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Abstract Epilepsy is a prevalent neurological disease that impacts around 70 million individuals globally. Anti‐seizure medications (ASMs) are the first choice for clinicians to control unprovoked epileptic seizures. Although more than 30 ASMs are available in the market, patients with epilepsy (PWEs) still show poor responses to adequate drug treatment. Meanwhile, long‐term medications not only bring heavy financial burdens but also lead to undesirable side effects. Music, a ubiquitous art form throughout human history, has been confirmed as therapeutically effective in various neurological conditions, including epilepsy. This alternative therapy offers convenience and a relatively safe approach to alleviating epileptic symptoms. Paradoxically, besides anti‐convulsant effect, some particular music would cause seizures inversely, indicating the pro‐convulsant effect of it. Considering that investigating the impact of music on epilepsy emerges as a compelling subject. In this review, we tried to present the following sections of content on this topic. Initially, we overviewed the impact of music on the brain and the significant progress of music therapy in central neurological disorders. Afterward, we classified the anti‐convulsant and pro‐convulsant effects of music in epilepsy, relying on both clinical and laboratory evidences. Finally, possible mechanisms and neural basis of the music effect were concluded, and the translational potentials and some future outlooks about the music effect in epilepsy were proposed. Plain Language Summary Epilepsy is an extremely severe neurological disorder. Although anti‐seizure medications are preferred choice to control seizures, the efficacy is not satisfied due to the tolerance. Anecdotal music effect had been deemed functional diversity but not clarified on epilepsy, pro‐convulsive, or anti‐convulsive. Here, we reviewed this interesting but puzzling topic, as well as illustrating the potential mechanisms and its translational potential.

This study explores the effects of Zn addition through micro-alloying on the microstructure and discharge performance of Mg-Al-Mn-Ca alloy anodes for magnesium-air batteries. The results show that the second-phase particles (d > 1 μm) in a Mg-Al-Mn-Ca alloy promote dynamic recrystallization (DRX) via particle-stimulated nucleation (PSN), resulting in a uniform equiaxed grain structure and fiber texture. In contrast, Zn and Ca co-segregation in a Mg-Al-Mn-Ca-Zn alloy facilitates continuous dynamic recrystallization (CDRX) and, combined with the PSN mechanism, forms a unique structure where three types of grains with different grain boundary densities coexist. The addition of Zn and Ca effectively reduces the c/a axis ratio, promoting texture homogenization. The Mg-Al-Mn-Ca alloy exhibits rough discharge surfaces due to simultaneous discharge at numerous grain boundaries and severe hydrogen evolution corrosion from micro-galvanic effects, inducing the chunk effect (CE). Conversely, the structure where three types of grains with different grain boundary densities coexist in the Mg-Al-Mn-Ca-Zn alloy promotes discharge product detachment through stress cracking, achieving uniform discharge and significantly enhancing discharge performance. The uniform texture reduces hydrogen evolution corrosion, improving anode utilization. This study demonstrates that controlling the microstructure, particularly grain boundary density and grain texture, enables the development of high-performance Mg-Al-Mn-Ca-Zn alloy anodes, especially at higher current densities, offering a new strategy for designing efficient magnesium alloy anode materials.

Heavy metal(loid)s (HMs) and disinfection by-products (DBPs) in drinking water pose risks to human health and jeopardize drinking water. Water-related behaviors vary significantly among different age groups and regions. In this study, the carcinogenic and non-carcinogenic risks of HMs (As, Cd, Cr6+, Cu, Pb, and Zn) and DBPs (bromodichloromethane (BDCM), bromoform, chloroform, dibromochloromethane (DBCM), dichloroacetic acid (DCAA), and trichloroacetic acid (TCAA)) in drinking water in two Chinese megacities (Beijing in North China and Guangzhou in South China) via multiple exposure pathways were assessed. The results showed that children aged 9 months to 2 years had a total carcinogenic risk (TCR) and hazard index (HI) above acceptable levels, indicating that despite the drinking water quality in the selected megacities meeting the current Chinese national standards (GB 5749–2022), the health risks of exposure to HMs and DBPs in drinking water for local young children should not be neglected. Specifically, the carcinogenic risk (CR) of exposure to As in drinking water for children

Site-selective functionalization of pyridines is a crucial tool for the synthesis of diverse pharmaceuticals and materials. We introduced diiminium pyridine adducts as highly convenient and potent Lewis acids. We report that tributylphosphine selectively adds to the 4-position of pyridine in tetramethyldiiminium pyridine ditrifluoromethanesulfonate, resulting in the formation of the title compound. This finding represents an advancement towards the utilization of diiminium units as organic reagents or catalysts for pyridine functionalization. We also employ computational models to determine fluoride and hydride ion affinities, Fukui function f+(r), molecular electrostatic potential, and pKa values, providing valuable insights for future investigations in this area.

