Connection between Mechanical Relaxation and Equilibration Kinetics in a High-Entropy Metallic Glass.

The slow transition from an out-of-equilibrium glass towards a supercooled liquid is a complex relaxation phenomenon. In this Letter, we study the correlation between mechanical relaxation and equilibration kinetics in a Pd_{20}Pt_{20}Cu_{20}Ni_{20}P_{20} high-entropy metallic glass. The evolution of stress relaxation with aging time was obtained with an unprecedented detail, allowing us to pinpoint new interesting features. The long structural relaxation towards equilibrium contains a wide distribution of activation energies, instead of being just associated to the ß relaxation as commonly accepted. The stress relaxation time can be correlated with the equilibration rate and we observe a decrease of microstructural heterogeneity which contrasts with an increase of dynamic heterogeneity. These results significantly enhance our insight of the interplay between relaxation dynamics and thermodynamics in metallic glasses.

Interface thermal conductivities induced by van der Waals interactions.

The interface heat transfer of two layers induced by van der Waals (vdW) contacts is theoretically investigated, based on first-principles calculations at low temperatures. The results suggest that out-of-plane acoustic phonons with low frequencies dominate the interface thermal transport due to the vdW interaction. The interface thermal conductivity is proportional to the cubic of temperature at very low temperatures, but becomes linearly proportional to temperature as temperature increases. We show that manipulating the strain alters vdW coupling, leading to increased interfacial thermal conductivity at the interface. Our findings provide valuable insights into the interface heat transport in vdW heterostructures and support further design and optimization of electronic and optoelectronic nanodevices based on vdW contacts.

Association between garden work and risk of incident dementia in an older population in China: a national cohort study.

OBJECTIVES: Evidence on the association between garden work and risk of incident dementia in the older Chinese population is limited. This study aimed to explore the association between the frequency of garden work and risk of incident dementia in an older population in China. STUDY DESIGN: This was a national cohort study. METHODS: This study analysed data from 8676 participants (median age: 86 years) from the Chinese Longitudinal Healthy Longevity Survey. Cox proportional hazard models were used to assess the association between the frequency of garden work and risk of incident dementia using hazard ratios (HRs) and 95% confidence intervals (CIs). Multiplicative and additive interaction effects were calculated between the frequency of garden work and age, sex or residence on incident dementia; subgroup analyses of the association were also conducted by age, sex and residence. In addition, sensitivity analyses were performed to assess the robustness of the results. RESULTS: During 4.31 years (median) of follow-up, 633 participants developed dementia. Compared with participants who did not engage in garden work, the adjusted risk of incident dementia for those who regularly or almost daily engaged in garden work decreased by 28% (HR = 0.72, 95% CI: 0.57-0.93). An additive interaction effect between frequency of garden work and age on incident dementia was observed, with subgroup analyses demonstrating similar statistically significant associations among participants aged ≥85 years, women and city or town residents. Sensitivity analyses were consistent with the primary analysis in the present study. CONCLUSIONS: Frequent engagement in garden work may be associated with a reduced risk of dementia and may be an effective measure to prevent incident dementia in the older population in China.

[Analysis of risk factors for venous thromboembolism in patients with polycythemia vera and establishment of a prediction model].

