A Prognostic Model Based on Nutritional Indexes for Patients With Pan-Cancer: A Real-World Cohort Study.

BACKGROUND: The aim was to identify the nutritional indexes, construct a prognostic model, and develop a nomogram for predicting individual survival probability in pan-cancers. METHODS: Nutritional indicators, clinicopathological characteristics, and previous major treatment details of the patients were collected. The enrolled patients were randomly divided into training and validation cohorts. Least absolute shrinkage and selection operator (Lasso) regression cross-validation was used to determine the variables to include in the cox regression model. The training cohort was used to build the prediction model, and the validation cohort was used to further verify the discrimination, calibration, and clinical effectiveness of the model. RESULTS: A total of 2020 patients were included. The median OS was 56.50 months (95% CI, 50.36-62.65 months). In the training cohort of 1425 patients, through Lasso regression cross-validation, 13 characteristics were included in the model. Cox proportional hazards model was developed and visualized as a nomogram. The C-indexes of the model for predicting 1-, 3-, 5-, and 10-year OS were 0.848, 0.826, 0.814, and 0.799 in the training cohort and 0.851, 0.819, 0.814, and 0.801 in the validation cohort. The model showed great calibration in the two cohorts. Patients with a score of less than 274.29 had a better prognosis (training cohort: HR, 6.932; 95% CI, 5.723-8.397; log-rank p < 0.001; validation cohort: HR, 8.429; 95% CI, 6.180-11.497; log-rank p < 0.001). CONCLUSION: The prognostic model based on the nutritional indexes of pan-cancer can divide patients into different survival risk groups and performed well in the validation cohort.

Epidemiology of injuries among snowboarding athletes in the talent transfer program: A prospective cohort study of 39,880 athlete-exposures.

BACKGROUND: Talent transfer (TT) program is an appropriate approach to address the talent gap evident in specific sports activities, while little is known about the injury characteristics of snowboarding athletes involved in the TT program. OBJECTIVE: To determine the epidemiology of injuries among snowboarders involved in the TT program. METHODS: A total of 244 athletes who were not previously engaged in winter sports were selected for training in snowboarding that lasted for 109 days. The injuries and at-risk exposures (A-Es) data were recorded by physicians. Injury rates (IRs), incidence rate ratios (IRRs), and injury proportion ratios (IPRs) were calculated and compared by sex and age groups. RESULTS: The overall and time loss (TL) IR were 32.4/1000 A-Es and 12.2/1000 A-Es respectively. The overall and non-time loss (NTL) IRR were higher for female athletes than for male athletes. Additionally, the overall IRR and TL-IRR for female athletes were higher in those athletes who aged ≤15 years old. Over 93% of TL injuries resulted in participation restriction time of ≤7 days (male athletes, 93.94%; female athletes, 94.10%). Trunk (28.43%), knee joints (21.33%), and hand/wrist (16.53%) were found as the common sites of injury in both female and male athletes. The most frequent type of injury was contusion (male athletes: 53.00%, female athletes: 59.10%) resulted from ground/apparatus contact (male athletes: 75.10%, female athletes: 75.20%). CONCLUSION: The risk injury among snowboarding athletes involved in the TT program during the first snow season training was found noticeable, especially for younger female athletes. The high incidence of ground/apparatus contact-related injuries suggested the necessity of specifically designed training programs and braces for snowboarding athletes involved in the TT program.

[Ecological environment quality of the Shanxi section of the Yellow River Basin under different development scenarios]. / ä¸åŒå‘å±•æƒ æ™¯ä¸‹é»„æ²³æµåŸŸå±±è¥¿æ®µç”Ÿæ€çŽ¯å¢ƒè´¨é‡.

