Search

Guiling Li,1 Li Wang,2 Heguang Zhang,1 Ying Luan,1 Qi Sun,1 Libo Duo1 1Department of Clinical Laboratory, the Second Hospital Affiliated to Harbin Medical University, Harbin, Heilongjiang, 150086, People’s Republic of China; 2Department of Clinical Laboratory, School of Medicine, Chengdu Women’s and Children’s Central Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, 611731, People’s Republic of ChinaCorrespondence: Libo Duo, Department of Clinical Laboratory, the Second Hospital affiliated to Harbin Medical University, No. 246 XueFu Road, NanGang District, Harbin, Heilongjiang, 150086, People’s Republic of China, Tel +86 045186605382, Email duolibo@163.comObjective: In this study, we constructed ampG knock-out and knock-in strains from a clinically isolated Kp1strain carrying ampR-ampC in its plasmid and compared them with the Kp NTUH-K2044 strain to investigate the relationship between ampG and ampR-ampC-induced expression.Methods: We created the ampG gene deletion mutant strains Kp1-ΔampG and Kp NTUH-K2044-ΔampG with pKO3-km plasmid using homologous recombination technology. We constructed the Kp NTUH-K2044-RC and Kp NTUH-K2044-ΔampG-RC drug resistance model strains with plasmid pACYC184. We constructed the ampG knock-in strains by introducing the ampG genes of Kp1, Enterobacter cloacae 029M, Pseudomonas aeruginosa PAO1, Escherichia coli ATCC25922, and Salmonella typhimurium LT2 into the ampG gene-deleted strains with carrier pet-30a. Real-time polymerase chain reaction (real-time PCR) was used to detect the relative expressions of ampC and ampG mRNAs.Results: Compared with Kp1, the induction phenotype of the ampC of Kp1-ΔampG strain disappeared, the ampC expression was reduced, and the minimal inhibitory concentration (MIC) values of cefoxitin and ceftazidime significant decrease from 128 μg/mL to 1 μg/mL. Based on Kp1, five strain were successfully constructed to complement the ampG genes from five knock-in strain, and all of the above complemented strains showed inducible expression of ampC and restored the expression of ampG to varying degrees, as well as restored resistance to the antimicrobial drugs cefoxitin and ceftazidime (P < 0.05). The ampC and ampG genes were barely expressed in Kp NTUH-K2044-ΔampG-RC when compared with Kp NTUH-K2044-RC. The expressions of ampG and ampC in each knock-in strain were recovered, the induction phenotype of ampC was restored, and the MIC values of cefoxitin and ceftazidime were increased. (P < 0.05).Conclusion: In this study, we found that ampG was an essential regulator for the plasmid-mediated ampC-induced expression in K. pneumoniae.Keywords: ampC inducible expression, AmpG regulator, gene knockout, gene knock-in, Klebsiella pneumoniae

The CH3I structural deformation induced by strong laser fields is revealed by time- and frequencyresolved ro-vibrational spectra. The experimental results show that the CH3I molecule undergoes ultrafast structural deformation of CH3 "umbrella-closing" induced by the strong fs laser field (more than 1011W/cm²) and followed by a structural relaxation of "umbrella-opening" within an exponential decay time scale of ~620 fs. This study provides a first glimpse of the immense potential of the timeand frequency-resolved vibrational spectra in studying molecular deformation dynamics. [ABSTRACT FROM AUTHOR]

Background Inherited epidermodysplasia verruciformis (EV) is a rare skin disorder characterized by susceptibility to specific types of human papilloma virus (HPV) and is strongly associated with skin carcinomas. Inactivating mutations in EVER1/EVER2 account for most cases of EV. However, more phenotypes related to but distinct from EV have been reported with an immunodeficiency state but without EVER1/EVER2 mutation, and the genetic basis for these atypical EV cases is poorly understood. Objectives To identify the causative gene responsible for three siblings affected by atypical EV but without EVER1/EVER2 mutation. Methods Whole-exome sequencing followed by Sanger sequencing was performed to identify the gene responsible for the patients with atypical EV enrolled in our study. Results A homozygous splicing mutation was detected in LCK (c.188-2A>G). This mutation resulted in an exon 3 deletion T lymphocyte-specific protein tyrosine kinase isoform, which further led to frameshift mutation and subsequent mRNA decay. Conclusions We demonstrate a novel mutation in LCK in a family affected by atypical EV with T-cell defects, HPV infection and virus-induced malignancy, providing new clues in the understanding of host defences against HPV and better genetic counselling of patients with the EV phenotype. [ABSTRACT FROM AUTHOR]

