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Ehrlichia canis is the primary etiologic agent of canine monocytic ehrlichiosis, a serious and sometimes fatal hemorrhagic disease of dogs. Diagnosis of E. canis infection is often retrospectively confirmed by serologic detection of antibodies by immunofluorescent microscopy. Our laboratory previously identified numerous major immunoreactive proteins with species-specific linear antibody epitopes that are useful for immunodiagnosis of CME. More recently, we have defined the entire antibody-reactive immunome of E. canis, substantially increasing the number of major immunoreactive proteins known to exist. In this study, we analyzed and compared seven recently identified antibody reactive E. canis proteins with established diagnostic antigens including tandem repeat proteins TRP19, TRP36 and TRP140 and observed comparable immunoreactivity. Many of these proteins were conserved in different E. canis strains. Multiple linear antibody epitopes were mapped in a highly conserved TRP (Ecaj_0126), including within the tandem repeat domain. Temporal antibody responses were examined, and multiple proteins reacted with antibodies in sera as early as 21 days post experimental infection. Host-specific expression of the proteins was examined which revealed that some proteins exhibited higher expression in mammalian cells, while others in tick cells. This study has identified new immunodiagnostic candidates that exhibit different host expression patterns, information which may be useful for developing ultrasensitive immunodiagnostics and effective vaccines for CME.

PurposeThe overall survival of patients with pancreatic cancer is extremely low. We aimed to establish machine learning (ML) based model to accurately predict three-year survival and prognosis of pancreatic cancer patients.MethodsWe analyzed pancreatic cancer patients from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2021. Univariate and multivariate logistic analysis were employed to select variables. Recursive Feature Elimination (RFE) method based on 6 ML algorithms was utilized in feature selection. To construct predictive model, 13 ML algorithms were evaluated by area under the curve (AUC), area under precision-recall curve (PRAUC), accuracy, sensitivity, specificity, precision, cross-entropy, Brier scores and Balanced Accuracy (bacc) and F Beta Score (fbeta). An optimal ML model was constructed to predict three-year survival, and the predictive results were explained by SHapley Additive exPlanations (SHAP) framework. Meanwhile, 101 ML algorithm combinations were developed to select the best model with highest C-index to predict prognosis of pancreatic cancer patients.ResultsA total of 20,064 pancreatic cancer patients from SEER database was consecutively enrolled. We utilized eight clinical variables to establish prediction model for three-year survival. CatBoost model was selected as the best prediction model, and AUC was 0.932 [0.924, 0.939], 0.899 [0.873, 0.934] and 0.826 [0.735, 0.919] in training, internal test and external test sets, with 0.839 [0.831, 0.847] accuracy, 0.872 [0.858, 0.887] sensitivity, 0.803 [0.784, 0.825] specificity and 0.832 [0.821, 0.853] precision. Surgery type had the greatest effects on three-year survival according to SHAP results. For prognosis prediction, “RSF+GBM” algorithm was the best prognostic model with C-index of 0.774, 0.722 and 0.674 in training, internal test and external test sets.ConclusionsOur ML models demonstrate excellent accuracy and reliability, offering more precise personalized prognostic prediction to pancreatic cancer patients.

BackgroundThe thickness and motion of the Interatrial Septum (IAS) possibly serves as indicators of both structural and functional remodeling of left atrium. This study aims to use transesophageal echocardiography (TEE) to assess IAS motion in non-valvular atrial fibrillation (NVAF) and investigate its correlation with the risk of spontaneous echo contrast (SEC) and thrombus (TH).MethodsWe conducted a cross-sectional study on 318 patients with NVAF who underwent transthoracic echocardiography and TEE. IAS motion was defined as the maximum displacement of IAS observed throughout the cardiac cycles using M-mode TEE.ResultsThe prevalence of SEC/TH was 39.9% (127/318) in the overall group. In paroxysmal atrial fibrillation (PAF), the prevalence rate of SEC/TH was 25.3% (47/186), compared to 60.6% (80/132) in persistent atrial fibrillation (PeAF). Multivariable analyses showed that LA volume index (LAVI), mean E/e’, S/D ratio, IAS motion and CHA2DS2-VASc scores were significantly associated with SEC/TH. Patients with lower IAS motion showed a higher prevalence of SEC/TH compared to those with higher IAS motion (71.3% vs. 11.6%; P

BackgroundType 2 diabetes (T2D) frequently co-occurs with respiratory system diseases such as chronic obstructive pulmonary disease (COPD), bronchial asthma, lung cancer, interstitial lung disease, and pulmonary tuberculosis. Although a potential association is noted between these conditions, the available research is limited.ObjectiveTo investigate the causal relationship between patients with T2D and respiratory system diseases using two-sample Mendelian randomization analysis.MethodsCausal relationships were inferred using a two-sample Mendelian randomization (MR) analysis based on publicly available genome-wide association studies. We employed the variance inverse-weighted method as the primary analytical approach based on three key assumptions underlying MR analysis. To bolster the robustness and reliability of our results, we utilized MR Egger’s intercept test to detect potential pleiotropy, Cochran’s Q test to assess heterogeneity, funnel plots to visualize potential bias, and “leave-one-out” sensitivity analysis to ensure that our findings were not unduly influenced by any single genetic variant.ResultThe inverse variance weighted (IVW) analysis indicated a causal relationship between T2D and COPD [Odds Ratio (OR) = 0.87; 95% Confidence Interval (CI) = 0.82–0.96; p 0.05), and the statistical power calculations indicated that the results were reliable. The IVW analysis showed a negative causal relationship between T2D and bronchial asthma [OR = 0.85; 95% CI = 0.81–0.89; p

IntroductionRevealing individual characteristics is supportive for identifying individuals in forensic crime. As saliva is one of the most common biological samples used in crime scenes, it is important to make full use of the rich individual information contained in saliva. The aim of this study was to explore the application of the microbiome in forensic science by analysing differences in the salivary microbiome and metabolome of healthy individuals with different dietary habits.MethodsWe performed 16S rDNA sequencing analysis based on oral saliva samples collected from 12 vegetarians, 12 seafood omnivores and 12 beef and lamb omnivores. Non-targeted metabolomics analyses were also performed based on saliva samples from healthy individuals.ResultsThe results showed that the dominant flora of vegetarians was dominated by Neisseria (belonging to the phylum Proteobacteria), while seafood omnivores and beef and lamb omnivores were dominated by Streptococcus (belonging to the phylum Firmicutes). NDMS-based and cluster analyses showed that vegetarian dieters were significantly differentiated from meat dieters (seafood omnivores and beef and lamb omnivores), which may be related to the fact that high-fiber diets can create a different salivary flora structure. Variants were also detected in salivary metabolic pathways, including positive correlations with Lipid metabolism, Amino acid metabolism, Carbohydrate metabolism, and Nucleotide metabolism in vegetarians, and correlations in seafood omnivores. In order to select salivary microorganisms and metabolic markers that can distinguish different dietary profiles, a random forest classifier model was constructed in this study, and the results showed that individuals with different dietary profiles could be successfully distinguished based on the core genera and metabolites such as Streptococcus, Histidinyl-Valine.ConclusionOur study provides a supportive basis for the application of salivary polyomics in order to reveal the dietary characteristics of individuals for forensic investigation and crime solving.

