Patients With Type 2 Diabetes Mellitus and Early Diabetic Kidney Disease Exhibit Lower Computed Tomography-measured Skeletal Muscle Attenuation Values: A Propensity Score-matched Study.

OBJECTIVE: To investigate the association between computed tomography-measured quality characteristics of skeletal muscle (SM) and early diagnosis of diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). METHODS: This retrospective study included patients diagnosed with T2DM, with and without early DKD, between January 2019 and December 2021. To reduce potential bias, propensity score matching (PSM) was performed. The area and computed tomography attenuation values for SM and different abdominal adipose depots were measured. After PSM, logistic and multiple linear regression analyze were performed to analyse risk factors for early DKD. RESULTS: A total of 267 patients were enrolled (mean age, 61.67 years ± 10.87; 155 men) and divided into two groups: T2DM with early DKD (n = 133); and T2DM without DKD (n = 134). After PSM, 230 patients were matched (T2DM with early DKD [n = 115]; and T2DM without DKD [n = 115]), with no statistical differences in general characteristics between the two groups (P > .05). In multivariate logistic regression analysis, high-density lipoprotein cholesterol (odds ratio [OR] 0.14; 95% confidence interval [CI] 0.04-0.49; P = .002), uric acid (OR 1.01; 95% CI 1.00-1.01; P = .006), and SM attenuation value (OR 0.94; 95% CI 0.90-0.98; P = .003) were independent risk factors for early DKD. Multiple linear regression analysis revealed significant correlations between SM attenuation value and cystatin C (ß = -0.39, P = .004), urine albumin-to-creatinine ratio (ß = -0.26, P = .026), and estimated glomerular filtration rate (ß = 0.31 P = .009) after adjustment for confounders. CONCLUSION: Patients with T2DM and lower SM attenuation values may exhibit a higher risk for early DKD than those with higher values, which provides a potential imaging biomarker for early DKD diagnosis.

Biomimetic Nanovesicle with Mitochondria-Synthesized Sonosensitizer and Mitophagy Inhibition for Cancer Sono-Immunotherapy.

Mitochondria are crucial for both sonodynamic therapy and antitumor immunity. However, how to accurately damage mitochondria and meanwhile prevent the mitophagy and immune checkpoint inhibition is still a great challenge. Herein, hexyl 5-aminolevulinate hydrochloride (HAL) and 3-methyladenine (3MA) are loaded into the tumor cell-derived microparticle (X-MP), which can direct the target delivery of the prepared HAL/3MA@X-MP to the tumor cells. HAL induces the confined biosynthesis and accumulation of sonosensitizer PpIX in mitochondria, leading to the localized generation of reactive oxygen species (ROS) upon ultrasound irradiation and, thus, the efficient mitochondrial damage. Meanwhile, 3MA not only inhibits mitophagy but also down-regulates the PD-L1 expression, promoting the immunogenic cell death (ICD) while blocking the immune checkpoint recognition. The smart synergism of precise mitochondrial damage, mitophagy inhibition and antitumor immunity results in potent therapeutic efficacy without obvious side effects.

MALAT1 regulates network of microRNA-15a/16-VEGFA to promote tumorigenesis and angiogenesis in multiple myeloma.

MALAT1 is one of the most hopeful members implicated in angiogenesis in a variety of non-malignant diseases. In multiple myeloma (MM), MALAT1 is recognized as the most highly expressed long non-coding RNA. However, the functional roles of MALAT1 in angiogenesis and the responsible mechanisms have not yet been explored. Herein, we discovered a novel regulatory network dependent on MALAT1 in relation to MM tumorigenesis and angiogenesis. We observed that MALAT1 was upregulated in MM and significantly associated with poor overall survival. MALAT1 knockdown suppressed MM cell proliferation and promoted apoptosis, while restricting endothelial cells angiogenesis. Moreover, MALAT1 directly targeted microRNA-15a/16, and microRNA-15a/16 suppression partly reverted the effects of MALAT1 deletion on MM cells in vitro as well as tumor growth and angiogenesis in vivo. In addition, further study indicated that MALAT1 functioned as a competing endogenous RNA for microRNA-15a/16 to regulate vascular endothelial growth factor A (VEGFA) expression. Our results suggest that MALAT1 plays an important role in the regulatory axis of microRNA-15a/16-VEGFA to promote tumorigenicity and angiogenesis in MM. Consequently, MALAT1 could serve as a novel promising biomarker and a potential antiangiogenic target against MM.

