Expression and clinical significance of short-chain fatty acids in patients with intrahepatic cholestasis of pregnancy.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver condition that typically arises in the middle and late stages of pregnancy. Short-chain fatty acids (SCFAs), prominent metabolites of the gut microbiota, have significant connections with various pregnancy complications, and some SCFAs hold potential for treating such complications. However, the metabolic profile of SCFAs in patients with ICP remains unclear. AIM: To investigate the metabolic profiles and differences in SCFAs present in the maternal and cord blood of patients with ICP and determine the clinical significance of these findings. METHODS: Maternal serum and cord blood samples were collected from both patients with ICP (ICP group) and normal pregnant women (NP group). Targeted metabolomics was used to assess the SCFA levels in these samples. RESULTS: Significant differences in maternal SCFAs were observed between the ICP and NP groups. Most SCFAs exhibited a consistent declining trend in cord blood samples from the ICP group, mirroring the pattern seen in maternal serum. Correlation analysis revealed a positive correlation between maternal serum SCFAs and cord blood SCFAs [r (Pearson) = 0.88, P = 7.93e-95]. In both maternal serum and cord blood, acetic and caproic acids were identified as key metabolites contributing to the differences in SCFAs between the two groups (variable importance for the projection > 1). Receiver operating characteristic analysis demonstrated that multiple SCFAs in maternal blood have excellent diagnostic capabilities for ICP, with caproic acid exhibiting the highest diagnostic efficacy (area under the curve = 0.97). CONCLUSION: Compared with the NP group, significant alterations were observed in the SCFAs of maternal serum and cord blood in the ICP group, although they displayed distinct patterns of change. Furthermore, the SCFA levels in maternal serum and cord blood were significantly positively correlated. Notably, certain maternal serum SCFAs, specifically caproic and acetic acids, demonstrated excellent diagnostic efficiency for ICP.

Computed tomography-based radiomics diagnostic approach for differential diagnosis between early- and late-stage pancreatic ductal adenocarcinoma.

BACKGROUND: One of the primary reasons for the dismal survival rates in pancreatic ductal adenocarcinoma (PDAC) is that most patients are usually diagnosed at late stages. There is an urgent unmet clinical need to identify and develop diagnostic methods that could precisely detect PDAC at its earliest stages. AIM: To evaluate the potential value of radiomics analysis in the differentiation of early-stage PDAC from late-stage PDAC. METHODS: A total of 71 patients with pathologically proved PDAC based on surgical resection who underwent contrast-enhanced computed tomography (CT) within 30 d prior to surgery were included in the study. Tumor staging was performed in accordance with the 8th edition of the American Joint Committee on Cancer staging system. Radiomics features were extracted from the region of interest (ROI) for each patient using Analysis Kit software. The most important and predictive radiomics features were selected using Mann-Whitney U test, univariate logistic regression analysis, and minimum redundancy maximum relevance (MRMR) method. Random forest (RF) method was used to construct the radiomics model, and 10-times leave group out cross-validation (LGOCV) method was used to validate the robustness and reproducibility of the model. RESULTS: A total of 792 radiomics features (396 from late arterial phase and 396 from portal venous phase) were extracted from the ROI for each patient using Analysis Kit software. Nine most important and predictive features were selected using Mann-Whitney U test, univariate logistic regression analysis, and MRMR method. RF method was used to construct the radiomics model with the nine most predictive radiomics features, which showed a high discriminative ability with 97.7% accuracy, 97.6% sensitivity, 97.8% specificity, 98.4% positive predictive value, and 96.8% negative predictive value. The radiomics model was proved to be robust and reproducible using 10-times LGOCV method with an average area under the curve of 0.75 by the average performance of the 10 newly built models. CONCLUSION: The radiomics model based on CT could serve as a promising non-invasive method in differential diagnosis between early and late stage PDAC.

Eukaryotic initiation factor 3a promotes the development of diffuse large B-cell lymphoma through regulating cell proliferation.

