bluuebunny/crossref_metadata_2025 huggingface dataset:
Oxidative Stress of Cadmium and Lead at Environmentally Relevant Concentrations on Hepatopancreas of Macrobrachium nipponensis and Their Mixture Interactivity: Implications for Water Quality Criteria Amendment
Authors: Liu Xiang , Deng Qianzhen , Yang Hao , Wang Jingyao , Wang Min
Published: December 2022

The biotoxicity of heavy metals in water has always been the focus of ecological health research. In this study, the oxidative stress-associated toxicity of cadmium (Cd) and lead (Pb) at environmentally relevant concentrations on the hepatopancreas of Macrobrachium nipponensis was investigated based on multiple biomarker responses in a 28-day indoor exposure study. Changes in integrated biomarker responses (IBR) and their interactivity were subsequently analyzed. No dead individuals were found across any of the tested conditions. The chronic toxicity of heavy metals depended on their type and exposure time at the same concentration. At low concentrations, organisms have a regulatory capacity to cope with the excess reactive oxygen species (ROS) induced by Pb stress over time. In detail, the activity of superoxide dismutase (SOD) was inhibited by Pb stress at a high concentration as time passed. The sensitivity of metallothionein (MT) to Cd was stronger than Pb, and the potential for Cd to cause lipid peroxidation damage was higher than Pb. At the same time, Pb had a greater disturbance effect on the nervous system than Cd, especially in the early exposure stage. The contribution of Cd and Pb to the interaction effect varied dynamically with time and concentration of exposure, but mostly showed antagonism. The results of this study have important significance for guiding the diagnosis of ecological water health, the amendment of water quality criteria, and the management of wastewater discharge.
Differences in Carbon and Nitrogen Migration and Transformation Driven by Cyanobacteria and Macrophyte Activities in Taihu Lake
Authors: Han Chaonan , Wu Hao , Sun Ningning , Tang Yu , Dai Yan , Dai Tianhao
Published: December 2022

The metabolic activities of primary producers play an important role in the migration and transformation of carbon (C) and nitrogen (N) in aquatic environments. This study selected two typical areas in Taihu Lake, a cyanobacteria-dominant area (Meiliang Bay) and a macrophyte-dominant area (in the east area of the lake), to study the effects of cyanobacteria and macrophyte activities on C and N migration and transformation in aquatic environments. The results showed that total N and total particulate N concentrations in the water of the cyanobacteria-dominant area were much higher than those in the macrophyte-dominant area, which was mainly due to the assimilated intracellular N in cyanobacteria. Macrophyte activity drove a significantly higher release of dissolved organic C (DOC) in the water than that driven by cyanobacteria activity, and the DOC contents in the water of the macrophyte-dominant area were 2.4~4.6 times the DOC contents in the cyanobacteria-dominant area. In terms of the sediments, organic matter (OM), sediment total N and N species had positive correlations and their contents were higher in the macrophyte-dominant area than in the cyanobacteria-dominant area. Sediment OM contents in the macrophyte-dominant area increased from 4.19% to 9.33% as the sediment deepened (0~10 cm), while the opposite trend was presented in the sediments of the cyanobacteria-dominant area. Sediment OM in the macrophyte-dominant area may contain a relatively high proportion of recalcitrant OC species, while sediment OM in the cyanobacteria-dominant area may contain a relatively high proportion of labile OC species. Compared with the macrophyte-dominant area, there was a relatively high richness and diversity observed in the bacterial community in the sediments in the cyanobacteria-dominant area, which may be related to the high proportion of labile OC in the OM composition in its sediments. The relative abundances of most OC-decomposing bacteria, denitrifying bacteria, Nitrosomonas and Nitrospira were higher in the sediments of the cyanobacteria-dominant area than in the macrophyte-dominant area. These bacteria in the sediments of the cyanobacteria-dominant area potentially accelerated the migration and transformation of C and N, which may supply nutrients to overlying water for the demands of cyanobacteria growth. This study enhances the understanding of the migration and transformation of C and N and the potential effects of bacterial community structures under the different primary producer habitats.
The Availability, Appropriateness, and Integration of Services to Promote Indigenous Australian Youth Wellbeing and Mental Health: Indigenous Youth and Service Provider Perspectives
Authors: McCalman Janya Robyn , Fagan Ruth , McDonald Tina , Jose Semara , Neal Paul , Blignault Ilse , Askew Deborah , Cadet-James Yvonne
Published: December 2022

Concerns about the complexity, fragmentation and inefficiency of Australia’s current youth mental health service systems have led policy makers to seek improvements through a shift to community-based solutions. However, there is little evidence of how communities can make this shift. This paper examines the efforts of one Aboriginal and Torres Strait Islander (hereafter, respectfully, Indigenous) community—Yarrabah in north Queensland—to develop strategies for mental health and wellbeing service system improvements for school-aged youth (5–18 years). The research was co-designed with Yarrabah’s community-controlled health service and explores the perceptions of Yarrabah youth and service providers. Iterative grounded theory methods were used to collect and analyse data from 32 youth aged 11–24 years and 24 service providers. Youth were reluctant to seek help, and did so only if they felt a sense of safety, trust, relationality and consistency with providers. Young people’s four suggestions for improvement were access to (1) information and awareness about mental health; (2) youth facilities, spaces and activities; (3) safe and available points of contact; and (4) support for recovery from mental illness. Service providers highlighted an appetite for youth-guided community change and recommended five improvement strategies: (1) listening to youth, (2) linking with community members, (3) providing wellbeing promotion programs, (4) intervening early, and (5) advocating to address the determinants of youth mental health. Overall, both groups realised a disjunct between youth need and service provision, but a willingness to work together for systems change. This study demonstrates the importance of community-driven efforts that harness both youth and service providers’ perspectives, and suggests a need for ongoing dialogue as the basis for co-designing and implementing improvements to wellbeing supports and mental health services for Indigenous youth.
EEG Emotion Recognition Applied to the Effect Analysis of Music on Emotion Changes in Psychological Healthcare
Authors: Zhou Tie Hua , Liang Wenlong , Liu Hangyu , Wang Ling , Ryu Keun Ho , Nam Kwang Woo
Published: December 2022

