Complete Removal of Residual Particles and Realization of Mechanical Properties to Improve Osseointegration in Additively Manufactured Ti6Al4 V Scaffolds through Flowing Acid Etching.

Massive unmelted Ti6Al4 V (Ti64) particles presented across all surfaces of additively manufactured Ti64 scaffolds significantly impacted the designed surface topography, mechanical properties, and permeability, reducing the osseointegration of the scaffolds. In this study, the proposed flowing acid etching (FAE) method presented high efficiency in eliminating Ti64 particles and enhancing the surface modification capacity across all surfaces of Ti64 scaffolds. The Ti64 particles across all surfaces of the scaffolds were completely removed effectively and evenly. The surface topography of the scaffolds closely resembled the design after the 75 s FAE treatment. The actual elastic modulus of the treated scaffolds (3.206 ± 0.040 GPa) was closer to the designed value (3.110 GPa), and a micrometer-scale structure was constructed on the inner and outer surfaces of the scaffolds after the 90 s FAE treatment. However, the yield strength of scaffolds was reduced to 89.743 ± 0.893 MPa from 118.251 ± 0.982 MPa after the 90 s FAE treatment. The FAE method also showed higher efficiency in decreasing the roughness and enhancing the hydrophilicity and surface energy of all of the surfaces. The FAE treatment improved the permeability of scaffolds efficiently, and the permeability of scaffolds increased to 11.93 ± 0.21 × 10-10 mm2 from 8.57 ± 0.021 × 10-10 mm2 after the 90 s FAE treatment. The treated Ti64 scaffolds after the 90 s FAE treatment exhibited optimized osseointegration effects in vitro and in vivo. In conclusion, the FAE method was an efficient way to eliminate unmelted Ti64 particles and obtain ideal surface topography, mechanical properties, and permeability to promote osseointegration in additively manufactured Ti64 scaffolds.

Revealing the specific regulations of nitric oxide on the postharvest ripening and senescence of bitter melon fruit.

Bitter melon fruit is susceptible to yellowing, softening, and rotting under room-temperature storage conditions, resulting in reduced commercial value. Nitric oxide (NO) is an important signaling molecule and plays a crucial role in regulating the fruit postharvest quality. In this study, we investigated the effects of NO treatment on changes in sensory and firmness of bitter melon fruit during postharvest storage. Moreover, transcriptomic, metabolomic, and proteomic analyses were performed to elucidate the regulatory mechanisms through which NO treatment delays the ripening and senescence of bitter melon fruit. Our results show that differentially expressed genes (DEGs) were involved in fruit texture (CSLE, ß-Gal, and PME), plant hormone signal transduction (ACS, JAR4, and AUX28), and fruit flavor and aroma (SUS2, LOX, and GDH2). In addition, proteins differentially abundant were associated with fruit texture (PLY, PME, and PGA) and plant hormone signal transduction (PBL15, JAR1, and PYL9). Moreover, NO significantly increased the abundance of key enzymes involved in the phenylpropanoid biosynthetic pathway, thus enhancing the disease resistance and alleviating softening of bitter melon fruit. Finally, differential metabolites mainly included phenolic acids, terpenoids, and flavonoids. These results provide a theoretical basis for further studies on the physiological changes associated with postharvest ripening and senescence of bitter melon fruit. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-023-00110-y.

Telomerase-related advances in hepatocellular carcinoma: A bibliometric and visual analysis.

BACKGROUND: As a critical early event in hepatocellular carcinogenesis, telomerase activation might be a promising and critical biomarker for hepatocellular carcinoma (HCC) patients, and its function in the genesis and treatment of HCC has gained much attention over the past two decades. AIM: To perform a bibliometric analysis to systematically assess the current state of research on HCC-related telomerase. METHODS: The Web of Science Core Collection and PubMed were systematically searched to retrieve publications pertaining to HCC/telomerase limited to "articles" and "reviews" published in English. A total of 873 relevant publications related to HCC and telomerase were identified. We employed the Bibliometrix package in R to extract and analyze the fundamental information of the publications, such as the trends in the publications, citation counts, most prolific or influential writers, and most popular journals; to screen for keywords occurring at high frequency; and to draw collaboration and cluster analysis charts on the basis of coauthorship and co-occurrences. VOSviewer was utilized to compile and visualize the bibliometric data. RESULTS: A surge of 51 publications on HCC/telomerase research occurred in 2016, the most productive year from 1996 to 2023, accompanied by the peak citation count recorded in 2016. Up to December 2023, 35226 citations were made to all publications, an average of 46.6 citations to each paper. The United States received the most citations (n = 13531), followed by China (n = 7427) and Japan (n = 5754). In terms of national cooperation, China presented the highest centrality, its strongest bonds being to the United States and Japan. Among the 20 academic institutions with the most publications, ten came from China and the rest of Asia, though the University of Paris Cité, Public Assistance-Hospitals of Paris, and the National Institute of Health and Medical Research (INSERM) were the most prolific. As for individual contributions, Hisatomi H, Kaneko S, and Ide T were the three most prolific authors. Kaneko S ranked first by H-index, G-index, and overall publication count, while Zucman-Rossi J ranked first in citation count. The five most popular journals were the World Journal of Gastroenterology, Hepatology, Journal of Hepatology, Oncotarget, and Oncogene, while Nature Genetics, Hepatology, and Nature Reviews Disease Primers had the most citations. We extracted 2293 keywords from the publications, 120 of which appeared more than ten times. The most frequent were HCC, telomerase and human telomerase reverse transcriptase (hTERT). Keywords such as mutational landscape, TERT promoter mutations, landscape, risk, and prognosis were among the most common issues in this field in the last three years and may be topics for research in the coming years. CONCLUSION: Our bibliometric analysis provides a comprehensive overview of HCC/telomerase research and insights into promising upcoming research.