Introduction: Genomic profiling has revolutionized therapeutic interventions and the clinical management of liver cancer. However, pathogenetic mechanisms, molecular determinants of recurrence, and predictive biomarkers for first-line treatment (anti-PD-(L)1 plus bevacizumab) in liver cancer remain incompletely understood.Materials and methods: Targeted next-generation sequencing (tNGS) (a 603-cancer-gene panel) was applied for the genomic profiling of 232 hepatocellular carcinoma (HCC) and 22 intrahepatic cholangiocarcinoma (ICC) patients, among which 47 unresectable/metastatic HCC patients underwent anti-PD-1 plus bevacizumab therapy. Genomic alterations were estimated for their association with vascular invasion (VI), location of onset, recurrence, overall survival (OS), recurrence-free survival (RFS), and anti-PD-1 plus bevacizumab therapy response.Results: The genomic landscape exhibited that the most commonly altered genes in HCC were TP53, FAT3, PDE4DIP, KMT2C, FAT1, and MYO18A, while TP53, FAT1, FAT3, PDE4DIP, ROS1, and GALNT11 were frequently altered in ICC; notably, KRAS (18.18% vs. 1.29%) and BAP1 (13.64% vs. 1.29%) alterations were significantly more prevalent in ICC. Comparison analysis demonstrated the distinct clinicopathological/genomic characterizations between Chinese and Western HCC cohorts. Genomic profiling of HCC underlying VI showed that LDLR, MSH2, KDM5D, PDE3A, and FOXO1 were frequently altered in the VI group compared to patients without VIs. Compared to the right hepatic lobes of HCC patients, the left hepatic lobe of HCC patients had superior OS (median OS: 36.77 months vs. unreached, p < 0.05). By further comparison, Notch signaling pathway-related alterations were significantly prevalent among the right hepatic lobes of HCC patients. Of note, multivariate Cox regression analysis showed that altered RB1, NOTCH3, MGA, SYNE1, and ZFHX3, as independent prognostic factors, were significantly correlated with the OS of HCC patients. Furthermore, altered LATS1 was abundantly enriched in the HCC-recurrent group, and impressively, it was independent of clinicopathological features in predicting RFS (median RFS of altered type vs. wild-type: 5.57 months vs. 22.47 months, p < 0.01). Regarding those treated HCC patients, TMB value, altered PTPRZ1, and cell cycle-related alterations were identified to be positively associated with the objective response rate (ORR), but KMT2D alterations were negatively correlated with ORR. In addition, altered KMT2D and cell cycle signaling were significantly associated with reduced and increased time to progression-free survival (PFS), respectively.Conclusion: Comprehensive genomic profiling deciphered distinct molecular characterizations underlying VI, location of onset, recurrence, and survival time in liver cancer. The identification of novel genetic predictors of response to anti-PD-1 plus bevacizumab in HCC facilitated the development of an evidence-based approach to therapy.

Osteoporosis is a systemic metabolic disease characterized by disrupted bone formation/resorption and homeostasis. Flavonoids extracted from traditional Chinese medicinal plants regulate bone homeostasis by intervening in differentiating bone marrow mesenchymal stem cells, balancing the bone immune system, inhibiting oxidative stress response, and reversing iron overload. The target molecules and signaling pathways, such as Wnt/β-catenin and OPG/RANKL/RANK, directly affect osteoblast/osteoclast activity, exhibiting significant potential in the treatment of OP. Therefore, this study presents a systematic review of the recent literature to provide comprehensive information on the traditional Chinese medicine flavonoids involved in the regulation of bone homeostasis. Also, the molecular mechanisms and pharmacological uses of these metabolites are summarized, and their clinical translation and development potential are discussed.

BackgroundAtrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with a high risk of stroke. This study was designed to investigate the relationship between hemodynamic parameters and left atrial thrombus/spontaneous echo contrast (LAT/SEC) in non-valvular atrial fibrillation (NVAF) patients and establish a predictive nomogram that integrates hemodynamic parameters with clinical predictors to predict the risk of LAT/SEC.MethodsFrom January 2019 to September 2022, a total of 354 consecutive patients with NVAF were enrolled in this cross-sectional study at the First Affiliated Hospital of Guangxi Medical University. To identify the optimal predictive features, we employed least absolute shrinkage and selection operator (LASSO) regression. A multivariate logistic regression model was subsequently constructed, and the results were visualized with a nomogram. We evaluated the model's performance using discrimination, calibration, and the concordance index (C-index).ResultsWe observed a 38.7% incidence of SEC/TH in NVAF patients. Independent influencing factors of LAT/SEC were identified through LASSO and multivariate logistic regression. Finally, four indicators were included, namely, previous stroke/transient ischaemic attack (OR = 4.25, 95% CI = 1.57–12.23, P = 0.006), left atrial volume index (LAVI) (OR = 1.04, 95% CI = 1.01–1.06, P = 0.001), S/D ratio (OR = 0.27, 95% CI = 0.11–0.59, P = 0.002), and left atrial acceleration factor (OR = 4.95, 95% CI = 2.05–12.79, P = 0.001). The nomogram, which incorporated these four influencing factors, demonstrated excellent predictive ability. The training set had a C-index of 0.878, while the validation set had a C-index of 0.872. Additionally, the calibration curve demonstrated great consistency between the predicted probabilities and the observed outcomes, and the decision curve analysis confirmed the important clinical advantage of the model for patients with NVAF.ConclusionOur findings indicate that an enlarged left atrium and abnormal hemodynamic parameters in the left atrial and pulmonary veins are linked to a greater risk of LAT/SEC. Previous stroke/transient ischaemic attack, LAVI, the S/D ratio, and left atrial acceleration factor were independently associated with LAT/SEC in NVAF patients. With the incorporation of these four variables, the developed nomogram effectively predicts the risk of LAT/SEC and outperforms the CHA2DS2-VASc score.

Purpose: This systematic review and meta-analysis aimed to evaluate the efficacy of whole-body vibration training (WBVT) in patients with stroke, specifically focusing on its effects on physical function, activities of daily living (ADL), and quality of life (QOL). Additionally, potential moderators influencing WBVT outcomes were explored.Methods: We conducted a systematic search of PubMed, Embase, and Cochrane Library from inception to September 2022. Eligible studies were randomized controlled trials employing WBVT in patients with stroke. Two investigators independently extracted the data and calculated the standardized mean difference (SMD) using random-effect models.Results: Twenty-five studies involving 991 patients were included in this meta-analysis. WBVT demonstrated significant reductions in spasticity (SMD = −0.33, 95% CI = −0.61 to −0.06, p = 0.02), improvements in motor function (SMD = 0.39, 95% CI = 0.16 to 0.61, p < 0.01), and enhancements in balance function (SMD = 0.28, 95% CI = 0.09 to 0.47, p < 0.01) in patients with stroke. However, no significant effects were observed for gait (SMD = −0.23, 95% CI = −0.50 to 0.04, p = 0.10), ADL (SMD = −0.01, 95% CI = −0.46 to 0.44, p = 0.97), or QOL (SMD = 0.12, 95% CI = −0.30 to 0.53, p = 0.59). Subgroup analyses revealed that variable frequency vibration and side-alternating vibration exhibited significant efficacy in reducing spasticity and improving motor and balance functions, while fixed frequency vibration and vertical vibration did not yield significant therapeutic benefits in these domains.Conclusion: Our findings indicate that WBVT may serve as a viable adjunct therapy for stroke patients to alleviate spasticity and enhance motor and balance functions. Variable frequency and side-alternating vibration appear to be crucial factors influencing the therapeutic effects of WBVT on these dysfunctions. Nonetheless, WBVT did not show significant effects on gait, ADL, or QOL in stroke patients.Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier (CRD42022384319)

For decades, the defined antibody reactive proteins of Ehrlichia chaffeensis and E. canis were limited to a small group with linear antibody epitopes. Recently, our laboratory has utilized an immunomics-based approach to rapidly screen and identify undefined Ehrlichia chaffeensis and E. canis antigenic proteins and antibody epitopes. In this study, we analyzed the remaining portion (~50%) of the E. chaffeensis and E. canis proteomes (n = 444 and n = 405 proteins, respectively), that were not examined in previous studies, to define the complete immunomes of these important pathogens. Almost half of the E. chaffeensis proteins screened (196/444) reacted with antibodies in convalescent HME patient sera, while only 43 E. canis proteins reacted with CME dog sera. New major immunoreactive proteins were identified in E. chaffeensis (n = 7) and E. canis (n = 1), increasing the total number of E. chaffeensis (n = 14) and E. canis proteins (n = 18) that exhibited antibody reactivity comparable to well-defined major antigenic proteins (TRP120 and TRP19). All of the E. chaffeensis but only some E. canis major immunoreactive proteins contained major conformation-dependent antibody epitopes. The E. chaffeensis immunoreactive proteins were generally small (< 250 amino acids; ~27kDa) and the E. canis proteins were slightly larger (> 320 amino acids; ~35 kDa). The majority of these new Ehrlichia major immunoreactive proteins were predicted to be type I secreted effectors, some of which contained transmembrane domains. Characterization of the immunomes of E. chaffeensis and E. canis and understanding the host specific Ehrlichia immune responses will facilitate identification of protective antigens and define the biophysical epitope characteristics vital to effective vaccine development for the ehrlichioses.