Music therapy is increasingly being used to promote physical health. Emotion semantic recognition is more objective and provides direct awareness of the real emotional state based on electroencephalogram (EEG) signals. Therefore, we proposed a music therapy method to carry out emotion semantic matching between the EEG signal and music audio signal, which can improve the reliability of emotional judgments, and, furthermore, deeply mine the potential influence correlations between music and emotions. Our proposed EER model (EEG-based Emotion Recognition Model) could identify 20 types of emotions based on 32 EEG channels, and the average recognition accuracy was above 90% and 80%, respectively. Our proposed music-based emotion classification model (MEC model) could classify eight typical emotion types of music based on nine music feature combinations, and the average classification accuracy was above 90%. In addition, the semantic mapping was analyzed according to the influence of different music types on emotional changes from different perspectives based on the two models, and the results showed that the joy type of music video could improve fear, disgust, mania, and trust emotions into surprise or intimacy emotions, while the sad type of music video could reduce intimacy to the fear emotion.
Practical Approaches to Transvenous Lead Extraction Procedures—Clinical Case Series
Authors: Boarescu Paul-Mihai , Popa Iulia Diana , Trifan Cătălin Aurelian , Roşian Adela Nicoleta , Roşian Ştefan Horia
Published: December 2022

Transvenous lead extraction (TLE) is regarded as the first-line strategy for the management of complications associated with cardiac implantable electronic devices (CIEDs), when lead removal is mandatory. The decision to perform a lead extraction should take into consideration not only the strength of the clinical indication for the procedure but also many other factors such as risks versus benefits, extractor and team experience, and even patient preference. TLE is a procedure with a possible high risk of complications. In this paper, we present three clinical cases of patients who presented different indications of TLE and explain how the procedures were successfully performed. In the first clinical case, TLE was necessary because of device extravasation and suspicion of CIED pocket infection. In the second clinical case, TLE was necessary because occlusion of the left subclavian vein was found when an upgrade to cardiac resynchronization therapy was performed. In the last clinical case, TLE was necessary in order to remove magnetic resonance (MR) non-conditional leads, so the patient could undergo an MRI examination for the management of a brain tumor.
A Descriptive Analysis of Human Rabies in Mainland China, 2005–2020
Authors: Yue Yujuan , Chen Qiulan , Mu Di , Li Yu , Yin Wenwu
Published: December 2022

Epidemiological characteristics of human rabies in mainland China, 2005–2020 were analyzed to evaluate the effect of rabies control in China in recent years. A total of 24,319 human rabies cases were recorded in 2097 counties in 321 cities of 31 provinces in mainland China. Only 202 cases, located in 143 counties, were recorded in 2020, compared with 3305 cases in 992 counties in 2007; however, rabies was still relatively severe in Hunan Province even in 2020. Peak periods occurred in July–November; August was often the month with the most cases. Guizhou, Hunan, Guangdong, and Guangxi Provinces, in the central and southern regions, accounted for 50.0% of the cases in 2005–2020. Cases occurred almost exclusively in rural areas with 96.7% versus 3.3% in urban areas. A paradoxical relative expansion from southern, eastern, and central towards southwestern, northwestern, northern, and northeastern regions was observed along with the overall reduction of cases. Some regions witnessed complete elimination. The male-to-female ratio was 2.33:1; 66.8% of all cases were reported in the 0–10 (13.8%) and 41–70 (53.0%) age groups. Farmers (68.3%), followed by students (12.2), and diaspora children (6.5%) were most frequently involved. Our results provide objective information for the improvement of rabies prevention and control efforts. This will aid policymakers in China and elsewhere achieve the “Zero human deaths from dog-mediated rabies by 2030” global goal.
Bacterial Community Composition and Function of Tropical River Ecosystem along the Nandu River on Hainan Island, China
Authors: Li Jinbiao , Zhai Yangni , Ge Guojian , Xu Yang , Wang Can , Hu Anyong , Han Yujie , Shan Nan , Liu Bo , Chen Jinlin , Wang Wenlin
Published: December 2022

