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Abstract The brain integrates activity across networks of interconnected neurons to generate behavioral outputs. Several physiological and imaging-based approaches have been previously used to monitor responses of individual neurons. While these techniques can identify cellular responses greater than the neuron’s action potential threshold, less is known about the events that are smaller than this threshold or are localized to subcellular compartments. Here we use NEAs to obtain temporary intracellular access to neurons allowing us to record information-rich data that indicates action potentials, and sub-threshold electrical activity. We demonstrate these recordings from primary hippocampal neurons, induced pluripotent stem cell-derived (iPSC) neurons, and iPSC-derived brain organoids. Moreover, our results show that our arrays can record activity from subcellular compartments of the neuron. We suggest that these data might enable us to correlate activity changes in individual neurons with network behavior, a key goal of systems neuroscience.

Based on the matching of the database of China Industry Business Performance and China Customs Trade from 2000 to 2013, this paper constructs the digital product import index, and adopts the method of panel data modeling to systematically investigate the impact and mechanism of digital product import on the domestic value-added rate of Chinese enterprises' export from the theoretical and empirical aspects. The research finds that the import of digital products significantly promotes the improvement of the domestic value-added rate of enterprises' export, and the core conclusion is still valid after considering the endogeneity of variables, changing the measurement index and estimation method. The mechanism test finds that the import of digital products improves the domestic value-added rate of enterprises' export through two channels: cost markup and relative price. In addition, the heterogeneity test finds that the import of digital products has a stronger effect on the improvement of the domestic value-added rate of enterprises' export in non-export enterprises, pure general trading enterprises, foreign-funded enterprises, labor-intensive enterprises and enterprises in the eastern region.

Plant–microbe–soil interactions control over the forest biogeochemical cycling. Adaptive plant–soil interactions can shape specific microbial taxa in determining the ecosystem functioning. Different trees produce heterogeneous soil properties and can alter the composition of soil microbial community, which is relevant to the forest internal succession containing contrasting stand types such as the pine-oak forests. Considering representative microbial community characteristics are recorded in the original soil where they had adapted and resided, we constructed a soil transplant incubation experiment in a series of in situ root-ingrowth cores in a subtropical pine-oak forest, to simulate the vegetational pine-oak replacement under environmental succession. The responsive bacterial and fungal community discrepancies were studied to determine whether and how they would be changed. The pine and oak forest stands had greater heterogeneity in fungi composition than bacteria. Original soil and specific tree root status were the main factors that determined microbial community structure. Internal association network characters and intergroup variations of fungi among soil samples were more affected by original soil, while bacteria were more affected by receiving forest. Specifically, dominant tree roots had strong influence in accelerating the fungi community succession to adapt with the surrounding forest. We concluded that soil microbial responses to forest stand alternation differed between microbiome groups, with fungi from their original forest possessing higher resistance to encounter a new vegetation stand, while the bacteria community have faster resilience. The data would advance our insight into local soil microbial community dynamics during ecosystem succession and be helpful to enlighten forest management.

The main purpose of this paper is to investigate the happiness factors and assess the performance of machine learning techniques on predicting the happiness levels of European immigrants and natives. Two types of machine learning methods, Ordinal Logistic Regression (OLR) and Artificial Neural Network (ANN), are employed for analytical modeling. Our results with a total sample size of 196,724 respondents from nine rounds of the European Social Survey (ESS) indicate that the determinants of happiness for immigrants and natives are significantly inconsistent. Therefore, variables should be specifically selected to predict the happiness levels of these two different groups. The sensitivity analysis shows that satisfaction with life, subjective general health, and the highest level of education are the three most prominent determinants that contribute to the happiness of immigrants and natives. The overall accuracies of OLR and ANN baseline models are >80%. This can be further improved by building models for each individual country. The application of OLR and ANN implies that machine learning algorithms can be a useful tool for predicting happiness levels. The greater knowledge of migration and happiness will allow us to better understand the decision-making processes and construct more effective policies.

Human capital and ICT have a significant role in determining human development. The impacts of ICT and human capital on green growth and environmental sustainability should be explored for sustainable economic development. This research contributes to the literature on the role of ICTs and human capital in the determination of green growth and environmental performance. Based on time-series data 1990–2019, the study intends to investigate the impact of ICTs and human capital on environmental and green growth performance for China. The study reports that ICTs tend to reduce CO2 emissions and improve green growth in the long-run. However, education reduces CO2 emissions in the long-run but does not produce any significant impact on green growth in the long-run. It is suggested that government should invest in environmental efficiency and environmental technologies simultaneously with human capital that could significantly contribute to pollution reduction. Lastly, policies to increase human capital should be implemented simultaneously with policies to promote ICTs contribution in order to confirm green growth and environmental protection.

