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The effects of adult crowding on two components of fitness were studied in three sets of Drosophila melanogaster populations, subjected to life-stage-specific, density-dependent natural selection in the laboratory for over 50 generations. Three days of crowding, early in adult life, were observed to increase mortality significantly during the episode of crowding, as well as decrease subsequent fecundity. Populations selected for adaptation to high adult densities suffered significantly lower mortality during episodes of adult crowding, as compared to populations selected specifically for adaptation to larval crowding, as well as control populations typically maintained at low larval and adult densities. Moreover, populations adapted to larval crowding seemed to be adversely affected by adult crowding to a greater extent than the controls, raising the possibility of trade-offs between adaptations to larval and adult crowding, respectively. Preliminary evidence suggests that the populations adapted to adult crowding may have evolved a propensity to stay away from the food medium, which is where most deaths occur when adults are crowded in culture vials.

Lignocellulosic ethanol is produced by yeast fermentation of lignocellulosic hydrolysates generated by chemical pretreatment and enzymatic hydrolysis of plant cell walls. The conversion of xylose into ethanol in hydrolysates containing microbial inhibitors is a major bottleneck in biofuel production. We identified sodium salts as the primary yeast inhibitors, and evolved a Saccharomyces cerevisiae strain overexpressing xylose catabolism genes in xylose or glucose-mixed medium containing sodium salts. The fully evolved yeast strain can efficiently convert xylose in the hydrolysates to ethanol on an industrial scale. We elucidated that the amplification of xylA, XKS1 and pentose phosphate pathway-related genes TAL1, RPE1, TKL1, RKI1, along with mutations in NFS1, TRK1, SSK1, PUF2 and IRA1, are responsible and sufficient for the effective xylose utilization in corn stover hydrolysates containing high sodium salts. Our evolved or reverse-engineered yeast strains enable industrial-scale production of lignocellulosic ethanol and the genetic foundation we uncovered can also facilitate transfer of the phenotype to yeast cell factories producing chemicals beyond ethanol., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: The assessment information of tumor margins is extremely important for the success of the breast cancer surgery and whether the patient undergoes a second operation. However, conducting surgical margin assessments is a time-consuming task that requires pathology-related skills and equipment, and often cannot be provided in a timely manner. To address this challenge, digital breast tomosynthesis technology was utilized to generate detailed cross-sectional images of the breast tissue and integrate deep learning algorithms for image segmentation, achieving an assessment of tumor margins during surgery., Methods: this study utilized post-operative tissue samples from 46 patients who underwent breast-conserving treatment, and generated image sets using digital breast tomosynthesis for the training and evaluation of deep learning models., Results: Deep learning algorithms effectively identifying the tumor area. They achieved a Mean Intersection over Union (MIoU) of 0.91, global accuracy of 99%, weighted IoU of 44%, precision of 98%, recall of 83%, F1 score of 89%, and dice coefficient of 93% on the training dataset; for the testing dataset, MIoU was at 83%, global accuracy at 97%, weighted IoU at 38%, precision at 87%, recall rate at 69%, F1 score at 76%, dice coefficient at 86%., Conclusions: The initial evaluation suggests that the deep learning-based image segmentation method is highly accurate in measuring breast tumor margins. This helps provide information related to tumor margins during surgery, and by using different datasets, this research method can also be applied to the surgical margin assessment of various types of tumors.

Rationale and Objectives: The aim of this study was to compare the use of computed tomography (CT) with automatic rib unfolding and three-dimensional (3D) volume-rendered imaging in the detection and characterization of rib fractures and flail chest., Materials and Methods: A total of 130 patients with blunt chest trauma underwent whole-body CT, and five independent readers assessed the presence and characterization of rib fractures using traditional CT images, automatic rib unfolding, and 3D volume-rendered images in separate readout sessions at least 2 weeks apart. A gold standard was established by consensus among the readers based on the combined analysis of conventional and reformatted images., Results: Automatic rib unfolding significantly reduced mean reading time by 47.5%-74.9% (P < 0.0001) while maintaining a comparable diagnostic performance for rib fractures (positive predictive value [PPV] of 82.1%-93.5%, negative predictive value [NPV] of 96.8%-98.2%, and 69.4%-94.2% and 96.9%-99.1% for conventional axial images and 70.4%-85.1% and 95.2%-96.6% for 3D images) and better interobserver agreement (kappa of 0.74-0.87). For flail chest, automatic rib unfolding showed a PPV of 85.7%-100%, NPV of 90.4%-99.0%, and 80.0%-100% and 89.7%-100% for conventional axial images and 76.9%-100% and 89.0%-92.1% for 3D images., Conclusion: Automatic rib unfolding demonstrated equivalent diagnostic performance to conventional images in detecting acute rib fractures and flail chest, with good interobserver agreement and time-saving benefits., Competing Interests: DECLARATION OF COMPETING INTEREST The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Objective: To explore the bidirectional relationship of late-onset epilepsy (LOE) with dementia and Alzheimer's disease (AD)., Methods: Using the common electronic databases, including PubMed, Cochrane Library databases and EMBASE, we systematically reviewed published cohort studies that assessed the risk of LOE in individuals comorbid with dementia or AD, and those with dementia or AD comorbid with LOE that had been published up to 31 March 2023. The data extraction process was carried out independently by two authors. The summary adjusted relative ratio (aRR) was calculated by employing Rev Man 5.3 for the inclusion of studies. To investigate the origins of heterogeneity, we conducted both subgroup and sensitivity analyses. In the presence of heterogeneity, a random-effects model was employed. To evaluate potential publication bias, we utilized the funnel plot and conducted Begg's and Egger's tests., Results: We included 20 eligible studies in the final analysis after a rigorous screening process. Pooled results indicated that LOE was association with an increased risk of all-cause dementia (aRR: 1.34, 95% confidence interval [CI]: 1.13-1.59) and AD (aRR: 2.49, 95% CI: 1.16-5.32). In addition, the pooled effect size for LOE associated with baseline AD and all-cause dementia were 3.51 (95% CI: 3.47-3.56) and 2.53 (95% CI: 2.39-2.67), respectively. Both sensitivity and subgroup analyses showed that these positive correlations persisted. According to the results of the Egger's and Begg's tests, as well as visual inspection of funnel plots, none of the studies appeared to be biased by publication., Conclusion: The findings suggested that LOE is a potential risk factor for dementia and AD, and vice versa, dementia and AD are both potential risk indicators for LOE. Since there is substantial heterogeneity among the cohorts analyzed and more cohort studies should be conducted to confirm the correlations found in the current study., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Sentinel lymph node biopsy (SLNB) is the standard of care for axillary staging in early breast cancer patients with low-burden axillary metastasis (≤ 2 positive nodes). This study aimed to determine the diagnostic performances of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and breast magnetic resonance imaging in detecting axillary lymph node (ALN) metastases and the reliability to predict ALN burden., Methods: A total of 275 patients with primary operable breast cancer receiving preoperative PET/CT and upfront surgery from January 2001 to December 2022 in a single institution were enrolled. A total of 244 (88.7%) of them also received breast MRI. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PET/CT and breast MRI were assessed. The predictive values to determine ALN burden were evaluated using radio-histopathological concordance., Results: PET/CT demonstrated a sensitivity of 53.4%, specificity of 82.1%, PPV of 65.5%, NPV of 73.5%, and accuracy of 70.9% for detecting ALN metastasis, and the corresponding values for MRI were 71.8%, 67.8%, 56%, 80.8%, and 69.2%, respectively. Combining PET/CT and MRI showed a significantly higher PPV than MRI (72.7% vs 56% for MRI alone, p = 0.037) and a significantly higher NPV than PET/CT (84% vs 73.5% for PET/CT alone, p = 0.041). For predicting low-burden axillary metastasis (1-2 positive nodes), the PPVs were 35.9% for PET/CT, 36.7% for MRI, and 55% for combined PET/CT and MRI. Regarding patients with 0-2 positive ALNs in imaging, who were indicated for SLNB, the predictive correctness was 96.1% for combined PET/CT and MRI, 95.7% for MRI alone, and 88.6% for PET/CT alone., Conclusions: PET/CT and breast MRI exhibit high predictive values for identifying low-burden axillary metastasis in patients with operable breast cancer with ≦ 2 positive ALNs on imaging., (© 2024. The Author(s).)