ACSL4: a double-edged sword target in multiple myeloma, promotes cell proliferation and sensitizes cell to ferroptosis.

Overactive fatty acid metabolism is usually found in hematological malignancies including multiple myeloma (MM), but the underlying mechanisms remain unclear. Here, we reveal that acyl-CoA synthetase long-chain family member 4 (ACSL4) is abnormally overexpressed in MM cell lines and MM patients compared to healthy donors. Knockdown of ACSL4 inhibited MM cell proliferation and reduced fatty acid levels possibly by regulating lipid metabolism genes including c-Myc and sterol regulatory element binding proteins (SREBPs). As a propellent in ferroptosis, ACSL4 also determines the sensitivity of MM cells to ferroptosis inducer RSL3. Knockdown of ACSL4 rendered MM cells resistance to ferroptosis. Our findings suggest that ACSL4 is a double-edged sword target in MM. Based on the high expression of ACSL4, ferroptosis induction represents a promising therapeutic strategy for MM.

Perivascular fat attenuation index value and plaque volume increased in non-target lesions of coronary arteries after stenting.

BACKGROUND: Progression of non-target lesions (NTLs) after stenting has been reported and is associated with the triggering of an inflammatory response. The perivascular fat attenuation index (FAI) may be used as a novel imaging biomarker for the direct quantification of coronary inflammation. OBJECTIVES: To investigate whether FAI values can help identify changes in inflammation status in patients undergoing stent implantation, especially in NTLs. METHODS: Patients who underwent pre- and post-stenting coronary computed tomography angiography (CCTA) examination between January 2015 and February 2021 were consecutively enrolled. The pre- and post-stenting FAIs of the full coronary arteries were compared in both the non- and stent-implanted coronary arteries. Moreover, local FAI values were measured and compared between the NTLs and target lesions in the stent implantations. We also compared changes in plaque type and volume in NTLs before and after stenting. RESULTS: A total of 89 patients (mean age 61 years; male 59) were enrolled. The perivascular FAI values in the full coronary arteries decreased after stenting in both the non- and stent-implanted coronary arteries, similar to those in the target lesions. Conversely, the perivascular FAI values in the NTLs increased after stenting (p < 0.05). In addition, the plaque volumes significantly increased in the NTLs after stenting, regardless of whether they were non-calcified, mixed, or calcified (p < 0.05). CONCLUSION: Perivascular FAI values and plaque volumes increased in the NTLs after stenting. Perivascular FAI can be a promising imaging biomarker for monitoring coronary inflammation after stenting and facilitate long-term monitoring in clinical settings. CLINICAL RELEVANCE STATEMENT: Perivascular fat attenuation index, a non-invasive imaging biomarker, may help identify coronary arteries with high inflammation in non-target lesions and facilitate long-term monitoring, potentially providing an opportunity for more targeted treatment. KEY POINTS: • Perivascular fat attenuation index (FAI) values and plaque volumes increased in the non-target lesions (NTLs) after stenting, suggesting potential focal inflammation progression after stenting. However, stenting along with anti-inflammatory treatment ameliorated inflammation in the full coronary arteries. • Perivascular FAI, a non-invasive imaging biomarker, may help identify coronary arteries with high inflammation in NTLs and facilitate long-term monitoring, potentially providing an opportunity for more targeted treatment.

FTO promotes multiple myeloma progression by posttranscriptional activation of HSF1 in an m6A-YTHDF2-dependent manner.

N6-methyladenosine (m6A), as the most pervasive internal modification of eukaryotic mRNA, plays a crucial role in various cancers, but its role in multiple myeloma (MM) pathogenesis has not yet been investigated. In this study, we revealed significantly decreased m6A methylation in plasma cells (PCs) from MM patients and showed that the abnormal m6A level resulted mainly from upregulation of the demethylase fat mass and obesity-associated protein (FTO). Gain- and loss-of-function studies demonstrated that FTO plays a tumor-promoting and pro-metastatic role in MM. Combined m6A and RNA sequencing (RNA-seq) and subsequent validation and functional studies identified heat shock factor 1 (HSF1) as a functional target of FTO-mediated m6A modification. FTO significantly promotes MM cell proliferation, migration, and invasion by targeting HSF1/HSPs in a YTHDF2-dependent manner. FTO inhibition, especially when combined with bortezomib (BTZ) treatment, synergistically inhibited myeloma bone tumor formation and extramedullary spread in NOD-Prkdcem26Cd52il2rgem26Cd22/Nju (NCG) mice. We demonstrated the functional importance of m6A demethylase FTO in MM progression, especially in promoting extramedullary myeloma (EMM) formation, and proposed the FTO-HSF1/HSP axis as a potential novel therapeutic target in MM.

