Memory consolidation drives the enhancement of remote cocaine memory via prefrontal circuit.

Remote memory usually decreases over time, whereas remote drug-cue associated memory exhibits enhancement, increasing the risk of relapse during abstinence. Memory system consolidation is a prerequisite for remote memory formation, but neurobiological underpinnings of the role of consolidation in the enhancement of remote drug memory are unclear. Here, we found that remote cocaine-cue associated memory was enhanced in rats that underwent self-administration training, together with a progressive increase in the response of prelimbic cortex (PrL) CaMKII neurons to cues. System consolidation was required for the enhancement of remote cocaine memory through PrL CaMKII neurons during the early period post-training. Furthermore, dendritic spine maturation in the PrL relied on the basolateral amygdala (BLA) input during the early period of consolidation, contributing to remote memory enhancement. These findings indicate that memory consolidation drives the enhancement of remote cocaine memory through a time-dependent increase in activity and maturation of PrL CaMKII neurons receiving a sustained BLA input.

Preventing incubation of drug craving to treat drug relapse: from bench to bedside.

In 1986, Gawin and Kleber reported a progressive increase in cue-induced drug craving in individuals with cocaine use disorders during prolonged abstinence. After years of controversy, as of 2001, this phenomenon was confirmed in rodent studies using self-administration model, and defined as the incubation of drug craving. The intensification of cue-induced drug craving after withdrawal exposes abstinent individuals to a high risk of relapse, which urged us to develop effective interventions to prevent incubated craving. Substantial achievements have been made in deciphering the neural mechanisms, with potential implications for reducing drug craving and preventing the relapse. The present review discusses promising drug targets that have been well investigated in animal studies, including some neurotransmitters, neuropeptides, neurotrophic factors, and epigenetic markers. We also discuss translational exploitation and challenges in the field of the incubation of drug craving, providing insights into future investigations and highlighting the potential of pharmacological interventions, environment-based interventions, and neuromodulation techniques.

Epidemiology, clinical presentation, pathophysiology, and management of long COVID: an update.

The increasing number of coronavirus disease 2019 (COVID-19) infections have highlighted the long-term consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection called long COVID. Although the concept and definition of long COVID are described differently across countries and institutions, there is general agreement that it affects multiple systems, including the immune, respiratory, cardiovascular, gastrointestinal, neuropsychological, musculoskeletal, and other systems. This review aims to provide a synthesis of published epidemiology, symptoms, and risk factors of long COVID. We also summarize potential pathophysiological mechanisms and biomarkers for precise prevention, early diagnosis, and accurate treatment of long COVID. Furthermore, we suggest evidence-based guidelines for the comprehensive evaluation and management of long COVID, involving treatment, health systems, health finance, public attitudes, and international cooperation, which is proposed to improve the treatment strategies, preventive measures, and public health policy making of long COVID.

Regulatory distance and corporate environmental performance: From the perspective of rent-seeking distance.

This paper investigates the impact of regulatory distance on corporate environmental performance using data from Chinese A-share listed companies. The results demonstrate that staying away from regulatory agencies significantly improves corporate environmental performance. The potential impact mechanism is that the increase in regulatory distance significantly suppresses rent-seeking activities. The above impacts are particularly pronounced in companies with weak CEO political and financial connections, state-owned enterprises, and firms in regions with low levels of marketization, owing to the fact that these company characteristics influence firms' ability or inclination to participate in rent-seeking. Further evidence indicates that the effect of regulatory distance on environmental performance will be significantly enhanced by strengthening media regulation and anti-corruption efforts.

The rising human footprint in the Tibetan Plateau threatens the effectiveness of ecological restoration on vegetation growth.

Ecological restoration projects in the Tibetan Plateau aimed to reverse ecosystem degradation and safeguard the fragile alpine ecological environment. However, it is still being determined if the vegetation restoration is successful on a large scale or reaches the expected magnitude, restricting our ability to adapt practices to maximise the benefit. With multiple vegetation indices (VIs: NDVI, LAI, and GPP) from satellite observations and random forest machine-learning models, we performed an attribution study on vegetation growth trends caused by climate change and human activities. Then, we further explored the relationship between vegetation growth and ecological projects and human footprint without the influence of climate. The results showed that climatic change was a relatively strong driver of vegetation growth. The positive contributions of ecological restoration occurred only in half of the plateau due to the increased human footprint. Vegetation enhancement resulting from ecological restoration occurred in 13.1%-23.1% of the plateau. Among these values, ecological restoration counteracted the negative climate effects in 4.7%-8.3% of the plateau (about half of the negative climate effect area). In forest and grassland protection areas, the ecological restoration was more successful. The study provides a better understanding of the role of ecological projects in vegetation restoration and potential threats to its effectiveness. This is essential to improve future restoration projects.