Widening of narrow urethral plates with lateral skin in TIP hypospadias repair: single center series.

BACKGROUND: To compare the outcomes of hypospadias repair using tubularized incised plate (TIP) urethroplasty and modified TIP with lateral skin to widen the urethral plate (WTIP). MATERIALS AND METHODS: Data were obtained from pre-pubertal boys who underwent primary hypospadias repair between May 2018 and July 2023. The cases were divided into two groups; one group underwent TIP with urethral plate ≥ 6 mm width and the other group with urethral plate width < 6 mm underwent WTIP. WTIP urethroplasty was performed by widening incisions on the outer margins of the urethral plate to incorporate penile and glandular skin lateral to the urethral plate to facilitate tubularization. Complication rates and urinary functions were compared. RESULTS: A total of 157 patients were enrolled in this study. Eighty-eight cases with narrow urethral plate were subjected to WTIP urethroplasty, and the rest were subjected to TIP urethroplasty. The preoperative glans width in WTIP group was less than that in TIP group (P < 0.001), and 44.3% had midshaft meatus in WTIP group compared to 17.4% in TIP group (P < 0.001). However, the incidences of postoperative complications (17.6% vs. 21.6%, P = 0.550) were not statistically different between the TIP and WTIP groups. In addition, both groups did not differ significantly in postoperative uroflowmetry assessment. CONCLUSIONS: The described technique helps to create an adequately caliber aesthetic neomeatus and facilitates tubularization, especially in hypospadias with a narrow urethral plate. Our data suggest that augmentation of a narrow urethral plate with WTIP has a similar surgical outcome to that of the TIP procedure in patients with a wide urethral plate.

Long-term outcome of adjuvant radiotherapy upon postoperative relapse of centrally located hepatocellular carcinoma: a real-world study.

Despite that surgical resection is widely regarded as the most effective approach to the treatment of liver cancer, its safety and efficacy upon centrally located hepatocellular carcinoma (HCC) remain unsatisfactory. In consequence, seeking an integrated treatment, like combined with adjuvant radiotherapy, to enhance the prognosis of patients is of critical importance. By recruiting patients undergoing surgical resection for centrally located HCC ranging from June 2015 to 2020, they were divided into liver resection combined with adjuvant radiotherapy (LR + RT) and mere liver resection (LR) groups. The calculation of propensity score and model of Cox proportional hazards regression were utilized. 193 patients were recruited in aggregation, containing 88 ones undergoing LR + RT, while 105 handled with LR. RT was verified to be an independent factor of prognosis for relapse (HR 0.60). In propensity-score analyses, significant association existed between adjuvant radiotherapy and better disease-free survival (DFS) (Matched, HR 0.60; Adjustment of propensity score, HR 0.60; Inverse probability weighting, HR 0.63). The difference of DFS was apparent within two groups (p value = 0.022), and RT significantly down-regulated early relapse (p value < 0.05) in subgroup analysis. The calculation of E-value revealed robustness of unmeasured confounding. The combination of liver surgical resection with RT is safe and effective towards patients with centrally located HCC, which would notably enhance the prognosis and decrease the early relapse of HCC.

A Study on Interobserver and Intraobserver Reliability of the Huashan Radiologic Classification System for Cervical Spinal Cord Injury Without Fracture and Dislocation.

