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Enhancing the thermal shock resistance of Y2O3 ceramic crucibles, coupled with advancements in melting and casting technologies to reduce the adverse influence of interfacial reactions, is essential for producing low-energy consumption, high-quality titanium-aluminum (TiAl) alloys. In this study, the Y2O3 ceramic crucible with good thermal shock resistance was developed through the optimization of particle size distribution and sintering holding time. The interaction mechanisms between Y2O3 ceramics and TiAl alloys under extreme conditions were investigated, and strategies for enhancing the mechanical properties of TiAl alloys through the integration of Y2O3 crucibles with centrifugal casting were discussed. The results indicated that introducing large particles of 1–3 mm under sintering conditions of 2023 K and 6 h effectively enhances the thermal shock resistance of Y2O3 crucible. The interaction between Y2O3 and TiAl alloys primarily involved physical erosion (spalling/dispersion), dissolution of separated particles, and surface modification of interface layer particles (reaction). Physical erosion played an important role in this dynamic interaction, with the extent of erosion intensifying through continuous use of the crucible, while electromagnetic forces ensured the uniform distribution of inclusions within the TiAl alloy matrix. Moreover, the application of centrifugal casting technology substantially refines the grain size and reduces the inclusion count, thereby significantly enhancing the mechanical properties of TiAl alloy.

Abstract Objective The aim of this study was to investigate the role and mechanisms of miR-155 in chronic spontaneous urticaria (CSU). Methods The expression level of miR-155 in the skin tissues of patients with CSU and experimental rats were detected by RT-qPCR, followed by the measurement of the histamine release rate in the serum through the histamine release test. Besides, hematoxylin & eosin staining was used to observe the pathological changes of the skin tissues; Corresponding detection kits and flow cytometry to measure the changes of immunoglobulins, inflammatory cytokines and T cell subsets in the serum of rats in each group; and western blot to check the expression level of proteins related to JAK/STAT signaling pathway in the skin tissues. Results Knockdown of miR-155 reduced the number and duration of pruritus, alleviated the skin damage, and decreased the number of eosinophils in CSU rats. Moreover, knockdown of miR-155 elevated the serum levels of IgG and IgM, decreased the levels of IgA and inflammatory cytokines, and reduced the proportion of CD4 + and CD4 + CD25 + T cells, as well as the CD4+/CD8 + ratio in CSU rats. However, Tyr705 intervention could reverse the effects of knockdown of miR-155 on CSU model rats. Furthermore, we found that knockdown of miR-155 significantly reduced the protein expression of IRF-9, as well as the P-JAK2/JAK2 and P-STAT3/STAT3 ratios in the skin tissues of CSU rats. Conclusion Knockdown of miR-155 can alleviate skin damage and inflammatory responses and relieve autoimmunity in CSU rats by inhibiting the JAK/STAT3 signaling pathway.

Abstract Background Haemaphysalis concinna, carrying multiple pathogens, has attracted increasing attention because of its expanded geographical range and significant role in disease transmission. This study aimed to identify the potential public health risks posed by H. concinna and H. concinna-associated pathogens. Methods A comprehensive database integrating a field survey, literature review, reference book, and relevant websites was developed. The geographical distribution of H. concinna and its associated pathogens was illustrated using ArcGIS. Meta-analysis was performed to estimate the prevalence of H. concinna-associated microbes. Phylogenetic and geographical methods were used to investigate the role of birds in the transmission of H. concinna-associated microbes. The potential global distribution of H. concinna was predicted by ecological niche modeling. Results Haemaphysalis concinna was distributed in 34 countries across the Eurasian continent, predominantly in China, Russia, and Central Europe. The tick species carried at least 40 human pathogens, including six species in the Anaplasmataceae family, five species of Babesia, four genospecies in the complex Borrelia burgdorferi sensu lato, ten species of spotted fever group rickettsiae, ten species of viruses, as well as Francisella, Coxiella, and other bacteria. Haemaphysalis concinna could parasitize 119 host species, with nearly half of them being birds, which played a crucial role in the long-distance transmission of tick-borne microbes. Our predictive modeling suggested that H. concinna could potentially survive in regions where the tick has never been previously recorded such as central North America, southern South America, southeast Oceania, and southern Africa. Conclusions Our study revealed the wide distribution, broad host range, and pathogen diversity of H. concinna. Authorities, healthcare professionals, and the entire community should address the growing threat of H. concinna and associated pathogens. Tick monitoring and control, pathogen identification, diagnostic tools, and continuous research should be enhanced. Graphical Abstract

Background: Hypervirulent carbapenem-resistant Klebsiella pneumoniae (Hv-CRKP) triggered a significant public health challenge. This study explored the prevalence trends and key genetic characteristics of Hv-CRKP in one Shanghai suburbs hospital during 2014–2018. Methods: During five years, Hv-CRKP strains identified from 2579 CRKP by specific PCR, were subjected to performed short- and long-read sequencing technology; epidemiological characteristics, antimicrobial-resistance genes (ARGs), virulence determinants, detailed plasmid profiles and conjugation efficiency were comprehensively investigated. Results: 155 Hv-CRKP and 31 non-Hv-CRKP strains were sequenced. Hv-CRKP strains exhibited significant resistance to six common antibiotic classes (>92%). ST11 steadily increased and became the most prevalent ST (85.2%), followed by ST15 (8.5%), ST65 (2.6%), ST23 (1.9%), and ST86 (0.6%). ST11-KL64 (65.2%) rapidly increased from 0 in 2014 to 93.9% in 2018. blaKPC-2 was the primary carbapenemase gene (97.4%). Other ARGs switched from aac(3)-IId to aadA2 in aminoglycoside and from sul1 to sul2 in sulfanilamide. The time-dated phylogenetic tree was divided into four independent evolutionary clades. Clade 1 and 3 strains were mostly limited in the ICU, whereas Clade 2 strains were distributed among multiple departments. Compared to ybt14 in ICEKp12 in Clade 1, Clade 3 strains harbored ybt9 in ICEKp3 and blaCTX-M-65. Hv-CRKP infected more wards than non-Hv-CRKP and showed greater transmission capacity. Three plasmids containing crucial carbapenemase genes demonstrated their early transmission across China. Conclusion: The Hv-CRKP ST11-KL64 has rapidly replaced ST11-KL47 and emerged as the predominant epidemic subtype in various hospital wards, highlighting the importance of conducting comprehensive early surveillance for Hv-CRKP, especially in respiratory infections.

Abstract Background Malaria remains a significant public health concern in Niger, with the number of cases increasing from 592,334 in 2000 to 3,138,696 in 2010. In response, a concerted campaign against the disease has been initiated. However, the implementation of these malaria interventions and their association with epidemiological behaviour remains unclear. Methods A time-series study was conducted in Niger from 2010 to 2019. Multiple data sources concerning malaria were integrated, encompassing national surveillance data, Statistic Yearbook, targeted malaria control interventions, and meteorological data. Incidence rate, mortality rate, and case fatality ratio (CFR) by different regions and age groups were analysed. Joinpoint regression models were used to estimate annual changes in malaria. The changes in coverage of malaria interventions were evaluated. Results Between 2010 to 2019, the incidence rate of malaria decreased from 249.43 to 187.00 cases per 1,000 population in Niger. Niamey had a high annual mean incidence rate and the lowest CFR, while Agadez was on the contrary. Joinpoint regression analysis revealed a declining trend in malaria incidence for all age groups except the 10–24 years group, and the mortality rate and the CFR initially decreased followed by an increase in all age groups. Niger has implemented a series of malaria interventions, with the major ones being scaled up to larger populations during the study period. Conclusions The scale-up of multi-interventions in Niger has significantly reduced malaria incidence, but the rise in mortality rate and CFR addresses the challenges in malaria control and elimination. Malaria endemic countries should enhance surveillance of malaria cases and drug resistance in Plasmodium, improve diagnosis and treatment, expand the population coverage of insecticide-treated bed nets and seasonal malaria chemoprevention, and strengthen the management of severe malaria cases.