A systematic review and meta-analysis on prevalence of and risk factors associated with depression, anxiety and insomnia in infectious diseases, including COVID-19: a call to action.

Infectious disease epidemics have become more frequent and more complex during the 21st century, posing a health threat to the general public and leading to psychological symptoms. The current study was designed to investigate the prevalence of and risk factors associated with depression, anxiety and insomnia symptoms during epidemic outbreaks, including COVID-19. We systematically searched the PubMed, Embase, Web of Science, OVID, Medline, Cochrane databases, bioRxiv and medRxiv to identify studies that reported the prevalence of depression, anxiety or insomnia during infectious disease epidemics, up to August 14th, 2020. Prevalence of mental symptoms among different populations including the general public, health workers, university students, older adults, infected patients, survivors of infection, and pregnant women across all types of epidemics was pooled. In addition, prevalence of mental symptoms during COVID-19 was estimated by time using meta-regression analysis. A total of 17,506 papers were initially retrieved, and a final of 283 studies met the inclusion criteria, representing a total of 948,882 individuals. The pooled prevalence of depression ranged from 23.1%, 95% confidential intervals (95% CI: [13.9-32.2]) in survivors to 43.3% (95% CI: [27.1-59.6]) in university students, the pooled prevalence of anxiety ranged from 25.0% (95% CI: [12.0-38.0]) in older adults to 43.3% (95% CI: [23.3-63.3]) in pregnant women, and insomnia symptoms ranged from 29.7% (95% CI: [24.4-34.9]) in the general public to 58.4% (95% CI: [28.1-88.6]) in university students. Prevalence of moderate-to-severe mental symptoms was lower but had substantial variation across different populations. The prevalence of mental problems increased over time during the COVID-19 pandemic among the general public, health workers and university students, and decreased among infected patients. Factors associated with increased prevalence for all three mental health symptoms included female sex, and having physical disorders, psychiatric disorders, COVID infection, colleagues or family members infected, experience of frontline work, close contact with infected patients, high exposure risk, quarantine experience and high concern about epidemics. Frequent exercise and good social support were associated with lower risk for these three mental symptoms. In conclusion, mental symptoms are common during epidemics with substantial variation across populations. The population-specific psychological crisis management are needed to decrease the burden of psychological problem and improve the mental wellbeing during epidemic.

Does China's green power trading policy play a role? - Evidence from renewable energy generation enterprises.

Green power trading is an institutional innovation proposed by China to promote green and sustainable development. This policy aims to relieve the serious debt pressure of renewable energy generation enterprises, thus laying the foundation for achieving carbon reduction targets. This paper empirically examines the role of green power trading by constructing the difference-in-differences (DID) model. Our findings indicate that green power trading significantly reduces the debt levels of policy-covered generation enterprises. This effect is more pronounced for state-owned enterprises, companies with better ESG performance, companies in regions with higher degree of marketization and companies specializing in renewable energy power generation. Further research discusses the impact mechanism of green power trading in terms of external and internal environmental channels. We find that a strong green development atmosphere, especially the external atmosphere, will significantly reinforce the weakening effect of green power trading on corporate debt. Our research provides empirical evidence for the success of green power trading policy in its pilot phase.

Divergent responses of ecosystem services to afforestation and grassland restoration in the Tibetan Plateau.

Afforestation and grassland restoration have been proposed as important pathways for nature-based solutions. However, the effects of different ecological restoration projects on multiple ecosystem services are poorly understood, inhibiting our ability to maximize ecosystem services for further restoration. Here, we provide a comprehensive assessment of the impact of different ecological projects on ecosystem services (carbon storage, water conservation, soil retention), using a pairwise comparative study of samples from 90 project-control pairs in the Tibetan Plateau. Our results found that afforestation increased carbon storage (31.3%) and soil retention (37.6%), but the effects of grassland restoration on services were mixed, while the overall changes in water conservation were negligible. Prior land use/measures and the age of project implementation were key factors in regulating ecosystem service responses. For example, afforestation on bare land increased carbon storage and soil retention but indirectly decreased water conservation by influencing vegetation cover, while cropland afforestation increased water and soil retention. Ecosystem services increased with project age after afforestation. For grassland restoration, short-term recovery increased carbon storage but was not effective in improving water and soil retention. Climate and topography also directly or indirectly controlled the response of ecosystem services by affecting the changes in total nitrogen, total porosity, clay and fractional vegetation cover following the projects. This study improves our current understanding of the mechanisms underlying the responses of ecosystem services to afforestation and grassland restoration. Our results suggest that sustainable restoration management taking into account prior land use/measures, implementation age, climate, topography and other resources is critical for optimizing ecosystem services.

