Except for Robust Outliers, Rapamycin Increases Lesion Burden in a Murine Model of Cerebral Cavernous Malformations.

Cerebral cavernous malformation (CCM) is a hemorrhagic cerebrovascular disease where lesions develop in the setting of endothelial mutations of CCM genes, with many cases also harboring somatic PIK3CA gain of function (GOF) mutations. Rapamycin, an mTORC1 inhibitor, inhibited progression of murine CCM lesions driven by Ccm gene loss and Pik3ca GOF, but it remains unknown if rapamycin is beneficial in the absence of induction of Pik3ca GOF. We investigated the effect of rapamycin at three clinically relevant doses on lesion development in the Ccm3-/-PDGFb-icreERPositive murine model of familial CCM disease, without induction of Pik3ca GOF. Lesion burden, attrition, and acute and chronic hemorrhaging were compared between placebo and rapamycin-treated mice. Plasma miRNome was compared to identify potential biomarkers of rapamycin response. Outlier, exceptionally large CCM lesions (> 2 SD above the mean lesion burden) were exclusively observed in the placebo group. Rapamycin, across all dosages, may have prevented the emergence of large outlier lesions. Yet rapamycin also appeared to exacerbate mean lesion burden of surviving mice when outliers were excluded, increased attrition, and did not alter hemorrhage. miR-30c-2-3p, decreased in rapamycin-treated mouse plasma, has gene targets in PI3K/AKT and mTOR signaling. Progression of outlier lesions in a familial CCM model may have been halted by rapamycin treatment, at the potential expense of increased mean lesion burden and increased attrition. If confirmed, this can have implications for potential rapamycin treatment of familial CCM disease, where lesion development may not be driven by PIK3CA GOF. Further studies are necessary to determine specific pathways that mediate potential beneficial and detrimental effects of rapamycin treatment, and whether somatic PIK3CA mutations drive particularly aggressive lesions.

Damage evolution law of multi-hole blasting igneous rock and quantitative evaluation model of damage degree based on fractal theory and clustering algorithm.

The geological phenomenon of igneous rock invading coal seam is widely distributed, which induces mining risk and affects efficient mining. The pre-splitting blasting method of igneous rock is feasible but difficult to implement accurately, resulting in unnecessary safety and environmental pollution risks. In this paper, the blasting model with penetrating structural plane and the multi-hole blasting model with different hole spacing were established based on the Riedel-Hiermaier-Thoma (RHT) damage constitutive to explore the stress wave propagation law under detonation. The damage cloud diagram and damage degree algorithm were used to quantitatively describe the spatio-temporal evolution of blasting damage. The results show that the explosion stress wave presents a significant reflection stretching effect under the action of the structural plane, which can effectively aggravate the presplitting blasting degree of the rock mass inside the structural plane. The damage range of rock mass is synchronously evolved with the change of blasting hole spacing. The blasting in the igneous rock intrusion area of the 21,914 working face is taken as an application example, and the damage degree of rock mass is reasonably evaluated by the box-counting dimension and K-means clustering method, which proves the effectiveness of the blasting scheme and provides reference value for the implementation of related blasting projects.

Analysis of size effect and its influencing factors of brittle red sandstone with different heights.

We carried out uniaxial compression tests on brittle red sandstone with different heights. The test results show that the uniaxial compressive strength of rock sample increases first and then tends to be stable with the increase of the size, which is approximately stable between 75 and 81 MPa. Both elastic energy and dissipated energy increase with the increase of rock sample size. In order to further analyze the mechanism behind these phenomena, we combined advanced numerical simulation and theoretical analysis to explain these phenomena, and systematically analyzed the end face effect as one of the key factors affecting the uniaxial compression characteristics of brittle red sandstone for the first time. Small sized rock samples are very sensitive to end effect. The middle of the large sized rock samples is in a uniform compression state, and the effect of end effect is weakend. When there are rigid pads at both ends of the rock sample, there is an obvious elastic vertebral body during the loading process of the rock sample. The bearing capacity of rock samples with rigid pads is greater than that of rock samples without rigid pads, and the energy released during instantaneous failure of rock samples without rigid pads is greater than that of rock samples with rigid pads. The findings of this paper make a valuable contribution to establishing optimal study sample sizes and advancing the utilization of laboratory test mechanics parameters in engineering applications.