STUDY DESIGN: Observational study. OBJECTIVE: To assess the reproducibility and reliability of the system. BACKGROUND: The Huashan radiologic classification system for cervical spinal cord injury without fracture and dislocation (CSCIWFD) was recently proposed and found useful for clinical practice. PATIENTS AND METHODS: Patients diagnosed with CSCIWFD between 2015 and 2021 were recruited. Six spine surgeons from different institutions, three experienced and other inexperienced respectively, were trained as observers of the system, and these surgeons classified the recruited patients using the system. Then, 8 weeks later, they repeated the classification on the same patients in a different order. The interobserver and intraobserver agreement between the results was analyzed using percentage agreement, weighted kappa, and Cohen kappa (κ) statistics. RESULTS: A total of 60 patients were included in the analysis. Type I was the most frequent type (29 cases, 48.3%), followed by type II (13 cases, 21.7%), type III (12 cases, 20%), and type IV (6 cases, 10%). For all the observers, experienced observers, and inexperienced observers, the overall agreement percentages were 77.6% (κ = 0.78), 84.4% (κ = 0.84), and 72.8% (κ = 0.74), respectively, indicating substantial to nearly perfect interobserver reproducibility. A higher level of agreement was found for differentiating type I from other types, with the percentage agreement ranging from 87.8% to 94.4% (κ= 0.74-0.88). For distinguishing compression on the spinal cord (types I and II vs types III and IV) among the different groups of observers, the percentage agreement was 97.8% (κ = 0.94), indicating nearly perfect reproducibility. As for intraobserver agreement, the percentage agreement ranged from 86.7% to 96.7% (κ = 0.78-0.95), indicating at least substantial reliability. CONCLUSIONS: The Huashan radiologic classification system for CSCIWFD was easy to learn and apply in a clinical environment, showing excellent reproducibility and reliability. Therefore, it would be promising to apply and promote this system for the precise evaluation and personalized treatment strategy.

Insights into the hierarchical structure and physicochemical properties of starch isolated from fermented dough.

Understanding the hierarchical structure and physicochemical properties of starch isolated from fermented dough with different times (0-120 min) is valuable for improving the quality of fermented dough-based products. The results indicate that fermentation disrupted the starch granule surface and decreased the average particle size from 19.72 µm to 18.45 µm. Short-term fermentation (< 60 min) disrupted the crystalline, lamellar, short-range ordered molecular and helical structures of starch, while long-term fermentation (60-120 min) elevated the ordered degree of these structures. For example, relative crystallinity and double helix contents increased from 23.7 % to 26.8 % and 34.4 % to 37.2 %, respectively. During short-term fermentation, the structural amorphization facilitated interactions between starch molecular chains and water molecules, which increased the peak viscosity from 275.4 to 320.6 mPa·s and the swelling power from 7.99 to 8.52 g/g. In contrast, starches extracted from long-term fermented dough displayed the opposite results. Interestingly, the hardness and springiness of starch gels gradually decreased as fermentation time increased. These findings extend our understanding of the starch structure-property relationship during varied fermentation stages, potentially benefiting the production of better-fermented foods.

Hairless (Hr) Deficiency Mitigates High-Fat Diet-Induced Obesity and Insulin Resistance in Mice.

Obesity is a significant global health concern linked to excessive dietary energy intake. This research focuses on the mammalian hairless protein (HR), known for its role in skin and hair function, and its impact on metabolism. Examining male wild-type (Hr+/+) and Hr null (Hr-/-) mice over a 14-week normal chow diet (NCD) or high-fat diet (HFD) intervention. This study reveals that HR deficiency exhibited a protective effect against HFD-induced obesity and insulin resistance. This protective effect is attributed to increased energy expenditure in Hr-/- mice. Moreover, the brown adipose tissue (BAT) of Hr-/- mice displays elevated levels of the thermogenic protein, uncoupling protein 1 (Ucp1), and its key transcriptional regulators (PPARγ and PGC1α), compared to Hr+/+ mice. In summary, the findings underscore the protective role of HR deficiency in countering HFD-induced adiposity by enhancing insulin sensitivity, raising energy expenditure, and augmenting thermogenic factors in BAT. Further exploration of HR metabolic regulation holds promise for potential therapeutic targets in addressing obesity-related metabolic disorders.

[Gene Profile and Clinical Significance of Concomitant Mutations in CN-AML Patients with CEBPA Mutation].

