Therapeutic effects of Kangxian Yanshen formula on patients with chronic kidney disease stages 3-4: a retrospective cohort study.

Background: This study retrospectively evaluated the actual efficacy of Kangxian Yanshen Formula Chinese medicine on renal function-related indicators in chronic kidney disease (CKD) stage 3-4 patients. Methods: In this retrospective cohort study, we collected 212 adult CKD patients with baseline estimated glomerular filtration rate (eGFR) of 15-60 ml/min/1.73 m2. All participants received usual care (i.e., Western medications), and participants in the exposure group (n = 109) were additionally prescribed Kangxian Yanshen Formula Chinese medicine. The primary outcome was an adjusted hazard risk and 95% confidence interval (95% CI) of a 30% decrease in eGFR at month 36 from baseline. Results: In terms of eGFR, among participants treated with additional Kangxian Yanshen Formula, after adjusting for covariates, there was a 57.1% reduction in the risk of a 30% decline from baseline in eGFR among participants in the Kangxian Yanshen Formula group compared with the Western medicine group (adjusted hazard risk: 0.429; 95% CI 0.269-0.682). In addition, participants in the Kangxian Yanshen Formula group had a significantly higher change in eGFR from baseline to month 12 than those in the western medicine group (3.40 ± 11.62 versus -3.87 ± 8.39; between-group difference Δ5.61 [± 2.26 standard deviation] mL/min/1.73 m2; P = 0.014). Participants in both groups showed a decreasing trend in eGFR at months 24 and 36. Conclusion: In patients with stage 3-4 CKD, Kangxian Yanshen Formula Chinese medicine therapy may help delay eGFR decline, but high-quality randomized controlled trials are needed to validate the results further.

Esophageal Inflammatory Pseudotumor on Al18F-FAPI-74 and 18F-FDG PET/CT.

ABSTRACT: A 25-year-old woman experiencing dysphagia for 2 years underwent 18F-FDG and Al18F-FAPI-74 PET/CT. The scans showed local thickening of the cervical and upper thoracic esophageal wall with several calcifications, accompanied by increased and heterogeneous FDG uptake and more intense FAPI activity. Histopathological analysis following thoracoscopic esophagectomy confirmed the diagnosis of esophageal inflammatory pseudotumor.

Validation of a genome-based model for adjusting radiotherapy dose (GARD) in patients with locally advanced rectal cancer.

Neoadjuvant radiotherapy is the standard care of locally advanced rectal cancer. Although a majority of patients received the same dose, the curative efficacy varies among individuals. In recent years, cancer treatment has entered the era of precise medical care, and how to identify patients for proper treatment by molecular signature is an important path of individualized therapy. This study aimed to establish and validate a genome-based model for adjusting radiation dose (GARD) for Chinese locally advanced rectal cancer through gene expression microarrays, and to evaluate the response of the GARD model in predicting the efficacy of neoadjuvant radiotherapy. Fresh-frozen primary tumor from 64 patients with locally advanced rectal cancer undergoing neoadjuvant radiotherapy from 2015 to 2018 were included. The gene expression profile was analyzed using Affymetrix 3000Dx gene-chip scanner. The radiosensitivity index (RSI) and GARD were calculated using the pGRT™ algorithm. Neoadjuvant rectal cancer score (NAR) was selected as efficacy evaluation indicators. Patients were divided into high and low NAR scoring groups, and two-sample t-test was used to analyze the differences in GARD values between different NAR subgroups. ROC curves were used to calculate the cut-off values and the area under the curve (AUC) for assessing the validity of the GARD models. The personalized radiation dose ( pGRT dose )can be computed using the formula nd = GARD / (α + ßd). Among patients, 1.5% T2, 46.3% T3, and 52.2% T4. Wherein pCR (n = 10; 15.6%) and no pCR (n = 54; 84.4%). The median NAR is 8.43 (rang from 0 to 50.34, IQR 3.75-14.98). NAR > 8.43 (n = 27; 42.2%) and NAR ≤ 8.43 (n = 37; 57.8%), suggesting that there are significant individual differences in clinical efficacy of patients with similar tumor stages and under the same treatment conditions. The median RSI is 0.48 (rang from 0.22 to 0.92, IQR 0.41-0.55). Median GARD was 18.40 rang from (rang from 2.26 to 37.52, IQR 14.94-22.28) within tumor tissue, suggesting individual differences in the efficacy of radiation therapy. The RSI value was significantly lower in the NAR low group (NAR ≤ 8.43) than in NAR high group (NAR > 8.43) (0.44 vs. 0.54, p = 0.0003). The GARD value was significantly higher in the NAR low group (NAR ≤ 8.43) than in NAR high group (NAR > 8.43) (21.01 vs. 15.88, p = 0.0004). Using the Receiver Operating Characteristic (ROC) curve analysis, a GARD threshold of 17 was identified as optimal, covering 37.5% of the 64-patient sample, with an area under the curve (AUC) of 0.75. In the external validation cohort, the high GARD score group demonstrated superior DFS compared to the low GARD score group(p < 0.001). Only 17% of patients had pGRT dose within the guideline recommended dose (45-50 Gy). The differences in NAR values among LARC patients receiving standard neoadjuvant radiotherapy suggest significant individual differences in clinical outcomes among patients with similar tumor stage and the same treatment conditions. Patients with a GARD value exceeding 17 exhibit a more favorable prognosis. Our results suggest that the gene expression-based pGRT™ algorithm has good efficacy prediction performance in preoperative concurrent radiotherapy for locally advanced rectal cancer, suggesting the potential clinical application of this method to guide the designation of individualized radiotherapy doses.