BACKGROUND: One-third of diffuse large B-cell lymphoma (DLBCL) patients suffer relapse after standard treatment. Eukaryotic initiation factor 3a (eIF3a) is a key player in the initial stage of translation, which has been widely reported to be correlated with tumorigenesis and therapeutic response. This study aimed to explore the biological role of eIF3a, evaluate its prognostic and therapeutic potential in DLBCL. METHODS: RNA-seq datasets from GEO database were utilized to detect the expression and prognostic role of eIF3a in DLBCL patients. Protein level of eIF3a was estimated by western blot and immunohistochemical. Next, DLBCL cells were transfected with lentiviral vector either eIF3a-knockdown or empty to assess the biological role of eIF3a. Then, samples were divided into 2 clusters based on eIF3a expression and differentially expressed genes (DEGs) were identified. Function enrichment and mutation analysis of DEGs were employed to detect potential biological roles. Moreover, we also applied pan-cancer and chemosensitivity analysis for deep exploration. RESULTS: eIF3a expression was found to be higher in DLBCL than healthy controls, which was associated with worse prognosis. The expression of eIF3a protein was significantly increased in DLBCL cell lines compared with peripheral blood mononuclear cells (PBMCs) from healthy donors. eIF3a knockdown inhibited the proliferation of DLBCL cells and the expression of proliferation-related proteins and increase cell apoptosis rate. Besides, 114 DEGs were identified which had a close linkage to cell cycle and tumor immune. eIF3a and DEGs mutations were found to be correlated to chemosensitivity and vital signal pathways. Pan-cancer analysis demonstrated that high eIF3a expression was associated with worse prognosis in several tumors. Moreover, eIF3a expression was found to be related to chemosensitivity of several anti-tumor drugs in DLBCL, including Vincristine and Wee1 inhibitor. CONCLUSIONS: We firstly revealed the high expression and prognostic role of eIF3a in DLBCL, and eIF3a might promote the development of DLBCL through regulating cell proliferation and apoptosis. eIF3a expression was related to immune profile and chemosensitivity in DLBCL. These results suggest that eIF3a could serve as a potential prognostic biomarker and therapeutic target in DLBCL.

Optimizing dietary rumen-degradable starch to rumen-degradable protein ratio improves lactation performance and nitrogen utilization efficiency in mid-lactating Holstein dairy cows.

The dietary rumen-degradable starch (RDS) to rumen-degradable protein (RDP) ratio, denoted as the RDS-to-RDP ratio (SPR), has been proven to enhance in vitro rumen fermentation. However, the effects of dietary SPR in vivo remain largely unexplored. This study was conducted to investigate the effect of dietary SPR on lactation performance, nutrient digestibility, rumen fermentation patterns, blood indicators, and nitrogen (N) partitioning in mid-lactating Holstein cows. Seventy-two Holstein dairy cows were randomly assigned to three groups (24 head/group), balanced for (mean ± standard deviation) days in milk (116 ± 21.5), parity (2.1 ± 0.8), milk production (42 ± 2.1 kg/d), and body weight (705 ± 52.5 kg). The cows were fed diets with low (2.1, control), medium (2.3), or high (2.5) SPR, formulated to be isoenergetic, isonitrogenous, and iso-starch. The study consisted of a one-week adaptation phase followed by an eight-week experimental period. The results indicated that the high SPR group had a lower dry matter intake compared to the other groups (p < 0.05). A quadratic increase in milk yield and feed efficiency was observed with increasing dietary SPR (p < 0.05), peaking in the medium SPR group. The medium SPR group exhibited a lower milk somatic cell count and a higher blood total antioxidant capacity compared to other groups (p < 0.05). With increasing dietary SPR, there was a quadratic improvement (p < 0.05) in the total tract apparent digestibility of crude protein, ether extract, starch, neutral detergent fiber, and acid detergent fiber. Although no treatment effect was observed in rumen pH, the rumen total volatile fatty acids concentration and microbial crude protein synthesis increased quadratically (p < 0.05) as dietary SPR increased. The molar proportion of propionate linearly increased (p = 0.01), while branched-chain volatile fatty acids linearly decreased (p = 0.01) with increasing dietary SPR. The low SPR group (control) exhibited higher concentration of milk urea N, rumen ammonia N, and blood urea N than other groups (p < 0.05). Despite a linear decrease (p < 0.05) in the proportion of urinary N to N intake, increasing dietary SPR led to a quadratic increase (p = 0.01) in N utilization efficiency and a quadratic decrease (p < 0.05) in the proportion of fecal N to N intake. In conclusion, optimizing dietary SPR has the potential to enhance lactation performance and N utilization efficiency. Based on our findings, a medium dietary SPR (with SPR = 2.3) is recommended for mid-lactating Holstein dairy cows. Nevertheless, further research on rumen microbial composition and metabolites is warranted to elucidate the underlying mechanisms of the observed effects.