Prevalence of posttraumatic stress disorder after infectious disease pandemics in the twenty-first century, including COVID-19: a meta-analysis and systematic review.

Pandemics have become more frequent and more complex during the twenty-first century. Posttraumatic stress disorder (PTSD) following pandemics is a significant public health concern. We sought to provide a reliable estimate of the worldwide prevalence of PTSD after large-scale pandemics as well as associated risk factors, by a systematic review and meta-analysis. We systematically searched the MedLine, Embase, PsycINFO, Web of Science, CNKI, WanFang, medRxiv, and bioRxiv databases to identify studies that were published from the inception up to August 23, 2020, and reported the prevalence of PTSD after pandemics including sudden acute respiratory syndrome (SARS), H1N1, Poliomyelitis, Ebola, Zika, Nipah, Middle Eastern respiratory syndrome coronavirus (MERS-CoV), H5N1, and coronavirus disease 2019 (COVID-19). A total of 88 studies were included in the analysis, with 77 having prevalence information and 70 having risk factors information. The overall pooled prevalence of post-pandemic PTSD across all populations was 22.6% (95% confidence interval (CI): 19.9-25.4%, I2: 99.7%). Healthcare workers had the highest prevalence of PTSD (26.9%; 95% CI: 20.3-33.6%), followed by infected cases (23.8%: 16.6-31.0%), and the general public (19.3%: 15.3-23.2%). However, the heterogeneity of study findings indicates that results should be interpreted cautiously. Risk factors including individual, family, and societal factors, pandemic-related factors, and specific factors in healthcare workers and patients for post-pandemic PTSD were summarized and discussed in this systematic review. Long-term monitoring and early interventions should be implemented to improve post-pandemic mental health and long-term recovery.

Dynamic Linkage between Bitcoin and Traditional Financial Assets: A Comparative Analysis of Different Time Frequencies.

This study employs the ADCC-GARCH approach to investigate the dynamic correlation between bitcoin and 14 major financial assets in different time-frequency dimensions over the period 2013-2021, for which the risk diversification, hedging and safe-haven properties of bitcoin for those traditional assets are further examined. The results show that, first, bitcoin is positively linked to risk assets, including stock, bond and commodity, and negatively linked to the U.S. dollar, which is a safe-haven asset, so bitcoin is closer in nature to a risk asset than a safe-haven asset. Second, the high short-term volatility and speculative nature of the bitcoin market makes its long-term correlation with other assets stronger than the short-term. Third, the positive linkage between the prices of bitcoin and risk assets increases sharply under extreme shocks (e.g., the outbreak of COVID-19 in early 2020). Fourth, bitcoin can hedge against the U.S. dollar, and in the long term, bitcoin can hedge against the Chinese stock market and act as a safe haven for the U.S. stock market and crude oil. However, for most other traditional assets, bitcoin is only an effective diversifier.

Evaluation of bone metabolism-associated biomarkers in Tibet, China.

AIM: To measure and evaluate the distribution and possible contributing factors of seven bone metabolism-associated biomarkers in Tibet, a plateau province of China. METHODS: A total of 1615 individuals were recruited from Tibet at three different altitudes. The levels and possible contributing factors of serum calcium, serum phosphorus, ALP, 25OHD, PINP, CTX, and PTH were evaluated. RESULTS: In total, 1246 Tibetan adults (males: n = 543) were eventually enrolled in this study. Multiple linear regression recognized age, sex, altitude, and BMI as the major effect factors. The levels of ALP, PINP, and CTX in males continuously decreased with age; however, those in females increased after approximately 39 years of age. Males had higher 25OHD levels (23.9 vs. 15.4 ng/ml) but lower levels of serum phosphorus (1.12 vs. 1.19 mmol/L) and PTH (41.3 vs. 47.4 pg/ml) than females. Before the age of 50, males had higher levels of calcium, ALP, PINP, and CTX than females, and the opposite trend was observed after the age of 50. The highest levels of serum calcium and phosphorus and the lowest levels of PINP and CTX were found in the Shigatse/Lhasa region, suggesting a better bone metabolism status. Compared with reports from plain areas of China, significantly higher levels of PINP (65.3 vs. 49.36 ng/ml) and CTX (0.46 vs. 0.37 ng/ml) were recorded in Tibetan adults. CONCLUSION: A more active bone turnover status was found in Tibetan adults than in individuals from the plain areas of China.