DNA-templated spatially controlled proteolysis targeting chimeras for CyclinD1-CDK4/6 complex protein degradation.

Constraining proximity-based drugs, such as proteolysis-targeting chimeras (PROTACs), into its bioactive conformation can significantly impact their selectivity and potency. However, traditional methods for achieving this often involve complex and time-consuming synthetic procedures. Here, we introduced an alternative approach by demonstrating DNA-templated spatially controlled PROTACs (DTACs), which leverage the programmability of nucleic-acid based self-assembly for efficient synthesis, providing precise control over inhibitors' spacing and orientation. The resulting constructs revealed distance- and orientation-dependent selectivity and degradation potency for the CyclinD1-CDK4/6 protein complex in cancer cells. Notably, an optimal construct DTAC-V1 demonstrated the unprecedented synchronous degradation of entire CyclinD1-CDK4/6 complex. This resulted in the effective cell cycle arrest in G1 phase, and further therapeutic studies showed its potent anti-tumor effects compared to inhibitors alone. These findings present a novel framework for PROTACs design, offering critical insights that may inform the development of other proximity-induced therapeutic modalities.

Analysis of the Genetic Diversity and Genetic Structure of Jiangshan Black Pigs Using Single Nucleotide Polymorphism (SNP) Chips.

The Jiangshan black pig is an indigenous pig breed in China, renowned for its superior meat quality and adaptability to roughage. However, the population of Jiangshan black pigs has dwindled due to the introduction of cosmopolitan pig breeds and the outbreak of African swine fever, putting them at risk of extinction. To offer insights into the conservation and breeding of Jiangshan black pigs, this study involved 118 Jiangshan black pigs as the research subjects and employed the Zhongxin-1 Porcine Breeding Array PLUS chip to detect whole-genome SNPs. Additionally, various software tools were utilized to accurately analyze the genetic diversity, phylogenetic relationship, inbreeding coefficient, and pedigree structure of the Jiangshan black pig conservation population. The findings indicated that the effective population size (Ne) of the Jiangshan black pig was 4.9, with an average inbreeding coefficient of 0.253 within the population. A genetic relationship analysis identified that the 16 male pigs were clustered into four families, and the 100 female pigs were also assigned to these familial groups. Furthermore, two female pigs were classified as "other" due to their distant genetic relatedness to all the males. These results contribute to a better understanding of the current status of the conservation of the Jiangshan black pig population and offer a theoretical foundation for the development of conservation strategies.

Construction of Vine-Inspired Antimicrobial Filter with Multiscale 3D Nanonetwork for High-Efficiency Air Filtration.