Experimental study of the effects of the void located at the pile tip on the load capacity of rock-socketed piles.

To address the design challenge of the rock-socketed piles posed by the void located below the pile tip, the physical laboratory model tests were designed and performed to simulate rock socketed piles using similar materials. The study investigates the behavior of the single pile under axial loading with the void located at varying distances from the pile tip. Through multi-level load tests, the variations of unit pile side friction, pile tip resistance, pile axial force and pile settlement are obtained for different positions of the void from the pile tip, as well as after grouting. Its comparison to the rock-socketed pile without void is performed as a reference to quantify the reduction in its bearing capacity. The results are presented in the form of graphs for different void positions and its grouting shows the influence on pile bearing capacity and emphasizes the importance of its detailed cautious investigation and introduction in the analysis. The 2D finite element modeling of the model pile-the void based on ABAQUS is performed to further investigate the influence of the void below pile tip on the bearing capacity of model pile, applying the Mohr Coulomb model as the constitutive model of rock mass behavior. The critical distance of the void below the pile tip is determined.

Investigation of rock genesis and geodynamic significance based on Sr-Yb granite classification and geochemical characteristics: A case study from Guangxi, China.

The intrusive bodies in the study area are categorized into two intrusive units, γπK2 and ηoπK2, based on rock structure characteristics and intrusive contact relationships. The primary lithologies are granite porphyry and quartz monzonite porphyry. Through LA-ICP-MS zircon U-Pb dating, the weighted mean ages of zircon ^206Pb/^238U for these two units were determined to be 84.09 ± 0.86 Ma and 86.10 ± 0.76 Ma, respectively. According to geochemical characteristics and Sr-Yb granite classification, the quartz monzonite porphyry is classified as Zhejiang-Fujian type granite, and the granite porphyry as Nanling type granite. The study explores the geodynamic significance of granites in the area based on Sr-Yb granite classification, identifying the lower crust metamorphic facies as amphibolite facies. The source rocks are primarily basic granulites and felsic granulites, reflecting a thermally active lower crust with poorly developed fluids. Additionally, Sr-Yb granite classification aids in determining the crustal thickness of the lower crust, which is crucial for understanding continental geological evolution. This paper discusses the optimal locations and conditions for mineralizing fluid precipitation, noting that tungsten-tin mineralization is associated with Nanling type granites and that the mineralization process generally occurs later than the diagenetic process under conditions of low pressure and low oxygen fugacity. Tungsten-tin prospecting should focus on areas where the surrounding rock temperature ranges from 300 to 500 °C, with particular attention to the contact zones of sedimentary rocks or near structural fault zones.

Asymmetric analogous hyperbola model of overburden movement and its verification.

The extraction of underground coal resources induces the fracture and movement of overlying strata, leading to geological hazards such as surface deformation, cracks, and even subsidence. Utilizing the analogous hyperbola model of overlying strata movement, we conducted a mechanical analysis to examine the asymmetric fracture mechanism resulting from coal seam mining in thick loose strata. An asymmetric analogous hyperbola model was established by introducing distinct virtual half-axis lengths (b). The thickness impact of thick loose layers (H) and bedrock layer (h) on the asymmetric movement of overlying rock during mining was also discussed. Similarity model tests were conducted to research the migration characteristics and surface subsidence patterns of overburdened rock and thick loose layers at different mining stages and validate the hypothesis of asymmetric overburdened rock migration. Additionally, the discrete element numerical model for thick and loose layers mining was established by using UDEC and discussed the asymmetric analogous hyperbola behaviour of overburden movement and surface subsidence. The comparison results show that the established asymmetric hyperbolic model can effectively predict the movement law of overlying strata and surface subsidence characteristics. Therefore, the proposed model can provide valuable theoretical support for predicting the movement patterns of overburden under thick loose layers and mitigating surface subsidence disasters.