Osteoporosis is a systemic bone disease characterized by an imbalance in the relationship between osteoblasts, osteocytes, and osteoclasts. This imbalance in bone metabolism results in the destruction of the bone’s microstructure and an increase in bone brittleness, thereby increasing the risk of fractures. Osteoporosis has complex causes, one of which is related to the dysregulation of 5-hydroxytryptamine, a neurotransmitter closely associated with bone tissue metabolism. Dysregulation of 5-HT directly or indirectly promotes the occurrence and development of osteoporosis. This paper aims to discuss the regulation of 5-HT by Traditional Chinese Medicine and its impact on bone metabolism, as well as the underlying mechanism of action. The results of this study demonstrate that Traditional Chinese Medicine has the ability to regulate 5-HT, thereby modulating bone metabolism and improving bone loss. These findings provide valuable insights for future osteoporosis treatment.

Osteoarthritis impairs the functions of various joints, such as knees, hips, hands and spine, which causes pain, swelling, stiffness and reduced mobility in joints. Multiple factors, including age, joint injuries, obesity, and mechanical stress, could contribute to osteoarthritis development and progression. Evidence has demonstrated that genetics and epigenetics play a critical role in osteoarthritis initiation and progression. Noncoding RNAs (ncRNAs) have been revealed to participate in osteoarthritis development. In this review, we describe the pivotal functions and molecular mechanisms of numerous lncRNAs in osteoarthritis progression. We mention that long noncoding RNAs (lncRNAs) could be biomarkers for osteoarthritis diagnosis, prognosis and therapeutic targets. Moreover, we highlight the several compounds that alleviate osteoarthritis progression in part via targeting lncRNAs. Furthermore, we provide the future perspectives regarding the potential application of lncRNAs in diagnosis, treatment and prognosis of osteoarthritis.

The phenotypic spectrum of myelin oligodendrocyte glycoprotein (MOG)- IgG–associated disorders (MOGAD) has broadened in the past few years, and atypical phenotypes are increasingly recognized. Isolated seizures and MRI-negative brainstem and cerebellar symptoms or encephalitis have rarely been reported as a feature of MOGAD and represent a diagnostic challenge. Meanwhile, the coexistence of MOG IgG and other CNS autoimmune antibodies is infrequent. We report a patient presented with isolated epileptic onset, relapsed with MRI-negative brainstem symptoms and MRI-negative encephalitis. He was positive for MOG IgG throughout the disease course while concomitant NMDAR IgG was not detected positive until second relapse. He showed decreasing response to conventional first-line therapy. The last relapse was during a COVID-19 epidemic with limited inpatient resources. Fortunately, he was ultimately controlled on subcutaneous ofatumumab, a novel fully humanized anti-CD20 mAb. This is the first report about subcutaneous ofatumumab treatment in MOG and NMDAR IgG double positive encephalitis with 12-month follow-up, depicting its potential as a therapeutic option.

ObjectiveCerebral white matter hyperintensity can lead to cerebral small vessel disease, MRI images in the brain are used to assess the degree of pathological changes in white matter regions. In this paper, we propose a framework for automatic 3D segmentation of brain white matter hyperintensity based on MRI images to address the problems of low accuracy and segmentation inhomogeneity in 3D segmentation. We explored correlation analyses of cognitive assessment parameters and multiple comparison analyses to investigate differences in brain white matter hyperintensity volume among three cognitive states, Dementia, MCI and NCI. The study explored the correlation between cognitive assessment coefficients and brain white matter hyperintensity volume.MethodsThis paper proposes an automatic 3D segmentation framework for white matter hyperintensity using a deep multi-mapping encoder-decoder structure. The method introduces a 3D residual mapping structure for the encoder and decoder. Multi-layer Cross-connected Residual Mapping Module (MCRCM) is proposed in the encoding stage to enhance the expressiveness of model and perception of detailed features. Spatial Attention Weighted Enhanced Supervision Module (SAWESM) is proposed in the decoding stage to adjust the supervision strategy through a spatial attention weighting mechanism. This helps guide the decoder to perform feature reconstruction and detail recovery more effectively.ResultExperimental data was obtained from a privately owned independent brain white matter dataset. The results of the automatic 3D segmentation framework showed a higher segmentation accuracy compared to nnunet and nnunet-resnet, with a p-value of

PurposeTo explore fecal immune-related proteins that can be used for colorectal cancer (CRC) diagnosis.Patients and methodsThree independent cohorts were used in present study. In the discovery cohort, which included 14 CRC patients and 6 healthy controls (HCs), label-free proteomics was applied to identify immune-related proteins in stool that could be used for CRC diagnosis. Exploring potential links between gut microbes and immune-related proteins by 16S rRNA sequencing. The abundance of fecal immune-associated proteins was verified by ELISA in two independent validation cohorts and a biomarker panel was constructed that could be used for CRC diagnosis. The validation cohort I included 192 CRC patients and 151 HCs from 6 different hospitals. The validation cohort II included 141 CRC patients, 82 colorectal adenoma (CRA) patients, and 87 HCs from another hospital. Finally, the expression of biomarkers in cancer tissues was verified by immunohistochemistry (IHC).ResultsIn the discovery study, 436 plausible fecal proteins were identified. And among 67 differential fecal proteins (|log2 fold change| > 1, P< 0.01) that could be used for CRC diagnosis, 16 immune-related proteins with diagnostic value were identified. The 16S rRNA sequencing results showed a positive correlation between immune-related proteins and the abundance of oncogenic bacteria. In the validation cohort I, a biomarker panel consisting of five fecal immune-related proteins (CAT, LTF, MMP9, RBP4, and SERPINA3) was constructed based on the least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression. The biomarker panel was found to be superior to hemoglobin in the diagnosis of CRC in both validation cohort I and validation cohort II. The IHC result showed that protein expression levels of these five immune-related proteins were significantly higher in CRC tissue than in normal colorectal tissue.ConclusionA novel biomarker panel consisting of fecal immune-related proteins can be used for the diagnosis of CRC.

BackgroundIn the pathogenesis of osteoarthritis (OA) and metabolic syndrome (MetS), the immune system plays a particularly important role. The purpose of this study was to find key diagnostic candidate genes in OA patients who also had metabolic syndrome.MethodsWe searched the Gene Expression Omnibus (GEO) database for three OA and one MetS dataset. Limma, weighted gene co-expression network analysis (WGCNA), and machine learning algorithms were used to identify and analyze the immune genes associated with OA and MetS. They were evaluated using nomograms and receiver operating characteristic (ROC) curves, and finally, immune cells dysregulated in OA were investigated using immune infiltration analysis.ResultsAfter Limma analysis, the integrated OA dataset yielded 2263 DEGs, and the MetS dataset yielded the most relevant module containing 691 genes after WGCNA, with a total of 82 intersections between the two. The immune-related genes were mostly enriched in the enrichment analysis, and the immune infiltration analysis revealed an imbalance in multiple immune cells. Further machine learning screening yielded eight core genes that were evaluated by nomogram and diagnostic value and found to have a high diagnostic value (area under the curve from 0.82 to 0.96).ConclusionEight immune-related core genes were identified (FZD7, IRAK3, KDELR3, PHC2, RHOB, RNF170, SOX13, and ZKSCAN4), and a nomogram for the diagnosis of OA and MetS was established. This research could lead to the identification of potential peripheral blood diagnostic candidate genes for MetS patients who also suffer from OA.

Background: Stroke is one of the leading causes of mortality and permanent disability worldwide. However, the current stroke treatment has a limited effect. Therefore, a new treatment is urgently needed. Stem cell therapy is a cutting-edge treatment for stroke patients. This study aimed to gain better understanding of global stem cell trends in stroke via a bibliometric analysis.Methods: We used the Web of Science Core Collection to search pertinent articles about stem cells in stroke published between 2004 and 2022. Analysis was conducted using CiteSpace, VOSviewer, and the R package “bibliometrix” to identify publication outputs, countries/regions, institutions, authors/co-cited authors, journals/co-cited journals, co-cited references, and keywords.Results: A total of 6,703 publications were included in the bibliometric analysis. The total number of citations significantly and rapidly increased between 2004 and 2022, with the most pronounced growth pattern observed in the period of 2008–2009. In terms of authoritarian countries, the USA had the most publications among the countries. As for institutions and authors, the most prolific institution was the University of South Florida, followed by Oakland University and then Shanghai Jiao Tong University, and Chopp, M. and Borlongan, Cesario V, had the most output among the authors. Regarding the journals, Cell Transplantation had the highest publication, followed by Brain Research. As for references, “Mesenchymal stem cells as trophic mediators” was the most frequently cited (2,082), and the article entitled Neuronal replacement from endogenous precursors in the adult brain after stroke had the strongest burstiness (strength = 81.35). Emerging hot words in the past decade included “adhesion molecule,” “mesenchymal stromal cell,” “extracellular vesicle,” “pluripotent stem cells,” “signaling pathway,” “plasticity,” and “exosomes.”Conclusion: Between 2004 and 2022, the terms “neurogenesis,” “angiogenesis,” “mesenchymal stem cells,” “extracellular vesicle,” “exosomes,” “inflammation,” and “oxidative stress” have emerged as the hot research areas for research on stem cells in stroke. Although stem cells exert a number of positive effects, the main mechanisms for mitigating the damage caused by stroke are still unknown. Clinical challenges may include complicating factors that can affect the efficacy of stem cell therapy, which are worth a deep exploration.