The present study was conducted in one of the major agriculture areas to check farmers indigenous knowledge about the impacts of floods on their farming lives, food security, sustainable development, and risk assessment. In the current study, primary data was used to analyze the situation. A semi-structured questionnaire was distributed among farmers. We have collected a cross-sectional dataset and applied the PLS-SEM dual-stage hybrid model to test the proposed hypotheses and rank the social, economic, and technological factors according to their normalized importance. Results revealed that farmers’ knowledge associated with adaption strategies, food security, risk assessment, and livelihood assets are the most significant predictors. Farmers need to have sufficient knowledge about floods, and it can help them to adopt proper measurements. A PLS-SEM dual-stage hybrid model was used to check the relationship among all variables, which showed a significant relationship among DV, IV, and control variables. PLS-SEM direct path analysis revealed that AS (b = −0.155; p 0.001), FS (b = 0.343; p 0.001), LA (b = 0.273; p 0.001), RA (b = 0.147; p 0.006), and for FKF have statistically significant values of beta, while SD (b = −0.079NS) is not significant. These results offer support to hypotheses H1 through H4 and H5 being rejected. On the other hand, age does not have any relationship with farmers’ knowledge of floods. Our study results have important policy suggestions for governments and other stakeholders to consider in order to make useful policies for the ecosystem. The study will aid in the implementation of effective monitoring and public policies to promote integrated and sustainable development, as well as how to minimize the impacts of floods on farmers’ lives and save the ecosystem and food.

The internal hemorrhoid, rectal tumor, hypertrophic anal papilla, and secret fecal mass are regarded as the blocks embedded in the rectum. The above blocks hinder defecation, which will inevitably lead to excessive opening of the anal caliber. Once the limit is exceeded, the skin of the anal canal will tear and form anal fissure. Based on the study of historical evolution, hypothesis reasoning, clinical verification and comparison with other theories, a new concept of anal fissure etiology–impaction theory is proposed. The so-called impaction theory refers to the impaction (various primary lesions) in anorectum, which hinders defecation. When defecating, the anal canal expands beyond the limit, and the whole layer of anal canal skin splits, that is to say, anal fissure is formed. Resumo: A hemorroida interna, o tumor retal, a papila anal hipertrófica e a massa fecal secreta são considerados os blocos incrustados no reto. Os bloqueios acima impedem a defecação, o que inevitavelmente levará a uma abertura excessiva do calibre anal. Uma vez que o limite é excedido, a pele do canal anal rasga e forma uma fissura anal. Com base no estudo da evolução histórica, raciocínio de hipóteses, verificação clínica e comparação com outras teorias, um novo conceito de etiologia da fissura anal – a teoria da impactação – é proposto. A chamada teoria da impactação refere-se à impactação (várias lesões primárias) no anorreto, o que dificulta a defecação. Na defecação, o canal anal se expande além do limite e toda a camada da pele do canal anal rasga, ou seja, forma-se a fissura anal.

Over the years, Pakistan and China have developed strong bilateral trade and economic linkages. China Pakistan economic corridors (CPEC) is a multidimensional development plan, encircling several diverse projects and the Chinese government is going to invest a huge amount in China-Pakistan Economic Corridor on several different projects. CPEC is an approach toward economic stability for both countries in the globalized world and is known as a game changer in this region. In the present study China-Pakistan economics door has been discussed, to check the CPEC implementations situation, its restraints, challenges, and benefits. An empirical process was adopted to check public opinion about it with aimed public perceptions About Foreign Investment, A PLS-SEM Analysis toward republic sustainable infrastructure. PLS-SEM direct path analysis revealed that there is direct relationship among IV and DV, these results offer support to hypotheses H1-H6 accepted. We have also looked at the levels of education and gender of the respondents as control variables, gender and education showed insignificant relationships with CPEC. It means there is no direct relationship between gender and education to DV. Age significantly moderates the relationship of CPEC associated with IV, depicts the moderation role of age on the relationship, under this research H2a and H3a have significant relationships with age as a moderator while other moderators did not show any relationship. In the current study, there is a significant relationship among all parameters, and there is a medium to strong correlation between diverse variables. The study showed that CPEC will have positive and strong impacts on the economic development of both countries and public of Pakistan consider it can open many doors for them for education, jobs and tourism. This study can help policy makers to make policy to make more effective policy in this are for sustainable development.

