Childhood unpredictability and sleep quality in adulthood: the mediating roles of life history strategy and perceived stress.

Background: Early environmental risk have been found to be related to lifelong health. However, the impact of childhood unpredictability, a type of early environmental risk, on health, especially on sleep quality in adulthood, has not been adequately studied. The present study aimed to examine the relationship between childhood unpredictability and sleep quality in adulthood and to explore the possible mediating roles of life history strategy and perceived stress. Methods: A cross-sectional study was conducted on 472 participants from a university in Zhejiang Province, China. The questionnaire inquired about demography, childhood unpredictability, life history strategy (Mini-K), perceived stress (14-item Perceived Stress Scale), and Sleep Quality (Pittsburgh Global Sleep Quality Index). Results: Higher childhood unpredictability was significantly associated with worse sleep quality in adulthood. Moreover, the link between higher childhood unpredictability and worse sleep quality in adulthood was explained by the chain mediation of life history strategy and perceived stress. Conclusion: In line with the life history theory, individuals who have experienced higher unpredictability in childhood tend to develop a faster life history strategy and become more sensitive to stress in adulthood, and subsequently suffer a decrease in sleep quality.

Facile fabrication of nanocellulose-supported membrane composited with modified carbon nitride and HKUST-1 for efficient photocatalytic degradation of formaldehyde.

As a cellulose-derived material, nanocellulose possesses unique properties that make it an ideal substrate for various functional composite materials. In this study, we developed a novel composite membrane material capable of adsorbing and photo-catalyzing formaldehyde by immobilizing HKUST-1 (copper open framework composed of 1,3,5-benzenetricarboxylic acid) onto NFC (Nano-fibrillated cellulose) membranes and subsequently loading modified carbon nitride. The synthesized CNx@HN composite membrane (consisting of NFC membrane with anchored HKUST-1 and modified g-C3Nx nanosheets) was thoroughly characterized, and its photocatalytic degradation performance towards low concentrations of formaldehyde (3.0 mg/m3) was investigated. The results demonstrated that HKUST-1's porous nature exhibited a concentrated adsorption capacity for formaldehyde, while the modified CNx (Modified g-C3Nx nanosheets) displayed robust photocatalytic degradation of formaldehyde. The synergistic effect of HKUST-1 and modified CNx on the NFC membrane significantly enhanced the efficiency of formaldehyde degradation. Under xenon lamp irradiation, CNx@HN-5 achieved a total removal efficiency of 86.9 % for formaldehyde, with a photocatalytic degradation efficiency of 48.45 %, showcasing its exceptional ability in both adsorption and photocatalytic degradation of formaldehyde. Furthermore, after 10 cycles of recycling, the composite membrane exhibited excellent stability for the photocatalytic degradation process. Therefore, this study presents a green and facile strategy to fabricate nanocellulose-supported composite membranes with great potential for practical applications in formaldehyde degradation.

Pangolin HKU4-related coronaviruses found in greater bamboo bats from southern China.

Coronavirus (CoV) spillover originating from game animals, particularly pangolins, is currently a significant concern. Meanwhile, vigilance is urgently needed for coronaviruses carried by bats, which are known as natural reservoirs of many coronaviruses. In this study, we collected 729 anal swabs of 20 different bat species from nine locations in Yunnan and Guangdong provinces, southern China, in 2016 and 2017, and described the molecular characteristics and genetic diversity of alphacoronaviruses (αCoVs) and betacoronaviruses (ßCoVs) found in these bats. Using RT-PCR, we identified 58 (8.0%) bat CoVs in nine bat species from six locations. Furthermore, using the Illumina platform, we obtained two representative full-length genomes of the bat CoVs, namely TyRo-CoV-162275 and TyRo-CoV-162269. Sequence analysis showed that TyRo-CoV-162275 shared the highest identity with Malayan pangolin (Manis javanica) HKU4-related coronaviruses (MjHKU4r-CoVs) from Guangxi Province, whereas TyRo-CoV-162269 was closely related to HKU33-CoV discovered in a greater bamboo bat (Tylonycteris robustula) from Guizhou Province. Notably, TyRo-CoV-162275 has a putative furin protease cleavage site in its S protein and is likely to utilize human dipeptidyl peptidase-4 (hDPP4) as a cell-entry receptor, similar to MERS-CoV. To the best of our knowledge, this is the first report of a bat HKU4r-CoV strain containing a furin protease cleavage site. These findings expand our understanding of coronavirus geographic and host distributions.

