 14 Sr-isotope records. The database also has increased spatiotemporal coverage for stable oxygen (892) and carbon (620) isotope records compared with SISALv2 (which consists of 673 and 430 stable oxygen and carbon records, respectively). Additional meta information has been added to improve the machine-readability and filtering of data. Standardized chronologies are included for all new entities along with the originally published chronologies. Thus, the SISALv3 database constitutes a unique resource of speleothem palaeoclimate information that allows regional to global palaeoclimate analyses based on multiple geochemical proxies, permitting more robust interpretations of past hydroclimate and comparisons with isotope-enabled climate models and other Earth system and hydrological models. The database can be accessed at 10.5287/ora-2nanwp4rk (Kaushal et al., 2024). [ABSTRACT FROM AUTHOR]

Speleothem fluorescence can provide insights into past vegetation dynamics and stalagmite chronology. However, its origin and especially the formation of fluorescent laminations in stalagmites are poorly understood. We conducted a year-long monthly monitoring of drip water fluorescence in La Vallina Cave (northern Iberian Peninsula) and compared the results to drip water chemistry and active speleothems from the same sites. Drip waters were analyzed using fluorescence spectroscopy and parallel factor analysis (PARAFAC). The resulting five-component model indicates contributions from vegetation, microbial activity, and bedrock. Intra-site fluorescence variability is mainly influenced by changes in overlying vegetation, water reservoir time, and respiration rates. Contrary to prevailing views, we find no systematic increase in drip water fluorescence during rainy conditions across drip sites and seasonal variations in drip water fluorescence are absent at a location where present-day speleothem layers form. Our findings challenge the notion of a higher abundance of humic-like fluorescence during the rainy season as the primary cause for layer formation and suggest additional controls on drip water fluorescence, such as bedrock interaction and microbial reprocessing. We also propose that growth rate may control the dilation of the fluorescence signal in stalagmites, indicating other potential mechanisms for fluorescent layer formation. [ABSTRACT FROM AUTHOR]

We present the 'SISAL webApp'—a web-based tool to query the Speleothem Isotope Synthesis and AnaLysis (SISAL) database. The software provides an easy-to-use front-end interface to mine data from the SISAL database while providing the SQL code alongside as a learning tool. It allows for simple and increasingly complex querying of the SISAL database based on various data and metadata fields. The SISAL webApp version currently hosts SISALv2 of the database with 691 records from 294 sites, 512 of which have standardized chronologies. The SISAL webApp has sufficient flexibility to host future versions of the SISAL database, which may include allied speleothem information such as trace elements and cave-monitoring records. The SISAL webApp will increase accessibility to the SISAL database while also functioning as a learning tool for more advanced ways of querying paleoclimate databases. The SISAL webApp is available at http://geochem.hu/SISAL_webApp. [ABSTRACT FROM AUTHOR]

Paleoclimate information on multiple climate variables at different spatiotemporal scales is increasingly important to understand environmental and societal responses to climate change. A lack of high-quality reconstructions of past hydroclimate has recently been identified as a critical research gap. Speleothems, with their precise chronologies, widespread distribution, and ability to record changes in local to regional hydroclimate variability, are an ideal source of such information. Here we present a new version of the Speleothem Isotopes Synthesis and AnaLysis database (SISALv3), which has been expanded to include trace element ratios and Sr-isotopes as additional, hydroclimate-sensitive geochemical proxies. The oxygen and carbon isotope data included in previous versions of the database have been substantially expanded. SISALv3, contains speleothem data from 364 sites from across the globe, including 94 Mg/Ca, 83 Sr/Ca, 51 Ba/Ca, 25 U/Ca, 29 P/Ca and 14 Sr-isotope records. The database also has increased spatiotemporal coverage for stable oxygen (831) and carbon (588) isotope records compared to SISALv2. Additional meta information has been added to improve machine-readability and filtering of data. Standardized chronologies are included for all new entities together with the originally published chronologies. The SISALv3 database thus constitutes a unique resource of speleothem paleoclimate information that allows regional-to-global paleoclimate analyses based on multiple geochemical proxies, allowing more robust interpretations of past hydroclimate and comparisons with isotope-enabled climate models and other earth system and hydrological models. [ABSTRACT FROM AUTHOR]