OBJECTIVE: To analyze the occurrence of concomitant gene mutations in cytogenetically normal acute myeloid leukemia (CN-AML) patients with CEBPA mutation and its impact on the clinical characteristics and prognosis of the patients. METHODS: 151 newly diagnosed patients with CN-AML in the Second Hospital of Shanxi Medical University from June 2013 to June 2020 were analyzed retrospectively. 34 common genetic mutations associated with hematologic malignancies were detected by next-generation sequencing technology. The occurrence of concomitant gene mutations in patients with CEBPA positive and negative groups was compared, and the correlation between concomitant mutations in different functional groups and the clinical characteristics and prognosis of CN-AML patients with CEBPA mutation was analyzed. RESULTS: In 151 patients with CN-AML, 55 (36.42%) were positive for CEBPA mutation (including 36 cases of CEBPAdm and 19 cases of CEBPAsm), of which 41 (74.55%) had co-mutations with other genes. The main mutated genes were GATA2 (25.45%, 14/55), TET2 (21.82%, 12/55), FLT3 (20.00%, 11/55), NRAS (12.73%, 7/55) and WT1 (9.09%, 9/55), etc. Some cases had two or more concomitant gene mutations. Grouping the mutant genes according to their functions showed that CEBPA+ group had lower mutation rates of histone methylation (P =0.002) and chromatin modification genes (P =0.002, P =0.033), and higher mutation rates of transcription factors (P =0.037) than CEBPA- group. In 55 patients with CEBPA+ CN-AML, the platelet count at diagnosis in signaling pathway gene mutation-positive group was lower than that in the mutation-negative group (P =0.005), the proportion of bone marrow blasts in transcription factor mutation-positive group was higher than that in the mutation-negative group (P =0.003), and the onset age in DNA methylation gene mutation-positive group and chromatin modifier mutation-positive group was older than that in the mutation-negative group, respectively (P =0.002, P =0.008). DFS of CEBPA+ CN-AML patients in signaling pathway gene mutation group was shorter than that in signaling pathway gene mutation-negative group (median DFS: 12 months vs not reached) (P =0.034). Compared with DNA methylation gene mutation-negative group, CEBPA+ CN-AML patients with DNA methylation gene mutation had lower CR rate (P =0.025) significantly shorter OS and DFS (median OS: 20 months vs not reached, P =0.006; median DFS: 15 months vs not reached, P =0.049). OS in patients with histone methylation gene mutation was significantly shorter than that in the histone methylation gene mutation-negative group (median OS: 12 months vs 40 months) (P =0.008). Multivariate analysis of prognostic factors showed that the proportion of bone marrow blasts (P =0.046), concomitant DNA methylation gene mutation (P =0.006) and histone methylation gene mutation (P =0.036) were independent risk factors affecting the prognosis. CONCLUSION: CN-AML patients with CEBPA mutation have specific concomitant gene profile, and the concomitant mutations of different functional genes have a certain impact on the clinical characteristics and prognosis of the patients.

Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR) and Monocyte-to-Lymphocyte Ratio (MLR) as Biomarkers in Diagnosis Evaluation of Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Retrospective, Observational Study.

Purpose: Hierarchical management is advocated in China to effectively manage chronic obstructive pulmonary disease (COPD) patients and reduce the incidence and mortality of acute exacerbation of COPD (AE-COPD). However, primary and community hospitals often have limited access to advanced equipment and technology. Complete blood count (CBC), which is commonly used in these hospitals, offers the advantages of being cost-effective and easily accessible. This study aims to evaluate the significance of routine blood indicators in aiding of diagnosing AE-COPD. Patients and Methods: In this research, we enrolled a total of 112 patients diagnosed with AE-COPD, 92 patients with stable COPD, and a control group comprising 60 healthy individuals. Clinical characteristics, CBC parameters, and serum CRP levels were collected within two hours. To assess the associations between NLR/PLR/MLR and CRP by Spearman correlation test. The diagnostic accuracy of NLR, PLR and MLR in AE-COPD was assessed using Receiver Operating Characteristic Curve (ROC) and the area under the curve (AUC). Binary Logistic Regression analysis was conducted for the indicators of NLR, PLR and MLR. Results: We found that patients with AE-COPD had significantly higher levels of NLR, PLR and MLR in contrast to patients with stable COPD. Additionally, the study revealed a noteworthy correlation between CRP and NLR (rs=0.5319, P<0.001), PLR (rs=0.4424, P<0.001), and MLR (rs=0.4628, P<0.001). By utilizing specific cut-off values, the amalgamation of NLR, PLR and MLR augmented diagnostic sensitivity. Binary logistic regression analysis demonstrated that heightened NLR and MLR act as risk factors for the progression of AE-COPD. Conclusion: The increasing levels of NLR, PLR and MLR could function as biomarkers, akin to CRP, for diagnosis and assessment of acute exacerbations among COPD patients. Further research is required to validate this concept.

The application of machine learning based on computed tomography images in the identification of renal tumors in children.