The subiculum is known to contribute to seizures in epilepsy. Here the authors investigate the circuit mechanism by which the subiculum contributes to initiation and propagation of hippocampal seizures in a mouse model.

Abstract Gastric cancer (GC) is the second cause of cancer-related death and metastasis is an important cause of death. Considering difficulties in searching for metastatic driver mutations, we tried a novel strategy here. We conducted an integrative genomic analysis on GC and identified early drivers lead to metastasis. Whole-exome sequencing (WES), transcriptomes sequencing and targeted-exome sequencing (TES) were performed on tumors and matched normal tissues from 432 Chinese GC patients, especially the comparative analysis between higher metastatic-potential (HMP) group with T1 stage and lymph-node metastasis, and lower metastatic-potential (LMP) group without lymph-nodes or distant metastasis. HMP group presented higher mutation load and heterogeneity, enrichment in immunosuppressive signaling, more immune cell infiltration than LMP group. An integrated mRNA-lncRNA signature based on differentially expressed genes was constructed and its prognostic value was better than traditional TNM stage. We identified 176 candidate prometastatic mutations by WES and selected 8 genes for following TES. Mutated TP53 and MADCAM1 were significantly associated with poor metastasis-free survival. We further demonstrated that mutated MADCAM1 could not only directly promote cancer cells migration, but also could trigger tumor metastasis by establishing immunosuppressive microenvironment, including promoting PD-L1-mediated immune escape and reprogramming tumor-associated macrophages by regulating CCL2 through Akt/mTOR axis. In conclusion, GCs with different metastatic-potential are distinguishable at the genetic level and we revealed a number of potential metastatic driver mutations. Driver mutations in early-onset metastatic GC could promote metastasis by establishing an immunosuppressive microenvironment. This study provided possibility for future target therapy of GC.

Soil contamination with heavy metal(loid)s may influence microbial activities in the soil, and consequently jeopardize soil health. Microbial responses to soil contamination play an important role in ecological risk assessment. This study investigated the effect of heavy metal(loid)s contamination on microbial community structure and abundance in the surrounding soil of an abandoned antimony (Sb) smelter in Qinglong county, Guizhou province, Southwest China. A total of 46 soil samples were collected from ten sampling sites (labelled as A–I, and CK) across the study area at depths of 0–2, 2–10, 10–20, 20–30, 30–40, and 40–50 cm. The soil samples were analyzed for total and bioavailable heavy metal(loid) concentrations, bacterial, fungal, and archaeal community structures, diversities, and functions, together with soil basic physicochemical properties. Much greater ecological risk of Sb and arsenic (As) was present in the surface soil (0–2 cm) compared to that in the subsoils. The activities of dominant microorganisms tended to be associated with soil pH and heavy metal(loid)s (i.e., Sb, As, lead (Pb), cadmium (Cd), and chromium (Cr)). Bacteria associated with IMCC26256, Rhizobiales, Burkholderiales, and Gaiellales, and archaea associated with Methanocellales were estimated to be tolerant to high concentrations of Sb and As in the soil. In addition, the magnitude of soil microbial responses to Sb and As contamination was in the order of archaea > bacteria > fungi. In contrast to the negligible response of fungi and negative response of bacteria to Sb and As contamination, there was a strongly positive correlation between archaeal activity and total Sb and As concentrations in the soil. Our findings provide a theoretical basis for the remediation of Sb smelter-affected soil.

