Exploring the diagnostic value of endothelial cell and angiogenesis-related genes in Hashimoto's thyroiditis based on transcriptomics and single cell RNA sequencing.

(1) BACKGROUND: Hashimoto's thyroiditis (HT) can cause angiogenesis in the thyroid gland. However, the molecular mechanism of endothelial cells and angiogenesis related genes (ARGs) has not been extensively studied in HT. (2) METHODS: The HRA001684, GSE29315 and GSE163203 datasets were included in this study. Using single-cell analysis, weighted gene co-expression network analysis (WGCNA), functional enrichment analysis, machine learning algorithms and expression analysis for exploration. And receiver operator characteristic (ROC) curves was draw. Gene set enrichment analysis (GSEA) was utilized to investigate the biological function of the biomarkers. Meanwhile, we investigated into the relationship between biomarkers and different types of immune cells. Additionally, the expression of biomarkers in the TCGA-TC dataset was examined and the mRNA-drug interaction network was constructed. (3) RESULTS: We found 14 cell subtypes were obtained in HT samples after single-cell analysis. A total of 5 biomarkers (CD52, CD74, CD79A, HLA-B and RGS1) were derived, and they had excellent diagnostic performance. Then, 27 drugs targeting biomarkers were predicted. The expression analysis showed that CD74 and HLA-B were significantly up-regulated in HT samples. (4) CONCLUSION: In this study, 5 biomarkers (CD52, CD74, CD79A, HLA-B and RGS1) were screened and their expressions in endothelial cells was compared to offer a new reference for the recognition and management of HT.

Clear cell and non-clear cell renal cell carcinoma in young adults: clinicopathological features, survival outcomes and prognostic factors.

OBJECTIVES: Renal cell carcinoma (RCC) is infrequent among young adults. Few studies reported the outcome of RCC in young adults by pathological subtypes. The purpose of this study was to explore the clinicopathological features, survival outcomes and prognostic factors of young adult patients with clear cell (CCRCC) and non-clear cell renal cell carcinoma (NCCRCC). METHODS: This study included young adult patients aged 18-40 years who were diagnosed as renal cell carcinoma (RCC) between 2012 and 2022 at Peking University Third Hospital. All patients underwent either partial nephrectomy or radical nephrectomy, and some received adjuvant therapy. A comparative analysis was performed to investigate the differences in clinicopathological characteristics between the cohort of CCRCC and NCCRCC. Kaplan-Meier survival analysis was utilized to plot survival curves for young adults with RCC. The univariate and multifactorial prognostic analyses were conducted using the log-rank test and COX proportional hazards model. RESULTS: A total of 300 RCC patients aged 18-40 years were performed, of which 201 were diagnosed with CCRCC (67%) and 99 were diagnosed with NCCRCC(33%). The NCCRCC included 29 cases (9.7%) of chromophobe RCC, 28 cases (9.3%) of MiT family translocation RCC, 22 cases (7.3%) of papillary RCC, 11 cases (3.7%) of low malignant potential multifocal cystic RCC, and 6 cases of unclassified RCC (2.0%), 2 cases of mucinous tubule and spindle cell carcinoma (0.7%), and 1 case of FH-deficient RCC (0.3%).The mean age was 33.4 ± 6.1 years old. The overall and progression free 5-year survival rate was 99.1 and 95.3%, respectively. The NCCRCC cohort demonstrated a statistically significant decrease in progression-free survival (PFS) rate when compared to the CCRCC cohort (p < 0.001). There was no statistically significant difference observed in overall survival (OS) (p = 0.069). Pathological stage was a significant independent predictor for OS (p = 0.045). Pathological stage and nuclear grade were both independent predictors for PFS (p = 0.020; p = 0.005). CONCLUSIONS: The clinical and pathological features of young adults diagnosed with CCRCC exhibit notable distinctions from those of NCCRCC patients. The survival outcome was significantly influenced by the pathological stage, while both the nuclear grade and pathological stage had a significant impact on tumor progression. This study offered significant contributions to the understanding of the clinicopathological characteristics and prognostic determinants of renal cell carcinoma (RCC) in young adults.

Nomogram for predicting survival of renal cell carcinoma with tumor thrombus based on perioperative clinicopathological factors from a Chinese high-volume center.