Background: The clinical manifestations of Wilms tumor and non-Wilms tumor in children are similar, and the only way to confirm the diagnosis is by postoperative pathology. Computed tomography (CT) is one of the main methods for preoperative diagnosis of the two, but it is also difficult to distinguish because it is easily affected by the subjective influence and the experience of the radiologists. Methods: The CT images of 82 children with renal tumors admitted to the Department of Pediatric Urology, Shandong Provincial Hospital from January 2011 to March 2022 were retrospectively analyzed. First, we drew the two-dimensional (2D) region of interest (ROI) of the largest cross-section on the corticomedullary phase (CMP) and nephrogenic phase (NP) images, and extracted seven types of 107 features in the ROI. Then, the texture features with similarity greater than 95% and repetition less than 90% were screened out, and the remaining texture features were further screened by analysis of variance (ANOVA) and recursive feature elimination (RFE). Finally, 15 texture feature were used to build the machine learning (ML) models. We used the synthetic minority oversampling technique (SMOTE) and 10-fold cross-validation to build ML models and verified them in the training, testing, and internal validation sets. The area under the receiver-operating characteristic curve (AUC) and calibration curve were used to evaluate the diagnostic performance. Results: We collected 77 CMP and 81 NP images, which were randomly divided into the training set and the testing set according to the ratio of 7:3. In the internal validation of CMP, the Mean-PCC-ANOVA-5-AE pipeline model achieved the highest AUC 0.792 [95% confidence interval (CI): 0.653-0.930], and its accuracy (ACC), sensitivity (SEN), and specificity (SPE) were 0.833, 0.539 and 0.927, respectively. Correspondingly, in NP, the Mean-PCC-ANOVA-2-LR pipeline model achieved the highest AUC 0.655 (95% CI: 0.485-0.82) in the internal validation. The ACC, SEN, and SPE were 0.696, 0.539, and 0.744, respectively. Conclusions: The ML models based on CT images have good diagnostic efficiency in differentiating Wilms tumors from non-Wilms tumors in children.

Biochemical characterization of a multiple prenyltransferase from Tolypocladium inflatum.

Prenylation plays a pivotal role in the diversification and biological activities of natural products. This study presents the functional characterization of TolF, a multiple prenyltransferase from Tolypocladium inflatum. The heterologous expression of tolF in Aspergillus oryzae, coupled with feeding the transformed strain with paxilline, resulted in the production of 20- and 22-prenylpaxilline. Additionally, TolF demonstrated the ability to prenylated the reduced form of paxilline, ß-paxitriol. A related prenyltransferase TerF from Chaunopycnis alba, exhibited similar substrate tolerance and regioselectivity. In vitro enzyme assays using purified recombinant enzymes TolF and TerF confirmed their capacity to catalyze prenylation of paxilline, ß-paxitriol, and terpendole I. Based on previous reports, terpendole I should be considered a native substrate. This work not only enhances our understanding of the molecular basis and product diversity of prenylation reactions in indole diterpene biosynthesis, but also provides insights into the potential of fungal indole diterpene prenyltransferase to alter their position specificities for prenylation. This could be applicable for the synthesis of industrially useful compounds, including bioactive compounds, thereby opening up new avenues for the development of novel biosynthetic strategies and pharmaceuticals. KEY POINTS: • The study characterizes TolF as a multiple prenyltransferase from Tolypocladium inflatum. • TerF from Chaunopycnis alba shows similar substrate tolerance and regioselectivity compared to TolF. • The research offers insights into the potential applications of fungal indole diterpene prenyltransferases.

Enhanced outcomes in residual or recurrent craniopharyngioma: evaluating combined gamma knife and phosphorus-32 brachytherapy.

BACKGROUND: Managing residual and recurrent craniopharyngioma effectively is crucial for improving patient outcomes. This study evaluates the combined use of gamma knife and phosphorus-32 brachytherapy, offering insights into alternative, less invasive treatment strategies. METHODS: We conducted a retrospective analysis of 97 patients treated from 2010 to 2016 for residual and recurrent craniopharyngioma using gamma knife and phosphorus-32 brachytherapy. We classified these patients into three groups: superficial solid (Group A), simple cystic (Group B), and mixed cystic-solid (Group C). We assessed the treatment's effectiveness by the tumor control rates and evaluated safety by monitoring vision, endocrine function improvements, and complication rates. RESULTS: The treatment achieved complete and adequate control rates of 49.5% and 87.6%, respectively. We observed improvements in vision or visual fields in 55.1% of the patients. The morbidity rate was 15.5%. The study found no significant differences in tumor control rates among the various lesion types. CONCLUSION: The combination of gamma knife and phosphorus-32 brachytherapy presents a viable, minimally invasive alternative for treating residual and recurrent craniopharyngioma. It offers high tumor control and functional improvement rates, suggesting its potential as a preferred strategy in some instances.