Abstract Background Some medical conditions may increase the risk of developing pulmonary tuberculosis (PTB); however, no systematic study on PTB-associated comorbidities and comorbidity clusters has been undertaken. Methods A nested case-control study was conducted from 2013 to 2017 using multi-source big data. We defined cases as patients with incident PTB, and we matched each case with four event-free controls using propensity score matching (PSM). Comorbidities diagnosed prior to PTB were defined with the International Classification of Diseases-10 (ICD-10). The longitudinal relationships between multimorbidity burden and PTB were analyzed using a generalized estimating equation. The associations between PTB and 30 comorbidities were examined using conditional logistic regression, and the comorbidity clusters were identified using network analysis. Results A total of 4265 cases and 17,060 controls were enrolled during the study period. A total of 849 (19.91%) cases and 1141 (6.69%) controls were multimorbid before the index date. Having 1, 2, and ≥ 3 comorbidities was associated with an increased risk of PTB (aOR 2.85–5.16). Fourteen out of thirty comorbidities were significantly associated with PTB (aOR 1.28–7.27), and the associations differed by sex and age. Network analysis identified three major clusters, mainly in the respiratory, circulatory, and endocrine/metabolic systems, in PTB cases. Conclusions Certain comorbidities involving multiple systems may significantly increase the risk of PTB. Enhanced awareness and surveillance of comorbidity are warranted to ensure early prevention and timely control of PTB.

Abstract According to statistics, the incidence of liver cancer is increasing yearly, and effective treatment of liver cancer is imminent. For early liver cancer, resection surgery is currently the most effective treatment. However, resection does not treat the disease in advanced patients, so finding a method with a better prognosis is necessary. In recent years, ferroptosis and cuproptosis have been gradually defined, and related studies have proved that they show excellent results in the therapy of liver cancer. Cuproptosis is a new form of cell death, and the use of cuproptosis combined with ferroptosis to inhibit the production of hepatocellular carcinoma cells has good development prospects and is worthy of in-depth discussion by researchers. In this review, we summarize the research progress on cuproptosis combined with ferroptosis in treating liver cancer, analyze the value of cuproptosis and ferroptosis in the immune of liver cancer, and propose potential pathways in oncotherapy with the combination of cuproptosis and ferroptosis, which can provide background knowledge for subsequent related research.

Dermacentor nuttalli, a member of family Ixodidae and genus Dermacentor, is predominantly found in North Asia. It transmits various pathogens of human and animal diseases, such as Lymphocytic choriomeningitis mammarenavirus and Brucella ovis, leading to severe symptoms in patients and posing serious hazards to livestock husbandry. To profile pathogen abundances of wild D. nuttalli, metagenomic sequencing was performed of four field-collected tick samples, revealing that Rickettsia, Streptomyces, and Pseudomonas were the most abundant bacterial genera in D. nuttalli. Specifically, four nearly complete Rickettsia genomes were assembled, closely relative to Rickettsia conorii subsp. raoultii. Then, a comprehensive meta-analysis was performed to evaluate its potential threats based on detected pathogens and geographical distribution positions reported in literature, reference books, related websites, and field surveys. At least 48 pathogens were identified, including 20 species of bacteria, seven species of eukaryota, and 21 species of virus. Notably, Rickettsia conorii subsp. raoultii, Coxiella burnetii, and Brucella ovis displayed remarkably high positivity rates, which were known to cause infectious diseases in both humans and livestock. Currently, the primary distribution of D. nuttalli spans China, Mongolia, and Russia. However, an additional 14 countries in Asia and America that may also be affected by D. nuttalli were identified in our niche model, despite no previous reports of its presence in these areas. This study provides comprehensive data and analysis on the pathogens carried by D. nuttalli, along with documented and potential distribution, suggesting an emerging threat to public health and animal husbandry. Therefore, there is a need for heightened surveillance and thorough investigation of D. nuttalli.

Abstract There has been increasing global concern about the spillover transmission of pangolin-associated microbes. To assess the risk of these microbes for emergence as human pathogens, we integrated data from multiple sources to describe the distribution and spectrum of microbes harbored by pangolins. Wild and trafficked pangolins have been mainly recorded in Asia and Africa, while captive pangolins have been reported in European and North American countries. A total of 128 microbes, including 92 viruses, 25 bacteria, eight protists, and three uncharacterized microbes, have been identified in five pangolin species. Out of 128 pangolin-associated microbes, 31 (including 13 viruses, 15 bacteria, and three protists) have been reported in humans, and 54 are animal-associated viruses. The phylogenetic analysis of human-associated viruses carried by pangolins reveals that they are genetically close to those naturally circulating among human populations in the world. Pangolins harbor diverse microbes, many of which have been previously reported in humans and animals. Abundant viruses initially detected in pangolins might exhibit risks for spillover transmission.

Genetic mutations leading to premature termination codons are known to have detrimental effects. Using the Lepidoptera model insect, the silkworm (Bombyx mori), we explored the genetic compensatory response triggered by mutations with premature termination codons. Additionally, we delved into the molecular mechanisms associated with the nonsense-mediated mRNA degradation pathway. CRISPR/Cas9 technology was utilized to generate a homozygous bivoltine silkworm line BmTrpA1−/− with a premature termination. Transcript levels were assessed for the BmTrpA paralogs, BmPyrexia and BmPainless as well as for the essential factors Upf1, Upf2, and Upf3a involved in the nonsense-mediated mRNA degradation (NMD) pathway. Upf2 was specifically knocked down via RNA interference at the embryonic stage. The results comfirmed that the BmTrpA1 transcripts with a 2-base deletion generating a premature termination codon in the BmTrpA1−/− line. From day 6 of embryonic development, the mRNA levels of BmPyrexia, BmPainless, Upf1, and Upf2 were significantly elevated in the gene-edited line. Embryonic knockdown of Upf2 resulted in the suppression of the genetic compensation response in the mutant. As a result, the offspring silkworm eggs were able to hatch normally after 10 days of incubation, displaying a non-diapause phenotype. It was observed that a genetic compensation response does exist in BmTrpA1−/− B. mori. This study presents a novel discovery of the NMD-mediated genetic compensation response in B. mori. The findings offer new insights into understanding the genetic compensation response and exploring the gene functions in lepidopteran insects, such as silkworms.

Abstract The growth of endophytic bacteria is influenced by the host plants and their secondary metabolites and activities. In this study, P. megaterium P-NA14 and P. megaterium D-HT207 were isolated from potato tuber and dendrobium stem respectively. They were both identified as Priestia megaterium. The antimicrobial activities and metabolites of both strains were explored. For antimicrobial activities, results showed that P. megaterium P-NA14 exhibited a stronger inhibition effect on the pathogen of dendrobium, while P. megaterium D-HT207 exhibited a stronger inhibition effect on the pathogen of potato. The supernatant of P. megaterium P-NA14 showed an inhibition effect only on Staphylococcus aureus, while the sediment of P. megaterium D-HT207 showed an inhibition effect only on Escherichia coli. For metabolomic analysis, the content of L-phenylalanine in P. megaterium P-NA14 was higher than that of P. megaterium D-HT207, and several key downstream metabolites of L-phenylalanine were associated with inhibition of S. aureus including tyrosine, capsaicin, etc. Therefore, we speculated that the different antimicrobial activities between P. megaterium P-NA14 and P. megaterium D-HT207 were possibly related to the content of L-phenylalanine and its metabolites. This study preliminarily explored why the same strains isolated from different hosts exhibit different activities from the perspective of metabolomics.