Microorganisms play a pivotal role in nutrient cycling in aquatic ecosystems. Understanding bacterial diversity and its functional composition are crucial for aquatic ecology and protection. We investigated the bacterial community structure using 16S rRNA gene amplicons high-throughput sequencing in this study. Results showed that 105 amplicon sequence variants (ASVs) account for 43.8% of the total sequences shared by the Nandu River’s lower, middle, and upper reach and the Songtao Reservoir. The dominant bacterial phylum in the Nandu River and its connected Songtao Reservoir were Proteobacteria and Actinobacteriota, respectively. The highest Chao1 and Shannon index values were found in the lower reach of the Nandu River. Beta diversity analysis showed the divergence in bacterial communities in the Nandu River and Songtao Reservoir, but not in different reaches. Among the water properties, based on the Mantel test, dissolved oxygen, total nitrogen, and nitrite significantly affected the bacterial communities. The functional profiles predicted by Tax4Fun2 showed that metabolism was the most abundant function group. The relative abundance of genetic information processing was significantly higher in the Songtao Reservoir than in the Nandu River, while the relative abundance of human diseases was significantly lower in the Songtao Reservoir than in the Nandu River. The appearance of the xenobiotics biodegradation and metabolism function group requires us to pay more attention to possible water pollution, especially at the upper reach of the Nandu River.
What Decides the Well-Being of the Relationship between Parents and Adolescents
Authors: Tafà Mimma , Bracaglia Fabrizia , Inguscio Lucio , Carone Nicola
Published: December 2022

The literature indicates a variety of factors that contribute to adolescent well-being: among these, the parent–adolescent relationship has a key role. The present article offered an overview of studies on parent–adolescent relationships across diverse family forms, not limited to the traditional family but also including “non-traditional” and “modern” families. To do so, this article described the evolution of the concept of family over the last fifty years and traced the significant family variables that guarantee adolescent well-being. Additionally, this article discussed the changes that occurred in family research, shifting from studies that considered only the family structure to more recent studies that investigated family processes and contextual factors. Overall, the reviewed studies indicated that the quality of parent–adolescent relationship, the interparental conflict and the consequent spillover effect on the child subsystem, and the changes in the economic situation following parental separation/divorce override the effect of the family structure. Finally, this article pointed out the need to examine, in the future research, adolescent well-being across diverse families by adopting more fine-grained methodologies, collecting data from the entire family system, and using a multi-method assessment to obtain a more ecological view of family complexity.
Exploring the Effects of Industrial Land Transfer on Urban Air Quality Using a Geographically and Temporally Weighted Regression Model
Authors: Song Lan , Huang Zhiji
Published: December 2022

This paper explores the spatial-temporal heterogeneity of the impact of industrial land transfer on urban air quality using the air quality index (AQI) and primary land market transaction data of 284 cities from 2015 to 2019 in China. Based on a three-dimensional conceptual framework including scale, price and style effect of industrial land transfer, we find that: (1) The scale effect shows an obvious characteristic of spatial agglomeration, and the agglomerations transfer from central and northern China to the western and southeast coastal regions. (2) Industrial land transfer price has a greater impact on air quality than transfer scale no matter whether the effect is positive or negative, which may be because the expansion scale of construction land is restricted strictly by indicators. (3) The scale of industrial land transferred by agreement in the west and northeast will reduce the air quality. (4) The impact of industrial land price transferred by bidding, auction and listing on AQI is gradually decreasing, but that of land transferred by agreement is still high in the northwest and northeast regions. Finally, we put forward policy recommendations based on the spatial and temporal heterogeneity of these effects, which will help alleviate or avoid environmental problems caused by land resources mismatch and industrial development.
Examining the Human Activity-Intensity Change at Different Stages of the COVID-19 Pandemic across Chinese Working, Residential and Entertainment Areas
Authors: Ma Shuang , Cao Kang , Li Shuangjin , Luo Yaozhi , Wang Ke , Liu Wei , Sun Guohui
Published: December 2022

The COVID-19 pandemic has already resulted in more than 6 million deaths worldwide as of December 2022. The COVID-19 has also been greatly affecting the activity of the human population in China and the world. It remains unclear how the human activity-intensity changes have been affected by the COVID-19 spread in China at its different stages along with the lockdown and relaxation policies. We used four days of Location-based services data from Tencent across China to capture the real-time changes in human activity intensity in three stages of COVID-19—namely, during the lockdown, at the first stage of work resuming and at the stage of total work resuming—and observed the changes in different land use categories. We applied the mean decrease Gini (MDG) approach in random forest to examine how these changes are influenced by land attributes, relying on the CART algorithm in Python. This approach was also compared with Geographically Weighted Regression (GWR). Our analysis revealed that the human activity intensity decreased by 22–35%, 9–16% and 6–15%, respectively, in relation to the normal conditions before the spread of COVID-19 during the three periods. The human activity intensity associated with commercial sites, sports facilities/gyms and tourism experienced the relatively largest contraction during the lockdown. During the relaxations of restrictions, government institutions showed a 13.89% rise in intensity at the first stage of work resuming, which was the highest rate among all the working sectors. Furthermore, the GDP and road junction density were more influenced by the change in human activity intensity for all land use categories. The bus stop density was importantly associated with mixed-use land recovery during the relaxing stages, while the coefficient of density of population in entertainment land were relatively higher at these two stages. This study aims to provide additional support to investigate the human activity changes due to the spread of COVID-19 at different stages across different sectors.
Chronic Facial Pain in Fibromyalgia: May ElectroMagnetic Field Represent a Promising New Therapy? A Pilot Randomized-Controlled Study
Authors: Storari Marco , Zerman Nicoletta , Salis Benedetta , Spinas Enrico
Published: December 2022

