bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of the microbiota dynamics associated with Moniliophthora roreri, causal agent of cocoa frosty pod rot disease, reveals new viral species
Authors: Reyes Brayan Maudiel Diaz , Fonseca Paula Luize Camargos , Heming Neander Marcel , Conceição Lucas Barbosa de Amorim , Nascimento Katiucia Ticila de Souza , Gramacho Karina Peres , Arevalo-Gardini Enrique , Pirovani Carlos Priminho , Aguiar Eric Roberto Guimarães Rocha
Published: February 2023

Introduction

Theobroma cacao, the cocoa tree, is a target for pathogens, such as fungi from the genera Phytophthora, Moniliophthora, Colletotrichum, Ceratocystis, among others. Some cacao pathogens are restricted to specific regions of the world, such as the Cacao swollen shoot virus (CSSV) in West African countries, while others are expanding geographically, such as Moniliophthora roreri in the Americas. M. roreri is one of the most threatening cacao pathogens since it directly attacks the cacao pods driving a significant reduction in production, and therefore economic losses. Despite its importance, the knowledge about the microenvironment of this pathogen and the cocoa pods is still poorly characterized.

Methods

Herein we performed RNA sequencing of spores in differential stages of culture in a medium supplemented with cacao pod extract and mycelium collected of the susceptible variety ICT 7121 naturally infected by the pathogen to evaluate the diversity and transcriptional activity of microorganisms associated with the in vitro sporulation of M. roreri.

Results

Our data revealed a great variety of fungi and bacteria associated with M. roreri, with an exceptional diversity of individuals from the genus Trichoderma sp. Interestingly, the dynamics of microorganisms from different kingdoms varied proportionally, suggesting they are somehow affected by M. roreri culture time. We also identified three sequences similar to viral genomes from the Narnaviridae family, posteriorly confirmed by phylogenetic analysis as members of the genus Narnavirus. Screening of M. roreri public datasets indicated the virus sequences circulating in samples from Ecuador, suggesting a wide spread of these elements. Of note, we did not identify traces of the viral sequences in the M. roreri genome or DNA sequencing, restricting the possibility of these sequences representing endogenized elements.

Discussion

To the best of our knowledge, this is the first report of viruses infecting the fungus of the genus Moniliophthora and only the third description of viruses that are able to parasite elements from the Marasmiaceae family.
Identification of natural compounds as SARS-CoV-2 inhibitors via molecular docking and molecular dynamic simulation
Authors: Han Tiantian , Luo Ziqing , Ji Lichun , Wu Peng , Li Geng , Liu Xiaohong , Lai Yanni
Published: February 2023

Background

Base mutations increase the contagiousness and transmissibility of the Delta and Lambda strains and lead to the severity of the COVID-19 pandemic. Molecular docking and molecular dynamics (MD) simulations are frequently used for drug discovery and relocation. Small molecular compounds from Chinese herbs have an inhibitory effect on the virus. Therefore, this study used computational simulations to investigate the effects of small molecular compounds on the spike (S) protein and the binding between them and angiotensin-converting enzyme 2 (ACE2) receptors.

Methods

In this study, molecular docking, MD simulation, and protein–protein analysis were used to explore the medicinal target inhibition of Chinese herbal medicinal plant chemicals on SARS-CoV-2. 12,978 phytochemicals were screened against S proteins of SARS-CoV-2 Lambda and Delta mutants.

Results

Molecular docking showed that 65.61% and 65.28% of the compounds had the relatively stable binding ability to the S protein of Lambda and Delta mutants (docking score ≤ −6). The top five compounds with binding energy with Lambda and Delta mutants were clematichinenoside AR2 (−9.7), atratoglaucoside,b (−9.5), physalin b (−9.5), atratoglaucoside, a (−9.4), Ochnaflavone (−9.3) and neo-przewaquinone a (−10), Wikstrosin (−9.7), xilingsaponin A (−9.6), ardisianoside G (−9.6), and 23-epi-26-deoxyactein (−9.6), respectively. Four compounds (Casuarictin, Heterophylliin D, Protohypericin, and Glansrin B) could interact with S protein mutation sites of Lambda and Delta mutants, respectively, and MD simulation results showed that four plant chemicals and spike protein have good energy stable complex formation ability. In addition, protein–protein docking was carried out to evaluate the changes in ACE2 binding ability caused by the formation of four plant chemicals and S protein complexes. The analysis showed that the binding of four plant chemicals to the S protein could reduce the stability of the binding to ACE2, thereby reducing the replication ability of the virus.

Conclusion

To sum up, the study concluded that four phytochemicals (Casuarictin, Heterophylliin D, Protohypericin, and Glansrin B) had significant effects on the binding sites of the SARS-CoV-2 S protein. This study needs further in vitro and in vivo experimental validation of these major phytochemicals to assess their potential anti-SARS-CoV-2.