The research on solid waste based soft soil solidifying materials has received extensive attention in recent years. However, the properties of deep mixing piles are significantly affected by the construction technology. In view of this, this work carried out the systematic study on the influence of materials, the mixing tool and process optimization on the integrity and mechanical properties of deep mixing piles. Factors considered include the shape of the blade (strip and meniscus), the types of solidifying materials (PO 42.5 cement, self-developed soft soil solidifying agent), the content (50 kg/m, 65 kg/m, 80 kg/m and 100 kg/m) and how many times the materials needed to be mixed (two, four and six times). The solidification mechanism was analyzed. The results showed that the utilization of a meniscus blade contributed to the excellent integrity of the deep mixing pile, as well as solved the problems of oozing slurry and wrapped blade during construction. Mixing the materials four times is the most suitable for the construction of deep mixing piles in organic clay. The solidifying agent deep mixing pile showed satisfactory early and late strength. Microscopic analysis showed that more calcium silicate hydrate and ettringite formed in the solidifying agent solidified soil. Organic clay particles were better cemented and pores were fully filled, so that the solidified soil showed an integral and dense structure. The microscopically integral and dense structure contributed to the excellent integrity and mechanical properties of the solidifying agent deep mixing pile.

The present study employs panel data of 29 provinces and municipalities in mainland China from 2003 to 2016 to empirically investigate the influence of international students on China’s outward FDI. The results show that international students in China can significantly promote outward FDI in various Chinese provinces. Moreover, we observe a substitution effect with export scale and wage level, that is, attracting international students can offset the negative impact of insufficient export scale and low wages on regional OFDI (outward foreign direct investment). From a regional perspective, the growth in international students’ inflows in China has a significant positive impact on OFDI of provinces along “the 21st Century Maritime Silk Road”, but has no significant impact on the provinces along “the Silk Road Economic Belt”. The above conclusions not only elaborate the regional distribution mechanism of OFDI in China, but also provide a reference for each province to formulate more favorable policies to attract foreign talent to effectively implement the strategy of “going global”.

The present study was conducted in one of the major agriculture areas to check farmers indigenous knowledge about the impacts of floods on their farming lives, food security, sustainable development, and risk assessment. In the current study, primary data was used to analyze the situation. A semi-structured questionnaire was distributed among farmers. We have collected a cross-sectional dataset and applied the PLS-SEM dual-stage hybrid model to test the proposed hypotheses and rank the social, economic, and technological factors according to their normalized importance. Results revealed that farmers' knowledge associated with adaption strategies, food security, risk assessment, and livelihood assets are the most significant predictors. Farmers need to have sufficient knowledge about floods, and it can help them to adopt proper measurements. A PLS-SEM dual-stage hybrid model was used to check the relationship among all variables, which showed a significant relationship among DV, IV, and control variables. PLS-SEM direct path analysis revealed that AS (b = -0.155; p 0.001), FS (b = 0.343; p 0.001), LA (b = 0.273; p 0.001), RA (b = 0.147; p 0.006), and for FKF have statistically significant values of beta, while SD (b = -0.079NS) is not significant. These results offer support to hypotheses H1 through H4 and H5 being rejected. On the other hand, age does not have any relationship with farmers' knowledge of floods. Our study results have important policy suggestions for governments and other stakeholders to consider in order to make useful policies for the ecosystem. The study will aid in the implementation of effective monitoring and public policies to promote integrated and sustainable development, as well as how to minimize the impacts of floods on farmers' lives and save the ecosystem and food. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a degenerative joint disease that affects both cartilage and bone. A better understanding of the early molecular changes in subchondral bone may help elucidate the pathogenesis of OA. We used microarray technology to investigate the time course of molecular changes in the subchondral bone in the early stages of experimental osteoarthritis in a rat model. We identified 2,234 differentially expressed (DE) genes at 1 week, 1,944 at 2 weeks and 1,517 at 4 weeks post-surgery. Further analyses of the dysregulated genes indicated that the events underlying subchondral bone remodeling occurred sequentially and in a time-dependent manner at the gene expression level. Some of the identified dysregulated genes that were identified have suspected roles in bone development or remodeling; these genes include Alp, Igf1, Tgf β1, Postn, Mmp3, Tnfsf11, Acp5, Bmp5, Aspn and Ihh. The differences in the expression of these genes were confirmed by real-time PCR, and the results indicated that our microarray data accurately reflected gene expression patterns characteristic of early OA. To validate the results of our microarray analysis at the protein level, immunohistochemistry staining was used to investigate the expression of Mmp3 and Aspn protein in tissue sections. These analyses indicate that Mmp3 protein expression completely matched the results of both the microarray and real-time PCR analyses; however, Aspn protein expression was not observed to differ at any time. In summary, our study demonstrated a simple method of separation of subchondral bone sample from the knee joint of rat, which can effectively avoid bone RNA degradation. These findings also revealed the gene expression profiles of subchondral bone in the rat OA model at multiple time points post-surgery and identified important DE genes with known or suspected roles in bone development or remodeling. These genes may be novel diagnostic markers or therapeutic targets for OA.