Objective: To investigate the risk factors of venous thrombosis in patients with polycythemia vera (PV) and establish a prediction model for venous thrombosis. Methods: PV patients with JAK2V617F gene mutation positive in the Second Hospital of Tianjin Medical University from September 2017 to November 2023 were retrospectively included. The patients were divided into groups according to whether they had venous thrombosis. After matching age and gender factors with propensity scores, 102 patients were included in the venous thrombosis group [46 males, 56 females, with a median age M (Q1, Q3) of 52 (44, 60) years] and 204 cases were included in the group without venous thrombosis [92 males, 112 females, with a median age of 52 (44, 59) years]. The clinical and laboratory characteristics, disease progression and incidence of gene mutation were compared between the two groups. The follow-up cohort ended on November 20, 2023, with a median follow-up [M (Q1, Q3)] of 11 (1, 53) years. Multivariate Cox risk model was used to analyze the influencing factors of venous thrombosis in PV patients, and establish a scoring system for the venous thrombosis risk factor prediction model of PV patients. Receiver operating characteristic (ROC) curve was used to evaluate the predictive efficiency of the model. Results: Hemoglobin concentration, the ratio of hematopoietic volume≥55%, neutrophil to lymphocyte ratio≥5, hypertension, subcostal spleen≥5 cm and secondary myelofibrosis in venous thrombosis group were higher than those in non-venous thrombosis group (all P<0.05). In addition, the proportion of history of thromboembolism, V617F gene mutation load (V617F%)≥50%, diabetes mellitus, ASXL1 mutation and secondary reticular silver staining≥3 in the venous thrombosis group were higher than those in the non-venous thrombosis group (all P<0.05). The proportion of PV patients with 3 or more gene mutations was 44.1% (45/102) in venous thrombosis group, which was higher than that of PV patients without venous thrombosis 29.9% (61/204) (P=0.014). The proportion of ASXL1 gene mutation in venous thrombosis group was 17.6% (18/102), which was higher than the 4.9% (10/204) in non-venous thrombosis group (P<0.001). Multivariate Cox risk model analysis showed that previous thromboembolism history (HR=2.031, 95%CI: 1.297-3.179, P=0.002), V617F%≥50% (HR=2.141, 95%CI: 1.370-3.347, P=0.001), ASXL1 mutation (HR=4.632, 95%CI: 1.497-14.336, P=0.008), spleen subcostal≥5 cm (HR=1.771, 95%CI: 1.047-2.996, P=0.033) are the risk factors of venous thrombosis in PV patients. According to HR values, a score system for predicting risk of venous thrombosis in PV patients was established: previous history of thromboembolism, V617F%≥50% and spleen subcostoal≥5 cm were assigned 1 point respectively, and ASXL1 mutation was assigned 2 points. Low risk group: score 0, medium risk group: score 1-2, high risk group: score≥3. The ROC curve analysis of the model for predicting venous thrombosis in PV patients showed that the area under the curve (AUC) was 0.807 (95%CI: 0.755-0.860), with the sensitivity of 88.2% and the specificity of 59.8% when the Youden index was 0.48. Conclusions: Previous thromboembolism history, V617F%≥50%, ASXL1 mutation, spleen subcostoal≥5 cm are risk factors of venous thrombosis in PV patients. The established prediction model has good prediction efficiency.

[Clinical features and outcomes of digestive tract perforation in pediatric mature B-cell non-Hodgkin lymphoma].

To summarize the clinical features and prognosis of pediatric mature B-cell non-Hodgkin lymphoma (mB-NHL) with digestive tract perforation. The clinical manifestations, laboratory and imaging examinations, treatment and outcomes of mB-NHL children complicated with digestive tract perforation admitted to Beijing Children's Hospital of Capital Medical University from January 2016 to June 2023 were retrospectively analyzed. A total of 12 patients were included, with 11 males and 1 female, aged 0.8-16.0 (7.5±5.4) years. Among them, there were 10 cases of Burkitt lymphoma, 1 case of high-grade B-cell lymphoma (HGBL) and 1 case of diffuse large B-cell lymphoma (DLBCL), respectively. Intestinal involvement was involved in all cases, with St.Jude staging ranging from stage Ⅲ to Ⅳ. Eleven cases had large abdominal mass. In 7 cases, abdominal X-ray examination showed free gas under the diaphragm. Eleven cases experienced digestive tract perforation after chemotherapy, and the time of perforation after initiation of chemotherapy was 2.0-111.0 (41.2±33.6) days. The most common site of perforation was ileum (6 cases), followed by gastric wall (2 cases), jejunum (1 case), colon (1 case) and appendix (1 case). Eight patients underwent surgery, and the time between surgery and re-chemotherapy was 7.0-45.0 (17.6±12.0) days. One case with perforation before chemotherapy died after giving up treatment. The remaining 11 cases received conservative treatment or surgical intervention, followed by regular chemotherapy after symptom and infection control. The follow-up time was 6.0-82.0 (45.0±26.1) months, and all survived.