Background: The value and utility of axillary lymph node (ALN) evaluation with MRI in breast cancer were not clear for various intrinsic subtypes. The aim of the current study is to test the potential of combining breast MRI and clinicopathologic factors to identify low-risk groups of ALN metastasis and improve diagnostic performance., Material and Methods: Patients with primary operable invasive breast cancer with pre-operative breast MRI and post-operative pathologic reports were retrospectively collected from January 2009 to December 2021 in a single institute. The concordance of MRI and pathology of ALN status were determined, and also analyzed in different intrinsic subtypes. A stepwise strategy was designed to improve MRI-negative predictive value (NPV) on ALN metastasis., Results: 2473 patients were enrolled. The diagnostic performance of MRI in detecting metastatic ALN was significantly different between intrinsic subtypes (p = 0.007). Multivariate analysis identified tumor size and histologic type as independent predictive factors of ALN metastases. Patients with HER-2 (MRI tumor size ≤ 2 cm), or TNBC (MRI tumor size ≤ 2 cm) were found to have MRI-ALN-NPV higher than 90%, and these false cases were limited to low axillary tumor burden., Conclusion: The diagnostic performance of MRI to predict ALN metastasis varied according to the intrinsic subtype. Combined pre-operative clinicopathologic factors and intrinsic subtypes may increase ALN MRI NPV, and further identify some groups of patients with low risks of ALN metastasis, high NPV, and low burdens of axillary disease even in false-negative cases., (© 2023. The Author(s).)

Three new species of Nazeris Fauvel, 1873 from the Jiuwan Mountain, Guangxi, China, are described and illustrated: N. jiuwanensis, sp. n., N. qingshuius, sp. n. and N. yangmeius sp. n. An identification key to the Nazeris species in Guangxi is provided.

Objective: Previous studies have found the potential role of gout or hyperuricemia in subsequent development of Alzheimer's disease (AD) but reported inconsistent results. We conducted the current meta-analysis to evaluate whether an association exists between gout/ hyperuricemia and AD., Methods: We systematically searched PubMed and EMBASE for the published cohort studies that measured the risk of AD in subject with gout/ hyperuricemia up to May 20, 2023. Data extraction was employed by two authors independently. Rev Man 5.3 and Stata 15.0 software were used to calculate the relative ratio (RR) or hazard ratio (HR) for including studies. Subgroup analysis was performed to assess the sources of heterogeneity. A random-effects model was adopted when heterogeneity was present. The funnel plot, Begg's test, and and Egger's test were used to assess publication bias., Results: After rigorous screening, seven eligible studies were included in the final analyses. Pooled results indicated that gout or hyperuricemia decreases the risk of AD (RR: 0.69, 95% CI: 0.64∼0.72), with a high heterogeneity of 93%. Subgroup analyses showed that regional distribution was the source of heterogeneity. Egger's and Begg's tests as well as visual inspection of funnel plot suggested no publication bias in the studies., Conclusion: The findings suggested that gout or hyperuricemia might have a protective effect against AD. This negative correlation should be verified by more cohort studies due to the existence of substantial heterogeneity., (© 2023 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Pulmonary epithelioid hemangioendothelioma (PEH) is a rare tumour of vascular origin with low to intermediate malignancy. Typical radiological finding on CT is multiple small nodules in bilateral lungs, and some will have punctate calcifications and pleural thickening. The diagnosis of PEH is confirmed by histopathological findings and positive immunohistochemistry staining. We report a case of a woman in her 50s with a medical history of lung adenocarcinoma. Later, regular chest CT during a routine cancer follow-up revealed multiple small pulmonary nodules and increased sizes of these nodules on serial images, initially misdiagnosed as multiple lung metastases. The histopathological diagnosis was made on a pulmonary wedge resection. Finally, PEH was diagnosed on the basis of positive immunohistochemical staining for CD31, ERF and TFE3. In the current study, the clinicopathological features and review of the literature were investigated. Our case highlights the importance of a histological diagnosis to avoid misdiagnosis., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Prospective studies on postoperative residual breast tissue (RBT) after robotic-assisted nipple-sparing mastectomy (R-NSM) for breast cancer are limited. RBT presents an unknown risk of local recurrence or the development of new cancer after curative or risk-reducing mastectomies. This study investigated the technical feasibility of using magnetic resonance imaging (MRI) to evaluate RBT after R-NSM in women with breast cancer., Materials and Methods: In this prospective pilot study, 105 patients, who underwent R-NSM for breast cancer at Changhua Christian Hospital between March 2017 and May 2022, were subjected to postoperative breast MRI to evaluate the presence and location of RBT. The postoperative MRI scans of 43 patients (age, 47.8 ± 8.5 years), with existing preoperative MRI scans, were evaluated for the presence and location of RBT. In total, 54 R-NSM procedures were performed. In parallel, we reviewed the literature on RBT after nipple-sparing mastectomy, considering its prevalence., Results: RBT was detected in 7 (13.0%) of the 54 mastectomies (6 of the 48 therapeutic mastectomies and 1 of the 6 prophylactic mastectomies). The most common location for RBT was behind the nipple-areolar complex (5 of 7 [71.4%]). Another RBT was found in the upper inner quadrant (2 of 7 [28.6%]). Among the six patients who underwent RBT after therapeutic mastectomies, one patient developed a local recurrence of the skin flap. The other five patients with RBT after therapeutic mastectomies remained disease-free., Conclusion: R-NSM, a surgical innovation, does not seem to increase the prevalence of RBT, and breast MRI showed feasibility as a noninvasive imaging tool for evaluating the presence and location of RBT., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2023 The Korean Society of Radiology.)

Objective: To investigate the misdiagnosis of area postrema syndrome (APS) manifesting as intractable nausea, vomiting and hiccups in neuromyelitis optic spectrum disease (NMOSD) and reduce the risk of misdiagnosis. Methods: We retrospectively analyzed data from NMOSD patients attending the Department of Neurology at the First Medical Center of PLA General Hospital between January 2019 and July 2021. SPSS25.0 was then used to analyze the manifestations, misdiagnosis, and mistreatment of APS. Results: A total of 207 patients with NMOSD were included, including 21 males and 186 females. The mean age of onset was 39±15 years (range: 5-72 years). The proportion of patients who were positive for serum aquaporin 4 antibody was 82.6% (171/207). In total, 35.7% (74/207) of the NMOSD patients experienced APS during the disease course; of these patients, 70.3% (52/74) had APS as the first symptom and 29.7% (22/74) had APS as a secondary symptom. The misdiagnosis rates for these conditions were 90.4% (47/52) and 50.0% (11/22), respectively. As the first symptom, 19.2% (10/52) of patients during APS presented only with intractable nausea, vomiting and hiccups; 80.8% (42/52) of patients experienced other neurological symptoms. The Departments of Gastroenterology and General Medicine were the departments that most frequently made the first diagnosis of APS, accounting for 54.1% and 17.6% of patients, respectively. The most common misdiagnoses related to diseases of the digestive system and the median duration of misdiagnosis was 37 days. Conclusions: APS is a common symptom of NMOSD and is associated with a high rate of misdiagnosis. Other concomitant symptoms often occur with APS. Gaining an increased awareness of this disease/syndrome, obtaining a detailed patient history, and performing physical examinations are essential if we are to reduce and avoid misdiagnosis.