In contrast to "white pollution" originating from waste plastics, waste rubber is often referred to as "black pollution." The quantity and variety of waste rubber are increasing at an alarming rate, with a considerable fraction entering the global ecosystem via various pathways. This study presents the first critical review of waste rubber research with a focus on the risks associated with toxicant discharge and existing problems in waste rubber disposal, management, and recycling practices. We aim to obtain a comprehensive understanding of current research, particularly regarding the ecological impacts of these wastes, highlight major gaps, and propose the most significant research directions. A total of 192 studies published in journals were critically analysed. The importance of conducting long-term and large-scale experiments and developing efficient waste rubber recycling systems is also emphasised. This study highlights the need to address the challenges posed by waste rubber pollution and offers insights and references for undertaking ecological risk assessments and understanding the mechanisms underlying toxicant behaviour. Suggestions and countermeasures are proposed with ecosystem sustainability as the ultimate goal. Further long-term, comprehensive, and systematic research in this area is required., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) target the reabsorption of sodium and glucose in the kidney proximal tubules to reduce blood sugar levels. However, clinical randomized controlled trials on SGLT2i have yielded inconsistent results, necessitating further research into their efficacy and safety for specific cardiac and renal diseases., Methods: "Sodium in urine" was selected as a downstream biomarker of SGLT2i. Single nucleotide polymorphisms were extracted from genome-wide association study data as instrumental variables. Mendelian randomization analysis was then conducted for cardiac and renal diseases and potential adverse events. The causal effects of SGLT2i on these diseases were determined based on inverse variance weighted results, followed by sensitivity and pleiotropy tests., Results: SGLT2i had a significant protective effect against nephrotic syndrome (odds ratio [OR] 0.0011, 95% confidence interval [CI] 0.000-0.237), chronic glomerulonephritis (OR 0.0002, 95% CI 0.000-0.21), and hypertensive nephropathy (OR 0.0003, 95% CI 0.000-0.785). No causal effects were observed between SGLT2i and cardiac diseases or potential adverse events., Conclusions: SGLT2i can act as protective factors against nephrotic syndrome, chronic glomerulonephritis, and hypertensive nephropathy., Competing Interests: Declaration of conflicting interestThe authors declare that there is no conflict of interest.

Introduction: The transition from conventional cytotoxic chemotherapy to targeted cancer therapy with small-molecule anticancer drugs has enhanced treatment outcomes. This approach, which now dominates cancer treatment, has its advantages. Despite the regulatory approval of several targeted molecules for clinical use, challenges such as low response rates and drug resistance still persist. Conventional drug discovery methods are costly and time-consuming, necessitating more efficient approaches. The rise of artificial intelligence (AI) and access to large-scale datasets have revolutionized the field of small-molecule cancer drug discovery. Machine learning (ML), particularly deep learning (DL) techniques, enables the rapid identification and development of novel anticancer agents by analyzing vast amounts of genomic, proteomic, and imaging data to uncover hidden patterns and relationships., Area Covered: In this review, the authors explore the important landmarks in the history of AI-driven drug discovery. They also highlight various applications in small-molecule cancer drug discovery, outline the challenges faced, and provide insights for future research., Expert Opinion: The advent of big data has allowed AI to penetrate and enable innovations in almost every stage of medicine discovery, transforming the landscape of oncology research through the development of state-of-the-art algorithms and models. Despite challenges in data quality, model interpretability, and technical limitations, advancements promise breakthroughs in personalized and precision oncology, revolutionizing future cancer management.