Shanxi Province holds an important strategic position in the overall ecological pattern of the Yellow River Basin. To investigate the changes of the ecological environment in the Shanxi section of the Yellow River Basin from 2000 to 2020, we selected MODIS remote sensing image data to determine the remote sensing ecological index (RSEI) based on the principal component analysis of greenness, humidity, dryness, and heat. Then, we analyzed the spatial and temporal variations of ecological quality in this region to explore the influencing factors. We further used the CA-Markov model to simulate and predict the ecological environment under different development scenarios in the Shanxi section of the Yellow River Basin in 2030. The results showed that RSEI had good applicability in the Shanxi section of the Yellow River Basin which could be used to monitor and evaluate the spatiotemporal variations in its ecological environment. From 2000 to 2020, the Shanxi section of the Yellow River Basin was dominated by low quality habitat areas, in which the ecological environment quality continued to improve from 2000 to 2010 and decreased from 2010 to 2020. The high quality habitat areas mainly located on the mountainous areas with superior natural conditions and rich biodiversity, while the low ecological quality areas were mainly in the Taiyuan Basin and the northern part of the study area, where the mining industry developed well. Climate factors were negatively correlated with ecological environment quality in the northern and central parts of the study area, and positively correlated with that in the mountainous area. Under all three development scenarios, the area of cultivated land, forest, water and construction land increased in 2030 compared to that in 2020. Compared to the natural development scenario and the cultivated land protection scenario, the ecological constraint scenario with RSEI as the limiting factor had the highest area of new forest and the lowest expansion rate of cultivated land and construction land. The results would provide a reference for land space planning and ecological environment protection in the Shanxi section of the Yellow River Basin.

Aberrant social reward dynamics in individuals with melancholic major depressive disorder: An ERP study.

BACKGROUND: Compared to monetary rewards, depressive symptoms are specifically associated with abnormal social reward processing. In addition, individuals with melancholic depression may exhibit more significant reward-related impairments. However, there is still limited understanding of the specific alterations in social reward processing in individuals with melancholic depression. METHODS: Forty patients with melancholic major depressive disorder (MDD), forty patients with non-melancholic MDD, and fifty healthy controls participated in the social incentive delay (SID) tasks with event-related potential (ERP) recording. We measured one anticipatory ERP(cue-N2) and two consummatory ERPs (FRN, fb-P3). Furthermore, we examined correlation between FRN and consummatory anhedonia. RESULTS: Melancholic MDD patients showed less anticipation of social rewards (cue-N2). Concurrently, melancholic individuals demonstrated diminished reception of social rewards, as evidenced by reduced amplitudes of FRN. Notably, the group x condition interaction effect on FRN was significant (F (2, 127) = 4.15, p = 0.018, η2ρ = 0.061). Melancholic MDD patients had similar neural responses to both gain and neutral feedback (blunted reward positivity), whereas non-melancholic MDD patients (t (39) = 3.09, p = 0.004) and healthy participants (t (49) = 5.25, p < 0.001) had smaller FRN amplitudes when receiving gain feedback relative to neutral feedback. In addition, there was a significant correlation between FRN and consummatory anhedonia in MDD patients. CONCLUSIONS: Our findings indicated that individuals with melancholic MDD exhibit attenuated neural responses to both anticipated and consumed social rewards. This suggests that aberrant processing of social rewards could serve as a potential biomarker for melancholic MDD.

Capmatinib is an effective treatment for MET-fusion driven pediatric high-grade glioma and synergizes with radiotherapy.

BACKGROUND: Pediatric-type diffuse high-grade glioma (pHGG) is the most frequent malignant brain tumor in children and can be subclassified into multiple entities. Fusion genes activating the MET receptor tyrosine kinase often occur in infant-type hemispheric glioma (IHG) but also in other pHGG and are associated with devastating morbidity and mortality. METHODS: To identify new treatment options, we established and characterized two novel orthotopic mouse models harboring distinct MET fusions. These included an immunocompetent, murine allograft model and patient-derived orthotopic xenografts (PDOX) from a MET-fusion IHG patient who failed conventional therapy and targeted therapy with cabozantinib. With these models, we analyzed the efficacy and pharmacokinetic properties of three MET inhibitors, capmatinib, crizotinib and cabozantinib, alone or combined with radiotherapy. RESULTS: Capmatinib showed superior brain pharmacokinetic properties and greater in vitro and in vivo efficacy than cabozantinib or crizotinib in both models. The PDOX models recapitulated the poor efficacy of cabozantinib experienced by the patient. In contrast, capmatinib extended survival and induced long-term progression-free survival when combined with radiotherapy in two complementary mouse models. Capmatinib treatment increased radiation-induced DNA double-strand breaks and delayed their repair. CONCLUSIONS: We comprehensively investigated the combination of MET inhibition and radiotherapy as a novel treatment option for MET-driven pHGG. Our seminal preclinical data package includes pharmacokinetic characterization, recapitulation of clinical outcomes, coinciding results from multiple complementing in vivo studies, and insights into molecular mechanism underlying increased efficacy. Taken together, we demonstrate the groundbreaking efficacy of capmatinib and radiation as a highly promising concept for future clinical trials.