Effects of different concentrations of nicotinamide on hematopoietic stem cells cultured in vitro.

BACKGROUND: In vitro expansion to increase numbers of hematopoietic stem cells (HSCs) in cord blood could improve clinical efficacy of this vital resource. Nicotinamide (NAM) can promote HSC expansion ex vivo, but its effect on hematopoietic stem and progenitor cells (HSPCs, CD34+CD38) and functional subtypes of HSCs - short-term repopulating HSCs (ST-HSCs, CD34+CD38CD45RACD49f+) and long-term repopulating HSCs (LT-HSCs, CD34+CD38CD45RACD49f+CD90+) is not yet known. As a sirtuin 1 (SIRT1) inhibitor, NAM participates in regulating cell adhesion, polarity, migration, proliferation, and differentiation. However, SIRT1 exhibits dual effects by promoting or inhibiting differentiation in different tissues or cells. We propose that the concentration of NAM may influence proliferation, differentiation, and SIRT1 signaling of HSCs. AIM: To evaluate the effects and underlying mechanisms of action of different concentrations of NAM on HSC proliferation and differentiation. METHODS: CD34+ cells were purified from umbilical cord blood using MacsCD34 beads, and cultured for 10-12 d in a serum-free medium supplemented with cytokines, with different concentrations of NAM added according to experimental requirements. Flow cytometry was used to detect phenotype, cell cycle distribution, and apoptosis of the cultured cells. Real-time polymerase chain reaction was used to detect the transcription levels of target genes encoding stemness-related factors, chemokines, components of hypoxia pathways, and antioxidant enzymes. Dichloro-dihydro-fluorescein diacetate probes were used to evaluate intracellular production of reactive oxygen species (ROS). Determination of the effect of different culture conditions on the balance of cytokine by cytometric bead array. RESULTS: Compared with the control group, the proportion and expansion folds of HSPCs (CD34+CD38) incubated with 5 mmol/L or 10 mmol/L NAM were significantly increased (all P < 0.05). The ST-HSCs ratio and fold expansion of the 5 mmol/L NAM group were significantly higher than those of the control and 10 mmol/L NAM groups (all P < 0.001), whereas the LT-HSCs ratio and fold expansion of the 10 mmol/L NAM group were significantly higher than those of the other two groups (all P < 0.05). When the NAM concentration was > 10 mmol/L, cell viability significantly decreased. In addition, compared with the 5 mmol/L NAM group, the proportion of apoptotic cells in the 10 mmol/L NAM group increased and the proportion of cells in S and G2 phase decreased. Compared with the 5 mmol/L NAM group, the HSCs incubated with 10 mmol/L NAM exhibited significantly inhibited SIRT1 expression, increased intracellular ROS content, and downregulated expression of genes encoding antioxidant enzymes (superoxide dismutase 1, peroxiredoxin 1). CONCLUSION: Low concentrations (5 mmol/L) of NAM can better regulate the balance between proliferation and differentiation, thereby promoting expansion of HSCs. These findings allow adjustment of NAM concentrations according to expansion needs.

Effects of isorhamnetin on liver injury in heat stroke-affected rats under dry-heat environments via oxidative stress and inflammatory response.

Isorhamnetin is a natural flavonoid compound, rich in brass, alkaloids, and sterols with a high medicinal value. This study investigated the effects of isorhamnetin on liver injury and oxidative and inflammatory responses in heat-stroke-affected rats in a dry-heat environment. Fifty Sprague Dawley rats were randomly divided into five groups: normal temperature control (NC, saline), dry-heat control (DHC, saline), low-dose isorhamnetin-pretreated (L-AS, 25 mg/Kg), medium-dose isorhamnetin-pretreated (M-AS, 50 mg/Kg), and high-dose isorhamnetin-pretreated (H-AS, 100 mg/Kg) group. Saline was administered to the NC and DHC groups and corresponding concentrations of isorhamnetin were administered to the remaining three groups for 1 week. Blood and liver tissue were analyzed for oxidative stress and inflammation. The liver histopathological injury score, serum liver enzyme (alanine transaminase, aspartate transaminase, and lactate dehydrogenase), liver oxidative stress index (superoxide dismutase [SOD], catalase [CAT], and malondialdehyde), and inflammation index (tumor necrosis factor α [TNF-α], interleukin [IL]-1ß, IL-6, and lipopolysaccharides) were significantly higher in the DHC group than in the NC group (P < 0.05). These index values in the L-AS, M-AS, and H-AS groups were significantly lower than those in the DHC group (P < 0.05). The index values decreased significantly with an increase in the concentration of isorhamnetin (P < 0.05), while the index values of CAT and SOD showed the opposite tendency (P < 0.05). The expression of liver tissue nuclear factor kappa B (NF-κB), caspase-3, and heat shock protein (HSP-70) was higher in the DHC group than in the NC group (P < 0.05). Comparison between the isorhamnetin and DHC groups revealed that the expression of NF-кB and caspase-3 was decreased, while that of HSP-70 continued to increase (P < 0.05). The difference was significant for HSP-70 among all the isorhamnetin groups (P < 0.05); however, the NF-кB and caspase-3 values in the L-AS and H-AS groups did not differ. In summary, isorhamnetin has protective effects against liver injury in heat-stroke-affected rats. This protective effect may be related to its activities concerning antioxidative stress, anti-inflammatory response, inhibition of NF-кB and caspase-3 expression, and enhancement of HSP-70 expression.