Phytochemical Engineered Bacterial Outer Membrane Vesicles for Photodynamic Effects Promoted Immunotherapy.

Cancer vaccines are emerging as an attractive modality for tumor immunotherapy. However, their practical application is seriously impeded by the complex fabrication and unsatisfactory outcomes. Herein, we construct bacterial outer membrane vesicles (OMVs)-based in situ cancer vaccine with phytochemical features for photodynamic effects-promoted immunotherapy. By simply fusing thylakoid membranes with OMVs, bacteria-plant hybrid vesicles (BPNs) are prepared. After systemic administration, BPNs can target tumor tissues and stimulate the activation of immune cells, including dendritic cells (DCs). The photodynamic effects derived from thylakoid lead to the disruption of local tumors and then the release of tumor-associated antigens that are effectively presented by DCs, inducing remarkable tumor-specific CD8+T cell responses. Moreover, BPNs can efficiently ameliorate the immunosuppressive tumor microenvironment and further boost immune responses. Therefore, both tumor development and metastasis can be efficiently prevented. This work provides a novel idea for developing a versatile membrane-based hybrid system for highly efficient tumor treatment.

Differentiating nontuberculous mycobacterium pulmonary disease from pulmonary tuberculosis through the analysis of the cavity features in CT images using radiomics.

OBJECTIVE: To differentiate nontuberculous mycobacteria (NTM) pulmonary diseases from pulmonary tuberculosis (PTB) by analyzing the CT radiomics features of their cavity. METHODS: 73 patients of NTM pulmonary diseases and 69 patients of PTB with the cavity in Shandong Province Chest Hospital and Qilu Hospital of Shandong University were retrospectively analyzed. 20 patients of NTM pulmonary diseases and 20 patients of PTB with the cavity in Jinan Infectious Disease Hospitall were collected for external validation of the model. 379 cavities as the region of interesting (ROI) from chest CT images were performed by 2 experienced radiologists. 80% of cavities were allocated to the training set and 20% to the validation set using a random number generated by a computer. 1409 radiomics features extracted from the Huiying Radcloud platform were used to analyze the two kinds of diseases' CT cavity characteristics. Feature selection was performed using analysis of variance (ANOVA) and least absolute shrinkage and selection operator (LASSO) methods, and six supervised learning classifiers (KNN, SVM, XGBoost, RF, LR, and DT models) were used to analyze the features. RESULTS: 29 optimal features were selected by the variance threshold method, K best method, and Lasso algorithm.and the ROC curve values are obtained. In the training set, the AUC values of the six models were all greater than 0.97, 95% CI were 0.95-1.00, the sensitivity was greater than 0.92, and the specificity was greater than 0.92. In the validation set, the AUC values of the six models were all greater than 0.84, 95% CI were 0.76-1.00, the sensitivity was greater than 0.79, and the specificity was greater than 0.79. In the external validation set, The AUC values of the six models were all greater than 0.84, LR classifier has the highest precision, recall and F1-score, which were 0.92, 0.94, 0.93. CONCLUSION: The radiomics features extracted from cavity on CT images can provide effective proof in distinguishing the NTM pulmonary disease from PTB, and the radiomics analysis shows a more accurate diagnosis than the radiologists. Among the six classifiers, LR classifier has the best performance in identifying two diseases.

Smart Tumor-Cell-Derived Microparticles Provide On-Demand Photosensitizer Synthesis and Hypoxia Relief for Photodynamic Therapy.