The main purpose of this paper is to investigate the happiness factors and assess the performance of machine learning techniques on predicting the happiness levels of European immigrants and natives. Two types of machine learning methods, Ordinal Logistic Regression (OLR) and Artificial Neural Network (ANN), are employed for analytical modeling. Our results with a total sample size of 196,724 respondents from nine rounds of the European Social Survey (ESS) indicate that the determinants of happiness for immigrants and natives are significantly inconsistent. Therefore, variables should be specifically selected to predict the happiness levels of these two different groups. The sensitivity analysis shows that satisfaction with life, subjective general health, and the highest level of education are the three most prominent determinants that contribute to the happiness of immigrants and natives. The overall accuracies of OLR and ANN baseline models are >80%. This can be further improved by building models for each individual country. The application of OLR and ANN implies that machine learning algorithms can be a useful tool for predicting happiness levels. The greater knowledge of migration and happiness will allow us to better understand the decision-making processes and construct more effective policies. [ABSTRACT FROM AUTHOR]

Lanthipeptides are an important subfamily of ribosomally synthesized and posttranslationally modified peptides, and the removal of their N-terminal leader peptides by a designated protease(s) is a key step during maturation. Whereas proteases for class I and II lanthipeptides are well-characterized, the identity of the protease(s) responsible for class III leader processing remains unclear. Herein, we report that the class III lanthipeptide NAI-112 employs a bifunctional Zn-dependent protease, AplP, with both endo- and aminopeptidase activities to complete leader peptide removal, which is unprecedented in the biosynthesis of lanthipeptides. AplP displays a broad substrate scope in vitro by processing a number of class III leader peptides. Furthermore, our studies reveal that AplP-like proteases exist in the genomes of all class III lanthipeptide-producing strains but are usually located outside the biosynthetic gene clusters. Biochemical studies show that AplP-like proteases are universally responsible for the leader removal of the corresponding lanthipeptides. In addition, AplP-like proteases are phylogenetically correlated with aminopeptidase N from Escherichia coli, and might employ a single active site to catalyze both endo- and aminopeptidyl hydrolysis. These findings solve the long-standing question as to the mechanism of leader peptide processing during class III lanthipeptide biosynthesis, and pave the way for the production and bioengineering of this class of natural products. [ABSTRACT FROM AUTHOR]

Lantibiotics are antimicrobial peptides belonging to the family of ribosomally synthesized and posttranslationally modified peptides (RiPPs) and feature thioether linkages in their structures. In this study, we identified the biosynthetic gene cluster of a cinnamycin analog, named mathermycin, from Marinactinospora thermotolerans SCSIO 00652 and reconstituted its biosynthesis in Streptomyces lividans and Escherichia coli. Key posttranslational modification enzymes of mathermycin were characterized. Mathermycin exhibited antimicrobial activity and therefore represents an example of cinnamycin-like lantibiotics from Marinactinospora species. [ABSTRACT FROM AUTHOR]

This is a reflection on the notion of “self,” primarily on the basis of a story in the Zhuangzi in which the protagonist claims: “I lost myself.” Chen first reiterates the grammatical differences between the uses of 吾 (wu) and 我 (wo), and continues with a reflection on their philosophical meaning. He argues that the notion of “wo” is more spatial, connected to the body, and distinguished from others; “wu” is more temporal, related to one’s memory and self-understanding. The loss of “wo” by “wu” is a liberation from interpersonal tensions and the emphasis on one’s body. [ABSTRACT FROM AUTHOR]