Nanodrug-bacteria conjugates-mediated oncogenic collagen depletion enhances immune checkpoint blockade therapy against pancreatic cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) cancer cells specifically produce abnormal oncogenic collagen to bind with integrin α3ß1 receptor and activate the downstream focal adhesion kinase (FAK), protein kinase B (AKT), and mitogen-activated protein kinase (MAPK) signaling pathway. Collectively, this promotes immunosuppression and tumor proliferation and restricts the response rate of clinical cancer immunotherapies. METHODS: Here, by leveraging the hypoxia tropism and excellent motility of the probiotic Escherichia coli strain Nissle 1917 (ECN), we developed nanodrug-bacteria conjugates to penetrate the extracellular matrix (ECM) and shuttle the surface-conjugated protein cages composed of collagenases and anti-programmed death-ligand 1 (PD-L1) antibodies to PDAC tumor parenchyma. FINDINGS: We found the oncogenic collagen expression in human pancreatic cancer patients and demonstrated its interaction with integrin α3ß1. We proved that reactive oxygen species (ROS) in the microenvironment of PDAC triggered collagenase release to degrade oncogenic collagen and block integrin α3ß1-FAK signaling pathway, thus overcoming the immunosuppression and synergizing with anti-PD-L1 immunotherapy. CONCLUSIONS: Collectively, our study highlights the significance of oncogenic collagen in PDAC immunotherapy, and consequently, we developed a therapeutic strategy that can deplete oncogenic collagen to synergize with immune checkpoint blockade for enhanced PDAC treatment efficacy. FUNDING: This work was supported by the University of Wisconsin Carbone Cancer Center Research Collaborative and Pancreas Cancer Research Task Force, UWCCC Transdisciplinary Cancer Immunology-Immunotherapy Pilot Project, and the start-up package from the University of Wisconsin-Madison (to Q.H.).

Projected soil carbon loss with warming in constrained Earth system models.

The soil carbon-climate feedback is currently the least constrained component of global warming projections, and the major source of uncertainties stems from a poor understanding of soil carbon turnover processes. Here, we assemble data from long-term temperature-controlled soil incubation studies to show that the arctic and boreal region has the shortest intrinsic soil carbon turnover time while tropical forests have the longest one, and current Earth system models overestimate intrinsic turnover time by 30 percent across active, slow and passive carbon pools. Our constraint suggests that the global soils will switch from carbon sink to source, with a loss of 0.22-0.53 petagrams of carbon per year until the end of this century from strong mitigation to worst emission scenarios, suggesting that global soils will provide a strong positive carbon feedback on warming. Such a reversal of global soil carbon balance would lead to a reduction of 66% and 15% in the current estimated remaining carbon budget for limiting global warming well below 1.5 °C and 2 °C, respectively, rendering climate mitigation much more difficult.

Bionanoengineered 2D monoelemental selenene for piezothrombolysis.

