NLRP3 Inflammasome: An Emerging Therapeutic Target for Alzheimer's Disease.

Alzheimer's disease (AD) is currently the most prevalent neurological disease, and no effective and practical treatments and therapies exist. The nucleotide-binding oligomerization domain-, leucine-rich repeat-, and pyrin domain- containing receptor 3 (NLRP3) inflammasome is vital in the human innate immune response. However, when the NLRP3 inflammasome is overactivated by persistent stimulation, several immune-related diseases, including AD, atherosclerosis, and obesity, result. This review will focus on the composition and activation mechanism of the NLRP3 inflammasome, the relevant mechanisms of involvement in the inflammatory response to AD, and AD treatment targeting NLRP3 inflammasome. This review aims to reveal the pathophysiological mechanism of AD from a new perspective and provide the possibility of more effective and novel strategies for preventing and treating AD.

The complex dynamics of the 2023 Kahramanmaras, Turkey, Mw 7.8-7.7 earthquake doublet.

The destructive 2023 moment magnitude (Mw) 7.8-7.7 earthquake doublet ruptured multiple segments of the East Anatolian Fault system in Turkey. We integrated multiscale seismic and space-geodetic observations with multifault kinematic inversions and dynamic rupture modeling to unravel the events' complex rupture history and stress-mediated fault interactions. Our analysis reveals three subshear slip episodes during the initial Mw 7.8 earthquake with a delayed rupture initiation to the southwest. The Mw 7.7 event occurred 9 hours later with a larger slip and supershear rupture on its western branch. Mechanically consistent dynamic models accounting for fault interactions can explain the unexpected rupture paths and require a heterogeneous background stress. Our results highlight the importance of combining near- and far-field observations with data-driven and physics-based models for seismic hazard assessment.

A retrospective study on expression and clinical significance of PHH3, Ki67 and P53 in bladder exophytic papillary urothelial neoplasms.

Background: Exophytic papillary urothelial neoplasms (EPUN) are difficult to diagnose pathologically and are well-known for their heterogeneous prognoses. Thus, searching for an objective and accurate diagnostic marker is of great clinical value in improving the outcomes of EPUN patients. PHH3 was reported to be expressed explicitly in the mitotic phase of the cell cycle, and recent studies have shown that PHH3 expression was associated with the differential diagnosis and prognosis of many tumors. However, its significance in EPUN remains unclear. This study aimed to determine the expression of PHH3 in different EPUN, compare its expression with cell-cycle related proteins Ki67 and P53, and analyze its significance in the differential diagnosis and prognostic value for high-grade papillary urothelial carcinoma (HGPUC), low-grade papillary urothelial carcinoma (LGPUC), papillary urothelial neoplasm of low malignant potential (PUNLMP) and urothelial papilloma (UP). Methods: We retrospectively analyzed the pathological diagnosis and clinical features of 26 HGPUC cases, 43 LGPUC cases, 21 PUNLMP cases and 11 UP cases. PHH3, Ki67 and P53 were detected by immunohistochemistry in 101 EPUN cases samples. The cut-off values of PHH3 mitosis count (PHMC), HE mitosis count (HEMC), Ki67 and P53 in the different EPUN were determined using the ROC curve. The distribution of counts in each group and its relationship with clinical parameters and prognosis of EPUN patients were also analyzed. Results: The determination coefficient (R2 = 0.9980) of PHMC were more potent than those of HEMC (R2 = 0.9734) in the EPUN mitotic counts microscopically by both pathologists. Of the 101 EPUN cases investigated, significant positive linear correlations were found between PHMC and HEMC, PHMC and Ki67, and HEMC and Ki67 (P < 0.0001). In HGPUC, LGPUC, PUNLMP and UP, a decreasing trend was observed in the median and range of PHMC/10HPFs, HEMC/10HPFs, Ki67 (%) and P53 (%). PHMC, HEMC, Ki67 and P53 were associated with different clinical parameters of EPUN. PHMC, HEMC, Ki67 and P53 were found to exhibit substantial diagnostic values among different EPUN and tumor recurrence. Based on the ROC curve, when PHMC was >48.5/10HPFs, a diagnosis of HGPUC was more likely, and when PHMC was >13.5/10HPFs, LGPUC was more likely. In addition, when PHMC was >5.5/10HPFs, the possibility of non-infiltrating LGPUC was greater. Kaplan-Meier survival curve analysis showed that the median recurrence-free survival (RFS) for cases with PHMC > 13.5/10HPFs and HEMC > 14.5/10HPFs were 52.5 and 48 months, respectively, and their respective hazard ratio was significantly higher (Log-rank P < 0.05). Conclusion: PHH3 exhibited high specificity and sensitivity in diagnosing EPUN. Combined with HEMC, Ki67 and P53, it can assist in the differential diagnosis of EPUN and estimate its clinical progression with high predictive value to a certain extent.