Bacterial or viral infections, such as Brucella , mumps virus, herpes simplex virus, and Zika virus, destroy immune homeostasis of the testes, leading to spermatogenesis disorder and infertility. Of note, recent research shows that SARS-CoV-2 can infect male gonads and destroy Sertoli and Leydig cells, leading to male reproductive dysfunction. Due to the many side effects associated with antibiotic therapy, finding alternative treatments for inflammatory injury remains critical. Here, we found that Dmrt1 plays an important role in regulating testicular immune homeostasis. Knockdown of Dmrt1 in male mice inhibited spermatogenesis with a broad inflammatory response in seminiferous tubules and led to the loss of spermatogenic epithelial cells. Chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) revealed that Dmrt1 positively regulated the expression of Spry1 , an inhibitory protein of the receptor tyrosine kinase (RTK) signaling pathway. Furthermore, immunoprecipitation-mass spectrometry (IP-MS) and co-immunoprecipitation (Co-IP) analysis indicated that SPRY1 binds to nuclear factor kappa B1 (NF-κB1) to prevent nuclear translocation of p65, inhibit activation of NF-κB signaling, prevent excessive inflammatory reaction in the testis, and protect the integrity of the blood-testis barrier. In view of this newly identified Dmrt1 - Spry1 -NF-κB axis mechanism in the regulation of testicular immune homeostasis, our study opens new avenues for the prevention and treatment of male reproductive diseases in humans and livestock.

Background: The purpose of this study is to identify clinicopathologic factors and/or preoperative MRI vascular patterns in the prediction of ischemia necrosis of the nipple-areola complex (NAC) or skin flap post nipple-sparing mastectomy (NSM)., Methods: We performed a retrospective analysis of 441 NSM procedures from January 2011 to September 2021 from the breast cancer database at our institution. The ischemia necrosis of NAC or skin flap was evaluated in correlation with clinicopathologic factors and types of skin incision. Patients who received NSM with preoperative MRI evaluation were further evaluated for the relationship between vascular pattern and the impact on ischemia necrosis of NAC or skin flap., Results: A total of 441 cases with NSM were enrolled in the current study, and the mean age of the cases was 49.1 ± 9.8 years old. A total of 41 (9.3%) NSM procedures were found to have NAC ischemia/necrosis. Risk factors were evaluated of which old age, large mastectomy specimen weight (> 450 g), and peri-areola incision were identified as predictors of NAC necrosis. Two-hundred seventy NSM procedures also received preoperative MRI, and the blood supply pattern was 18% single-vessel type and 82% double-vessel pattern. There were no correlations between MRI blood supply patterns or types of skin flap incisions with ischemia necrosis of NAC. There were also no correlations between blood loss and the pattern or size of the blood vessel., Conclusion: Factors such as the type of skin incision, age, and size of mastectomy weight played an important role in determining ischemia necrosis of NAC; however, MRI vascular (single or dual vessel supply) pattern was not a significant predictive factor., (© 2023. The Author(s).)

A novel water-stable Cd II -based metal-organic framework, namely {[Cd(BIBT)(TDC)]·2H 2 O} n (JXUST-28, BIBT = 4,7-bi(1 H -imidazol-1-yl)benzo-[2,1,3]thiadiazole and H 2 TDC = 2,5-thiophenedicarboxylic acid), was synthesized using a mixed-ligand strategy. Structural analysis demonstrates that JXUST-28 exhibits a two-dimensional layer structure with 4-connected sql topology. Intriguingly, JXUST-28 presents good stability in boiling water (at least 5 days), common organic solvents and aqueous solutions with different pH values of 2-12 (more than 24 hours). Furthermore, fluorescence experiments revealed that JXUST-28 could sense Hg 2+ ions in aqueous solution via a quenching effect with a detection limit of 0.097 μM. Meanwhile, JXUST-28 can also be regenerated at least 5 times to detect Hg 2+ ions. In addition, light-emitting diode lamps, luminescent films, and test papers of JXUST-28 have been successfully developed for practical applications.

Background: Echinococcosis is a parasitic zoonotic disease that threatens human health and economic development. In China, 370 counties are endemic for echinococcosis. Qinghai-Tibet Plateau has the most patients and people at risk. Therefore, analyzing the societal factors related to susceptibility to the disease is critical for efficient prevention and control of echinococcosis., Methods: The demographic characteristics and lifestyle of echinococcosis cases were clustered using K-means cluster analysis to determine the main factors of risk of echinococcosis., Results: Middle-aged and young people as well as those with a low education level and herdsmen are at risk of contracting echinococcosis. Nomadism, domestic and feral dogs in the surrounding environment, and drinking heavily polluted natural surface water are the main behavioral risk factors. The cystic echinococcosis (CE) and alveolar echinococcosis (AE) cluster analysis focused on female, middle-aged, and young people, winter settlement and summer nomadism, and domestic and feral dogs in the surrounding environment. There were significant differences in lifestyle between Qinghai-Tibet Plateau cases and non-Qinghai-Tibet-Plateau cases., Conclusion: According to the distribution of cases and CE and AE, this study identified the factors of risk of echinococcosis in the Qinghai-Tibet Plateau and non-Qinghai-Tibet Plateau. Adapted control techniques appropriate for the various epidemic areas should be established to serve as a reference for echinococcosis prevention., (© 2022. The Author(s).)

The genus Colletotrichum includes important plant pathogens, endophytes, saprobes and human pathogens. Even though the polyphasic approach has facilitated Colletotrichum species identification, knowledge of the overall species diversity and host distribution is largely incomplete. To address this, we examined 952 Colletotrichum strains isolated from plants representing 322 species from 248 genera, or air and soil samples, from 87 locations in China, as well as 56 strains from Saudi Arabia, Thailand, Turkey, and the UK. Based on morphological characteristics and multi-locus phylogenetic analyses, the strains were assigned to 107 species, including 30 new species described in this paper and 18 new records for China. The currently most comprehensive backbone tree of Colletotrichum , comprising 16 species complexes (including a newly introduced C. bambusicola species complex) and 15 singleton species, is provided. Based on these analyses, 280 species with available molecular data are accepted in this genus, of which 139 have been reported in China, accounting for 49.6 % of the species. Colletotrichum siamense , C. karsti , C. fructicola , C. truncatum , C. fioriniae , and C. gloeosporioides were the most commonly detected species in China, as well as the species with the broadest host range. By contrast, 76 species were currently found to be associated with a single plant species or genus in China. To date, 33 Colletotrichum species have been exclusively reported as endophytes. Furthermore, we generated and assembled whole-genome sequences of the 30 new and a further 18 known species. The most comprehensive genome tree comprising 94 Colletotrichum species based on 1 893 single-copy orthologous genes was hence generated, with all nodes, except four, supported by 100 % bootstrap values. Collectively, this study represents the most comprehensive investigation of Colletotrichum diversity and host occurrence to date, and greatly enhances our understanding of the diversity and phylogenetic relationships in this genus. Taxonomic novelties: New species: Colletotrichum arecacearum F. Liu, W.P. Wu & L. Cai, Colletotrichum bicoloratum F. Liu, W.P. Wu & L. Cai, Colletotrichum bromeliacearum F. Liu, W.P. Wu & L. Cai, Colletotrichum buxi F. Liu, W.P. Wu & L. Cai, Colletotrichum chamaedoreae F. Liu, W.P. Wu & L. Cai, Colletotrichum crousii F. Liu, W.P. Wu & L. Cai, Colletotrichum danxiashanense F. Liu, W.P. Wu & L. Cai, Colletotrichum diversisporum F. Liu, W.P. Wu & L. Cai, Colletotrichum diversum F. Liu, W.P. Wu & L. Cai, Colletotrichum dolichoconidiophori F. Liu, W.P. Wu & L. Cai, Colletotrichum iris F. Liu, W.P. Wu & L. Cai, Colletotrichum monsterae F. Liu, W.P. Wu & L. Cai, Colletotrichum multiseptatum F. Liu, W.P. Wu & L. Cai, Colletotrichum nageiae F. Liu, W.P. Wu & L. Cai, Colletotrichum obovoides F. Liu, W.P. Wu & L. Cai, Colletotrichum parabambusicola F. Liu, W.P. Wu & L. Cai, Colletotrichum paraendophytum F. Liu, W.P. Wu & L. Cai, Colletotrichum reniforme F. Liu, W.P. Wu & L. Cai, Colletotrichum schimae F. Liu, W.P. Wu & L. Cai, Colletotrichum shivasii F. Liu, W.P. Wu & L. Cai, Colletotrichum sinuatum F. Liu, W.P. Wu & L. Cai, Colletotrichum subacidae F. Liu, Z.Y. Ma & L. Cai, Colletotrichum subsalicis F. Liu, W.P. Wu & L. Cai, Colletotrichum subvariabile F. Liu, W.P. Wu & L. Cai, Colletotrichum syngoniicola F. Liu, W.P. Wu & L. Cai, Colletotrichum telosmae F. Liu, W.P. Wu & L. Cai, Colletotrichum tibetense F. Liu, W.P. Wu & L. Cai, Colletotrichum variabile F. Liu, W.P. Wu & L. Cai, Colletotrichum zhaoqingense F. Liu, W.P. Wu & L. Cai. Colletotrichum zhejiangense Liu F, Ma ZY, Hou LW, Diao YZ, Wu WP, Damm U, Song S, Cai L (2022). Updating species diversity of Citation: Liu F, Ma ZY, Hou LW, Diao YZ, Wu WP, Damm U, Song S, Cai L (2022). Updating species diversity of Colletotrichum , with a phylogenomic overview. Studies in Mycology 101 : 1-56. doi: 10.3114/sim.2022.101.01., Competing Interests: The authors declare that there is no conflict of interest., (© 2022 Westerdijk Fungal Biodiversity Institute.)