Genome Sequence Resource of Fusarium proliferatum f. sp. malus domestica MR5, the Causative Agent of Apple Replant Disease.

Apple replant disease (ARD) caused by the fungal pathogen Fusarium proliferatum f. sp. malus domestica (Fpmd) MR5 brings annual losses to apple production within China. However, the genomic information of the pathogen is not yet available. Here, we obtained the whole-genome sequence of the highly virulent Fpmd MR5 using the Illumina PE150 platform. The genome size was 42.76 Mb and consisted of 9,047 genes. The GC content was 48.80%, and several genes potentially associated with pathogenicity were identified, such as carbohydrate-active enzymes, secreted proteins, and secondary metabolite gene clusters. There were 260 specific virulence factor genes, mainly related to fungal vegetative growth and the production of cell wall-degrading enzymes. These data will aid future studies investigating host-pathogen interactions and help us develop suitable disease management strategies.

[The 500th case: pain in both hip joints, headache, and diplopia].

A male child, aged 5 years and 3 months, was admitted to the Oncology Department with a history of pain in both hip joints, headache, and diplopia lasting for 40 days. Physical examination did not reveal definitive signs or obvious abnormalities in the nervous system. Imaging studies showed only abnormalities in the craniocerebrum and spinal cord. Routine cerebrospinal fluid (CSF) analysis revealed elevation in the total number of white blood cells, mainly mononuclear cells. Biochemical analysis of CSF showed normal glucose and chloride levels, and increased protein concentrations. The possibility of central nervous system (CNS) infection was initially considered. Subsequently, antibacterial and antiviral therapy was administered; however, this treatment was ineffective. Further examination of CSF through immunophenotyping revealed mature B-cell lymphoma with CNS involvement; there were no neoplastic lesions detected elsewhere in the body. Thus, the patient was diagnosed with primary central nervous system lymphoma (PCNSL). Complete remission was achieved after chemotherapy with the CNCL-2017-mature B-cell lymphoma regimen. Thus far, all chemotherapy cycles have been completed, the patient remains in complete remission, and the follow-up is ongoing. Clinicians should pay close attention to PCNSL in children.

[Research progress on the burden of respiratory syncytial virus infection in the elderly].

Human Respiratory Syncytial Virus (HRSV) is a serious threat to the population health. The elderly are one of the susceptible populations. The prevalence of HRSV in the elderly is generally higher than that in other age groups except children, which has gradually attracted attention in recent years. This paper reviewed the prevalence, common complications and major complications of HRSV in the elderly, briefly expounded the economic burden of HRSV infection, and proposed that attention should be paid to the disease burden of the elderly after HRSV infection, timely treat common complications, so as to reduce the occurrence of adverse survival outcomes and provide scientific evidence for the prevention and control of HRSV infection in the elderly.

[Analysis of mortality trend and characteristic of chronic obstructive pulmonary disease among residents in China from 2004 to 2020].