Urine manganese, cadmium, lead, arsenic, and selenium among autism spectrum disorder children in Kuala Lumpur.

Background: The development of autism spectrum disorder (ASD) may stem from exposure to environmental pollutants such as heavy metals. The primary objective of this study is to determine the role of heavy metals of concern such as manganese (Mn), cadmium (Cd), lead (Pb), arsenic (As), and essential trace element selenium (Se) among ASD children in Kuala Lumpur, Malaysia. Method: A total of 155 preschoolers in Kuala Lumpur between the ages 3 to 6 participated in an unmatched case-control study, comprising ASD children (n = 81) recruited from an early intervention program for autism, and 74 children without autism who were recruited from public preschools. Urine samples were collected at home, delivered to the study site, and transported to the environmental lab within 24 hours. Inductively coupled plasma mass spectrometry (ICP-MS) was applied to measure the concentration of heavy metals in the samples. Data were analysed using bivariate statistical tests (Chi-square and T-test) and logistic regression models. Result: This study demonstrated that Cd, Pb, and As urine levels were significantly greater in children without autism relative to those affected with ASD (p < 0.05). No significant difference was in the levels of Se (p = 0.659) and Mn (p = 0.875) between children with ASD and the control group. The majority of children in both groups have urine As, Pb, and Cd values lower than 15.1 µg/dL, 1.0 µg/dL, and 1.0 µg/dL, respectively which are the minimal risk values for noncarcinogenic detrimental human health effect due to the heavy metal's exposure . Factors associated with having an ASD child included being a firstborn, male, and higher parental education levels (adjusted odds ratios (aOR) > 1, p < 0.05). Conclusion: Preschoolers in this study demonstrated low levels of heavy metals in their urine samples, which was relatively lower in ASD children compared to the healthy matched controls. These findings may arise from the diminished capacity to excrete heavy metals, especially among ASD children, thereby causing further accumulation of heavy metals in the body. These findings, including the factors associated with having an ASD child, may be considered by healthcare professionals involved in child development care, for early ASD detection. Further assessment of heavy metals among ASD children in the country and interventional studies to develop effective methods of addressing exposure to heavy metals will be beneficial for future reference.

A hybrid finite-discrete element method for modelling cracking processes in sandy mudstone containing a single edge-flaw under cyclic dynamic loading.

Rock mass deformation and failure are macroscopic manifestations of crack initiation, propagation, and coalescence. However, simulating the transition of rocks from continuous to discontinuous media under cyclic dynamic loading remains challenging. This study proposes a hybrid finite-discrete element method (HFDEM) to model crack propagation, incorporating a frequency-dependent cohesive-zone model. The mechanical properties of standard sandy mudstone under quasi-static and cyclic dynamic loading were simulated using HFDEM, and the method's reliability was verified through experimental comparison. The comparative analysis demonstrates that HFDEM successfully captures crack interaction mechanisms and accurately simulates the overall failure behavior of specimens. Additionally, the effects of pre-existing flaw inclination angle and dynamic loading frequency on rock failure mechanisms were investigated. The numerical results reveal that rock samples exhibit significantly higher compressive strength under dynamic loading compared to quasi-static loading, with compressive strength increasing with higher cyclic dynamic load frequencies. Furthermore, by analyzing the strength characteristics, crack propagation, and failure modes of the samples, insights into the failure mechanisms of rocks under different frequency loads were obtained. This study provides valuable insights into crack development and failure of rocks under seismic loads, offering guidance for engineering practices.

miRNA-mediated inhibition of an actomyosin network in hippocampal pyramidal neurons restricts sociability in adult male mice.