Fibromyalgic Syndrome is an important public health burden and affects up to 5% of the world population. It requires a complex treatment plan, possibly including antidepressants, anticonvulsants and benzodiazepines, which may in turn affect the patients’ quality of life: hence the need to find additional therapies. The current pilot randomized-controlled study analyzes the effect of electromagnetic field locally administered as add-on therapy in the treatment of cervico-facial pain in patients with fibromyalgic syndrome. 17 patients were selected and low-frequency electromagnetic field was applied via small patches worn in the neck area, between vertebrae C3–C4. Patients were divided into 2 groups, Treated, receiving the therapy, and Placebo, receiving an identical device which was not working,, with respectively 8 and 9 patients. The whole follow up period was 12 months and facial/cervical pain levels were rated using VAS scale. Significant differences were found between patients who received placebo and those treated. Treated patients showed statistically significant improvements in facial/cervical pain at each time-point, both with respect to the previous one and if compared to placebo. In conclusion, low frequency electromagnetic field emerged as beneficial in treating cervico-facial pain in patients with Fibromyalgic syndrome, with no side effects.
Multi-Index Geophysical Monitoring and Early Warning for Rockburst in Coalmine: A Case Study
Authors: Liu Xiaofei , Zhang Siqing , Wang Enyuan , Zhang Zhibo , Wang Yong , Yang Shengli
Published: December 2022

Rockburst is a major disaster in deep mining, restricting the safety and the production efficiency of the Laohutai Coal Mine in Fushun, Liaoning Province. To predict and prevent coalmine rockbursts, a comprehensive method based on multi-instrument monitoring is proposed by using a YDD16 acoustic-electromagnetic monitor and microseismic monitoring system, including microseismic (MS) monitoring, electromagnetic radiation (EMR) monitoring, and acoustic emission (AE) monitoring. Field investigation shows that MS, AE, and EMR signals have abnormal precursors before rockbursts in a new working face. Based on the fluctuation theory and D-S evidence theory, the multi-index geophysical monitoring and early warning technology for rockburst disasters in the Laohutai Coal Mine are established. The method has been applied to the prediction of rockbursts in the Laohutai Coal Mine. The application shows that the acoustic-electromagnetic synchronous monitoring and early warning technology can accurately identify the potential rockburst risk and trigger an early warning, which is more reliable than a single method. The case study of the Laohutai rockburst shows that the joint early warning method of multi-instrument comprehensive monitoring can predict the possibility of rockbursts.
Interprofessional Collaboration and Team Effectiveness of Pharmacists in General Practice: A Cross-National Survey
Authors: Sudeshika Thilini , Naunton Mark , Peterson Gregory M. , Deeks Louise S. , Guénette Line , Sharma Ravi , Freeman Christopher , Niyonsenga Theo , Kosari Sam
Published: December 2022

As team-based care continues to evolve, pharmacists have been included in general practice teams in many countries, to varying extents, to improve medication use and patient safety. However, evidence on interprofessional collaboration and team effectiveness of pharmacists in general practice is sparse. This study aimed to compare the extent of interprofessional collaboration and team effectiveness of general practice pharmacists in Australia with international sites (Canada and the UK), and identify the factors associated with interprofessional collaboration and team effectiveness. General practice pharmacists from Australia, Canada, and the UK were identified through professional organisations and networks, and invited to participate in an online survey, adapted from existing validated tools. The survey explored interprofessional collaboration through four sub-domains (professional interactions, relationship initiation, trust and role clarity, and commitment to collaboration) and team effectiveness of general practice pharmacists. Of the 101 respondents (26 from Australia, 44 from Canada and 31 from the UK), 79% were female and 78% were aged below 50 years. Interprofessional collaboration and team effectiveness appeared to be high and similar between countries. Total scores for collaboration of pharmacists were 86.1 ± 7.4 in Australia, 88.5 ± 7.5 in the UK, and 89.1 ± 7.3 in Canada (mean ± SD, where higher scores represent more advanced collaboration), while the team effectiveness scores of the pharmacists were 88.6 ± 14.6 in Canada, 91.8 ± 14.6 in Australia and 97.5 ± 14.0 in the UK. Pharmacists who had worked in general practice for a longer time showed advanced interprofessional collaboration while those who worked exclusively in general practice had higher scores for team effectiveness. Overall, general practice pharmacists in the three countries were highly collaborative with general practitioners. Long-term employment and longer work hours could enhance interprofessional collaboration and team effectiveness in general practice pharmacists by improving trust and working relationships over time.
Factors Influencing Access to Health Services among Chronically Ill Older Adults with Physical Disabilities in the Era of the COVID-19 Outbreak
Authors: Nanthamongkolchai Sutham , Tojeen Athicha , Yodmai Korravarn , Suksatan Wanich
Published: December 2022