Enhancing the antimicrobial activity of high-efficiency particulate air (HEPA) filters while maintaining filtration efficiency and pressure drop is currently an urgent issue for preventing the spread of pathogenic microorganisms. Herein, inspired by vines which can enwind fences to fix as well as decorate them, a flexible antimicrobial chitin nanofiber (ChNF@CuOx) was fabricated and loaded onto the rigid glass fiber (GF) skeleton of a HEPA filter. Through the physical interaction, ChNF@CuOx was spontaneously enwound on GF, and ChNF@CuOx itself interweaved to form a new nanonetwork between the GF skeleton. The obtained antimicrobial air filter (ChNF@CuOx/GF) with a unique nanonetwork increased the filtration efficiency of the HEPA filter. Meanwhile, it possessed excellent inactivation ability against Staphylococcus aureus, Escherichia coli, and Candida albicans due to the urchin-like in situ grown CuOx on the ChNF. In particular, the oxygen vacancies generated unexpectedly in CuOx enabled it to produce reactive oxygen species. After eight cycles of antimicrobial assays, the antimicrobial rates of bacteria were higher than 99.5%, and those of fungi were greater than 98.3%. The successful synthesis of antimicrobial fibers and the construction of multidimensional nanoscale structures through a simple postprocessing method provide a new design mentality for antimicrobial functionalization for HEPA filters.

Effectiveness of the frailty index in predicting recurrent pneumonia and death in long-term hospitalized patients with vascular cognitive impairment.

OBJECTIVE: The aim was to predict the effectiveness of using frailty, defined by the frailty index (FI), for predicting recurrent pneumonia and death in patients 50 years and older with vascular cognitive impairment (VCI) during long-term hospitalization. MEASUREMENTS: This retrospective cohort study was conducted at a teaching hospital in western China and included VCI patients aged ≥50 years undergoing long-term hospitalization. The relevant data were collected from the electronic medical record system. The FI was based on 31 parameters and groups were defined using a cutoff value (0.2) as robust (FI < 0.2) and FRAIL (≥0.2). The definition of recurrent pneumonia was a minimum of two episodes within a year, with the symptoms, signs, and imaging results of pneumonia disappearing completely between episodes, and a minimum interval between episodes of seven days. Death was recorded by the hospital as the result of cardiac and respiratory arrest and survival was defined as the interval between hospital admission and confirmed death. Logistic regression models were used to assess the association between FI and recurrent pneumonia, while associations between FI and death were assessed by Cox proportional hazards models. RESULTS: A total of 252 long-term hospitalized VCI patients ≥50 years old were enrolled, of whom 115 were male (45.6 %). Ninety-seven patients (38.5 %) were defined as FRAIL. The median length of stay for hospitalized patients was 37 months. Overall, 215 patients developed pneumonia during hospitalization, which occurred an average of 14.5 months after admission, while 151 (59.9 %) had recurrent pneumonia, and 155 (61.5 %) died. Of these, 143 died in the hospital and 12 died after discharge. No significant differences were seen in the incidence of recurrent pneumonia between FRAIL and robust long-term hospitalized VCI patients (FRAIL vs. robust: 66.0 % vs. 56.1 %, P = 0.121) while FRAIL patients had a higher mortality rate than robust patients (FRAIL vs. robust: 71.1 % vs. 55.5 %, P = 0.013). After further Cox regression analysis and adjustment for possible confounders found to be significant in the univariate analysis (including age, sex, smoking history, and activities of daily living (ADL) score), FRAIL patients had a higher risk of death than healthy patients (HR = 1.595, 95 % CI: 1.149-2.213). In addition, based on Model 2, confounding variables that were not statistically significant in the univariate analysis but may have had an impact on the results (including marital status, educational level, drinking history, comorbidity and rehabilitation treatment) were incorporated into Model 3 for further correction. The result remained unchanged, namely, that compared with robust patients, FRAIL patients had a higher risk of death (HR = 1.771, 95 % CI: 1.228-2.554). CONCLUSIONS AND IMPLICATIONS: Frailty defined by the FI was effective for predicting the risk of mortality but not that of recurrent pneumonia in long-term hospitalized VCI patients aged 50 or older.

Design, Synthesis, and Antimicrobial Activity Evaluation of Novel Isocryptolepine Derivatives against Phytopathogenic Fungi and Bacteria.

