Melatonin ameliorates multiorgan injuries induced by severe acute pancreatitis in mice by regulating the Nrf2 signaling pathway.

Severe acute pancreatitis (SAP) is a complicated inflammatory reaction that impacts the pancreas, often resulting in damage to numerous organs. This disorder encompasses a range of processes such as inflammation, oxidative stress, and pancreatitis. The hormone melatonin (MT) is primarily secreted by the pineal gland and plays a crucial role in mitigating inflammation, countering the harmful effects of free radicals, and regulating oxidative stress. The aim of this research was to investigate the potential protective impact and the underlying mechanism of melatonin in mice afflicted with SAP. The biochemical and histological assessments unequivocally demonstrated that melatonin effectively inhibited necrosis, infiltration, edema and cell death in pancreatic tissues, thereby suppressing acute pancreatitis. Notably, melatonin also alleviated the consequent harm to distant organs, notably the lungs, liver, and kidneys. Furthermore, both preventive and therapeutic administration of melatonin prompted nuclear factor E2-related factor 2 (Nrf2) activation followed by Nrf2 target gene expression. Nrf2 initiates the activation of antioxidant genes, thereby providing defense against oxidative stress. Conversely, Nrf2 reduction may contribute to impaired antioxidant protection in SAP. The beneficial impact of Nrf2 on antioxidants was absent in Nrf2-knockout mice, leading to the accumulation of LDH and exacerbation of cell death. This deterioration in both pancreatitis and injuries in distant organs intensified significantly. The results indicate that melatonin has an enhanced ability to protect against multiorgan damage caused by SAP, which is accomplished through the increase in Nrf2 expression. Additionally, Nrf2 initiates the activation of antioxidant genes that offer defense against cell death.

Comparison of metastasis and prognosis between early-onset and late-onset hepatocellular carcinoma: A population-based study.

Background: While hepatocellular carcinoma (HCC) represents a highly heterogeneous disease with variable oncogenesis mechanisms and biological features, little is understood about differences in distant metastasis (DM) and prognosis between early-onset and late-onset HCC. This study defined early-onset disease as cancer diagnosed at age younger than 50 years and aimed to present a comprehensive analysis to characterize these disparities based on age. Methods: Information of HCC patients was retrospectively collected from the SEER database and our hospital. Patient demographics, tumor characteristics, and survival were compared between the two groups. A 1:1 propensity score matching (PSM) was adopted to adjust confounding factors. Logistic and cox analysis were utilized to explore risk factors of DM and prognosis, respectively. Besides, the survival differences were assessed by the Kaplan-Meier curve and log-rank test. Results: In total, 19187 HCC patients obtained from the SEER database and 129 HCC patients obtained from our own center were enrolled. Among 19187 patients with HCC, 3376 were identified in the matched cohort, including 1688 early-onset patients and 1688 late-onset patients. Compared with late-onset HCC, early-onset HCC was more likely to occur in female (25.2% vs. 22.9%, P = 0.030), have large tumors (>10.0 cm, 24.1% vs. 14.6%, P = 0.000), harbor poorly differentiated/undifferentiated cancers (17.0% vs. 14.0%, P = 0.003), present advanced clinical stage (T3+T4, 33.7% vs. 28.5%; N1, 9.2% vs. 6.7%; P = 0.000), and develop DM (13.0% vs. 9.5%, P = 0.000). After adjustment for confounders by PSM, we discovered that early-onset HCC remained an independent risk factor for DM. However, combined with Kaplan-Meier curve and cox analysis, early-onset HCC was an independent favorable predictor of survival. We validated these data on an independent cohort from our hospital. Conclusion: In this population-based study, despite developing DM more frequently, early-onset HCC exhibited a superior prognosis than late-onset HCC. Nevertheless, further research is warranted to understand the underlying aetiologic basis for the disparities.