The association between uric acid and erectile dysfunction in US adults: NHANES 2001-2004.

BACKGROUND: -Recent evidence suggests that hyperuricemia may act as independent risk factors for erectile dysfunction (ED), in addition to the already established factors. The current evidence supporting this relationship remains insufficient. METHODS AND RESULTS: -A total of 3,810 participants from the NHANES pool between 2001 and 2004 were included in our study, comprising 1,093 individuals with ED and 2,717 individuals without ED. Univariable and multivariable logistic regression analyses were conducted to examine the relationship between uric acid (UA) and the prevalence of ED. In the fully adjusted model, no significant association was observed between UA and ED (OR = 1.02, 95% CI: 0.84-1.24), and no significant differences were noted among the various UA levels (p = 0.5). In our sensitivity analyses, employing a stricter definition for ED, no significant results were found in the fully adjusted model (OR = 0.85, 95% CI: 0.60-1.19). Furthermore, no significant differences were observed among the various UA levels (p = 0.083). CONCLUSIONS: -Our study did not establish a correlation between UA levels and ED. Nonetheless, further research with larger sample cohorts is required to verify these findings.

Hit-to-Lead Optimization of the Natural Product Oridonin as Novel NLRP3 Inflammasome Inhibitors with Potent Anti-Inflammation Activity.

Targeting NLRP3 inflammasome with inhibitors is a novel strategy for NLRP3-driven diseases. Herein, hit compound 5 possessing an attractive skeleton was identified from our in-house database of oridonin, and then a potential lead compound 32 was obtained by optimization of 5, displaying two-digit nanomolar inhibition on NLRP3. Moreover, compound 32 showed enhanced safety index (SI) relative to oridonin (IC50 = 77.2 vs 780.4 nM, SI = 40.5 vs 8.5) and functioned through blocking ASC oligomerization and interaction of NLRP3-ASC/NEK7, thereby suppressing NLRP3 inflammasome assembly and activation. Furthermore, diverse agonists-induced activations of NLRP3 could be impeded by compound 32 without altering NLRC4 or AIM2 inflammasome. Crucially, compound 32 possessed tolerable pharmaceutical properties and significant anti-inflammatory activity in MSU-induced gouty arthritis model. Therefore, this work enriched the SAR of NLRP3 inflammasome inhibitors and provided a potential candidate for the treatment of NLRP3-associated diseases.

Deciphering dissolved organic matter characteristics and its fate in a glacier-fed desert river-the Tarim river, China.

The bioavailable diverse dissolved organic matter (DOM) present in glacial meltwater significantly contributes to downstream carbon cycling in mountainous regions. However, the comprehension of molecular-level characteristics of riverine DOM, from tributary to downstream and their fate in glacier-fed desert rivers remains limited. Herein, we employed spectroscopic and high-resolution mass spectrometry techniques to study both optical and molecular-level characteristics of DOM in the Tarim River catchment, northwest China. The results revealed that the DOC values in the downstream were higher than those in the tributaries, yet they remained comparable to those found in other glacier-fed streams worldwide. Five distinct components were identified using EEM-PARAFAC analysis in both tributary and downstream samples. The dominance of three protein-like components in tributary samples, contrasting with a higher presence of humic-like components in downstream samples, which implied that the dilution and alterations of the glacier DOM signature and overprinting with terrestrial-derived DOM. Molecular composition revealed that thousands of compounds with higher molecular weight and increased aromaticity were transformed, generated and introduced from terrestrial inputs during downstream transportation. The twofold rise in polycyclic aromatic and polyphenolic compounds observed downstream compared to tributaries indicated a greater influx of terrestrial organic matter introduced into the downstream during water transportation. The study suggests that the glacier-sourced DOM experienced minimal photodegradations, with limited influence from human activities, while also being shaped by terrestrial inputs during its transit in the alpine-arid region. This unique scenario offers valuable insights into comprehending the fate of DOM originating from glacial meltwater in arid mountainous regions.