This research adopted the Fischer indole synthesis method to continue constructing a novel drug-like chemical entity based on the guidance of isocryptolepine and obtained four series of derivatives: Y, Da, Db, and Dc. The antimicrobial activity of these derivatives against plant pathogens was further evaluated. The results showed that Dc-2 had the best antifungal effect against Botrytis cinerea, and its EC50 value was up to 1.29 µg/mL. In addition, an in vivo activity test showed that the protective effect of Dc-2 on apples was 82.2% at 200 µg/mL, which was better than that of Pyrimethanil (45.4%). Meanwhile, it was found by scanning electron microscopy and transmission electron microscopy that the compound Dc-2 affected the morphology of mycelia. The compound Dc-2 was found to damage the cell membrane by PI and ROS staining. Through experiments such as leakage of cell contents, it was found that the compound Dc-2 changed the permeability of the cell membrane and caused the leakage of substances in the cell. According to the above studies, compound Dc-2 can be used as a candidate lead compound for further structural optimization and development.

Population-based prevalence of self-reported pediatric diabetes and screening for undiagnosed type 2 diabetes in Chinese children in years 2017-2019, a cross-sectional study.

Background: The worldwide geographical and temporal variation in the prevalence of diabetes represents a challenge, but also an opportunity for gaining etiological insights. Encompassing the bulk of East Asians, a large and distinct proportion of the world population, China can be a source of valuable epidemiological insights for diabetes, especially in early life, when pathophysiology begins. We carried out a nationwide, epidemiological survey of Prevalence and Risk of Obesity and Diabetes in Youth (PRODY) in China, from 2017 to 2019, to estimate the population-based prevalence of diagnosed pediatric diabetes and screen for undiagnosed pediatric type 2 diabetes (T2D). Methods: PRODY was a nation-wide, school population-based, cross-sectional, multicenter survey by questionnaire, fasting urine glucose test and simple oral glucose tolerance test (s-OGTT), among a total number of 193,801 general-population children and adolescents (covered a pediatric population of more than 96.8 million), aged 3-18, from twelve provinces across China. The prevalence of the self-reported pediatric diabetes, the proportion of subtypes, the crude prevalence of undiagnosed T2D and prediabetes in general juvenile population and the main risk factors of type 1 (T1D) and type 2 (T2D) diabetes had been analyzed in the study. Findings: The prevalence of all self-reported pediatric diabetes was estimated at 0.62/1000 (95% CI: 0.51-0.74), with T1D at 0.44/1000 (95% CI: 0.35-0.54) and T2D at 0.18/1000 (95% CI: 0.13-0.25). For undiagnosed T2D, the crude prevalence was almost ten-fold higher, at 1.59/1000, with an estimated extra 28.45/1000 of undiagnosed impaired glucose tolerance (IGT) and 53.74/1000 of undiagnosed impaired fasting glucose (IFG) by s-OGTT screening. Maternal diabetes history is the major risk factors for all subtypes of pediatric diabetes in China. Interpretation: The PRODY study provides the first population-based estimate of the prevalence of pediatric diabetes China and reveals a magnitude of the problem of undiagnosed pediatric T2D. We propose a practical screening strategy by s-OGTT to address this serious gap. Funding: The National Key Research and Development Programme of China, Key R&D Program of Zhejiang, the National Natural Science Foundation of China and the Zhejiang Provincial Key Disciplines of Medicine, Key R&D Program Projects in Zhejiang Province.

[Corrigendum] Adenoviral neutral endopeptidase gene delivery in combination with paclitaxel for the treatment of prostate cancer.

Subsequently to the publication of the above article, an interested reader drew to the authors' attention that, for the immunostaining experiments shown in Fig. 3C on p. 1195, the 'NEP' and 'PTX' panels contained overlapping data, such that data which were intended to show the results of differently performed experiments had apparently been derived from the same original source. After re­examining their original data, the authors have realized that the 'PTX' data panel in Fig. 3C had inadvertently been selected incorrectly. The revised and corrected version of Fig. 3, showing the correct data for the 'PTX' data panel in Fig. 3C, is shown on on the next page. The authors are grateful to the Editor of International Journal of Oncology for allowing them this opportunity to publish this Corrigendum, and all the authors agree with its publication. Furthermore, the authors apologize to the readership for any inconvenience caused. [International Journal of Oncology 41: 1192­1198, 2012; DOI: 10.3892/ijo.2012.1586].

Current development and structure-activity relationship study of berberine derivatives.

Berberine is a quaternary ammonium isoquinoline alkaloid derived from traditional Chinese medicines Coptis chinensis and Phellodendron chinense. It has many pharmacological activities such as hypoglycemic, hypolipidemic, anti-tumor, antimicrobial and anti-inflammatory. Through structural modifications at various sites of berberine, the introduction of different groups can change berberine's physical and chemical properties, thereby improving the biological activity and clinical efficacy, and expanding the scope of application. This paper reviews the research progress and structure-activity relationships of berberine in recent years, aiming to provide valuable insights for the exploration of novel berberine derivatives.