O-GlcNAcylation promotes the progression of nonalcoholic fatty liver disease by upregulating the expression and function of CD36.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) and its progressive variant, nonalcoholic steatohepatitis (NASH), constitute a burgeoning worldwide epidemic with no FDA-approved pharmacotherapies. The multifunctional immunometabolic receptor, fatty acid translocase CD36 (CD36), plays an important role in the progression of hepatic steatosis. O-GlcNAcylation is a crucial posttranslational modification that mediates the distribution and function of CD36, but its involvement in NAFLD remains poorly understood. METHODS: O-GlcNAcylation and CD36 expression were evaluated in human liver tissues obtained from NASH patients and normal control. Mice with hepatocyte-specific CD36 knockout were administered adeno-associated viral vectors expressing wild-type CD36 (WT-CD36) or CD36 O-GlcNAcylation site mutants (S468A&T470A-CD36) and were provided with a high-fat/high-cholesterol (HFHC) diet for 3 months. RT-qPCR analysis, immunoblotting, dual-luciferase reporter assays, chromatin immunoprecipitation, and coimmunoprecipitation were performed to explore the mechanisms by which O-GlcNAcylation regulates CD36 expression. Membrane protein extraction, immunofluorescence analysis, site-directed mutagenesis, and fatty acid uptake assays were conducted to elucidate the impact of O-GlcNAcylation on CD36 function. RESULTS: O-GlcNAcylation and CD36 expression were significantly increased in patients with NASH, mouse models of NASH, and palmitic acid-stimulated hepatocytes. Mechanistically, the increase in O-GlcNAcylation facilitated the transcription of CD36 via the NF-κB signalling pathway and stabilized the CD36 protein by inhibiting its ubiquitination, thereby promoting CD36 expression. On the other hand, O-GlcNAcylation facilitated the membrane localization of CD36, fatty acid uptake, and lipid accumulation. However, site-directed mutagenesis of residues S468 and T470 of CD36 reversed these effects. Furthermore, compared with their WT-CD36 counterparts, HFHC-fed S468A&T470A-CD36 mice exhibited decreases in systemic insulin resistance, steatosis severity, inflammation and fibrosis. Pharmacological inhibition of O-GlcNAcylation and CD36 also mitigated the progression of NASH. CONCLUSIONS: O-GlcNAcylation promotes the progression of NAFLD by upregulating CD36 expression and function. Inhibition of CD36 O-GlcNAcylation protects against NASH, highlighting a potentially effective therapeutic approach for individuals with NASH.

Taxonomic resurrection of Saxifraga lancangensis (Saxifragaceae).

BACKGROUND: Accurate species delimitation is fundamental for testing evolutionary theory and provides essential implications for conservation management. The arctic-alpine genus Saxifraga L. (Saxifragaceae) is taxonomically complex and many species have not been critically assessed. The taxonomic and phylogenetic status of Saxifraga lancangensis Y.Y.Qian, considered as a synonym of Saxifraga mengtzeana Engl. & Irmsch. in previous studies, is re-evaluated in light of new evidence presented here. RESULTS: Evidence from morphological comparison and sequencing of plastid genome indicate that S. lancangensis belongs to Saxifraga sect. Irregulares Haw., and is closely related to Saxifraga geifolia Balf.f., and S. mengtzeana. However, S. lancangensis can be diagnosed by its petals with red and clawless base, leaf blade orbicular and leaf margin shallowly dentate. CONCLUSIONS: The morphological and molecular evidence support the resurrection of S. lancangensis as a distinct species. An updated morphological description based on protologue and fresh material, diagnostic characters, and original photographs of the resurrected species are presented.

Platinum-Ruthenium Dual-Atomic Sites Dispersed in Nanoporous Ni0.85 Se Enabling Ampere-Level Current Density Hydrogen Production.