Social deficits are frequently observed in patients suffering from neurodevelopmental disorders, but the molecular mechanisms regulating sociability are still poorly understood. We recently reported that the loss of the microRNA (miRNA) cluster miR-379-410 leads to hypersocial behavior and anxiety in mice. Here, we show that ablating miR-379-410 in excitatory neurons of the postnatal mouse hippocampus recapitulates hypersociability, but not anxiety. At the cellular level, miR-379-410 loss in excitatory neurons leads to larger dendritic spines, increased excitatory synaptic transmission, and upregulation of an actomyosin gene network. Re-expression of three cluster miRNAs, as well as pharmacological inhibition of the actomyosin activator ROCK, is sufficient to reinstate normal sociability in miR-379-410 knockout mice. Several actomyosin genes and miR-379-410 family members are reciprocally dysregulated in isogenic human induced pluripotent stem cell (iPSC)-derived neurons harboring a deletion present in patients with Williams-Beuren syndrome, characterized by hypersocial behavior. Together, our results show an miRNA-actomyosin pathway involved in social behavior regulation.

Chemical characteristics and water stability evaluation of groundwater in the CKDu Zone of Sri Lanka.

Groundwater is the main source of drinking water for the rural population in the chronic kidney disease of unknown etiology (CKDu) zone of the North Central Province (NCP) in Sri Lanka. In this study, a total of 334 groundwater samples (311 dug wells, 21 tube wells and 2 springs) during the wet season from two aquifers in the NCP were collected, and investigated their chemical characteristics and evaluate their water quality, including groundwater chemistry, main ion sources, the corrosion and scaling potential of groundwater. The results showed that the two hydrochemical types of groundwater in the NCP were mainly of the Ca-HCO3, Na·Ca-HCO3 types, with the main HCO3-, Na+ and Ca2+ ions in both types of groundwater originating from silicate and evaporite salt dissolution and influenced by alternating cation adsorption, while the presence of NO3- was mainly anthropogenic. Evaluation of water stability using namely Langelier saturation index (LSI), Ryznar stability index (RSI), Puckorius scaling index (PSI) and Larson-Skold index (LS), indicated that most groundwater presents corrosion potential and has corrosion behavior tendency of metals to some degrees. The water quality of Polonnaruwa was better than that of Anuradhapura in the NCP, and when the groundwater was worse than the "good" grade, which must be properly treated before it is used as drinking water.

Multi-method characterization of groundwater nitrate and sulfate contamination by karst mines in southwest China.

Groundwater contamination by nitrate and sulfate in mining areas is a significant challenge. Consequently, the inputs sources of these contaminants and their evolution have received considerable attention, with the knowledge gained critical for improved management of water quality. This study integrated data on multiple stable isotopes and water chemistry data and a Bayesian isotope mixing model to investigate the relative contributions of inputs sources of sulfate and nitrate sources to bodies of water in a karst mining area in southwest China. The outcomes indicated that hydrochemical component in the water bodies of the study area is mainly derived from the dissolution of silicate rocks, carbonate rocks and sulfate minerals as well as the oxidation of sulfides. The human and agricultural wastewater, soil nitrogen, and fertilizers were the predominant inputs sources of nitrate to the mine water environment; the predominant inputs sources of sulfide were mineral oxidation, evaporite dissolution, atmospheric deposition, and sewage. Groundwater is mainly recharged from atmospheric precipitation, and surface water is closely hydraulically connected to groundwater. Nitrogen and oxygen isotope composition and water chemistry indicative of nitrification dominate the nitrogen cycle in the study area. The oxidation of pyrite and bacterial sulfate reduction (SRB) had no significant impact on the stable isotopes of groundwater. The results of this study demonstrate the inputs of different sources to nitrate and sulfate in karst mines and associated transformation processes. The results of this study can assist in the conservation of groundwater quality in mining areas and can act as a reference for future related studies.

Fluoride-induced hypertension by regulating RhoA/ROCK pathway and phenotypic transformation of vascular smooth muscle cells: In vitro and in vivo evidence.