Inhibition of LNC EBLN3P Enhances Radiation-Induced Mitochondrial Damage in Lung Cancer Cells by Targeting the Keap1/Nrf2/HO-1 Axis.

Lung cancer remains the leading cause of cancer-related deaths in both women and men, claiming millions of lives worldwide. Radiotherapy is an effective modality for treating early-stage lung cancer; however, it cannot completely eradicate certain tumor cells due to their radioresistance. Radioresistance is commonly observed in conventionally fractionated radiotherapy, which can lead to treatment failure, metastasis, cancer recurrence, and poor prognosis for cancer patients. Identifying the underlying molecular mechanisms of radioresistance in lung cancer can promote the development of effective radiosensitizers, thereby improving patients' life expectancy and curability. In this study, we identified LNC EBLN3P as a regulator of lung cancer cell proliferation and radiosensitivity. The repression of LNC EBLN3P could increase ROS production and mitochondrial injury in NSCLC cells. In addition, knocking down LNC EBLN3P increased the binding of Nrf2 to Keap1, resulting in enhanced Nrf2 degradation, decreased translocation of Nrf2 to the nucleus, reduced expression of antioxidant protein HO-1, weakened cellular antioxidant capacity, and increased radiosensitivity of NSCLC cells. These findings suggest that targeting LNC EBLN3P could be a promising strategy for developing novel radiosensitizers in the context of conventional radiotherapy for NSCLC.

The difference in the composition of gut microbiota is greater among bats of different phylogenies than among those with different dietary habits.

Bats have a very long evolutionary history and are highly differentiated in their physiological functions. Results of recent studies suggest effects of some host factors (e.g., phylogeny and dietary habit) on their gut microbiota. In this study, we examined the gut microbial compositions of 18 different species of bats. Results showed that Firmicutes, Gammaproteobacteria, and Actinobacteria were dominant in all fecal samples of bats. However, the difference in the diversity of gut microbiota among bats of different phylogenies was notable (p = 0.06). Various species of Firmicutes, Actinobacteria, and Gammaproteobacteria were found to contribute to the majority of variations in gut microbiota of all bats examined, and Aeromonas species were much more abundant in bats that feed on both insects and fish than in those of insectivores. The abundance of various species of Clostridium, Euryarchaeota, and ancient bacterial phyla was found to vary among bats of different phylogenies, and various species of Vibrio varied significantly among bats with different dietary habits. No significant difference in the number of genes involved in various metabolic pathways was detected among bats of different phylogenies, but the abundance of genes involved in 5 metabolic pathways, including transcription; replication, recombination, and repair; amino acid transport and metabolism; and signal transduction mechanisms, was different among bats with different dietary habits. The abundance of genes in 3 metabolic pathways, including those involved in stilbenoid, diarylheptanoid, and gingerol biosynthesis, was found to be different between insectivorous bats and bats that feed on both insects and fish. Results of this study suggest a weak association between dietary habit and gut microbiota in most bats but a notable difference in gut microbiota among bats of different phylogenies.

Confirmation of the existence of Himalayan long-eared bats, Plecotushomochrous (Chiroptera, Vespertilionidae), in China.