OBJECTIVES: To investigate perioperative clinicopathological predictors and establish a predictive nomogram for survival in patients with renal cell carcinoma and venous tumor thrombus undergoing nephrectomy and thrombectomy. METHODS: Patients with renal cell carcinoma and venous tumor thrombus undergoing nephrectomy and thrombectomy were included in the study between January 2014 and June 2020. Cox regression analysis was used for univariate and multivariate survival analyses. A predictive nomogram for survival was established and internally validated using bootstrap resampling method. RESULTS: A total of 228 patients were enrolled in this study. The median age was 60 years (interquartile range 53-66 years), consisting of 174 (76.3%) males and 54 (23.7%) females. The median follow-up time was 17.5 months (range 1-74 months), 26.8% (61 of 228) patients died of all causes. In multivariable analysis, hemoglobin less than the lower limit of normal (hazard ratio 1.73; 95% confidence interval 1.01-2.96; P = 0.045), sarcomatoid feature (hazard ratio 3.67; 95% confidence interval 1.97-6.82; P < 0.001), perirenal fat invasion (hazard ratio 1.80; 95% confidence interval 1.05-3.09; P = 0.033), histological subtype (hazard ratio 2.74; 95% confidence interval 1.39-5.41; P = 0.004), and metastasis at surgery (hazard ratio 1.71; 95% confidence interval 1.01-2.90; P = 0.047) were independently associated with overall survival. The result of internal validation presented that the predictive performance of the nomogram for survival measured by C-index was 0.77. CONCLUSIONS: We developed a predictive nomogram with well-internal validation for survival in patients with renal cell carcinoma and venous tumor thrombus, which can greatly promote risk stratification and treatment planning.

Preliminary experience of oblique occlusion technique in robot-assisted infrahepatic inferior vena cava thrombectomy: step-by-step procedures and short term outcomes.

BACKGROUND: We aimed to compare the oncological outcomes between the oblique occlusion technique and the traditional technique for robot-assisted radical nephrectomy (RARN) with inferior vena cava (IVC) thrombectomy, and to explore the safety and effectiveness of the oblique occlusion technique. METHODS: Overall, 21 patients with renal cell carcinoma (RCC) and IVC tumor thrombus (TT) were admitted to our hospital from August 2019 to June 2020. All the patients underwent RARN with IVC thrombectomy, of which the IVC oblique occlusion technique was used in 11 patients and traditional occlusion technique was used in 10 patients. The oblique occlusion technique refers to oblique blocking from the upper corner of the right renal vein to the lower corner of the left renal vein using a vessel tourniquet or a vessel clamp (left RCC with IVCTT as an example). RESULTS: Compared with patients in the traditional group, those in the oblique group had lower serum creatinine at follow-up (3 month) (95 ± 21.1 vs. 131 ± 30.7 µmol/L, P = 0.03). There was no significant difference in operation time [149 (IQR 143-245) min vs. 148 (IQR 108-261) min, p = 0.86], IVC clamping time [18 (IQR 12-20) min vs. 20 (IQR 14-23) min, p = 0.41], and estimated intraoperative blood loss [300 (IQR 100-800) mL vs. 500 (IQR 175-738) mL, p = 0.51] between both groups. During a 16-month (range, 15-23 months) follow-up period, two cases progressed in the oblique group and three cases progressed in the traditional group. CONCLUSIONS: The modified IVC oblique occlusion technique procedure is relatively safe and effective in RARN with IVC thrombectomy. The IVC oblique occlusion technique may play a role in the protection of renal function.

Pure retroperitoneal laparoscopic radical nephrectomy and thrombectomy with delayed occlusion of the proximal inferior vena cava (DOPI) technique for renal tumor with level II-III venous tumor thrombus.