The ATP1A3 gene, which encodes the Na+/K+-ATPase α3 catalytic subunit, plays a crucial role in both physiological and pathological conditions in the brain, and mutations in this gene have been associated with a wide variety of neurological diseases by impacting the whole infant development stages. Cumulative clinical evidence suggests that some severe epileptic syndromes have been linked to mutations in ATP1A3, among which inactivating mutation of ATP1A3 has been intriguingly found to be a candidate pathogenesis for complex partial and generalized seizures, proposing ATP1A3 regulators as putative targets for the rational design of antiepileptic therapies. In this review, we introduced the physiological function of ATP1A3 and summarized the findings about ATP1A3 in epileptic conditions from both clinical and laboratory aspects at first. Then, some possible mechanisms of how ATP1A3 mutations result in epilepsy are provided. We think this review timely introduces the potential contribution of ATP1A3 mutations in both the genesis and progression of epilepsy. Taken that both the detailed mechanisms and therapeutic significance of ATP1A3 for epilepsy are not yet fully illustrated, we think that both in-depth mechanisms investigations and systematic intervention experiments targeting ATP1A3 are needed, and by doing so, perhaps a new light can be shed on treating ATP1A3-associated epilepsy.

Research on greenhouse gas (GHG; CO2, CH4, N2O) emissions from hydropower reservoirs has attracted widespread attention due to the potential effect on global climate change. However, few attempts have been made to conduct the research progress in this field from a global perspective. In this study, knowledge mapping research was conducted by applying scientometric analysis to explore research hotspots, frontiers and emerging trends of this field from 1993 to 2021, and five research priorities were recommended for the further study. The results showed that the research on GHG emissions from hydropower reservoirs was interdisciplinary, and there was an exponential increase in yearly publication outputs. Additionally, China, Brazil, Canada, America, and France were the leading contributors with high publication outputs, and the Chinese Academy of Science was the most productive and influential institution. Furthermore, the research hotspots in the field mainly focused on CO2, CH4, and N2O emissions and their spatiotemporal characteristics due to great contributions to greenhouse effect and heterogeneities of the GHG emissions from hydropower reservoirs. Research frontiers mainly concentrated on the Three Gorges Reservoir, bubble-mediated gas exchange, GHG emissions across different interfaces and gas transfer velocity. Meanwhile, the first three research frontiers were regarded as emerging trends in recent years. Although great progress has been made in the field, there were still some research challenges. Future research priorities were recommended to strengthen: 1) Application of remote sensing in the research on GHG emissions from hydropower reservoirs, 2) improvement of life cycle assessment research, 3) standardization research on the measurement methods, 4) anthropogenic impacts on carbon dynamics, and 5) international cooperation and database construction. Finally, several mitigation measures were suggested to provide useful insights into the management and control of GHG emissions. In contrast to previous reviews, this paper provides an insight for the visual study of the research on GHG emissions from hydropower reservoirs, helping researchers understand the current research status and future perspectives from a global perspective.

Antibiotics have been detected in tiny environmental matrices all over the world, which caused a lot of concern. To solve this problem, biological treatment can be a low-cost and high-efficiency way. The use of biochar adsorbents made from the residual sludge of sewage for wastewater treatment can achieve pollutant removal while realizing pollutant reduction and reuse, which is of great significance for green development. In this study, a prepared biochar-based adsorbent (PBA) was modified and used for norfloxacin (NOR) removal. The composition of the adsorbent was characterized, and the influence of application factors on adsorption performance was investigated. After being modified and optimized, an overall removal efficiency of 84% was achieved for NOR in 4 h. The adsorption behavior was spontaneous and consistent with the Lagergren pseudo-second kinetic model and Langmuir model. The adsorption capacity of PBA reached 8.69 mg·L−1 for NOR. A total removal efficiency of 62% was obtained for five mixed quinolone antibiotics by PBA. The PBA could be well regenerated and reused five times. This study explored a new method of the bio-waste utilization of sewage sludge for antibiotic removal from wastewater.

Companies increasingly tender knowledge-intensive tasks using crowdsourcing platforms to gain access to scarce knowledge and skills otherwise out of reach, and in this way, gaining competitive advantage. Despite its potential, existing crowdsourcing platforms encounter several challenges, including (1) fragmentation of expertise, as there are many platforms, (2) distrust between task providers and crowdsourcing participants, as identity and past performance are often not known, and (3) inability to learn from experience due to a lack of openness. A reference architecture for blockchain-based knowledge-intensive crowdsourcing platforms to mediate transactions between demand and supply of knowledge is designed in this paper to overcome these challenges. A design science research method is followed to develop the architecture. The reference architecture shows how blockchain and smart contract components can be integrated to support and coordinate knowledge-intensive crowdsourcing activities. By removing traditional e-commerce intermediaries, blockchain reduces search friction, knowledge transfer costs, and cheating by task providers or crowdsourcing participants.