Cirbp suppression compromises DHODH-mediated ferroptosis defense and attenuates hypothermic cardioprotection in an aged donor transplantation model.

Hypothermia is commonly used to protect donor hearts during transplantation. However, patients transplanted with aged donor hearts still have severe myocardial injury and decreased survival rates, but the underlying mechanism remains unknown. Because aged hearts are not considered suitable for donation, the number of patients awaiting heart transplants is increasing. In this study, we examined whether hypothermic cardioprotection was attenuated in aged donor hearts during transplantation and evaluated potential therapeutic targets. Using a rat heart transplantation model, we found that hypothermic cardioprotection was impaired in aged donor hearts but preserved in young donor hearts. RNA-Seq showed that cold-inducible RNA-binding protein (Cirbp) expression was decreased in aged donor hearts, and these hearts showed severe ferroptosis after transplantation. The young donor hearts from Cirbp-KO rats exhibited attenuated hypothermic cardioprotection, but Cirbp overexpression in aged donor hearts ameliorated hypothermic cardioprotection. Cardiac proteomes revealed that dihydroorotate dehydrogenase (DHODH) expression was significantly decreased in Cirbp-KO donor hearts during transplantation. Consequently, DHODH-mediated ubiquinone reduction was compromised, thereby exacerbating cardiac lipid peroxidation and triggering ferroptosis after transplantation. A cardioplegic solution supplemented with CIRBP agonists improved hypothermic cardioprotection in aged donor hearts, indicating that this method has the potential to broaden the indications for using aged donor hearts in transplantation.

Importance of AIM2 as a serum marker for reflecting severity and predicting a poor outcome of human severe traumatic brain injury: A prospective longitudinal cohort study.

BACKGROUND: Absent in melanoma 2 (AIM2) participates in neuroinflammation. Here, the prognostic significance of serum AIM2 was explored in severe traumatic brain injury (sTBI). METHODS: A total of 135 sTBI patients and 80 healthy controls were recruited in this prospective cohort study. Serum C-reactive protein (CRP) and AIM2 levels were measured. Glasgow Coma Scale (GCS) and Rotterdam computed tomography (CT) classification were recorded as the severity indicators. Prognostic parameters were posttraumatic six-month extended Glasgow outcome scale (GOSE) scores and poor outcome (GOSE scores of 1-4). RESULTS: As opposed to controls, there were significantly elevated serum AIM2 levels after sTBI. Serum AIM2 levels were independently correlated with serum CRP levels, GCS scores, Rotterdam CT scores, GOSE scores and poor outcome. Also, serum AIM2 levels were efficiently predictive of poor outcome under the receiver operating characteristic (ROC) curve. Under the restricted cubic spline, serum AIM2 levels were linearly correlated with risk of poor outcome. Using subgroup analysis, serum AIM2 levels did not significantly interact with other indices, such as age, gender, alcohol drinking, cigarette smoking, etc. Also, combination model, in which serum AIM2, GCS scores and Rotterdam CT scores were merged, was outlined using nomogram and performed well under calibration curve, ROC curve and decision curve. CONCLUSIONS: Raised serum AIM2 levels after sTBI, in intimate correlation with systemic inflammation and trauma severity, are independently discriminative of posttraumatic six-month neurological outcome, substantializing serum AIM2 as an inflammatory prognostic biomarker of sTBI.

KCNQ1 rs2237895 gene polymorphism increases susceptibility to type 2 diabetes mellitus in Asian populations.