Alkaline anion-exchange-membrane water electrolyzers (AEMWEs) using earth-abundant catalysts is a promising approach for the generation of green H2 . However, the AEMWEs with alkaline electrolytes suffer from poor performance at high current density compared to proton exchange membrane electrolyzers. Here, atomically dispersed Pt-Ru dual sites co-embedded in nanoporous nickel selenides (np/Pt1 Ru1 -Ni0.85 Se) are developed by a rapid melt-quenching approach to achieve highly-efficient alkaline hydrogen evolution reaction. The np/Pt1 Ru1 -Ni0.85 Se catalyst shows ampere-level current density with a low overpotential (46 mV at 10 mA cm-2 and 225 mV at 1000 mA cm-2 ), low Tafel slope (32.4 mV dec-1 ), and excellent long-term durability, significantly outperforming the benchmark Pt/C catalyst and other advanced large-current catalysts. The remarkable HER performance of nanoporous Pt1 Ru1 -Ni0.85 Se is attributed to the strong intracrystal electronic metal-support interaction (IEMSI) between Pt-Se-Ru sites and Ni0.85 Se support which can greatly enlarge the charge redistribution density, reduce the energy barrier of water dissociation, and optimize the potential determining step. Furthermore, the assembled alkaline AEMWE with an ultralow Pt and Ru loading realizes an industrial-level current density of 1 A cm-2 at 1.84 volts with high durability.

Influence paradigms of soil moisture on land surface energy partitioning under different climatic conditions.

Soil moisture (SM) directly controls the land surface energy partition which plays an important role in the formation of extreme weather events. However, its dependence on specific climatic conditions is not thoroughly understood due to the complexity of soil moisture effects. Here, we examine the relationship between SM and surface energy partitioning under different climate conditions, and identify the influence paradigms of soil moisture on surface energy partition. We find that temperature changes can explicitly determine the impact paradigm of different physical processes, i.e. evapotranspiration, soil freezing and thawing, and such influence paradigms are also affected by atmospheric aridity (VPD). Globally, there are five paradigms that effects on surface energy partitioning, including the warm-wet paradigm (WW), transitional paradigm (TP), warm-dry paradigm (WD), cool-wet paradigm (CW) and cold paradigm (CP). Since 1981, the global area proportion for TP is observed to increase pronouncedly. We also find that the critical SM threshold exhibits regional variations and the global average is 0.45 m3/m3. The identified paradigms and their long-term change trends provide new insights into the global intensification of land-atmosphere interaction, which has important implications for global warming and the formation of heatwaves.

Red-Fluorescent Covalent Organic Framework Nanospheres for Trackable Anticancer Drug Delivery.

Covalent organic frameworks (COFs) have emerged as promising drug carriers due to their structural variability, inherent porosity, and customizable functions. However, most COFs used in drug delivery suffer from low cellular bioavailability and poor luminescence properties. In this study, we designed a series of size-tunable, crystalline, and red-fluorescent COF nanospheres (COFNSs) for trackable anticancer drug delivery. The semiconducting COFNSs were prepared by condensations of 1,3,5-triformylbenzene (TFB) with various dihydrazide blocks through the Schiff-base reaction, resulting in red emission at 647 nm and excellent fluorescence stability (∼100% for 1 h). Such fluorescence property allowed for systematic investigation of the cellular endocytosis pathway of COFNSs, visualization of drug delivery, and observation of the cell apoptosis process. The COFNSs exhibited high cell viability (>90%), a loading capacity of 183 wt % for the anticancer drug camptothecin (CPT), and significant enhancement in inhibiting 4T1 cancers both in vitro and in vivo as the CPT nanocarrier. This progress presents a valuable approach to design COF nanocarriers with integrated fluorescent and drug delivery functions.

Protective and Adverse Roles of DDX3X in Different Cell Types in Nonalcoholic Steatohepatitis Progression.

