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Abstract Aging increases the risk for Alzheimer’s disease (AD), driving pathological changes like amyloid-β (Aβ) buildup, inflammation, and oxidative stress, especially in the prefrontal cortex (PFC). We present the first subcellular-resolution spatial transcriptome atlas of the human prefrontal cortex (PFC), generated with Stereo-seq from six male AD cases at varying neuropathological stages and six age-matched male controls. Our analyses revealed distinct transcriptional alterations across PFC layers, highlighted disruptions in laminar structure, and exposed AD-related shifts in layer-to-layer and cell-cell interactions. Notably, we identified genes highly upregulated in stressed neurons and nearby glial cells, where AD diminished stress-response interactions that promote Aβ clearance. Further, cell-type-specific co-expression analysis highlighted three neuronal modules linked to neuroprotection, protein dephosphorylation, and Aβ regulation, with all modules downregulated as AD progresses. We identified ZNF460 as a transcription factor regulating these modules, offering a potential therapeutic target. In summary, this spatial transcriptome atlas provides valuable insight into AD’s molecular mechanisms.

Adult neural stem cells divide to produce neurons that migrate to preexisting neuronal circuits in a process named adult neurogenesis. Adult neurogenesis is one of the most exciting areas of current neuroscience, and it may be involved in a range of brain functions, including cognition, learning, memory, and social and behavior changes. While there is a growing number of multi-omics studies on adult neurogenesis, generalized analyses from a multi-omics perspective are lacking. In this review, we summarize studies related to genomics, metabolomics, proteomics, epigenomics, transcriptomics, and microbiomics of adult neurogenesis, and then discuss their future research priorities and potential neighborhoods. This will provide theoretical guidance and new directions for future research on adult neurogenesis.

Epilepsy is a neurological disorder characterized by high morbidity, high recurrence, and drug resistance. Enhanced signaling through the excitatory neurotransmitter glutamate is intricately associated with epilepsy. Metabotropic glutamate receptors (mGluRs) are G protein-coupled receptors activated by glutamate and are key regulators of neuronal and synaptic plasticity. Dysregulated mGluR signaling has been associated with various neurological disorders, and numerous studies have shown a close relationship between mGluRs expression/activity and the development of epilepsy. In this review, we first introduce the three groups of mGluRs and their associated signaling pathways. Then, we detail how these receptors influence epilepsy by describing the signaling cascades triggered by their activation and their neuroprotective or detrimental roles in epileptogenesis. In addition, strategies for pharmacological manipulation of these receptors during the treatment of epilepsy in experimental studies is also summarized. We hope that this review will provide a foundation for future studies on the development of mGluR-targeted antiepileptic drugs.

Abstract Background Alopecia areata (AA) is a common autoimmune hair loss disease with increasing incidence. Corticosteroids are the most widely used for hair loss treatment; however, long-term usage of hormonal drugs is associated with various side effects. Mesenchymal stem cells (MSCs) therapy has been studied extensively to curb autoimmune diseases without affecting immunity against diseases. Methods Hair follicle-derived MSCs (HF-MSCs) were harvested from the waste material of hair transplants, isolated and expanded. The therapeutic effect of HF-MSCs for AA treatment was investigated in vitro AA-like hair follicle organ model and in vivo C3H/HeJ AA mice model. Results AA-like hair follicle organ in vitro model was successfully established by pre-treatment of mouse vibrissa follicles by interferon-γ (IFN-γ). The AA-like symptoms were relieved when IFN-γ induced AA in vitro model was co-cultured with HF-MSC for 2 days. In addition, when skin grafted C3H/HeJ AA mice models were injected with 106 HF-MSCs once a week for 3 weeks, the transcription profiling and immunofluorescence analysis depicted that HF-MSCs treatment significantly decreased mouse hair loss and reduced inflammation around HF both in vitro and in vivo. Conclusions This study provides a new therapeutic approach for alopecia areata based on HF-MSCs toward its future clinical application.