Fluoride exposure has been implicated as a potential risk factor for hypertension, but the underlying mechanisms remain unclear. This study investigated the role of the RhoA/ROCK signaling pathway in fluoride-induced hypertension. Male Wistar rats were divided into different groups and exposed to varying concentrations of sodium fluoride (NaF) or sodium chloride (NaCl) via drinking water. The rats' blood pressure was measured, and their aortic tissue was utilized for high-throughput sequencing analysis. Additionally, rat and A7r5 cell models were established using NaF and/or Fasudil. The study evaluated the effects of fluoride exposure on blood pressure, pathological changes in the aorta, as well as the protein/mRNA expression levels of phenotypic transformation indicators (a-SMA, calp, OPN) in vascular smooth muscle cells (VSMCs), along with the RhoA/ROCK signaling pathway (RhoA, ROCK1, ROCK2, MLC/p-MLC). The results demonstrated that fluoride exposure in rats led to increased blood pressure. High-throughput sequencing analysis revealed differential gene expression associated with vascular smooth muscle contraction, with the RhoA/ROCK signaling pathway emerging as a key regulator. Pathological changes in the rat aorta, such as elastic membrane rupture and collagen fiber deposition, were observed following NaF exposure. However, fasudil, a ROCK inhibitor, mitigated these pathological changes. Both in vitro and in vivo models confirmed the activation of the RhoA/ROCK signaling pathway and the phenotypic transformation of VSMCs from a contractile to a synthetic state upon fluoride exposure. Fasudil effectively inhibited the activities of ROCK1 and ROCK2 and attenuated the phenotypic transformation of VSMCs. In conclusion, fluoride has the potential to induce hypertension through the activation of the RhoA/ROCK signaling pathway and phenotypic changes in vascular smooth muscle cells. These results provide new insights into the mechanism of fluoride-induced hypertension.

Chemical characterization of green liquor dregs from 16 Swedish pulp and paper mills between 2017 and 2019.

Green liquor dregs (GLD) is an alkaline by-product from the pulp and paper industry with a pH between 10 and 14. Today most of the produced GLD in Sweden is landfilled. As a fine-grained alkaline material, it might be possible to use it for acid-generating mining waste remediation. To increase the utilization, quality characteristics and environmental performance need to be determined. In this study samples were collected 5 times from 16 mills during a period of 2.5 years, and were characterized by analyzing dry matter content, loss on ignition (LOI) 550 °C and LOI 950 °C, elemental analysis, pH, electrical conductivity, and calorific value. The results were then evaluated using multivariate statistics (PCA) as well as being compared to other studies and Swedish till. The results show that even if GLD is heterogenous (both within a mill and between different mills) trends can be seen for samples from most mills. When samples do stand out, it is predominately related to the same four mills. Most of the studied parameters showed characteristics favorable for use as a remediant; however, TOC, sulfur, and some of the elements require further study. In general, this study concludes that GLD can be a viable option for the remediation of small orphaned sulfidic mining sites and thus worthy of further studies on the interaction between GLD and acidic mining waste.Overall, GLD can be a good alternative for cost-effective remediation of smaller orphaned mining sites. It is readily available in large quantities, has the qualities needed for remediation of many orphaned acidic mining sites, and can often be locally sourced near the mining site. The use of GLD for mining site remediation is likely also a more sustainable method compared to traditional remediation methods.

Enhanced RHO-ROCK signaling is associated with CRELD2 production and fibroblast recruitment in cutaneous squamous cell carcinoma.

A key characteristic of cancer cells is their ability to induce changes in their microenvironment that render it permissive to tumor growth, invasion and metastasis. Indeed, these changes are required for tumor progression. Consequently, the tumor microenvironment is emerging as a key source of new targets against cancer, with novel therapies aimed at reversing tumor-promoting changes, reinstating a tumor-hostile microenvironment and suppressing disease progression. RHO-ROCK signaling, and consequent tension within the cellular actomyosin cytoskeleton, regulates a paracrine signaling cascade that establishes a tumor-promoting microenvironment. Here, we show that consistent with our observations in breast cancer, enhanced ROCK activity and consequent production of CRELD2 is associated with the recruitment and tumor-promoting polarization of cancer-associated fibroblasts in cutaneous squamous cell carcinoma. Our observations provide support for the notion that the role of RHO-ROCK signaling in establishing a tumor-promoting microenvironment may be conserved across patients and potentially also different cancer types.