Thrombosis-related diseases represent the leading causes of disability or death worldwide. However, conventional thrombolytic therapies are subjected to narrow therapeutic window, short circulation half-life and bleeding. Herein, we rationally design and develop a safe and efficient nonpharmaceutical thrombolysis strategy based on a specific piezocatalytic effect arising from platelet membrane (PM)-conjugated two-dimensional (2D) piezoelectric selenene, Se-PM nanosheets (NSs). The 2D selenene is fabricated from nonlayered bulk selenium powder by a facile liquid-phase exfoliation method, and the PM conjugation confers selenene with the distinct thrombus-homing feature. Under ultrasonic activation, the piezoelectric characteristic of selenene triggers electrons and holes separation, resulting in generation of reactive oxygen species (ROS) by reacting with surrounding H2O and O2 in the thrombosis microenvironment for thrombolysis. Both systematic in vitro and in vivo assessments demonstrate that the biocompatible Se-PM NSs efficiently degrade erythrocytes, fibrin and artificial blood clots under ultrasound irradiation. Compared to the clinical thrombolytic drug urokinase plasminogen activator, the engineered Se-PM NSs possess excellent thrombolytic efficacy by single treatment in the tail thrombosis animal model without bleeding risk. The engineered Se-PM nanoplatform marks an exciting jumping-off point for research into the application of piezocatalysis in clinical treatment of thrombosis.

Multimodal Imaging-Guided Photoimmunotherapy of Pancreatic Cancer by Organosilica Nanomedicine.

Immune checkpoint blockade (ICB) treatments have contributed to substantial clinical progress. However, challenges persist, including inefficient drug delivery and penetration into deep tumor areas, inadequate response to ICB treatments, and potential risk of inflammation due to over-activation of immune cells and uncontrolled release of cytokines following immunotherapy. In response, this study, for the first time, presents a multimodal imaging-guided organosilica nanomedicine (DCCGP) for photoimmunotherapy of pancreatic cancer. The novel DCCGP nanoplatform integrates fluorescence, magnetic resonance, and real-time infrared photothermal imaging, thereby enhancing diagnostic precision and treatment efficacy for pancreatic cancer. In addition, the incorporated copper sulfide nanoparticles (CuS NPs) lead to improved tumor penetration and provide external regulation of immunotherapy via photothermal stimulation. The synergistic immunotherapy effect is realized through the photothermal behavior of CuS NPs, inducing immunogenic cell death and relieving the immunosuppressive tumor microenvironment. Coupling photothermal stimulation with αPD-L1-induced ICB, the platform amplifies the clearance efficiency of tumor cells, achieving an optimized synergistic photoimmunotherapy effect. This study offers a promising strategy for the clinical application of ICB-based combined immunotherapy and presents valuable insights for applications of organosilica in precise tumor immunotherapy and theranostics.

Joining of metallic glasses in liquid via ultrasonic vibrations.

Joining processes especially for metallic materials play critical roles in manufacturing industries and structural applications, therefore they are essential to human life. As a more complex technique, under-liquid joining has far-reaching implications for national defense, offshore mining. Furthermore, up-to-now, the effective joining of metals in extreme environments, such as the flammable organo-solvent or the arctic liquid nitrogen, is still uninvestigated. Therefore, an efficient under-liquid joining approach is urgently called for. Here we report a method to join different types of metallic glasses under water, seawater, alcohol and liquid-nitrogen. The dynamic heterogeneity and liquid-like region expansion induces fluid-like behavior under ultrasonic vibration to promote oxide layer dispersion and metal bonding, allowing metallic glasses to be successfully joined in heat-free conditions, while still exhibiting excellent tensile strength (1522 MPa), bending strength (2930 MPa) and improved corrosion properties. Our results provide a promising strategy for manufacturing under offshore, polar, oil-gas and space environments.

Research on the crisis propagation in the global coal trade under the Russia-Ukraine conflict.