Antibiotics on H2 producing bacteria shall be considered as being one of the critical elements in biological H2 production utilizing livestock manure as raw resources. Despite the fact that the manure stands a significance role in bio-fermentation, the possibility of antibiotics being contained in excreta shall not be eliminated. Findings of whether the above saying might threaten the safety of bio-H2 production needs to be further studied. The experiment subjects include: six single and three combined antibiotics were tested and analyzed by the application of the gradient experiment method. Along with the H2 production rate, CHO content, pH and OD600 were used to analyze the effects of various antibiotics introduction on the hydrolysis, fermentation and H2 production. To a further extent, four typical representative samples were selected for biodiversity analysis from the single antibiotic experiment groups. Amounting more than 6000 pieces of data were obtained in a series of experiments. Data suggested that remarkable measure of antibiotics have various degrees of H2 production inhibition, while some antibiotics, Penicillin G, Streptomycin Sulfate, and their compound antibiotics, could promote the growth of Ethanoligenens sp. and improve H2 yield in the contrary. Correspondent to the transition of key metabolic intermediates and end products, the mechanism of each antibiotic type and dose on H2 production were summarized as follows: the main inhibitory mechanisms were: (1) board-spectrum inhibition, (2) partial inhibition, (3) H2 consumption enhancement; and the enhancement mechanisms were: (1) enhance the growth of H2-producing bacteria, (2) enhanced starch hydrolysis, (3) inhibitory H2 consumption or release of acid inhibition. Meanwhile, data analysis found that the effect of antibiotics on H2 producing was not only related to type, but also to dosage. Even one kind of antibiotic may have completely opposite effects on H2-producing bacteria under different dosage conditions. Inhibition of H2 yield was highest with Levofloxacin at 6.15 mg/L, gas production was reduced by 88.77%; and enhancement of H2 yield was highest with Penicillin G at 7.20 mg/L, the gas production increased by 72.90%.

Temporal lobe epilepsy (TLE) is the most frequent type of focal epilepsy in adults, typically resistant to pharmacological treatment, and mostly presents with cognitive impairment and psychiatric comorbidities. The most common neuropathological hallmark in TLE patients is hippocampal sclerosis (HS). However, the underlying molecular mechanisms involved remain poorly characterized. The dentate gyrus (DG), one specific hippocampal subarea, structural and functional changes imply a key involvement of the DG in the development of TLE. In this study, a isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic technique was performed for the analysis of hippocampal DG obtained from patients with TLE-HS compared to control samples obtained from autopsy. Our proteomic data identified 5,583 proteins, of which 82 proteins were upregulated and 90 proteins were downregulated. Bioinformatics analysis indicated that differentially expressed proteins were enriched in “synaptic vesicle,” “mitochondrion,” “cell-cell adhesion,” “regulation of synaptic plasticity,” “ATP binding,” and “oxidative phosphorylation.” Protein-protein interaction network analysis found a pivotal module of 10 proteins that were related to “oxidative phosphorylation.” This study has investigated proteomic alterations in the DG region of TLE-HS patients, and paved the way for the better understanding of epileptogenesis mechanisms and future therapeutic intervention.

Extensive studies have been conducted on unmanned vehicle recently due to its bright prospect. However, few of them have studied the technology of driverless bus. In this paper, a path planning and navigation control system is designed for 12-m length driverless electric bus. The global path planning is adopted by the Dijkstra algorithm based on the analysis tool of ArcGIS. For local planning, a triple-layer finite-state machine is proposed to plan the driving maneuver, and it reduces computational complexity and improves driving effectiveness. Then, optimal trajectory is generated by a curve fitting technique based on path planning and driving maneuver, which takes full account of the safety and kinetics for driverless bus. In addition, we address the speed planning by expert rules to imitate an experienced driver. Finally, the trajectory tracking controller is devised by an adaptive rolling window. Moreover, a heading error compensation model and a self-adaptive strategy of controller parameters are set up to improve the control precision. Finally, simulation by TruckSim and scenes experiments verify the validity and practicability of our proposed path planning and navigation control system for driverless bus.