Graphical abstract
Immobilization of bacterial mixture of Klebsiella variicola FH-1 and Arthrobacter sp. NJ-1 enhances the bioremediation of atrazine-polluted soil environments
Authors: Pan Zequn , Wu Yulin , Zhai Qianhang , Tang Yanan , Liu Xuewei , Xu Xuanwei , Liang Shuang , Zhang Hao
Published: February 2023

In this study, the effects of the immobilized bacterial mixture (IM-FN) of Arthrobacter sp. NJ-1 and Klebsiella variicola strain FH-1 using sodium alginate-CaCl2 on the degradation of atrazine were investigated. The results showed that the optimal ratio of three types of carrier materials (i.e., rice straw powder, rice husk, and wheat bran) was 1:1:1 with the highest adsorption capacity for atrazine (i.e., 3774.47 mg/kg) obtained at 30°C. On day 9, the degradation efficiency of atrazine (50 mg/L) reached 98.23% with cell concentration of 1.6 × 108  cfu/ml at pH 9 and 30°C. The Box–Behnken method was used to further optimize the culture conditions for the degradation of atrazine by the immobilized bacterial mixture. The IM-FN could be reused for 2–3 times with the degradation efficiency of atrazine maintained at 73.0% after being stored for 80 days at 25°C. The population dynamics of IM-FN was explored with the total soil DNA samples specifically analyzed by real-time PCR. In 7 days, the copy numbers of both PydC and estD genes in the IM-FN were significantly higher than those of bacterial suspensions in the soil. Compared with bacterial suspensions, the IM-FN significantly accelerated the degradation of atrazine (20 mg/kg) in soil with the half-life shortened from 19.80 to 7.96 days. The plant heights of two atrazine-sensitive crops (wheat and soybean) were increased by 14.99 and 64.74%, respectively, in the soil restored by immobilized bacterial mixture, indicating that the IM-FN significantly reduced the phytotoxicity of atrazine on the plants. Our study evidently demonstrated that the IM-FN could significantly increase the degradation of atrazine, providing a potentially effective bioremediation technique for the treatment of atrazine-polluted soil environment and providing experimental support for the wide application of immobilized microorganism technology in agriculture.
Pseudorabies virus exploits N6-methyladenosine modification to promote viral replication
Authors: Yu Pei-Lun , Wu Rui , Cao San-Jie , Wen Yi-Ping , Huang Xiao-Bo , Zhao Shan , Lang Yi-Fei , Zhao Qin , Lin Ju-Chun , Du Sen-Yan , Yu Shu-Min , Yan Qi-Gui
Published: February 2023

Introduction

Pseudorabies virus (PRV) is the pathogenic virus of porcine pseudorabies (PR), belonging to the Herpesviridae family. PRV has a wide range of hosts and in recent years has also been reported to infect humans. N6-methyladenosine (m6A) modification is the major pathway of RNA post-transcriptional modification. Whether m6A modification participates in the regulation of PRV replication is unknown.

Methods

Here, we investigated that the m6A modification was abundant in the PRV transcripts and PRV infection affected the epitranscriptome of host cells. Knockdown of cellular m6A methyltransferases METTL3 and METTL14 and the specific binding proteins YTHDF2 and YTHDF3 inhibited PRV replication, while silencing of demethylase ALKBH5 promoted PRV output. The overexpression of METTL14 induced more efficient virus proliferation in PRV-infected PK15 cells. Inhibition of m6A modification by 3-deazaadenosine (3-DAA), a m6A modification inhibitor, could significantly reduce viral replication.

Results and Discussion

Taken together, m6A modification played a positive role in the regulation of PRV replication and gene expression. Our research revealed m6A modification sites in PRV transcripts and determined that m6A modification dynamically mediated the interaction between PRV and host.
A genome-wide cross-cancer meta-analysis highlights the shared genetic links of five solid cancers
Authors: Guo Hongping , Cao Wenhao , Zhu Yiran , Li Tong , Hu Boheng
Published: February 2023

Breast, ovarian, prostate, lung, and head/neck cancers are five solid cancers with complex interrelationships. However, the shared genetic factors of the five cancers were often revealed either by the combination of individual genome-wide association study (GWAS) approach or by the fixed-effect model-based meta-analysis approach with practically impossible assumptions. Here, we presented a random-effect model-based cross-cancer meta-analysis framework for identifying the genetic variants jointly influencing the five solid cancers. A comprehensive genetic correlation analysis (genome-wide, partitioned, and local) approach was performed by using GWAS summary statistics of the five cancers, and we observed three cancer pairs with significant genetic correlation: breast–ovarian cancer (rg = 0.221, p = 0.0003), breast–lung cancer (rg = 0.234, p = 7.6 × 10−6), and lung–head/neck cancer (rg = 0.652, p = 0.010). Furthermore, a random-effect model-based cross-trait meta-analysis was conducted for each significant cancer pair, and we found 27 shared genetic loci between breast and ovarian cancers, 18 loci between breast and lung cancers, and three loci between lung and head/neck cancers. Functional analysis indicates that the shared genes are enriched in human T-cell leukemia virus 1 infection (HTLV-1) and antigen processing and presentation (APP) pathways. Our study investigates the shared genetic links across five solid cancers and will help to reveal their potential molecular mechanisms.
Definition of a microbial signature as a predictor of endoscopic post-surgical recurrence in patients with Crohn’s disease
Authors: Oliver Lia , Camps Blau , Julià-Bergkvist David , Amoedo Joan , Ramió-Pujol Sara , Malagón Marta , Bahí Anna , Torres Paola , Domènech Eugeni , Guardiola Jordi , Serra-Pagès Mariona , Garcia-Gil Jesus , Aldeguer Xavier
Published: February 2023

Background and aims: Although there are several effective drugs for the treatment of Crohn’s disease (CD), almost 70% of patients will require surgical resection during their lifetime. This procedure is not always curative, as endoscopic recurrence occurs in 65%–90% of patients in the first year after surgery. The aetiology of the recurrence is unknown; however, several studies have shown how the resident microbiota is modified after surgery. The aim of this study was to evaluate samples from patients with Crohn’s disease before and after an intestinal resection to determine whether there were differences in the abundance of different microbial markers, which may predict endoscopic recurrence at baseline.