Krill oil (KO), extracted from the Antarctic marine crustacean Euphausia superba , is a nutrient-dense substance that includes rich profiles of n -3 polyunsaturated fatty acids ( n -3 PUFAs), phospholipids (PLs), astaxanthin (ASX), as well as vitamins A and E, minerals, and flavonoids. As a high-quality lipid resource, KO has been widely used as a dietary supplement for its health-protective properties in recent years. KO has various benefits, including antioxidative, anti-inflammatory, metabolic regulatory, neuroprotective, and gut microbiome modulatory effects. Especially, the antioxidant and anti-inflammatory effects make KO have potential in skin care applications. With increasing demands for natural skin anti-aging solutions, KO has emerged as a valuable nutraceutical in dermatology, showing potential for mitigating the effects of skin aging and enhancing overall skin health and vitality. This review provides an overview of existing studies on the beneficial impact of KO on the skin, exploring its functional roles and underlying mechanisms through which it contributes to dermatological health and disease management., Competing Interests: JY and ZW were employed by Jiangsu Sunline Deep Sea Fishery Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Duo, Yang, Wang, Zhang, Zhao, Zou, Wang and Li.)

Background: Progress in cardiovascular health is increasingly concentrated in high-income countries, while the burden of cardiovascular disease (CVD) is high in low- and middle-income countries, a clear health inequity that must be urgently addressed., Objective: This study aims to evaluate the prevalence and clustering of CVD risk factors in the three Lancang-Mekong regions., Methods: We conducted a population-based cross-sectional survey from January 2021 to March 2023 in China, Laos, and Cambodia. We compared the prevalence and clustering of CVD risk factors-including hypertension, dyslipidemia, diabetes mellitus, overweight/obesity, current smoking status, current drinking status, inadequate vegetable and fruit intake, and insufficient physical activity-across the three regions, further stratifying the data by gender and age. Multivariate logistic regression models were performed to explore factors influencing the aggregation of CVD risk factors (≥2, ≥3, ≥4)., Results: A total of 11,005 adults were included in the study. Hypertension emerged as the primary metabolic risk factor in Laos (36.8%) and Cambodia (23.5%), whereas overweight/obesity was the primary risk factor in China (37.6%). In terms of behavioral risk factors, participants in all three regions showed insufficient vegetable and fruit intake. The prevalence of individuals without CVD risk factors was 10% in China, 1.9% in Laos, and 5.2% in Cambodia. Meanwhile, the prevalence of two or more risk factors was 64.6% in China, 79.2% in Laos, and 76.0% in Cambodia. Multivariate logistic regression models revealed that the propensity for CVD risk factors clustering was higher in men and increased with age in all three countries., Conclusions: CVD risk factors and multiple clustering are pressing health threats among adults in low- and middle-income areas along the Lancang-Mekong River Basin. This study highlights the urgent need for proactive tailored strategies to control CVD risk factors., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