PURPOSE: To explore the safety and effectiveness of delayed occlusion of the proximal inferior vena cava (DOPI) technique in retroperitoneal laparoscopic radical nephrectomy (LRN) and thrombectomy for renal tumor with level II-III venous tumor thrombus (VTT). MATERIALS AND METHODS: From August 2016 to October 2018, a total of 145 patients with renal tumor and VTT were admitted to our centre. Seventy-five patients underwent laparoscopic surgery, and 70 patients underwent open surgery. Among these patients, 17 patients underwent retroperitoneal LRN and thrombectomy with the DOPI technique. Clinical data were collected retrospectively, and a descriptive statistical analysis was conducted. RESULTS: All the patients successfully underwent retroperitoneal laparoscopic surgery. The mean operation time was 345.9 ± 182.9 min, the mean estimated blood loss was 466.7 ± 245.5 ml. Postoperative complications occurred in three patients, including two patients of Clavien grading system level IVa and one patient of level II. There were no complications related to carbon dioxide pneumoperitoneum, such as gas embolism, acidosis, and subcutaneous emphysema. During 21 months of median follow-up time, no local recurrence was found, and distant metastasis occurred in four patients. Cancer-specific death occurred in two patients. CONCLUSIONS: The DOPI technique is safe and feasible in the treatment of renal tumor and level II-III VTT. With the DOPI technique, the procedures of dissociating and exposing proximal inferior vena cava are simplified.

Polyamine biomarkers as indicators of human disease.

The significant increase of periodontitis, chronic kidney disease (CKD), Alzheimer's disease and cancer can be attributed to an ageing population. Each disease produces a range of biomarkers that can be indicative of disease onset and progression. Biomarkers are defined as cellular (intra/extracellular components and whole cells), biochemical (metabolites, ions and toxins) or molecular (nucleic acids, proteins and lipids) alterations which are measurable in biological media such as human tissues, cells or fluids. An interesting group of biomarkers that merit further investigation are the polyamines. Polyamines are a group of molecules consisting of cadaverine, putrescine, spermine and spermidine and have been implicated in the development of a range of systemic diseases, in part due to their production in periodontitis. Cadaverine and putrescine within the periodontal environment have demonstrated cell signalling interfering abilities, by way of leukocyte migration disruption. The polyamines spermine and spermidine in tumour cells have been shown to inhibit cellular apoptosis, effectively prolonging tumorigenesis and continuation of cancer within the host. Polyamine degradation products such as acrolein have been shown to exacerbate renal damage in CKD patients. Thus, the use of such molecules has merit to be utilized in the early indication of such diseases in patients.

Inferior vena cava interruption in renal cell carcinoma with tumor thrombus: surgical strategy and perioperative results.

BACKGROUND: To analyze the influence of inferior vena cava (IVC) interruption for perioperative and oncological results in patients with renal cell carcinoma and tumor thrombus and summarize the surgical strategies of IVC interruption for different situations. METHODS: We retrospectively analyzed the clinical and pathological data of 103 patients in our center. Patients were divided into two groups with 32 cases (31.1%) underwent IVC interruption (Group 1) while 71 cases (68.9%) did not. For comparison of continuous variables, the Mann-Whitney U test was used. For comparison of categorical variables, Chi-square tests were used. A propensity score based matching method was used to eliminate possible bias. Kaplan-Meier plots were performed to evaluate the influence of IVC interruption on overall survival and cancer specific survival. All the statistical analyses were performed using SPSS 24. A P value < 0.05 was considered statistically significant. RESULTS: Among the 32 patients who underwent IVC interruption, the median age was 61 years and the median tumor size was 7.7 cm. There were 28 males and 23 tumors were on the right side. We successfully matched 29 patients who underwent IVC interruption to 29 patients without this procedure in 1:1 ratio. No significant differences existed in baseline characteristics between the groups. The comparison of perioperative data showed that patients who underwent IVC interruption had significantly longer median postoperative hospital stays (13 vs 9 days, P = 0.022) and a higher overall postoperative complication rate (79.3 vs 51.7%, P = 0.027). According to the side and shape of tumor thrombus, it could be divided into four categories. There were 15 cases (46.9%) with right filled-type tumor thrombus (RFTT), 8 cases (25.0%) with right non-filled-type tumor thrombus (RNFTT), 1 case (3.1%) with left filled-type tumor thrombus (LFTT) and 8 cases (25.0%) with left non-filled-type tumor thrombus (LNFTT). According to different categories, different surgical procedures were adopted. CONCLUSIONS: IVC interruption will increase the incidence of overall postoperative complications, but not the risk of major postoperative complications. Tumor thrombus should be divided into four categories, and different sides and shapes of renal tumor thrombus need different operative procedure of IVC interruption.