Objective: To analyze the mortality trend and characteristics of chronic obstructive pulmonary disease (COPD) among residents in China from 2004 to 2020. Methods: From the area, gender, region, and age dimensions, the Joinpoint regression model was used to analyze the trend of COPD mortality rate from 2004 to 2020, extracted from the China Death Surveillance Dataset. Results: From 2004 to 2020, the mortality rate and age-adjusted mortality rate of COPD showed a downward trend (AAPC=-3.68%, P<0.001; AAPC=-7.27%, P<0.001), which were consistent with urban and rural subpopulations (mortality rate: AAPC=-3.62%, P=0.009, AAPC=-3.23%, P=0.014; age-adjusted mortality rate: AAPC=-7.26%, P<0.001, AAPC=-6.78%, P<0.001). The mortality rate of COPD in rural was higher than that of urban subpopulations (P<0.001). Also, the mortality rate and age-adjusted mortality rate of COPD showed a downward trend in males and females (mortality rate: AAPC=-3.00%, P<0.001, AAPC=-4.37%, P<0.001; age-adjusted mortality rate: AAPC=-6.73%, P<0.001, AAPC=-8.11%, P<0.001), and the COPD mortality rate for male was generally higher than female (P<0.001). Meanwhile, the mortality rate of COPD in eastern, central and western regions also showed a downward trend (AAPC=-3.87%, P<0.001; AAPC=-3.12%, P<0.001; AAPC=-1.37%, P=0.001), and western regions were significantly higher than that in central (P<0.001) and eastern (P<0.001) regions. The mortality rate of COPD in the age group of Chinese people showed a downward trend in<45, 45-59, and≥60 years groups (AAPC=-9.48%, P<0.001; AAPC=-9.03%, P<0.001; AAPC=-5.91%, P<0.001). Among them,≥60 years groups was significantly higher than that in<45 (P<0.001) and 45-59 (P<0.001) years groups, and the decline rate was slowest. Conclusion: In China, the mortality rate of COPD decreases from 2004 to 2020, and more efforts are needed to reduce COPD mortality, especially in western regions, rural populations, males and the elderly.

[Research progress on the effect of tenofovir disoproxil fumarate on blood lipid profile].

Tenofovir disoproxil fumarate (TDF) is a novel nucleotide reverse transcriptase inhibitor that is mainly used to treat human immunodeficiency virus (HIV) and hepatitis B virus (HBV) infections. In recent years, an increasing number of studies have demonstrated that TDF treatment can reduce blood lipid levels in patients with AIDS and chronic hepatitis B and has a close correlation with the severity of the disease and the occurrence of cardiovascular events. This article reviews the research progress on the effect of TDF on blood lipid profiles, with the aim of providing a basis for rational use of TDF.

[Impact of nucleosides analogues and nucleotide analogues on the outcomes related to chronic hepatitis B based on non-antiviral effects].

Nucleoside analogues and nucleotide analogues can not only achieve long-term viral suppression in the treatment of most CHB patients but also have a positive impact on other CHB therapeutic goals and an improved prognosis. A certain difference can be observed in the impact of nucleotide analogues such as TDF and TAF and nucleoside analogues such as ETV on the clinical outcomes of CHB. Studies on the mechanism of action indicate that apart from inhibiting the direct antiviral effects of HBV reverse transcriptase, these two categories of drugs exhibit distinct impacts on immune-related signaling pathways, gene expression, genome stability, and other non-antiviral mechanisms. This article reviews the evidence on the potential non-antiviral mechanism of action of nucleoside analogues and nucleotide analogues and proposes a preliminary explanation for the observation trend of nucleotide analogues having a comparative advantage in clinical outcomes in CHB patients based on the latest research advancement.

[Study on the 5-year trend and influencing factors of lipoprotein (a) concentration in community-based population].