This paper presents a proposal for riparian area delineation relying on topographical, hydrological, vegetation, and soil data together with numerical modelling of the river hydrodynamics. The two-dimensional model Iber is used to simulate 2.5, 10, 50, and 100-years return period flood events, and new code is developed to simulate the main hydrological processes of the river-riparian system to generate riparian zone maps. Results show that changes in topography and discharge direction between river and groundwater both influence the riparian area extent, and that temporal evolution of the riparian zone is much slower than that of the flood, and its extension can continue to increase while the flood recedes, but only to a certain extent, conditioned by topography, soil characteristics, and vegetation. A simple but efficient numerical code for understanding and simulating the riparian dynamics has been developed, which constitutes a proposal for a new riparian delineation approach useful for research and management applications, and which can also be a useful tool for gaining a better understanding of the riparian boundary behavior under different ecohydrological conditions., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Lan Duo reports financial support was provided by National Scholarship Fund of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Posterior capsule opacification (PCO), as one of the most common late complications after intraocular lens (IOL) implantation in cataract surgery, seriously affects patients' postoperative vision and surgical satisfaction, and can only be treated by laser incision of the posterior capsule. Although drug eluting coating modification have been proved to inhibit PCO effectively, the complicated coating methods and the potential toxicity of the antiproliferative drugs hinders its actual application. In this study, an indocyanine green (ICG) loaded polydopamine (PDA) coating modified IOL (IP-IOL) was designed to prevented PCO. In vitro and in vivo studies have shown that IP-IOL can effectively eliminate lens epithelial cells and significantly reduce the degree of PCO. At the same time, it still has good imaging quality and optical properties. Furthermore, both the near-infrared irradiation and ICG loaded PDA coating modified IOLs have proved to possess high biological safety to eyes. Thus, with easy preparation and safer near-infrared irradiated photothermal/photodynamic synchronous properties, such ICG loaded PDA coating provides an effective yet easier and safer PCO prevention after IOL implantation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Overactivation of the rat sarcoma virus (RAS) signaling is responsible for 30% of all human malignancies. Son of sevenless 1 (SOS1), a crucial node in the RAS signaling pathway, could modulate RAS activation, offering a promising therapeutic strategy for RAS-driven cancers. Applying machine learning (ML)-based virtual screening (VS) on small-molecule databases, we selected a random forest (RF) regressor for its robustness and performance. Screening was performed with the L-series and EGFR-related datasets, and was extended to the Chinese National Compound Library (CNCL) with more than 1.4 million compounds. In addition to a series of documented SOS1-related molecules, we uncovered nine compounds that have an unexplored chemical framework and displayed inhibitory activity, with the most potent achieving more than 50% inhibition rate in the KRAS G12C/SOS1 PPI assay and an IC 50 value in the proximity of 20 μg mL -1 . Compared with the manner that known inhibitory agents bind to the target, hit compounds represented by CL01545365 occupy a unique pocket in molecular docking. An in silico drug-likeness assessment suggested that the compound has moderately favorable drug-like properties and pharmacokinetic characteristics. Altogether, our findings strongly support that, characterized by the distinctive binding modes, the recognition of novel skeletons from the carboxylic acid series could be candidates for developing promising SOS1 inhibitors., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Mineral extraction in resource-based cities has caused serious damage to the original ecology, resulting in poor regional vegetation growth, reduced carbon sequestration capacity, and reduced ecosystem resilience. Especially in resource-based cities with fragile ecology, the overall anti-interference ability of the environment is relatively worse. Seeking ecological network optimization solutions that can improve vegetation growth conditions on a large scale is an effective way to enhance the resilience of regional ecosystems. This paper introduces carbon sequestration indicators and designs a differential ecological networks (ENs) optimization model (FTCC model) to achieve the goal of improving ecosystem resilience. The model identifies the patches that need to be optimized and their optimization directions based on the differences in ecological function-topology-connectivity-carbon sequestration of the patches. Finally, the resilience of the ecological network before and after optimization was compared, proving that the model is effective. The results show that the sources in the Yulin ENs form three main clusters, with connectivity between clusters relying on only a few patches. The patches in the northeastern and southwest clusters are large but their ecological functions need to be improved. After optimization, 16 new stepping stones were added, 38 new corridors were added, and the ecological function of 39 patches was enhanced. The optimized ecological network resilience was improved in terms of structure, function, and carbon sinks, and carbon sinks increased by 6364.5 tons. This study provides a reference for measures to optimize landscape space and manage ecosystem resilience enhancement in resource-based cities., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Understanding the competition and coexistence of flagship carnivores is key to creating strategies for their conservation in the face of global carnivore declines. Although studies exploring the dynamics and competition between tigers (Panthera tigris) and leopards (P. pardus) span decades, there is a lack of understanding regarding the factors that influence their coexistence mechanisms on a broad scale, as well as the drivers determining their exploitative and interference competition. We gathered a comprehensive list of research papers among which 36 papers explored the interspecific interactions between tigers and leopards and tested the influence of biotic and abiotic factors on the coexistence mechanisms along three dimensions using multiple response variables regression models; we also tested the influence of ecological drivers determining the exploitative or interference competition between tigers and leopards. Elevation and ungulate density were the most important predictors in regulating the coexistence mechanisms. Tigers and leopards exhibited more positive relations/higher overlaps as elevation increased in the spatial niche. In addition, they showed a higher dietary overlap in the prey-rich regions. We determined that interference competition between tigers and leopards was less frequently observed in habitats with dense tree cover and homogeneous vegetation structures. Meanwhile, studies with multiple metrics would promote the detection of interference competition. Our study provides new insight into the competitive interactions and coexistence mechanisms of tigers and leopards on a broad scale. Policy-makers and managers should pay more attention to the factors of elevation, prey abundance, and habitat structures for the conservation of tigers and leopards., (© 2023 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.)