The existence of Himalayan long-eared bats, Plecotushomochrous (Chiroptera, Vespertilionidae), in China has not been previously confirmed. In this study, four bats captured with harp traps from two sites in the Maoershan National Nature Reserve in Guangxi, China were investigated. These bats have long, wide auricles, each with a prominent tragus. The length of each auricle is about the same as that of a forearm. Hairs on the ventral fur have a dark base with mixed grey and yellowish tips; those on the dorsal fur also have a dark base and are bicolored with brown tips. The thumbs are very short. A concavity is present in the front of the dorsal side of the cranium. Based on morphological characteristics and phylogeny using Cyt b gene sequences, these bats were identified as P.homochrous, thus confirming the existence of Himalayan long-eared bats in China.

Epigenetic modifications in radiation-induced non-targeted effects and their clinical significance.

BACKGROUND: Ionizing radiation (IR) plays an important role in the diagnosis and treatment of cancer. Besides the targeted effects, the non-targeted effects, which cause damage to non-irradiated cells and genomic instability in normal tissues, also play a role in the side effects of radiotherapy and have been shown to involve both alterations in DNA sequence and regulation of epigenetic modifications. SCOPE OF REVIEW: We summarize the recent findings regarding epigenetic modifications that are involved in radiation-induced non-targeted effects as well as their clinical significance in radiotherapy and radioprotection. MAJOR CONCLUSIONS: Epigenetic modifications play an important role in both the realization and modulation of radiobiological effects. However, the molecular mechanisms underlying non-targeted effects still need to be clarified. GENERAL SIGNIFICANCE: A better understanding of the epigenetic mechanisms related to radiation-induced non-targeted effects will guide both individualized clinical radiotherapy and individualized precise radioprotection.

Radiation-induced bystander effect and its clinical implications.

For many years, targeted DNA damage caused by radiation has been considered the main cause of various biological effects. Based on this paradigm, any small amount of radiation is harmful to the organism. Epidemiological studies of Japanese atomic bomb survivors have proposed the linear-non-threshold model as the dominant standard in the field of radiation protection. However, there is increasing evidence that the linear-non-threshold model is not fully applicable to the biological effects caused by low dose radiation, and theories related to low dose radiation require further investigation. In addition to the cell damage caused by direct exposure, non-targeted effects, which are sometimes referred to as bystander effects, abscopal effects, genetic instability, etc., are another kind of significant effect related to low dose radiation. An understanding of this phenomenon is crucial for both basic biomedical research and clinical application. This article reviews recent studies on the bystander effect and summarizes the key findings in the field. Additionally, it offers a cross-sectional comparison of bystander effects caused by various radiation sources in different cell types, as well as an in-depth analysis of studies on the potential biological mechanisms of bystander effects. This review aims to present valuable information and provide new insights on the bystander effect to enlighten both radiobiologists and clinical radiologists searching for new ways to improve clinical treatments.

voxel2vec: A Natural Language Processing Approach to Learning Distributed Representations for Scientific Data.

Relationships in scientific data, such as the numerical and spatial distribution relations of features in univariate data, the scalar-value combinations' relations in multivariate data, and the association of volumes in time-varying and ensemble data, are intricate and complex. This paper presents voxel2vec, a novel unsupervised representation learning model, which is used to learn distributed representations of scalar values/scalar-value combinations in a low-dimensional vector space. Its basic assumption is that if two scalar values/scalar-value combinations have similar contexts, they usually have high similarity in terms of features. By representing scalar values/scalar-value combinations as symbols, voxel2vec learns the similarity between them in the context of spatial distribution and then allows us to explore the overall association between volumes by transfer prediction. We demonstrate the usefulness and effectiveness of voxel2vec by comparing it with the isosurface similarity map of univariate data and applying the learned distributed representations to feature classification for multivariate data and to association analysis for time-varying and ensemble data.

Diatomite Composited with a Zeolitic Imidazolate Framework for Removing Phosphate from Water.