The outbreak of the 2022 Russia-Ukraine conflict exacerbated the natural gas supply shortage in European countries. European countries restarted coal-fired power plants to maintain economic and social operations. The uneven distribution of coal resources in the world makes coal international trade inevitable. The intricate trade relations between trading countries have formed a coal trade network. When a country's coal exports are limited due to geopolitical factors, it will cause coal supply risks. The risk will spread to more countries along the trade network, eventually leading to the collapse of the trade network. This paper builds a crisis propagation model of the coal supply under the Russia-Ukraine conflict using the cascading failure model. The results showed that the Czech Republic, Ireland, Portugal, and Bulgaria become abnormal as the proportion of coal exports ß increases. When the Russian Federation reduced its coal exports by 80% and countries maintained only 10% coal exports against crisis, 23 European countries were the worst. Iceland, Ireland, Turkey and other countries were spread by the indirect risk and became abnormal countries. The Czech Republic and Bulgaria were spread by multiple risk and became abnormal countries.

All-fiberized linearly polarized superfluorescent fiber source with 5 kW power output.

A superfluorescent fiber source (SFS) is a special fiber source that commonly possesses high temporal stability and a wide spectral linewidth. In this work, an all-fiberized linearly polarized SFS with, to our knowledge, record output power and near-diffraction-limited beam quality is presented. Up to 5.03 kW SFS is achieved at a pump power of 6.18 kW with a corresponding conversion efficiency of ∼81.1%. At maximum output power, the signal-to-noise ratio to background spectral noise is over 50 dB, the polarization extinction ratio is ∼17d B, and the beam quality factor is M x 2=1.49, M y 2=1.44. Further comparisons confirm the power scalability of fiber amplifiers employing SFSs as seed lasers. Overall, this work could provide a good reference for potential exploration of high-power fiber laser systems.

Differential diagnostic value of tumor markers and contrast-enhanced computed tomography in gastric hepatoid adenocarcinoma and gastric adenocarcinoma.

Objective: This study aimed to investigate the effectiveness of tumor markers and contrast-enhanced computed tomography (CE-CT) in differentiating gastric hepatoid adenocarcinoma (GHA) from gastric adenocarcinoma (GA). Methods: This retrospective study included 160 patients (44 with GHA vs. 116 with GA) who underwent preoperative CE-CT. Preoperative serum concentrations of tumor biomarkers and CT imaging features were analyzed, including alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 125 (CA125), tumor location, growth pattern, size, enhancement pattern, cystic changes, and mass contrast enhancement. Multivariate logistic regression analyses were performed to evaluate useful tumor markers and CT imaging features for differentiating GHA from GA. Results: When compared to GA, GHA showed a higher serum AFP [13.27 ng/ml (5.2-340.1) vs. 2.7 ng/ml (2.2-3.98), P <0.001] and CEA levels [4.07 ng/ml (2.73-12.53) vs. 2.42 ng/ml (1.38-4.31), P <0.001]. CT imaging showed GHA with a higher frequency of tumor location in the gastric antrum (P <0.001). GHA had significantly lower attenuation values at the portal venous phase [PCA, (82.34 HU ± 8.46 vs. 91.02 HU ± 10.62, P <0.001)] and delayed phase [DCA, (72.89 HU ± 8.83 vs. 78.27 HU ± 9.51, P <0.001)] when compared with GA. Multivariate logistic regression analyses revealed that tumor location, PCA, and serum AFP level were independent predictors of differentiation between GHA and GA. The combination of these three predictors performed well in discriminating GHA from GA, with an AUC of 0.903, a sensitivity of 86.36%, and a specificity of 81.90%. Conclusions: Integrated evaluation of tumor markers and CT features, including tumor location, PCA, and serum AFP, allowed for more accurate differentiation of GHA from GA.

Nitrogen availability constrains grassland plant diversity in response to grazing.

Grassland plant diversity has been observed with divergent responses in grazing experiments around the world. However, the dominant role of nitrogen (N) availability in controlling this global variation has not been well explored, impeding our capacity to formulate effective strategies for preserving grassland plant diversity. Here, we synthesized data from 306 grazing experiments that measured plant diversity and soil N content across global grasslands. Overall, grazing reduced plant diversity by 7.63 %, with substantial variations observed across the dataset. Our study revealed that these contrasting effects were best explained by soil N change. Plant diversity under enhanced soil N showed a strong increase in response to grazing. We found that lower grazing intensity and higher background N deposition could collectively enhance soil N, thereby promoting diversity. These results suggest that while avoiding high grazing intensity is crucial in maintaining biodiversity of grazed grasslands, it alone is not sufficient. In regions with lower N deposition (< 500 mg N m-2 yr-1), additional management strategies that target improving soil fertility are needed. Our analysis propounds that local environmental conditions should be incorporated into decision-making of grassland biodiversity conservation, or ignoring this may lead to counterproductive impacts.