Persistent hepatic cellular metabolic stress and liver inflammatory stimuli are key signatures of nonalcoholic steatohepatitis (NASH). DDX3X is a vital molecule involved in cell fate decisions in both pro-survival stress granule (SG) and pro-death NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome assembly in response to stress signals. However, the role of DDX3X in NASH remains unclear. We characterized the cell type-specific roles of DDX3X in NASH. Human liver tissues from NASH patients and normal control subjects were collected to assess DDX3X expression and distribution. Nutritional steatohepatitis models were constructed by feeding macrophage-specific DDX3X knockout (DDX3XΔMφ), hepatocyte-specific DDX3X knockout (DDX3XΔhep), and wild-type control (DDX3Xfl/fl) mice a high-fat and high-cholesterol (HFHC) diet, a methionine- and choline-deficient (MCD) diet, and a high-fat/high-iron/high-fructose/high-cholesterol, low-methionine, and choline-deficient (HFHIHFHC-MCD) diet. The study demonstrated that DDX3X was predominantly expressed in macrophages and hepatocytes in control liver tissues, and its expression was down-regulated in patients or mice with NASH. Compared to DDX3Xfl/fl littermates, DDX3XΔMφ mice showed improved liver histology in nutritional steatohepatitis models. Loss of macrophage DDX3X inhibited NLRP3 inflammasome-mediated pyroptosis, causing anti-inflammatory M2 polarization and alleviating hepatocyte steatohepatitic changes. DDX3XΔhep mice developed marked steatohepatitis in multiple nutritional steatohepatitis models compared to DDX3Xfl/fl littermates. DDX3X-deleted hepatocytes showed impaired SG assembly, leading to increased sensitivity and intolerance to metabolic stimulation and resultant steatohepatitis. In conclusion, DDX3X plays opposite roles in different cell types during the progression of NASH. A better understanding of the cell-specific differences in the crosstalk between SG formation and NLRP3 activation is crucial for developing prospective targeted DDX3X inhibitors for the treatment of NASH.

Hepatocyte DDX3X protects against drug-induced acute liver injury via controlling stress granule formation and oxidative stress.

Drug-induced liver injury (DILI) is the leading cause of acute liver failure (ALF). Continuous and prolonged hepatic cellular oxidative stress and liver inflammatory stimuli are key signatures of DILI. DEAD-box helicase 3, X-linked (DDX3X) is a central regulator in pro-survival stress granule (SG) assembly in response to stress signals. However, the role of DDX3X in DILI remains unknown. Herein, we characterized the hepatocyte-specific role of DDX3X in DILI. Human liver tissues of DILI patients and control subjects were used to evaluate DDX3X expression. APAP, CCl4 and TAA models of DILI were established and compared between hepatocyte-specific DDX3X knockout (DDX3XΔhep) and wild-type control (DDX3Xfl/fl) mice. Hepatic expression of DDX3X was significantly decreased in the pathogenesis of DILI compared with controls in human and mice. Compared to DDX3Xfl/fl mice, DDX3XΔhep mice developed significant liver injury in multiple DILI models. DDX3X deficiency aggravates APAP induced oxidative stress and hepatocyte death by affecting the pro-survival stress granule (SG) assembly. Moreover, DDX3X deficiency induces inflammatory responses and causes pronounced macrophage infiltration. The use of targeted DDX3X drug maybe promising for the treatment of DILI in human.

TATA-box-binding protein promotes hepatocellular carcinoma metastasis through epithelial-mesenchymal transition.

BACKGROUND: HCC characterizes malignant metastasis with high incidence and recurrence. Thus, it is pivotal to discover the mechanisms of HCC metastasis. TATA-box-binding protein (TBP), a general transcriptional factor (TF), couples with activators and chromatin remodelers to sustain the transcriptional activity of target genes. Here, we investigate the key role of TBP in HCC metastasis. METHODS: TBP expression was measured by PCR, western blot, and immunohistochemistry. RNA-sequencing was performed to identify downstream proteins. Functional assays of TBP and downstream targets were identified in HCC cell lines and xenograft models. Luciferase reporter and chromatin immunoprecipitation assays were used to demonstrate the mechanism mediated by TBP. RESULTS: HCC patients showed high expression of TBP, which correlated with poor prognosis. Upregulation of TBP increased HCC metastasis in vivo and in vitro, and muscleblind-like-3 (MBNL3) was the effective factor of TBP, positively related to TBP expression. Mechanically, TBP transactivated and enhanced MBNL3 expression to stimulate exon inclusion of lncRNA-paxillin (PXN)-alternative splicing (AS1) and, thus, activated epithelial-mesenchymal transition for HCC progression through upregulation of PXN. CONCLUSIONS: Our data revealed that TBP upregulation is an HCC enhancer mechanism that increases PXN expression to drive epithelial-mesenchymal transition.