In this paper, we consider the simultaneous inversion of the source term and the initial data for a time-fractional diffusion equation based on the additional temperatures at two fixed times $ t=T_{1} $ and $ t=T_{2} $ . The inverse problem is formulated on the basis of the Fourier method as an operator equation of the first kind. For the overdetermined system of linear equations, we apply the conjugate gradient method with an appropriate stopping criterion to solve the least-squares problems. The method is not only able to converge quickly, but also it can solve large-scale linear equations. Based on the proposed results, it can be seen that the iteration numbers play a role of a regularization parameter. Four numerical examples are provided to demonstrate the effectiveness of the proposed method.

Abstract Background GnRHa treatment was established for improving final adult height (FAH) in children presenting with Idiopathic central precocious puberty (ICPP) up to age 8, while several controversies remained for older age groups. The primary objective was to evaluate whether boys diagnosed with ICPP over 9 years of chronological age (CA) could achieve a height benefit from GnRHa treatment. Methods We retrospectively evaluated the medical records of 23 boys treated for idiopathic central precocious puberty between January 2018 and January 2021 at Jiangsu Children’s Medical Center. All patients started treatment with intramuscular depot GnRHa at a dose of 80–100 μg/kg, followed by continuous intramuscular injection every 28 days at a dose of 60–80 μg/kg. The hormonal parameters, bone age/chronological age ratio, FAH, growth velocity (GV), tanner staging and body mass index (BMI) were assessed during the treatment period. Results After one course of treatment (3 months), the basal FSH and testosterone levels were reduced, while the basal LH value was not significantly changed compared with those before treatment. Furthermore, the mean BA/CA ratio reduction was statistically significant at month 12. The mean PAH following administration of GnRHa after 12 months was statistically improved compared with those at baseline. In addition, the clinical sign of puberty and GV were significantly improved and the BMI remained unchanged as desired at month 12. Conclusions This analysis highlighted the positive outcome on the decrease in the rate of bone maturation, with a favorable effect on progression of clinical signs of puberty. Furthermore, our study confirmed PAH was improved even in the older children at onset of treatment (ages 9–10), emphasizing the importance of personalized treatment in such population.

ObjectiveTo underscore the paramount significance of incorporating comprehensive rehabilitation therapy as a crucial aspect of managing lymphedema caused by breast cancer surgery, and to illuminate our first-hand experience and insights gained in utilizing this approach.MethodsWe present a case report of a breast cancer survivor who had been suffering from persistent left upper-limb edema for over 15 years, who was effectively treated with a combination of conventional rehabilitation (seven-step decongestion therapy) and a comprehensive rehabilitation program (seven-step decongestion therapy, along with core and respiratory function training, as well as functional brace wearing). The efficacy of the rehabilitation therapy was evaluated through a comprehensive assessmentResultsAlthough the patient underwent the conventional rehabilitation program for one month, only limited improvement was observed. However, after an additional month of comprehensive rehabilitation treatment, the patient exhibited significant improvement in both lymphedema and the overall function of the left upper limb. The patient’s progress was quantified by measuring the reduction in arm circumference, which demonstrated a notable decrease. Furthermore, improvements in joint range of motion were observed, with forward flexion of the shoulder enhancing by 10°, forward flexion improving by 15°, and elbow flexion increasing by 10°. In addition, manual muscular strength tests revealed an increase in strength from Grade 4 to Grade 5. The patient’s quality of life was also significantly improved, as evidenced by the increase in the Activities of Daily Living score from 95 to 100 points, the increase in the the Functional Assessment of Cancer Therapy: Breast score from 53 to 79 points, and the decrease in the Kessler Psychological Distress Scale score from 24 to 17 points.ConclusionWhile seven-step decongestion therapy has been shown to be effective in reducing upper-limb lymphedema caused by breast cancer surgery, it has limitations in treating more chronic cases of the condition. However, when combined with core and respiratory function training and functional brace wearing, seven-step decongestion therapy has been shown to be even more effective in reducing lymphedema and improving limb function, ultimately leading to significant improvements in quality of life.

The increasing incidence and range expansion of tick-borne diseases have caused global threats to human and animal health under the background of climate and socioeconomic changes. As an efficient vector in transmission of tick-borne diseases, a growing burden caused by Ixodes persulcatus and associated pathogens could not be underestimated. This study summarized the distribution, hosts, and pathogens of I. persulcatus, and predicted the suitable habitats of this tick species worldwide. An integrated database involving a field survey, reference book, literature review, and related website was constructed. Location records of I. persulcatus and associated pathogens were incorporated into distribution maps using ArcGIS software. Positive rates for I. persulcatus-associated agents were estimated by meta-analysis. The global distribution of the tick species was predicted using Maxent model. I. persulcatus was distributed in 14 countries across the Eurasian continent, involving Russia, China, Japan, and several Baltic Sea states, which ranged between 21°N to 66°N. The tick species fed on 46 species of hosts, and 51 tick-borne agents could be harbored by I. persulcatus. The predictive model showed that I. persulcatus could be predominantly distributed in northern Europe, western Russia, and northern China. Our study fully clarified the potential public health risks posed by I. persulcatus and I. persulcatus-borne pathogens. Surveillance and control measures of tick-borne diseases should be enhanced to promote the health of humans, animals, and ecosystems.

Abstract Background The expression changes of some proteins are associated with cancer progression, and can be used as biomarkers in cancer diagnosis. Automated systems have been frequently applied in the large-scale detection of protein biomarkers and have provided a valuable complement for wet-laboratory experiments. For example, our previous work used an immunohistochemical image-based machine learning classifier of protein subcellular locations to screen biomarker proteins that change locations in colon cancer tissues. The tool could recognize the location of biomarkers but did not consider the effect of protein expression level changes on the screening process. Results In this study, we built an automated classification model that recognizes protein expression levels in immunohistochemical images, and used the protein expression levels in combination with subcellular locations to screen cancer biomarkers. To minimize the effect of non-informative sections on the immunohistochemical images, we employed the representative image patches as input and applied a Wasserstein distance method to determine the number of patches. For the patches and the whole images, we compared the ability of color features, characteristic curve features, and deep convolutional neural network features to distinguish different levels of protein expression and employed deep learning and conventional classification models. Experimental results showed that the best classifier can achieve an accuracy of 73.72% and an F1-score of 0.6343. In the screening of protein biomarkers, the detection accuracy improved from 63.64 to 95.45% upon the incorporation of the protein expression changes. Conclusions Machine learning can distinguish different protein expression levels and speed up their annotation in the future. Combining information on the expression patterns and subcellular locations of protein can improve the accuracy of automatic cancer biomarker screening. This work could be useful in discovering new cancer biomarkers for clinical diagnosis and research.

The Dayin’gezhuang gold deposit is located in the central part of the Zhaoping Fault metallogenic belt in the Jiaodong gold province —the world ’s third-largest gold metallogenic area. It is a typical successful case of prospecting at a depth of 500‒2000 m in recent years, with cumulative proven gold resources exceeding 180 t. The main orebodies (No. 1 and No. 2 orebody) generally have a pitch direction of NNE and a plunge direction of NEE. As the ore-controlling fault, the Zhaoping Fault is a shovel-shaped stepped fault, with its dip angle presenting stepped high-to-low transitions at the elevation of −2000‒0 m. The gold mineralization enrichment area is mainly distributed in the step parts where the fault plane changes from steeply to gently, forming a stepped metallogenic pattern from shallow to deep. It can be concluded from previous studies that the gold mineralization of the Dayin’gezhuang gold deposit occurred at about 120 Ma. The ore-forming fluids were H2O-CO2-NaCl-type hydrothermal solutions with a medium-low temperature and medium-low salinity. The H-O isotopic characteristics indicate that the fluids in the early ore-forming stage were possibly magmatic water or mantle water and that meteoric water gradually entered the ore-forming fluids in the late ore-forming stage. The S and Pb isotopes indicate that the ore-forming materials mainly originate from the lower crust and contain a small quantity of mantle-derived components. The comprehensive analysis shows that the Dayin ’gezhuang gold deposit was formed by thermal uplifting-extensional tectonism. The strong crust-mantle interactions, large-scale magmatism, and the material exchange arising from the transformation from adakitic granites to arc granites and from the ancient lower crust to the juvenile lower crust during the Early Cretaceous provided abundant fluids and material sources for mineralization. Moreover, the detachment faults formed by the rapid magmatic uplift and the extensional tectonism created favorable temperature and pressure conditions and space for fluid accumulation and gold precipitation and mineralization.©2022 China Geology Editorial Office.