[Relationship between the Age of Diagnosis and Clinical Outcomes in Children with Chronic Immune Thrombocytopenia].

OBJECTIVE: To explore the relationship between age at diagnosis and clinical outcomes in children with chronic immune thrombocytopenia (cITP). METHODS: A retrospective analysis was conducted on 117 children with cITP, according to the age at which the patient was diagnosed with ITP, they were divided into two groups: the<10 year old group and the ≥10 year old group, the general information and clinical outcomes of the two groups of children were compared and analyzed. Logistic regression analysis was used to analyzed the impact of age at the time of diagnosis on clinical outcomes, and the predictive evaluation value of age on outcomes was assessed by the receiver operation characteristic. RESULTS: Compared with the group with diagnosed age<10 years old, the proportion of second-line drug treatment (41.46% vs 18.42%) in the diagnosed age group ≥10 years old was significantly higher, and the proportion of ≥grade 3 bleeding (36.59% vs 13.16%) was significantly higher, which was significant statistical differences ( P < 0.05). However, there was no statistically significant difference in the proportion of untreated CR between the two groups after 5 years of diagnosis (P >0.05). Logistic regression results show that age (older) was an unfavorable/dangerous influencing factor for the occurrence of ≥grade 3 bleeding after second-line treatment (OR >1, P < 0.05). For the occurrence of CR after 5 years of diagnosis without treatment, age was not the influencing factor (P >0.05). ROC analysis showed that age have a certain predictive and evaluative effect on the use of second-line treatment and the occurrence of ≥grade 3 bleeding, with AUC of 0.741(95%CI : 0.549-0.938) and 0.786(95%CI : 0.605-0.940), respectively. However, there was basically no predictive evaluation value for the occurrence of CR after 5 years of diagnosis without treatment. CONCLUSION: Older age at the time of diagnosis is not conducive to the prognosis of cITP patients.

MR Molecular Imaging of Extradomain-B Fibronectin for Assessing Progression and Therapy Resistance of Prostate Cancer.

Accurate assessment and characterization of the progression and therapy response of prostate cancer are essential for precision healthcare of patients diagnosed with the disease. MRI is a clinical imaging modality routinely used for diagnostic imaging and treatment planning of prostate cancer. Extradomain B fibronectin (EDB-FN) is an oncofetal subtype of fibronectin highly expressed in the extracellular matrix of aggressive cancers, including prostate cancer. It is a promising molecular target for the detection and risk-stratification of prostate cancer with high-resolution MR molecular imaging (MRMI). In this study, we investigated the effectiveness of MRMI with an EDB-FN specific contrast agent MT218 for assessing the progression and therapy resistance of prostate cancer. Low grade LNCaP prostate cancer cells became an invasive phenotype LNCaP-CXCR2 with elevated EDB-FN expression after acquisition of the C-X-C motif chemokine receptor 2 (CXCR2). MT218-MRMI showed brighter signal enhancement in LNCaP-CXCR2 tumor xenografts with a ∼2-fold contrast-to-noise (CNR) increase than in LNCaP tumors in mice. Enzalutamide-resistant C4-2-DR prostate cancer cells were more invasive, with higher EDB-FN expression than parental C4-2 cells. Brighter signal enhancement with a ∼2-fold CNR increase was observed in the C4-2-DR xenografts compared to that of C4-2 tumors in mice with MT218-MRMI. Interestingly, when invasive PC3 prostate cancer cells developed resistance to paclitaxel, the drug-resistant PC3-DR cells became less invasive with reduced EDB-FN expression than the parental PC3 cells. MT218-MRMI detected reduced brightness in the PC3-DR xenografts with more than 2-fold reduction of CNR compared to PC3 tumors in mice. The signal enhancement in all tumors was supported by the immunohistochemical staining of EDB-FN with the G4 monoclonal antibody. The results indicate that MRMI of EDB-FN with MT218 has promise for detection, risk stratification, and monitoring the progression and therapy response of invasive prostate cancer.

Effects of straw biochar on microbial-derived carbon: A global meta-analysis.