Association between interleukin-6 and lower urinary tract symptoms of benign prostatic hyperplasia / Relación entre la interleucina-6 y los síntomas urinarios de la hiperplasia prostática benigna

Objective: To evaluate the association between IL-6 in prostatic tissue/blood sample and BPH-LUTS, so as to preliminarily discover an indicator of inflammation that could show the severity of LUTS. Patients and methods: The prostatic tissues and blood samples were collected from 56 patients who underwent transurethral plasmakinetic resection of the prostate (TUPKRP). The association between IL-6 detected on prostatic tissues/blood sample and LUTS parameters, including international prostate symptom score (IPSS), peak flow rate (Qmax) and urodynamic parameters were analyzed with SPSS version 18.0, and p-value <0.05 was chosen as the criterion for statistical significance. Results: The TPSA and prostate volume (PV) were found to be higher in the inflammation group (p=0.021, 0.036). There was a positive association between prostate tissue inflammation and LUTS ([IPSS, storage symptoms score (SSS), voiding symptoms score (VSS), p<0.05], [Qmax, p=0.025], [obstruction, p=0.027] and [AUR, p=0.018]). The level of serum IL-6 was significantly higher in inflammatory group (p=0.008). However, no differences were observed in different degrees of inflammation (p=0.393). The level of IL-6 in prostatic tissue significantly increased with the degree of inflammation (p<0.001), and the intensity of IL-6 expression was statistically correlative with the degree of inflammation (p<0.001). The IL-6 expression in prostatic tissue was statistically relevant with IPSS (p=0.018) and SSS (p=0.012). Conclusion: IL-6 expression in prostatic tissue is associated with storage IPSS, suggesting chronic inflammation might contribute to storage LUTS. (AU)

Objetivo: Evaluar la relación entre il-6 y bph-lut en muestras de tejido prostático/sangre, con el fin de identificar indicadores de inflamación que reflejen la gravedad de los lut. Pacientes y métodos: Se recolectaron muestras de tejido prostático y sangre de 56 pacientes sometidos a una plasmatectomía transuretral prostática. Se aplicó la versión 18.0 de SPSS para analizar la correlación entre el il-6 de tejido prostático/muestra de sangre y los parámetros relacionados con los LUTS (puntuación internacional de síntomas prostáticos (IPSS), flujo máximo (Qmax), parámetros urodinámicos), con UN valor p<0,05 como criterio para una diferencia estadísticamente significativa. Resultados: Hubo diferencias estadísticamente significativas (p=0,021, 0,036) entre el grupo con inflamación y el grupo sin inflamación en TPSA y PV. La inflamación del tejido prostático se relacionó positivamente con LUTS ([IPSS, puntuación de síntomas de almacenamiento (SSS), puntuación de síntomas de micción (VSS), p<0,001), y la intensidad de la expresión de il-6 se correlacionó estadísticamente con el grado de inflamación (p<0,001). La expresión de il-6 en el tejido prostático fue estadísticamente significativa con IPSS (p=0,018) y SSS (p=0,012). Conclusiones: La expresión de il-6 en el tejido prostático está relacionada con el almacenamiento de IPSS, lo que sugiere que la inflamación crónica puede estar involucrada en el almacenamiento de LUTS. (AU)

Combined influence of soil moisture and atmospheric humidity on land surface temperature under different climatic background.

Soil moisture (SM) and atmospheric humidity (AH) are crucial climatic variables that significantly affect the climate system. However, the combined influencing mechanisms of SM and AH on the land surface temperature (LST) under global warming are still unclear. Here, we systematically analyzed the interrelationships among annual mean values of SM, AH, and LST using ERA5-Land reanalysis data and revealed the role of SM and AH on the spatiotemporal variations of LST through mechanism analysis and regression methods. The results showed that net radiation, SM, and AH could well model the long-term variability of LST well and explain 92% of the variability. Moreover, SM played an essential and different role under the different LST backgrounds. The AH always displayed a greenhouse effect on the LST. This study provides essential insights into the global climate change mechanism from the surface hydrothermal processes perspective.

The use of car safety seats for children in China: A questionnaire survey based on the theory of planned behavior.