Aim: Our study developed a prednisolone acetate polymeric micelles (PM) system for ocular inflammation related to allergic uveitis. Methods: For PM development, a thin-film hydration procedure was used. Irritation, in vitro, ex vivo transcorneal permeation, micelle size, entrapment efficiency and histology within the eye were all calculated for PM. Results: The optimized in situ gel (A4) showed superior ex vivo transcorneal permeation with zero-order kinetics. Conclusion: The developed formulation could be a promising candidate for treating anterior uveitis via topical application to the anterior segment of the eye. [ABSTRACT FROM AUTHOR]

The riverine flux of terrigenous dissolved organic matter (tDOM) to the ocean is a significant contributor to the global carbon cycle. In response to anthropogenic drivers the flux is expected to increase. This may impact the availability of sunlight in coastal ecosystems, and the seawater carbonate system and coastal CO2 fluxes. Despite its significance, there are few long‐term and high‐resolution time series of tDOM parameters. Corals incorporate fluorescent tDOM molecules from the chromophoric dissolved organic matter (CDOM) pool in their skeletons. The resulting coral skeletal luminescence variability has traditionally been used to reconstruct hydroclimate variation. Here, we use two replicate coral cores and concurrent in‐situ biogeochemical data from the Sunda Shelf Sea in Southeast Asia, where peatlands supply high tDOM inputs, to show that variability in coral luminescence green‐to‐blue ratios (coral G/B) can be used to quantitatively reconstruct terrigenous dissolved organic carbon (tDOC) concentration. Moreover, coral G/B can be used to reconstruct the CDOM absorption spectrum from 230 to 550 nm, and the specific ultraviolet absorbance at 254 nm (SUVA254) of the DOM pool. Comparison to a core from Borneo shows that there may be site‐specific offsets in the G/B–CDOM absorption relationship, but that the slope of the relationship is very similar, validating the robustness of the proxy. By demonstrating that corals can be used to estimate past changes in coastal tDOC and CDOM, we establish a method to study drivers of land–ocean tDOM fluxes and their ecological consequences in tropical coastal seas over decadal to centennial time scales. Plain Language Summary: Understanding the different processes of the carbon cycle is a critical priority to make increasingly accurate predictions of future CO2 concentration. The riverine flux of dissolved organic carbon (DOC) to the coastal ocean may impact the availability of sunlight to coastal life forms, cause coastal water acidification and further degas to the atmosphere as CO2. This DOC flux is particularly significant in regions with peatland soils with a high carbon content and where the flux is being further exacerbated by anthropogenic land‐use changes. Despite this, there are few long‐term instrumental measurements for DOC, and these are largely restricted to North America and Europe. In order to increase our understanding of the fate of DOC, we calibrate a method to reconstruct DOC records using luminescence measurements of coral cores. Coral skeletal luminescence is caused by the incorporation of humic acids, an integral component of terrestrial DOC. We use two replicate coral cores from coastal Singapore and concurrent biogeochemical measurements of coastal Singapore waters to show that coral luminescence measurements are quantitatively related to terrestrial DOC concentration measurements. Our proposed method can be used to reconstruct terrestrial DOC variability over centennial timescales allowing us to better understand the processes and consequences of its variability. Key Points: Coral luminescence green‐to‐blue ratio (coral G/B) is a quantitative proxy for terrigenous dissolved organic carbon concentration in river‐influenced tropical coastal oceansCoral G/B can also be used to reconstruct the absorption spectrum of terrigenous chromophoric dissolved organic matter over the wavelength range 230–550 nmDowncore luminescence G/B variability can therefore be used to investigate temporal variability in terrigenous dissolved organic carbon input and its impacts on optical water quality [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative disease that affects a wide range of populations and is the primary cause of death in various countries. The treatment of AD is still restricted to oral conventional medicines that act only superficially. Fabrication of intranasal solid lipid nanoparticulate system for the uptake of therapeutic agents will act as a convincing approach with limited off-site toxicity and increased pharmacological activity. The objective of this study was to formulate, optimize, and evaluate the efficiency of rivastigmine tartrate (RT)-loaded intranasal solid lipid nanoparticles (SLNs) employing the solvent-evaporation diffusion method. To optimize the formulation parameters, the central composite design (CCD) was used. Lipid concentration (X1) and surfactant concentration (X2) were considered to be independent variables, while particle size (Y1), percentage entrapment efficiency (Y2), and percentage drug release (Y3) were considered as responses. The solid lipid was glyceryl monostearate, while the surfactant was polysorbate 80. The optimized formulation has a particle size of 110.2 nm, % entrapment efficiency of 82.56%, and % drug release of 94.86%. The incompatibility of drug excipients was established by differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR). Nasal histopathology tests on sheep mucosa revealed that the developed SLNs were safe to utilize for intranasal delivery with no toxicity. Ex vivo permeation investigations revealed that the flux and diffusion coefficients for RT solid lipid nanoparticles and RT solution were 3.378 g/cm²/h and 0.310-3 cm²/h, respectively. Stability studies demonstrated that the developed SLNs were stable when stored under various storage conditions. The viability and vitality of adopting a lipid particle delivery system for improved bioavailability via the intranasal route were also established in the in vivo pharmacokinetic investigations. According to the histopathological and pharmacokinetic investigations, the developed formulations were safe, non-lethal, efficient, and robust. These results suggest the potentiality provided by rivastigmine tartrate-loaded solid lipid nanoparticles for nasal delivery. [ABSTRACT FROM AUTHOR]