Positioning essential elements of photodynamic therapy (PDT) near to mitochondria can conquer the rigorous spatiotemporal limitations of reactive oxygen species (ROS) transfer and make considerable differences in PDT. However, precise accumulation of photosensitizer (PS) and oxygen within mitochondria is still challenging. We simultaneously encapsulated hexyl 5-aminolevulinate hydrochloride (HAL) and 3-bromopyruvic acid (3BP) into microparticles collected from X-ray-irradiated tumor cells (X-MP). After systemic administration, the developed HAL/3BP@X-MP can specifically target and recognize tumor cells, where HAL induces efficient accumulation of PpIX in mitochondria via the intrinsic haem biosynthetic pathway. Meanwhile, 3BP remarkably increases the oxygen supply by inhibiting mitochondrial respiration. The accurate co-localization and prompt encounter of PpIX and oxygen produce sufficient ROS to directly disrupt mitochondria, resulting in significantly improved PDT outcomes.

Abdominal adipose tissue and type 2 diabetic kidney disease: adipose radiology assessment, impact, and mechanisms.

Diabetic kidney disease (DKD) is a significant healthcare burden worldwide that substantially increases the risk of kidney failure and cardiovascular events. To reduce the prevalence of DKD, extensive research is being conducted to determine the risk factors and consequently implement early interventions. Patients with type 2 diabetes mellitus (T2DM) are more likely to be obese. Abdominal adiposity is associated with a greater risk of kidney damage than general obesity. Abdominal adipose tissue can be divided into different fat depots according to the location and function, including visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), perirenal adipose tissue (PAT), and renal sinus adipose tissue (RSAT), which can be accurately measured by radiology techniques, such as computed tomography (CT) and magnetic resonance imaging (MRI). Abdominal fat depots may affect the development of DKD through different mechanisms, and radiologic abdominal adipose characteristics may serve as imaging indicators of DKD risk. This review will first describe the CT/MRI-based assessment of abdominal adipose depots and subsequently describe the current studies on abdominal adipose tissue and DKD development, as well as the underlying mechanisms in patients of T2DM with DKD.

Multiparametric MRI manifestations of the spontaneous intratumoral coagulative necrosis in HCC.

PURPOSE: To investigate the MRI manifestations of the spontaneous intratumoral coagulative necrosis (iCN) in patients with hepatocellular carcinoma (HCC) and its value in predicting the postoperative early recurrence (≤ 2 years). METHODS: Patients with HCC who underwent preoperative multiparametric MRI between January 2015 and February 2019 were enrolled in this retrospective study. The MRI manifestations of iCNs on TIWI, T2WI, and ADC were recorded. The sensitivity and specificity of MRI for the detection of iCNs were also evaluated. A multivariable Cox proportional hazards model and the Kaplan-Meier method were used to verify the value of histologically-confirmed and MRI-identified iCNs, respectively, in predicting early recurrence. RESULTS: A total of 163 patients (median age, 56 years; interquartile range, 49-64 years; 139 men) with HCCs were evaluated, of whom 27(16.6%) had histologically-confirmed iCNs. MRI identified 92.6% (25 of 27; 95% confidence interval [CI] 74.2%, 98.7%) of iCNs (sensitivity), with a specificity of 79.4% (78 of 136; 95% CI 71.4%, 85.7%), based on non-enhancement on post-contrast MRI. And the MRI-identified iCNs were characterized by a similar appearance to surrounding tumour tissue shown on pre-contrast MRI but not enhanced on post-contrast MRI. The multivariable Cox proportional hazards model revealed that only the presence of histologically-confirmed iCN was independently associated with early HCC recurrence (hazard ratio = 2.73; 95% CI 1.20, 6.21; P = 0.017). The Kaplan-Meier curve showed that the presence of MRI-identified iCN was also associated with early recurrence (P < 0.001). CONCLUSION: Multiparametric MRI identified iCNs with high sensitivity and modest specificity. The presence of iCNs is associated with early HCC recurrence.

Association between higher intermuscular adipose tissue and decreased renal function in patients with systemic lupus erythematosus mediated by insulin resistance.

