Global land subsidence mapping reveals widespread loss of aquifer storage capacity.

Groundwater overdraft gives rise to multiple adverse impacts including land subsidence and permanent groundwater storage loss. Existing methods are unable to characterize groundwater storage loss at the global scale with sufficient resolution to be relevant for local studies. Here we explore the interrelation between groundwater stress, aquifer depletion, and land subsidence using remote sensing and model-based datasets with a machine learning approach. The developed model predicts global land subsidence magnitude at high spatial resolution (~2 km), provides a first-order estimate of aquifer storage loss due to consolidation of ~17 km3/year globally, and quantifies key drivers of subsidence. Roughly 73% of the mapped subsidence occurs over cropland and urban areas, highlighting the need for sustainable groundwater management practices over these areas. The results of this study aid in assessing the spatial extents of subsidence in known subsiding areas, and in locating unknown groundwater stressed regions.

Identification of Potential Diuretic and Laxative Drug Candidates from Avicennia officinalis L. Bark through In Vivo Mice Model Studies and In Vitro Gas Chromatography-Mass Spectrometry and Molecular Docking Analysis.

Background: Avicennia officinalis is a medicinal plant that has traditionally been used as a diuretic, anti-infective, and antiasthmatic. Our investigation was designed to explore the diuretic and laxative potentials of different fractions of this plant's bark extract as well as the identification of possible drug candidates for the activity. Methods: Collected bark was extracted in ethanol and fractionated in different polar and nonpolar solvents, i.e., water, chloroform, ethyl acetate, and n-hexane. Phytoconstituents were identified following the published protocols and gas chromatography-mass spectrometry (GC-MS). In the diuretic test, Na+ and K+ ions were measured using a flame photometer whereas the Cl- ion content was measured by titrimetric method against AgNO3. In the laxative test, feces amount and consistency were also measured. Molecular docking analysis was conducted using the "Vina Wizard" program in PyRx-Python Prescription 0.8. Results: Phytochemical analysis indicated that alkaloids, tannins, flavonoids, saponins, glycosides, and terpenoids were detected in the most bioactive crude extracts, whereas alkaloids, terpenoids, saponins, and gums were found in bioactive n-hexane fraction and steroids, glycosides, and terpenoids were found positive in chloroform fraction. Almost all the fractions demonstrated a dose-dependent increment of stool production with a soft consistency; however, the chloroform fraction was found to be the most active (p < 0.001). The crude extract and n-hexane fractions significantly increased (p < 0.01) the urinary output at the dose of 200 and 400 mg/kg. The concentrations of Na+, K+, and Cl- in collected urine were found to be more compared with the control group. The GC-MS analysis identified seven compounds in bioactive n-hexane fraction (phenolic and ester-type mainly) whereas seven other compounds (acidic and ester-type mainly) were identified in chloroform fraction. In molecular docking, two drug candidates of this extract (2,4-bis(2-phenylpropan-2-yl)phenol and 2-[4-[2-(dimethylamino)-2-oxo-1,1-diphenylethyl]phenyl]-2-phenylacetic acid) showed excellent binding affinity with the receptor compared with furosemide. Conclusion: A. officinalis bark might be a potential source of bioactive compounds for treating hypertension, edema, and constipation.

Curcumin and its Multi-target Function Against Pain and Inflammation: An Update of Pre-clinical Data.

Pain is an unpleasant sensation that has complex and varying causative etiology. Modern drug discovery focuses on identifying potential molecules that target multiple pathways with a safer profile compared to those with a single target. The current treatment of pain and inflammation with the available therapeutics has a number of major side effects. Pain is one of the major clinical problems that need functional therapeutics which act on multiple targets and with low toxicity. Curcumin, a naturally occurring polyphenolic compound from Curcuma longa, has been used for years in Ayurvedic, Chinese, and in many other systems of traditional medicine. Pre-clinical data published thus far demonstrated that curcumin possesses multi-target biological functions, suggesting its potential use to cure different diseases. However, there is no or very brief systematic review of its potential use in pain and inflammation with underlying mechanisms for such activities. Accordingly, the aim of the current review was to update the pre-clinical data of curcumin and its multiple targeting pathways for analgesic and anti-inflammatory effects, and to further propose a molecular mechanism(s). A literature study was conducted using different known databases, including Pubmed, SciFinder, Google Scholar, and Science Direct. Available pre-clinical data suggest the ameliorating effect of curcumin in pain and inflammation is rendered through the modulation of pain pathways, including inhibition of a number of pro-inflammatory mediators, inhibition of oxidative stress and cyclooxygenase-2 (COX-2), down-regulation of Ca2+/calmodulin-depend protein kinase II (CaMKIIα) and calcium channels like transient receptor potential (TRP), modulation of metabotropic glutamate receptor-2 (mGlu2), modulation of monoamine system, inhibition of JAK2/STAT3 signaling pathway, remodeling of extracellular matrix proteins, inhibition of apoptosis, inhibition of JNK/MAPK and ERK/CREB signaling pathway, and activation of the opioid system. Taken all together, it is evident that curcumin is one of the promising, safe, and natural polyphenolic molecules that target multiple molecular pathways in pain and can be beneficial in the treatment and management of pain and inflammation.

In Silico, Molecular Docking and In Vitro Antimicrobial Activity of the Major Rapeseed Seed Storage Proteins.

BACKGROUND: In addition to their use as an edible oil and condiment crop, mustard and rapeseed (Brassica napus L., B. juncea (L.) Czern., B. nigra (L.) W.D.J.Koch, B. rapa L. and Sinapis alba L.) have been commonly used in traditional medicine for relieving pain, coughs and treating infections. The seeds contain high amounts of oil, while the remaining by-product meal after oil extraction, about 40% of seed dry weight, has a low value despite its high protein-content (~85%). The seed storage proteins (SSP) 2S albumin-type napin and 12S globulin-type cruciferin are the two predominant proteins in the seeds and show potential for value adding to the waste stream; however, information on their biological activities is scarce. In this study, purified napin and cruciferin were tested using in silico, molecular docking, and in vitro approaches for their bioactivity as antimicrobial peptides. MATERIALS AND METHODS: The 3D-structure of 2S albumin and 12S globulin storage proteins from B. napus were investigated to predict antimicrobial activity employing an antimicrobial peptide database survey. To gain deeper insights into the potential antimicrobial activity of these SSP, in silico molecular docking was performed. The purified B. napus cruciferin and napin were then tested against both Gram-positive and Gram-negative bacteria for in vitro antimicrobial activity by disc diffusion and microdilution antimicrobial susceptibility testing. RESULTS: In silico analysis demonstrated both SSP share similar 3D-structure with other well studied antimicrobial proteins. Molecular docking revealed that the proteins exhibited high binding energy to bacterial enzymes. Cruciferin and napin proteins appeared as a double triplet and a single doublet, respectively, following SDS-PAGE. SDS-PAGE and Western blotting also confirmed the purity of the protein samples used for assessment of antimicrobial activity. Antimicrobial susceptibility testing provided strong evidence for antimicrobial activity for the purified napin protein; however, cruciferin showed no antimicrobial activity, even at the highest dose applied. DISCUSSION: In silico and molecular docking results presented evidence for the potential antimicrobial activity of rapeseed cruciferin and napin SSP. However, only the in vitro antimicrobial activity of napin was confirmed. These findings warrant further investigation of this SSP protein as a potential new agent against infectious disease.