Methods: In this observational study, a stool sample was obtained from 25 patients with Crohn’s disease before undergoing surgery, recruited at three Catalan hospitals. From each sample, DNA was purified and the relative abundance of nine microbial markers was quantified using qPCR.

Results: An algorithm composed of four microbial markers (E. coli, F. prausnitzii phylogroup I, Bacteroidetes, and Eubacteria) showed a sensitivity and specificity of 90.91% and 85.71%, respectively, and a positive and negative predictive value of 83.33% and 92.31%, respectively.

Conclusion: A microbial signature to determine patients who will have post-surgical recurrence was identified. This tool might be very useful in daily clinical practice, allowing the scheduling of personalized therapy and enabling preventive treatment only in patients who really require it.
Hsp70.1 carbonylation induces lysosomal cell death for lifestyle-related diseases
Authors: Yamashima Tetsumori , Seike Takuya , Oikawa Shinji , Kobayashi Hatasu , Kido Hidenori , Yanagi Masahiro , Yamamiya Daisuke , Li Shihui , Boontem Piyakarn , Mizukoshi Eishiro
Published: February 2023

Alzheimer’s disease, type 2 diabetes, and non-alcoholic steatohepatitis (NASH) constitute increasingly prevalent disorders. Individuals with type 2 diabetes are well-known to be susceptible to Alzheimer’s disease. Although the pathogenesis of each disorder is multifactorial and the causal relation remains poorly understood, reactive oxygen species (ROS)-induced lipid and protein oxidation conceivably plays a common role. Lipid peroxidation product was recently reported to be a key factor also for non-alcoholic steatohepatitis, because of inducing hepatocyte degeneration/death. Here, we focus on implication of the representative lipid-peroxidation product ‘hydroxynonenal’ for the cell degeneration/death of brain, pancreas, and liver. Since Hsp70.1 has dual roles as a chaperone and lysosomal membrane stabilizer, hydroxynonenal-mediated oxidative injury (carbonylation) of Hsp70.1 was highlighted. After intake of high-fat diets, oxidation of free fatty acids in mitochondria generates ROS which enhance oxidation of ω-6 polyunsaturated fatty acids (PUFA) involved within biomembranes and generate hydroxynonenal. In addition, hydroxynonenal is generated during cooking deep-fried foods with vegetable oils especially containing linoleic acids. These intrinsic and exogenous hydroxynonenal synergically causes an increase in its serum and organ levels to induce Hsp70.1 oxidation. As it is amphiphilic; being water-soluble but displays strong lipophilic characteristics, hydroxynonenal can diffuse within the cells and react with targets like senile and/or atheromatous plaques outside the cells. Hydroxynonenal can deepen and expand lysosomal injuries by facilitating ‘calpain-mediated cleavage of the carbonylated Hsp70.1’. Despite the unique anatomical, physiological, and biochemical characteristics of each organ for its specific disease, there should be a common cascade of the cell degeneration/death which is caused by hydroxynonenal. This review aims to implicate hydroxynonenal-mediated Hsp70.1 carbonylation for lysosomal membrane permeabilization/rupture and the resultant cathepsin leakage for inducing cell degeneration/death. Given the tremendous number of worldwide people suffering various lifestyle-related diseases, it is valuable to consider how ω-6 PUFA-rich vegetable oils is implicated for the organ disorder.
Bio-inspired neural networks for decision-making mechanisms and neuromodulation for motor control in a differential robot
Authors: Guerrero-Criollo Roberto Jose , Castaño-López Jason Alejandro , Hurtado-López Julián , Ramirez-Moreno David Fernando
Published: February 2023

The aim of this work is to propose bio-inspired neural networks for decision-making mechanisms and modulation of motor control of an automaton. In this work, we have adapted and applied cortical synaptic circuits, such as short-term memory circuits, winner-take-all (WTA) class competitive neural networks, modulation neural networks, and nonlinear oscillation circuits, in order to make the automaton able to avoid obstacles and explore simulated and real environments. The performance achieved by using biologically inspired neural networks to solve the task at hand is similar to that of several works mentioned in the specialized literature. Furthermore, this work contributed to bridging the fields of computational neuroscience and robotics.
Asthma's effect on brain connectivity and cognitive decline
Authors: Wang Tao , Huang Xin , Wang Jun
Published: February 2023

Objective

To investigate the changes in dynamic voxel mirror homotopy connection (dVMHC) between cerebral hemispheres in patients with asthma.

Methods

Our study was designed using a case-control method. A total of 31 subjects with BA and 31 healthy subjects with matching basic information were examined using rsfMRI. We also calculated and obtained the dVMHC value between the cerebral cortexes.

Results

Compared with the normal control group, the dVMHC of the lingual gyrus (Ling) and the calcarine sulcus (CAL), which represented the visual network (VN), increased significantly in the asthma group, while the dVMHC of the medial superior frontal gyrus (MSFG), the anterior/middle/posterior cingulate gyrus (A/M/PCG), and the supplementary motor area (SMA) of the sensorimotor network decreased significantly in the asthma group.