Background: The Basic Public Health Service (BPHS), a recently announced free healthcare program, aims to combat the most prevalent Noncommunicable Disease-"Hypertension" (HTN)-and its risk factors on a nationwide scale. In China, there is a rife that HTN less impacts women during their lifetime. We, therefore, aimed to evaluate the sex disparity in hypertension patients with comorbidities among south-west Chinese and the contribution of BPHS to address that concern., Methods: We have opted for a multistage stratified random sampling method to enroll hypertensive patients of 35 years and older, divided them into BPHS and non-BPHS groups. We assessed the sex disparity in HTN patients with four major comorbidities- Dyslipidemia, Diabetes Mellitus (DM), Cardiovascular Disease (CVD), and Chronic Kidney Disease (CKD), and descriptive data were compiled. Odds ratios from logistic regression models estimated the effectiveness of BPHS in the management of HTN with comorbidities., Results: Among 1521 hypertensive patients,1011(66.5%) were managed in the BPHS group. The proportion of patients who had at least one comorbidity was 70.7% (95% confidence interval [CI]: 66.3-76.8%), patients aged 65 years and older were more likely to have coexisting comorbidities. Participants who received the BPHS showed significant blood pressure (BP) control with two comorbidities (odds ratio [OR] = 2.414, 95% CI: 1.276-4.570), three or more (OR = 5.500, 95%CI: 1.174-25.756). Patients with dyslipidemia and DM also benefited from BPHS in controlling BP (OR = 2.169, 95% CI: 1.430-3.289) and (OR = 2.785, 95%CI: 1.242-6.246), respectively. In certain high-income urban survey centers, there was sex differences in the HTN management provided by BPHS, with men having better BP control rates than women., Conclusions: Perhaps this is the first study in China to succinctly show the effectiveness and sex disparity regarding "management of hypertensive comorbidities". This supports that the BPHS program plays a pivotal role in controlling BP, therefore should recommend the national healthcare system to give women a foremost priority in BPHS, especially to those from low-socioeconomic and low-scientific literacy regions., (© 2024. The Author(s).)

Aβ aggregation leads to the formation of both insoluble amyloid fibrils and soluble oligomers. Understanding the structures of Aβ oligomers is important for delineating the mechanism of Aβ aggregation and developing effective therapeutics. Here, we use site-directed spin labeling and electron paramagnetic resonance (EPR) spectroscopy to study Aβ42 oligomers prepared by using the protocol of Aβ-derived diffusible ligands. We obtained the EPR spectra of 37 Aβ42 oligomer samples, each spin-labeled at a unique residue position of the Aβ42 sequence. Analysis of the disordered EPR components shows that the N-terminal region has a lower local structural stability. Spin label mobility analysis reveals three structured segments at residues 9-11, 15-22, and 30-40. Intermolecular spin-spin interactions indicate a parallel in-register β-sheet structure, with residues 34-38 forming the structural core. Residues 16-21 also adopt the parallel in-register β-structure, albeit with weaker intermolecular packing. Our results suggest that there is a structural class of Aβ oligomers that adopt fibril-like conformations.