Adsorption technology based on various adsorbents has been widely applied in wastewater treatment containing phosphate. A novel diatomite adsorbent composited with ZIF-8 (CZD) was developed for removing phosphate from water in this work. The chitosan was used to pre-modify the diatomite so that ZIF-8 could be anchored on the surface of the diatomite solidly and uniformly. The diatomite composited with ZIF-8 was then used to remove phosphate in water by an adsorption process, the process variables such as adsorption time, temperature, pH, and competitive ions were investigated. The electrostatic attraction was the primary mechanism of phosphate removal. The adsorption reached equilibrium within 90 min, and its sorption capacity increased when adsorption time and temperature increased. Especially, CZD had a rapid adsorption rate and 85% of the phosphate in the solution can be adsorbed within the first 10 min. The maximum phosphate adsorption capacities of the modified diatomite reached 13.46, 13.55, and 13.95 mg/g at 25, 35, and 45 °C, respectively. The removal efficiencies of CZD for phosphate were more than 98% and even came up to 100% at 45 °C. The adsorption isotherms fit well with the Langmuir isotherm model. The Freundlich isotherm and Temkin isotherm showed that the adsorption process is physical in nature. The kinetic data of the adsorption process were fitted by the pseudo-second-order kinetics. Thermodynamic parameters indicated that the adsorption process was endothermic. This adsorbent provided an alternative for phosphate removal on account of the high adsorption efficiency in a short time. Therefore, CZD could be a promising and eco-friendly phosphate adsorbent for wastewater treatment.

Diatomite Modified with an Alkyl Ketene Dimer for Hydrophobicity of Cellulosic Paper.

Multifunctionalization of papermaking chemicals is one of the main developing strategies. Fillers and internal sizing agents are often mutually restricted in practice. Therefore, it is feasible to prepare a new papermaking chemical by combining the functions of both. A process of diatomite modified with an alkyl ketene dimer (AKD) was developed in this study. The modified diatomite (AD) can concurrently play the role of a mineral filler and sizing agent in the papermaking process. With the equal dosage of AKD, the AD showed better sizing and retention performance than the commercial AKD emulsion in the case of cationic polyacrylamide (CPAM) and the CPAM/bentonite retention system. The sizing mechanism of the AD can be interpreted to be due to numerous hydrophobic sites and the microsurface structure of the paper sheet caused by the AD. Since ketones were not detected in Fourier-transform infrared spectra of the paper sheet filled by the AD, the chemical reaction may not be indispensable for its sizing performance. What is more, an interesting "sticky" hydrophobicity phenomenon was observed when filling with AD. The approach in this study to prepare the "sticky" hydrophobic paper sheet can find its applications in some nontraditional application fields of cellulosic paper.

A map of bat virus receptors derived from single-cell multiomics.

Bats are considered reservoirs of many lethal zoonotic viruses and have been implicated in several outbreaks of emerging infectious diseases, such as SARS-CoV, MERS-CoV, and SARS-CoV-2. It is necessary to systematically derive the expression patterns of bat virus receptors and their regulatory features for future research into bat-borne viruses and the prediction and prevention of pandemics. Here, we performed single-nucleus RNA sequencing (snRNA-seq) and single-nucleus assay for transposase-accessible chromatin using sequencing (snATAC-seq) of major organ samples collected from Chinese horseshoe bats (Rhinolophus affinis) and systematically checked the expression pattern of bat-related virus receptors and chromatin accessibility across organs and cell types, providing a valuable dataset for studying the nature of infection among bat-borne viruses.

Ecological study of cave nectar bats reveals low risk of direct transmission of bat viruses to humans.