OBJECTIVES: To quantify the relationship between abdominal computed tomography (CT)-based body composition parameters and renal function in systemic lupus erythematosus (SLE) patients and evaluate the potential effect of insulin resistance on this relationship. METHODS: SLE patients from institutions A and B between January 2017 and August 2023 were enrolled. Areas and attenuation values of subcutaneous adipose tissue, visceral adipose tissue, intermuscular adipose tissue (IMAT), and skeletal muscle index on CT images were measured at the L3 vertebral level. Logistic regression analysis was used to identify risk factors associated with decreased renal function. Linear regression models were used to describe the relationships between body composition parameters and estimated glomerular filtration rate (eGFR). Finally, we used a single-point insulin sensitivity estimator to indirectly reflect the degree of insulin resistance and assess its mediating effect on the association between IMAT area and decreased renal function. RESULTS: Three-hundred thirty-nine SLE patients from institution A (internal dataset) and 114 SLE patients from institution B (external validation dataset) were included. Multivariate logistic regression revealed that IMAT area (odds ratio (OR)institution A: 1.05 (95% confidence intervals (95% CI): 1.01, 1.10), and ORinstitution B: 1.19 (95% CI: 1.03, 1.39)) was an independent risk factor for decreased renal function in SLE patients. In the adjusted linear regression model, high IMAT area was significantly associated with reduced eGFR (ßinstitution A = -1.15, Pinstitution A = 0.005; ßinstitution B = -0.98, Pinstitution B = 0.049). Additionally, insulin resistance contributed a mediating role of 22.8% to the association. CONCLUSION: High IMAT area was associated with decreased renal function in SLE patients and insulin resistance mediated this relationship. CRITICAL RELEVANCE STATEMENT: High intermuscular adipose tissue area is associated with decreased renal function in systemic lupus erythematosus patients mediated by insulin resistance and is correlated with chronicity index in lupus nephritis patients. KEY POINTS: High intramuscular adipose tissue (IMAT) area was associated with decreased renal function in systemic lupus erythematosus (SLE) patients. Insulin resistance mediated the association between IMAT area and eGFR. IMAT area was associated with chronicity index in lupus nephritis patients.

Circulating plasma cells as a predictive biomarker in Multiple myeloma: an updated systematic review and meta-analysis.

BACKGROUND: Circulating plasma cells (CPCs) are defined by the presence of peripheral blood clonal plasma cells, which would contribute to the progression and dissemination of multiple myeloma (MM). An increasing number of studies have demonstrated the predictive potential of CPCs in the past few years. Therefore, there is a growing need for an updated meta-analysis to identify the specific relationship between CPCs and the prognosis of MM based on the current research status. METHODS: The PubMed, Embase, and Cochrane Library databases were screened to determine eligible studies from inception to November 5, 2023. Publications that reported the prognostic value of CPCs in MM patients were included. Hazard ratios (HRs) with 95% confidence intervals (CIs) of overall survival (OS) and progression-free survival (PFS) were extracted to pool the results. Subgroup analyses were performed based on region, sample size, cut-off value, detection time, initial treatment, and data type. The association between CPCs level and clinicopathological characteristics, including the International Staging System (ISS), Revised-ISS (R-ISS), and cytogenetic abnormalities were also evaluated. Statistical analyses were conducted using STATA 17.0 software. RESULTS: Twenty-two studies with a total of 5637 myeloma patients were enrolled in the current meta-analysis. The results indicated that myeloma patients with elevated CPCs were expected to have a poor OS (HR = 2.19, 95% CI: 1.81-2.66, p < 0.001) and PFS (HR = 2.45, 95% CI: 1.93-3.12, p < 0.001). Subgroup analyses did not alter the prognostic role of CPCs, regardless of region, sample size, cut-off value, detection time, initial treatment, or data type. Moreover, the increased CPCs were significantly related to advanced tumour stage (ISS III vs. ISS I-II: pooled OR = 2.89, 95% CI: 2.41-3.46, p < 0.001; R-ISS III vs. R-ISS I-II: pooled OR = 3.65, 95% CI: 2.43-5.50, p < 0.001) and high-risk cytogenetics (high-risk vs. standard-risk: OR = 2.22, 95% CI: 1.60-3.08, p < 0.001). CONCLUSION: Our meta-analysis confirmed that the increased number of CPCs had a negative impact on the PFS and OS of MM patients. Therefore, CPCs could be a promising prognostic biomarker that helps with risk stratification and disease monitoring.

There is a growing need for an updated meta-analysis to identify the specific relationship between CPCs and the prognosis of MM based on the current research status.Our meta-analysis revealed that a high CPCs level was significantly associated with worse OS and PFS in MM patients.CPCs could be a promising predictive biomarker that helps with risk stratification and disease monitoring.

Sex-Specific Computed Tomography Abdominal Fat and Skeletal Muscle Characteristics in Type 2 Diabetic Retinopathy Patients With/Without Comorbid Diabetic Kidney Disease.