Objective: To explore the trend and influencing factors of serum lipoprotein (a) (Lp(a)) concentration over time in Chinese community populations. Methods: This study is a prospective cohort study. The participants were enrolled from Chinese Multi-provincial Cohort Study- Beijing projects, completed the cardiovascular disease risk factor surveys in 2002 and 2007, and the serum Lp (a) concentration were measured. Based on the Lp(a) concentration at baseline (2002) and follow-up (2007), the participants were classified into subgroups of <30.0 mg/dl (1 mg/dl=0.01 g/L) group, 30.0 to 49.9 mg/dl group, and ≥50.0 mg/dl group, respectively. Multivariable logistic regression analysis was used to identify influencing factors associated with Lp (a) absolute change (≥20 mg/dl) and relative change (≥20%) within 5 years. Results: Among 1 955 participants with age of (56.5±8.0) years old and 821 male (42.0%) at baseline, there were 1 657 (84.8%), 184 (9.4%) and 114 (5.8%) participants in Lp(a)<30.0 mg/dl group, 30.0 to 49.9 mg/dl group and ≥50.0 mg/dl group, respectively. Among the baseline Lp(a) concentration of 30.0-49.9 mg/dl group, 68 (37.0%) participants progressed to Lp(a) ≥50.0 mg/dl after 5 years follow-up, and 102 (55.4%) remained at this level. Participants with baseline Lp(a)<30.0 mg/dl (92%, 1 524/1 657) or Lp(a)≥50.0 mg/dl (94.7%, 108/114) tended to be maintained at their respective levels. The results of the multivariate logistic regression analysis showed that, in addition to the high level of baseline Lp(a) concentration, family history of cardiovascular disease, elevated fasting blood glucose and usage of oral lipid-lowering drugs were the influencing factors of Lp(a) changes over time (P<0.05). Conclusions: Adults with borderline-high Lp(a) concentrations (30.0 to 49.9 mg/dl) could be considered for repeated testing, especially for those with a family history of cardiovascular disease, elevated fasting blood glucose and usage of statins.

[Characteristics of SPECT/CT-derived pulmonary perfusion imaging in chronic pulmonary vascular stenosis with different etiologies].

Objective: To explore the characteristics of pulmonary blood flow perfusion imaging of single photo emission computer tomography/computer tomography (SPECT/CT) in chronic pulmonary vascular Stenosis (CPVS) caused by different etiological factors. Methods: This is a retropective study. Present study screened 50 consecutive cases diagnosed with chronic pulmonary vascular stenosis from January 2019 to January 2020 in the department of cardiology of Gansu Provincial Hospital and underwent SPECT/CT pulmonary blood flow perfusion examination. Thirteen patients were excluded because of pulmonary vascular lesions with a disease course of less than 3 months and poor image quality. According to the etiology, patients were divided into fibrosing mediastinitis (FM) group, Takyasu's arteritis (PTA) group, and chronic thromboembolic pulmonary hypertension/chronic thromboembolic pulmonary disease (CTEPH/CTED) group. The severity of pulmonary blood flow perfusion was evaluated in accordance with the Begic scoring principle in the three groups. The overall Begic score, lung lobe scores among three groups were compared. CT signs of lung SPECT/CT, such as enlargement of hilar lymph node, atelectasis, bronchial stenosis, were also analyzed in three groups. Results: A total of 37 patients with chronic pulmonary vascular stenosis were finally enrolled (18 in the FM group, 5 in the PTA group, and 14 in the CTEPH/CTED group). The total Begic score of pulmonary perfusions was similar among the three groups (F=0.657,P>0.05). There was a statistically significant difference in the left upper lobe Begic score among the three groups (H=4.081, P<0.05). The left upper lobe Begic score was higher in the FM group than in the PTA group (3.44±2.50 vs. 1.60±0.55, P<0.05). As compared to other two groups, patients in FM group were featured with CT signs of higher percent of hilar enlargement (FM group vs. PTA group: 16/18 vs. 1/5, P=0.008; FM group vs. CTEPH/CTED group: 16/18 vs. 3/14, P=0.000 2), enlargement of the pulmonary hilum lymph nodes (FM group vs. PTA group: 14/18 vs. 1/5, P=0.033; FM group vs. CTEPH/CTED group: 14/18 vs. 2/14, P=0.001), and calcification of mediastinal soft tissue (FM group vs. PTA group: 11/18 to 0/5, P=0.037; FM group vs. CTEPH/CTED group: 11/18 vs. 1/14, P=0.003). The proportion of CT signs of bronchial stenosis (9/18 vs. 0/14, P=0.002) and atelectasis (9/18 vs. 1/14, P=0.002) was also higher in the FM group than in the CTEPH/CTED group. In case of abnormal pulmonary blood flow perfusion, the diagnostic accuracy of CT signs hilar enlargement, hilar lymph node enlargement, mediastinal soft tissue calcification, bronchial stenosis, and atelectasis for the diagnosis of FM were 81.1%, 83.8%, 78.4%, 75.7%, and 73.0%, respectively. Conclusion: There is no significant difference in the Begic score of SPECT/CT pulmonary blood flow perfusion imagines among the three groups of patients. Impaired pulmonary blood flow perfusion combined with typical CT signs is useful for identifying patients with FM.