Highly efficient removal of phosphonates by ferrate-induced oxidation coupled with in situ coagulation.

Phosphonates, as a kind of important organic phosphorus in wastewater, should be removed in terms of their environmental risks. Unfortunately, traditional biological treatments fail to remove phosphonates effectively due to their biological inertness. The reported advanced oxidation processes (AOPs) usually require pH adjustment or coupling with other technologies to achieve high removal efficiency. Thus, a simple and efficient method for phosphonate removal is urgently needed. Herein, ferrate was found to remove phosphonates effectively in one-step under near-neutral circumstances by coupling oxidation and in-situ coagulation. Nitrilotrimethyl-phosphonic acid (NTMP), a typical phosphonate, could be efficiently oxidized by ferrate to release phosphate. The fraction of phosphate release increased with increasing ferrate dosage and reached 43.1% when 0.15 mM ferrate was added. Fe(VI) was responsible for NTMP oxidation, while Fe(V), Fe(IV) and ⋅OH played a minor role. Ferrate-induced phosphate release facilitated total phosphorus (TP) removal, because the phosphate is more easily removed via ferrate-resultant Fe(III) coagulation than the phosphonates. The coagulation removal of TP could reach up to 90% within 10 min. Furthermore, ferrate exerted high removal efficiencies for other commonly used phosphonates with approximately or up to 90% TP removal. This work provides a one-step efficient method to treat phosphonate-containing wastewaters.

The role of leucine-rich alpha-2-glycoprotein-1 in proliferation, migration, and invasion of tumors.

BACKGROUND: Leucine-rich alpha-2-glycoprotein-1 (LRG1) is widely involved in proliferation, migration, and invasion of various tumor cells. Recent studies have evaluated the potential of LRG1 as both an early tumor and a prognostic biomarker. METHOD: The relevant literature from PubMed is reviewed in this article. RESULTS: It has been found that LRG1 mainly acts on the regulatory mechanisms of angiogenesis, epithelial-mesenchymal transition (EMT), and apoptosis by transforming growth factor (TGF-ß) signaling pathway as well as affecting the occurrence and development of the tumors. Moreover, with advancement of research, LRG1 regulation pathways which are independent of TGF-ß signaling pathway have been gradually revealed in different tumor cells; There are several studies on the biological effects of LRG1 as an inflammatory factor, vascular growth regulator, cell adhesion, and a cell viability influencing factor. In addition, various tumor suppression methods which are based on regulation of LRG1 levels have also shown high potential clinical value. CONCLUSIONS: LRG1 are critical for the processes of tumorigenesis, development, and metastasis in various tumors. The present study reviewed the latest research on the achievements of LRG1 in tumor genesis and development. Further, this study also discussed the related molecular mechanisms of various biological functions of LRG1.

Molecular insight into the variation of dissolved organic phosphorus in a wastewater treatment plant.