A high performance liquid chromatography(HPLC) method was established to analyze the components in Shengjiang Powder(SJP) such as emodin and curcumin and explore its therapeutic effect on experimental autoimmune encephalomyelitis(EAE) mice. To be specific, HPLC was performed to determine the content of compounds in SJP such as emodin and curcumin. A total of 72 female SPF C57 BL/6 mice were randomized into control group(equivalent volume of ultrapure water, ig), model group(equivalent volume of ultrapure water, ig), low-, medium-, and high-dose SJP groups(SJP, ig), and positive control group(prednisone acetate, ig), 12 each group. EAE was induced in mice except the control group. Administration began from the first day after immunization. The general conditions, symptom score, and body weight of the mice were recorded. On the 21 st day, mouse brain tissues were separrated. Then hematoxylin-eosin(HE) staining and Luxol Fast Blue(LFB) staining were used to detect the pathological changes of brain tissues. Immunohistochemistry(IHC) was employed to determine the myelin basic protein(MBP) level, and Western blot the expression of occludin and claudin-5, as well as the levels of interleukin-6(IL-6) and proteins in the Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3) pathway and their phosphorylation levels. The mRNA expression of IL-6, JAK2, and STAT3 was detected by real-time quantitative polymerase chain reaction(qPCR). Finally, molecular docking of six main active components in SJP, including emodin and curcumin, with IL-6, JAK2 and STAT3 was performed, and the binding affinity was evaluated. The results showed that the established HPLC method demonstrated high precision, reproducibility, stability, and high recovery of samples. Compared with the model group, SJP reduced the clinical symptom score and alleviate the inflammatory infiltration of brain white matter and demyelination of EAE mice. At the same time, SJP increased the expression of occludin and claudin-5, down-regulated the mRNA expression of IL-6, JAK2, and STAT3, as well as the levels of IL-6/JAK/STAT3 proteins and the phosphorylation levels, with significant difference. Molecular docking suggested that the six active components in SJP had high binding energy with IL-6, JAK2, and STAT3 proteins. The established HPLC method is simple, accurate, and highly sensitive, which can simultaneously determine the content of emodin and curcumin in SJP. SJP may alleviate the clinical symptoms of EAE by inhibiting IL-6/JAK2/STAT3 signaling pathway, protecting the blood-brain barrier, and relieving the inflammatory response and demyelinization of brain tissue.

Echinococcosis is a serious zoonotic parasitic disease caused by infections with larval Echinococcus . The life cycle of Echinococcus involves a variety of animal hosts, including hoofed animals and rodents as intermediate hosts and carnivores as definitive hosts. The transmission of human echinococcosis is closely associated with the life cycle of E. granulosus and E. multilocularis among animal hosts in nature. This review summarizes the recent advances in the prevalence and influencing factors of E. granulosus and E. multilocularis infections in animal hosts, so as to provide insights into precision control of echinococcosis.

Background: We hypothesized that different BMI might have different impact on pre-operative MRI axillary lymph node (ALN) prediction accuracy and thereby subsequent surgical lymph node management. The aim of this study is to evaluate the effect of BMI on presentation, surgical treatment, and MRI performance characteristics of breast cancer with the main focus on ALN metastasis evaluation., Methods: The medical records of patients with primary invasive breast cancer who had pre-operative breast MRI and underwent surgical resection were retrospectively reviewed. They were categorized into 3 groups in this study: underweight (BMI < 18.5), normal (BMI of 18.5 to 24), and overweight (BMI > 24). Patients' characteristics, surgical management, and MRI performance for axillary evaluation between the 3 groups were compared., Results: A total of 2084 invasive breast cancer patients with a mean age of 53.4 ± 11.2 years were included. Overweight women had a higher rate of breast conserving surgery (56.7% vs. 54.5% and 52.1%) and initial axillary lymph node dissection (15.9% vs. 12.2% and 8.5%) if compared to normal and underweight women. Although the post-operative ALN positive rates were similar between the 3 groups, overweight women were significantly found to have more axillary metastasis on MRI compared with normal and underweight women (50.2% vs 37.7% and 18.3%). There was lower accuracy in terms of MRI prediction in overweight women (65.1%) than in normal and underweight women (67.8% and 76.1%)., Conclusion: Our findings suggest that BMI may influence the diagnostic performance on MRI on ALN involvement and the surgical management of the axilla in overweight to obese women with breast cancer., (© 2022. The Author(s).)

Circular RNAs (circRNAs) have been established to be involved in numerous processes in the human genome, but their function in vascular aging remains largely unknown. In this study, we aimed to characterize and analyze the function of a circular intronic RNA, ciPVT1, in endothelial cell senescence. We observed significant downregulation of ciPVT1 in senescent endothelial cells. In proliferating endothelial cells, ciPVT1 knockdown induced a premature senescence-like phenotype, inhibited proliferation, and led to an impairment in angiogenesis. An in vivo angiogenic plug assay revealed that ciPVT1 silencing significantly inhibited endothelial tube formation and decreased hemoglobin content. Conversely, overexpression of ciPVT1 in old endothelial cells delayed senescence, promoted proliferation, and increased angiogenic activity. Mechanistic studies revealed that ciPVT1 can sponge miR-24-3p to upregulate the expression of CDK4, resulting in enhanced Rb phosphorylation. Moreover, enforced expression of ciPVT1 reversed the senescence induction effect of miR-24-3p in endothelial cells. In summary, the present study reveals a pivotal role for ciPVT1 in regulating endothelial cell senescence and may have important implications in the search of strategies to counteract the development of age-associated vascular pathologies., (© 2021 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Background: Echinococcosis is a zoonotic parasitic disease caused by larval stages of cestodes belonging to the genus Echinococcus. The infection affects people's health and safety as well as agropastoral sector. In China, human echinococcosis is a major public health burden, especially in western China. Echinococcosis affects people health as well as agricultural and pastoral economy. Therefore, it is important to understand the prevalence status and spatial distribution of human echinococcosis in order to advance our knowledge of basic information for prevention and control measures reinforcement., Methods: Report data on echinococcosis were collected in 370 counties in China in 2018 and were used to assess prevalence and spatial distribution. SPSS 21.0 was used to obtain the prevalence rate for CE and AE. For statistical analyses and mapping, all data were processed using SPSS 21.0 and ArcGIS 10.4, respectively. Chi-square test and Exact probability method were used to assess spatial autocorrelation and spatial clustering., Results: A total of 47,278 cases of echinococcosis were recorded in 2018 in 370 endemic counties in China. The prevalence rate of human echinococcosis was 10.57 per 10,000. Analysis of the disease prevalence showed obvious spatial positive autocorrelation in globle spatial autocorrelation with two aggregation modes in local spatial autocorrelation, namely high-high and low-high aggregation areas. The high-high gathering areas were mainly concentrated in northern Tibet, western Qinghai, and Ganzi in the Tibetan Autonomous Region and in Sichuan. The low-high clusters were concentrated in Gamba, Kangma and Yadong counties of Tibet. In addition, spatial scanning analysis revealed two spatial clusters. One type of spatial clusters included 71 counties in Tibet Autonomous Region, 22 counties in Qinghai, 11 counties in Sichuan, three counties in Xinjiang Uygur Autonomous Region, two counties in Yunnan, and one county in Gansu. In the second category, six types of spatial clusters were observed in the counties of Xinjiang Uygur Autonomous Region, and the Qinghai, Gansu, and Sichuan Provinces., Conclusion: This study showed a serious prevalence of human echinococcosis with obvious spatial aggregation of the disease prevalence in China. The Qinghai-Tibet Plateau is the "hot spot" area of human echinococcosis in China. Findings from this study indicate that there is an urgent need of joint strategies to strengthen efforts for the prevention and control of echinococcosis in China, especially in the Qinghai-Tibet Plateau., Competing Interests: The authors have declared that no competing interests exist.