[Design for online monitoring of occupational hazard factors based on internet of things].

At present, there are disadvantages with the detection for occupational hazard factors, such as insufficient monitoring data, poor timeliness, weak representativeness, long detection cycles, and inability to continuously monitor. Taking advantages of internet of things technology, an online monitoring platform for occupational hazard factors has been designed. The platform collects the concentration (intensity) of hazard factors through sensors, transmits the occupational hazards data collected online in realtime. The online monitoring cloud center for occupational hazard factors processes and analyzes online monitoring data in realtime, stores the hazard factors data to form database management, and provides user application services to form an intelligent online monitoring service model for occupational hazard factors. Based on the online monitoring platform of occupational hazard factors, multi-level government health supervision departments and employers can grasp the status of hazard factors in real time, which is conducive to improving the level of occupational hazard supervision.

Intrinsic Correlation between the Fraction of Liquidlike Zones and the ß Relaxation in High-Entropy Metallic Glasses.

Lacking the structural information of crystalline solids, the origin of the relaxation dynamics of metallic glasses is unclear. Here, we report the evolution of stress relaxation of high-entropy metallic glasses with distinct ß relaxation behavior. The fraction of liquidlike zones, determined at each temperature by the intensity of stress decay, is shown to be directly related to both the aging process and the spectrum of relaxation modes obtained by mechanical spectroscopy. The results shed light on the intrinsic correlation between the static and dynamic mechanical response in high-entropy and conventional metallic glasses, pointing toward a sluggish diffusion high-entropy effect in the liquid dynamics.

Erratum: Intrinsic Correlation between the Fraction of Liquidlike Zones and the ß Relaxation in High-Entropy Metallic Glasses [Phys. Rev. Lett. 129, 175501 (2022)].

This corrects the article DOI: 10.1103/PhysRevLett.129.175501.

Performance of a generative adversarial network using ultrasound images to stage liver fibrosis and predict cirrhosis based on a deep-learning radiomics nomogram.

AIM: To investigate the performance of a generative adversarial network (GAN) model for staging liver fibrosis and its radiomics-based nomogram for predicting cirrhosis. MATERIALS AND METHODS: This two-centre retrospective study included 434 patients for whom input data of ultrasound images and histopathological data (obtained within 1 month of ultrasound examinations) were assigned to the training cohort (249 patients), the internal cohort (92 patients), and the external (93 patients) cohort. A data augmentation method based on a GAN model was used. The discriminative performance was evaluated for classifying fibrosis of S4 and ≥S3. Deep-learning radiomics features were extracted for the prediction of cirrhosis (S4). To perform feature reduction and selection, the least absolute shrinkage and selection operator (LASSO) algorithm was applied. Radiomics scores, along with clinical factors, were incorporated into a nomogram using multivariable logistic regression analysis. The performance of the models was estimated with respect to discrimination power, calibration, and clinical benefits. RESULTS: The areas under the receiver operating characteristic curve (AUCs) values of the GAN were 0.832/0.762 (≥S3), and 0.867/0.835 (S4) for internal/external test sets, respectively. The radiomics nomogram that intergrated radiomics scores and clinical factors showed good calibration and discrimination ability of 0.922 (AUC) in the training dataset, 0.896 in the internal dataset, and 0.861 in the external dataset. Decision curve analysis (DCA) demonstrated that the nomogram outperformed radiologist and haematological indices in terms of the most clinical benefits. CONCLUSIONS: The GAN model could be applied to discriminate fibrosis stages, and a favourable predictive accuracy for diagnosing cirrhosis was achieved using a deep-learning radiomics nomogram.