Basolateral amygdala is required for reconsolidation updating of heroin-associated memory after prolonged withdrawal.

Postretrieval extinction procedures are effective nonpharmacological interventions for disrupting drug-associated memories. Nonetheless, the conditioned stimulus (CS) memory retrieval-extinction procedure is ineffective in inhibiting drug craving and relapse after prolonged withdrawal, which significantly undermines its therapeutic potential. In the present study, we showed that, unlike the CS memory retrieval-extinction procedure, noncontingent heroin injections (unconditioned stimulus [UCS]) 1 hour before the extinction sessions decreased the heroin-priming-induced reinstatement, renewal, and spontaneous recovery of heroin seeking after 28 days of withdrawal (ie, remote heroin-associated memories) in rats. The UCS retrieval manipulation induced reactivation of the basolateral amygdala (BLA) after prolonged withdrawal, and this reactivation was absent with the CS retrieval manipulation. Chemogenetic inactivation of the BLA abolished the inhibitory effect of the UCS memory retrieval-extinction procedure on heroin-priming-induced reinstatement after prolonged withdrawal. Furthermore, the combination of chemogenetic reactivation of BLA and CS retrieval-extinction procedure resembled the inhibitory effect of UCS retrieval-extinction procedure on heroin seeking after prolonged withdrawal. We also observed that the inhibitory effect of the UCS retrieval-extinction procedure is mediated by regulation of AMPA receptor endocytosis in the BLA. Our results demonstrate critical engagement of the BLA in reconsolidation updating of heroin-associated memory after prolonged withdrawal, extending our knowledge of the boundary conditions of the reconsolidation of drug-associated memories.

Splenic irradiation combined with tumor irradiation promotes T cell infiltration in the tumor microenvironment and helps in tumor control.

Locally applied radiation to the tumor is reported to stimulate systemic immune response. During radiotherapy to the abdominal cancer, spleen often receives certain dose, though as an important immune organ, little is known about the impact of splenic irradiation (SI) on systemic immune and local tumor control. Through a mice model, we found that the combination of SI with tumor irradiation (TI) helped in local control. The analysis of the tumor infiltrating leucocytes demonstrated that SI plus TI brought more T cell aggregation in the tumor microenvironment (TME), which helped in tumor control. Increased T cell infiltration may be partly due to higher expression of T cell chemokine in the TME and more expression of CXCR3 on the T cells in the spleen after SI. SI produced more IL-1ß in the spleen, IL-1ß stimulated the expression of CXCR3 on the T cells, and enhanced their migration ability. Taken together, radiation to the spleen combined with TI helped in local control through promoting T cell infiltration, and may be a considerable means to enhance the immunomodulatory of radiotherapy.

Targeted next-generation sequencing extends the mutational spectrums for OPA1 mutations in Chinese families with optic atrophy.

Purpose: We aim to reveal the disease-causing mutations in 15 Chinese families with optic atrophy (OA). Methods: In total, 15 families with OA were recruited in the present study. Medical histories were carefully reviewed and comprehensive ophthalmic examinations were received by all recruited patients. Targeted next-generation sequencing (NGS) was selectively performed on all probands for mutation detection. Intrafamilial cosegregation and in-silico analyses were subsequently applied to predict the potential pathogenic effects of identified mutations. Results: All included patients presented bilateral vision loss. Their fundus photographs showed temporal or total pallor of the optic discs. Fourteen mutations in the optic atrophy 1 (OPA1) gene were revealed as disease-causing mutations for the 15 families, including eight novel (c.968A>G, c.193C>G, c.1071dupT, c.987_988del, c.2012+2T>G, c.1036-1G>C, c.2126A>G, and c.1036_1038del) and six recurrent (c.1499G>A, c.1800C>A, c.1034G>A, c.2873_2876del, c.112C>T, and c.804_805del) mutations. Conclusions: In conclusion, our study expands the mutational spectrum for the OPA1 gene and implies targeted NGS as an effective approach for the genetic diagnosis of OA, which might help to improve the clinical diagnosis for patients with OA.

Social health insurance vs private health insurance in China: Revisit crowd-out effect based on a multiple mediation analysis.