Pyrolyzing biomass (e.g., crop straw) to produce biochar is a sustainable strategy in agricultural farmlands. Straw-derived biochar could increase soil organic carbon (SOC) and microbial-derived carbon (C) compared to no addition, while it is imperative to understand the effects of straw-derived biochar compared to its feedstock (e.g., straw). We retrieved 321 and 387 observations to investigate the effects of straw-derived biochar on microbial-derived C (e.g., microbial biomass C (MBC) and microbial necromass C (MNC)) taking no addition and straw as control, respectively. Notably, straw-derived biochar significantly increased dissolved organic C (DOC) by 24.9% and provided available substrates for microbial utilization, thus improving MBC by 16.7% and MNC by 19.7% compared to no addition. Nevertheless, compared to its feedstock (crop straw), straw-derived biochar significantly decreased MBC by 26.1% and MNC by 18.0% attributed to lower DOC, supported by a positive correlation between MBC and DOC (R2 = 0.53). A negative correlation between changes in MBC and SOC indicated the adverse of microbial activity for C accrual under conversion from straw to biochar. Moreover, soil layer, experiment duration, and initial C/N ratio are the crucial factors affecting MBC under the conversion from straw to biochar. Specifically, with significant variations among subgroups, when compared to straw addition, straw-derived biochar had lower reduction in MBC observed on 0-5 cm layers, mean annual precipitation ≥550 mm, mean annual temperature ≥10 °C, clay loam soil, experiment duration≥1 yr, initial SOC≥14 g kg-1, pH≥8, and bulk density ≥1.28 g cm-3. Straw-derived biochar even increased MBC by 32.8% in an anaerobic environment, associated with biochar produced under limited oxygen and anaerobic microorganisms dominating the microbial community. This study concludes that the conversion from crop straw to biochar increases SOC but constrains microbial-derived C, which may disturb the microbial-mediated C-cycling process.

Integrated Morphological, Comparative Transcriptomic, and Metabolomic Analyses Reveal Mechanisms Underlying Seasonal Patterns of Variation in Spines of the Giant Spiny Frog (Quasipaa spinosa).

Quasipaa spinosa, commonly known as the spiny frog, is an economically valued amphibian in China prized for its tender meat and nutritional value. This species exhibits marked sexual dimorphism, most notably the prominent spiny structures on males that are pivotal for mating success and species identification. The spines of Q. spinosa exhibit strong seasonal variation, changing significantly with the reproductive cycle, which typically spans from April to October. Sexually mature males develop densely packed, irregularly arranged round papillae with black spines on their chests during the breeding season, which may then reduce or disappear afterward, while females have smooth chest skin. Despite their ecological importance, the developmental mechanisms and biological functions of these spines have been inadequately explored. This study integrates morphological, transcriptomic, and metabolomic analyses to elucidate the mechanisms underlying the seasonal variation in spine characteristics of Q. spinosa. Our results demonstrate that spine density inversely correlates with body size and that spine development is accompanied by significant changes in epidermal thickness and keratinization during the breeding season. Comparative transcriptomic analysis across different breeding stages revealed significant gene expression alterations in pathways related to extracellular matrix interactions, tyrosine metabolism, Wnt signaling, and melanogenesis. Metabolomic analysis further identified significant seasonal shifts in metabolites essential for energy metabolism and melanin synthesis, including notable increases in citric acid and ß-alanine. These molecular changes are consistent with the observed morphological adaptations, suggesting a complex regulatory mechanism supporting spine development and functionality. This study provides novel insights into the molecular basis of spine morphogenesis and its seasonal dynamics in Q. spinosa, contributing valuable information for the species' conservation and aquaculture.

MR Molecular Image Guided Treatment of Pancreatic Cancer with Targeted ECO/miR-200c Nanoparticles in Immunocompetent Mouse Tumor Models.