Renal cell carcinoma with tumor thrombus growing against the direction of venous return: an indicator of complicated surgery and poor prognosis.

PURPOSE: To explore the effect of tumor thrombus growing against the direction of venous return (GADVR) tumor thrombus on the choice of surgical approach, the impact on the complexity of the surgery and the prognosis. METHODS: We retrospectively analyzed the clinicopathological data of 213 patients, who underwent surgery in a single center of Peking University Third Hospital between January 2016 and June 2020. For right renal cell carcinoma (RCC) and venous tumor thrombus (VTT), imaging revealed a filling defect in the left renal vein, which was significantly enhanced in enhanced imaging, suggesting that the tumor thrombus grew against the direction of venous return into the left renal vein. For left RCC and VTT, at least one of the left renal vein branches has tumor thrombus. The branches include the left adrenal vein, the left gonadal vein (testicular vein or ovarian vein), and the left ascending lumbar vein. The patients were divided into two groups according to whether they were GADVR tumor thrombus, and we compare the clinicopathological characteristics of GADVR tumor thrombus and non-GADVR tumor thrombus. Univariate and multivariate Cox regression analyses were performed to explore the risk factors that affect the prognosis of patients with RCC and VTT. Kaplan-Meier plots were conducted to evaluate the effect of GADVR on progression-free survival (PFS). RESULTS: Compared with non-GADVR tumor thrombus, patients with GADVR tumor thrombus had a higher proportion of open surgery (76.2% vs. 52.1%, P = 0.035), a higher proportion of tumor thrombus adhering to the inferior vena cava (IVC) vessel wall (81% vs. 45.8%, P = 0.002), a higher proportion of segmental resection of the IVC vessel wall (61.9% vs. 15.6%, P < 0.001); higher preoperative serum creatinine value (110.0 µmol/L vs. 91.0 µmol/L, P = 0.015), a higher proportion of tumor thrombus combined with bland thrombus (non-tumor thrombus) (57.1% vs. 19.8%, P < 0.001). In terms of surgical complexity, patients with GADVR tumor thrombus had a longer median operation time (379 min vs. 308 min, P = 0.038), more median surgical blood loss (1400 mL vs. 600 mL, P = 0.018), and more postoperative complications (52.4% vs. 30.7%, P = 0.045). Multivariate Cox regression analysis showed that GADVR tumor thrombus, symptoms, postoperative serum creatinine, distant metastasis, sarcomatoid feature, pathological type, lymph node dissection were independent risk factors for PFS. Patients with GADVR tumor thrombus's median survival time was 14.0 months, while patients with non-GADVR tumor thrombus were 32.0 months (P = 0.016). GADVR tumor thrombus is an independent risk factor for PFS in patients with RCC and VTT. CONCLUSION: GADVR tumor thrombus is a characteristic feature of tumor thrombus, with an incidence of 9.9%. It has a higher proportion of open surgery and higher surgical complexity, which is an independent risk factor for PFS.

The effect of renal function change on renal cell carcinoma patients with tumor thrombus after nephrectomy and thrombectomy: a large Chinese center experience.