Chronically ill older adults with physical disabilities frequently face difficulties in their daily lives and require essential health service access, especially in the COVID-19 context. This study aimed to examine the association between social support, perception of benefits due to disability and access to health services among chronically ill older adults with physical disabilities during this crisis in Thailand. A total of 276 chronically ill older adults with physical disabilities were included in this cross-sectional study. Self-reported questionnaires were assessed through multi-stage random sampling. Correlations between the independent variables and health service access were examined using multiple regression analysis. Of the respondents, 159 were female (59.6%). Most participants perceived benefits (58.8%) and access to health services (56.2%) at good levels, while social support was at a moderate level (47.9%). Stepwise multiple regression analysis showed that social support (β = 0.351), perception of benefits (β = 0.257) and age (β = 0.167) were positively correlated with health service access. The findings are relevant for health care providers and multi-professional teams, who should enhance older adults’ social support and perception of benefits to improve their access to health services, particularly among chronically ill older adults with physical disabilities, in the era of COVID-19.
Relationship between Lifestyle and Residence Area with 25(OH)D Levels in Older Adults
Authors: Isidorio Ubiraídys de Andrade , de Assis Elisangela Vilar , Lacerda Sheylla Nadjane Batista , Feitosa Ankilma do Nascimento Andrade , Alves Beatriz da Costa Aguiar , Gascón Thais , da Veiga Glaucia Luciano , Fonseca Fernando Luiz Affonso
Published: December 2022

The aim of this study was to investigate whether the habitat of older adults living in the urban and rural areas is a contributing factor to altered serum 25(OH)D levels. An analytical, cross-sectional research with a quantitative approach was conducted in the upper backwoods of Paraíba with older adults registered at the Reference Center for Social Assistance (CRAS), addressing residents of both rural area (n = 41) and urban area (n = 43) who were randomly chosen to participate in the study. Data collection took place between January and February 2020. Higher rates of handgrip strength were observed in rural older adults (29.22 ± 8.92 Kgf) with serum 25(OH)D levels in the range of 30 to 40 ng/mL when compared to older adults with concentrations below 30 ng/mL (21.82 ± 5.00 Kgf) and above 40 ng/mL (23.47 ± 6.88 Kgf). Older people living in the urban area, with 25(OH)D levels above 40 ng/mL, presented a lower muscle power index when compared to individuals with vitamin levels from 21 to 29 ng/mL (17.40 ± 6.34 s; 15.33 ± 2.00 s). The urbanization associated with 25(OH)D levels can cause changes in skeletal and respiratory muscle strength, because the habitat associated with 25(OH)D levels affects the parameters of muscle strength of the upper limbs for older adults living in a rural area and the muscle strength of the lower limbs for those living in an urban area.
Preoperative Risk Factors for Conversion from Laparoscopic to Open Cholecystectomy: A Systematic Review and Meta-Analysis
Authors: Magnano San Lio Roberta , Barchitta Martina , Maugeri Andrea , Quartarone Serafino , Basile Guido , Agodi Antonella
Published: December 2022

Laparoscopic cholecystectomy is a standard treatment for patients with gallstones in the gallbladder. However, multiple risk factors affect the probability of conversion from laparoscopic cholecystectomy to open surgery. A greater understanding of the preoperative factors related to conversion is crucial to improve patient safety. In the present systematic review, we summarized the current knowledge about the main factors associated with conversion. Next, we carried out several meta-analyses to evaluate the impact of independent clinical risk factors on conversion rate. Male gender (OR = 1.907; 95%CI = 1.254–2.901), age > 60 years (OR = 4.324; 95%CI = 3.396–5.506), acute cholecystitis (OR = 5.475; 95%CI = 2.959–10.130), diabetes (OR = 2.576; 95%CI = 1.687–3.934), hypertension (OR = 1.931; 95%CI = 1.018–3.662), heart diseases (OR = 2.947; 95%CI = 1.047–8.296), obesity (OR = 2.228; 95%CI = 1.162–4.271), and previous upper abdominal surgery (OR = 3.301; 95%CI = 1.965–5.543) increased the probability of conversion. Our analysis of clinical factors suggested the presence of different preoperative conditions, which are non-modifiable but could be useful for planning the surgical scenario and improving the post-operatory phase.
The Coupling Coordination Degree of Economic, Social and Ecological Resilience of Urban Agglomerations in China
Authors: Xu Xin , Wang Meimei , Wang Mingfeng , Yang Yongchun , Wang Yuliang
Published: December 2022

This paper refines the fuzzy logic method, while constructing a theoretical model of the relationship between economic resilience, social resilience and ecological resilience, and evaluates the coupling coordination between the economic-social-ecological resilience of 197 prefecture-level cities in China’s urban agglomerations in 2019. Findings include: (1) The mean ecological resilience of China’s urban agglomerations in 2019 was the highest, followed by economic and social resilience. (2) Promoting urban agglomerations had higher resilience scores in the three dimensions, especially in the economic dimension. Growing urban agglomerations had low resilience values on the whole, especially economic resilience. (3) The mean coupling coordination degree of economic-social-ecological resilience ranged from near-incoordination to narrow balance. (4) The coupling coordination degree between the two coincided with the positioning of existing urban agglomerations. (5) Economic resilience had the most significant impact on the coupling coordination. Finally, we give differentiated countermeasures to improve the resilience of urban agglomerations. This study aims to contribute to the promotion of urban resilience research, and helps to plan and design more rational urban economic-social-ecological systems, thereby enhancing the ability of cities to cope with any uncertainties and contingencies.
Impact of Environmental Regulation on Regional Innovative Ability: From the Perspective of Local Government Competition
Authors: Wang Dongling , Zhang Yuming , Zhang Xiaoyi
Published: December 2022