Reconstruction of past changes in monsoon climate from speleothem oxygen isotope (δ18O) records is complex because δ18O signals can be influenced by multiple factors including changes in precipitation, precipitation recycling over land, temperature at the moisture source, and changes in the moisture source region and transport pathway. Here, we analyse >150 speleothem records of the Speleothem Isotopes Synthesis and AnaLysis (SISAL) database to produce composite regional trends in δ18O in monsoon regions; compositing minimises the influence of site-specific karst and cave processes that can influence individual site records. We compare speleothem δ18O observations with isotope-enabled climate model simulations to investigate the specific climatic factors causing these regional trends. We focus on differences in δ18O signals between the mid-Holocene, the peak of the Last Interglacial (Marine Isotope Stage 5e) and the Last Glacial Maximum as well as on δ18O evolution through the Holocene. Differences in speleothem δ18O between the mid-Holocene and the Last Interglacial in the East Asian and Indian monsoons are small, despite the larger summer insolation values during the Last Interglacial. Last Glacial Maximum δ18O values are significantly less negative than interglacial values. Comparison with simulated glacial–interglacial δ18O shows that changes are principally driven by global shifts in temperature and regional precipitation. Holocene speleothem δ18O records show distinct and coherent regional trends. Trends are similar to summer insolation in India, China and southwestern South America, but they are different in the Indonesian–Australian region. Redundancy analysis shows that 37 % of Holocene variability can be accounted for by latitude and longitude, supporting the differentiation of records into individual monsoon regions. Regression analysis of simulated precipitation δ18O and climate variables show significant relationships between global Holocene monsoon δ18O trends and changes in precipitation, atmospheric circulation and (to a lesser extent) source area temperature, whereas precipitation recycling is non-significant. However, there are differences in regional-scale mechanisms: there are clear relationships between changes in precipitation and δ18O for India, southwestern South America and the Indonesian–Australian regions but not for the East Asian monsoon. Changes in atmospheric circulation contribute to δ18O trends in the East Asian, Indian and Indonesian–Australian monsoons, and a weak source area temperature effect is observed over southern and central America and Asia. Precipitation recycling is influential in southwestern South America and southern Africa. Overall, our analyses show that it is possible to differentiate the impacts of specific climatic mechanisms influencing precipitation δ18O and use this analysis to interpret changes in speleothem δ18O. [ABSTRACT FROM AUTHOR]