BACKGROUND: To explore the influencing factors of perioperative renal function change and their relationship with prognosis on renal cell carcinoma (RCC) patients with tumor thrombus after nephrectomy and thrombectomy. METHODS: The clinical and pathological data of 135 patients with RCC and tumor thrombus, who underwent nephrectomy and thrombectomy at Peking University Third Hospital from May 2015 to July 2018, was retrospectively analyzed. Absolute change in estimated glomerular filtration rate (eGFR) (ACE) and percent change in eGFR (PCE) were calculated by preoperative and postoperative renal function. Linear regression analysis was used to explore the influencing factors of ACE and PCE, and logistic regression analysis was used to explore the influencing factors of worse postoperative renal function [eGFR≤60 mL/(min × 1.73 m^2)]. Cancer-specific survival (CSS) was estimated by Kaplan-Meier method and multivariate Cox regression, which were used to explore the effect of ACE and PCE on prognosis. RESULTS: Of all the 135 patients, 101 patients (74.8%) were male and 34 patients (25.2%) were female. The mean preoperative eGFR was 73.9 ± 21.8 mL/(min × 1.73 m^2) and postoperative eGFR was 69.5 ± 25.2 mL/(min × 1.73 m^2). In multivariate linear regression analysis, preoperative eGFR (P < 0.001) and pathological type (P = 0.038) were significant predictive factors of ACE. In aspect of PCE, preoperative eGFR (P < 0.001) and pathological type (P = 0.002) were significant predictors. In multivariate logistic regression analysis, preoperative eGFR (P = 0.016) was the only risk factor of predicting worse postoperative renal function. During follow-up, 22 patients (16.3%) were dead due to RCC. According to ROC analysis, the cut off value of ACE and PCE was 13.9 and 0.16, respectively. ACE> 13.9 and PCE > 0.16 indicated worse CSS (P = 0.006 and P = 0.047, respectively). However, in multivariate Cox regression analysis of several related factors, perinephric tissues invasion (P = 0.001), sarcomatoid differentiation (P = 0.001) and ACE> 13.9 (P = 0.002) were significant prognostic factors for CSS. PCE > 0.16 seemed to be not (P = 0.055). CONCLUSION: We explored several clinicopathological risk factors of predicting renal function change and their relationship with prognosis of RCC patients with tumor thrombus after nephrectomy and thrombectomy. The renal function change, which was associated with preoperative eGFR and pathological type, was prognostic risk factor for CSS and ACE> 13.9 indicated the worse prognosis.

Laparoscopic conversion to open surgery in radical nephrectomy and tumor thrombectomy: causal analysis, clinical characteristics, and treatment strategies.

BACKGROUND: We aimed to explore the causal analysis, clinical characteristics and treatment strategies of laparoscopic conversion to open approach (LCTOA) in radical nephrectomy and tumor thrombectomy. METHODS: We included all patients with Mayo level I-III renal tumors with inferior vena cava (IVC) tumor thrombus who underwent laparoscopic radical nephrectomy and tumor thrombectomy as the first choice from May 2015 to July 2019. RESULTS: There were 70 cases of renal tumor with IVC tumor thrombus treated with a laparoscopic approach as the first choice; 31 Mayo level I, 30 Mayo level II, and 9 Mayo level III. A completely laparoscopic approach was performed in 51 cases (72.9%), and 19 cases (27.1%) underwent active or passive LCTOA. The LCTOA group had higher median preoperative serum creatinine (110.0 µmol/L vs 92.0 µmol/L; P = 0.026), longer postoperative hospital stay (9 days vs 7 days; P = 0.008), longer median operation time (374 min vs 311 min; P = 0.017), higher median intraoperative hemorrhage volume (1300 vs 600 ml; P = 0.020), and higher proportion of male patients (94.7% vs 66.7%; P = 0.016) vs the completely laparoscopic group, respectively. Although preoperative serum creatinine and gender were risk factors in the univariate analysis, multivariate analysis revealed no independent risk factors for LCTOA. We divided the reasons for LCTOA into active conversion and passive conversion; 4 (21.1%) cases underwent active conversion, and 15 (78.9%) underwent passive conversion. Most of the patients undergoing passive conversion had multiple concurrent risk factors, among which perirenal adhesion (30.9%), organ invasion (16.4%), and IVC adhesion (25.5%) were the most common. Fourteen (73.7%) cases underwent renal treatment, and 5 (26.3%) cases underwent tumor thrombus treatment. CONCLUSIONS: The LCTOA group had a higher median preoperative serum creatinine concentration, longer hospital stay, longer median operation time, and higher median intraoperative hemorrhage volume. However, none of the predictors in our study was an independent risk factor for LCTOA. Perirenal adhesion, organ invasion, and IVC adhesion were the most common causes of LCTOA. Considering the limitations of this study, studies with large sample sizes are required to validate our conclusions.

Modular Synthesis and Biological Investigation of 5-Hydroxymethyl Dibenzyl Butyrolactones and Related Lignans.