Background: Women with unilateral breast cancer are at an increased risk for the development of contralateral breast cancers. We hypothesis that combined breast MRI would detect more contralateral synchronous breast cancer than conventional imaging alone, and resulted in less contralateral metachronous breast cancer during follow-up., Methods: We retrospectively collected two groups of breast cancer patients diagnosed from 2009 to 2013 for evaluating the effectiveness and value of adding pre-operative breast MRI to conventional breast images (mammography and sonography) for detection of contralateral synchronous breast cancer. The new metachronous contralateral breast cancer diagnosed during follow-up was prospectively evaluated and compared., Results: Group A (n = 733) comprised patients who underwent conventional preoperative imaging and group B (n = 735) combined with MRI were enrolled and compared. Seventy (9.5%) of the group B patients were found to have contralateral lesions detected by breast MRI, and 65.7% of these lesions only visible with MRI. The positive predictive value of breast MRI detected contralateral lesions was 48.8%. With the addition of breast MRI to conventional imaging studies, more surgical excisions were performed in contralateral breasts (6% (44/735) versus 1.4% (10/733), P< 0.01), more synchronous contralateral breast cancer detected (2.9% (21/735) versus 1.1% (8/733), P = 0.02), and resulted in numerical less (2.2% (16/714) versus 3% (22/725), p = 0.3) metachronous contralateral breast cancer during a mean follow-up of 102 months., Conclusions: Our study provides useful estimates of the pre-operative breast MRI for the increased detection of contralateral synchronous breast cancer and less subsequent contralateral metachronous breast cancer., Competing Interests: The authors have declared that no competing interests exist.

Most randomized trials for acute promyelocytic leukemia (APL) have investigated highly selected patients under idealized conditions, and the findings need to be validated in the real world. We conducted a population-based study of all APL patients in Zhejiang Province, China, with a total population of 82 million people, to assess the generalization of all-trans retinoic acid (ATRA) and arsenic as front-line treatment. The outcomes of APL patients were also analyzed. Between January 2015 and December 2019, 1,233 eligible patients were included in the final analysis. The rate of ATRA and arsenic as front-line treatment increased steadily from 66.2% in 2015 to 83.3% in 2019, with no difference among the size of the center (≥5 or <5 patients per year, p = 0.12) or age (≥60 or <60 years, p = 0.35). The early death (ED) rate, defined as death within 30 days after diagnosis, was 8.2%, and the 3-year overall survival (OS) was 87.9% in the whole patient population. Age (≥60 years) and white blood cell count (>10 × 10 9 /L) were independent risk factors for ED and OS in the multivariate analysis. This population-based study showed that ATRA and arsenic as front-line treatment are widely used under real-world conditions and yield a low ED rate and a high survival rate, which mimic the results from clinical trials, thereby supporting the wider application of APL guidelines in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhu, Ma, Yu, Ouyang, Luo, Pei, Xu, Hu, Mo, Xu, Lan, Shen, Shou, Qian, Feng, Zhao, Jiang, Hu, Zhang, Qian, Wu, Wu, Qiu, Li, Lang, Chen, Chen, Guo, Cao, Jiang, Xia, Le, Zhao, Huang, Zhang, Lv, Hua, Hong, Zheng, Wang, Hu, Chen, Zhang, Tao, Xie, Kuang, Luo, Su, Guo, Wu, Jiang, Zhang, Zhang, Chen, Xu, Guo, Tu, Hu, Yan, Yao, Lou, Jin and the APL Cooperative Group of Zhejiang Province.)

Almost all prey live in habitats with predators with different hunting modes; however, most studies on predation have investigated the effects of only one predator at a time. In this study, we aimed to investigate whether qingbo (Spinibarbus sinensis), a common cyprinid fish, responds differently to active hunting and ambush predators and how qingbo responds when both types of predators coexist. Juvenile qingbo were subjected to catfish (Clarias fuscus, active hunter) exposure, snakehead fish (Channa argus, ambush hunter) exposure, or mixed predator exposure (catfish and snakehead coexistence) for a duration of 60 days. Then, their growth, behaviors, swimming performance, and metabolism were measured. Qingbo subjected to active hunting predator exposure exhibited decreased activity and predator inspection and improved fast-start escape performance compared to those in the control group. However, none of the parameters of the fish subjected to ambush predator exposure changed significantly. Fish subjected to mixed predator exposure exhibited improved fast-start escape performance but increased maintenance energy expenditure, whereas no changes were observed in any of the behavioral variables. Qingbo showed a stronger anti-predator response to active hunting predators than to ambush predators, suggesting that the fish exhibit a stronger anti-predator response to a current direct threat than to a potential threat (a predator exists nearby but seldom presents in attack behavior). Additionally, the response of prey fish to multiple predators was quite complex, and the coexistence and interaction of multiple predator species with different hunting modes may lead to serious stress responses and confound the prey's behavioral responses to each predator., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: The optimal axillary lymph node (ALN) management strategy in patients diagnosed with ductal carcinoma in situ (DCIS) preoperatively remains controversial. The value of breast magnetic resonance imaging (MRI) to predict ALN metastasis pre-operative DCIS patients was evaluated., Methods: Patients with primary DCIS with or without pre-operative breast MRI evaluation and underwent breast surgery were recruited from single institution. The value of breast MRI for ALN evaluation, predictors of breast and ALN surgeries, upgrade from DCIS to invasive cancer, and ALN metastasis were analyzed., Results: A total of 682 cases with pre-operative diagnosis of DCIS were enrolled in current study. The rate of upgrade to invasive cancer were found in 34.2% of specimen, and this upgrade rate is 23% for patients who received breast conserving surgery and 40.7% for mastectomy (p < 0.01). Large pre-operative imaging tumor size and post-operative invasive component were risk factors to ALN metastasis. Breast MRI had 53.8% sensitivity, 77.8% specificity, 14.9% positive predictive value, 95.9% negative predictive value (NPV), and 76.2% accuracy to predict ALN metastasis in pre-OP DCIS patients. In MRI node-negative breast cancer patients with MRI tumor size < 3 cm, the NPV was 96.4%, and all these false-negative cases were N1. Pre-OP diagnosed DCIS patients with MRI tumor size < 3 cm and node negative suitable for BCS could safely omit SLNB if whole breast radiotherapy is to be performed., Conclusion: Breast MRI had high NPV to predict ALN metastasis in pre-OP DCIS patients, which is useful and could be provided as shared decision-making reference., (© 2021. The Author(s).)