Conclusion

This study showed that the ability of emotion regulation and the efficiency of visual and cognitive information processing in patients with BA was lower than in those in the HC group. The dVMHC analysis can be used to sensitively evaluate oxygen saturation, visual function changes, and attention bias caused by emotional disorders in patients with asthma, as well as to predict airway hyperresponsiveness, inflammatory progression, and dyspnea.
Specific profiles of new-onset vs. non-inaugural status epilepticus: From diagnosis to 1-year outcome
Authors: Benaiteau Marie , Valton Luc , Gardy Ludovic , Denuelle Marie , Debs Rachel , Wucher Valentin , Rulquin Florence , Barbeau Emmanuel J. , Bonneville Fabrice , Pariente Jérémie , Curot Jonathan
Published: February 2023

While new-onset status epilepticus (NOSE) is a harbinger of chronic epilepsy, prospective medical data are sparse in terms of specifying whether the evolution of status epilepticus (SE) and seizure expression in NOSE resembles what occurs in patients who have already been diagnosed with epilepsy [non-inaugural SE (NISE)] in all aspects apart from its inaugural nature. The aim of this study was to compare the clinical, MRI, and EEG features that could distinguish NOSE from NISE. We conducted a prospective monocentric study in which all patients ≥18 years admitted for SE over a 6-month period were included. A total of 109 patients (63 NISE and 46 NOSE cases) were included. Despite similar modified Rankin scores before SE, several aspects of the clinical history distinguished NOSE from NISE patients. NOSE patients were older and frequently had neurological comorbidity and preexisting cognitive decline, but they had a similar prevalence of alcohol consumption to NISE patients. NOSE and NISE evolve in the same proportions as refractory SE (62.5% NOSE, 61% NISE) and share common features such as the same incidence (33% NOSE, 42% NISE, and p = 0.53) and volumes of peri-ictal abnormalities on MRI. However, in NOSE patients, we observed greater non-convulsive semiology (21.7% NOSE, 6% NISE, and p = 0.02), more periodic lateral discharges on EEG (p = 0.004), later diagnosis, and higher severity according to the STESS and EMSE scales (p < 0.0001). Mortality occurred in 32.6% of NOSE patients and 21% of NISE patients at 1 year (p = 0.19), but with different causes of death occurring at different time points: more early deaths directly linked to SE at 1 month occurred in the NOSE group, while there were more remote deaths linked to causal brain lesions in the NISE group at final follow-up. In survivors, 43.6% of the NOSE cases developed into epilepsy. Despite acute causal brain lesions, the novelty related to its inaugural nature is still too often associated with a delay in diagnosing SE and a poorer outcome, which justifies the need to more clearly specify the various types of SE to constantly raise awareness among clinicians. These results highlight the relevance of including novelty-related criteria, clinical history, and temporality of occurrence in the nosology of SE.
Two distinct types of color spreading induced by different luminance and color conditions in static flank transparency displays
Authors: Kimura Eiji
Published: February 2023

Flank transparency refers to illusory, phenomenally transparent color spreading induced when narrow colored flanks are added to line segments located within a virtual region. We investigated whether the luminance conditions that induced flank transparency were consistent with predictions based on luminance-contrast-based boundary interactions and the episcotister model for perceptual transparency. Examination of the requirements for the boundary interaction and perceptual transparency revealed that similar luminance conditions are necessary for both; that is, the flank luminance needs to be intermediate between the line and background luminances. We used green and achromatic flanks and systematically varied the luminance of the flanks, line segments, and background. We then asked the observers to rate the subjective certainty of color spreading using a five-point scale. The results showed that the perception of color spreading depended on color as well as luminance conditions. Generally, color spreading was convincing and phenomenally transparent when luminance conditions were consistent with the requirements for boundary interaction and perceptual transparency. In addition, color conditions worked in a facilitatory and inhibitory manner. Moreover, the results revealed that another convincing color spreading could be observed when the flank luminance was lower than the line or background luminance, that is, when the luminance condition for perceptual transparency was not satisfied. The observers’ verbal reports indicated that phenomenal transparency was not evident in this color spreading. Overall, the present findings demonstrate that typical transparent color spreading is not the only one observed in the flank transparency display. Different color and luminance conditions can modulate the phenomenal appearance of color spreading, resulting in distinct types of color spreading.
Opioid-induced short-term consciousness improvement in patients with disorders of consciousness
Authors: Ge Qianqian , Wang Yanjun , Zhuang Yutong , Li Qinghua , Han Ruquan , Guo Wenzhi , He Jianghong
Published: February 2023

Introduction

Effective treatment to facilitate recovery from prolonged disorders of consciousness is a complex topic for the medical community. In clinical practice, we have found that a subset of patients has a short-term improvement of consciousness after general anesthesia.

Methods

To determine the clinical factors responsible for the consciousness improvement, we enrolled 50 patients with disorders of consciousness who underwent surgery from October 2021 to June 2022. Their states of consciousness were evaluated before surgery, within 48 h after surgery, and 3 months after surgery. Clinical-related factors and intraoperative anesthetic drug doses were collected and compared between patients with and without consciousness improvement. Independent associations between selected factors and postoperative improvement were assessed using multivariate logistical regression analyses.

Results

Postoperative short-term consciousness improvement was found in 44% (22/50) of patients, with significantly increased scores of auditory and visual subscales. Patients with traumatic etiology, a preoperative diagnosis of minimally conscious state, and higher scores in the auditory, visual, and motor subscales were more likely to have postoperative improvement. This short-term increase in consciousness after surgery correlated with patients’ abilities to communicate in the long term. Furthermore, the amount of opioid analgesic used was significantly different between the improved and non-improved groups. Finally, analgesic dose, etiology, and preoperative diagnosis were independently associated with postoperative consciousness improvement.