Abstract Microbial communities in sediments play an important role in alpine lake ecosystems. However, the microbial diversity and community composition of alpine lake sediments from the Hengduan Mountains remain largely unknown. Therefore, based on the Illumina MiSeq platform, high‐throughput sequencing analysis of the 16S rRNA gene was performed on 15 alpine lake sediments collected at different locations in the Hengduan Mountains. The abundance‐based coverage estimate (ACE), Chao1, and Shannon indices indicated that the microbial abundance and diversity of these sediments were high. There are some differences in the composition of microbial communities among sediments. However, in general, Proteobacteria accounted for the largest proportion of all sediments (22.3%–67.6%) and was the dominant phylum. Followed by Bacteroidetes, Acidobacteria, Chloroflexi, and Planctomycetes. In addition, the operational taxonomic unit (OTU) interactions network had modular structures and suggested more cooperation than competition in the microbial community. Besides, we also found that temperature has a significant contribution to the sample–environment relationship. This study revealed the diversity and composition of microbial communities in alpine lake sediments from the Hengduan Mountains, and describe the correlation between microbial community structure and different environmental variables.

Subarachnoid hemorrhage (SAH) is a life-threatening cerebrovascular disease that usually has a poor prognosis. Heat shock proteins (HSPs) have been implicated in the mechanisms of SAH-associated damage, including increased inflammation and reduced neurogenesis. The aim of this study was to investigate the effects of HSP90 inhibition on inflammation and neurogenesis in a mouse model of experimental SAH induced by endovascular surgery. Western blotting showed HSP90 levels to be decreased, while neurogenesis, evaluated by 5-bromo-2’-deoxyuridine (BrdU) immunohistochemistry, was decreased in the hippocampuses of SAH mice. SAH also induced pro-inflammatory factors such as interleukin-1β (IL-1β), capase-1 and the NLRP3 inflammasome. However, intraperitoneal administration of the specific HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) reduced the levels of HSP90, NLRP3, ASC, caspase-1 and IL-1β, while increasing the levels of brain-derived neurotrophic factor and doublecortin (DCX), as well as the number of BrdU-positive cells in SAH mice. In addition, 17-AGG improved short- and long-term neurobehavioral outcomes. The neuroprotective and anti-inflammatory effects of 17-AGG were reversed by recombinant HSP90 (rHSP90); this detrimental effect of HSP90 was inhibited by the specific P2X7 receptor (P2X7R) inhibitor A438079, indicating that SAH-induced inflammation and inhibition of neurogenesis were likely mediated by HSP90 and the P2X7R/NLRP3 inflammasome pathway. HSP90 inhibition by 17-AAG may be a promising therapeutic strategy for the treatment of SAH.

Currently, since the model of a driverless bus is not clear, it is difficult for most traditional path tracking methods to achieve a trade-off between accuracy and stability, especially in the case of driverless buses. In terms of solving this problem, a path-tracking controller based on a Fuzzy Pure Pursuit Control with a Front Axle Reference (FPPC-FAR) is proposed in this paper. Firstly, the reference point of Pure Pursuit is moved from the rear axle to the front axle. It relieves the influence caused by the ignorance of the bus’s lateral dynamic characteristics and improves the stability of Pure Pursuit. Secondly, a fuzzy parameter self-tuning method is applied to improve the accuracy and robustness of the path-tracking controller. Thirdly, a feedback-feedforward control algorithm is devised for velocity control, which enhances the velocity tracking efficiency. The proportional-integral (PI) controller is indicated for feedback control, and the gravity acceleration component in the car’s forward direction is used in feedforward control. Finally, a series of experiments is conducted to illustrate the excellent performances of proposed methods.

A framework of path planning for autonomous electric bus is presented. ArcGIS platform is utilized for map-building and global path planning. Firstly, a high-precision map is built based on GPS in ArcGIS for global planning. Then the global optimal path is obtained by network analysis tool in ArcGIS. To facilitate local planning, WGS-84 coordinates in the map are converted to local coordinates. Secondly, a double-layer finite state machine (FSM) is devised to plan driving behavior under different driving scenarios, such as structured driving, lane changing, turning, and so on. Besides, local optimal trajectory is generated by cubic polynomial, which takes full account of the safety and kinetics of the electric bus. Finally, the simulation results show that the framework is reliable and feasible for driving behavior planning and trajectory generation. Furthermore, its validity is proven with an autonomous bus platform 12 m in length.