Abstract Background The placental barrier protects the fetus from exposure to some toxicants and is vital for drug development and risk assessment of environmental chemicals. However, in vivo experiments for assessing the placental barrier permeability of chemicals is not ethically acceptable. Although ex vivo placental perfusion methods provide good alternatives for the assessment of placental barrier permeability, the application to a large number of test chemicals could be time- and resource-consuming. Computational prediction models for ex vivo placental barrier permeability are therefore desirable. Methods A total of 87 chemicals and corresponding 1444 physicochemical properties were divided into training and test datasets. Three types of algorithms including linear regression, random forest, and ensemble models were applied to develop prediction models for ex vivo placental barrier permeability. Results Among the tested models, the ensemble model integrating the previous two methods performed best for predicting ex vivo human placental barrier permeability with correlation coefficients of 0.887 and 0.825 when considering the applicability domain. An additional test on seven newly curated chemicals from the literature showed a good correlation coefficient of 0.879 which was further improved to 0.921 by considering the variation of experiments. Conclusion In this study, the first valid predicting model for ex vivo human placental barrier permeability was developed following the OECD guideline. The model is expected to be useful for assessing the human placental barrier permeability and can be integrated with developmental toxicity prediction models for investigating the toxic effects of chemicals on the fetus.

Background: Despite the significant survival benefits of anti-PD-1/PD-L1 immunotherapy, non-small cell lung cancer (NSCLC) remains one of the most common tumors and major causes of cancer-related deaths worldwide. Thus, there is an urgent need to identify new therapeutic targets for this refractory disease.Methods: In this study, microarray datasets GSE27262, GSE75037, GSE102287, and GSE21933 were integrated by Venn diagram. We performed functional clustering and pathway enrichment analyses using R. Through the STRING database and Cytoscape, we conducted protein-protein interaction (PPI) network analysis and identified the key genes, which were verified by the GEPIA2 and UALCAN portal. Validation of actin-binding protein anillin (ANLN) was performed by quantitative real-time polymerase chain reaction and Western blotting. Additionally, Kaplan-Meier methods were used to compute the survival analyses.Results: In total, 126 differentially expressed genes were identified, which were enriched in mitotic nuclear division, mitotic cell cycle G2/M transition, vasculogenesis, spindle, and peroxisome proliferator-activated receptor signaling pathway. 12 central node genes were identified in the PPI network complex. The survival analysis revealed that high transcriptional levels were associated with inferior survival in NSCLC patients. The clinical implication of ANLN was further explored; its protein expression showed a gradually increasing trend from grade I to III.Conclusion: These Key genes may be involved in the carcinogenesis and progression of NSCLC, which may serve as useful targets for NSCLC diagnosis and treatment.

Abstract Background The current surveillance system only focuses on notifiable infectious diseases in China. The arrival of the big-data era provides us a chance to elaborate on the full spectrum of infectious diseases. Methods In this population-based observational study, we used multiple health-related data extracted from the Shandong Multi-Center Healthcare Big Data Platform from January 2013 to June 2017 to estimate the incidence density and describe the epidemiological characteristics and dynamics of various infectious diseases in a population of 3,987,573 individuals in Shandong province, China. Results In total, 106,289 cases of 130 infectious diseases were diagnosed among the population, with an incidence density (ID) of 694.86 per 100,000 person-years. Besides 73,801 cases of 35 notifiable infectious diseases, 32,488 cases of 95 non-notifiable infectious diseases were identified. The overall ID continuously increased from 364.81 per 100,000 person-years in 2013 to 1071.80 per 100,000 person-years in 2017 (χ 2 test for trend, P

AIM: To explore the performance in diabetic retinopathy (DR) screening of artificial intelligence (AI) system by evaluating the image quality of a handheld Optomed Aurora fundus camera in comparison to traditional tabletop fundus cameras and the diagnostic accuracy of DR of the two modalities. METHODS: Overall, 630 eyes were included from three centers and screened by a handheld camera (Aurora, Optomed, Oulu, Finland) and a table-top camera. Image quality was graded by three masked and experienced ophthalmologists. The diagnostic accuracy of the handheld camera and AI system was evaluated in assessing DR lesions and referable DR. RESULTS: Under nonmydriasis status, the handheld fundus camera had better image quality in centration, clarity, and visible range (1.47, 1.48, and 1.40) than conventional tabletop cameras (1.30, 1.28, and 1.18; P

This study adopts a bibliometric approach to explore a focus on the general state of SRs worldwide, and analyzes the differences between SR writings with and without medical librarian involvement in terms of the differences in the number of authors, the country of institutional affiliation of the main author, the number of citing, and the number of times cited. The research objects were 22 journals that are included in the MEDLINE database were obtained a total of 9,030 SR articles published between 2014 and 2017. The results of the study revealed the following: A steady increase in the number of SR articles with librarians involved over the years. In terms of the characteristics of SR authors, the number of authors largely fell between three and seven regardless. A dominant proportion of institutional affiliations of the main authors for SR articles with librarians involved were located in the United States, exhibited librarians in highly developed countries had a higher rate of participation in SR. In terms of SR article citations, according to the t-test results, there was no significant difference in the number of citing between the presence and absence of librarian involvement, but a significant difference in the number of times cited between two. Suggestions of this study are as follows: Collaboration between clinical personnel and librarians in writing SRs should be encouraged, the state should enact SR relevant policies, and draw on SR-related services initiated by other libraries.

ABSTRACT Early and late gene expressions of baculoviruses have been known to rely on host RNA polymerase II and a virus-encoded RNA polymerase, separately. In this study, we found that Autographa californica multiple nucleopolyhedrovirus (AcMNPV) recombinant bacmids with the individual RNA polymerase subunit genes deleted could support low levels of expression of a reporter gene under the control of the promoter of a typical late gene, vp39, in transfected Sf9 cells. Through multistep subcloning of a genomic library of the virus and transient expression assay analysis, ie1 was identified to be the only viral gene that was responsible for activation of late gene expression in the absence of the viral RNA polymerase. Furthermore, IE1 was found to be capable of activating reporter gene expression from the promoters of additional late genes polh, p6.9, odv-e18, odv-e25, and gp41, independent of any additional viral factors. Deletion of ie1 from the virus genome eliminated late gene expression. The IE1-activated late gene expression was enhanced by the viral hr4b. It was shown to be insensitive to inhibition of α-amanitin and did not appear to have stable transcription start sites. It is proposed that IE1 may serve to recruit newly synthesized viral RNA polymerase to viral DNA by activating low levels of pretranscription of the late genes to create an appropriate DNA conformation. IMPORTANCE The late gene expression of baculovirus has been known to depend on the virus-encoded RNA polymerase, which consists of four subunits. The immediate-early gene ie1 was found to be required for viral early gene expression, late gene expression, and DNA replication. How it functions in late gene expression remains unclear. In this study, we found that AcMNPV IE1 could activate low levels of gene expression from late gene promoters independently of any additional viral factors, with nonspecific transcription start sites. This new finding will shed light on the role of IE1 in the regulation of late gene expression and the understanding of the mechanism of late gene transcription initiation.