Background: Idiopathic membranous nephropathy (IMN) is a type of nephrotic syndrome and the leading cause of chronic kidney disease. As far as we know, no predictive model for assessing the prognosis of IMN is currently available. This study aims to establish a nomogram to predict remission probability in patients with IMN and assists clinicians to make treatment decisions., Methods: A total of 266 patients with histopathology-proven IMN were included in this study. Least absolute shrinkage and selection operator regression was utilized to identify the most important variables. Subsequently, multivariate Cox regression analysis was conducted to construct a nomogram, and bootstrap resampling was employed for internal validation. Receiver operating characteristic and calibration curves and decision curve analysis (DCA) were utilized to assess the performance and clinical utility of the developed model., Results: A prognostic nomogram was established, which incorporated creatinine, glomerular&#95;basement&#95;membrane&#95;thickening, gender, IgG&#95;deposition, low-density lipoprotein cholesterol, and fibrinogen. The areas under the curves of the 3-, 12-, 24-month were 0.751, 0.725, and 0.830 in the training set, and 0.729, 0.730, and 0.948 in the validation set respectively. These results and calibration curves demonstrated the good discrimination and calibration of the nomogram in the training and validation sets. Additionally, DCA indicated that the nomogram was useful for remission prediction in clinical settings., Conclusion: The nomogram was useful for clinicians to evaluate the prognosis of patients with IMN in early stage., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

The mitotic quiescence of prospermatogonia is the event known to occur during genesis of the male germline and is tied to the development of the spermatogenic lineage. The regulatory mechanisms and the functional importance of this process have been demonstrated in mice; however, regulation of this process in human and domestic animal is still largely unknown. In this study, we employed single-cell RNA sequencing to identify transcriptional signatures of prospermatogonia and major somatic cell types in testes of goats at E85, E105, and E125. We identified both common and specific Gene Ontology categories, transcription factor regulatory networks, and cell-cell interactions in cell types from goat testis. We also analyzed the transcriptional dynamic changes in prospermatogonia, Sertoli cells, Leydig cells, and interstitial cells. Our datasets provide a useful resource for the study of domestic animal germline development., (© 2023 Federation of American Societies for Experimental Biology.)

The large-scale production and utilization of graphene oxide (GO) have raised concerns regarding its environmental exposure and potential risks. However, existing research on GO toxicity has primarily focused on individual organisms. Little attention has been given to the interaction between GO and the nitrogen-fixing symbiosis of legume-rhizobium. In this study, we focused on alfalfa (Medicago sativa L.), a typical leguminous nitrogen-fixing plant, to investigate the effects of GO on various aspects of this symbiotic relationship, including root nodulation, rhizobial viability, nodule nitrogen fixation, DNA damage, and the composition of the rhizobial community in the rhizosphere. As the dosage of GO increased, a significant inhibition in nodulation development was observed. Exposure to GO resulted in decreased growth and viability of rhizobia, as well as induced DNA damage in nodule cells. Furthermore, with increasing GO dosage, there were significant reductions in nitrogenase activity, leghemoglobin level, and cytoplasmic ammonia content within the root nodules. Additionally, the presence of GO led to notable changes in the rhizobial community in the rhizosphere. Our findings support the existence of the damage promoted by GO in the symbiosis of nitrogen fixing rhizobia with legumes. This underscores the importance of careful soil GO management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Environmental filtering is deemed to play a predominant role in regulating the abundance and distribution of animals during the urbanization process. However, the current knowledge about the effects of urbanization on the population densities of terrestrial mammals is limited. In this study, we compared two invasive mammals (dogs Canis lupus familiaris and cats Felis silvestris ) and three indigenous mammals (Siberian weasels Mustela sibirica , Amur hedgehogs Erinaceus amurensis , and Tolai hares Lepus tolai ) in response to urbanization using camera trap distance sampling (CTDS) in the rural-urban landscape of Tianjin, China. We used generalized additive mixed models (GAMMs) to test the specific responses of their densities to levels of urbanization. Invasive dogs (2.63 individuals/km 2 , 95% CI: 0.91-7.62) exhibited similar density estimations to cats (2.15 individuals/km 2 , 95% CI: 1.31-3.50). Amur hedgehogs were the most abundant species (6.73 individuals/km 2 , 95% CI: 3.15-14.38), followed by Tolai hares (2.22 individuals/km 2 , 95% CI: 0.87-5.68) and Siberian weasels (2.15 individuals/km 2 , 95% CI: 1.06-4.36). The densities of cats, Siberian weasels, and Amur hedgehogs increased with the level of urbanization. The population densities of dogs and cats were only influenced by urban-related variables, while the densities of Siberian weasels and Amur hedgehogs were influenced by both urban-related variables and nature-related variables. Our findings highlight that the CTDS is a suitable and promising method for wildlife surveys in rural-urban landscapes, and urban wildlife management needs to consider the integrated repercussions of urban- and nature-related factors, especially the critical impacts of green space habitats at finer scales., Competing Interests: We have no conflicts of interest to report for this manuscript., (© 2023 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