Long-term particulate matter 2.5 exposure and dementia: a systematic review and meta-analysis.

OBJECTIVES: This study aimed to analyse the existing evidence on the association between particulate matter 2.5 (PM2.5) and dementia, including two of its subtypes, namely, Alzheimer's disease (AD) and vascular dementia (VaD). STUDY DESIGN: This was a systematic review and meta-analysis. METHODS: The PubMed, EMBASE, Cochrane and Web of Science databases were comprehensively searched for articles published between January 1900 and June 2022. All cohort studies that reported the influence of long-term exposure to PM2.5 on dementia, together with its subtypes, in adults aged ≥40 years, without any regional restriction were included. A random effects model was used to pool the hazard ratios (HRs) of PM2.5 for dementia, AD and VaD. Funnel plots, sensitivity analyses and subgroup analyses were performed to test publication bias and result stability. In addition, an explanation for the heterogeneity of the results was suggested. RESULTS: In total, 20 articles were selected for review; 18 included results on the long-term effects of PM2.5 on dementia, 13 on AD, and eight on VaD. Three group meta-analyses were performed to obtain the HRs and 95% confidence intervals (CIs). The pooled HRs were 1.40 (95% CI 1.23, 1.60) for dementia, 1.47 (95% CI 1.22, 1.78) for AD and 2.00 (95% CI 1.30, 3.08) for VaD per 10.0 µg/m3 PM2.5 increase. CONCLUSIONS: Long-term exposure to PM2.5 may increase the risk of dementia, including AD and VaD. These results highlight the need for further study on the detrimental impact of PM2.5 and the importance of strategies to mitigate increasing air pollution.

Discovery of Fusarium proliferatum f. sp. malus domestica Causing Apple Replant Disease in China.

Apple replant disease (ARD) is the most serious threat facing the apple industry globally. ARD is mainly manifested as decreased plant growth, serious root rot disease, and considerable yield loss. Microbial factors are the dominant factors leading to the occurrence of ARD. Research on soil-borne pathogenic fungi leading to the occurrence of ARD in China is limited. In the present study, we selected 16 replanting orchards from the Northwest Loess region and around the Bohai Gulf. Diseased roots and rhizosphere soil from healthy apple trees and trees showing ARD symptoms were sampled at random. High-throughput sequencing was used to study the fungal communities in the rhizosphere soil, which showed that the composition of the rhizosphere soil fungal community of ARD-symptomatic and healthy apple trees was different. Nectriaceae at the family level and Fusarium at the genus level dominated the rhizosphere soil fungal community in the two regions, while for healthy apple trees, the relative abundance of Mortierella, Minimedusa, Tetracladium, and Chaetomium was higher. Tissue separation and serial dilution were used to separate fungi, and a total of 89 genera and 219 species were obtained, most of which were Fusarium. Fusarium was further confirmed to be the most abundant pathogen species leading to the occurrence of ARD in China through pathogenicity assays. A pathogenicity assay was carried out by the dip-and-cut technique using different host plants. It was found that Fusarium MR5 showed strong aggressiveness to apple rootstocks. Diseased seedlings specifically exhibited chlorosis of the leaves, browning from the edge of the leaf, followed by rolling and yellowing of the leaves, resulting in wilting and eventually death. Strain MR5 was preliminarily identified as F. proliferatum according to the morphological and cultural characteristics. A maximum likelihood analysis of identities based on six gene sequence (ITS, TUB2, IGS, mtSSU, RPB2, and the TEF gene) alignments between the MR5 strain and other strains showed 99 to 100% homology with F. proliferatum. Based on our test results, strain MR5 was identified as F. proliferatum f. sp. malus domestica, which is of great significance for finding new measures to control ARD in China.