BACKGROUND: The association of single nucleotide polymorphism of KCNQ1 gene rs2237895 with type 2 diabetes mellitus (T2DM) is currently controversial. It is unknown whether this association can be gene realized across different populations. AIM: To determine the association of KCNQ1 rs2237895 with T2DM and provide reliable evidence for genetic susceptibility to T2DM. METHODS: We searched PubMed, Embase, Web of Science, Cochrane Library, Medline, Baidu Academic, China National Knowledge Infrastructure, China Biomedical Liter-ature Database, and Wanfang to investigate the association between KCNQ1 gene rs2237895 and the risk of T2DM up to January 12, 2022. Review Manager 5.4 was used to analyze the association of the KCNQ1 gene rs2237895 polymorphism with T2DM and to evaluate the publication bias of the selected literature. RESULTS: Twelve case-control studies (including 11273 cases and 11654 controls) met our inclusion criteria. In the full population, allelic model [odds ratio (OR): 1.19; 95% confidence interval (95%CI): 1.09-1.29; P < 0.0001], recessive model (OR: 1.20; 95%CI: 1.11-1.29; P < 0.0001), dominant model (OR: 1.27. 95%CI: 1.14-1.42; P < 0.0001), and codominant model (OR: 1.36; 95%CI: 1.15-1.60; P = 0.0003) (OR: 1.22; 95%CI: 1.10-1.36; P = 0.0002) indicated that the KCNQ1 gene rs2237895 polymorphism was significantly correlated with susceptibility to T2DM. In stratified analysis, this association was confirmed in Asian populations: allelic model (OR: 1.25; 95%CI: 1.13-1.37; P < 0.0001), recessive model (OR: 1.29; 95%CI: 1.11-1.49; P = 0.0007), dominant model (OR: 1.35; 95%CI: 1.20-1.52; P < 0.0001), codominant model (OR: 1.49; 95%CI: 1.22-1.81; P < 0.0001) (OR: 1.26; 95%CI: 1.16-1.36; P < 0.0001). In non-Asian populations, this association was not significant: Allelic model (OR: 1.06, 95%CI: 0.98-1.14; P = 0.12), recessive model (OR: 1.04; 95%CI: 0.75-1.42; P = 0.83), dominant model (OR: 1.06; 95%CI: 0.98-1.15; P = 0.15), codominant model (OR: 1.08; 95%CI: 0.82-1.42; P = 0.60. OR: 1.15; 95%CI: 0.95-1.39; P = 0.14). CONCLUSION: KCNQ1 gene rs2237895 was significantly associated with susceptibility to T2DM in an Asian population. Carriers of the C allele had a higher risk of T2DM. This association was not significant in non-Asian populations.

Heavy metal induced shifts in microbial community composition and interactions with dissolved organic matter in coastal sediments.

Heavy metals can impact the structure and function of coastal sediment. The dissolved organic matter (DOM) pool plays an important role in determining both the heavy metal toxicity and microbial community composition in coastal sediments. However, how heavy metals affect the interactions between microbial communities and DOM remains unclear. Here, we investigated the influence of heavy metals on the microbial community structure (including bacteria and archaea) and DOM composition in surface sediments of Beibu Gulf, China. Our results revealed firstly that chromium, zinc, cadmium, and lead were the heavy metals contributing to pollution in our studied area. Furthermore, the DOM chemical composition was distinctly different in the contaminated area from the uncontaminated area, characterized by a higher average O/C ratio and increased prevalence of carboxyl-rich alicyclic molecules (CRAM) and highly unsaturated compounds (HUC). This indicates that DOM in the contaminated area was more recalcitrant compared to the uncontaminated area. Except for differences in archaeal diversity between the two areas, there were no significant variations observed in the structure of archaea and bacteria, as well as the diversity of bacteria, across the two areas. Nevertheless, our co-occurrence network analysis revealed that the B2M28 and Euryarchaeota, dominating bacterial and archaeal groups in the contaminated area were strongly related to CRAM. The network analysis also unveiled correlations between active bacteria and elevated proportions of nitrogen-containing DOM molecules. In contrast, the archaea-DOM network exhibited strong associations with nitrogen- and sulfur-containing molecules. Collectively, these findings suggest that heavy metals indeed influence the interaction between microbial communities and DOM, potentially affecting the accumulation of recalcitrant compounds in coastal sediments.