Naringin is the main component of Drynaria. Modern pharmacological studies have shown that naringin has a wide range of pharmacological activities, including antioxidant, anti-inflammatory, anti-apoptotic, anti-ulcer, and anti-osteoporosis effects. Its therapeutic effects have been observed in various clinical models, such as atherosclerosis, cardiovascular diseases, diabetes, neurodegenerative diseases, and rheumatic diseases. This review investigates the pharmacological effects of naringin and the associated mechanisms in improving flap survival. This review will also provide a reference for future rational application of naringin, especially in research to improve flap survival.

PurposeTo analyze and predict the possibility of visual field (VF) recovery after endoscopic transsphenoidal surgery (ETSS) in patients with pituitary adenoma, we investigated the factors affecting the improvement of the visual field defect (VFD) and built a nomogram predictive model based on these risk factors. We further investigated specific recovery regions of VF associated with the improvement of VFD.MethodsThe clinical data of patients who underwent ETSS for pituitary adenomas at a single center between the January 2021 and April 2022 were retrospectively analyzed. Univariate and multivariate analyses were used to determine the predictive factors affecting the improvement in the VF defect and specific recovery regions in patients with pituitary adenomas after ETSS.ResultsWe enrolled 28 patients (56 eyes) who were hospitalized at our institution. Four clinical features, including compression of the optic chiasm, preoperative mean defect (MD), diffuse defect, and duration of the visual symptom, were chosen from the least absolute shrinkage and selection operator regression analysis to establish the predictive nomogram. The nomogram’s area under the curve (AUC) was 0.912, indicating a good degree of differentiation. A calibration plot was used to evaluate the predictive model’s calibration, and a decision curve was used to evaluate its clinical application value. The VF defects were improved in the 270–300° range (270–300: RR = 361.00, 95% CI: 21.01–6,202.41).ConclusionWe developed a predictive nomogram model based on significant visual field improvement-associated factors after ETSS in patients with pituitary adenoma. Postoperative visual field improvement is likely to begin at 270–300° in the inferior temporal quadrant. This improvement would enable personalized counselling for individual patients by precisely predicting the visual field recovery after surgery.

ObjectiveToday, cerebrovascular disease has become an important health hazard. Therefore, it is necessary to perform a more accurate and less time-consuming registration of preoperative three-dimensional (3D) images and intraoperative two-dimensional (2D) projection images which is very important for conducting cerebrovascular disease interventions. The 2D–3D registration method proposed in this study is designed to solve the problems of long registration time and large registration errors in 3D computed tomography angiography (CTA) images and 2D digital subtraction angiography (DSA) images.MethodsTo make a more comprehensive and active diagnosis, treatment and surgery plan for patients with cerebrovascular diseases, we propose a weighted similarity measure function, the normalized mutual information-gradient difference (NMG), which can evaluate the 2D–3D registration results. Then, using a multi-resolution fusion optimization strategy, the multi-resolution fused regular step gradient descent optimization (MR-RSGD) method is presented to attain the optimal value of the registration results in the process of the optimization algorithm.ResultIn this study, we adopt two datasets of the brain vessels to validate and obtain similarity metric values which are 0.0037 and 0.0003, respectively. Using the registration method proposed in this study, the time taken for the experiment was calculated to be 56.55s and 50.8070s, respectively, for the two sets of data. The results show that the registration methods proposed in this study are both better than the Normalized Mutual (NM) and Normalized Mutual Information (NMI).ConclusionThe experimental results in this study show that in the 2D–3D registration process, to evaluate the registration results more accurately, we can use the similarity metric function containing the image gray information and spatial information. To improve the efficiency of the registration process, we can choose the algorithm with gradient optimization strategy. Our method has great potential to be applied in practical interventional treatment for intuitive 3D navigation.

Background: Pancreatic adenocarcinoma (PAAD) is one of the most aggressive tumors of the digestive tract, with low surgical resection rate and insensitivity to radiotherapy and chemotherapy. Existing evidence suggests that regulation of ferroptosis can induce PAAD cell death, inhibit tumor growth, and may synergistically improve the sensitivity of other antitumor drugs. However, there is little of systematic research on iron metabolism-related genes in PAAD. In this study, a risk-score system of PAAD iron metabolism-related genes was designed and tested, and verified to be robust.Materials and Methods: The TCGA database was used to download 177 PAAD patients’ message RNA (mRNA) expression profiles and clinical characteristics. By identifying dysregulated iron metabolism-related genes between PAAD related tissues and adjacent normal tissues, univariate Cox proportional hazards regression and LASSO regression algorithm were used to establish prognostic risk-score system and construct nomogram to estimate the 1-, 2-, 3-year survival in PAAD patients. Finally, selected genes were validated by quantitative PCR (q-PCR).Results: A 9-gene related to iron metabolism risk-score system of PAAD was constructed and validated. The clinicopathological characteristics of age, histologic grade, pathologic stage, T stage, residual tumor, and primary therapy outcome were all worse in patients with a higher risk-score. Further, immunohistochemistry results of SLC2A1, MBOAT2, XDH, CTSE, MOCOS, and ATP6V0A4 confirmed that patients with higher expression are more malignant. Then, a nomogram with 9-gene risk score system as a separate clinical factor was utilized to foretell the 1-, 2-, 3-year overall survival rate of PAAD patients. Results of q-PCR showed that 8 of the 9 genes screened were significantly up-regulated in at least one PAAD cell line, and one gene was significantly down-regulated in three PAAD cell lines.Conclusion: To conclude, we generated a nine-gene system linked to iron metabolism as an independent indicator for predicting PAAD prognosis, therefore presenting a possible prognostic biomarker and potential treatment targets for PAAD.

IntroductionAcute pancreatitis (AP) is an inflammatory disease with very poor outcomes. However, the order of induction and coordinated interactions of systemic inflammatory response syndrome (SIRS) and compensatory anti-inflammatory response syndrome (CARS) and the potential mechanisms in AP are still unclear.MethodsAn integrative analysis was performed based on transcripts of blood from patients with different severity levels of AP (GSE194331), as well as impaired lung (GSE151572), liver (GSE151927) and pancreas (GSE65146) samples from an AP experimental model to identify inflammatory signals and immune response-associated susceptibility genes. An AP animal model was established in wild-type (WT) mice and Tlr2-deficient mice by repeated intraperitoneal injection of cerulein. Serum lipase and amylase, pancreas impairment and neutrophil infiltration were evaluated to assess the effects of Tlr2 in vivo.ResultsThe numbers of anti-inflammatory response-related cells, such as M2 macrophages (P = 3.2 × 10–3), were increased with worsening AP progression, while the numbers of pro-inflammatory response-related cells, such as neutrophils (P = 3.0 × 10–8), also increased. Then, 10 immune-related AP susceptibility genes (SOSC3, ITGAM, CAMP, FPR1, IL1R1, TLR2, S100A8/9, HK3 and MMP9) were identified. Finally, compared with WT mice, Tlr2-deficient mice exhibited not only significantly reduced serum lipase and amylase levels after cerulein induction but also alleviated pancreatic inflammation and neutrophil accumulation.DiscussionIn summary, we discovered SIRS and CARS were stimulated in parallel, not activated consecutively. In addition, among the novel susceptibility genes, TLR2might be a novel therapeutic target that mediates dysregulation of inflammatory responses during AP progression.