Dibenzyl butyrolactone lignans are well known for their excellent biological properties, particularly for their notable anti-proliferative activities. Herein we report a novel, efficient, convergent synthesis of dibenzyl butyrolactone lignans utilizing the acyl-Claisen rearrangement to stereoselectively prepare a key intermediate. The reported synthetic route enables the modification of these lignans to give rise to 5-hydroxymethyl derivatives of these lignans. The biological activities of these analogues were assessed, with derivatives showing an excellent cytotoxic profile which resulted in programmed cell death of Jurkat T-leukemia cells with less than 2% of the incubated cells entering a necrotic cell death pathway.

Prostate cancer incidentally discovered at the time of radical cystoprostatectomy does not decrease overall survival: Results from a large Chinese medical center.

PURPOSE: To investigate the incidence and pathologic characteristics of prostate cancer (PCa) incidentally discovered at the time of radical cystectomy and its impact on overall survival. MATERIALS AND METHODS: A single center retrospective study of 762 male patients who underwent radical cystoprostatectomy from Jan 1994 to Dec 2012. RESULTS: Of all included patients, 132 (17.3%) were found to have PCa. Patients with incidental PCa had a significantly higher mean age (69.2 vs. 62.2 years, P=0.015). Among the 132 patients with PCa, prostate specific antigen (PSA) analysis was available in 76 patients (57.6%), with a median value of 1.06ng/mL, and 61 (80.3%) patients had a PSA value below 4ng/mL. Four hundred and thirty-six patients (57.1%) were successfully followed, with a median duration of 46.5 months. The overall 5-year survival rate was 62.1%, and the 5-year cancer-specific survival rate was 72%. PCa recurrence was defined by two consecutive PSA values of >0.2 ng/mL and rising, and no PCa recurrence occurred. According to a univariate analyses, incidental PCa was not associated with cancer-specific survival (P=0.192) or overall survival (P=0.493). According to univariate analyses, the overall survival of patients with PCa was not associated with prostate cancer staging, PSA value, or Gleason score (All P values>0.05). CONCLUSIONS: Prostate cancer incidentally discovered at the time of radical cystectomy does not decrease overall survival. Patients with incidental PCa were older than those without. The PSA value before operation is not helpful for predicting incidental prostate cancers.

Analysis of Factors Influencing Mayo Adhesive Probability Score in Partial Nephrectomy.

BACKGROUND To retrospectively explore the factors influencing Mayo Adhesive Probability (MAP) score in the setting of partial nephrectomy. MATERIAL AND METHODS Data of 93 consecutive patients who underwent laparoscopic and open partial nephrectomy from September 2015 to June 2016 were collected and analyzed retrospectively. Preoperative radiological elements were independently assessed by 2 readers. Ordinal logistic regression analyses were performed to evaluate radiological and clinicopathologic influencing factors of MAP score. RESULTS On univariate analysis, MAP score was associated with male sex, older age, higher body mass index (BMI), history of hypertension and diabetes mellitus, and perirenal fat thickness (posterolateral, lateral, anterior, anterolateral, and medial). On multivariate analysis, only posterolateral perirenal fat thickness (odds ratio [OR]=0.88 [0.82-0.95], p=0.001), medial perirenal fat thickness (OR=0.90 [0.83-0.98], p=0.01), and history of diabetes mellitus (OR=5.42 [1.74-16.86], p=0.004) remained statistically significant. Tumor type (malignant vs. benign) was not statistically different. In patients with renal cell carcinoma (RCC), there was no difference in tumor stage or grade. CONCLUSIONS MAP score is significantly correlated with some preoperative factors such as posterolateral and medial perirenal fat thickness and diabetes mellitus. A new radioclinical scoring system including these patient-specific factors may become a better predictive tool than MAP score alone.

Research progress of green antisolvent for perovskite solar cells.

Conventional antisolvents such as chlorobenzene and benzotrifluoride are highly toxic and volatile, and therefore not preferred for large-scale fabrication. As such, green antisolvents are favored for the eco-friendly fabrication of perovskite films. This review primarily discusses the impact of various green antisolvents on the fabrication of thin perovskite films and analyzes the main chemical characteristics of these green antisolvents. It also interprets the impact of green antisolvent treatment on crystal growth and nucleation crystallization mechanisms. It introduces the effective fabrication of large-area devices using green antisolvents and analyzes the mechanisms by which green antisolvents enhance device stability. Subsequently, several green antisolvents capable of preparing highly stable and efficient devices are listed. Finally, we outline the key challenges and future prospects of antisolvent treatment. This review paves the way for green fabrication of industrial perovskite solar cells.