We empirically investigate the relationship between environmental regulation and regional innovative ability from the perspective of government competition with a dynamic spatial model, using the 2011–2020 Chinese interprovincial panel dataset as the sample. Empirical underpinnings reveal the interconnection between environmental regulation and regional innovative ability. Further, it has been substantiated as follows: (1) environmental regulation affects regional innovative ability significantly. From the national level perspective, environmental regulation is negatively correlated with regional innovative ability. Further, vigorous environmental regulation deters regional innovative ability and produces a crowding out effect; (2) Environmental regulation has a significant spatial spillover effect on regional technological innovative ability. Meanwhile, the promulgation of environmental policy in the region will affect the innovative ability of neighboring regions; (3) It has also been concluded that there is a strategic competition among local governments in promulgation of environmental regulation, specifically in eastern and central regions which has been signified through regional regressions result. Comprehensively, the current study provides recommendations to governments for allocation of environmental policy under the aegis of regional innovation for improving regional innovative ability.
MicroRNAs in T Cell-Immunotherapy
Authors: Dosil Sara G. , Rodríguez-Galán Ana , Sánchez-Madrid Francisco , Fernández-Messina Lola
Published: December 2022

MicroRNAs (miRNAs) act as master regulators of gene expression in homeostasis and disease. Despite the rapidly growing body of evidence on the theranostic potential of restoring miRNA levels in pre-clinical models, the translation into clinics remains limited. Here, we review the current knowledge of miRNAs as T-cell targeting immunotherapeutic tools, and we offer an overview of the recent advances in miRNA delivery strategies, clinical trials and future perspectives in RNA interference technologies.
Genome-Wide Characterization and Evolutionary Expansion of Poplar NAC Transcription Factors and Their Tissue-Specific Expression Profiles under Drought
Authors: Meng Lu , Chen Siyuan , Li Dawei , Huang Minren , Zhu Sheng
Published: December 2022

The NAC (NAM, ATAF1/2 and CUC2) is a large gene family of plant-specific transcription factors that play a pivotal role in various physiological processes and abiotic stresses. Due to the lack of genome-wide characterization, intraspecific and interspecific synteny, and drought-responsive expression pattern of NAC genes in poplar, the functional characterization of drought-related NAC genes have been scarcely reported in Populus species. Here, we identified a total of 170 NAC domain-containing genes in the P. trichocarpa genome, 169 of which were unevenly distributed on its nineteen chromosomes. These NAC genes were phylogenetically divided into twenty subgroups, some of which exhibited a similar pattern of exon–intron architecture. The synteny and Ka/Ks analysis indicated that the expansion of NAC genes in poplar was mainly due to gene duplication events occurring before and after the divergence of Populus and Salix. Ten PdNAC (P. deltoids × P. euramericana cv.’Nanlin895’) genes were randomly selected and cloned. Their drought-responsive expression profiles showed a tissue-specific pattern. The transcription factor PdNAC013 was verified to be localized in the nucleus. Our research results provide genomic information for the expansion of NAC genes in the poplar genome, and for further characterizing putative poplar NAC genes associated with water-deficit.
Hypothermia Does Not Boost the Neuroprotection Promoted by Umbilical Cord Blood Cells in a Neonatal Hypoxia-Ischemia Rat Model
Authors: Serrenho Inês , Cardoso Carla M. , Grãos Mário , Dinis Alexandra , Manadas Bruno , Baltazar Graça
Published: December 2022

Neonatal hypoxic-ischemic encephalopathy (HIE) is one of the leading causes of death and long-term disability in the perinatal period. Currently, therapeutic hypothermia is the standard of care for this condition with modest efficacy and strict enrollment criteria. Therapy with umbilical cord blood cells (UCBC) has come forward as a strong candidate for the treatment of neonatal HIE, but no preclinical studies have yet compared the action of UCBC combined with hypothermia (HT) with the action of each therapy by itself. Thus, to evaluate the potential of each therapeutic approach, a hypoxic-ischemic brain lesion was induced in postnatal day ten rat pups; two hours later, HT was applied for 4 h; and 24, 48, and 72 h post-injury, UCBC were administered intravenously. The neonatal hypoxic-ischemic injury led to a brain lesion involving about 48% of the left hemisphere that was not improved by HT (36%) or UCBC alone (28%), but only with the combined therapies (25%; p = 0.0294). Moreover, a decrease in glial reactivity and improved functional outcomes were observed in both groups treated with UCBC. Overall, these results support UCBC as a successful therapeutic approach for HIE, even when treatment with therapeutic hypothermia is not possible.
Ultra-Short Cyclized β-Boomerang Peptides: Structures, Interactions with Lipopolysaccharide, Antibiotic Potentiator and Wound Healing
Authors: Sinha Sheetal , Dhanabal Vidhya Bharathi , Manivannen Veronica Lavanya , Cappiello Floriana , Tan Suet-Mien , Bhattacharjya Surajit
Published: December 2022