Backgroud:In-situ thrombosis is a significant pathophysiological basis for the development of pulmonary hypertension (PH). However, thrombolytic therapy for in-situ thrombus in PH was often hampered by the apparent side effects and the low bioavailability of common thrombolytic medications. Nanoscale cyclic RGD (cRGD)-decorated liposomes have received much attention thanks to their thrombus-targeting and biodegradability properties. As a result, we synthesized urokinase-loaded cRGD-decorated liposome (UK-cRGD-Liposome) for therapy of in-situ thrombosis as an exploration of pulmonary hypertensive novel therapeutic approaches.Purpose: To evaluate the utilize of UK-cRGD-Liposome for targeted thrombolysis of in-situ thrombus in PH and to explore the potential mechanisms of in-situ thrombus involved in the development of PH.Methods: UK-cRGD-Liposome nanoscale drug delivery system was prepared using combined methods of thin-film hydration and sonication. Induced PH via subcutaneous injection of monocrotaline (MCT). Fibrin staining (modified MSB method) was applied to detect the number of vessels within-situ thrombi in PH. Echocardiography, hematoxylin-eosin (H & E) staining, and Masson’s trichrome staining were used to analyze right ventricular (RV) function, pulmonary vascular remodeling, as well as RV remodeling.Results: The number of vessels with in-situ thrombi revealed that UK-cRGD-Liposome could actively target urokinase to in-situ thrombi and release its payload in a controlled manner in the in vivo environment, thereby enhancing the thrombolytic effect of urokinase. Pulmonary artery hemodynamics and echocardiography indicated a dramatical decrease in pulmonary artery pressure and a significant improvement in RV function post targeted thrombolytic therapy. Moreover, pulmonary vascular remodeling and RV remodeling were significantly restricted post targeted thrombolytic therapy.Conclusion: UK-cRGD-Liposome can restrict the progression of PH and improve RV function by targeting the dissolution of pulmonary hypertensive in-situ thrombi, which may provide promising therapeutic approaches for PH.

Background: In recent years, gallstones have become a major condition affecting people’s health. Cholecystectomy remains an effective treatment method, but it has large risk factors. It is well known that the hepatoenteric axis plays a key role in gallstone formation, and it is gradually becoming a research focus. Cholesterol homeostasis can be regulated by the liver and intestinal tract in our bodies, and intestinal flora can regulate the digestion and absorption of cholesterol. These two factors are closely related to the formation of gallstones.Aim: To investigate the effects of tauroursodeoxycholic acid (TUDCA) and/or intestinal probiotics on serum biochemical indexes and bile composition in patients with cholecystolithiasis.Methods: For this study, 96 patients with cholecystolithiasis were recruited at our hospital. The patients were randomly divided into four groups according to a random number table: group Ⅰ (TUDCA, 24 cases), group Ⅱ (intestinal probiotics, 24 cases), group Ⅲ (TUDCA and intestinal probiotics, 24 cases) and group Ⅳ (control group, 24 cases). All patients underwent laparoscopic gallbladder-preserving lithotomy or laparoscopic cholecystectomy. Bile samples were identified and extracted during the operation.Results: The results revealed that the levels of serum total bile acid (TBA), serum total cholesterol (TCHOL) and serum triglyceride in groups I, II and III before and after the intervention were statistically significant (p < 0.05). There were significant differences in serum low-density lipoprotein cholesterol (LDL-C) between groups I and II before and after the intervention (p < 0.05), but the serum LDL-C level in group Ⅲ before and after the intervention was similar (p > 0.05). Regarding bile, TBA levels demonstrated no significant difference between groups I and III (p > 0.05), and the differences between the other two groups were statistically significant (p < 0.05). No significant difference was identified in phospholipid and TCHOL levels between groups I and Ⅲ (p > 0.05), and the differences between the other two groups were statistically significant (p < 0.05). There were significant differences in the levels of free Ca2+, pH value and glycoprotein in bile among the four groups (p < 0.05). The levels of cholic acid, chenodeoxycholic acid and deoxycholic acid in bile were significantly different among the four groups (p < 0.05). The level of lithocholic acid (LCA) in groups Ⅱ and Ⅲ was similar, as was the level of LCA in groups I and ⅠV, but the difference in level between the other two groups was statistically significant (p < 0.05).Conclusion: The combination of TUDCA and intestinal probiotics did not enhance the effect of either treatment. The use of intestinal probiotics alone can maximise the reverse development of bile composition in patients with cholecystolithiasis compared with TUDCA alone and a combination of TUDCA and intestinal probiotics, thereby reducing gallstone formation.

The microbial community plays an important role on the solid-state fermentation (SSF) of Chinese cereal vinegar, where acetic acid bacteria (AAB) and lactic acid bacteria (LAB) are the dominant bacteria. In this study, the top-down (in situ) and bottom-up (in vitro) approaches were employed to reveal the interaction of AAB and LAB in SSF of Shanxi aged vinegar (SAV). The results of high-throughput sequencing indicates that Acetobacter pasteurianus and Lactobacillus helveticus are the predominant species of AAB and LAB, respectively, and they showed negative interrelationship during the fermentation. A. pasteurianus CGMCC 3089 and L. helveticus CGMCC 12062, both of which were isolated from fermentation of SAV, showed no nutritional competition when they were co-cultured in vitro. However, the growth and metabolism of L. helveticus CGMCC 12062 were inhibited during SSF due to the presence of A. pasteurianus CGMCC 3089, indicating an amensalism phenomenon between these two species. The transcriptomic results shows that there are 831 differentially expressed genes (|log2 (Fold Change)| > 1 and, p ≤ 0.05) in L. helveticus CGMCC 12062 under co-culture condition comparing to its mono-culture, which are mainly classified into Gene Ontology classification of molecular function, biological process, and cell composition. Of those 831 differentially expressed genes, 202 genes are up-regulated and 629 genes are down-regulated. The down-regulated genes were enriched in KEGG pathways of sugar, amino acid, purine, and pyrimidine metabolism. The transcriptomic results for A. pasteurianus CGMCC 3089 under co-culture condition reveals 529 differentially expressed genes with 393 up-regulated and 136 down-regulated, and the genes within KEGG pathways of sugar, amino acid, purine, and pyrimidine metabolism are up-regulated. Results indicate an amensalism relationship in co-culture of A. pasteurianus and L. helveticus. Therefore, this work gives a whole insight on the interaction between the predominant species in SSF of cereal vinegar from nutrient utilization, endogenous factors inhibition and the regulation of gene transcription.

ObjectivesThe success of the rat model of pulmonary hypertension (PH) is primarily dependent on the measurement of pulmonary artery pressure. We herein demonstrate a novel method for measuring pulmonary artery pressure through a high-frequency ultrasound-guided transthoracic puncture in rats. The efficacy and time of this novel method are also discussed.MethodsA single subcutaneous injection of monocrotaline (MCT) was used to establish a rat model of PH. Through the heat shaping method, the tip of that puncture cannula was maintained at a certain angle after the needle core was removed. In-plane real-time guided trocar puncture of the right ventricular outflow tract was performed in the short-axis section of the parasternal aorta. The external pressure sensor was used to record the real-time waveform of right ventricular systolic pressure, pulmonary artery systolic pressure, and diastolic pressure.ResultsThe success rates of which using this novel method in the model group and the control group were 88.5 and 86.7%, respectively. The time of puncture pressure measurement was 164 ± 31 and 235 ± 50 s, respectively. The right ventricular systolic blood pressure, pulmonary systolic blood pressure, and diastolic blood pressure of the model group were higher than those of the control group.ConclusionThe modified method for trocar is helpful for accurately positioning pulmonary artery manometry. The method described in this paper has a high success rate and short operation time. It can simultaneously measure systolic blood pressure, diastolic blood pressure, and mean pressure of the right ventricle and pulmonary artery. It has a broad application prospect in verifying the rat PH model and pulmonary artery pressure monitoring.

BackgroundThe optimal timing of enteral nutrition (EN) initiation in predicted severe acute gallstone pancreatitis (SAGP) and its influence on disease outcomes are not well known.MethodsWe conducted a retrospective study of patients with predicted SAGP treated with endoscopic retrograde cholangiopancreatography and EN. The patients were classified into two groups according to the timing of EN initiation after admission: within 48 h, and more than 48 h. The primary outcome was in-hospital mortality. The secondary outcomes were length of hospital stay, need for intensive care admission, need for surgical intervention, improvements in blood test results after 7-10 days of EN, incidence of pancreatic necrosis and infection, and hospital care costs. The microbiological profiles of infectious complications were also evaluated.ResultsOf the 98 patients, 31 and 67 started EN within 48 h, and more than 48 h after admission, respectively. Early EN was associated with a decrease in in-hospital mortality (0 vs. 11.9%; p=0.045), length of hospital stay (median:18 vs. 27 days; p=0.001), need for intensive care admission (3.2% vs. 20.9%; p=0.032), and hospital care costs (median:9,289 vs. 13,518 US$; p=0.007), compared to delayed EN. Moreover, early EN for 7-10 days had more beneficial effects on blood test results than delayed EN, including total protein (p=0.03) and CRP (p=0.006) levels. However, the need for surgical intervention and incidence of pancreatic necrosis did not differ between the two groups. In our study, Gram-negative bacteria were the main responsible pathogens (50.5%). Infection with multidrug-resistant organisms (MDRO) was found in 19.4% of the patients. The most common MDRO was MDR Enterococcus faecium. Early EN was not superior in reducing incidence of infected pancreatic necrosis, bacteremia, polymicrobial infection, or MDROs.ConclusionsIn patients with predicted SAGP, early EN is associated with a decrease in in-hospital mortality, length of hospital stay, need of intensive care admission, and hospital care costs, compared to delayed EN. There are no significant benefits of early EN in reducing the rate of infection-related complications. Further studies with larger sample sizes are warranted.