This paper compares speculative or textbook philosophy with kite flying risking to lose touch with the topic of reflection. The alternative that Chen defends here is a more experience-grounded, concrete, and imaginary reflection on less often discussed ideas and on allegories. He carves out this approach from four related disciplinary methodologies: the “philological” focus on textual matters, the “history of thought” focusing on past eras, “scholastic history” (a term from Qian Mu) connecting past ideas with their future, and “history of philosophy” immediately searching Chinese equivalents for Western notions. The experience that Chen stresses is that of the text’s original authors and later interpreters. This approach can also leads toward universal insights and the pleasure of an unending interpretive dialogue. [ABSTRACT FROM AUTHOR]

This article analyzes three well-known stories—the child about to fall in a well from Mencius, the butterfly dream in Zhuangzi, and the spear-shield contradiction in Han Feizi —to illustrate a type of philosophical argumentation that the author finds particularly inspiring but little explored in the reading of early Chinese texts. As opposed to the more speculative and abstract mode of philosophizing that has been largely imported from (or stimulated by) the West and that dominates at philosophy departments, a careful reflection on allegories, based on concrete experience and a lively imagination, leads to insights that are also universal and endlessly inspiring. Their interpretation can be very different from Western philosophical insights that seem similar at first sight. [ABSTRACT FROM AUTHOR]

This article presents a phenomenological analysis of several Chinese notions of shame—embarrassment (xiu), chagrin (kui), shame (chi), and disgrace (ru). It elaborates on their structural connections and related experiences, more particularly concerning interpersonal conditions and emotional or physical reactions. Chen focuses on the notion of moral shame, its connection to the Confucian tradition, and its weakening in the current society, due to ideational and technical circumstances, such as the increased sense of individual self and the booming of internet culture. [ABSTRACT FROM AUTHOR]

Obesity-related kidney disease is related to caloric excess promoting deleterious cellular responses. Accumulation of saturated free fatty acids in tubular cells produces lipotoxicity involving significant cellular dysfunction and injury. The objectives of this study were to elucidate the role of reninangiotensin system (RAS) activation in saturated fatty acid-induced endoplasmic reticulum (ER) stress in cultured human proximal tubule epithelial cells (HK2) and in mice fed with a high-fat diet. Treatment with saturated fatty acid palmitic acid (PA; 0.8 mM) for 24 h induced ER stress in HK2, leading to an unfolded protein response as reflected by increased expressions of the ER chaperone binding immunoglobulin protein (BiP) and proapoptotic transcription factor C/EBP homologous protein (CHOP) protein as evaluated by immunoblotting. PA treatment also induced increased protein expression of inositol requiring protein 1α (IRE1α), phosphorylated eukaryotic initiation factor-α (eIF2α), and activating transcription factor 4 (ATF4) as well as activation of caspase-3. PA treatment was associated with increased angiotensin II levels in cultured medium. The angiotensin II type 1 receptor (AT1R) blocker valsartan or renin inhibitor aliskiren dramatically suppressed PA-induced upregulation of BiP, CHOP, IRE1α, p-eIF2α, and ATF4 in HK2 cells. In contrast, valsartan or aliskiren did not prevent ER stress induced by tunicamycin. C57BL/6 mice fed with a high-fat diet for 14 wk exhibited increased protein expressions of BiP and CHOP compared with control mice, which were significantly attenuated by the valsartan treatment. Increased angiotensin II levels in serum and urine were observed in mice fed with a high-fat diet when compared with controls. It is suggested that the intrarenal RAS activation may play an important role in diabetic kidney injury via mediating ER stress induced by saturated fatty acid. [ABSTRACT FROM AUTHOR]

Starting from the time the twentieth century embarked on the last ten years of its course, and following a great tumult as of "roaring mountains and raging seas" in the cultural domain, conservatism finally welcomed its age of felicity and bliss. The influence of conservatism, as superficially characterized by the Chinese Traditional Studies Heat (guoxue re), cannot compare with that of the radicalism that was characterized by the Culture Heat. But in scale-as opposed to the scale of other conservative movements in the current century-it is definitely the largest of all such movements. (Chen Lai has furnished some explanations for this situation in "Chinese Traditional Studies-Hard-Pressed in the 1990s"; see issue no. 5 [sic], 1995, of Dongfang.) There have been people rooting for it everywhere, from foreign countries to the Chinese mainland, and from official quarters to academic circles. Yet, in the final analysis, what future does it have? This is a question that people are not necessarily clear about, but which arouses their concern. When one looks at the prospects of an ongoing movement, it is best to start by inquiring into its origins. [ABSTRACT FROM AUTHOR]