Abstract Pazopanib (PAZ), an oral multi-tyrosine kinase inhibitor, demonstrates promising cytostatic activities against various human cancers. However, its clinical utility is limited by substantial side effects and therapeutic resistance. We developed a nanoplatform capable of delivering PAZ for enhanced anti-breast cancer therapy. Nanometer-sized PAZ@Fe-MOF, compared to free PAZ, demonstrated increased anti-tumor therapeutic activities in both syngeneic murine 4T1 and xenograft human MDA-MB-231 breast cancer models. High-throughput single-cell RNA sequencing (scRNAseq) revealed that PAZ@Fe-MOF significantly reduced pro-tumorigenic M2-like macrophage populations at tumor sites and suppressed M2-type signaling pathways, such as ATF6-TGFBR1-SMAD3, as well as chemokines including CCL17, CCL22, and CCL24. PAZ@Fe-MOF reprogramed the inhibitory immune microenvironment and curbed tumorigenicity by blocking the polarization of M2 phenotype macrophages. This platform offers a promising and new strategy for improving the cytotoxicity of PAZ against breast cancers. It provides a method to evaluate the immunological response of tumor cells to PAZ-mediated treatment.

In this paper, we considered a singular parabolic -Laplacian equation with logarithmic nonlinearity in a bounded domain with homogeneous Dirichlet boundary conditions. We established the local solvability by the technique of cut-off combining with the method of Faedo-Galerkin approximation. Based on the potential well method and Hardy-Sobolev inequality, the global existence of solutions was derived. In addition, we obtained the results of the decay. The blow-up phenomenon of solutions with different indicator ranges was also given. Moreover, we discussed the blow-up of solutions with arbitrary initial energy and the conditions of extinction.

Environmental pollution, including air pollution, plastic contamination, and heavy metal exposure, is a pressing global issue. This crisis contributes significantly to pollution-related diseases and is a critical risk factor for chronic health conditions, including cancer. Mounting evidence underscores the pivotal role of N6-methyladenosine (m6A) as a crucial regulatory mechanism in pathological processes and cancer progression. Governed by m6A writers, erasers, and readers, m6A orchestrates alterations in target gene expression, consequently playing a vital role in a spectrum of RNA processes, covering mRNA processing, translation, degradation, splicing, nuclear export, and folding. Thus, there is a growing need to pinpoint specific m6A-regulated targets in environmental pollutant-induced carcinogenesis, an emerging area of research in cancer prevention. This review consolidates the understanding of m6A modification in environmental pollutant-induced tumorigenesis, explicitly examining its implications in lung, skin, and bladder cancer. We also investigate the biological mechanisms that underlie carcinogenesis originating from pollution. Specific m6A methylation pathways, such as the HIF1A/METTL3/IGF2BP3/BIRC5 network, METTL3/YTHDF1-mediated m6A modification of IL 24, METTL3/YTHDF2 dynamically catalyzed m6A modification of AKT1, METTL3-mediated m6A-modified oxidative stress, METTL16-mediated m6A modification, site-specific ATG13 methylation-mediated autophagy, and the role of m6A in up-regulating ribosome biogenesis, all come into play in this intricate process. Furthermore, we discuss the direction regarding the interplay between pollutants and RNA metabolism, particularly in immune response, providing new information on RNA modifications for future exploration.