Endothelial cell senescence is one of the most important causes of vascular dysfunction and atherosclerosis. Circular RNAs (circRNAs) are endogenous RNA molecules with covalently closed-loop structures, which have been reported to be abnormally expressed in many human diseases. However, the potential role of circRNAs in endothelial cell senescence and atherosclerosis remains largely unknown. Here, we compared the expression patterns of circRNAs in young and senescent human endothelial cells with RNA sequencing. Among the differentially expressed circRNAs, circGNAQ, a circRNA enriched in vascular endothelium, was significantly downregulated in senescent endothelial cells. circGNAQ silencing triggered endothelial cell senescence, as determined by a rise in senescence-associated β-galactosidase activity, reduced cell proliferation, and suppressed angiogenesis; circGNAQ overexpression showed the opposite effects. Mechanistic studies revealed that circGNAQ acted as an endogenous miR-146a-5p sponge to increase the expression of its target gene PLK2 by decoying the miR-146a-5p, thereby delaying endothelial cell senescence. In vivo studies showed that circGNAQ overexpression in the endothelium inhibited endothelial cell senescence and atherosclerosis progression. These results suggest that circGNAQ plays critical roles in endothelial cell senescence and consequently the pathogenesis of atherosclerosis, implying that the management of circGNAQ provides a potential therapeutic approach for limiting the progression of atherosclerosis., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)

Key Message: In the soybean variant V94-5152, a BCMV-resistance gene was mapped near to the region of SMV-resistance Rsv4 locus, raising a possibility that V94-5152 may rely on Rsv4 locus to resist against both SMV and BCMV. Both Soybean mosaic virus (SMV) and Bean common mosaic virus (BCMV) can induce soybean mosaic diseases, but few studies have explored soybean resistance against BCMV so far. In this study, V94-5152, a soybean variant resistant to BCMV and SMV, was crossed with a susceptible cultivar, Williams 82 to map the resistance gene. By inoculating 292 F 2 individuals with a BCMV isolate HZZB011, a segregation ratio of 3 resistant: 1 susceptible was observed, suggesting that V94-5152 possesses a single-dominant resistance gene against BCMV-HZZB011. Bulk segregation analysis (BSA) then revealed that the resistance gene is closely linked to BARCSOYSSR&#95;02&#95;0617, a simple sequence repeat (SSR) marker on chromosome 2. Genotyping neighboring SSR markers among the 292 F 2 individuals enabled us to draw a genetic linkage map, which indicated that the BCMV-resistance gene is located 0.2 cM downstream of BARCSOYSSR&#95;02&#95;0617. Amplification and sequencing ten candidate genes (Glyma02g121300 to Glyma02g122200) around this marker then revealed four genes containing nonsynonymous changes or indels. Also, this location is near to the recently cloned SMV-resistance Rsv4 locus from the cultivar Peking. By obtaining ten more sequences of Rsv4 locus from cultivated and wild soybean materials, we further investigated the variation and evolutionary patterns of this virus-resistance locus. It was evident that positive selections had been acting on this locus, with one critical amino acid change (R55P) shared by all resistance soybeans tested., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The size and quality of chemical libraries to the drug discovery pipeline are crucial for developing new drugs or repurposing existing drugs. Existing techniques such as combinatorial organic synthesis and high-throughput screening usually make the process extraordinarily tough and complicated since the search space of synthetically feasible drugs is exorbitantly huge. While reinforcement learning has been mostly exploited in the literature for generating novel compounds, the requirement of designing a reward function that succinctly represents the learning objective could prove daunting in certain complex domains. Generative adversarial network-based methods also mostly discard the discriminator after training and could be hard to train. In this study, we propose a framework for training a compound generator and learn a transferable reward function based on the entropy maximization inverse reinforcement learning (IRL) paradigm. We show from our experiments that the IRL route offers a rational alternative for generating chemical compounds in domains where reward function engineering may be less appealing or impossible while data exhibiting the desired objective is readily available., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: To investigate the effectiveness of a new health education pathway for echinococcosis control among primary school students in regions highly prevalent for echinococcosis in China., Methods: Six primary schools were randomly selected from echinococcosis hyper-endemic regions, with 13 classes assigned to the intervention group and 9 to the control group, and all students in these 21 classes were recruited as the study subjects. Echinococcosis health education was performed through the pathway of assessing the current status-strengthening the building of teaching resources-focusing on practices in the intervention group, while routine health education was given in the control group. A questionnaire survey was performed to assess the score of echinococcosis control knowledge (including theoretical knowledge score and mean daily practical capability score) before and after the health education interventions to evaluate the effectiveness of this new health education pathway for echinococcosis control., Results: The mean score of echinococcosis control knowledge was 68.86 ± 18.70 points at baseline, with the mean theoretical knowledge score of 40.97 ± 10.75 points, and the mean daily practical capability score of 27.89 ± 12.50 points. Clustering analysis showed three types of populations, including "unsatisfactory", "learn and apply creatively", and "rote learning", which accounted for 24.62% (240/975), 45.74% (446/975) and 29.64% (289/975), respectively. The mean score of echinococcosis control knowledge was 81.08 ± 18.15 points in the intervention group during the final assessment, with the mean theoretical knowledge score of 43.65 ± 9.40 points, and the mean daily practical capability score of 37.43 ± 12.22 points, and both were significantly higher relative to baseline ( t = -4.201 and -15.202, both P values < 0.01). The mean score of echinococcosis control knowledge was comparable between at baseline (70.55 ± 19.46 points) and final assessment (71.74 ± 19.37 points) in the control group ( t = -0.87, P > 0.05)., Conclusions: The awareness of echinococcosis control knowledge is fair among primary school students in echinococcosis hyper-endemic regions; however, the capability of combining theoretical learning and practices requires to be improved. The health education mode based on the pathway of assessing the current status-strengthening the building of teaching resources-focusing on practices seems to remarkably improve the understanding of echinococcosis control knowledge among primary school students in echinococcosis hyper-endemic regions.

Echinococcoses are serious zoonotic diseases in China's vast, western and north-western pastoral areas that has one of the highest prevalence in the world. The two most common forms, cystic echinococcosis (CE) and alveolar echinococcosis (AE), are co-epidemic in some areas causing a grave threat to people's health and economic development. Echinococcus spp. are transmitted through domestic, sylvatic and mixed cycles involving many kinds of host. Successful transmission requires a favourable environment for the growth of the parasites and survival of their eggs, while the unique customs and religious beliefs in the endemic areas pose a challenge to the prevention and control of these parasites. Based on previous epidemiological studies, this paper reviews the particular factors affecting the transmission of Echinococcus parasites in China, with a focus on biological (parasite genotype and the species, age, sex and density of hosts), environmental (landscape and climate) and social (age, gender, ethnicity, education, occupation, life style, cultural customs, living conditions and hygiene practices of humans in the endemic areas). These three factors interact with each other and jointly determine the parasites' transmission intensity, the study of which supports the formulation of the strategies and measures that are significant for control of these infections., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Amorphous/crystalline nanolaminate composites have aroused extensive research interest because of their high strength and good plasticity. In this paper, the nanoindentation behavior of Cu 64 Zr 36 /Cu amorphous/crystalline nanolaminates (ACNLs) is investigated by molecular dynamics (MD) simulation while giving special attention to the plastic processes occurring at the interface. The load-displacement curves of ACNLs reveal small fluctuations associated with shear transformation zone (STZ) activation in the amorphous layer, whereas larger fluctuations associated with dislocations emission occur in the crystalline layer. During loading, local STZ activation occurs and the number of STZs increases as the indentation depth in the amorphous layer increases. These STZs are mostly located around the indenter, which correlates to the high stresses concentrated around the indenter. When the indenter penetrates the crystalline layer, dislocations emit from the interface of amorphous/crystalline, and their number increases with increasing indentation depth. During unloading, the overall number of STZs and dislocations decreases, while other new STZs and dislocations become activated. These results are discussed in terms of stress distribution, residual stresses, indentation rate and indenter radius.