Bats are reservoirs of various viruses. The widely distributed cave nectar bat ( Eonycteris spelaea) is known to carry both filoviruses and coronaviruses. However, the potential transmission of theses bat viruses to humans is not fully understood. In this study, we tracked 16 E. spelaea bats in Mengla County, Yunnan Province, China, using miniaturized GPS devices to investigate their movements and potential contact with humans. Furthermore, to determine the prevalence of coronavirus and filovirus infections, we screened for the nucleic acids of the Menglà virus (MLAV) and two coronaviruses (GCCDC1-CoV and HKU9-CoV) in anal swab samples taken from bats and for antibodies against these viruses in human serum samples. None of the serum samples were found to contain antibodies against the bat viruses. The GPS tracking results showed that the bats did not fly during the daytime and rarely flew to residential areas. The foraging range of individual bats also varied, with a mean cumulative nightly flight distance of 25.50 km and flight speed of up to 57.4 km/h. Taken together, these results suggest that the risk of direct transmission of GCCDC1-CoV, HKU9-CoV, and MLAV from E. spelaea bats to humans is very low under natural conditions.

Epidemiology and Genomic Characterization of Two Novel SARS-Related Coronaviruses in Horseshoe Bats from Guangdong, China.

Severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) and SARS-CoV-2, the causative agents of SARS, which broke out in 2003, and coronavirus disease 2019 (COVID-2019), which broke out in 2019, probably originated in Rhinolophus sinicus and R. affinis, respectively. Rhinolophus bats are important hosts for coronaviruses. Many SARS-related coronaviruses (SARSr-CoVs) have been detected in bats from different areas of China; however, the diversity of bat SARSr-CoVs is increasing, and their transmission mechanisms have attracted much attention. Here, we report the findings of SARSr-CoVs in R. sinicus and R. affinis from South China from 2008 to 2021. The full-length genome sequences of the two novel SARSr-CoVs obtained from Guangdong shared 83 to 88% and 71 to 72% nucleotide identities with human SARS-CoV and SARS-CoV-2, respectively, while sharing high similarity with human SARS-CoV in hypervariable open reading frame 8 (ORF8). Significant recombination occurred between the two novel SARSr-CoVs. Phylogenetic analysis showed that the two novel bat SARSr-CoVs from Guangdong were more distant than the bat SARSr-CoVs from Yunnan to human SARS-CoV. We found that transmission in bats contributes more to virus diversity than time. Although our results of the sequence analysis of the receptor-binding motif (RBM) and the expression pattern of angiotensin-converting enzyme 2 (ACE2) inferred that these viruses could not directly infect humans, risks still exist after some unpredictable mutations. Thus, this study increased our understanding of the genetic diversity and transmission of SARSr-CoVs carried by bats in the field. IMPORTANCE Severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2 probably originated from the SARS-related coronaviruses (SARSr-CoVs) carried by Rhinolophus bats from Yunnan, China. Systematic investigations of the reservoir hosts carrying SARSr-CoVs in Guangdong and the reservoir distribution and transmission are urgently needed to prevent future outbreaks. Here, we detected SARSr-CoV in Rhinolophus bat samples from Guangdong in 2009 and 2021 and found that the transmission of SARSr-CoV from different host populations contributes more to increased virus diversity than time. Bat SARSr-CoVs in Guangdong had genetic diversity, and Guangdong was also the hot spot for SARSr-CoVs. We once again prove that R. sinicus plays an important role in the maintenance of the SARS-CoVs. Besides, the SARSr-CoVs are mainly transmitted through the intestines in bats, and these SARSr-CoVs found in Guangdong could not use human ACE2 (hACE2), but whether they can pass through intermediate hosts or directly infect humans requires further research. Our findings demonstrate the ability of SARSr-CoVs to spread across species.

IsoExplorer: an isosurface-driven framework for 3D shape analysis of biomedical volume data.