The hair follicle (HF) is the fundamental unit for fleece and cashmere production in cashmere goats and is crucial in determining cashmere yield and quality. The mechanisms regulating HF development in cashmere goats during the embryonic period remain unclear. Growing evidence suggests that HF development involves complex developmental stages and critical events, and identifying the underlying factors can improve our understanding of HF development. In this study, samples were collected from embryonic day 75 (E75) to E125, the major HF developmental stages. The embryonic HFs of cashmere goats were subjected to proteomic and metabolomic analyses, which revealed dynamic changes in the key factors and signalling pathways controlling HF development at the protein and metabolic levels. Gene ontology and the Kyoto Encyclopaedia of Genes and Genomes were used to functionally annotate 1784 significantly differentially expressed proteins and 454 significantly differentially expressed metabolites enriched in different HF developmental stages. A joint analysis revealed that the oxytocin signalling pathway plays a sustained role in embryonic HF development by activating the MAPK and Ca 2+ signalling pathways, and a related regulatory network map was constructed. This study provides a global perspective on the mechanism of HF development in cashmere goats and enriches our understanding of embryonic HF development.

Background: The growth of urbanization in the 20th and 21st centuries has resulted in unprecedented ecological security issues. The imbalance between urban development and internal ecological security is a growing concern., Methods: Based on the urban development process and the characteristics of ecosystem resilience, the corresponding urbanization evaluation system ("scale-structure-benefit") and ecosystem resilience assessment model ("resistance-adaptability-restoring") were constructed to explore the changes in each dimension as well as to analyze the spatial and temporal changes and driving effects of the coupled coordination level of urbanization and ecological resilience using the coupled coordination degree (CCD) model and geographically and temporally weighted regression (GTWR)., Results: (1) From 2005 to 2020, urbanization levels increased (from 0.204 to 0.264, respectively), whereas the level of ecological resilience gradually decreased (from 0.435 to 0.421, respectively). The spatial distribution of urbanization is rather steady, with a "high-northeast low-southwest" pattern of regional distribution; however, the spatial distribution pattern of ecological resilience is essentially the reverse. (2) During the study period, there was an improvement in the level of coordination between urbanization and ecological resilience, with an increase from 0.524 to 0.540. However, the main coordination type remained the same, with over 46% being at the basic coordination stage. The relative development type was dominated by the lagging urbanization stage, with the lagging ecological resilience and synchronous development stages accounting for a smaller proportion, and the space was distributed in a block-like cluster. (3) The running results of the GTWR show that the core dimensions of the whole region are scale, benefit, and structure, and the impact of each dimension shows obvious spatial heterogeneity. Cities with different levels of relative development also have different central dimensions. This research will provide support for the coordination of urban development in areas where economic construction and ecological resilience are not coordinated, and will contribute to the sustainable development of urban areas., Competing Interests: The authors declare there are no competing interests., (©2023 Xiao et al.)