Multidrug-Resistant Escherichia coli Remains Susceptible to Metal Ions and Graphene-Based Compounds.

Escherichia coli is listed as a priority 1 pathogen on the World Health Organization (WHO) priority pathogen list. For this list of pathogens, new antibiotics are urgently needed to control the emergence and spread of multidrug-resistant strains. This study assessed eighteen metal ions, graphene, and graphene oxide for their antimicrobial efficacy against E. coli in both planktonic and biofilm growth states and the potential synergy between metal ions and graphene-based compounds. Molybdenum and tin ions exhibited the greatest antimicrobial activity against the planktonic states of the isolates with minimal inhibitory concentrations (MIC) ranging between 13 mg/L and 15.6 mg/L. Graphene oxide had no antimicrobial effect against any of the isolates, while graphene showed a moderate effect against E. coli (MIC, 62.5 mg/L). Combinations of metal ions and graphene-based compounds including tin-graphene, tin-graphene oxide, gold-graphene, platinum-graphene, and platinum-graphene oxide exhibited a synergistic antimicrobial effect (FIC ≤ 0.5), inhibiting the planktonic and biofilm formation of the isolates regardless of their antibiotic-resistant profiles. The bactericidal effect of the metal ions and the synergistic effects when combined with graphene/graphene oxide against medically relevant pathogens demonstrated that the antimicrobial efficacy was increased. Hence, such agents may potentially be used in the production of novel antimicrobial/antiseptic agents.

Distortion Effect on the UHPC Box Girder with Vertical Webs: Theoretical Analysis and Case Study.

Distortion deformation usually imposes a potential threat to bridge safety. In order to comprehensively understand the distortion effect on thin-walled ultra-high performance concrete (UHPC) box girders, an innovative approach encompassing the governing distortion differential equation is introduced in this study based on the general definition of distortion angle within the cross-section plane. The analytical results obtained from the proposed method are in accordance with those obtained from the energy method, and exhibit favorable agreement with experimental findings documented in the existing literature. Furthermore, a finite element model is developed on the ANSYS 2021 R1 software platform with the employment of a Shell 63 element. Numerical outcomes are also in good agreement with the experimental data, affirming the validity and reliability of the findings. In addition, parameter analysis results indicate that the distortion angle remains approximately constant at a location approximately 1/10 of the span from the mid-span cross-section of the box girder, regardless of changes in the span-to-depth ratio. Increasing the web thickness yields a notable reduction in the distortion effects, and decreasing the wall thickness can effectively mitigate the distortion-induced transverse bending moment. Compared with normal-strength concrete box girders, UHPC box girders can reduce the distortion angle within the span range, which is beneficial for maintaining the overall stability of the box girders. The outcomes obtained from this study yield engineers an enhanced understanding of distortion effect on the UHPC girder performance.

Gallic acid pretreatment mitigates parathyroid ischemia-reperfusion injury through signaling pathway modulation.

Thyroid surgery often results in ischemia-reperfusion injury (IRI) to the parathyroid glands, yet the mechanisms underlying this and how to ameliorate IRI remain incompletely explored. Our study identifies a polyphenolic herbal extract-gallic acid (GA)-with antioxidative properties against IRI. Through flow cytometry and CCK8 assays, we investigate the protective effects of GA pretreatment on a parathyroid IRI model and decode its potential mechanisms via RNA-seq and bioinformatics analysis. Results reveal increased apoptosis, pronounced G1 phase arrest, and significantly reduced cell proliferation in the hypoxia/reoxygenation group compared to the hypoxia group, which GA pretreatment mitigates. RNA-seq and bioinformatics analysis indicate GA's modulation of various signaling pathways, including IL-17, AMPK, MAPK, transient receptor potential channels, cAMP, and Rap1. In summary, GA pretreatment demonstrates potential in protecting parathyroid cells from IRI by influencing various genes and signaling pathways. These findings offer a promising therapeutic strategy for hypoparathyroidism treatment.