Exploring the key genetic association between chronic pancreatitis and pancreatic ductal adenocarcinoma through integrated bioinformatics.

Background: Pancreatic ductal adenocarcinoma (PDAC) develops rapidly and has a poor prognosis. It has been demonstrated that pancreatic ductal adenocarcinoma and chronic pancreatitis (CP) have a close connection. However, the underlying mechanisms for chronic pancreatitis transforming into pancreatic ductal adenocarcinoma are still unclear. The purpose of this study was to identify real hub genes in the development of chronic pancreatitis and pancreatic ductal adenocarcinoma. Methods: RNA-seq data of chronic pancreatitis and pancreatic ductal adenocarcinoma were downloaded from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was performed to construct a gene co-expression network between chronic pancreatitis and pancreatic ductal adenocarcinoma. GEO2R and a Venn diagram were used to identify differentially expressed genes. Then visualized networks were constructed with ClueGO, and modules of PPI network were calculated by MCODE plugin. Further validation of the results was carried out in two additional cohorts. Analyses of CEL-coexpressed genes and regulators including miRNAs and transcription factors were performed by using the corresponding online web tool. Finally, the influence of CEL in the tumor immune microenvironment (TIME) was assessed by immune contextual analysis. Results: With the help of WGCNA and GEO2R, four co-expression modules and six hub genes were identified, respectively. ClueGO enrichment analysis and MCODE cluster analysis revealed that the dysfunctional transport of nutrients and trace elements might contribute to chronic pancreatitis and pancreatic ductal adenocarcinoma development. The real hub gene CEL was identified with a markedly low expression in pancreatic ductal adenocarcinoma in external validation sets. According to the miRNA-gene network construction, hsa-miR-198 may be the key miRNA. A strong correlation exists between CEL and TIME after an evaluation of the influence of CEL in TIME. Conclusion: Our study revealed the dysfunctional transport of nutrients and trace elements may be common pathogenesis of pancreatic ductal adenocarcinoma and chronic pancreatitis. Examination on these common pathways and real hub genes may shed light on the underlying mechanism.

Cuproptosis-related risk score based on machine learning algorithm predicts prognosis and characterizes tumor microenvironment in head and neck squamous carcinomas.

Cuproptosis is a recently discovered type of programmed cell death that shows significant potential in the diagnosis and treatment of cancer. It has important significance in the prognosis of HSNC. This study aims to construct a cuproptosis-related prognostic model and risk score through new data analysis methods such as machine learning algorithms for the prognosis analysis of HSNC. Protein-protein interaction network and machine learning methods were employed to identify hub genes that were used to construct a TreeGradientBoosting model for predicting overall survival. The relationship between the risk scores obtained from the model and features such as tumor microenvironment (TME) and tumor immunity was explored. The C-indexes of the TreeGradientBoosting model in the training and validation cohorts were 0.776 and 0.848, respectively. The nomogram based on risk scores and clinical features showed good performance, and distinguished the TME and immunity between high-risk and low-risk groups. The cuproptosis-associated risk score can be used to predict prognoses, TME, and tumor immunity of HNSC patients.

Initial exploration on potential fire hazards detection from coal spontaneous combustion applied by acoustic wave.