Plenty of scholars have studied social health insurance and private health insurance in different economies, and many concentrate on crowd-out effect. Different results have been presented due to various data choices and empirical methodologies, but few of them have revealed the transaction mechanism. We study this issue based on updated Chinese provincial panel data from 2002 to 2014 and improved methods. We focus on how the crowd-out effect happens through 3 channels-saving, demographic factor, and medical expenditure using multiple mediator models. Besides, we apply Panel VAR model to study magnitude of the impact these 3 channels contribute, corporately and respectively. Results clearly show that social health insurance has crowd-out effect in penetration but crowd-in effect in density caused by different mediation variables. In addition, the 3 channels have shown lasting and dynamic influences on the crowd-out (in) effect. Finally, our paper provides the anti-crowd-out solutions from both perspectives according to our empirical analyses. For social health insurance system, it is necessary to improve the efficiency and fairness of the funds. For the private health insurance companies, insurance products innovation and privilege policy should be made to decrease the negative impact of saving and medical service overuse.

Low-Cost, Distributed Environmental Monitors for Factory Worker Health.

An integrated network of environmental monitors was developed to continuously measure several airborne hazards in a manufacturing facility. The monitors integrated low-cost sensors to measure particulate matter, carbon monoxide, ozone and nitrogen dioxide, noise, temperature and humidity. The monitors were developed and tested in situ for three months in several overlapping deployments, before a full cohort of 40 was deployed in a heavy vehicle manufacturing facility for a year of data collection. The monitors collect data from each sensor and report them to a central database every 5 min. The work includes an experimental validation of the particle, gas and noise monitors. The R² for the particle sensor ranges between 0.98 and 0.99 for particle mass densities up to 300 μg/m³. The R² for the carbon monoxide sensor is 0.99 for concentrations up to 15 ppm. The R² for the oxidizing gas sensor is 0.98 over the sensitive range from 20 to 180 ppb. The noise monitor is precise within 1% between 65 and 95 dBA. This work demonstrates the capability of distributed monitoring as a means to examine exposure variability in both space and time, building an important preliminary step towards a new approach for workplace hazard monitoring.

Magnetic solid-phase extraction based on carbon nanotubes for the determination of polyether antibiotic and s-triazine drug residues in animal food with LC-MS/MS.

Carbon nanotubes-magnetic nanoparticles, comprising ferroferric oxide nanoparticles and carbon nanotubes, were prepared through a simple one-step synthesis method and subsequently applied to magnetic solid-phase extraction for the determination of polyether antibiotic and s-triazine drug residues in animal food coupled with liquid chromatography with tandem mass spectrometry. The nanocomposites were characterized by transmission electron microscopy, X-ray diffraction, and vibrating sample magnetometry. The components within the nanocomposites endowed the material with high extraction performance and manipulative convenience. Compared with carbon nanotubes, the as-prepared carbon nanotubes-magnetic nanoparticles showed better extraction and separation efficiencies for polyether antibiotics and s-triazine drugs thanks to the contribution of the iron-containing magnetic nanoparticles. Various experimental parameters affecting the extraction efficiency had been investigated in detail. Under the optimal conditions, the good linearity ranging from 1 to 200 µg/kg for diclazuril, toltrazuril, toltrazuril sulfone, lasalocid, monensin, salinomycin, narasin, nanchangmycin, and maduramicin, low limits of detection ranging from 1 to 5 µg/kg, and satisfactory spiked recoveries (77.1-91.2%, with the inter relative standard deviation values from 4.0 to 12.2%) were shown. It was confirmed that this novel method was an efficient pretreatment and enrichment procedure and could be successfully applied for extraction and determination of polyether and s-triazine drug residues in complex matrices.

Up-regulation of plakophilin-2 is correlated with the progression of glioma.

Glioma is the most common type of primary brain tumor in the CNS. Due to its poor prognosis and high mortality rates, it is urgent to find out more effective therapies. Plakophilin-2 (PKP2) is a widespread desmosomal plaque protein. Recently, the important roles of PKP2 in the proliferation and migration of cancer cells and tumor progression has been shown. However, the expression and potential function of PKP2 in glioma was still unclear. In this study, we demonstrated that PKP2 protein expression level was increased in glioma tissues compared with normal brain tissues, and its level was significantly associated with the Ki-67 expression and WHO grade by Western blot analysis and immunohistochemistry. Clinically, high PKP2 expression was tightly related to poor prognosis of glioma patients. Interestingly, we found that down-regulated PKP2 expression was shown to inhibit the migration of cells in glioma. Moreover, cell counting kit (CCK)-8 and colony formation analyses proved that reduced expression of PKP2 could weaken glioma cell proliferation. Taken together, these data uncover a potential role for PKP2 in the pathogenic process of glioma, suggesting that PKP2 may be a promising therapeutic target of glioma.