Abstract The state-of-the-art alkaline hydrogen evolution catalyst of united ruthenium single atoms and small ruthenium nanoparticles has sparked considerable research interest. However, it remains a serious problem that hydrogen evolution primarily proceeds on the less active ruthenium single atoms instead of the more efficient small ruthenium nanoparticles in the catalyst, hence largely falling short of its full activity potential. Here, we report that by combining highly oxophilic cerium single atoms and fully-exposed ruthenium nanoclusters on a nitrogen functionalized carbon support, the alkaline hydrogen evolution centers are facilely reversed to the more active ruthenium nanoclusters driven by the strong oxophilicity of cerium, which significantly improves the hydrogen evolution activity of the catalyst with its mass activity up to −10.1 A mg−1 at −0.05 V. This finding is expected to shed new light on developing more efficient alkaline hydrogen evolution catalyst by rational regulation of the active centers for hydrogen evolution.

In this paper, we consider the well-posedness and asymptotic behavior of Dirichlet initial boundary value problem for a fourth-order equation with strong damping and logarithmic nonlinearity. We establish the local solvability by the technique of cut-off combining with the method of Faedo–Galerkin approximation. By means of potential well method and Rellich inequality, we obtain the global existence and the decay estimate of global solutions under some appropriate conditions. Furthermore, we prove the finite time blow-up results of weak solutions, and establish the upper and lower bounds for blow-up time.

Abstract Synthetic polypeptides have emerged as versatile tools in both materials science and biomedical engineering due to their tunable properties and biodegradability. While the advancements of N-carboxyanhydride (NCA) ring-opening polymerization (ROP) techniques have aimed to expedite polymerization and reduce environment sensitivity, the broader implications of such methods remain underexplored, and the integration of ROP products with other materials remains a challenge. Here, we show an approach inspired by the success of many heterogeneous catalysts, using nanoscale metal-organic frameworks (MOFs) as co-catalysts for NCA-ROP accelerated also by peptide helices in proximity. This heterogeneous approach offers multiple advantages, including fast kinetics, low environment sensitivity, catalyst recyclability, and seamless integration with hybrid materials preparation. The catalytic system not only streamlines the preparation of polypeptides and polypeptide-coated MOF complexes (MOF@polypeptide hybrids) but also preserves and enhances their homogeneity, processibility, and overall functionalities inherited from the constituting MOFs and polypeptides.

Abstract Functionalizing porous materials with capping agents generates hybrid materials with enhanced properties, while the challenge is how to improve the selectivity and maintain the porosity of the parent framework. Herein, we developed a “Cage-on-MOF” strategy to tune the recognition and catalytic properties of MOFs without impairing their porosity. Two types of porous coordination cages (PCCs) of opposite charges containing secondary binding groups were developed to coordinatively functionalize two distinct porous MOFs, namely MOF@PCC nanocomposites. We demonstrated that the surface-capped PCCs can act as “modulators” to effectively tune the surface charge, stability, and adsorption behavior of different host MOF particles. More importantly, the MOF@PCCs can serve as selective heterogeneous catalysts for condensation reactions to achieve reversed product selectivity and excellent recyclability. This work sets the foundation for using molecular cages as porous surface-capping agents to functionalize and manipulate another porous material, without affecting the intrinsic properties of the parent framework.

Abstract Dihydroartemisinin (DHA), a natural product derived from the herbal medicine Artemisia annua, is recently used as a novel anti-cancer agent. However, some intrinsic disadvantages limit its potential for clinical management of cancer patients, such as poor water solubility and low bioavailability. Nowadays, the nanoscale drug delivery system emerges as a hopeful platform for improve the anti-cancer treatment. Accordingly, a metal-organic framework (MOF) based on zeolitic imidazolate framework-8 was designed and synthesized to carry DHA in the core (ZIF-DHA). Contrast with free DHA, these prepared ZIF-DHA nanoparticles (NPs) displayed preferable anti-tumor therapeutic activity in several ovarian cancer cells accompanied with suppressed production of cellular reactive oxygen species (ROS) and induced apoptotic cell death. 4D-FastDIA-based mass spectrometry technology indicated that down-regulated reactive oxygen species modulator 1 (ROMO1) might be regarded as potential therapeutic targets for ZIF-DHA NPs. Overexpression of ROMO1 in ovarian cancer cells significantly reversed the cellular ROS-generation induced by ZIF-DHA, as well as the pro-apoptosis effects. Taken together, our study elucidated and highlighted the potential of zeolitic imidazolate framework-8-based MOF to improve the activity of DHA to treat ovarian cancer. Our findings suggested that these prepared ZIF-DHA NPs could be an attractive therapeutic strategy for ovarian cancer.