Mallotus japonicus is a shrub species in the family of Euphorbiaceae. The study of plastome would be helpful for its phylogenetic study and species identification. The total length of complete plastome for Mallotus japonicus is of 164,912 bp, with typical part-four structure and gene content of angiosperm plastome, including two inverted repeat (IR) regions of 27,829 bp, a large single-copy (LSC) region of 90,319 bp, and a small single-copy (SSC) region of 18,935 bp. The plastome contains 125 genes, consisting of 80 unique protein-coding genes, 31 unique tRNA gene, four unique rRNA genes (5S rRNA, 4.5S rRNA, 16S rRNA, and 23S rRNA), and five pseudogenes. The overall G/C content in the plastome of Mallotus japonicus is 40.2%. The phylogenetic analysis indicates that M. japonicus is closer to M. peltatus than other species in this study. The complete plastome sequence is conducive to the exploitation and utilization of Euphorbiaceae resources and the phylogenetic study in future., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: Leishmaniasis is a regional infectious disease caused by the bite of Leishmania -carrying sandflies. The clinical symptoms include prolonged fever, spleen enlargement, anemia, emaciation, leukopenia, and increased serum globulin levels. If not appropriately treated, patients may die of complications caused by leishmaniasis within 1-2 years after the onset of the illness. Therefore, further investigation of the mechanisms of infection by this pathogen is required. Here, an epidemiological study of Leishmania carriers was conducted. The potential mechanism of infection through domestic animals as carriers of the parasite was investigated to identify potential reservoir hosts for Leishmania., Methods: The rK-39 strip test was performed on blood samples from previously infected patients. Blood samples were collected from the patients and their families. The blood, liver, spleen, and diaphragm muscle samples were collected from livestock. To perform nested polymerase chain reaction (PCR), DNA was extracted and the internal transcribed spacer sequence was used. The amplified products were then subjected to restriction fragment length polymorphism and phylogenetic analyses., Results: Among previously infected patients, 40% (12/30) showed positive results in the rK-39 strip test. The nested PCR positive rates for previously infected patients/relatives and livestock samples were 86% (77/90) and 80% (8/10), respectively. Moreover, the phylogenetic analysis showed that the pathogen was Leishmania infantum . Dogs, patients, and domesticated animals carrying Leishmania were found to be a potential source of infection for leishmaniasis., Conclusions: The results of this study provide a basis for developing disease prevention and control strategies for leishmaniasis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Han, Chen, Yang, Feng and Wu.)

Aim: To study the imaging features of leukoaraiosis (LA) and hemorrhage in cerebral amyloid angiopathy (CAA) patients., Methods: The earliest MRI images of probable CAA patients and non-CAA patients were collected. The characteristics of LA in the two groups were analyzed. Cerebral micro bleeding (CMB), superficial siderosis (SS), and intracranial hemorrhage (ICH) were recorded in the follow-up study. The space relationship between CMB or SS and ICH was assessed., Results: We found that 10/21 (47.6%) patients had occipital prominent LA and 14/21 (66.7%) patients had subcortical punctate LA before the ICH, which was higher than that of the ones in the control group ( p = 0.015 and 0.038, respectively). The recurrence rate of ICH was 100% (3/3) in patients with diffuse SS and 36.4% (4/11) in patients without. The recurrence rate of ICH was 60% (3/5) in patients with multiple-lobe CMBs and 44.4% (4/9) in those without. The location of the ICH and CMB was inconsistent. ICH occurred in the ipsilateral cerebral hemisphere of SS in three patients with diffuse SS., Conclusion: LA, diffuse SS, and multiple-lobe CMBs are important imaging characteristics of CAA, which may help make early diagnosis and predict the recurrence of ICH., Competing Interests: Conflict of interest: The authors state no conflict of interests., (© 2021 Shan-chun Zhang et al., published by De Gruyter.)

The middle cerebral artery occlusion (MCAO) model has been extensively applied to study ischaemic stroke. This study attempted to clarify effect of bone marrow stromal cells (BMSCs) on infarct injury of MCAO rats. BMSCs were isolated and identified by staining CD29/CD44 and CD31/CD45. CX3CL1 silencing vector (pLVX-shRNA-CX3CL1) was generated and infected to BMSCs. pLVX-shRNA-CX3CL1 infected BMSCs were transplanted into brain tissue of MCAO rats. Real-time PCR was used to determine CX3CL1 expression. Infarct areas were stained with TTC to evaluate infarct size. Double-staining immunofluorescence was conducted to determine anti-inflammatory type CD206 and pro-inflammatory type tumour necrosis factor a (TNF-a) microglia. Isolated BMSCs were positively presented for CD29/CD44, and negatively for CD31/CD45. CX3CL1 was significantly lower in the BMSC + pLVX-shRNA2-CX3-CL1 group compared to the BMSCs + pLVX group (p < 0.05). According to TTC and neurological scores, MCAO rats were successfully generated. BMSCs transplantation significantly increased CD206 microglia and decreased TNF-a microglia. However, shRNA-CX3CL1-infected BMSCs remarkably reduced CD206 microglia and enhanced TNF-a microglia compared to the MCAO + BMSCs group. In conclusion, BMSCs reverse microglia from pro-inflammatory type TNF-a microglia to anti-inflammatory type CD206 microglia in the infarct region of MCAO rats (3rd to 7th days post BMSC transplantation), through triggering of CX3CL1 secretion. Therefore, the potential effects of CX3CL1 secreted by BMSCs would provide an insight for stem cell-dependent therapeutic strategies in treating ischaemic stroke-associated disorders.

Aging is a complex biological process closely linked with the occurrence and development of age-related diseases. Despite recent advances in lifestyle management and drug therapy, the late diagnosis of these diseases causes severe complications, usually resulting in death and consequently impacting social economies. Therefore, the identification of reliable biomarkers and the creation of effective treatment alternatives for age-related diseases are needed. Circular RNAs (circRNAs) are a novel class of RNA molecules that form covalently closed loops capable of regulating gene expression at multiple levels. Several studies have reported the emerging functional roles of circRNAs in various conditions, providing new perspectives regarding cellular physiology and disease pathology. Notably, accumulating evidence demonstrates the involvement of circRNAs in the regulation of age-related pathologies, including cardio-cerebrovascular disease, neurodegenerative disease, cancer, diabetes, rheumatoid arthritis, and osteoporosis. Therefore, the association of circRNAs with these age-related pathologies highlights their potential as diagnostic biomarkers and therapeutic targets for better disease management. Here, we review the biogenesis and function of circRNAs, with a special focus on their regulatory roles in aging-related pathologies, as well as discuss their potential as biological biomarkers and therapeutic targets for these diseases., Competing Interests: Conflict of Interest The authors declare no conflict of interest., (copyright: © 2020 Pan et al.)