Stock enhancement based on hatchery-reared fish has become one of the most common forms of management practices in marine fisheries resource restoration. However, unnatural rearing environments may cause hatchery-reared fish to diverge phenotypically from wild conspecifics, with negative consequences for post-release performance in the natural environments. To better evaluate the suitability of releasing hatchery-reared fish, it is necessary to understand the phenotypic effects of captive rearing, through comparisons with wild conspecifics. In this study, we compared body morphology, swimming performance, and biochemical body composition between hatchery-reared and wild marbled rockfish (Sebastiscus marmoratus) from the same general gene pool. The results show that the overall body profile differed significantly between the groups, with hatchery-reared individuals having a deeper body (in particular in the head and trunk regions), narrower caudal peduncles, and higher condition factor, as compared to wild conspecifics. Hatchery-reared marbled rockfish also had relatively shorter fins, for a given size. In terms of swimming performance, the hatchery-reared marbled rockfish performed worse than the wild, with slower burst swimming speeds and poorer endurance. Wild rockfish had higher body protein content but lower lipid levels compared to the hatchery-reared individuals. These results suggest that hatchery rearing conditions have a great impact on the phenotypic development, with possibly high effects on their post-release performance of the hatchery-reared marbled rockfish. Modifications for the hatchery environment and operation should be investigated with an aim to minimize the divergence in phenotypic development for production of more wild-like fish for stocking.

Cerebral ischemia and the subsequent cerebral ischemia-reperfusion (I/R) injury usually result in neuronal impairment with serious disabilities. Although neural stem cell (NSC) transplantation can help with functional recovery after stroke, due to the improper cellular milieu after brain injury, direct NSC transplantation will result low cell survival rates and differentiation efficiency into neurons. Here a conductive hybrid hydrogel based on gelatin methacryloyl (GelMA) and poly(3,4-ethylenedioxythiophene): poly (styrene sulfonate) (PEDOT:PSS) was created as a NSC niche for the treatment of cerebral I/R injury. GelMA/PEDOT:PSS hybrid hydrogel promoted the development of NSCs into neurons. GelMA/PEDOT:PSS hydrogel along with NSCs could enhance neuronal activity and minimize apoptosis when co-cultured with oxygen-glucose deprivation/reperfusion (OGD/R) neurons. Furthermore, after 7 days of implantation, GelMA/PEDOT:PSS/NSCs on the infarcted brain of rats subjected to reperfusion injury after middle cerebral artery occlusion (MCAO) was verified to attenuate inflammatory responses. These findings show that the conductive GelMA/PEDOT:PSS hybrid hydrogel could regulate NSC development and act as promising cell niches for the treatment of cerebral I/R injury.

Pancreatic cancer is the leading cause of cancer-related deaths worldwide, with limited treatment options and low long-term survival rates. The complex and variable signal regulation networks are one of the important reasons why it is difficult for pancreatic cancer to develop precise targeted therapy drugs. Numerous studies have associated feedback loop regulation with the development and therapeutic response of cancers including pancreatic cancer. Therefore, we review researches on the role of feedback loops in the progression of pancreatic cancer, and summarize the connection between feedback loops and several signaling pathways in pancreatic cancer, as well as recent advances in the intervention of feedback loops in pancreatic cancer treatment, highlighting the potential of capitalizing on feedback loops modulation in targeted therapy for pancreatic cancer.

Obtaining high precision temperature data is crucial in spaceflight applications, considering the growing demand for high precision temperature measurement and the limited onboard resources with a harsh thermal environment in the spacecraft. How to obtain the data, however, becomes an urgent problem. Kalman filtering method is one of the solutions to obtain high precision temperature data with such limited resources. In this paper, the authors demonstrate the principle of temperature measurement system, the application of Kalman filter in temperature measurement including the processing method of sensor self-heating effect, and establishes the state space of measurement error and system error. Through the test, it could be seen that Kalman filtering can improve the temperature measurement resolution to the order of 100 μK while effectively reducing the temperature measurement bias.

Dual-state emission (DSE) luminogens, a type of luminescent material which can effectively emit light in both dilute solution and solid states, have attracted tremendous attention, due to their widespread applications in chemical sensing, biological imaging, organic electronic devices, and so on. They overcome the shortcomings of aggregation-induced emission (AIE)-type compounds that do not emit light in dilute solutions and aggregation-caused quenching (ACQ)-type compounds that do not emit light in a concentrated or aggregated state. This work reports a novel ionic DSE material based on rigid rod-shaped organic conjugated structure using 4,4′-bis(2-sulfonatostyryl) biphenyl disodium salt (BSBDS); the ion repulsion effect can reduce the strong π–π interaction in aggregation and achieve high-efficiency luminescence in solution and solid states. In addition to excellent DSE characteristics, BSBDS also exhibits a mechanochromic nature and sensitive detection performance for aluminum ion (Al3+).

Complete trajectory planning includes path planning, inverse solution solving and trajectory optimization. In this paper, a highly smooth and time-saving approach to trajectory planning is obtained by improving the kinematic and optimization algorithms for the time-optimal trajectory planning problem. By partitioning the joint space, the paper obtains an inverse solution calculation based on the partitioning of the joint space, saving 40% of the inverse kinematics solution time. This means that a large number of computational resources can be saved in trajectory planning. In addition, an improved sparrow search algorithm (SSA) is proposed to complete the solution of the time-optimal trajectory. A Tent chaotic mapping was used to optimize the way of generating initial populations. The algorithm was further improved by combining it with an adaptive step factor. The experiments demonstrated the performance of the improved SSA. The robot’s trajectory is further optimized in time by an improved sparrow search algorithm. Experimental results show that the method can improve convergence speed and global search capability and ensure smooth trajectories.

Injectable hydrogels offer a new therapy option for irregular bone deformities. Based on gelatin methacryloyl (GelMA), bone marrow mesenchymal stem cells (BMSCs), and bone morphogenetic protein 2 (BMP2), we created a photo-crosslinked composite bioactive scaffold. The composite scaffolds had appropriate mechanical properties for stem cells adhesion and proliferation, as well as good biocompatibility and the ability to stimulate BMSCs osteogenic differentiation in vitro. The synergistic effect of BMSCs and BMP2 enabled the composite bioactive scaffold to exhibit higher osteogenic potential in vivo than scaffolds loaded alone with BMSCs or BMP2, according to imaging and histology studies. In conclusion, by promoting the osteogenic differentiation of BMSCs, the composite bioactive scaffold based on BMSCs-BMP2-GelMA has demonstrated remarkable application potential in bone regeneration and bone defects repair.

Organic room temperature phosphorescence (RTP) materials have received considerable attention due to their fascinating photophysical properties. During the past decade, various organic luminogens exhibiting RTP emission in solid states were reported. However, the phosphorescence emission of organic compounds can hardly be observed in their solutions at room temperature. Herein, we reported two fluorene derivatives that can emit RTP in degassed organic solvents, polymer doped film, and crystalline states. Furthermore, those RTP luminogens emitted different colors with different phosphorescence lifetimes in multi-states. These results indicated that the phosphorescence performance can be adjusted flexibly in different condensed states. To our knowledge, this is the first example possessing diverse organic RTP at multi-states, including solution state.