AIM:To study the effect of vitamin E on the injury of human retinal pigment epithelial(hRPE)cells induced by high-dose blue light, and provide experimental evidence for intercepting blue light damaged hRPE cells. METHODS: The hRPE cell injury model was established with 3000±150Lx blue light. The apoptosis rate and reactive oxygen species(ROS)of the six groups of hRPE cells were detected by flow cytometry at 0, 3, 6, 9, 12 and 24h respectively. Apoptosis and ROS in hRPE cells were detected by cytometry in 0h-irradiation group, 6h-irradiation group, and vitamin E added groups(vitamin E concentration 10, 50, 100μmol/L)before or after 6h-irradiation. The fluorescence intensity of hRPE cells was observed under a fluorescence microscope using Hoechst 33258 staining reagent.RESULTS: Compared with the 0h-irradiation group, the relative amount of reactive oxygen species increased significantly in 3, 6, 9, 12 and 24h groups(all P

The regulation of adult neural stem cells (NSCs) is critical for lifelong neurogenesis. MicroRNAs (miRNAs) are a type of small, endogenous RNAs that regulate gene expression post-transcriptionally and influence signaling networks responsible for several cellular processes. In this study, miR-103-3p was transfected into neural stem cells derived from embryonic hippocampal neural stem cells. The results showed that miR-103-3p suppressed neural stem cell proliferation and differentiation, and promoted apoptosis. In addition, miR-103-3p negatively regulated NudE neurodevelopment protein 1-like 1 (Ndel1) expression by binding to the 3′ untranslated region of Ndel1. Transduction of neural stem cells with a lentiviral vector overexpressing Ndel1 significantly increased cell proliferation and differentiation, decreased neural stem cell apoptosis, and decreased protein expression levels of Wnt3a, β-catenin, phosphor-GSK-3β, LEF1, c-myc, c-Jun, and cyclin D1, all members of the Wnt/β-catenin signaling pathway. These findings suggest that Ndel1 is a novel miR-103-3p target and that miR-103-3p acts by suppressing neural stem cell proliferation and promoting apoptosis and differentiation. This study was approved by the Animal Ethics Committee of Nantong University, China (approval No. 20200826-003) on August 26, 2020.

Climate change combined with human activities has altered the spatial and temporal patterns of summer extreme heat in the Mu Us Desert. To determine how those rodents living in the desert respond to increased extreme heat in summer, in July 2022, during the hottest month, we examined the rodent species, vegetation coverage, and small-scale heterogeneity in ambient temperature in the southeastern Mu Us Desert. The results showed that Meriones meridianus, Meriones unguiculatus, and Cricetulus longicaudatus were found in the study area, where the vegetation coverage is 33.5–40.8%. Moreover, the maximum temperature of the desert surface was 61.8 °C. The maximum air temperature at 5 cm above the desert surface was 41.3 °C. The maximum temperature in the burrow at a depth of 15 cm was 31 °C. M. unguiculatus might experience 4–9.3 h of heat stress in a day when exposed outside the burrow, whereas M. meridianus would experience 8.5–10.8 h of heat stress. Yet, inside the burrow, both species were barely exposed to heat stress. In conclusion, adjustments in behavioral patterns can be the main way that rodents in the Mu Us Desert adapt to the extreme heat in the summer.

AIM: To observe the visual quality after implantation of regional refractive multifocal intraocular lens(MIOL)SBL-3. METHODS: A retrospective and controlled study. Fifty-seven cataract patients(68 eyes)in our hospital from September 2019 to July 2020 were enrolled. Totally 33 cases(36 eyes)received regional refractive MIOL SBL-3(SBL-3 group), while 24 cases(32 eyes)received aspheric single focal intraocular lens(SIOL)ZCB00(ZCB00 group). Uncorrected and corrected distance, middle and near visual acuity, defocus curve, OPDⅢ objective visual quality, the quality of vision(QoV)questionnaire, patient satisfaction and spectacle independence were evaluated 3mo postoperatively.RESULTS: No significant differences were found between the SBL-3 group and the ZCB00 group in terms of LogMAR value of corrected and uncorrected distance visual acuity(UDVA)at 3mo after the operation(0.13±0.09 vs 0.10±0.08, 0.06±0.06 vs 0.08±0.08, all P>0.05)and the UDVA was significantly improved compared with that before the operation(P

Background: The association between educational attainment (EA) and offspring birth weight (BW) has been reported by several traditional epidemiological studies. However, evidence for this association tends to be mixed and confounded. This study aimed to investigate the causal association between EA of parents and offspring BW.Methods: Here, we carried out a two-sample bidirectional Mendelian randomization (MR) analysis to examine the causal association between EA of males (n = 131,695) and females (n = 162,028) and offspring BW using genetic instruments. Summary statistics of EA associated single nucleotide polymorphisms (SNPs) were extracted from a GWAS incorporating 293,723 individuals of European descent performed by the Social Science Genetic Association Consortium (SSGAC), and the effects of these SNPs on offspring BW were estimated using a GWAS meta-analysis of 86,577 participants of European descent from 25 studies. Univariable MR analyses were conducted using the inverse-variance weighted (IVW) method and four other methods. Further sensitivity analyses were carried out to test the viability of the results. Multivariable MR was used to examine the confounders between the exposure and outcome.Results: The result shows evidence that the offspring BW is positively causally affected by female EA. Each one standard deviation (SD) increase in female EA was associated with 0.24 SD higher of offspring BW (95% confidence interval [CI], 0.10 to 0.37, p < 0.001 for the IVW method). Similarly, change in offspring BW was 0.21 SD (95% CI: 0.07 to 0.34, p = 2.82 × 10–3) per one SD higher in male EA. No causal effect of BW on EA was found by any of the five methods. The causal association between female EA and offspring BW maintained after adjusting for alcoholic drinks per week and BMI. The effect of male EA on offspring BW was attenuated when we adjusted for BMI and alcoholic drinks per week using multivariable MR analysis.Conclusion: Our study indicated that female EA is positively causally associated with offspring BW. The association between male EA and offspring BW may be confounded by alcoholic drinks per week and BMI.

Abstract The Loess Plateau in China has suffered severe soil erosion. To control soil erosion, extensive conservation measures aimed at redistributing rainfall, hindering flow velocity and intercepting sediment were implemented on the Loess Plateau. To accurately evaluate the combined effect of conservation measures in the Chabagou watershed, this study classified intra-event-based floods into four regimes via cluster and discriminant analyses. Regime A was characterized by short flood duration and low erosive energy, regime B was characterized by short flood duration and high erosive energy, regime C was characterized by long flood duration and low erosive energy, and regime D was characterized by long flood duration and high erosive energy. The results indicated that peak discharge (q p ), runoff depth (H), mean discharge (q m ), and runoff erosion power (E) decreased by 75.2%, 56.0%, 68.0% and 89.2%, respectively, in response to conservation measures. Moreover, area-specific sediment yield (SSY), average suspended sediment concentration (SCE), and maximum suspended sediment concentration (MSCE) decreased by 69.2%, 33.3% and 11.9%, respectively, due to conservation measures. The nonlinear regression analysis revealed a power function relationship between SSY and E in both the baseline (1961–1969) and measurement period (1971–1990) in all regimes. Conservation measures reduced sediment yield by not only reducing the runoff amount and soil erosion energy but also transforming the flood regime, for example, transforming a high-sediment-yield regime into a low-sediment-yield regime. Moreover, conservation measures altered the SSY-E relationship in regime A, whereas no obvious difference in regime B or C/D was observed between the measurement period and the baseline period. This study provides a better understanding of the mechanism of runoff regulation and the sediment yield reduction under comprehensive conservation measures in a small watershed on the Chinese Loess Plateau.