Rock crack initiation triggered by energy digestion.

The critical value of rock failure is determined by irreversible deformation (inelastic deformation, damage, and other internal dissipation) processes and external conditions before rock failure. Nevertheless, a thorough explanation of the mechanism causing cracks in rock material has not yet been provided. The strain energy theory is applied in this work to assess the initiation of rock cracks and investigate the relationship between energy digestion and rock strength. Firstly, the uniaxial compression test was conducted on sandstone samples under quasi-static loading conditions and the results of energy evolution, non-linear cumulative digestion, and stored ultimate energy were obtained. Then, a novel algorithm for assessing the initiation of rock cracks has been put forth. The concept of energy digestion index (EDI), which is the ratio of digested energy over the external loading energy, has been developed to characterize the energy absorption capacity of rock material. The result shows a relationship between the maximum growth rate of energy digestion and the increasing rate of variable elasticity modulus and crack initiation. The mechanical characteristics and peak strength of the rock material are negatively correlated with the EDI. By monitoring the digested energy status, an evaluation of the residual strength is introduced based on the relationships, which will initiate further research into in-situ monitoring and failure prediction.

Exploring Rare Earth Element behavior in the Mount Etna volcanic aquifers (Sicily).

This study presents the first data on REY (Rare Earth Elements plus Yttrium) in the aquifer of Mount Etna (Sicily, Italy). Patterns normalized to chondrites indicate strong water-rock interaction, facilitated by a slightly acidic pH resulting from the dissolution of magma-derived CO2. REY patterns provide insights into the processes of both mineral dissolution and the formation of secondary phases. The relative abundance of light to heavy rare earth elements is compatible with the prevailing dissolution of ferromagnesian minerals (e.g., olivine or clinopyroxenes), reinforced by its strong correlation with other proxies of mineral dissolution (e.g., Mg contents). Pronounced negative Ce anomalies and positive Y anomalies demonstrate an oxidizing environment with continuous formation of secondary iron and/or manganese oxides and hydroxides. The Y/Ho fractionation is strongly influenced by metal complexation with bicarbonate complexes, a common process in C-rich waters. In the studied system, the measured REY contents are always below the limits proposed by Sneller et al. (2000, RIVM report, Issue 601,501, p. 66) for surface water and ensure a very low daily intake from drinking water.

Deterioration mechanisms of tuff with surface fractures under freeze-thaw cycles.

In practical engineering, the development of surface cracks is one of the most important reasons for the destruction of the rock mass, and the development of complex morphology fractures on the rock mass surface significantly influences rock mass mechanics. This paper addresses the freeze-thaw damage issue in rock mass containing surface fractures in cold regions. Tuffs and a control group are selected as research samples, with the control group being prefabricated surface jointed specimens with an inclination angle of 70° and a fracture depth ratio d (crack depth) /t (sample width) of 0.26. The study analyzes the mass, wave velocity loss, macro-microcosmic fracture damage morphology, and mechanical properties of the two specimen groups through laboratory freeze-thaw cycle tests, uniaxial compression tests, and scanning electron microscopy examinations. The results show an overall decrease in mass, wave velocity, and uniaxial compressive strength as the cycle number increases, with the prefabricated jointed group samples showing more significant changes. However, the two specimen groups exhibit different macroscopic failure fracture states. In addition, scanning electron microscopy images illustrate that after freeze-thaw cycles, the large rock mass particles break into smaller fragments, resulting in looser particle arrangements and a transition from initial surface cementation to point contact., which weakens the compressive strength of the rock mass. The paper also explains the mechanism of the diminishing impact of freeze-thaw cycles on the strength of the rock mass after a certain number of cycles. The research outcomes hold significant reference value for engineering construction in cold regions.