Virtual Reality (VR) has been around for a long time but has come into the spotlight only recently. From an industrial perspective, this article serves as a proverbial scalpel to dissect the different use cases and commercial applications of VR in Singapore. Before researching the Singapore market, we examine how VR has evolved. At the moment, the global annual budget for VR (and augmented reality) is at an upward trend with a leading growth in market value for the training sector. VR in Singapore has also seen a rapid development in recent years. We discuss some of the Singapore government's initiatives to promote the commercial adoption of VR for the digital economy of the nation. To address the mass adoption of VR, we present VRcollab's business solutions for the construction and building industry. 2020 is one of the most important years for VR in history.

Secondary epileptogenesis is a common phenomenon in epilepsy, characterized by epileptiform discharges from the regions outside the primary focus. It is one of the major reasons for pharmacoresistance and surgical failure. Compared with primary epileptogenesis, the mechanism of secondary epileptogenesis is usually more complex and diverse. In this review, we aim to summarize the characteristics of secondary epileptogenesis from both clinical and laboratory studies in a historical view. Mechanisms of secondary epileptogenesis in molecular, cellular, and circuity levels are further presented. Potential treatments targeting the process are discussed as well. At last, we highlight the importance of circuitry studies, which would further illustrate precise treatments of secondary epileptogenesis in the future.

The first national-scale assessment of lead (Pb) contamination in agricultural soils across China was conducted based on >1900 articles published between 1979 and 2016. Pb concentrations, temporal and spatial variations, and influencing factors were analyzed. Children's blood lead levels (BLLs) were also estimated using the integrated exposure uptake biokinetic (IEUBK) model. Pb concentrations in different areas of China varied greatly, which was closely associated with the distribution of Pb-related industries, especially Pb-zinc mine smelting, non-ferrous polymetallic mine smelting, e-waste recycling, and leaded gasoline consumption. The year 2000 was a significant transition year for Pb concentrations, with a rapid increase pre-2000 and a subsequent slow upward trend. Pb concentrations were found to be strongly associated with indicators of economic and social development including gross domestic product (GDP), population size, and vehicle ownership. Leaded gasoline, coal combustion, and non-ferrous smelting were the main sources of atmospheric Pb during the different periods. Predicted BLLs were higher in South China than those in the north. This study details the overall Pb contamination status of agricultural soils in China, and thus provides insights for policymakers with respect to pollution prevention measures. Keywords: Lead, Agricultural soils, Influence factors, China, Tempo-spatial variations, BLLs

Abstract The monocytic MDSC (M‐MDSC) is one of the major types of MDSCs, which play important roles in suppression of antitumor immunity. However, the mechanisms underlying how M‐MDSCs so heavily accumulate in patients with cancer are still poorly understood. The purpose of this study was to identify miRNAs that regulate the proliferation and differentiation of M‐MDSCs. Microarray analysis was performed to identify differentially expressed miRNAs between tumor‐induced M‐MDSCs (TM‐MDSCs) and their counterparts from tumor‐free mice. The miRNAs and their target genes that regulate the proliferation and differentiation of myeloid cells were predicted by bioinformatics analysis and validated by RT‐qPCR. Luciferase reporter assays were used to analyze the relationships between miRNAs and target genes. Overexpression of candidate miRNAs and target genes in myeloid cells was conducted to verify their functions in cell proliferation, differentiation, and apoptosis. Our data showed that miR‐486 was overexpressed in TM‐MDSCs. Cebpa was predicted to be one of the target genes of miR‐486 that regulates the proliferation of myeloid cells. Expression of Cebpa was inversely correlated with miR‐486 in TM‐MDSCs, and we found that overexpression of miR‐486 suppressed the expression of Cebpa in both 293T cells determined by luciferase reporter assays and in myeloid cells determined by RT‐qPCR. Overexpression of miR‐486 promoted proliferation and suppressed apoptosis in myeloid cells, as opposed to overexpression of Cebpa, which promoted the opposing phenotype. Overexpression of either miR‐486 or Cebpa inhibited differentiation of myeloid cells. This study indicates that miR‐486 promotes proliferation and suppresses apoptosis in myeloid cells by targeting Cebpa in vitro, suggesting that miR‐486 and Cebpa might be involved in the expansion of TM‐MDSCs in tumor‐bearing mice.