The drug discovery stage is a vital aspect of the drug development process and forms part of the initial stages of the development pipeline. In recent times, machine learning-based methods are actively being used to model drug-target interactions for rational drug discovery due to the successful application of these methods in other domains. In machine learning approaches, the numerical representation of molecules is critical to the performance of the model. While significant progress has been made in molecular representation engineering, this has resulted in several descriptors for both targets and compounds. Also, the interpretability of model predictions is a vital feature that could have several pharmacological applications. In this study, we propose a self-attention-based multi-view representation learning approach for modeling drug-target interactions. We evaluated our approach using three benchmark kinase datasets and compared the proposed method to some baseline models. Our experimental results demonstrate the ability of our method to achieve competitive prediction performance and offer biologically plausible drug-target interaction interpretations., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To explore the correlation between preoperative serum hyaluronic acid (HA) level and prognosis of breast cancer patients. Methods: The 98 patients with breast cancer who underwent surgical treatment in the Oncology Department of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine from January 2004 to November 2014 in a historical cohort were included, aged (52.5±9.4) years.The preoperative serum HA contents of the patients were detected. According to the median of 53.7 μg/L, the patients were divided into high and low groups with 49 patients in each group.The χ 2 test was used to analyze the correlation between the serum HA content and the general clinical data of the patients, and the Kaplan-Meier method, Log-rank test and multivariate Cox regression model wereusedto analyze the correlation between HA content and patients' survival. Results: The percentages of patients with high HA levels in menopause and non-menopause patientswere 55.7% and 40.5%, respectively; in progesterone receptor (PR) positive and negative patients were 54.1% and 43.2%, respectively; in estrogen receptor (ER) positive and negative patients were 45.7% and 60.7%, respectively; in Ki-67 positive and negative patients were 55.6% and 43.2%, respectively; in the tumor size stage TⅠ, TⅡ, TⅢ, and TⅣ patients were 50.0%, 41.7%, 72.7%, and 1/1, respectively; in lymph node metastasis and non-metastasispatients were 45.7% and 53.8%, respectively. There was no significant correlation between the level of HA and the menopausal status, the expressions of PR, ER and Ki-67, tumor size, and lymph node metastasis in breast cancer patients (χ²=2.128, 1.086, 1.800, 1.485, 4.273, 0.656, P >0.05). Patients with high HA levels accounted for 30.9% of patients aged 52 years or less and 74.4% of patients older than 52 years (χ²=18.274, P =0.000); 43.4% of patients with early TNM and 72.7% of patients with advanced TNM (χ²=5.861, P =0.015); 45.2% of patients without distant metastasis and 78.6% of patients with distant metastasis (χ²=5.333, P =0.023); 38.1% of Her-2 negative patients and 58.9% of Her-2 positive patients(χ²=4.167, P =0.041); and the median survival of patients with high HA levels was 70 months, which was shorter than 83 months for patients with low HA levels (χ²=6.799, P =0.007). Therefore, ahigh HA content predicts an older age, a later tumor stage, higher risk of distant metastasis, positive expression of Her-2 and shorter survival. Multivariate Cox regression model analysis suggested that high levels of serum HA may be a risk factor for patients' survival, with HR (95% CI ) value of 9.98 (1.16-85.88) and P value of 0.036. Conclusion: The high level of preoperative serum HA has a certain correlation with the poor prognosis of breast cancer patients.

Talaromyces is a monophyletic genus containing seven sections. The number of species in Talaromyces grows rapidly due to reliable and complete sequence data contributed from all over the world. In this study agricultural soil samples from Fujiang, Guangdong, Jiangxi, Shandong, Tibet and Zhejiang provinces of China were collected and analyzed for fungal diversity. Based on a polyphasic approach including phylogenetic analysis of partial ITS, BenA , CaM and RPB2 gene sequences, macro- and micro-morphological analyses, six of them could not be assigned to any described species, and one cannot be assigned to any known sections. Morphological characters as well as their phylogenetic relationship with other Talaromyces species are presented for these putative new species. Penicillium resedanum is combined in Talaromyces section Subinflati as T. resedanus ., (Bing-Da Sun, Amanda J. Chen, Jos Houbraken, Jens C. Frisvad, Wen-Ping Wu, Hai-Lei Wei, Yu-Guang Zhou, Xian-Zhi Jiang, Robert A. Samson.)

CircFOXO3 plays an important role in the pathogenesis of coronary artery disease (CAD). Single nucleotide polymorphisms (SNPs) at circRNA flanking introns may change its back-splicing and influence circRNA formation. Here, we aimed to investigate the influence of the polymorphisms at the circFOXO3 flanking introns on individual susceptibility to CAD. A total of 1185 individuals were included in the case-control study. In a multivariate logistic regression analysis, we determined that the rs12196996 G variant was significantly associated with increased CAD risk (OR = 1.36, P = 0.014). A similar trend of the association was observed in the recessive model (OR = 2.57, P = 0.003). Stratified analysis revealed a more significant association with CAD risk among younger subjects and non-smokers. Consistent with these results, the haplotype rs12196996G-rs9398171C containing rs12196996G allele was also associated with increased CAD risk (OR = 1.31, P = 0.013). Further investigation revealed that the rs12196996 GG genotype was associated with decreased circFOXO3 expression, but not linear FOXO3 levels. Taken together, our data provide the first evidence that the rs12196996 polymorphism at the circFOXO3 gene flanking intron is associated with CAD risk in the Chinese Han population, which is probably due to influence circFOXO3 levels.

Background: Exosomes exist in almost all body fluid and contain diverse biological contents which may be reflective of disease state. Circular RNAs (circRNAs) are stable in structure and have a long half-life in exosomes without degradation, thus making them reliable biomarkers. However, the potential of exosomal circRNAs as biomarkers of coronary artery disease (CAD) remains to be established. Here, we aimed to investigate the expression levels and the potential use of exosomal circRNAs as diagnostic biomarkers for CAD., Methods: CircRNA expression levels in exosomes obtained from three plasma samples of CAD patients and three paired controls were analyzed using RNA sequencing. Exosomal circRNAs obtained in the profiling phase were then verified in two-center validation cohorts. Finally, the ability of exosomal circRNAs, adjusting for Framingham Heart Study (FHS) risk factors, was determined to discriminate between CAD patients and non-CAD controls., Results: 355 circRNAs were differentially expressed between these two groups: 164 were upregulated, and 191 were downregulated. Here, we selected the potential circRNAs (fold change > 4, P < 0.05) as candidate biomarkers for further validation. Our data showed that only hsa&#95;circ&#95;0005540 was significantly associated with CAD ( P < 0.0001). After adjustment for risk factors, hsa&#95;circ&#95;0005540 showed a high discriminatory power for CAD in ROC analyses (AUC = 0.853; 95%confidence interval (CI) = 0.799 - 0.906, P < 0.001)., Conclusion: Our results suggest that plasma exosomal hsa&#95;circ&#95;0005540 can be used as a promising diagnostic biomarker of CAD., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2020 Wei-peng Wu et al.)

Echinococcosis is considered by the World Health Organization (WHO) to be a neglected zoonotic disease in the world. Some Tibetan communities were found to be highly endemic for echinococcosis just 20 years ago. Until recently, we were able to understand the overall disease burden of echinococcosis in Tibetan communities after prevalence data being available from nationwide investigations from 2012 to 2016. Data were abstracted from 9 publications regarding to echinococcosis prevalence between 2016-2018; from 10 data bases on echinococcosis prevalence for 151 Tibetan counties; and statistics of population, Gross Domestic Product (GDP) and health staff from 44 local statistic bureaus and government websites at provincial, prefecture and county level, and 2 books of provincial yearly statistics. These data were used to estimate the Disability Adjusted Life Years (DALYs) due to cystic echinococcosis (CE) and alveolar echinococcosis (AE). The distribution of DALYs was presented geographically and economically. The echinococcosis DALYs in the Tibetan communities were estimated to be 126,159 (95%UI 122,415-137,675) annually using the method recommended by WHO. AE DALYs were estimated to be 105,829 (95%UI 101,969-117,090), which were more than CE DALYs of 20,330 (95%UI 19,690-21,581). Echinococcosis affects people more in underdeveloped areas. There was a tendency that a higher echinococcosis DALYs were usually correlated a higher altitude. Health services are also poorly provided in terms of number of health staff of 5.05 per 1000 population in comparison with the national average of 5.8 per 1000 population. The data suggest that the echinococcosis burden in the center region of Qinghai-Tibet plateau is higher than that of other regions, and consequently more control and health services should be provided to the region., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest concerning the MS “Disease burden of echinococcosis in Tibetan communities-a significant public health issue in an underdeveloped region of western China”., (Copyright © 2019 Elsevier B.V. All rights reserved.)