Association of serum 25-hydroxy-vitamin D concentration and risk of mortality in cancer survivors in the United States.

PURPOSE: Cancer survivors have a high risk of mortality, and vitamin D (VD) is associated with the risk of mortality. This study is aim to examine the impact of VD on mortality in cancer survivors. METHODS: A prospective study was conducted using data from the National Health and Nutrition Examination Survey. Participants were obtained information on their baseline characteristics, dietary habits, comorbidities, lifestyle, and serum 25-hydroxy VD [25(OH)D] concentrations. The weighted Cox proportional hazard and competing risk regression models were used to estimate the hazard ratio and 95% confidence intervals (HR, 95% CI) of mortality for different serum 25(OH)D concentrations. Restricted cubic spline (RCS) curves were utilized to illustrate the dose-response relationship between serum 25(OH)D concentrations and mortality. RESULTS: The study encompassed 2,495 participants with cancer diagnoses. Multivariate models indicated that, compared to serum 25(OH)D concentrations below 58.5 nmol/L, concentrations exceeding 81.6 nmol/L were associated with reduced HRs for all-cause mortality (HR = 0.70; 95% CI: 0.56-0.87), cardiovascular mortality (HR = 0.53; 95% CI: 0.32-0.86), and cancer-specific mortality (HR = 0.66; 95% CI: 0.45-0.99). RCS curves revealed "L-shaped" associations between serum 25(OH)D concentration and both all-cause and cancer-specific mortality, with threshold effects at 87.9 nmol/L and 84.6 nmol/L, respectively. Conversely, the relationship between serum 25(OH)D concentration and cardiovascular mortality exhibited a more linear pattern, with a threshold at 88.7 nmol/L. Subgroup analyses highlighted a gender-specific interaction that elevated serum 25(OH)D concentrations were significantly more protective against mortality in males than in females, especially regarding cancer-specific mortality (P-interaction = 0.009). CONCLUSION: Elevated serum 25(OH)D concentrations were correlated with decreased risks of all-cause, cardiovascular, and cancer-specific mortality in cancer survivors, with benefit thresholds at 87.9, 88.7, and 84.6 nmol/L, respectively. These findings suggested that cancer survivors might benefit from higher vitamin D recommendations than the general population.

Selective Orbital Coupling: An Adsorption Mechanism in Single-Atom Catalysis.

Quantitative understanding of the chemisorption on single-atom catalysts (SACs) by their electronic properties is crucial for the catalyst design. However, the physical mechanism is still under debate. Here, the CO catalytic oxidation on single transition metal (i.e., Sc, Ti, V, Cr, Mn, Fe, Co, Ni) dopants is used as a theoretical model to explore the correlations between the characteristics of electronic structures and the chemisorption on SACs. For these metal dopants, their atomic d orbitals form several nondegenerate and localized electronic states that are found to be selectively coupled with the π* orbital of the adsorbed O2, which we defined as selective orbital coupling. Based on the selective orbital coupling, we find that the alignment between the selected d state and the π* state determines the bond strength, regardless of the electron occupation number of the selected d states; the electron transfer to form M-O bonding can be provided by the support. Such electron transfer can be related with the electronic metal-support interaction. We attribute the origin of the chemisorption mechanism to the coexistence of the localized orbital of the single transition metal and the continuous energy band of the Au support. Finally, we illustrate how this mechanism dominates the variation trend of the reaction barriers. Our results unravel a fundamental adsorption mechanism in SAC systems.

Mechanosensitive protein polycystin-1 promotes periosteal stem/progenitor cells osteochondral differentiation in fracture healing.