RATIONALE AND OBJECTIVES: To investigate differences in sex-specific computed tomography abdominal fat and skeletal muscle (SM) characteristics between type 2 diabetic retinopathy (DR) patients with and without diabetic kidney disease (DKD). MATERIALS AND METHODS: This retrospective study included type 2 diabetes mellitus DR patients with/without DKD between January 2019 and July 2021. Visceral adipose tissue (VAT), subcutaneous adipose tissue, perirenal adipose tissue (PAT), intramuscular adipose tissue, and SM areas were measured. Univariate and multivariate logistic regression analyses were used to analyze risk factors for DKD. Correlation and multiple linear regression analyses were used to clarify the association between computed tomography abdominal fat, SM characteristics, and cystatin C. RESULTS: Two hundred and forty-one patients were enrolled and divided into DR with DKD group (n = 142) and DR without DKD group (n = 99). In men, hypertension (OR: 5.21; 95%CI: 1.93-14.05; p = 0.001), diastolic pressure (OR: 1.07; 95%CI: 1.01-1.12; p = 0.011), hemoglobin (OR: 0.94; 95%CI: 0.92-0.97; p < 0.001) and PAT attenuation value (OR: 1.09; 95%CI: 1.01-1.17; p = 0.026) were independent risk factors for DKD progression in DR patients, while the VAT index (VATI) (OR: 1.03; 95%CI: 1.01-1.05; p = 0.014) was an independent risk factor for female patients. Multiple linear regression analysis revealed significant correlations between hypertension (ß = 0.22, p = 0.002) and hemoglobin (ß = -0.53, p < 0.001) with cystatin C in men, and a significant correlation between VATI and cystatin C (ß = 0.35, p = 0.037) in women after adjustment for confounders. CONCLUSION: Female DR patients with elevated VAT level may suffer from a higher risk of DKD than that in male patients.

[Cloning, expression and purification of fructose-2, 6-bisphosphatase gene CpF2KP in papaya].

Papaya, which is mainly cultivated in the southeastern region of China, is one of the four famous fruits in Lingnan. It is favored by people because of its edible and medicinal value. Fructose-6-phosphate, 2-kinase/fructose-2, 6-bisphosphatase (F2KP) is a unique bifunctional enzyme with a kinase domain and an esterase domain that catalyzes the synthesis and degradation of fructose-2, 6-bisphosphate (Fru-2, 6-P2), an important regulator of glucose metabolism in organisms. In order to study the function of the gene CpF2KP encoding the enzyme in papaya, it is particularly important to obtain the target protein. In this study, the coding sequence (CDS) of CpF2KP, with a full-length of 2 274 bp, was got from the papaya genome. The amplified sequence of full-length CDS was cloned into the vector PGEX-4T-1 which was double digested with EcoR I and BamH I. The amplified sequence was constructed into a prokaryotic expression vector by genetic recombination. After exploring the induction conditions, the results of SDS-PAGE showed that the size of the recombinant GST-CpF2KP protein was about 110 kDa. The optimum IPTG concentration and temperature for CpF2KP induction were 0.5 mmol/L and 28 ℃, respectively. The purified sin[A1] gle target protein was obtained after purifying the induced CpF2KP protein. In addition, the expression level of this gene was detected in different tissues, and showed that the gene was expressed at the highest level in seeds and the lowest in pulp. This study provides an important basis for further revealing the function of CpF2KP protein and studying the involved biological processes of this gene in papaya.

Bacterial outer membrane vesicle based versatile nanosystem boosts the efferocytosis blockade triggered tumor-specific immunity.

Efferocytosis inhibition is emerging as an attractive strategy for antitumor immune therapy because of the subsequent leak of abundant immunogenic contents. However, the practical efficacy is seriously impeded by the immunosuppressive tumor microenvironments. Here, we construct a versatile nanosystem that can not only inhibit the efferocytosis but also boost the following antitumor immunity. MerTK inhibitor UNC2025 is loaded into the bacterial outer membrane vesicles (OMVs), which are then modified with maleimide (mU@OMVs). The prepared mU@OMVs effectively inhibits the efferocytosis by promoting the uptake while preventing the MerTK phosphorylation of tumor associated macrophages, and then captures the released antigens through forming universal thioether bonds. The obtained in situ vaccine effectively transfers to lymph nodes by virtue of the intrinsic features of OMVs, and then provokes intense immune responses that can efficiently prevent the growth, metastasis and recurrence of tumors in mice, providing a generalizable strategy for cancer immunotherapy.