Abstract Background Discovery of early-stage biomarkers is a long-sought goal of Alzheimer’s disease (AD) diagnosis. Age is the greatest risk factor for most AD and accumulating evidence suggests that age-dependent elevation of asparaginyl endopeptidase (AEP) in the brain may represent a new biological marker for predicting AD. However, this speculation remains to be explored with an appropriate assay method because mammalian AEP exists in many organs and the level of AEP in body fluid isn’t proportional to its concentration in brain parenchyma. To this end, we here modified gold nanoparticle (AuNPs) into an AEP-responsive imaging probe and choose transgenic APPswe/PS1dE9 (APP/PS1) mice as an animal model of AD. Our aim is to determine whether imaging of brain AEP can be used to predict AD pathology. Results This AEP-responsive imaging probe AuNPs-Cy5.5-A&C consisted of two particles, AuNPs-Cy5.5-AK and AuNPs-Cy5.5-CABT, which were respectively modified with Ala–Ala–Asn–Cys–Lys (AK) and 2-cyano-6-aminobenzothiazole (CABT). We showed that AuNPs-Cy5.5-A&C could be selectively activated by AEP to aggregate and emit strong fluorescence. Moreover, AuNPs-Cy5.5-A&C displayed a general applicability in various cell lines and its florescence intensity correlated well with AEP activity in these cells. In the brain of APP/PS1 transgenic mice , AEP activity was increased at an early disease stage of AD that precedes formation of senile plaques and cognitive impairment. Pharmacological inhibition of AEP with δ-secretase inhibitor 11 (10 mg kg−1, p.o.) reduced production of β-amyloid (Aβ) and ameliorated memory loss. Therefore, elevation of AEP is an early sign of AD onset. Finally, we showed that live animal imaging with this AEP-responsive probe could monitor the up-regulated AEP in the brain of APP/PS1 mice. Conclusions The current work provided a proof of concept that assessment of brain AEP activity by in vivo imaging assay is a potential biomarker for early diagnosis of AD. Graphical abstract

Abstract Background The COVID-19 pandemic and relevant prevention and control measures may affect the mental health and induce depressive symptoms in fathers with concurrent partner delivery exposure. This study aims to investigate the prevalence of depression in fathers with simultaneous exposure to COVID-19 pandemic and the effects of family functions on paternal perinatal depression (PPD) risk. Methods A cross-sectional study was conducted among the perinatal fathers recruited in a large tertiary hospital in Wuhan across the whole pandemic period from 31 December 2019 to 11 April 2020. Edinburgh Postnatal Depression Scale (EPDS) and APGAR family function scale were used to evaluate PPD and family function, respectively. Chi-square test and multivariable-adjusted logistic regression model were applied for data analysis. Results Among the 1187 participants, the prevalence of PPD was 13.82% throughout the COVID-19 pandemic. Compared with that in the time period before the announcement of human-to-human transmission on 19 January 2020, the depression risk was significantly lower during the traffic restriction (OR = 0.54, 95% CI: 0.34, 0.86) and public transportation reopening periods (OR = 0.29, 95% CI: 0.14, 0.59). Poor/fair family functions was associated with elevated depression risk (OR = 2.93, 95% CI: 1.90, 4.52). Individuals reporting a low family income and smoking had high depression risks. Conclusions A declined risk of PPD was observed over the traffic restriction period of the COVID-19 pandemic. An improved family function may help alleviate the risk of PPD during the pandemic. Health authorities are recommended to formulate targeted prevention and control strategies to handle PPD.

AIM: To compare the change of anterior chamber angle(ACA)and vault value before and after implantable collamer lens(ICL)in two implant positions.METHODS: Randomized controlled study. A total of 83 patients(154 eyes)underwent ICL(V4c, 12.6mm)surgery from 2018 to 2019 were enrolled and divided into two randomly, including into horizontal group(79 eyes)and into vertical group(75 eyes). Pentacam was used to measure the ACA at 0°, 90°, 180°, 270° points before and after implantation and the ACA changes were calculated.RESULTS: After 12mo, the changes of ACA at 0°, 90°, 180°, 270° position were 15.3°±6.1°, 13.9°±6.3°, 16.5°±5.5° and 12.9°±6.0° in horizontal group while 12.9°±3.7°, 14.5°±6.8°, 14.3°±5.4° and 13.2°±5.9° in vertical group. There was a significant difference in ACA change at 0°-180° position between the two groups(P0.05). The vault value of the vertical group at 1mo was significantly different from that at 6mo and 12mo after implantation(P

The NAC transcription factors play important roles in regulating plant growth, development, and senescence, and responding to biotic and abiotic stressors in plants. A novel coding sequence (1,059 bp) was cloned from hexaploid triticale in this study. The putative protein (352 amino acids) encoded by this sequence was over 95% similar to the amino acid sequence of a NAC protein from Aegilops tauschii (XP020161331), and it formed a clade with Ae. tauschii, durum wheat, and barley. The putative protein contained a conserved nature actomyosin (NAM) domain (129 consecutive amino acids) between the 20th and 148th amino acids at the N-terminus and three transcription activation regions at the C-terminus. The novel gene was identified as a triticale NAC gene localized in the nucleus and designated as TwNAC01 (GenBank accession MG736919). The expression levels of TwNAC01 were the highest in roots, followed by leaves and stems when triticale lines were exposed to drought, polyethylene glycol 6,000 (PEG6000), NaCl, cold, methyl jasmonate (MeJA), and abscisic acid (ABA). Transgenic Arabidopsis thaliana overexpressing TwNAC01 had significantly lower leaf water loss rates and longer roots than wild-type (WT) A. thaliana. Virus-induced silencing of the TwNAC01 gene in triticale delayed root development and decreased length of primary root. Under drought stress, leaves of TwNAC01-silenced triticale had higher levels of malondialdehyde (MDA) and hydrogen peroxide (H2O2), but lower relative water content (RWC), net photosynthetic rate, stomatal conductance, intercellular CO2 concentration, and transpiration rate than the leaves of the WT. Gene overexpression and silencing experiments suggested that TwNAC01 improves plant stress tolerance by increasing root length, regulating the water content of plant leaves by reducing MDA and H2O2 content, and adjusting respiration rate. The results suggest that TwNAC01 is a novel NAC transcription factor gene that can be exploited for triticale and cereal improvement.

Abstract Background Currently, there is no cure for Alzheimer’s disease (AD). Therapeutics that can modify the early stage of AD are urgently needed. Recent studies have shown that the pathogenesis of AD is closely regulated by an endo/lysosomal asparaginyl endopeptidase (AEP). Inhibition of AEP has been reported to prevent neural degeneration in transgenic mouse models of AD. However, more than 90% of AD cases are age-related sporadic AD rather than hereditary AD. The therapeutic efficacy of AEP inhibition in ageing-associated sporadic AD remains unknown. Methods The senescence-accelerated mouse prone 8 (SAMP8) was chosen as an approximate model of sporadic AD and treated with a selective AEP inhibitor,: δ-secretase inhibitor 11. Activation of AEP was determined by enzymatic activity assay. Concentration of soluble amyloid β (Aβ) in the brain was determined by ELISA. Morris water maze test was performed to assess the learning and memory-related cognitive ability. Pathological changes in the brain were explored by morphological and western blot analyses. Results The enzymatic activity of AEP in the SAMP8 mouse brain was significantly higher than that in the age-matched SAMR1 mice. The half maximal inhibitory concentration (IC50) for δ-secretase inhibitor 11 to inhibit AEP in vitro is was around 150 nM. Chronic treatment with δ-secretase inhibitor 11 markedly decreased the brain AEP activity, reduced the generation of Aβ1–40/42 and ameliorated memory loss. The inhibition of AEP with this reagent not only reduced the AEP-cleaved tau fragments and tau hyperphosphorylation, but also attenuated neuroinflammation in the form of microglial activation. Moreover, treatment with δ-secretase inhibitor 11 prevented the synaptic loss and alleviated dendritic disruption in SAMP8 mouse brain. Conclusions Pharmacological inhibition of AEP can intervene and prevent AD-like pathological progress in the model of sporadic AD. The up-regulated AEP in the brain could be a promising target for early treatment of AD. The δ-secretase inhibitor 11 can be used as a lead compound for translational development of AD treatment.