ABSTRACT: The high-resolution scanning devices developed in recent decades provide biomedical volume datasets that support the study of molecular structure and drug design. Isosurface analysis is an important tool in these studies, and the key is to construct suitable description vectors to support subsequent tasks, such as classification and retrieval. Traditional methods based on handcrafted features are insufficient for dealing with complex structures, while deep learning-based approaches have high memory and computation costs when dealing directly with volume data. To address these problems, we propose IsoExplorer, an isosurface-driven framework for 3D shape analysis of biomedical volume data. We first extract isosurfaces from volume data and split them into individual 3D shapes according to their connectivity. Then, we utilize octree-based convolution to design a variational autoencoder model that learns the latent representations of the shape. Finally, these latent representations are used for low-dimensional isosurface representation and shape retrieval. We demonstrate the effectiveness and usefulness of IsoExplorer via isosurface similarity analysis, shape retrieval of real-world data, and comparison with existing methods.

The willingness for dietary and behavioral changes in frontline epidemic prevention workers after experiencing the outbreak of COVID-19 in China: a cross-sectional study.

BACKGROUND: The 2019 novel coronavirus disease (COVID-19) has had a massive impact on public health, resulting in sudden dietary and behavioral habit changes. Frontline epidemic prevention workers play a pivotal role against COVID-19. They must face high-risk infection conditions, insufficient anti-epidemic material supplies, mental pressure, and so on. COVID-19 seriously affects their dietary and behavioral habits, and poor habits make them more susceptible to COVID-19. However, their baseline dietary and behavioral habits before COVID-19 and their willingness to change these habits after the outbreak of COVID-19 remain unclear for these workers in China. This study aimed to explore the baseline dietary and behavioral habits of frontline workers and their willingness to change these habits after the outbreak of the epidemic; in addition, susceptible subgroups were identified by stratified analyses as targets of protective measures to keep them from being infected with COVID-19. METHODS: A cross-sectional study was conducted through an online questionnaire using a sample of 22,459 valid individuals living in China, including 9402 frontline epidemic prevention workers. RESULTS: Before COVID-19, 23.9% of the frontline epidemic prevention workers reported a high-salt diet, 46.9% of them reported a high frequency of fried foods intake, and 50.9% of them smoked cigarettes. After the outbreak of COVID-19, 34.6% of them expressed a willingness to reduce salt intake, and 43.7% of them wanted to reduce the frequency of pickled vegetables intake. A total of 37.9% of them expressed a willingness to decrease or quit smoking, and 44.5% of them wanted to increase sleep duration. Significant differences in the baseline dietary and behavioral habits and the willingness to change their habits were observed between frontline epidemic prevention workers and other participants. Among the frontline epidemic prevention workers with poor dietary and behavioral habits before COVID-19, frontline epidemic prevention experience was a promoting factor for adopting worse dietary and behavioral habits, including those in the high-salt intake subgroup (OR, 2.824; 95% CI, 2.341-3.405) and the 11-20 cigarettes/day subgroup (OR, 2.067; 95% CI, 1.359-3.143). CONCLUSIONS: The dietary and behavioral habits of frontline epidemic prevention workers were worse than that those of other participants before COVID-19. They had a greater willingness to adopt healthy dietary and behavioral habits after experiencing the outbreak of COVID-19. However, frontline epidemic prevention workers with poor dietary and behavioral habits before COVID-19 continued in engage in these poor habits. Dietary and behavioral intervention policies should be drafted to protect their health, especially frontline epidemic prevention workers with poor habits at baseline.

Responses to child sexual assaults and associated factors among parents of young children / 中国学校卫生