Background: Mechanical forces are indispensable for bone healing, disruption of which is recognized as a contributing cause to nonunion or delayed union. However, the underlying mechanism of mechanical regulation of fracture healing is elusive. Methods: We used the lineage-tracing mouse model, conditional knockout depletion mouse model, hindlimb unloading model and single-cell RNA sequencing to analyze the crucial roles of mechanosensitive protein polycystin-1 (PC1, Pkd1) promotes periosteal stem/progenitor cells (PSPCs) osteochondral differentiation in fracture healing. Results: Our results showed that cathepsin (Ctsk)-positive PSPCs are fracture-responsive and mechanosensitive and can differentiate into osteoblasts and chondrocytes during fracture repair. We found that polycystin-1 declines markedly in PSPCs with mechanical unloading while increasing in response to mechanical stimulus. Mice with conditional depletion of Pkd1 in Ctsk+ PSPCs show impaired osteochondrogenesis, reduced cortical bone formation, delayed fracture healing, and diminished responsiveness to mechanical unloading. Mechanistically, PC1 facilitates nuclear translocation of transcriptional coactivator TAZ via PC1 C-terminal tail cleavage, enhancing osteochondral differentiation potential of PSPCs. Pharmacological intervention of the PC1-TAZ axis and promotion of TAZ nuclear translocation using Zinc01442821 enhances fracture healing and alleviates delayed union or nonunion induced by mechanical unloading. Conclusion: Our study reveals that Ctsk+ PSPCs within the callus can sense mechanical forces through the PC1-TAZ axis, targeting which represents great therapeutic potential for delayed fracture union or nonunion.

Electrochemical C-H Mono-/Multi-Bromination Regulation of N-Sulfonylanilines on a Cost-Effective Carbon Fiber Electrode and Its Prospective Electroactive Molecule Screening.

Electrochemical C-H mono/multi-bromination regulation of N-sulfonylanilines on the cost-effective CF electrode is described. This reaction proceeds smoothly under mild conditions with a broad substrate scope, affording diverse mono/multi-brominated anilines in moderate to good yields. Mechanism study reveals that this transformation involves anodic oxidation, aromatic electrophilic substitution, and deprotonation. Preliminary electroactive molecule screening results in its prospective application in electroactive MBs for electrochemical biosensors.

Early endoscopic management of an infected acute necrotic collection misdiagnosed as a pancreatic pseudocyst: A case report.

BACKGROUND: Infected acute necrotic collection (ANC) is a fatal complication of acute pancreatitis with substantial morbidity and mortality. Drainage plays an exceedingly important role as the first step in invasive intervention for infected necrosis; however, there is great controversy about the optimal drainage time, and better treatment should be explored. CASE SUMMARY: We report the case of a 43-year-old man who was admitted to the hospital with severe intake reduction due to early satiety 2 wk after treatment for acute pancreatitis; conservative treatment was ineffective, and a pancreatic pseudocyst was suspected on contrast-enhanced computed tomography (CT). Endoscopic ultrasonography (EUS) suggested hyperechoic necrotic tissue within the cyst cavity. The wall was not completely mature, and the culture of the puncture fluid was positive for A-haemolytic Streptococcus. Thus, the final diagnosis of ANC infection was made. The necrotic collection was not walled off and contained many solid components; therefore, the patient underwent EUS-guided aspiration and lavage. Two weeks after the collection was completely encapsulated, pancreatic duct stent drainage via endoscopic retrograde cholangiopancreatography (ERCP) was performed, and the patient was subsequently successfully discharged. On repeat CT, the pancreatic cysts had almost disappeared during the 6-month follow-up period after surgery. CONCLUSION: Early EUS-guided aspiration and lavage combined with late ERCP catheter drainage may be effective methods for intervention in infected ANCs.

EFFECT OF STRATIFIED DOSE OF NOREPINEPHRINE ON CELLULAR IMMUNE RESPONSE IN PATIENTS WITH SEPTIC SHOCK AND THE CONSTRUCTION OF A PROGNOSTIC RISK MODEL.