Discussion

In conclusion, postoperative consciousness improvement is related to the residual consciousness of the patient and can be used to evaluate prognosis. Administration of opioids may be responsible for this short-term improvement in consciousness, providing a potential therapeutic approach for disorders of consciousness.
Nuclear fuel irradiation testbed for nuclear security applications
Authors: Wilson Brandon A. , Conant Andrew , Ulrich Tashiema L. , Kercher Andrew , Sadergaski Luke R. , Gerczak Tyler , Nelson Andrew T. , Petrie Christian M. , Harp Jason , Shields Ashley E.
Published: February 2023

The nuclear security community has long been interested in the identification and quantification of nuclear material signatures to understand a material’s provenance, use, and ultimate application. New forensics signatures and methods intended for non-traditional or advanced nuclear fuel applications require fuel irradiation experiments to demonstrate viability and validity. Integral fuel irradiations have historically required significant costs and long timelines to design, irradiate, and characterize. This paper describes how a recently developed nuclear fuel irradiation testbed can be used to provide a low cost, rapid turnaround, modular test environment for irradiation and evaluation of nuclear fuel specimens for nuclear security applications. The irradiation testbed houses six small ‘MiniFuel’ samples within hermetically sealed capsules inside targets that can be removed in between each ∼25-day operating cycle of the High Flux Isotope Reactor (HFIR). As many as nine targets can be irradiated using a single irradiation position (reflector region) in HFIR, allowing for varying irradiation temperatures and burnups. A suite of hot cell capabilities have been established to perform post-irradiation examination for measuring performance (e.g., fuel swelling, fission gas release) and facilitating experiment disassembly for subsequent property measurements, microstructural analysis, or chemical assay. This new testbed allows fuel irradiations to be conducted on an accelerated timeframe to enable rapid proof of concept testing and to provide reference material for nuclear fuel security applications. Recent applications using this testbed include the testing of isotopic taggants in UO2 fuel (intentional forensics), testing of U-10Mo fuel for down-conversion of highly enriched uranium–fueled reactors, and the production of irradiated UO2 fuel material for signature analysis of its isotopic composition (plutonium, fission gases, etc.).
Hepatoid adenocarcinoma of the stomach: CT findings
Authors: Yang Qian , Liu Yulin , Zhang Shuixia
Published: February 2023

Objective

To analyze the CT findings of hepatoid adenocarcinoma of the stomach (HAS) and improve the diagnosis accuracy of this condition.

Methods

The CT images of 22 pathologically confirmed HAS patients were analyzed retrospectively. We investigated the location of lesions, morphology, enhancement features, area of invasion into surrounding organs, lymph node metastasis, and venous tumor thrombus.

Results

Among the 22 patients (17 men and 5 women, the mean age was 61.41 ± 9.83 years ranging from 36 to 80 years) with HAS; the morphology of tumors included mass (n = 5), focal ulcer (n = 7), and infiltrating ulcer (n = 10). Extraserous fat was invaded in 12 cases. Enhancement scans showed continuous enhancement in all cases. The CT values of unenhanced scan, the arterial phase, and the portal venous phase are 30.36 ± 6.46, 60.91 ± 17.80, and 75.64 ± 22.09 (Hounsfield Unit, HU), respectively. In six cases, the tumor infiltrated the surrounding organs: liver (n = 1), pancreas (n = 2), and both liver and pancreas (n = 3). In 16 out of 22 patients (72.3%), suspicious lymph node metastasis at CT imaging has then been confirmed by pathological specimens. Intrahepatic metastasis was found in 14 cases. Seven patients had venous tumor thrombus: three patients developed tumor thrombus in the main trunk and intrahepatic branches of the portal vein and two patients in the portal vein, splenic vein, and superior mesenteric vein simultaneously.

Conclusion

The CT scans of HAS often show a thickened gastric wall and infiltrating ulceration. Infiltration into extraserosal fat is often seen. Enhancement scans show a continuous and progressive enhancement of lesions. Lymph node metastasis, intrahepatic metastasis, and portal vein tumor thrombus are common in HAS patients.
Preliminary study on CT contrast-enhanced radiomics for predicting central cervical lymph node status in patients with thyroid nodules
Authors: Kong Dan , Shan Wenli , Zhu Yan , Xu Qingqing , Duan Shaofeng , Guo Lili
Published: February 2023

Objective

To explore the feasibility of using a contrast-enhanced CT image-based radiomics model to predict central cervical lymph node status in patients with thyroid nodules.

Methods

Pretreatment clinical and CT imaging data from 271 patients with surgically diagnosed and treated thyroid nodules were retrospectively analyzed. According to the pathological features of the thyroid nodules and central lymph nodes, the patients were divided into three groups: group 1: papillary thyroid carcinoma (PTC) metastatic lymph node group; group 2: PTC nonmetastatic lymph node group; and group 3: benign thyroid nodule reactive lymph node group. Radiomics models were constructed to compare the three groups by pairwise classification (model 1: group 1 vs group 3; model 2: group 1 vs group 2; model 3: group 2 vs group 3; and model 4: group 1 vs groups (2 + 3)). The feature parameters with good generalizability and clinical risk factors were screened. A nomogram was constructed by combining the radiomics features and clinical risk factors. Receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) were performed to assess the diagnostic and clinical value of the nomogram.

Results

For radiomics models 1, 2, and 3, the areas under the curve (AUCs) in the training group were 0.97, 0.96, and 0.93, respectively. The following independent clinical risk factors were identified: model 1, arterial phase CT values; model 2, sex and arterial phase CT values; model 3: none. The AUCs for the nomograms of models 1 and 2 in the training group were 0.98 and 0.97, respectively, and those in the test group were 0.95 and 0.87, respectively. The AUCs of the model 4 nomogram in the training and test groups were 0.96 and 0.94, respectively. Calibration curve analysis and DCA revealed the high clinical value of the nomograms of models 1, 2 and 4.