Objective@#To analyze the possible responses of parents of young children to Child sexual assault (CSA) and the potential influencing factors, so as to provide evidence for prevention programs of CSA.@*Methods@#Part of the data from "2016-2020 Child Injury Prevention Project" was used to analyze responses to CSA among parents of children younger than 3rd grade in primary school by chi square test and Logistic regression analysis.@*Results@#A total of 4 072 parents were included in the analysis. Among them, 86.8% of parents chose "to solve problems together", 51.0% of parents taking children to a "psychologist", 4.9% of parents "scolding children for being too careless", 2.9% of parents "letting child not disclose abuse" and 6.5% of parents chose "other" coping methods. Parents with foreign nationality [OR(95%CI)=2.58(1.25-5.15)] and lower education level (OR=0.26-0.64) tend to "blame" their children. Mothers [(OR(95%CI)=0.54(0.33-0.90)], higher parental education level (OR=0.27-0.72) were more reluctant to encourage their children to keep quiet. Mothers [OR(95%CI)=1.73(1.32-2.27)], older children (OR=1.33-1.78) and parents with higher education level (OR=1.65-2.99) tend to "accompany". Parents aged 30 or more, and from high school/technical school/technical secondary school tend to take their children to see a "psychologist" [OR(95%CI)=1.39(1.14-1.71), 1.79(1.26-2.53)].@*Conclusion@#Parents universally pay attention to the physical and mental health of children after CSA, but some parents still take negative coping methods, e.g. "blame" and "not disclose". Parenting educational level, duration of parent-child communication and age of children are primary factors associated with parental responses to child sexual assault. This study suggests that prevention secondary injury following child sexual assault should be farther strengthened, while fully considering the characteristics of the educated objects.

The association between subjective impact and the willingness to adopt healthy dietary habits after experiencing the outbreak of the 2019 novel coronavirus disease (COVID-19): a cross-sectional study in China.

To investigate the associations between subjective perception of impacts and willingness to change dietary habits in China after experiencing the outbreak of the 2019 novel coronavirus disease (COVID-19), an online questionnaire survey was carried out and 22,459 respondents in mainland China participated in the study, with an average age of 27.9±7.8 years old. Of them, 84.5% self-reported epidemic concern (middle or above), and 60.2%, 66.3% and 66.8% self-reported impact (middle or above) on psychology, life, work respectively. 31.9%, 46.0% and 41.0% of respondents reported their willingness to reduce their dietary intakes of salt, fried foods, and sugary foods, respectively. The stratified analysis of multinomial logistic regression models showed that, respondents with higher psychological impact were more likely to increase their dietary intake of salt, fried foods, sugary foods. Except as aforesaid, most respondents with higher epidemic concerns and higher impacts on psychology, life, work were more likely to reduce eating salt, fried foods, sugary foods. After the epidemic, early stage of positive improvement to a proper diet was observed, whereas the opposite tendency was also found in some respondents with higher impact on psychology. Thus, there is an urgent need for health care and lifestyle intervention policies for different subgroups.

Quantitative Assessment of Hippocampal Tau Pathology in AD and PART.

To quantitatively assess the distribution pattern of hippocampal tau pathology in Alzheimer's disease (AD) and primary age-related tauopathy (PART), we investigated the distribution of phosphorylated tau protein (AT8) in 6 anatomically defined subregions of the hippocampal formation and developed a mathematical algorithm to compare the patterns of tau deposition in PART and AD. We demonstrated regional patterns of selective vulnerability as distinguishing features of PART and AD in functionally relevant structures of the hippocampus. In AD cases, tau pathology was high in both CA1 and subiculum, followed by CA2/3, entorhinal cortex (EC), CA4, and dentate gyrus (DG). In PART, the severity of tau pathology in CA1 and subiculum was high, followed by EC, CA2/3, CA4, and DG. There are significant differences between sector DG and CA1, DG and subiculum in both AD and PART.

Development of a multivalent acetylcholinesterase inhibitor via dynamic combinatorial chemistry.

In this study, we report the generation of a polymer based dynamic combinatorial library (DCL) using aldehyde-functionalized linear poly(glycidol) and hydrazide derivatives as initial building blocks. In combination with tetrameric acetylcholinesterase (AChE), a certain type of amplified acylhydrazone side chain is identified and further used for the synthesis of a multivalent AChE inhibitor. The cytotoxicity and inhibition properties of the multivalent inhibitor are evaluated, and the results indicate superior bioactivity compared to the commercial reference Edrophonium chloride.