Abstract Internal solitary waves (ISWs) in the South China Sea (SCS) are considerably modulated by the background currents. In this study, a three-dimensional high-resolution non-hydrostatic model is configured to investigate how the Kuroshio influences the generation and evolution of ISWs in the northern SCS. Three runs are conducted, including one control experiment without the Kuroshio and two sensitivity experiments with the Kuroshio in different paths. In the Luzon Strait (LS), the Kuroshio reduces the westward baroclinic energy flux radiated into the SCS, resulting in weakened ISWs. In the SCS basin, the background currents further refract the ISWs. With the leaping Kuroshio, the A-waves have longer crest lines but lower amplitudes compared with those in the control run. In contrast, the B-waves are less affected by the leaping Kuroshio. In the presence of looping Kuroshio, the wave refraction caused by the intrusion currents in the SCS basin results in the weakest amplitudes and energy but the widest crest lines of ISWs. Moreover, the energy of the A-waves exhibits double-peak structure along the crest lines. The crest lines of the B-waves extend to 19.5° N, which are more south than those in summer. These results highlight the importance of the Kuroshio on the 3D features of ISWs in the SCS.

Abstract Bearings are very important components in mechanical equipment, and detecting bearing failures helps ensure healthy operation of mechanical equipment and can prevent catastrophic accidents. Most of the well-established detection methods do not take into account the correlation between signals and are difficult to accurately identify those fault samples that have a low degree of failure. To address this problem, we propose a graph neural network-based bearing fault detection (GNNBFD) method. The method first constructs a graph using the similarity between samples; secondly the constructed graph is fed into a graph neural network (GNN) for feature mapping, and the samples outputted by the GNN network fuse the feature information of their neighbors, which is beneficial to the downstream detection task; then the samples mapped by the GNN network are fed into base detector for fault detection; finally, the results determined by the integrated base detector algorithm are determined, and the top n samples with the highest outlier scores are the faulty samples. The experimental results with five state-of-the-art algorithms on publicly available datasets show that the GNNBFD algorithm improves the AUC by 6.4% compared to the next best algorithm, proving that the GNNBFD algorithm is effective and feasible.

Summary: Metal-organic frameworks (MOFs) are crystalline porous materials characterized by their high porosity and chemical tailorability. To realize the full potential of synthesized MOFs, it is important to transform them from crystalline solid powders into materials with integrated morphologies and properties. One promising approach is facet-controlled assembly, which involves arranging individual crystalline MOF particles into ordered macroscale structures by carefully controlling the interactions between particles. The resulting assembled MOF structures maintain the characteristics of individual particles while also exhibiting improved properties overall. In this article, we emphasize the essential concepts of MOF assembly, highlighting the impact of building blocks, surface interactions, and Gibbs free energy on the assembly process. We systematically examine three methods of guiding facet-controlled MOF assembly, including spontaneous assembly, assembly guided by external forces, and assembly through surface modifications. Lastly, we offer outlooks on future advancements in the fabrication of MOF-based material and potential application exploration.