To date, eutrophication becomes a great concern of vulnerable aquatic systems. Dissolved organic phosphorus (DOP) discharged from wastewater treatment plant (WWTP) holds a large source of phosphorus in receiving water. However, due to the complexity of DOP, their variation and fate in WWTP remain unknown at the molecular level, and are always overlooked. Here, the variation of DOP in a WWTP was uncovered via Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR MS). Results show that 95% of DOP in the influent could be removed by the secondary biological treatment processes. The removed DOP species were mainly lipids with the molecular characteristics of low oxygen content, low unsaturation and low aromaticity. Meanwhile, during biological treatments, some new DOP species, especially lignin/carboxylic rich alicyclic molecules (CRAM) that possessed high oxygen content, high unsaturation and high aromaticity, were produced and released into the secondary effluent. In the subsequent tertiary treatment, coagulation by aluminum salt tended to remove high molecular weight and high oxygen content DOP species in the secondary effluent, which was complementary to the biological treatment. However, the sand filter usually retained microorganisms, which would result in the generation of new DOP species in this process. During the final ultraviolet disinfection process, DOP was effectively mineralized to phosphate, especially the species with high molecular weight and highly unsaturated aromatic DOP species (e.g., lignin/CRAM and tannin), which had higher UV absorbance. The revealed variation of DOP in WWTP is beneficial to optimize the treatment processes to enhance the removal of DOP.

Stigma, Discrimination, and Hate Crimes in Chinese-Speaking World amid Covid-19 Pandemic.

The Covid-19 pandemic has given rise to stigma, discrimination, and even hate crimes against various populations in the Chinese language-speaking world. Using interview data with victims, online observation, and the data mining of media reports, this paper investigated the changing targets of stigma from the outbreak of Covid-19 to early April 2020 when China had largely contained the first wave of Covid-19 within its border. We found that at the early stage of the pandemic, stigma was inflicted by some non-Hubei Chinese population onto Wuhan and Hubei residents, by some Hong Kong and Taiwan residents onto mainland Chinese, and by some Westerners towards overseas Chinese. With the number of cases outside China surpassing that in China, stigmatization was imposed by some Chinese onto Africans in China. We further explore how various factors, such as the fear of infection, food and mask culture, political ideology, and racism, affected the stigmatization of different victim groups. This study not only improved our understanding of how stigmatization happened in the Chinese-speaking world amid Covid-19 but also contributes to the literature of how sociopolitical factors may affect the production of hate crimes.

DFT study on Ag loaded 2H-MoS2 for understanding the mechanism of improved photocatalytic reduction of CO2.

Transition metal modified molybdenum disulfide to improve the performance of photocatalytic reduction of carbon dioxide has been receiving much attention. Herein, a novel high-efficiency photocatalytic composite Ag/2H-MoS2 has been constructed and simulated using density functional theory (DFT) for unveiling the mechanism of improved photocatalytic reduction of CO2 in our experimental research. Our calculations about the band structure and electronic and optical properties indicate that the loading of Ag atoms enhances the photocatalytic performance of 2H-MoS2 nanosheets by transferring the photogenerated electrons from the valence band of 2H-MoS2 to the loaded Ag atoms. Furthermore, 20 wt% Ag loaded 2H-MoS2 is the most suitable for the thermodynamic requirement of reducing CO2 to CH4 among the catalysts with different Ag loadings, and the formation of *CHO in 20 wt% Ag/2H-MoS2 is the potential-determining step, whose Gibbs free energy reduces from 2.830 eV of 2H-MoS2 to 0.925 eV. Meanwhile the thermochemical results predict the best path for reducing CO2 on such a photocatalyst as CO2 → *COOH → *CO → *CHO → *CH2O → *OCH3 → *CH3OH → CH4. The photocatalytic performance of pristine 2H-MoS2 in CO2 reduction is therefore significantly improved by loading silver. This research provides a theoretical reference for transition metal modified 2H-MoS2 nanosheets.

Dissolved organic matter dominating the photodegradation of free DNA bases in aquatic environments.