Conclusion

The nomograms based on contrast-enhanced CT images had good predictive efficacy in classifying benign and malignant central cervical lymph nodes of thyroid nodule patients.
Dinutuximab beta combined with chemotherapy in patients with relapsed or refractory neuroblastoma
Authors: Wieczorek Aleksandra , Zaniewska-Tekieli Anna , Ehlert Karoline , Pawinska-Wasikowska Katarzyna , Balwierz Walentyna , Lode Holger
Published: February 2023

Prognosis in children with refractory and relapsed high-risk neuroblastoma is poor. Only a minority of patients obtain remission when treated with second-line chemotherapy regimens. Chemotherapy combined with anti-GD2 antibodies has previously been shown to increase response and survival rates. We retrospectively analyzed a cohort of 25 patients with relapsed or refractory high-risk neuroblastoma who were treated with irinotecan/temozolomide chemotherapy in combination with the anti-GD2 antibody dinutuximab beta. The therapy resulted in an objective response rate of 64%, with 32% of patients achieving a complete response. Response to treatment was observed in patients with refractory disease (n=5) and those with first (n=12) or consecutive (n=8) relapses, including patients with progressing disease. In four patients, best response was achieved after more than 5 cycles, suggesting that some patients may benefit from prolonged chemotherapy and dinutuximab beta treatment. Fourteen of our 25 patients had previously received dinutuximab beta, four of whom achieved complete response and six partial response (objective response rate 71%). The therapy was well tolerated, even in heavily pre-treated patients and those who had previously received dinutuximab beta treatment. Toxicities were comparable to those previously reported for the individual therapies, and no discontinuations due to toxicities occurred. Combination of chemotherapy with dinutuximab beta is a promising treatment option for patients with relapsed or refractory high-risk neuroblastoma and should be further explored in clinical studies.
Minimal adverse outcomes of postnatal cytomegalovirus infection in term or moderate and late preterm infants
Authors: Chen Jie , Zhou Yineng , Tang Jie , Xu Chenyu , Chen Liping , Xu Biyun , Dai Yimin , Hu Yali , Zhou Yi-Hua
Published: February 2023

Objective

The aim of study was to investigate at what extent breastfeeding and vaginal delivery can increase mother-to-child transmission of cytomegalovirus (CMV) and to observe the clinical outcomes of postnatal infection in term or moderate and late preterm infants.

Methods

In this retrospective study of prospectively collected clinical data and serum samples, during 2012–2015, 380 women with CMV IgG positive/IgM negative and their 384 infants (4 twin pairs) with gestational age ≥32 weeks were included. CMV IgG and IgM were measured with enzyme-linked immunosorbent assay.

Results

Of 384 infants followed up at 10.2 ± 2.3 months age, 177 (46.1%) were defined with CMV infection based on the presence of higher CMV IgG levels than in their mothers. The infection rate in 190 breastfed infants was higher than in 194 formula-fed infants (62.6% vs. 29.9%, P < 0.001). Vaginally delivered infants (172) had higher CMV infection rate than 212 infants delivered by caesarean section (55.2% vs. 38.7%, P = 0.001). Compared with formula feeding and caesarean section, breastfeeding and vaginal delivery increased postnatal CMV infection respectively (OR = 3.801, 95% CI 2.474–5.840, P < 0.001; OR = 1.818, 95% CI 1.182–2.796, P = 0.007). Nevertheless, compared to uninfected infants, CMV-infected infants had comparable height and body weight and showed no adverse effect on the liver enzymes.

Conclusion

Breastfeeding and vaginal delivery can increase postnatal CMV infection; however, the infection does not influence the growth of the term infants or preterm infants with gestational age ≥32 weeks. Thus, breastfeeding should be encouraged in these infants regardless of maternal CMV IgG status.
Neonatal sclerosing cholangitis with novel mutations in DCDC2 (doublecortin domain-containing protein 2) in Chinese children
Authors: Wei Xia , Fang Yuan , Wang Jian-She , Wang Yi-Zhen , Zhang Yuan , Abuduxikuer Kuerbanjiang , Chen Lian
Published: February 2023

Background

Neonatal sclerosing cholangitis (NSC) is a rare and severe autosomal recessive inherited liver disease with mutations in DCDC2, commonly requiring liver transplantation (LT) for decompensated biliary cirrhosis in childhood.

Methods

The information of four Chinese patients with NSC caused by mutations in DCDC2 from Children's Hospital of Fudan University were gathered. The four patients' clinicopathological and molecular features were summarized by clinical data, liver biopsy, immunohistochemical, and molecular genetic analysis.

Results

All patients presented with jaundice, hepatosplenomegaly, hyperbilirubinemia and bile embolism, and high serum γ-glutamyl transferase activity (GGT). Liver biopsies revealed varying degrees of bile duct hyperplasia, portal-tract inflammation, and/or fibrosis. Whole-exome sequencing (WES) found novel heterozygous variants of c.1024-1G > T /p.? and c.544G > A /p. Gly182Arg in the DCDC2.

Conclusion

This study expands the genetic spectrum of DCDC2 in NSC.
The mechanism of flavonoids from Cyclocarya paliurus on inhibiting liver cancer based on in vitro experiments and network pharmacology
Authors: Mo Jinggang , Tong Yingpeng , Ma Junxia , Wang Kunpeng , Feng Yifu , Wang Liezhi , Jiang Hao , Jin Chong , Li Junmin
Published: February 2023

Introduction:Cyclocarya paliurus (Batal.) Iljinsk., a subtropical tree belonging to the family Juglandaceae, is rich in polysaccharides, flavonoids, and terpenoids. It has important pharmacological effects such as lowering blood lipids, blood sugar, and blood pressure. However, little has been discerned regarding anti tumor effects and their potential mechanisms.