Full-Length Transcriptome Sequencing and Comparative Transcriptomic Analyses Provide Comprehensive Insight into Molecular Mechanisms of Flavonoid Metabolites Biosynthesis in Styphnolobium japonicum.

Styphnolobium japonicum L. is a commonly consumed plant in China, known for its medicinal and nutritional benefits. This study focuses on the medicinal properties influenced by flavonoid metabolites, which vary during flower development. Utilizing full-length transcriptome sequencing on S. japonicum flowers, we observed changes in gene expression levels as the flowers progressed through growth stages. During stages S1 and S2, key genes related to flavonoid synthesis (PAL, 4CL, CHS, F3H, etc.) exhibited heightened expression. A weighted gene co-expression network analysis (WGCNA) identified regulatory genes (MYB, bHLH, WRKY) potentially involved in the regulatory network with flavonoid biosynthesis-related genes. Our findings propose a regulatory mechanism for flavonoid synthesis in S. japonicum flowers, elucidating the genetic underpinnings of this process. The identified candidate genes present opportunities for genetic enhancements in S. japonicum, offering insights into potential applications for improving its medicinal attributes.

Targeting ESE3/EHF With Nifurtimox Inhibits CXCR2+ Neutrophil Infiltration and Overcomes Pancreatic Cancer Resistance to Chemotherapy and Immunotherapy.

BACKGROUND & AIMS: Because pancreatic cancer responds poorly to chemotherapy and immunotherapy, it is necessary to identify novel targets and compounds to overcome resistance to treatment. METHODS: This study analyzed genomic single nucleotide polymorphism sequencing, single-cell RNA sequencing, and spatial transcriptomics. Ehf-knockout mice, KPC (LSL-KrasG12D/+, LSL-Trp53R172H/+ and Pdx1-Cre) mice, CD45.1+ BALB/C nude mice, and CD34+ humanized mice were also used as subjects. Multiplexed immunohistochemistry and flow cytometry were performed to investigate the proportion of tumor-infiltrated C-X-C motif chemokine receptor 2 (CXCR2)+ neutrophils. In addition, multiplexed cytokines assays and chromatin immunoprecipitation assays were used to examine the mechanism. RESULTS: The TP53 mutation-mediated loss of tumoral EHF increased the recruitment of CXCR2+ neutrophils, modulated their spatial distribution, and further induced chemo- and immunotherapy resistance in clinical cohorts and preclinical syngeneic mice models. Mechanistically, EHF deficiency induced C-X-C motif chemokine ligand 1 (CXCL1) transcription to enhance in vitro and in vivo CXCR2+ neutrophils migration. Moreover, CXCL1 or CXCR2 blockade completely abolished the effect, indicating that EHF regulated CXCR2+ neutrophils migration in a CXCL1-CXCR2-dependent manner. The depletion of CXCR2+ neutrophils also blocked the in vivo effects of EHF deficiency on chemotherapy and immunotherapy resistance. The single-cell RNA-sequencing results of PDAC treated with Nifurtimox highlighted the therapeutic significance of Nifurtimox by elevating the expression of tumoral EHF and decreasing the weightage of CXCL1-CXCR2 pathway within the microenvironment. Importantly, by simultaneously inhibiting the JAK1/STAT1 pathway, it could significantly suppress the recruitment and function of CXCR2+ neutrophils, further sensitizing PDAC to chemotherapy and immunotherapies. CONCLUSIONS: The study demonstrated the role of EHF in the recruitment of CXCR2+ neutrophils and the promising role of Nifurtimox in sensitizing pancreatic cancer to chemotherapy and immunotherapy.