Free DNA bases are widely present in the environments, and can be utilized by bacteria for their nucleic acids synthesis or as nutrition sources. In sunlit natural waters, these free bases probably undergo photodegradation which would change the bioavailable bases contents. Though the photodegradation of DNA has been investigated, the photodegradation behaviors of free bases may be quite different from those of DNA-confined bases in consideration of their different chemical environments. Herein, the photodegradation of four free bases (guanine, adenine, thymine and cytosine) was investigated. Results show that direct photodegradation of free bases in phosphate buffer caused by UV was slow. However, the photodegradation of these free bases were greatly enhanced in dissolved organic matter (DOM) solution. In the presence of 10-50 mg/L DOM, the photodegradation rates of free bases were increased by 1.85-14.6 times compared to the controls without DOM. DOM could result in indirect photodegradation by producing hydroxyl radical (•OH) and singlet oxygen (1O2) under irradiation, and this indirect photodegradation enhanced and dominated the free bases photodegradation. The •OH was involved in all four bases photodegradation, while the 1O2 only participated in guanine photodegradation. In phosphate buffer, the fastest photodegradation bases were pyrimidine, however, guanine became the fastest photodegradation base in DOM solution due to the selective oxidation of guanine by 1O2. In summary, DOM may be a determinant for free bases photodegradation in natural waters and thereby deeply influence free bases fates in aquatic environments.

Redox state of microbial extracellular polymeric substances regulates reduction of selenite to elemental selenium accompanying with enhancing microbial detoxification in aquatic environments.

In nature, many microorganisms show resistance to toxic selenite by reducing selenite to non-soluble and low toxic elemental selenium. Extracellular polymeric substances (EPS), a high-molecular-weight biopolymers originated from microbial metabolism, contain many reducing groups and can induce reductive transformation of pollutants. However, the roles of EPS and its redox state in reductive detoxification or reduction removal of selenite, respectively, remain unknown yet. Herein, the reduction of selenite by different sources of EPS was investigated. Selenite was proved to be reduced by EPS and partly transformed to elemental selenium. The formed elemental selenium was mainly selenium nanoparticles confirmed by transmission electron microscopy coupled with energy dispersive spectroscopy. The redox state of EPS governed selenite reduction and elemental selenium formation, and the reduced state of EPS was in favor of selenite reduction. Dissolved oxygen concentration in water regulated EPS redox state and influenced selenite reduction. The thiols, aldehyde and phenolic groups in EPS were responsible for selenite reduction. Under selenite stress, EPS was capable of increasing cell survivability by enhancing microorganisms-mediated selenite reduction. This work revealed the previously undiscovered roles of EPS in selenite reduction and elemental selenium formation in aquatic environments and also suggested a possible crucial role of EPS in selenium biogeochemical cycle.

Unrecognized Contributions of Dissolved Organic Matter Inducing Photodamages to the Decay of Extracellular DNA in Waters.

Extracellular DNA (eDNA), which is derived from lysis or secretion of cells, is ubiquitous in various environments and crucial for gene dissemination, bacterial metabolism, biofilm integrity, and aquatic monitoring. However, these processes are largely influenced by damage to eDNA. Photodamage to eDNA, one of the most important types of DNA damage in natural waters, thus far remains unclear. In particular, the roles of the ubiquitous dissolved organic matter (DOM) in this process have yet to be determined. In this study, eDNA photodamage, including both deoxynucleoside damage and strand breaks, proved to be significantly influenced by DOM. DOM competed with eDNA for photons to inhibit the direct photodamage of eDNA. Nevertheless, DOM was photosensitized to produce reactive oxygen species (ROS) (i.e., hydroxyl radicals (·OH) and singlet oxygen (1O2)) to enhance the indirect photodamage of eDNA. The ·OH induced damage to four deoxynucleosides and strand breaks, and the 1O2 substantially enhanced deoxyguanosine damage. The presence of DOM changed the main photodamage products of deoxynucleosides, additional oxidation products induced by ROS formed besides pyrimidine dimers caused by UV. Results indicate that DOM-mediated indirect photodamage contributed significantly to eDNA photodamage in most water bodies. This study revealed the previously unrecognized crucial role of DOM in the decay of eDNA in waters.