Coal spontaneous combustion often wastes resources and causes environmental pollution. Rapid and accurate identification of high temperature areas in coal is essential to reducing such combustion and environmental pollution. The acoustic thermometry method has the benefits of large temperature measurement space, non-contact, and high interference resistance. Determining the attenuation characteristics of acoustic waves in loose coal is the basis and premise for realizing acoustic temperature measurement. Four types of bituminous coal were scanned by computer tomography equipment. A self-designed acoustic attenuation test device was used to test coal samples under different temperatures and particle sizes. The study result demonstrates that the distribution characteristics of loose coal voids are mainly related to the particle size. The smaller the particle size range, the more uniform the void distribution. As the size of the coal particles increases, the voids become larger. The acoustic attenuation coefficients of four coal samples showed an increasing trend as frequency increased. The influence of coal particle size distribution on the acoustic attenuation coefficient was greater than that of temperature and metamorphic degree. The peak values of coal sound attenuation for different particle sizes were around 400, 700, 1100, and 1600 Hz. This indicated that the distribution of voids was the main factor affecting the propagation of acoustic waves. By analysing the attenuation mechanism of the acoustic wave in loose coal, the attenuation of acoustic temperature measurement signal was caused by the combined effect of loose coal on acoustic wave absorption and scattering. The study results provide theoretical support for the realization of acoustic wave detection of high temperature point in loose coal spontaneous combustion.

Muscle-derived stem cell exosomes with overexpressed miR-214 promote the regeneration and repair of rat sciatic nerve after crush injury to activate the JAK2/STAT3 pathway by targeting PTEN.

Introduction: This study aimed to investigate the effect of muscle-derived stem cell (MDSC) exosomes with overexpressed miR-214 on the regeneration and repair of rat sciatic nerve after crush injury and its molecular mechanism. Methods: First, primary MDSCs, Schwann cells (SCs) and dorsal root ganglion (DRG) neurons were isolated and cultured, and the characteristics of MDSCs-derived exosomes were identified by molecular biology and immunohistochemistry. NC mimics and miR-214 mimics were transfected to obtain exo-NC and exo-miR-214. An in vitro co-culture system was established to determine the effect of exo-miR-214 on nerve regeneration. The restoration of sciatic nerve function of rats by exo-miR-214 was evaluated by walking track analysis. Immunofluorescence for NF and S100 was used to detect the regeneration of axon and myelin sheath in injured nerve. The Starbase database was used to analyze the downstream target genes of miR-214. QRT-PCR and dual luciferase reporter assays were used to validate the miR-214 and PTEN interaction relationship. And the expression of the JAK2/STAT3 pathway-related proteins in sciatic nerve tissues were detected by western blot. Results: The above experiments showed that MDSCs-derived exosomes with overexpressed miR-214 was found to promote the proliferation and migration of SCs, increase the expression of neurotrophic factors, promote axon extension of DRG neurons and positively affect the recovery of nerve structure and function. In addition, PTEN was a target gene of miR-214. Exo-miR-214 can significantly inhibit the expression level of PTEN, increase the protein expression levels of p-JAK2 and p-STAT3 and the ratio of p-JAK2/JAK2 and p-STAT3/STAT3, also MDSCs-derived exosomes with overexpressed miR-214 can reduce the occurrence of denervated muscle atrophy. Conclusion: In summary, the MDSCs-derived exosomes with overexpressed miR-214 is involved in peripheral nerve regeneration and repair in rats after sciatic nerve crush injury to activate the JAK2/ STAT3 pathway by targeting PTEN.

Diagnostic accuracy of apparent diffusion coefficient to differentiate intrapancreatic accessory spleen from pancreatic neuroendocrine tumors.