A capillary-based centrifugal indicator equipped with in situ pathogenic bacteria culture for fast antimicrobial susceptibility testing.

Antimicrobial resistance has become a major global health threat due to the misuse and overuse of antibiotics. Rapid, affordable, and high-efficiency antimicrobial susceptibility testing (AST) is among the effective means to solve this problem. Herein, we developed a capillary-based centrifugal indicator (CBCI) equipped with an in situ culture of pathogenic bacteria for fast AST. The bacterial incubation and growth were performed by macro-incubation, which seamlessly integrated the capillary indicator. Through simple centrifugation, all the bacterial cells were confined at the nanoliter-level capillary column. The packed capillary column height could linearly reflect the bacterial count, and the minimum inhibitory concentration (MIC) was determined based on the difference in the column height between the drug-added groups and the control group. The AST results could easily be determined by the naked eye or smartphone imaging. Thus, the CBCI realized the combination of macro-bacterial incubation and early micro assessment, which accelerated the phenotypic AST without complex microscopic counting or fluorescent labelling. The whole operation process was simple and easy to use. AST results could be determined for E. coli ATCC strains within 3.5 h, and the output results for clinical samples were consistent with the hospital reports. We expect this AST platform to become a useful tool in limiting antimicrobial resistance, especially in remote/resource-limited areas or in underdeveloped countries.

M3YOLOv5: Feature enhanced YOLOv5 model for mandibular fracture detection.

BACKGROUND: It is very important to detect mandibular fracture region. However, the size of mandibular fracture region is different due to different anatomical positions, different sites and different degrees of force. It is difficult to locate and recognize fracture region accurately. METHODS: To solve these problems, M3YOLOv5 model is proposed in this paper. Three feature enhancement strategies are designed, which improve the ability of model to locate and recognize mandibular fracture region. Firstly, Global-Local Feature Extraction Module (GLFEM) is designed. By effectively combining Convolutional Neural Network (CNN) and Transformer, the problem of insufficient global information extraction ability of CNN is complemented, and the positioning ability of the model to the fracture region is improved. Secondly, in order to improve the interaction ability of context information, Deep-Shallow Feature Interaction Module (DSFIM) is designed. In this module, the spatial information in the shallow feature layer is embedded to the deep feature layer by the spatial attention mechanism, and the semantic information in the deep feature layer is embedded to the shallow feature layer by the channel attention mechanism. The fracture region recognition ability of the model is improved. Finally, Multi-scale Multi receptive-field Feature Mixing Module (MMFMM) is designed. Deep separate convolution chains are used in this modal, which is composed by multiple layers of different scales and different dilation coefficients. This method provides richer receptive field for the model, and the ability to detect fracture region of different scales is improved. RESULTS: The precision rate, mAP value, recall rate and F1 value of M3YOLOv5 model on mandibular fracture CT data set are 97.18%, 96.86%, 94.42% and 95.58% respectively. The experimental results show that there is better performance about M3YOLOv5 model than the mainstream detection models. CONCLUSION: The M3YOLOv5 model can effectively recognize and locate the mandibular fracture region, which is of great significance for doctors' clinical diagnosis.

Effect of synthesis temperature on the structural morphology of a metal-organic framework and the capacitor performance of derived cobalt-nickel layered double hydroxides.

Three-dimensional interconnected nickel-cobalt layered double hydroxides (NiCo-LDHs) were prepared on nickel foam by ion exchange using a cobalt-based metal-organic framework (Co-MOF) as a template at different temperatures. The effects of the Co-MOF preparation temperature on the growth, mass, morphology, and electrochemical properties of the Co-MOF and derived NiCo-LDH samples were studied. The synthesis temperature from 30 to 50 °C gradually increased the mass of the active material and the thickness of the Co-MOF sheets grown on the nickel foam. The higher the temperature is, the larger the proportion of Co3+. ß-Cobalt hydroxide (ß-Co(OH)2) sheets were generated above 60 °C. The morphology and mass loading pattern of the derived flocculent layer clusters of NiCo-LDH were inherited from metal-organic frameworks (MOFs). The areal capacitance of NiCo-LDH shows an inverted U-shaped curve trend with increasing temperature. The electrode material synthesized at 50 °C had a tremendous specific capacitance of 7631 mF·cm-2 at a current density of 2 mA·cm-2. The asymmetric supercapacitor assembled with the sample and active carbon (AC) achieved an energy density of 55.0 Wh·kg-1 at a power density of 800.0 W·kg-1, demonstrating the great potential of the NiCo-LDH material for energy storage. This work presents a new strategy for designing and fabricating advanced green supercapacitor materials with large power and energy densities.