Enhanced Photodegradation of Extracellular Antibiotic Resistance Genes by Dissolved Organic Matter Photosensitization.

Extracellular antibiotic resistance genes (eARGs) contribute to antibiotic resistance, and as such, they pose a serious threat to human health. eARGs, regarded as an emerging contaminant, have been widely detected in various bodies of water. Degradation greatly weakens their distribution potential and environmental risks. Dissolved organic matter (DOM), mainly consisted of humic substances, carbohydrates, and organic acids, is ubiquitous in diverse waters and significantly affects the degradation of coexisting contaminants. However, the photodegradation of eARGs in natural water, especially regarding the roles of DOM in this process, remains unknown. Herein, we investigated the eARGs photodegradation in waters with and without DOM. Illumination has been found to effectively photodegrade eARGs, and this process was significantly enhanced by DOM. Further experiments revealed that photosensitization of DOM produced hydroxyl radicals (•OH) to enhance plasmid strand breaks and produced singlet oxygen (1O2) to accelerate the guanine oxidation, which in turn promoted the photodegradation of plasmid-carried eARGs. Transformation assays indicated that eARGs transformation efficiencies were reduced after their photodegradation. The presence of DOM accelerated the decreases of eARGs transformation efficiencies under illumination. DOM concentration and some ions (e.g., NO3-, NO2-, HCO3-, Br-, and Fe3+) affected •OH or 1O2 levels, further influencing the photodegradation of eARGs. Overall, eARGs photodegradation in aquatic environments is a crucial process both in the reduction of eARGs concentrations and in transformation efficiencies. This work facilitated us to better understand the fate of eARGs in waters.

Photomineralization of Effluent Organic Phosphorus to Orthophosphate under Simulated Light Illumination.

Organic phosphorus (OP), one of the main forms of phosphorus in effluent from biological wastewater treatment plants, may contribute to the bioavailable phosphorus pool as well as water eutrophication. However, little is known about the photomineralization of OP or the possible impacts on the phosphorus cycle in water bodies. Herein, the photomineralization of effluent OP was investigated. An increase in orthophosphate concentration was observed under illumination. The 31P liquid nuclear magnetic resonance spectra demonstrated that the release of orthophosphate resulted from photomineralization of OP. Furthermore, the photoproduced hydroxyl radicals (·OH) were proved to play a dominant role in the OP photomineralization. Nitrate, effluent organic matter (EfOM), and Fe(III) presented in effluent were the main chromophores for ·OH photoproduction, and their contributions to ·OH production and photomineralization of OP followed the order: nitrate > EfOM > Fe(III). Additionally, the carbonate (or bicarbonate) in the effluent and high pH were unfavorable for OP photomineralization. The present study revealed the photomineralization behavior of OP in actual effluent, suggesting that photomineralization of OP might contribute to eutrophication and may play a non-negligible role in phosphorus turnover in water bodies.

Local near instantaneously dynamically triggered aftershocks of large earthquakes.

Aftershocks are often triggered by static- and/or dynamic-stress changes caused by mainshocks. The relative importance of the two triggering mechanisms is controversial at near-to-intermediate distances. We detected and located 48 previously unidentified large early aftershocks triggered by earthquakes with magnitudes between ≥7 and 8 within a few fault lengths (approximately 300 kilometers), during times that high-amplitude surface waves arrive from the mainshock (less than 200 seconds). The observations indicate that near-to-intermediate-field dynamic triggering commonly exists and fundamentally promotes aftershock occurrence. The mainshocks and their nearby early aftershocks are located at major subduction zones and continental boundaries, and mainshocks with all types of faulting-mechanisms (normal, reverse, and strike-slip) can trigger early aftershocks.

A straightforward and efficient synthetic access to biologically active marine sesterterpenoids, sesterstatins 4 and 5.

A straightforward and efficient synthesis of sesterstatins 4 and 5 is reported, in which the reductive Heck cyclisation was employed as the key step for constructing the D ring.