Ecosystem vulnerability is an ecological response of the environment to external damage. Studying the influencing factors and spatiotemporal changes of ecosystem vulnerability is helpful to maintain ecological balance. At present, studies on ecosystem vulnerability are relatively homogeneous and rarely integrate climate change and human activities. Based on a habitat-function framework, this study analyzed the response of ecosystem vulnerability on climate change and human activities in the Poyang Lake City Group (PLCG) in 2010, 2015 and 2020. The spatial agglomeration of ecosystem vulnerability has been analyzed by using GeoDa model. The interaction of factors on ecosystem vulnerability have been analyzed by using geographical detector. It can be seen that the ecosystem vulnerability of the PLCG have increased from 2010 to 2020. The impacts of climate change to the ecosystem vulnerability have showed a positive correlation. Meanwhile, the key factors leading to the change of ecological vulnerability are still human activities. This methodology demonstrates a high level of robustness when applied to other research domains. This research is conducive to maintaining the integrity of the ecosystem, realizing the development of man and nature, and promoting the sound and rapid development of economic society., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Cashmere, a keratinised product of secondary hair follicles (SHFs) in cashmere goats, holds an important place in international high-end textiles. However, research on the complex molecular and signal regulation during the development and growth of hair follicles (HFs), which is essential for the development of the cashmere industry, is limited. Moreover, increasing evidence indicates that non-coding RNAs (ncRNAs) participate in HF development. Herein, we systematically investigated a competing endogenous RNA (ceRNA) regulatory network mediated by circular RNAs (circRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) in skin samples of cashmere goat embryos, using whole-transcriptome sequencing technology. We obtained 6468, 394, and 239 significantly differentially expressed mRNAs, circRNAs, and miRNAs, respectively. These identified RNAs were further used to construct a ceRNA regulatory network, mediated by circRNAs, for cashmere goats at a late stage of HF development. Among the molecular species identified, miR-184 and fibroblast growth factor (FGF) 10 exhibited competitive targeted interactions. In secondary HF dermal papilla cells (SHF-DPCs), miR-184 promotes proliferation, inhibits apoptosis, and alters the cell cycle via the competitive release of FGF10. This study reports that FGF10 and its interaction with ncRNAs significantly affect SHF-DPCs, providing a reference for research on the biology of HFs in cashmere goats and other mammals.

Background: Congenital heart disease (CHD) is the leading cause of mortality in childhood worldwide. However, a large number of children with CHD are not diagnosed promptly in low- and middle-income regions, due to limited healthcare resources and lack the ability of prenatal and postnatal ultrasound examinations. The research on asymptomatic CHD in the community is still blank, resulting in a large number of children with asymptomatic CHD can not be found and treated in time. Through the China-Cambodia collaborative health care initiative, the project team conducted research, screened children's CHD through a sampling survey in China and Cambodia, collected relevant data, and retrospectively analyzed the data of all eligible patients., Objectives: The project aimed to evaluate the prevalence of asymptomatic CHD in a sample population of 3-18years old and effects on their growth status and treatment outcomes., Methods: We examined the prevalence of 'asymptomatic CHD' among 3-18years old children and adolescents at the township/county levels in the two participating. A total of eight provinces in China and five provinces in Cambodia were analyzed from 2017 to 2020. During 1 year follow-up after treatment, the differences in heights and weights of the treated and control groups were evaluated., Results: Among the 3,068,075 participants screened from 2017 to 2020, 3967 patients with asymptomatic CHD requiring treatment were identified [0.130%, 95% confidence interval (CI) 0.126 -0.134%]. The prevalence rate of CHD ranged from 0.02 to 0.88%, and was negatively related to local per capita GDP (p = 0.028). The average height of 3310 treated CHD patients were 2.23% (95% CI: -2.51%~-1.9%) lower than that of the standard group and the average weight was - 6.41% (95% CI: -7.17%~-5.65%) lower, the developmental gap widening with advancing age. One year after treatment, the relative height difference remained comparable while that, in weight was reduced by 5.68% (95% CI: 4.27% ~7.09%)., Conclusions: Asymptomatic CHD now is often overlooked and is an emerging public health challenge. Early detection and treatment are essential to lower the potential burden of heart diseases in children and adolescents., (© 2023. The Author(s).)