Terrigenous dissolved organic matter (tDOM) carried by rivers represents an important carbon flux to the coastal ocean, which is thought to be increasing globally. Because tDOM is rich in light‐absorbent chromophoric dissolved organic matter (CDOM), it may also reduce the amount of sunlight available in coastal ecosystems. Despite its biogeochemical and ecological significance, there are few long‐term records of tDOM, hindering our understanding of its drivers and dynamics. Corals incorporate terrestrial humic acids, an important constituent of CDOM, resulting in luminescent bands that have been previously linked to rainfall and run‐off. We show that luminescence green‐to‐blue (G/B) ratios in a coral core growing in waters affected by peatland run‐off correlate strongly with remote sensing‐derived CDOM absorption. The 24‐year monthly resolution reconstructed record shows that rainfall controls land‐to‐ocean tDOM flux from this protected peatland catchment, and suggests an additional impact by solar radiation, which degrades tDOM at sea. Plain Language Summary: A critical priority in biogeochemistry is to improve our understanding of the global carbon cycle so that we can make accurate predictions of future CO2 concentrations. One important but still enigmatic aspect of the carbon cycle is the transport and fate of organic carbon from soils to the ocean. Our understanding of this flux is particularly limited by the lack of historical time‐series measurements. One way of obtaining such historical data is through satellite‐derived measurements, but this can only yield data for the most recent decades. Here, we show that historical records of terrestrial carbon can also be reconstructed from luminescence measurements of coral cores, which have the potential to yield centuries‐long time series of carbon concentrations. Corals are carbonate archives that record different environmental parameters during their skeleton formation. Luminescence is caused by the incorporation of humic acids, an integral component of terrestrially derived dissolved organic carbon. Our 24‐year long reconstruction from a coral core collected off Borneo suggests that organic carbon concentrations are driven by rainfall over adjacent peatlands, and by solar radiation that breaks down the organic carbon at sea. There is no long‐term shift, suggesting that this peatland catchment has stayed protected from land‐use change. Key Points: We show that luminescence in coral skeletons is a proxy for terrestrial chromophoric dissolved organic matter (CDOM)This proxy yields information on land‐to‐ocean dissolved organic matter (DOM) flux in historically under‐sampled tropical seasA 24‐year reconstructed CDOM record from Borneo shows large seasonal DOM flux from peatland, and likely influences of photodegradation [ABSTRACT FROM AUTHOR]

Characterizing the temporal uncertainty in palaeoclimate records is crucial for analysing past climate change, correlating climate events between records, assessing climate periodicities, identifying potential triggers and evaluating climate model simulations. The first global compilation of speleothem isotope records by the SISAL (Speleothem Isotope Synthesis and Analysis) working group showed that age model uncertainties are not systematically reported in the published literature, and these are only available for a limited number of records (ca. 15 %, n=107/691). To improve the usefulness of the SISAL database, we have (i) improved the database's spatio-temporal coverage and (ii) created new chronologies using seven different approaches for age–depth modelling. We have applied these alternative chronologies to the records from the first version of the SISAL database (SISALv1) and to new records compiled since the release of SISALv1. This paper documents the necessary changes in the structure of the SISAL database to accommodate the inclusion of the new age models and their uncertainties as well as the expansion of the database to include new records and the quality-control measures applied. This paper also documents the age–depth model approaches used to calculate the new chronologies. The updated version of the SISAL database (SISALv2) contains isotopic data from 691 speleothem records from 294 cave sites and new age–depth models, including age–depth temporal uncertainties for 512 speleothems. SISALv2 is available at 10.17864/1947.256 (Comas-Bru et al., 2020a). [ABSTRACT FROM AUTHOR]

Reconstruction of past changes in monsoon climate from speleothem oxygen isotope (δ[sup 18]O) records is complex because δ[sup 18]O signals can be influenced by multiple factors including changes in precipitation, precipitation recycling over land, temperature at the moisture source and changes in the moisture source region and transport pathway. Here, we analyse > 150 speleothem records from version 2 of the Speleothem Isotopes Synthesis and Analysis (SISAL) database to produce composite regional trends in δ[sup 18]O in monsoon regions; compositing minimises the influence of site-specific karst and cave processes that can influence individual site records. We compare speleothem δ[sup 18]O observations with isotope-enabled climate model simulations to investigate the specific climatic factors causing these regional trends. We focus on differences in δ[sup 18]O signals between interglacial (mid-Holocene and Last Interglacial) and glacial (Last Glacial Maximum) states, and on δ[sup 18]O evolution through the Holocene. Differences in speleothem δ[sup 18]O between the mid-Holocene and Last Interglacial in the East Asian and Indian monsoons are small, despite the larger summer insolation values during the Last Interglacial. Last Glacial Maximum δ[sup 18]O values are significantly less negative than interglacial values. Comparison with simulated glacial-interglacial δ[sup 18]O shows that changes are principally driven by global shifts in temperature and regional precipitation. Holocene speleothem δ[sup 18]O records show distinct and coherent regional trends. Trends are similar to summer insolation in India, China and southwestern South America, but different in the Indonesian-Australian region. Redundancy analysis shows that 37 % of Holocene variability can be accounted for by latitude and longitude, supporting the differentiation of records into individual monsoon regions. Regression analysis of simulated precipitation δ[sup 18]O and climate variables show that global Holocene monsoon δ[sup 18]O trends are driven by changes in precipitation, atmospheric circulation and (to a lesser extent) source area temperature, whilst precipitation recycling is non-significant. However, there are differences in regional scale mechanisms; there are clear relationships between changes in precipitation and in δ[sup 18]O for India, southwestern South America and the Indonesian-Australian regions, but not for the East Asian monsoon. Changes in atmospheric circulation contributes to δ[sup 18]O trends in the East Asian, Indian and Indonesian-Australian monsoons, and a weak source area temperature effect is observed over southern and central America and Asia. Precipitation recycling is influential in southwestern South America and southern Africa. Overall, our analyses show that it is possible to differentiate the impacts of specific climatic mechanisms influencing precipitation δ[sup 18]O and use this analysis to interpret changes in speleothem δ[sup 18]O. [ABSTRACT FROM AUTHOR]