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is characterized by desmoplasia due to increased deposition of extracellular matrix (ECM) proteins. This work investigates the efficacy of targeted ECO/miR-200c nanoparticles (ELNP) on ECM remodeling in PDAC and tumor proliferation with MR molecular imaging (MRMI) with MT218 in immunocompetent mouse models. METHODS: The miR-200c mediated regulation of EMT markers was measured in PDAC cells in vitro. Wild-type mice bearing mutated KRAS-driven KPC subcutaneous or orthotopic tumors were dosed weekly with RGD-ELNP/miR-200c at 1 mg-RNA/kg for a total of 4 doses. We utilized MT218-MRMI to non-invasively monitor the alteration of tumor ECM EDN-FN levels by miR-200c and tumor response to the treatment. The changes were also validated by posthumous histopathology. RESULTS: Transfection of PDAC cells with ELNP/miR-200c downregulated the expression of FN1 and EDB-FN and some mesenchymal markers, inhibiting 3D spheroid formation and migration of KPC PDAC cells. RGD-ELNP/miR-200c treatment resulted in significant signal reduction in the MT218 enhanced MRMI images of both subcutaneous and orthotopic KPC tumors compared to those prior to treatment and treated with a non-specific control. MT218-MRMI results were suggestive of EDB-FN downregulation in tumors, which was later confirmed by immunohistochemistry. Tumor growth in subcutaneous tumors was significantly attenuated with RGD-ELNP/miR-200c and was an observed trend in orthotopic tumors. Substantial necrosis and remodeling were observed in both models treated with RGD-ELNP/miR-200c based on H&E staining. CONCLUSION: These results demonstrate the feasibility of RGD-ELNP/miR-200c in modulating PDAC ECM and restraining tumor growth and the utility of MT218-MRMI for non-invasively monitoring miR-200c efficacy.

Constructing nitrogen-doped graphene quantum dots embedded in CNT supported layered (Ni0.5Co0.5)3V2O8 self-supporting film for high-performance supercapacitor.

To improve the electrochemical performance of positive electrode materials, constructing graded nanostructures is a worthwhile approach. This study successfully synthesized nitrogen-doped graphene quantum dots (NGQD) modified (Ni0.5Co0.5)3V2O8 on a carbon nanotube (CNT) substrate to construct self-supporting electrodes for high-performance supercapacitors. The (Ni0.5Co0.5)3V2O8 nanosheets were successfully wrapped onto the CNT surface through a solution impregnation process, which increased the specific surface area and interlayer spacing of the material. Furthermore, the electrochemical properties of the electrode material underwent significant enhancement due to the synergistic interplay between metal ions and the numerous redox centers. The embedding of the NGQD enriched the materials with active sites and further improved its specific capacity without compromising the structure intergrity of the layer configuration. Using CNT as the substrate ensured the self-supporting nature of the electrode. Consequently, the (Ni0.5Co0.5)3V2O8/NGQD@CNT composite exhibits an ultra-high specific capacitance of 3018.2 F g-1 at 1 A g-1 and 2332 F g-1 at 10 A g-1. The asymmetric supercapacitor constructed with (Ni0.5Co0.5)3V2O8/NGQD@CNT and activated carbon (AC) presented an impressive energy density of 160.2 Wh kg-1 at a power density of 800 W kg-1. After 8000 charge-discharge cycles, the capacity retention rate was 78.5 %, with a Coulo mbic efficiency consistently above 98 %.

Variations of soil metal content, soil enzyme activity and soil bacterial community in Rhododendron delavayi natural shrub forest at different elevations.

BACKGROUND: Rhododendron delavayi is a natural shrub that is distributed at different elevations in the karst region of Bijie, China, and that has an important role in preventing land degradation in this region. In this study, we determined the soil mineral element contents and soil enzyme activities. The composition of the soil bacterial community of R. delavayi at three elevations (1448 m, 1643 m, and 1821 m) was analyzed by high-throughput sequencing, and the interrelationships among the soil bacterial communities, mineral elements, and enzyme activities were determined. RESULTS: The Shannon index of the soil bacterial community increased and then decreased with increasing elevation and was highest at 1643 m. Elevations increased the number of total nodes and edges of the soil bacterial community network, and more positive correlations at 1821 m suggested stronger intraspecific cooperation. Acidobacteria, Actinobacteria and Proteobacteria were the dominant phyla at all three elevations. The Mantel test and correlation analysis showed that Fe and soil urease significantly affected bacterial communities at 1448 m; interestingly, Chloroflexi was positively related to soil urease at 1448 m, and Actinobacteria was positively correlated with Ni and Zn at 1821 m. Fe and soil urease significantly influenced the bacterial communities at lower elevations, and high elevation (1821 m) enhanced the positive interactions of the soil bacteria, which might be a strategy for R. delavayi to adapt to high elevation environments. CONCLUSION: Elevation significantly influenced the composition of soil bacterial communities by affecting the content of soil mineral elements and soil enzyme activity.