Abstract Background The influences of oncogenic Ezh2 on the progression and prognosis of gastric cancer (GC) and the underlying mechanisms are still poorly understood. Here, we aimed at investigating clinicopathological significance of Ezh2 in GC and the mechanisms underlying its function in GC development. Methods The expression level of Ezh2 was determined by qRT-PCR, immunoblot, and immunohistochemistry analysis in 156 pairs of GC tissues and adjacent normal gastric mucosa tissues. The biological functions of Ezh2 were assessed by in vitro and in vivo functional experiments. Chromatin immunoprecipitation (ChIP), luciferase, and Western blotting analyses were utilized to identify the relationship between Ezh2 and the PTEN/Akt signaling. Results The expression of Ezh2 was higher in gastric cancer tissues in comparison with para-nontumorous epithelium. High expression of Ezh2 was associated with more aggressive biological behavior and poor prognosis in GC. In vitro studies indicated that Ezh2 promoted GC cells’ proliferation and clonogenicity. Besides, Ezh2 led to the acquisition of epithelial–mesenchymal transition (EMT) phenotype of GC cells and enhanced GC cell migration and invasion capacity. In particular, Ezh2 strengthened sphere-forming capacity of GC cells, indicating its role in the enrichment of GC stem cells. Furthermore, we found that PTEN/Akt signaling contributed to the effects of Ezh2 on cancer stem cells (CSC) and EMT phenotype in GC cells, and blocking PTEN signaling significantly rescued the effects of Ezh2. Conclusions Taken together, Ezh2 has a central role in regulating diverse aspects of the pathogenesis of GC in part by involving PTEN/Akt signaling, indicating that it could be an independent prognostic factor and potential therapeutic target.

Electroacupuncture (EA) point specific (ST36-37) stimulation decreases cardiovascular reflex responses through supraspinal regions such as the hypothalamic paraventricular nucleus (PVN) while mechanical stimulation of acupoints decreases pressor responses through peripheral thermal transient receptor potential vanilloid type-1 (TRPV1). Moxibustion generating heat applied at acupoint in combination with antihypertensive drugs decreases elevated blood pressure. We hypothesized that moxibustion modulates sympathoexcitatory cardiovascular responses through the hypothalamic PVN and peripheral heat sensitive TRPV1 in the absence of antihypertensive drugs. Rats were anesthetized, ventilated, and heart rate and mean blood pressure were monitored. Gastric distention induced consistent pressor reflex responses every 10-min. Thirty-minutes of bilateral moxibustion at the acupoint ST36, overlying the deep peroneal nerves, reduced the gastric distention evoked elevation in blood pressure. Blood pressure reflex responses were not reduced by both EA and moxibustion at G39. The moxibustion inhibition but not EA inhibition of the cardiovascular responses was reversed with blockade of local heat sensitive TRPV1 at ST36. Accordingly, activation of thermal TRPV1 by moxibustion at an average of 44.2°C in contrast to 40°C reduced the pressor responses. Naloxone, an opioid receptor antagonist, microinjected into PVN inhibited transiently the effect of moxibustion. Thus, activation of peripheral heat sensitive TRPV1 mediated the moxibustion-inhibition, but not EA-inhibition, of sympathoexcitatory cardiovascular reflex responses through hypothalamic PVN opioid system.

The subiculum represents a crucial brain pivot in regulating seizure generalization in temporal lobe epilepsy (TLE), primarily through a synergy of local GABAergic and long-projecting glutamatergic signaling. However, little is known about how subicular GABAergic interneurons are involved in a cell-type-specific way. Here, employing Ca2+ fiber photometry, retrograde monosynaptic viral tracing, and chemogenetics in epilepsy models of both male and female mice, we elucidate circuit reorganization patterns mediated by subicular cell-type-specific interneurons and delineate their functional disparities in seizure modulation in TLE. We reveal distinct functional dynamics of subicular parvalbumin+ and somatostatin+ interneurons during secondary generalized seizure. These interneuron subtypes have their biased circuit organizations in terms of both input and output patterns, which undergo distinct reorganization in chronic epileptic condition. Notably, somatostatin+ interneurons exert more effective feedforward inhibition onto pyramidal neurons compared with parvalbumin+ interneurons, which engenders consistent antiseizure effects in TLE. These findings provide an improved understanding of different subtypes of subicular interneurons in circuit reorganization in TLE and supplement compelling proofs for precise treatment of epilepsy by targeting subicular somatostatin+ interneurons. [ABSTRACT FROM AUTHOR]