Rice stripe mosaic virus (RSMV), a newly discovered plant cytorhabdovirus, and rice gall dwarf virus (RGDV), a plant reovirus, are transmitted by leafhopper Recilia dorsalis in a persistent-propagative manner. In this study, field surveys in Luoding city, Guangdong province of southern China, showed that RSMV and RGDV frequently co-infected rice plants. Furthermore, this co-infection had a synergistic effect on viral replication potential and pathogenicity in rice plants. Meanwhile, RSMV and RGDV also co-infected R. dorsalis vectors, and RGDV significantly promoted the propagation of RSMV in co-infected vectors. Accordingly, co-infection significantly promoted the acquisition and transmission efficiencies of RSMV by R. dorsalis. However, such co-infection did not significantly affect the propagation of RGDV in vectors. More importantly, we also observed that non-viruliferous R. dorsalis preferred to feed on co-infected rice plants, and this process further affected the feeding behavior of R. dorsalis to enhance viral release into rice phloem. These results provided the clues as to why RSMV had been a gradually expanding problem, creating an increasing risk of damage to rice production. Our findings revealed that synergism between RSMV and RGDV in their host and vector enhanced the propagation and transmission of RSMV, which will help guide the formulation of viral control strategies.

Background: Serpin peptidase inhibitor clade H, member 1 (SERPINH1) is a gene encoding a member of the serpin superfamily of serine proteinase inhibitors. The upregulated of SERPINH1 was associated with poor prognosis in breast cancer, stomach adenocarcinoma, and esophageal carcinoma. However, the role of SERPINH1 in pan-cancer is largely unexplored.Methods: SERPINH1 expression and the correlation with prognosis in human pan-cancer were analyzed by the Cancer Genome Atlas and the Genotype-Tissue Expression dataset. Pearson correlation analysis was applied to evaluate the role of SERPINH1 expression in tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repair (MMR), DNA methyltransferase, and common immunoregulators. Spearman’s correlation test was used to analysis SERPINH1 expression in tumor immune infiltration and infiltrating immune cells via the Tumor Immune Evaluation Resource database. Furtherly, immunohistochemistry staining of SERPINH1 was acquired from the Human Protein Atlas database for validation.Results: SERPINH1 was abnormally expressed in fourteen cancers. The high expression of SERPINH1 significantly reduced the overall survival (OS), disease-specific survival, and progression free interval in eleven cancers. Moreover, SERPINH1 expression was correlated with MMR, MSI, TMB, and DNA methylation in multiple types of cancer. Also, SERPINH1 expression showed strong association with immunoregulators and immune checkpoint markers in testicular germ cell tumors, brain lower grade glioma (LGG), pheochromocytoma and paraganglioma. In addition, SERPINH1 expression was related to immune cell infiltration in multiple cancers, particularly in breast invasive carcinoma, LGG, and liver hepatocellular carcinoma. The result of immunohistochemistry verification shown that SERPINH1 staining was higher in tumor samples than in normal tissue in colon adenocarcinoma, head and neck squamous cell carcinoma, kidney renal papillary cell carcinoma and cervical squamous cell carcinoma, which was consistent with the result of OS.Conclusion: Overall, these results indicate that SERPINH1 may serve as an important prognostic biomarker and correlate with tumor immunity in human pan-cancer.

Diabetic kidney disease (DKD) is the most common cause of end-stage kidney disease worldwide and is the main microvascular complication of diabetes. The increasing prevalence of diabetes has increased the need for effective treatment of DKD and identification of new therapeutic targets for better clinical management. Mitophagy is a highly conserved process that selectively removes damaged or unnecessary mitochondria via the autophagic machinery. Given the important role of mitophagy in the increased risk of DKD, especially with the recent surge in COVID-19-associated diabetic complications, in this review, we provide compelling evidence for maintaining homeostasis in the glomeruli and tubules and its underlying mechanisms, and offer new insights into potential therapeutic approaches for treatment of DKD.

Background: Stomach adenocarcinoma (STAD) is a significant global health problem. It is urgent to identify reliable predictors and establish a potential prognostic model.Methods: RNA-sequencing expression data of patients with STAD were downloaded from the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) database. Gene expression profiling and survival analysis were performed to investigate differentially expressed genes (DEGs) with significant clinical prognosis value. Overall survival (OS) analysis and univariable and multivariable Cox regression analyses were performed to establish the prognostic model. Protein–protein interaction (PPI) network, functional enrichment analysis, and differential expression investigation were also performed to further explore the potential mechanism of the prognostic genes in STAD. Finally, nomogram establishment was undertaken by performing multivariate Cox regression analysis, and calibration plots were generated to validate the nomogram.Results: A total of 229 overlapping DEGs were identified. Following Kaplan–Meier survival analysis and univariate and multivariate Cox regression analysis, 11 genes significantly associated with prognosis were screened and five of these genes, including COL10A1, MFAP2, CTHRC1, P4HA3, and FAP, were used to establish the risk model. The results showed that patients with high-risk scores have a poor prognosis, compared with those with low-risk scores (p = 0.0025 for the training dataset and p = 0.045 for the validation dataset). Subsequently, a nomogram (including TNM stage, age, gender, histologic grade, and risk score) was created. In addition, differential expression and immunohistochemistry stain of the five core genes in STAD and normal tissues were verified.Conclusion: We develop a prognostic-related model based on five core genes, which may serve as an independent risk factor for survival prediction in patients with STAD.

Feed conversion efficiency (FCE) is an economically crucial trait in fish, however, little progress has been made in genetics and genomics for this trait because phenotypes of the trait are difficult to measure. In this study, we constructed a high-density and high-resolution genetic linkage map with 28,416 SNP markers for common carp (Cyprinus carpio) based on high throughput genotyping with the carp 250K single nucleotide polymorphism (SNP) array in a full-sib F1 family of mirror carp (Cyprinus carpio) consisting of 141 progenies. The linkage map contained 11,983 distinct loci and spanned 3,590.09 cM with an average locus interval of 0.33 cM. A total of 17 QTL for the FCE trait were detected on four LGs (LG9, LG20, LG28, and LG32), explaining 8.9–15.9% of the phenotypic variations. One major cluster containing eight QTL (qFCE1-28, qFCE2-28, qFCE3-28, qFCE4-28, qFCE5-28, qFCE6-28, qFCE7-28, and qFCE8-28) was detected on LG28. Two clusters consisting of four QTL (qFCE1-32, qFCE2-32, qFCE3-32, and qFCE4-32) and three QTL (qFCE1-20, qFCE2-20, and qFCE3-20) were detected on LG32 and LG20, respectively. Nine candidate genes (ACACA, SCAF4, SLC2A5, TNMD, PCDH1, FOXO, AGO1, FFAR3, and ARID1A) underlying the feed efficiency trait were also identified, the biological functions of which may be involved in lipid metabolism, carbohydrate metabolism, energy deposition, fat accumulation, digestion, growth regulation, and cell proliferation and differentiation according to GO (Gene Ontology). As an important tool, high-density and high-resolution genetic linkage maps play a crucial role in the QTL fine mapping of economically important traits. Our novel findings provided new insights that elucidate the genetic basis and molecular mechanism of feed efficiency and the subsequent marker-assisted selection breeding in common carp.

There is increasing evidence that the natural environment provides substantial benefits to human emotional well-being. The current study synthesized this body of research using the meta-analysis and assessed the positive and negative effects of exposure to both the natural and built environments. We searched four databases and 20 studies were included in the review. The meta-analysis results showed the most convincing evidence that exposure to the natural environment could increase positive affect (standardized mean difference, SMD = 0.61, 95% CI 0.41, 0.81) and decreased negative affect (SMD = −0.47, 95% CI −0.71, −0.24). However, there was extreme heterogeneity between the studies, and the risk of bias was high. According to the subgroup analysis, study region, study design, mean age of the sample, sample size, and type of natural and built environment were found to be important factors during exposure to the natural environment. The implications of these findings for the existing theory and research are discussed. These findings will help convince the health professionals and policymakers to encourage the residents to increase their time spent in the natural environment. These findings of this systematic review also suggested that the creation, maintenance, and enhancement of accessible greenspaces or existing natural environments may form part of a multidimensional approach to increasing emotional well-being of the local populations.

The purpose of this study was to evaluate the clinicopathological features of different degrees of extraglomerular renal vascular lesions (RVLs) in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated renal vasculitis and explore their clinical determinants. This is a retrospective study of 186 patients with ANCA-associated renal vasculitis diagnosed at the First Affiliated Hospital of Zhengzhou University from January 2014 to April 2019. The patients who met the inclusion criteria were divided into non-renal RVLs, mild RVLs, moderate RVLs, and severe RVLs. It was found that there were significant differences in serum creatinine (SCR), estimated glomerular filtration rate (eGFR), erythrocyte sedimentation rate (ESR), high-density lipoprotein (HDL), systolic blood pressure (SBP), the prevalence rate of hypertension, the proportion of normal glomeruli, and the proportion of sclerotic glomeruli and interstitial fibrosis integral. SCR and ESR are independent risk factors for RVLs. The participants were followed up for 1 year, and the progression to end-stage renal disease (ESRD) and death was defined as endpoint events. We found that the survival rate of patients without RVLs was significantly higher than that of patients with RVLs and that the RVLs were an independent risk factor for ESRD or death. Early intervention in the progression of RVLs can improve the prognosis.