BNIP3 is a proapoptotic protein that mediates apoptosis, necrosis and autophagy. However, the involvement of BNIP3 in cisplatin‐induced apoptosis in ovarian cancer is not clear. In this study, we examined the role of BNIP3 in ovarian cancer during cisplatin treatment and its correlation with clinical outcomes. We first measured cisplatin cytotoxicity and BNIP3 levels before and after cisplatin exposure for ovarian cancer cell lines A2780, SKOV3, OVCAR4, OV2008, ES2 and HO8910. BNIP3 was observed to be differentially expressed in these cell lines, and cisplatin induced a significant increase in BNIP3 levels in A2780 and OVCAR4. BNIP3 knockdown with siRNA in A2780 and OVCAR4 significantly reduced cisplatin cytotoxicity in these two cell lines and alleviated cisplatin‐induced apoptosis. We searched the online databases Gene Expression Omnibus and The Cancer Genome Atlas to analyze the correlation between BNIP3 level and overall survival and progression‐free survival in patients with ovarian cancer. Pooled analyses showed that higher BNIP3 level was correlated with poorer overall survival (95% confidence intervals; hazard ratio = 1.18, 1.04–1.34; P = 0.013) and progression‐free survival (95% confidence intervals; hazard ratio = 1.26, 1.10–1.43; P = 0.00049). However, the results of individual datasets and stratification analyses of histology, FIGO (Federation Internationale de Gynecolgie et d’Obstetrique) stage, chemotherapy regimen and P53 mutation status varied. These findings indicate that cisplatin‐induced apoptosis is dependent on BNIP3 level in ovarian cancer cell lines. Targeting BNIP3 may therefore be a potential way of restoring cisplatin sensitivity.

This study presents isotopic compositions and their vertical profile of meteoric and surface water samples collected in the Southern Himalaya since 2015, with elevations extending all the way up to Mt. Everest’s summit. The data covering a wide altitudinal ranges and rich water types are presented for the first time. The series of in situ samples up to 8848 m asl lead to the following discoveries: (1) the dominance of rainy-season precipitation to surface-water composition in the Southern Himalaya, (2) the high correlation and high similarity between meteoric and surface-snow isotopes, thus implying the representation of surface-snow isotopes to high-elevation climatology, (3) a significant altitude effect in river and ground water, with the higher altitudinal lapse rate in ground water δ18O highlighting strong local impacts on the vertical profile of surface-water isotopes, (4) different transitions suggested by the vertical profiles of δ18O variation in snow and ice in the Southern Himalaya, with the transition in snow δ18O at a vertical zone between 6030 and 6280 m asl, and that in ice at 5775 m asl, and (5) complex circulation processes on top of the Himalaya, featuring the interaction of large-scale circulation with local mountain valley circulation, katabatic wind, and sublimation in the extremely cold and high environment. They, thus, confirm the correlation between isotopes and altitudes in regions influenced by complex circulation patterns to clarify the altitude effect, and suggest the application of isotopic study/isotopic chemistry in geological study.

Background: Chronic lead (Pb) poisoning remains an environmental risk especially for the pediatric population, and it may affect brain development. Immature neurons expressing doublecortin (DCX+) exist around cortical layer II in various mammals, including adult guinea pigs and humans. Using young adult guinea pigs as an experimental model, the present study explored if chronic Pb exposure affects cortical DCX + immature neurons and those around the subventricular and subgranular zones (SVZ, SGZ). Results: Two month-old guinea pigs were treated with 0.2% lead acetate in drinking water for 2, 4 and 6 months. Blood Pb levels in these animals reached 10.27 ± 0.62, 16.25 ± 0.78 and 19.03 ± 0.86 µg/dL at the above time points, respectively, relative to ~3 µg/dL in vehicle controls. The density of DCX + neurons was significantly reduced around cortical layer II, SVZ and SGZ in Pb-treated animals surviving 4 and 6 months relative to controls. Bromodeoxyuridine (BrdU) pulse-chasing studies failed to find cellular colocalization of this DNA synthesis indicator in DCX + cells around layer II in Pb-treated and control animals. These cortical immature neurons were not found to coexist with active caspase-3 or Fluoro-Jade C labeling. Conclusion: Chronic Pb exposure can lead to significant reduction in the number of the immature neurons around cortical layer II and in the conventional neurogenic sites in young adult guinea pigs. No direct evidence could be identified to link the reduced cortical DCX expression with alteration in local neurogenesis or neuronal death. [ABSTRACT FROM AUTHOR]

The article presents a study which investigated lead exposure's effects on beta (β)-amyloid protein (Aβ) precursor protein cleavage enzyme-1 (BACE-1) in the retinal neurons of adult rats in the early period following the exposure. The study intraocularly injected different dosages of lead acetate to the rats. Results showed that BACE-1, retinal lead concentration, and the cleavage products increased in nearly all the lead exposure.