Many antibiotics are ineffective in killing Gram-negative bacteria due to the permeability barrier of the outer-membrane LPS. Infections caused by multi-drug-resistant Gram-negative pathogens require new antibiotics, which are often difficult to develop. Antibiotic potentiators disrupt outer-membrane LPS and can assist the entry of large-scaffold antibiotics to the bacterial targets. In this work, we designed a backbone-cyclized ultra-short, six-amino-acid-long (WKRKRY) peptide, termed cWY6 from LPS binding motif of β-boomerang bactericidal peptides. The cWY6 peptide does not exhibit any antimicrobial activity; however, it is able to permeabilize the LPS outer membrane. Our results demonstrate the antibiotic potentiator activity in the designed cWY6 peptide for several conventional antibiotics (vancomycin, rifampicin, erythromycin, novobiocin and azithromycin). Remarkably, the short cWY6 peptide exhibits wound-healing activity in in vitro assays. NMR, computational docking and biophysical studies describe the atomic-resolution structure of the peptide in complex with LPS and mode of action in disrupting the outer membrane. The dual activities of cWY6 peptide hold high promise for further translation to therapeutics.
HIV-Tat Exacerbates the Actions of Atazanavir, Efavirenz, and Ritonavir on Cardiac Ryanodine Receptor (RyR2)
Authors: Alomar Fadhel A. , Tian Chengju , Bidasee Sean R. , Venn Zachary L. , Schroder Evan , Palermo Nicholas Y. , AlShabeeb Mohammad , Edagwa Benson J. , Payne Jason J. , Bidasee Keshore R.
Published: December 2022

The incidence of sudden cardiac death (SCD) in people living with HIV infection (PLWH), especially those with inadequate viral suppression, is high and the reasons for this remain incompletely characterized. The timely opening and closing of type 2 ryanodine receptor (RyR2) is critical for ensuring rhythmic cardiac contraction–relaxation cycles, and the disruption of these processes can elicit Ca2+ waves, ventricular arrhythmias, and SCD. Herein, we show that the HIV protein Tat (HIV-Tat: 0–52 ng/mL) and therapeutic levels of the antiretroviral drugs atazanavir (ATV: 0–25,344 ng/mL), efavirenz (EFV: 0–11,376 ng/mL), and ritonavir (RTV: 0–25,956 ng/mL) bind to and modulate the opening and closing of RyR2. Abacavir (0–14,315 ng/mL), bictegravir (0–22,469 ng/mL), Rilpivirine (0–14,360 ng/mL), and tenofovir disoproxil fumarate (0–18,321 ng/mL) did not alter [3H]ryanodine binding to RyR2. Pretreating RyR2 with low HIV-Tat (14 ng/mL) potentiated the abilities of ATV and RTV to bind to open RyR2 and enhanced their ability to bind to EFV to close RyR2. In silico molecular docking using a Schrodinger Prime protein–protein docking algorithm identified three thermodynamically favored interacting sites for HIV-Tat on RyR2. The most favored site resides between amino acids (AA) 1702–1963; the second favored site resides between AA 467–1465, and the third site resides between AA 201–1816. Collectively, these new data show that HIV-Tat, ATV, EFV, and RTV can bind to and modulate the activity of RyR2 and that HIV-Tat can exacerbate the actions of ATV, EFV, and RTV on RyR2. Whether the modulation of RyR2 by these agents increases the risk of arrhythmias and SCD remains to be explored.
Single-Cell RNA-Sequencing Reveals Epithelial Cell Signature of Multiple Subtypes in Chemically Induced Acute Lung Injury
Authors: Cao Chao , Memete Obulkasim , Shao Yiru , Zhang Lin , Liu Fuli , Dun Yu , He Daikun , Zhou Jian , Shen Jie
Published: December 2022

Alveolar epithelial cells (AECs) play a role in chemically induced acute lung injury (CALI). However, the mechanisms that induce alveolar epithelial type 2 cells (AEC2s) to proliferate, exit the cell cycle, and transdifferentiate into alveolar epithelial type 1 cells (AEC1s) are unclear. Here, we investigated the epithelial cell types and states in a phosgene-induced CALI rat model. Single-cell RNA-sequencing of bronchoalveolar lavage fluid (BALF) samples from phosgene-induced CALI rat models (Gas) and normal controls (NC) was performed. From the NC and Gas BALF samples, 37,245 and 29,853 high-quality cells were extracted, respectively. All cell types and states were identified and divided into 23 clusters; three cell types were identified: macrophages, epithelial cells, and macrophage proliferating cells. From NC and Gas samples, 1315 and 1756 epithelial cells were extracted, respectively, and divided into 11 clusters. The number of AEC1s decreased considerably following phosgene inhalation. A unique SOX9-positive AEC2 cell type that expanded considerably in the CALI state was identified. This progenitor cell type may develop into alveolar cells, indicating its stem cell differentiation potential. We present a single-cell genome-scale transcription map that can help uncover disease-associated cytologic signatures for understanding biological changes and regeneration of lung tissues during CALI.
The Flavonoid Naringenin Alleviates Collagen-Induced Arthritis through Curbing the Migration and Polarization of CD4+ T Lymphocyte Driven by Regulating Mitochondrial Fission
Authors: Jiang Yue-Peng , Wen Jun-Jun , Zhao Xiao-Xuan , Gao Yuan-Cheng , Ma Xiao , Song Si-Yue , Jin Yan , Shao Tie-Juan , Yu Jie , Wen Cheng-Ping
Published: December 2022