OBJECTIVE: The purpose of this study was to analyze the psychological characteristics underlying Chinese parents' behaviors in using child car seats and to understand their decision-making processes. Based on the theory of planned behavior (TPB), three extended variables of perceived accident severity, perceived benefits, and perceived barriers were introduced. From the perspective of social psychology, the psychological factors that influence parents' use of child car seats and their interrelationships were explored. METHODS: A questionnaire was designed to collect data, including information on demographic characteristics, basic components of the TPB, and relevant extension variables. Using on online survey, 585 valid questionnaires were collected. Structural equation modeling was used to calibrate the data, and multiple group analysis was performed on the demographic variables. RESULTS: The extended TPB can effectively explain and predict parents' behaviors when using children's car seats. The results of the model show that parents' positive attitudes toward child safety seats (CSSs), others' recognition of their own use and perceptual control of the use of CSSs increase their willingness to use CSSs. Parents' willingness to use has a positive impact on the use of CSSs. Additionally, for the three extended variables introduced, perceived benefit significantly promoted parental intention and behavior to use CSS for children; perceived barriers significantly reduced parental use of CSS; and perceived accident severity had no significant effect on parental use of CSS. CONCLUSIONS: This study established the validity of the extended TPB model in predicting parents' behaviors in using car seats for their children. In addition, the current findings may provide a theoretical basis for policy development to promote CSS use.

Laparoscopic or open liver resection for intrahepatic cholangiocarcinoma: A meta-analysis and systematic review.

Background: Although laparoscopic hepatectomy has been widely used in the treatment of benign and malignant liver diseases, its applicability in intrahepatic cholangiocarcinoma (ICC) is controversial. We conducted a meta-analysis to compare the short-term and long-term outcomes of laparoscopic hepatectomy (Lap-ICC) and open hepatectomy (Open-ICC) in ICC patients. Methods: The PubMed, Web of science, Cochrane Library, China National Knowledge Infrastructure and other databases were searched for the relevant literature. The research data were extracted according to the inclusion and exclusion criteria. Results: Seventeen studies, including 3975 ICC patients, were selected for the meta-analysis. Compared to Open-ICC, Lap-ICC had lower rates of lymph node dissection (OR=0.44, P=0.01) and metastasis (OR=0.58, P=0.03), along with less intraoperative bleeding (MD=-128.43 ml, P<0.01) lower blood transfusion rate (OR=0.43, P<0.01), shorter hospital stay (MD=-2.75 day, P<0.01), higher R0 resection rate (OR=1.60, P<0.01), and lower tumor recurrence rate (OR=0.67, P=0.01). However, there was no difference between the two groups in terms of operation time, number of lymph node dissection, incision margin distance, overall complications rate, severe complications rate, and the 1-, 3- and 5-year DFS and OS rates. Conclusion: Laparoscopic hepatectomy is partially superior to open hepatectomy in terms of less bleeding, shorter hospital stay and higher R0 resection rate, while the long-term efficacy of the two approaches is similar.

Constructing the behavioral sequence of the takeover process-TOR, behavior characteristics and phases division: A real vehicle experiment.

Autonomous driving will still use human-machine co-driving to handle complex situations for a long term, which requires the driver to control the vehicle and avoid hazards by executing appropriate behavioral sequences after takeover prompts. Previous studies focused on the division of static behavioral indicators and major phases in the initial phase of takeover, while lacking the construction of behavioral sequences based on the dynamic changes of behavioral characteristics during the takeover process. This study divides the takeover process in a detailed manner and investigates the impact of audio types on the behavioral sequence at each phase. 20 professional drivers performed the NDRT in autonomous driving mode on real roads, and after receiving audio prompts, they took over the vehicle and performed hazard avoidance maneuvers. The results show that the behavioral characteristics could construct the behavioral sequence of different phases, with the dynamic characteristics of the takeover operation change. In addition, different types of audio prompts will affect the timing of the takeover operation and its driving performance. Choosing different audio prompts or combinations can help improve the effect of taking over the vehicle. This study helps to provide guidance on the design of human-machine interaction for behavior optimization at different phases, so that guiding the driver to take over the vehicle safely and effectively.