In the title compound, [NiCl2(C20H18N4)2]n, the Ni2+ cation is situated on an inversion center and is coordinated by two chloride ions and four imidazole N atoms of four different 4,4′-bis[(1H-imidazol-1-yl)methyl]-1,1′-biphenyl (BIMB), forming a slightly distorted octahedral geometry. Each BIMB ligand adopts a linear linker to connect Ni2+ ions, forming a two-dimensional layer with an sql network. In the crystal, neighboring layers repeat in an ABAB stacking mode, and weak intermolecular C—H...Cl hydrogen bonds between alternate layers lead to a three-dimensional, twofold interpenetrated, supramolecular framework with a pcu topology net.

As the unique component of Dendrobium, dendrobine-type sesquiterpenoid alkaloids (DSAs) possess a variety of medicinal properties. It has been well documented that plant endophytes can in vitro synthesize secondary metabolites identical or similar to metabolites produced by their host plants. This study aimed to investigate the composition and distribution of endophytic bacteria of Dendrobium stems by Illumina MiSeq platform sequencing and cultivation-dependent methods and then to assess the potential for endophytic bacteria to produce DSAs. Results indicated that it was necessary to combine both cultivation-dependent and cultivation-independent methods to analyze the community structure of endophytic bacterial in plants comprehensively. The length of the Dendrobium stems influenced the endophytic bacterial community. The diversity and richness of endophytic bacteria in group J10_15cm of stems were the highest, which showed a significant difference from the other stem groups. However, there was no certain connection between the diversity and richness of endophytic bacteria and the content of dendrobine. It was most likely due to the influence of several specific endophytic bacteria genera, such as Sphingomonas and Rhodococcus. Athelia rolfsii, Myrothecium roridum, as pathogenic fungi, and Pectobacterium carotovorum subsp. actinidiae, as pathogenic bacteria of Dendrobium, were used to determine the antimicrobial activities. In these assays, six strains belonging to five genera showed antimicrobial activity against at least two phytopathogens. The strain BL-YJ10_15-29 (Paracoccus pueri THG-N2.35, 98.98%) showed the best antimicrobial activity against the three phytopathogens. In addition, 2 DSAs (6-hydroxydendrobine and nobilonine) were identified in the fermentation supernatant of the strain CM-YJ10_15-44 (Pseudomonas protegens CHA0, 99.24%), whereas the whole-genome analysis results further demonstrated that the precursors of the two DSAs [geranyl-PP and (E, E)-famesyl-PP] were synthesized mainly through the methyl-D-erythritol 4-phosphate pathway in this strain. This study provides new insight into the studies on the biosynthesis of DSAs and provides potential biocontrol bacteria.

Objective: This study aimed to explore the relationships between the common variants of R-spondin/Wnt signaling genes, gut microbiota composition, and osteoporosis (OP) risk in elderly Chinese Han population.Design: Dual-energy X-ray absorptiometry was used to obtain the OP-associated measurements at multiple skeleton sites among all 1,168 participants. Genotyping data was obtained by using the next-generation sequencing in the discovery stage (n = 400, 228 OP patients) and SNPscan technology in the replication stage (n = 768, 356 OP patients). Bioinformatic analysis was performed to provide more evidence for the genotype-OP associations. The 16S ribosomal RNA gene high-throughput sequencing technology was adopted to explore OP-associated gut microbiota variations.Results: The genetic variants of rs10920362 in the LGR6 gene (P-FDR = 1.19 × 10–6) and rs11178860 in the LGR5 gene (P-FDR = 1.51 × 10–4) were found to associate with OP risk significantly. Several microbial taxa were associated with the BMDs and T-scores at multiple skeleton sites. The associations between rs10920362 and BMD-associated microbiota maintained significance after adjusting confounders. The rs10920362 CT/TT genotype associated with a decreased relative abundance of Actinobacteria (β = −1.32, P < 0.001), Bifidobacteriaceae (β = −1.70, P < 0.001), and Bifidobacterium (β = −1.70, P < 0.001) compared to the CC genotype.Conclusion: Our findings suggested that the variants loci of LGR6 may be associate with OP pathogenesis via gut microbiota modifications. The relationship between host genetics and gut microbiome provides new perspectives about OP prevention and treatment.

In mainland China, there remains a shortage of pediatric drugs. The Chinese government has recently launched policies and incentives to encourage pediatric drug development and clinical trials. However, data on the characteristics or development trends of these trials are limited. In this review, we extracted source data from the Chinese Clinical Trials Registry and Information Transparency Platform and systematically reviewed the pediatric clinical trials conducted in mainland China from 2009 to 2020, a comprehensive process evaluation of the pediatric drug clinical trials development in the past decade, providing data support to policy makers and industry stakeholders. We included 487 pediatric clinical trials. Over the past decade, the number of pediatric trials has increased, especially since 2016. The most common therapeutic areas were infectious diseases (n = 108, 22.2%), agents for preventive purpose (n = 99, 20.3%), and neurological and psychiatric diseases (n = 71, 14.6%). The number of clinical trials involving epilepsy (39, 10.1%), asthma (33, 8.5%), and influenza (24, 6.2%) were the highest. The distribution of leading institutions is unbalanced in mainland China, with most units in East China (34.0%) and few in Southwest China (6.9%). China has made progress in improving the research and development environment of pediatric drugs and increasing pediatric trials. However, a wide gap in pediatric drug development and clinical trials quality exists between China and the developed countries. The pharmaceutical industry in China has faced grim setbacks, including study duplication, lack of innovation, poor research design, and unbalanced resource allocation. Thus, we suggest that the Chinese government should adjust their policies to improve innovation and clinical design capacity, and optimize resource allocation between regions.

With the development of high-throughput sequencing technology, the posttranscriptional mechanism of alternative splicing is becoming better understood. From decades of studies, alternative splicing has been shown to occur in multiple tissues, including the brain, heart, testis, skeletal muscle, and liver. This regulatory mechanism plays an important role in physiological functions in most liver diseases. Currently, due to the absence of symptoms, chronic pediatric liver diseases have a significant impact on public health. Furthermore, the progression of the disease is accelerated in children, leading to severe damage to their liver tissue if no precautions are taken. To this end, this review article summarizes the current knowledge of alternative splicing in pediatric liver diseases, paying special attention to liver damage in the child stage. The discussion of the regulatory role of splicing in liver diseases and its potential as a new therapeutic target is also included.

Alzheimer’s disease (AD) is one of the leading causes of dementia. As the first common neurodegenerative disease, there are no effective drugs that can reverse the progression. The present study is to report the anti-AD effect of cryptotanshinone (CTS), a natural product isolated from Salvia castanea. It is found that it can alleviate AD-like features associated with Aβ1-42 toxicity in muscle cells as well as neuronal cells of Caenorhabditis elegans (C. elegans). Further studies showed that CTS reduced the level of reactive oxygen species (ROS) in nematodes, up-regulated the expression of sod-3, and enhanced superoxide dismutase activity. Cryptotanshinone reduced the level of Aβ monomers and highly toxic oligomers in C. elegans while inhibiting the abnormal aggregation of polyglutamine protein. In addition, CTS upregulated the expression of hsp-16.2 and downregulated the expression of ace-2. These results suggested that CTS could alleviate oxidative stress and reduce the level of abnormally aggregated proteins and has the potential to be developed as an anti-AD drug candidate.