MRI-based preoperative markers combined with narrow-margin hepatectomy result in higher early recurrence.

PURPOSE: To investigate the applicability of MRI-based preoperative risk markers in assisting clinicians to define an appropriate surgical margin width for patients with solitary hepatocellular carcinoma. METHODS: Patients who underwent preoperative MRI with hepatectomy were randomly divided into development (65%) and internal validation (35%) datasets between January 2015 and January 2019. Multivariate logistic analysis was used to evaluate MRI-based markers of early recurrence (≤2 years) in the development dataset. Independent factors in the development dataset were investigated using a multivariable Cox analysis. The multivariable logistic and Cox models were verified using the risk score system in the validation dataset. Recurrence-free survival (RFS) was calculated according to MRI-based preoperative markers together with a narrow or wide margin in all datasets. RESULTS: A narrow resection margin was identified as an independent risk factor for early postoperative recurrence (P < 0.001) according to multivariable Cox analysis. RFS was significantly shorter in patients with narrow resection margins than that of those with wide resection margins (P < 0.005). Patients with the three MRI-based preoperative markers (tumour size > 5 cm, substantial necrosis, and non-smooth margins) combined with a narrow resection margin had a shorter RFS than that of those with a wide margin (P < 0.005). Patients without these markers also benefitted from a wide margin (P < 0.05). CONCLUSIONS: MRI-based preoperative risk markers in combination with narrow resection margins were associated with a higher recurrence rate compared with wide resection margins, and hence, such patients may benefit from a wide-margin hepatectomy.

Auxin and cytokinin mediated regulation involved in vitro organogenesis of papaya.

In vitro organogenesis is a multistep process which is largely controlled by the balance between auxin and cytokinin. Previous studies revealed a complex network regulating in vitro organogenesis in Arabidopsis thaliana; however, our knowledge of the molecular mechanisms underlying de novo shoot formation in papaya (Carica papaya) remains limited. Here, we optimized multiple factors to achieve an efficient and reproducible protocol for the induction of papaya callus formation and shoot regeneration. Subsequently, we analyzed the dynamic transcriptome profiles of samples undergoing this process, identified 5381, 642, 4047, and 2386 differentially expressed genes (DEGs), including 447, 66, 350, and 263 encoding transcription factors (TFs), in four stage comparisons. The DEGs were mainly involved in phytohormone modulation and transduction processes, particularly for auxin and cytokinin. Of these, 21 and 7 candidate genes involved in the auxin and cytokinin pathways, respectively, had distinct expression patterns throughout in vitro organogenesis. Furthermore, we found two genes encoding key TFs, CpLBD19 and CpESR1, were sharply induced on callus induction medium and shoot induction medium, indicating these two TFs may serve as proxies for callus induction and shoot formation in papaya. We therefore report a regulatory network of auxin and cytokinin signaling in papaya according to the one previously modeled for Arabidopsis. Our comprehensive analyses provide insight into the early molecular regulation of callus initiation and shoot formation in papaya, and are useful for the further identification of the regulators governing in vitro organogenesis.

High Value-Added Application of Two Renewable Sources as Healthy Food: The Nutritional Properties, Chemical Compositions, Antioxidant, and Antiinflammatory Activities of the Stalks of Rheum officinale Baill. and Rheum tanguticum Maxim. ex Regel.

Rhubarb plants (Rheum officinale and R. tanguticum) have edible stalks. In this work, we aimed to compare the nutritional properties, chemical compositions, and bioactivities of R. officinale (SRO) and R. tanguticum (SRT) stalks and to analyze the composition-function relationship. Results showed that the two stalks were good sources of fiber, as well as minerals. They contained abundant essential amino acids and essential fatty acids to regulate the immunity and prevent some chronic diseases; the contents of polyunsaturated fatty acids were 2,244.32 mg/100 g and 2,844.69 mg/100 g, respectively. The antioxidant activity were also proved. Metabolomics showed that SRO and SRT contained abundant phenolic acids. Due to the higher concentrations of flavones, SRT has better antiinflammatory activities than SRO by inhibiting NF-κB signaling pathway. Rhubarb stalks exhibited good safety in acute toxicity and cytotoxicity tests. This work indicated that the two stalks have nutritional value, safety, and bioactivities, and could be used as sources of nutritional ingredients for regulating the immunity of body in food industry.