Background:Ligusticum chuanxiong Hort (LCH) is a famous ethnomedicine in Asia known for its excellent output on stroke treatment, and borneol usually acts as an assistant for its reducing permeability of the blood–brain barrier (BBB) after stroke. Although their synergy against brain ischemia was verified in previous studies, the potential mechanism is still unknown.Methods: The research aimed to explore the exact synergic mechanisms between LCH and borneol on neurogenesis within the areas of the dentate gyrus and subventricular zone. After treating middle cerebral artery occlusion rats with LCH (0.1 g/kg) and/or borneol (0.08 g/kg), the neurological severity score, brain infarct ratio, Nissl staining, Evans blue permeability, BBB ultrastructure, and expressions of von Willebrand factor and tight junction–associated proteins were measured. Co-localizations of Nestin+/BrdU+ and doublecortin+/BrdU+, and expressions of neuronal nuclei (NeuN) and glial fibrillary acidic protein (GFAP) were observed under a fluorescence microscope. Moreover, astrocyte polarization markers of complement component 3 and pentraxin 3, and relevant neurotrophins were also detected by immunoblotting.Results: Basically, LCH and borneol had different focuses, although both of them decreased infarct areas, and increased quantity of Nissl bodies and expression of brain-derived neurotrophic factor. LCH increased the neurological severity score, NeuN+ cells, and the ratios of Nestin+/BrdU+ and doublecortin+/BrdU+, and decreased GFAP+ cells and ciliary neurotrophic factor expression. Additionally, it regulated the expressions of complement component 3 and pentraxin 3 to transform astrocyte phenotypes. Borneol improved BBB ultrastructure and increased the expressions of von Willebrand factor, tight junction–associated proteins, vascular endothelial growth factor, and vascular endothelial growth factor receptor 2. Unexpectedly, their combined therapy showed more obvious regulations on the Nissl score, Evans blue permeability, doublecortin+/BrdU+, NeuN+ cells, brain-derived neurotrophic factor, and vascular endothelial growth factor than both of their monotherapies.Conclusions: The results indicated that LCH and borneol were complementary to each other in attenuating brain ischemia by and large. LCH mainly promoted neural stem cell proliferation, neurogenesis, and mature neuron preservation, which was probably related to the transformation of reactive astrocytes from A1 subtype to A2, while borneol preferred to maintain the integrity of the BBB, which provided neurogenesis with a homeostatic environment.

Landslides constitute a severe environmental problem in Jiangxi, China. This research was aimed at conducting landslide hazard assessment to provide technical support for disaster reduction and prevention action in the province. Fourteen geo-environmental factors, e.g., slope, elevation, road, river, fault, lithology, rainfall, and land cover types, were selected for this study. A test was made in two cases: (1) only based on the main linear features, e.g., main rivers and roads, and (2) with detailed complete linear features including all levels of roads and rivers. After buffering of the linear features, an information value (IV) analysis was applied to quantify the distribution of the observed landslides for each subset of the 14 factors. The results were inputted into the binary logistic regression model (LRM) for landslide risk modeling, taking the known landslide points as a training set (70% of the total 9,525 points). The calculated probability of a landslide was further classified into five grades with an interval of 0.2 for hazard mapping: very high (3.70%), high (4.05%), moderate (18.72%), low (27.17%), and stable zones (46.36%). The accuracy was evaluated by AUC [the area under the receiver operating characteristic (ROC) curve] vs. the validation set (30%, the remaining landslides). The final results show that with increasing the completeness of the linear features, the modeling reliability also significantly increased. We hence concluded that the tested methodology is capable of achieving the landslide hazard prediction at regional scale, and the results may provide technical support for geohazard reduction and prevention in the studied province.

The biliary microbiota is related to the pathogenesis of human bile duct stones. However, the extent to which a history of invasive endoscopic sphincterotomy (EST) affects the biliary bacterial community remains largely unknown. We collected bile samples from the common bile duct of 100 choledocholithiasis patients. We performed 16S rRNA sequencing to investigate and compare the biliary microbial community. The patients without antibiotic treatment (AT) were grouped into three clusters based on their biliary microbial compositions. The patients with a history of EST were significantly enriched in one cluster mainly consisting of gastrointestinal bacteria compared with the other two clusters consisting of oral and environmental bacteria. The β-diversities of patients with and without EST were also significantly different, whereas the α-diversities were comparable. The only significantly enriched bacterial genus associated with a history of EST was Pyramidobacter, while eight other genera were significantly decreased. For patients with AT, seven of these genera maintained their association with EST, including Pyramidobacter. However, after AT, the difference in β-diversities was diminished. EST induced a marked shift in the biliary microbial composition. A cluster of biliary bacteria was associated with a history of EST, and Pyramidobacter was specific to EST.

Backgroud: At present, therapeutic endoscopic retrograde cholangiopancreatography (ERCP) has gradually been used in the diagnosis and treatment of biliary and pancreatic diseases in children, but reports on and the application of ERCP in children, especially in infants, are still highly limited.Case Presentation: This case report describes a 99-day-old infant with choledocholithiasis who successfully underwent ERCP to relieve an obstruction. The infant developed obstructive jaundice during chemotherapy for a malignant tumor, and a routine blood examination showed signs of infection. Liver damage also occurred. B-ultrasound suggested stones in the lower segment of the common bile duct (CBD). After sufficient communication and preparation, biliary drainage was successfully carried out in the infant using adult duodenoscope (JF240) and related instruments with cooperation from the Department of Anesthesiology.Conclusions: This paper preliminarily introduces our experience with adult duodenoscope in children, providing a good example for hospitals without a special duodenoscope for children to carry out pediatric ERCP. Clinicians should pay close attention to the need of careful use of ERCP in infants.

The “green revolution” gene gibberellin oxidase contributes to the semidwarf phenotype, improving product and lodging resistance. Dissecting the function of GA biosynthetic genes would be helpful for dwarf maize breeding. In this study, we edited the maize GA20ox3 gene and generated semidwarf maize plants using CRISPR/Cas9 technology. Application of exogenous gibberellin can recover the dwarf phenotype, indicating that the mutants are gibberellin deficient. The contents of GA12 and GA53 were elevated in the mutants due to the disruption of GA20 oxidase, whereas the contents of other GA precursors (GA15, GA24, GA9, GA44, and GA20) were decreased in the mutants, and the accumulation of bioactive GA1 and GA4 was also decreased, contributing to the semidwarf phenotype. Transgene-free dwarf maize was selected from T2-generation plants and might be useful for maize breeding in the future.

Many plant rhabdoviruses are neurotropic and can persistently infect the central nervous system (CNS) of their insect vectors without causing significant cytopathology. The mechanisms by which the insect CNS resists infection by plant rhabdoviruses are largely unknown. Here, we report that the neural factor Hikaru genki homolog of the leafhopper Nephotettix cincticeps (NcHig) limits the spread of the nucleorhabdovirus rice yellow stunt virus (RYSV) in vector CNS. NcHig is predominantly expressed in the CNS of N. cincticeps, and the knockdown of NcHig expression by RNA interference enhances RYSV infection of the CNS. Furthermore, immuno-blockade of NcHig function by microinjection of N. cincticeps with NcHig antibody also enhances viral infection of the CNS. Thus, we conclude that the neuron-specific factor NcHig can control RYSV propagation in the CNS. Interestingly, we find the Hig homolog of the leafhopper Recilia dorsalis also has antiviral activity during the persistent infection of the cytorhabdovirus rice stripe mosaic virus (RSMV) in vector CNS. We further determine that RYSV and RSMV matrix proteins specifically interact with the complement control protein (CCP) domains of Higs. Thus, the matrix protein-binding ability of Hig is potentially essential for its antiviral activity in rice leafhoppers. Our results demonstrate an evolutionarily conserved antiviral mechanism for Hig to mediate the persistent infection of rice rhabdoviruses in the CNS of leafhopper vectors.