Reactive oxygen species (ROS) act as a signaling intermediate to promote cellular adaptation to maintain homeostasis by regulating autophagy during pathophysiological stress. However, the mechanism by which ROS promotes autophagy is still largely unknown. Here, we show that the ATM/CHK2/ULK1 axis initiates autophagy to maintain cellular homeostasis by sensing ROS signaling under metabolic stress. We report that ULK1 is a physiological substrate of CHK2, and that the binding of CHK2 to ULK1 depends on the ROS signal and the phosphorylation of threonine 68 of CHK2 under metabolic stress. Further, CHK2 phosphorylates ULK1 on serine 556, and this phosphorylation is dependent on the ATM/CHK2 signaling pathway. CHK2-mediated phosphorylation of ULK1 promotes autophagic flux and inhibits apoptosis induced by metabolic stress. Taken together, these results demonstrate that the ATM/CHK2/ULK1 axis initiates an autophagic adaptive response by sensing ROS, and it protects cells from metabolic stress-induced cellular damage.

Objectives Understanding the unmet needs of community-dwelling stroke survivors is essential for further intervention. This systematic review was performed to summarise their unmet needs from a quantitative viewpoint.Design Systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Data sources A comprehensive search of six databases was conducted from inception to February 2020: PubMed, EMBASE, CINAHL, PsycINFO, SCOPUS and CBM. The methodological quality of the studies was assessed. Unmet needs were categorised, and a pooled analysis of the main outcomes was conducted.Eligibility criteria for selecting studies We included quantitative studies focused on the unmet needs of stroke survivors who live at homes rather than in any other institutionalised organisation.Results In total, 32 of 2660 studies were included, and 1980 unmet needs were identified. The prevalence of patients with unmet needs ranged from 15.08% to 97.59%, with a median of 67.20%; the median number of unmet needs per patient ranged from 2 to 8 (0–31). The prevalence of unmet needs was high at 6 months post-stroke (62.14%) and 2 years post-stroke (81.37%). After categorisation, the main concerns among these patients were revealed to be information support, physical function and mental health; a few studies reported unmet needs related to leisure exercise, return to work and so on. Additionally, differences in the measurement tools used across studies affect what unmet needs participants report.Conclusions Sufficient, accurate, individualised and dynamic information support is a priority among community-dwelling stroke survivors. Physical function and mental health are also the most significant concerns for re-achieving social participation. It is essential to design and disseminate standard, effective and time-saving tools to assess unmet needs.Trial registration number CRD42018112181.

Diabetic retinal disease(DRD)is a disease with a sharp increase in the proportion of retinal disease(RD). Diabetic macular edema is the leading cause of vision loss. The treatment of diabetic macular edema has always been a hot topic in medicine. The diagnosis and treatment of diabetic macular edema is the latest treatment guideline for diabetic macular edema published by the European Association of Retinal Experts. It is considered to be the most representative guide at present. Detailed interpretation in this article will help the majority of ophthalmologists have a new understanding of the diagnosis and treatment of diabetic macular edema.

Abstract Background Diagnosis of tuberculosis (TB) in children is challenging. Epidemiological data of childhood pulmonary tuberculosis (PTB) are urgently needed. Methods We described trends in epidemiology, clinical characteristics, and treatment outcomes in seven cities of Shandong province, China, during 2005–2017. Data were collected from the China Information System for Disease Control and Prevention. Results Among 6283 (2.4% of all PTB) PTB cases aged

The structures of fullerenes, or buckyballs, are often very difficult to resolve. Here, the authors describe a decapyrrylcorannulene host with ten flexible pyrryl groups that can efficiently co-crystallize with diverse fullerene derivatives in a ‘hand-ball-hand’ fashion, allowing crystallographic identification of commonly known types of fullerenes.

MicroRNAs refer to a class of endogenous, short non-coding RNAs that mediate numerous biological functions. MicroRNAs regulate various physiological and pathological activities of peripheral nerves, including peripheral nerve repair and regeneration. Previously, using a rat sciatic nerve injury model, we identified many functionally annotated novel microRNAs, including miR-sc14. Here, we used real-time reverse transcription-polymerase chain reaction to examine miR-sc14 expression in rat sciatic nerve stumps. Our results show that miR-sc14 is noticeably altered following sciatic nerve injury, being up-regulated at 1 day and diminished at 7 days. EdU and transwell chamber assay results showed that miR-sc14 mimic promoted proliferation and migration of Schwann cells, while miR-sc14 inhibitor suppressed their proliferation and migration. Additionally, bioinformatic analysis examined potential target genes of miR-sc14, and found that fibroblast growth factor receptor 2 might be a potential target gene. Specifically, our results show changes of miR-sc14 expression in the sciatic nerve of rats at different time points after nerve injury. Appropriately, up-regulation of miR-sc14 promoted proliferation and migration of Schwann cells. Consequently, miR-sc14 may be an intervention target to promote repair of peripheral nerve injury. The study was approved by the Jiangsu Provincial Laboratory Animal Management Committee, China on March 4, 2015 (approval No. 20150304-004).

Selenium (Se) is essential for the basic functions of life, but the low daily intake of Se urges us to find reliable ways to increase food Se content. Plant-growth-promoting bacteria (PGPB) have shown potential in enhancing plant growth and Se accumulation. In this study, the soils collected from a Se tailing were used to isolate Se-tolerant PGPB. The results showed that a total of three strains were identified. Strain LWS1, belonging to Priestia sp., grew well in M9 medium and exhibited typical PGP characteristics by an IAA-production ability of 24.3 ± 1.37 mg·L−1, siderophore-production ability of 0.23 ± 0.04 and phosphate-solubilizing ability of 87.5 ± 0.21 mg·L−1. Moreover, LWS1 strain tolerated selenite (SeIV) up to 90 mM by a LC50 of 270.4 mg·L–1. Further investigations demonstrated that the inoculation of strain LWS1 resulted in up to 19% higher biomass and 75% higher Se concentration in rice (Oryza sativa L.) than uninoculated treatments. Our study has provided evidence that microbial Se biofortification through inoculating with Priestia sp. strain LWS1 is an alternative way to improve Se uptake in crops and maintain human health.

As an important global crop, the potato (Solanum tuberosum L.) contains the endotoxin solanine that leads to human poisoning and major economic losses. Poisoning symptoms and even acute poisoning may occur when the content of solanine in potatoes exceeds 200 mg/kg. In addition, potatoes are susceptible to some pathogenic bacteria, including Streptomyces scabies and Erwinia carotovora subsp. atroseptica (Van Hall) dye, which can cause potato scab and potato blackleg disease, respectively. In this study, 37 culturable endophytic bacteria strains were obtained from potato tubers based on the culture-dependent method. Results indicated that nine strains showed antimicrobial activity against at least one pathogen by antimicrobial activity screening and 23 strains showed inhibitory activity on solanine in potato tubers. Among them, strain P-NA2-14 (Bacillus megaterium NBRC 15308T, 99.31%) showed not only better antimicrobial activity against both the two indicator pathogens, but also the best inhibitory activity on solanine, which was proved to be a potential biocontrol bacterium. Meanwhile, the relationship between the distribution of the endophytic bacterial community and the content of solanine in potato tubers was studied by Illumina-based analysis, indicating that the distribution of the endophytic bacterial community was obviously influenced by the content of solanine. The results showed a new insight into the relationship between plant secondary metabolites and endophytic bacteria in potato tubers and provided potential new technical support for the biological control of potato storage.