Rheumatoid arthritis (RA) is a progressive autoimmune disease. Due to local infiltration and damage to the joints, activated CD4+ T cells play a crucial role in the progression of RA. However, the exact regulatory mechanisms are perplexing, which makes the effective management of RA frustrating. This study aimed to investigate the effect of mitochondria fission on the polarization and migration of CD4+ T cells as well as the regulatory mechanism of NAR, so as to provide enlightenment on therapeutic targets and novel strategies for the treatment of RA. In this study, a collagen-induced arthritis (CIA) model was established, and rats were randomly given saline or naringenin (NAR, 10 mg/kg, 20 mg/kg, 50 mg/kg, i.p.) once a day, before being euthanized on the 42nd day of primary immunization. The pain-like behavior, articular index scores, account of synovial-infiltrated CD4+ T cells, and inflammatory factors were investigated in each group. In vitro, spleen CD4+ T lymphocytes were derived from each group. In addition, mitochondrial division inhibitor 1 (Mdivi-1) or NAR was added to the cell medium containing C-X-C motif chemokine ligand 12 (CXCL12) in order to induce CD4+ T lymphocytes, respectively. The polarization capacity of CD4+ T cells was evaluated through the immunofluorescence intensity of the F-actin and myosin light chain phosphorylated at Ser19 (pMLC S19), and the mitochondrial distribution was determined by co-localization analysis of the translocase of outer mitochondrial membrane 20 (TOM20, the mitochondrial marker) and intercellular adhesion molecule 1 (ICAM1, the uropod marker). The mitochondrial fission was investigated by detecting dynamin-related protein 1 (Drp1) and mitochondrial fission protein 1 (Fis1) using Western blot and immunofluorescence. This study revealed that high-dose NAR (50 mg/kg, i.p.) alleviated pain-like behavior and articular index scores, reduced the serum level of interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α), and accounted for CD4+ T lymphocytes that infiltrated into the synovial membrane of the CIA group. Meanwhile, NAR (50 mg/kg, i.p.) suppressed the polarization of spleen CD4+ T lymphocytes, reduced the redistribution of mitochondria in the uropod, and inhibited the expression of Drp1 and Fis1 in the CIA model. Furthermore, the in vitro experiments confirmed that NAR reduced mitochondrial fission, which in turn inhibited the CXCL12-induced polarization and migration of CD4+ T lymphocytes. Our results demonstrated that the flavonoid NAR was a promising drug for the treatment of RA, which could effectively interfere with mitochondrial fission, thus inhibiting the polarization and migration of CD4+ T cells in the synovial membrane.
Childhood Hypophosphatasia Associated with a Novel Biallelic ALPL Variant at the TNSALP Dimer Interface
Authors: Martins Luciane , Lessa Luis Gustavo F. , Ali Taccyanna M. , Lazar Monize , Kim Chong A. , Kantovitz Kamila R. , Santamaria Mauro P. , Araújo Cássia F. , Ramos Carolina J. , Foster Brian L. , Franco José Francisco S. , Bertola Débora , Nociti Francisco H.
Published: December 2022

The goal of this study was to perform a clinical and molecular investigation in an eight-year-old female child diagnosed with hypophosphatasia (HPP). The proband and her family were evaluated by medical and dental histories, biochemical analyses, radiographic imaging, and genetic analysis of the tissue-nonspecific alkaline phosphatase (ALPL) gene. A bioinformatic analysis was performed to predict the structural and functional impact of the point mutations in the tissue-nonspecific alkaline phosphatase (TNSALP) molecule and to define their potential contribution to the phenotype. We identified a novel combination of heterozygous ALPL missense variants in the proband, p.Ala33Val and p.Asn47His, compatible with an autosomal recessive mode of inheritance and resulting in skeletal and dental phenotypes. Computational modeling showed that the affected Asn47 residue is located in the coil structure close to the N-terminal α-helix, whereas the affected Ala33 residue is localized in the N-terminal α-helix. Both affected residues are located close to the homodimer interface, suggesting they may impair TNSALP dimer formation and stability. Clinical and biochemical follow-up revealed improvements after six years of ERT. Reporting this novel combination of ALPL variants in childhood HPP provides new insights into genotype–phenotype associations for HPP and specific sites within the TNSALP molecule potentially related to a childhood-onset HPP and skeletal and dental manifestations. Beneficial effects of ERT are implicated in skeletal and dental tissues.
The Difference in Zinc Concentrations Required for Induction among Metallothionein Isoforms Can Be Explained by the Different MTF1 Affinities to MREs in Its Promoter
Authors: Ogushi Shoko , Kimura Tomoki
Published: December 2022

Metallothioneins (MTs) are cysteine-rich low-molecular-weight proteins that protect cells from heavy metal toxicity. MT1 and MT2 are considered ubiquitously expressed among the MT isoforms ranging from 1 to 4. These MT1 and MT2 transcriptions are regulated by metal regulatory transcription factor 1 (MTF1) binding to the metal response element (MRE) of the promoter, which is upregulated in response to zinc. The functional MT isoforms are MT1A, MT1B, MT1E, MT1F, MT1G, MT1H, MT1M, MT1X, and MT2A in humans, but these expressions were differently regulated. Here, MT1A was shown to be significantly less upregulated by zinc than MT1E, MT1G, MT1X, and MT2A. The poor responsiveness of the MT1A zinc was suggested to be due to the MRE sequence in the MT1A promoter region having a lower MTF1 binding affinity compared to the other isoforms. MT1A may be induced via pathways other than the MTF1–MRE binding pathway. These findings may help elucidate the differential regulation of MT isoform expression.