ABSTRACT: Objective: To explore the effect of a stratified dose of norepinephrine (NE) on cellular immune response in patients with septic shock, and to construct a prognostic model of septic shock. Methods: A total of 160 patients with septic shock (B group) and 58 patients with sepsis (A group) were given standard cluster therapy. Patients with septic shock were divided into four groups (B1-B4 groups: 0.01-0.2, 0.2-0.5, 0.5-1.0, and >1 µg/kg/min) according to the quartile method of the early (72 h) time-weighted average dose of NE and clinical application. The cellular immune indexes at 24 h (T0) and 4-7 days (T1) after admission were collected. The difference method was used to explore the effect of NE stratified dose on cellular immune effect in patients with septic shock. A multivariate COX proportional risk regression model was used to analyze the independent prognostic risk factors, and a prognostic risk model was constructed. Results: The differences of ΔIL-1ß, ΔIL-6, ΔIL-10, absolute value difference of T lymphocyte (ΔCD3+/CD45+#) and Th helper T cell (ΔCD3+ CD4+/CD45+#), CD64 infection index difference, ΔmHLA-DR, regulatory T lymphocyte ratio difference (ΔTregs%) between group A, B1, B2, B3, and B4 were statistically significant ( P < 0.05). There was a nonlinear relation between the stratified dose of NE and ΔIL-6, ΔIL-10, ΔCD3+/CD45+#, ΔmHLA-DR%. The threshold periods of NE-induced proinflammatory and anti-inflammatory immune changes were 0.3-0.5 µg/kg/min. Multivariate COX model regression analysis showed that age, nutritional patterns, weighted average dose of norepinephrine, IL-6, absolute value of T lymphocytes, and mHLA-DR were independent risk factors affecting the prognosis of patients with septic shock ( P < 0.05). The prognostic risk model was constructed (AUC value = 0.813, 95% CI: 0.752-0.901). Conclusion: NE has a certain inhibitory effect on cellular immune function in patients with septic shock. A prognostic risk model was constructed with stronger prediction efficiency for the prognosis of patients with septic shock.

Bottom-up and top-down controls on Alteromonas macleodii lead to different dissolved organic matter compositions.

The effects of both bottom-up (e.g. substrate) and top-down (e.g. viral lysis) controls on the molecular composition of dissolved organic matter have not been investigated. In this study, we investigated the dissolved organic matter composition of the model bacterium Alteromonas macleodii ATCC 27126 growing on different substrates (glucose, laminarin, extracts from a Synechococcus culture, oligotrophic seawater, and eutrophic seawater), and infected with a lytic phage. The ultra-high resolution mass spectrometry analysis showed that when growing on different substrates Alteromonas macleodii preferred to use reduced, saturated nitrogen-containing molecules (i.e. O4 formula species) and released or preserved oxidized, unsaturated sulfur-containing molecules (i.e. O7 formula species). However, when infected with the lytic phage, Alteromonas macleodii produced organic molecules with higher hydrogen saturation, and more nitrogen- or sulfur-containing molecules. Our results demonstrate that bottom-up (i.e. varying substrates) and top-down (i.e. viral lysis) controls leave different molecular fingerprints in the produced dissolved organic matter.

Enhancing Specific Fluorescence In Situ Hybridization with Quantum Dots for Single-Molecule RNA Imaging in Formalin-Fixed Paraffin-Embedded Tumor Tissues.

Single-molecule fluorescence in situ hybridization (smFISH) represents a promising approach for the quantitative analysis of nucleic acid biomarkers in clinical tissue samples. However, low signal intensity and high background noise are complications that arise from diagnostic pathology when performed with smFISH-based RNA imaging in formalin-fixed paraffin-embedded (FFPE) tissue specimens. Moreover, the associated complex procedures can produce uncertain results and poor image quality. Herein, by combining the high specificity of split DNA probes with the high signal readout of ZnCdSe/ZnS quantum dot (QD) labeling, we introduce QD split-FISH, a high-brightness smFISH technology, to quantify the expression of mRNA in both cell lines and clinical FFPE tissue samples of breast cancer and lung squamous carcinoma. Owing to its high signal-to-noise ratio, QD split-FISH is a fast, inexpensive, and sensitive method for quantifying mRNA expression in FFPE tumor tissues, making it suitable for biomarker imaging and diagnostic pathology.