Method:In vitro cell culture experiments were used to test the effect of C. paliurus total flavonoids (CTFs) extract on apoptosis mechanisms in HepG2 cells. Network pharmacology was applied to further explore the effects of CTFs on liver cancer as well as the mechanisms through which these effects might be achieved. Both 3 hydroxyflavone and luteolin were randomly selected to verify the effect on inducing apoptosis and inhibiting the proliferation of HepG2 cells.

Results and Discussion: Network pharmacological analysis was applied to these 62 compounds and their targets, and 13 flavonoids were further screened for their potential anti liver cancer activity. These 13 flavonoids included: tangeretin, baicalein, 7,3′-dihydroxyflavone, velutin, 3-hydroxyflavone, chrysin, kumatakenin, tricin, luteolin, chrysoeriol, apigenin, pinocembrin, and butin. Together, these flavonoids were predicted to interact with AKT1, MAPK3, PIK3CA, EGFR, MAP2K1, SRC, IGF1R, IKBKB, MET, and MAPK14. It was predicted that the inhibitory effect on hepatocellular carcinoma would be accomplished by regulation of core proteins relating to such KEGG pathways as cancer, PI3K-Akt, proteoglycans in cancer, microRNAs in cancer, and endocrine resistance via core target proteins. Both 3-hydroxyflavone and luteolin were demonstrated to induce apoptosis and inhibit the proliferation of HepG2 cells. Our study provides scientific evidence supporting the use of CTFs for the treatment of liver cancer.
Metformin attenuates fibroblast activation during pulmonary fibrosis by targeting S100A4 via AMPK-STAT3 axis
Authors: Ji Huimin , Dong Hongliang , Lan Yuejiao , Bi Yuqian , Gu Xuan , Han Yongyue , Yang Chongyang , Cheng Minghan , Gao Jian
Published: February 2023

Fibroblasts activation is a crucial process for development of fibrosis during idiopathic pulmonary fibrosis pathogenesis, and transforming growth factor (TGF)-β1 plays a key regulatory role in fibroblast activation. It has been reported that metformin (MET) alleviated bleomycin (BLM)-induced pulmonary fibrosis (PF) by regulating TGF-β1-induced fibroblasts activation, but the underlying mechanisms still deserve further investigations. In this study, MET blocked α-smooth muscle actin (α-SMA) accumulation in vivo accompanied with S100A4 expression and STAT3 phosphorylation inhibition, resulting in attenuating the progression of lung fibrosis after BLM administration. We determined that S100A4 plays critical roles in fibroblasts activation in vitro, evidenced by siRNA knockdown of S100A4 expression downregulated TGF-β1 induced α-SMA production in Human fetal lung fibroblast (HFL1) cells. Importantly, we found for the first time that the expression of S100A4 in fibroblasts was regulated by STAT3. Stattic, an effective small molecule inhibitor of STAT3 phosphorylation, reduced S100A4 level in TGF-β1- treated HFL1 cells accompanied with less α-SMA production. We further found that MET, which inhibits STAT3 phosphorylation by AMPK activation, also inhibits fibroblasts activation by targeting S100A4 in vitro. Together all these results, we conclude that S100A4 contributes to TGF-β1- induced pro-fibrogenic function in fibroblasts activation, and MET was able to protect against TGF-β1-induced fibroblasts activation and BLM-induced PF by down-regulating S100A4 expression through AMPK-STAT3 axis. These results provide a useful clue for a clinical strategy to prevent PF.
The protective roles of allicin on type 1 diabetes mellitus through AMPK/mTOR mediated autophagy pathway
Authors: Qian Rengcheng , Chen Huihui , Lin Hongzhou , Jiang Yalan , He Pingping , Ding Yinjuan , Wu Huilan , Peng Yongmiao , Wang Lingfei , Chen Congde , Wang Dexuan , Ji Weiping , Guo Xiaoling , Shan Xiaoou
Published: February 2023

Background: Type 1 diabetes mellitus (T1DM) is one of the most common endocrine and metabolic diseases in children. Pancreatic β cells are thought to be critical cells involved in the progression of T1DM, and their injury would directly lead to impaired insulin secretion.

Purpose: To investigate the protective effects of allicin on pancreatic β cell injury and elucidate the underlying mechanism.

Methods: The streptozotocin (STZ)-induced mouse T1DM model in vivo and STZ-induced pancreatic β cell Min6 model in vitro were used to explore the effects of allicin on T1DM. The experiments include fasting blood glucose test, oral glucose tolerance detection, HE staining, immunohistochemistry, immunofluorescence, TUNEL staining, western blot, real-time quantitative PCR (RT-qPCR), and flow cytometry.

Results: Allicin could significantly decrease blood glucose level, improve islet structure and insulin expression, and inhibit apoptosis to reduce STZ-induced pancreatic β cell injury and loss through activating AMPK/mTOR mediated autophagy pathway.