[CXCL5 inhibits tumor immune of lung cancer via modulating PD1/PD-L1 signaling].

Objective: To investigate the role of CXCL5 in tumor immune of lung cancer and to explore the potential molecular mechanisms. Methods: A total of 62 cases of patients with lung cancer admitted in the First Affiliated Hospital of Henan University from May 2018 to December 2019 were recruited as study object. Another 20 cases of patients with pulmonary infectious diseases and 20 cases of healthy control were selected as control. Enzyme-linked immunosorbent assay (ELISA) was used to determine serum levels of CXCL5 in patients with lung cancer, pulmonary infectious diseases and healthy control. Immunohistochemical staining (IHC) was used to detect the expressions of CXCL5 and PD-1/PD-L1 in tumor and paracarcinoma tissues of patients with lung cancer. Pearson correlation analysis was used to evaluate the correlation between CXCL5 and PD-1 in tumor and paracarcinoma tissues of patients with lung cancer. Lewis cells either expressing CXCL5 or vector plasmids were used to establish C57BL/6J mice model of lung cancer, and all mice were then divided into vehicle and PD-1 antibody treatment groups, 10 mice for each group. The mice survival and tumor growth curves were recorded. IHC was used to evaluate the expressions of CXCL5, PD-1 as well as the proportions of CD8(+) T and Treg cells in xenograft tumor tissues. Results: In patients with lung cancer, the serum level of CXCL5 [(351.7±51.5) ng/L] was significant higher than that in patients with pulmonary infectious diseases and healthy control [(124.7±23.4) ng/L, P<0.001]. The expression levels of CXCL5 (0.136±0.034), CXCR2 (0.255±0.050), PD-1 (0.054±0.012) and PD-L1 (0.350±0.084) in tumor were significant higher than those in paracarcinoma normal tissues [(0.074±0.022), (0.112±0.023), (0.041±0.007) and (0.270±0.043) respectively, P<0.001]. CXCL5 was significant positively correlated with PD-1 in tumor tissues of lung cancer (r=0.643, P<0.001), but not correlated with PD-1 in paracarcinoma tissues(r=0.088, P=0.496). The vector control group, CXCL5 overexpression group, vector control + anti-PD-1 antibody treatment group and CXCL5 overexpression + anti-PD-1 antibody treatment group all successfully formed tumors in mice, while CXCL5 overexpression increased the tumor growth significantly (P<0.01), which was abrogated by the treatment of anti-PD-1 antibody. CXCL5 overexpression decreased the mice survival time significantly (P<0.01), this effect was also abrogated by the treatment of anti-PD-1 antibody. The proportion of CD8(+) T cells in CXCL5 overexpression group [(10.40±2.00)%] was significant lower than that in vector control group [(21.20±3.30)%, P=0.002]. The proportion of CD4(+) Foxp3(+) Treg cells in CXCL5 overexpression group [(38.40±3.70)%] was significant higher than that in vector control group [(23.30±2.25)%, P<0.001]. After the treatment of anti-PD-1 antibody, no significant difference were observed for the proportion of CD8(+) T cells [(34.10±5.00)% and (33.40±4.00)% respectively] and Treg cells [(14.70±3.50)% and (14.50±3.30)% respectively] in xenograft tumor tissues between CXCL5 overexpression+ anti-PD-1 antibody treatment group and vector control + anti-PD-1 antibody treatment group (P>0.05). Conclusion: The expressions of CXCL5 and PD-1/PD-L1 are all increased significantly in the tumor tissues of patients with lung cancer, CXCL5 may inhibit tumor immune of lung cancer via modulating PD-1/PD-L1 signaling.