An exploration of gastric cancer with heterogeneous mismatch repair status.

Survival benefits or symptom alleviation from immune checkpoint blockade therapy can be seen in microsatellite instability-high (MSI-H) cases. However, genetic heterogeneity within a specific subgroup of MSI-H tumors may be associated with poor response and prognosis. We investigated the molecular changes and microsatellite status of the cases with heterogeneous MMR protein staining by polymerase chain reaction (PCR) and next-generation sequencing (NGS). Data from 3723 patients with gastric cancer were retrospectively analyzed to determine the mismatch repair (MMR) status by performing immunohistochemical staining of four major MMR proteins (MLH1, PMS2, MSH2, and MSH6). When heterogeneous MMR protein staining result was positive, PCR and NGS were performed. Heterogeneous MMR protein staining was observed in 12 cases. In microsatellite stable (MSS) cases, TP53 mutation appeared to accompany heterogeneous staining (HS) of MLH1. However, TP53 variation was not observed with MSI-H occurrence. Cases showing heterogeneous MSH6 protein staining revealed MSH6 mutations. Some cases with the same MMR protein staining set had varying MSI results. In one case whose primary and metastatic foci presented MLH1-HS and PMS2-HS, the microsatellite status was classified as MSS and MSI-H, respectively. Moreover, HS was also found in multiple biopsies and surgical specimens. This study found a preliminary relationship between heterogeneously stained MSH6 or MLH1 proteins and their gene mutations, as well as between MSI-H/TP53 - and MSS/TP53 + tumors. The microsatellite status of patients with heterogeneous MMR protein staining is unpredictable. Given the heterogeneity of mismatch repair, microsatellite status should be assessed for all specimens if sufficient specimens can be obtained.

Rapid Melt-Quenching Enables General Synthesis of High-Loading Single-Atom Catalysts with Bicontinuous Nanoporous Structure.

Single-atom catalysts have attracted extensive attention due to their unique atomic structures and extraordinary activities in catalyzing chemical reactions. However, the lack of general and efficient approaches for producing high-density single atoms on suitably tailored supporting matrixes hinders their industrial applications. Here, a rapid melt-quenching strategy with high throughput to synthesize single atoms with high metal-atom loadings of up to 9.7 wt% or 2.6 at% on nanoporous metal compounds is reported, representing several-fold improvements compared to benchmarks in the literature. Mechanism characterizations reveal that the high-temperature melting provides the essential liquid environment and activation energy to achieve the atomization of metals, while the following rapid-quenching pins the isolated metal atoms and stabilizes the coordination environment. In comparison with carbon-supported single-atom catalysts, various collaboration combinations of single atoms and nanoporous metal compounds can be synthesized using the strategy, thus achieving efficient hydrazine oxidation-assisted H2 production. This synthesis protocol is highly compatible with automatic operation, which provides a feasible and general route to design and manufacture specific single-atom catalysts with tunable atomic metal components and supporting matrixes, thus promoting the deployment of single-atom catalysts for various energy technology applications.

Association between interleukin-6 and lower urinary tract symptoms of benign prostatic hyperplasia.

OBJECTIVE: To evaluate the association between IL-6 in prostatic tissue/blood sample and BPH-LUTS, so as to preliminarily discover an indicator of inflammation that could show the severity of LUTS. PATIENTS AND METHODS: The prostatic tissues and blood samples were collected from 56 patients who underwent transurethral plasmakinetic resection of the prostate (TUPKRP). The association between IL-6 detected on prostatic tissues/blood sample and LUTS parameters, including international prostate symptom score (IPSS), peak flow rate (Qmax) and urodynamic parameters were analyzed with SPSS version 18.0, and p-value <0.05 was chosen as the criterion for statistical significance. RESULTS: The TPSA and prostate volume (PV) were found to be higher in the inflammation group (p=0.021, 0.036). There was a positive association between prostate tissue inflammation and LUTS ([IPSS, storage symptoms score (SSS), voiding symptoms score (VSS), p<0.05], [Qmax, p=0.025], [obstruction, p=0.027] and [AUR, p=0.018]). The level of serum IL-6 was significantly higher in inflammatory group (p=0.008). However, no differences were observed in different degrees of inflammation (p=0.393). The level of IL-6 in prostatic tissue significantly increased with the degree of inflammation (p<0.001), and the intensity of IL-6 expression was statistically correlative with the degree of inflammation (p<0.001). The IL-6 expression in prostatic tissue was statistically relevant with IPSS (p=0.018) and SSS (p=0.012). CONCLUSION: IL-6 expression in prostatic tissue is associated with storage IPSS, suggesting chronic inflammation might contribute to storage LUTS.