BACKGROUND: Intrapancreatic accessory spleen (IPAS) shares similar imaging findings with hypervascular pancreatic neuroendocrine tumors (PNETs), which may lead to unnecessary surgery. AIM: To investigate and compare the diagnostic performance of absolute apparent diffusion coefficient (ADC) and normalized ADC (lesion-to-spleen ADC ratios) in the differential diagnosis of IPAS from PNETs. METHODS: A retrospective study consisting of 29 patients (16 PNET patients vs 13 IPAS patients) who underwent preoperative contrast-enhanced magnetic resonance imaging together with diffusion-weighted imaging/ADC maps between January 2017 and July 2020 was performed. Two independent reviewers measured ADC on all lesions and spleens, and normalized ADC was calculated for further analysis. The receiver operating characteristics analysis was carried out for evaluating the diagnostic performance of both absolute ADC and normalized ADC values in the differential diagnosis between IPAS and PNETs by clarifying sensitivity, specificity, and accuracy. Inter-reader reliability for the two methods was evaluated. RESULTS: IPAS had a significantly lower absolute ADC (0.931 ± 0.773 × 10-3 mm2/s vs 1.254 ± 0.219 × 10-3 mm2/s) and normalized ADC value (1.154 ± 0.167 vs 1.591 ± 0.364) compared to PNET. A cutoff value of 1.046 × 10-3 mm2/s for absolute ADC was associated with 81.25% sensitivity, 100% specificity, and 89.66% accuracy with an area under the curve of 0.94 (95% confidence interval: 0.8536-1.000) for the differential diagnosis of IPAS from PNET. Similarly, a cutoff value of 1.342 for normalized ADC was associated with 81.25% sensitivity, 92.31% specificity, and 86.21% accuracy with an area under the curve of 0.91 (95% confidence interval: 0.8080-1.000) for the differential diagnosis of IPAS from PNET. Both methods showed excellent inter-reader reliability with intraclass correlation coefficients for absolute ADC and ADC ratio being 0.968 and 0.976, respectively. CONCLUSION: Both absolute ADC and normalized ADC values can facilitate the differentiation between IPAS and PNET.

Based on network pharmacology to explore the effect and mechanism of Yipibushen decoction in improving obese type 2 diabetes mellitus with oligoasthenotspermia.

ETHNOPHARMACOLOGICAL RELEVANCE: A traditional Chinese medicine experience compound known as Yipibushen (YPBS) decoction stimulates qi and nourishes yin, stimulates the kidney and solid essence, dissolves phlegm and eliminates stasis. YPBS decoction has proven to be successful in treating obese type 2 diabetes mellitus with oligoasthenotspermia in clinical settings. Nevertheless, the pharmacological mechanism is not understood. AIM OF THE STUDY: Investigating the mechanism of action of YPBS decoction in enhancing the obese type 2 diabetes mellitus with oligoasthenotspermia involved network pharmacology and animal validation techniques. METHODS AND MATERIALS: The YPBS Decoction' active components were found in the TCMSP database and their targets were identified using UniProtKB. Additionally, targets for the obese type 2 diabetes mellitus with oligoasthenotspermia were found in the GeneCard, DisGeNet, TTD and OMIM databases. The intersection of active ingredients, the obese type 2 diabetes mellitus with oligoasthenotspermia was chosen as the intersection target. The protein-protein interaction (PPI) network of the intersection target was built with the aid of Cytoscape 3.9.1, the core target of PPI was obtained through software analysis in R-project, GO enrichment and KEGG enrichment analysis was carried out on the core target. Finally, animal experiments were used to verify the intersection target. RESULTS: The research revealed 74 intersection targets of YPBS decoction active ingredients in the obese type 2 diabetes mellitus with oligoasthenotspermia. There were also 18 PPI core targets, GO enrichment analysis of PPI core targets involving response to oxidative stress, membrane raft, DNA-binding transcription regulator complex and other biological processes; KEGG involving endocrine resistance, PI3K/AKT signaling pathway, apoptosis and other signal pathways. In the obese type 2 diabetes mellitus with oligoasthenotspermia mice, animal studies have shown that YPBS decoction group could decrease blood glucose levels and improve insulin resistance; improve testicular function, enhance sperm count, sperm motility, sperm viability, and decrease the malformation rate. It could increase the levels of T-SOD and GSH-Px, and decrease the MDA level. In addition to this, it could improve the amount of testosterone hormone, and enhance the expression of PI3K, p-AKT and Bcl-2. CONCLUSION: By controlling the degree of oxidative stress and the PI3K/AKT/Bcl-2 pathway, YPBS decoction may enhance the obese type 2 diabetes mellitus with Oligoasthenotspermia, provide a scientific basis for clinical diagnosis and therapy.