Conclusion: Allicin treatment significantly reduced STZ-induced T1DM progression, suggesting that allicin may be a potential therapy option for T1DM patients.
Protein arginine methyltransferases in renal development, injury, repair, and fibrosis
Authors: Yu Jianjun , Yu Chao , Bayliss Georgia , Zhuang Shougang
Published: February 2023

Protein arginine methyltransferases (PRMTs) methylate a range of histone and non-histone substrates and participate in multiple biological processes by regulating gene transcription and post-translational modifications. To date, most studies on PRMTs have focused on their roles in tumors and in the physiological and pathological conditions of other organs. Emerging evidence indicates that PRMTs are expressed in the kidney and contribute to renal development, injury, repair, and fibrosis. In this review, we summarize the role and the mechanisms of PRMTs in regulating these renal processes and provide a perspective for future clinical applications.
Palbociclib impairs the proliferative capacity of activated T cells while retaining their cytotoxic efficacy
Authors: Arndt Claudia , Tunger Antje , Wehner Rebekka , Rothe Rebecca , Kourtellari Eleni , Luttosch Stephanie , Hannemann Katharina , Koristka Stefanie , Loureiro Liliana R. , Feldmann Anja , Tonn Torsten , Link Theresa , Kuhlmann Jan Dominik , Wimberger Pauline , Bachmann Michael Philipp , Schmitz Marc
Published: February 2023

The cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor palbociclib is an emerging cancer therapeutic that just recently gained Food and Drug Administration approval for treatment of estrogen receptor (ER)-positive, human epidermal growth factor receptor (Her)2-negative breast cancer in combination with the ER degrader fulvestrant. However, CDK4/6 inhibitors are not cancer-specific and may affect also other proliferating cells. Given the importance of T cells in antitumor defense, we studied the influence of palbociclib/fulvestrant on human CD3+ T cells and novel emerging T cell-based cancer immunotherapies. Palbociclib considerably inhibited the proliferation of activated T cells by mediating G0/G1 cell cycle arrest. However, after stopping the drug supply this suppression was fully reversible. In light of combination approaches, we further investigated the effect of palbociclib/fulvestrant on T cell-based immunotherapies by using a CD3-PSCA bispecific antibody or universal chimeric antigen receptor (UniCAR) T cells. Thereby, we observed that palbociclib clearly impaired T cell expansion. This effect resulted in a lower total concentration of interferon-γ and tumor necrosis factor, while palbociclib did not inhibit the average cytokine release per cell. In addition, the cytotoxic potential of the redirected T cells was unaffected by palbociclib and fulvestrant. Overall, these novel findings may have implications for the design of treatment modalities combining CDK4/6 inhibition and T cell-based cancer immunotherapeutic strategies.
Relative comparison of chronic kidney disease-mineral and bone disorder rat models
Authors: Zhang Xiaoqiong , Li Ting , Wang Lijuan , Li Yanhui , Ruan Taoren , Guo Xiaohong , Wang Qin , Meng Xianli
Published: February 2023

Objective: The aim of this study is to establish a suitable animal model of chronic kidney disease–mineral and bone disorder (CKD–MBD) by comparing CKD–MBD rat models induced by 5/6 Nx, AN, and UUO, accompanied by a low-calcium and high-phosphorus diet.

Methods: Sprague‒Dawley rats were randomly divided into four groups: control group, 5/6 nephrectomy (5/6 Nx) group, Adriamycin nephropathy (AN) group, and unilateral ureteral obstruction (UUO) group. Serum biochemical indices were measured to evaluate renal function, mineral and bone metabolism, the severity of CKD–MBD, and the status of bone transformation. Hematoxylin–eosin staining (HE) and Masson’s trichrome (Masson) staining were used for histopathological analysis of the kidney. Goldner’s trichrome (Goldner) and tartrate-resistant acid phosphatase (TRAP) staining were utilized to observe bone mineralization and osteoclasts in the femur, respectively. Micro-CT images were applied to study the structure of the femur. The expression levels of osterix and cathepsin K in the femur were measured by immunohistochemistry (IHC) to confirm the status of bone transformation.

Results: The levels of serum creatinine (Scr) and blood urea nitrogen (BUN) in the 5/6 Nx and AN group rats were significantly higher than those in the control rats, and this change was accompanied by marked changes in the levels of calcium (Ca), phosphate (Pi), intact parathyroid hormone (i-PTH), fibroblast growth factor 23 (FGF23), osteocalcin (OC), and cross-linked C-telopeptide of type 1 collagen (CTX-1); UUO group rats exhibited slight and inconsistent variations in the levels of Scr, BUN, Ca, Pi, i-PTH, FGF23, OC, and CTX-1 in serum. Histopathological analysis of the kidney showed that the UUO group rats suffered serious fibrosis and 5/6 Nx group rats exhibited severe focal calcification. Histopathological analysis of the femur showed that the AN group rats had minimal bone mineralization and that the 5/6 Nx group rats had overactive osteoclasts. Micro-CT revealed that the AN model had the most severe bone destruction and that the 5/6 Nx model had the least severe bone loss among the three models. The expression of cathepsin K in the femur was significantly increased in all models, while the expression of osterix in the femur was only significantly increased in the 5/6 Nx model.

Conclusion: 5/6 Nx, AN, and UUO accompanied by a low-calcium and high-phosphorus diet successfully induced CKD–MBD in rats. The 5/6 NX model presented the progression of high-turnover bone disease, with consistency between biochemical indices in serum and histomorphometric analysis of the femur, and the AN and UUO models developed a severe deterioration in bone quantity and severe bone resorption; however, the changes in biochemical indices were subtle in the UUO model, and liver injury was obvious in the AN model.
Design of anti-load perturbation flight trajectory stability controller for agricultural UAV
Authors: Wei Xu , XianYu Wu , Jiazhen Liu , Yasheng Yan
Published: February 2023

The unmanned aerial vehicle(UAV) used in agricultural fields usually has a load, which affects stability of flight trajectory. This problem is a great technical challenge and critical issue which has fascinated many researchers in this area. This research paper presents a flight dynamics model for agricultural UAV under load condition. The robust T-S fuzzy control method is applied in the attitude angle control part, and the traditional PID controller is used in the position loop control part. Results of simulation depict that the flight trajectory of agricultural UAV can reach certain stability when the load is relatively small.