Protective effects of Y-27632 against cisplatin-induced ototoxicity: A zebrafish model Y-27632 and cisplatin-induced ototoxicity.

Cisplatin is an effective chemotherapy agent against various solid malignancies; however, it is associated with irreversible bilateral sensorineural hearing loss, emphasizing the need for drug development to prevent this complication, with the current options being very limited. Rho-associated coiled-coil-containing protein kinase (ROCK) is a serine-threonine protein kinase involved in various cellular processes, including apoptosis regulation. In this study, we used a transgenic zebrafish model (Brn3C: EGFP) in which hair cells within neuromasts are observed in green under fluorescent microscopy without the need for staining. Zebrafish larvae were exposed to cisplatin alone or in combination with various concentrations of Y-27632, a potent ROCK inhibitor. Hair cell counts, apoptosis assessments using the terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling assay, FM1-43FX labeling assay and behavioral analyses (startle response and rheotaxis) were performed to evaluate the protective effects of Y-27632 against cisplatin-induced ototoxicity. Cisplatin treatment reduced the number of hair cells in neuromasts, induced apoptosis, and impaired zebrafish larval behaviors. Y-27632 demonstrated a dose-dependent protective effect against cisplatin-induced hair cell loss and apoptosis. These findings suggest that Y-27632, as a ROCK inhibitor, mitigates cisplatin-induced hair cell loss and associated ototoxicity in zebrafish.

The Application of Rho Kinase Inhibitors in the Management of Glaucoma.

Glaucoma is a chronic neurodegenerative disease that poses a significant threat of irreversible blindness worldwide. Current treatments for glaucoma focus on reducing intraocular pressure (IOP), which is the only modifiable risk factor. Traditional anti-glaucomatous agents, including carbonic anhydrase inhibitors, beta-blockers, alpha-2 agonists, and prostaglandin analogs, work by either improving uveoscleral outflow or reducing aqueous humor production. Rho kinase (ROCK) inhibitors represent a novel class of anti-glaucomatous drugs that have emerged from bench to bedside in the past decade, offering multifunctional characteristics. Unlike conventional medications, ROCK inhibitors directly target the trabecular meshwork outflow pathway. This review aims to discuss the mechanism of ROCK inhibitors in reducing IOP, providing neuroprotection, and preventing fibrosis. We also highlight recent studies and clinical trials evaluating the efficacy and safety of ROCK inhibitors, compare them with other clinical anti-glaucomatous medications, and outline future prospects for ROCK inhibitors in glaucoma treatment.

A holistic overview of the in-situ and ex-situ carbon mineralization: Methods, mechanisms, and technical challenges.

To mitigate anthropogenic CO2 emissions and address the climate change effects, carbon capture and storage by mineralization (CCSM) and industrial mineral carbonation are gaining attraction. Specifically, in-situ carbon mineralization in the subsurface geological formations occurs due to the transformation of silicate minerals into carbonates (e.g., CaCO3, MgCO3) while ex-situ carbon mineralization at the surface undergoes chemical reactions with metal cations - thus leading to permanent storage. However, both processes are complex and require a rigorous investigation to enable large-scale mineralization. This paper, therefore, aims to provide an overreaching review of the in-situ and ex-situ methods for carbon mineralization for different rock types, various engineered processes, and associated mechanisms pertinent to mineralization. Furthermore, the factors influencing in-situ and ex-situ processes, e.g., suitable minerals, optimal operating conditions, and technical challenges, have also been inclusively reviewed. Our findings suggest that in-situ carbon mineralization, i.e., subsurface permanent storage of CO2 by mineralization, arguably is more promising than ex-situ mineralization due to energy efficiency and large-scale storage potential. Furthermore, the effect of rock type can be ranked as igneous (basalt) > carbonates (sedimentary) > sandstone (sedimentary) to consider for rapid and large-scale CCSM. The findings of this review will, therefore, help towards a better understanding of carbon mineralization, which contributes towards large-scale CO2 storage to meet the global net-zero targets.