Design of size uniform and controllable covalent organic framework nanoparticles for high-performance anticancer drug delivery.

Covalent organic frameworks (COFs) receive much attention in biomedicine because of their unique adsorption, optical and biological properties, as well as highly variable structures. However, preparation of nanosized COFs with uniform and controllable size is still a challenge. Herein, we develop a facile interfacial method to prepare the COF nanoparticles (COFNPs) with the uniform size of 30-50 nm from p-benzoquinone (BQ) and 4-[1,2,2-tris(4-aminophenyl)ethenyl]aniline (TPEA) by Michael addition. The TPEA-BQ COFNPs show positive zeta potential and effectively load the hydrophobic anticancer drug camptothecin (CPT) with the capacity of up to 127wt%, and remarkably improved the CPT dispersibility in water due to the retention of quinone structure. In vitro assay reveals CPT@ TPEA-BQ significantly reduced cell viability to 29% after 24 h incubation, much lower than that of free CPT (51%) at the same concentration of 10 µg mL-1. Further in vivo experiment confirms the high anticancer drug delivery performance of the designed TPEA-BQ COFNPs. After 20 days of injection treatment, the CPT loaded in TPEA-BQ COFNPs inhibits the tumor growth by 60%, much higher than that of free CPT group (23%). This work demonstrates the feasibility to design advanced drug delivery systems based on highly structure-tunable COF system.

Analysis of risk factors for acute pancreatitis complicated with pancreatic sinistral portal hypertension and construction of predictive model.

Objective: Pancreatic sinistral portal hypertension (PSPH) is a common complication of acute pancreatitis (AP) and can cause massive gastrointestinal bleeding, which is one of the causes of AP-related mortality. However, there is currently no predictive model for AP concurrent with PSPH. This study aimed to identify the risk factors for AP concurrent with PSPH and use these factors to build a related predictive model. Materials and methods: We collected clinical data from 282 patients with AP. 192 patients were used as a training group and 90 patients as a validation group. Univariate and multivariate analyses were used to identify independent risk factors for AP complicated with PSPH, and then a nomogram was established. The models are cross verification and Internal verification. The predictive ability and accuracy of the model were evaluated based on the working curve of the subjects and the calibration curve, respectively. The clinical value of the model was evaluated using decision curve analysis (DCA). Results: The univariate analysis revealed significant differences in the occurrence of PSPH with respect to sex, recurrent AP, history of hypertension, smoking history, patency of the splenic vein, pancreatic necrosis or pancreatic pseudocyst formation, the most significant site of pancreatic swelling, presence of a Dmure D polymer, MCTSI, and involvement of lipase and amylase. The logistic multivariate regression analysis showed that male sex, splenic-vein stenosis or occlusion and swelling were located in the body-tail, and MCTSI was an independent risk factor for PSPH. The nomogram and ROC curve were constructed. The area under the working curve of the subjects was 0.91, and the sensitivity and specificity were 82.5% and 89.1%, respectively. In the validation group, the C-index is 0.826. The nomogram was internally validated using 1,000 bootstrap samples, and the c-index was 0.898. The calibration curve demonstrated that the predicted probability was concordant with the observed probability, and the DCA confirmed that the model had robust clinical utility. Conclusion: Male sex, splenic-vein stenosis or occlusion, recurrent AP, and swelling are located in the body-tail, and MCTSI is an independent risk factor for the occurrence of PSPH. The predictive model developed for AP complicated with PSPH may serve toward developing preventive and therapeutic approaches for PSPH.