As one of the most prominent seasonally recurring atmospheric circulation patterns, the Asian summer monsoon (ASM) plays a vital role for the life and livelihood of about one-third of the global population. Changes in the strength and seasonality of the ASM significantly affect the ASM region, yet the drivers of change and the varied regional responses of the ASM are not well understood. In the last two decades, there were a number of studies reconstructing the ASM using stalagmite-based proxies such as oxygen isotopes (\delta$^{18}$O). Such reconstructions allow examination of ASM drivers and responses, increasing monsoon predictability.In a review study [1], we focus on stalagmite \delta$^{18}$O records from India at the proximal end of the larger ASM region. Stalagmite-based time series are available from a number of caves in northern, northeastern and south Indian caves, as well as from the Andaman Islands. Despite widespread occurrence of carbonate rocks, data is lacking for Central and western India (the Vindhayans and Thar Desert), and Pakistan. We examine Indian stalagmite records collated in the Speleothem Isotope Synthesis and AnaLysis version 1 database [1] and support the database with a summary of record quality and regional climatic interpretations of the \delta$^{18}$O record during different climate states. Indian stalagmite \delta$^{18}$O records show well-dated, high-amplitude changes in response to the dominant drivers of the ASM on orbital to multi-centennial timescales, and indicate the magnitude of monsoon variability in response to these drivers.We suggest the most useful time periods (climatic events) and locations for further work using tools such as data-model comparisons, spectral analysis methods, multi-proxy investigations, and monitoring.References[1] Kaushal, N., Breitenbach, S.F.M., Lechleitner, F.A., Sinha, A., Tewari, V.C., Ahmad, S.M., Berkelhammer, M., Band, S., Yadava, M., Ramesh, R. and Henderson, G.M.: The Indian Summer Monsoon from a Speleothem $\delta^{18}$O Perspective -- A Review. Quaternary, 1, 29, https://doi.org/10.3390/quat1030029, 2018.\\[2] Atsawawaranunt, K., Comas-Bru, L., Amirnezhad Mozhdehi, S., Deininger, M., Harrison, S. P., Baker, A., Boyd, M., Kaushal, N., Ahmad, S. M., Ait Brahim, Y., Arienzo, M., Bajo, P., Braun, K., Burstyn, Y., Chawchai, S., Duan, W., Hatvani, I. G., Hu, J., Kern, Z., Labuhn, I., Lachniet, M., Lechleitner, F. A., Lorrey, A., P\'{e}rez-Mej\'{\i}as, C., Pickering, R., Scroxton, N., and SISAL Working Group Members: The SISAL database: a global resource to document oxygen and carbon isotope records from speleothems, Earth Syst. Sci. Data, 10, 1687-1713, https://doi.org/10.5194/essd-10-1687-2018, 2018. [ABSTRACT FROM AUTHOR]

Background: Various types of nano-formulations are being developed and tested for the delivery of the ocular drug. They also have anatomical and physiological limitations, such as tear turnover, nasal lachrymal waste, reflex squinting, and visual static and dynamic hindrances, which pose challenges and delay ocular drug permeation. As a result of these limitations, less than 5% of the dose can reach the ocular tissues., Objective: The basic purpose of designing these formulations is that they provide prolonged retention for a longer period and can also increase the course time., Methods: To address the aforementioned issues, many forms of polymeric micelles were developed. Direct dissolving, dialysis, oil-in-water emulsion, solvent evaporation, co-solvent evaporation, and freeze-drying are some of the methods used to make polymeric nano micelles., Results: Their stability is also very good and also possesses reversible drug loading capacity. When the drug is given through the topical route, then it has very low ocular bioavailability., Conclusion: The definition and preparation process of polymeric micelles and anti-inflammatory drugs used in uveitis and the relation between uveitis and micelles are illustrated in detail., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)