Highly crystalline cellulose microparticles from dealginated seaweed waste ameliorate high fat-sugar diet-induced hyperlipidemia in mice by modulating gut microbiota.

The effects of seaweed cellulose (SC) on high fat-sugar diet (HFSD)-induced glucolipid metabolism disorders in mice and potential mechanisms were investigated. SC was isolated from dealginated residues of giant kelp (Macrocystis pyrifera), with a crystallinity index of 85.51 % and an average particle size of 678.2 nm. Administering SC to C57BL/6 mice at 250 or 500 mg/kg BW/day via intragastric gavage for six weeks apparently inhibited the development of HFSD-induced obesity, dyslipidemia, insulin resistance, oxidative stress and liver damage. Notably, SC intervention partially restored the structure and composition of the gut microbiota altered by the HFSD, substantially lowering the Firmicutes to Bacteroidetes ratio, and greatly increasing the relative abundance of Lactobacillus, Bifidobacterium, Oscillospira, Bacteroides and Akkermansia, which contributed to improved short-chain fatty acid (SCFA) production. Supplementing with a higher dose of SC led to more significant increases in total SCFA (67.57 %), acetate (64.56 %), propionate (73.52 %) and butyrate (66.23 %) concentrations in the rectal contents of HFSD-fed mice. The results indicated that highly crystalline SC microparticles could modulate gut microbiota dysbiosis and ameliorate HFSD-induced obesity and related metabolic syndrome in mice. Furthermore, particle size might have crucial impact on the prebiotic effects of cellulose as insoluble dietary fiber.

Gleason Score-related MT1L as biomarker for prognosis in prostate adenocarcinoma and contribute to tumor progression in vitro.

BACKGROUND: The Gleason Score is well correlated with biological behavior and prognosis in prostate adenocarcinoma (PRAD). This study was derived to determine the clinical significance and function of Gleason-Score-related genes in PRAD. METHODS: RNA-sequencing profiles and clinical data were extracted from the The Cancer Genome Atlas PRAD database. The Gleason-Score-related genes were screened out by the Jonckheere-Terpstra rank-based test. The "limma" R package was performed for differentially expressed genes. Next, a Kaplan-Meier survival analysis was performed. Correlation MT1L expression levels with tumor stage, non-tumor tissue stage, radiation therapy, and residual tumor were analyzed. Further, MT1L expression was detected in PRAD cell lines by reverse transcription-quantitative polymerase chain reaction assay. Overexpression of MT1L was constructed and used for cell count kit-8, flow cytometric assay, transwell assay, and wound-healing assay. RESULTS: Survival analysis showed 15 Gleason-Score-related genes as prognostic biomarkers in PRAD. The high-frequency deletion of MT1L was verified in PRAD. Furthermore, MT1L expression was decreased in PRAD cell lines than RWPE-1 cells, and overexpression of MT1L repressed cell proliferation and migration, and induced apoptosis in PC-3 cells. CONCLUSION: Gleason-Score-related MT1L may serve as a biomarker of poor prognostic biomarker in PRAD. In addition, MT1L plays a tumor suppressor in PRAD progression, which is beneficial for PRAD diagnosis and treatment research.

An innate pathogen sensing strategy involving ubiquitination of bacterial surface proteins.

Sensing of pathogens by ubiquitination is a critical arm of cellular immunity. However, universal ubiquitination targets on microbes remain unidentified. Here, using in vitro, ex vivo, and in vivo studies, we identify the first protein-based ubiquitination substrates on phylogenetically diverse bacteria by unveiling a strategy that uses recognition of degron-like motifs. Such motifs form a new class of intra-cytosolic pathogen-associated molecular patterns (PAMPs). Their incorporation enabled recognition of nonubiquitin targets by host ubiquitin ligases. We find that SCFFBW7 E3 ligase, supported by the regulatory kinase, glycogen synthase kinase 3ß, is crucial for effective pathogen detection and clearance. This provides a mechanistic explanation for enhanced risk of infections in patients with chronic lymphocytic leukemia bearing mutations in F-box and WD repeat domain containing 7 protein. We conclude that exploitation of this generic pathogen sensing strategy allows conservation of host resources and boosts antimicrobial immunity.