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The purpose of our study was to evaluate the effect of surgery on the survival and prognosis of patients with multifocal intrahepatic cholangiocarcinoma (ICCA). Patients with multifocal ICCA were selected from the SEER (Surveillance, Epidemiology, and End Results) database between 2010 and 2016. Kaplan–Meier analyses and log-rank tests were used to evaluate the difference in survival between the surgery group and the non-surgery group. We applied the Cox proportional hazards regression model to identify prognostic factors of overall survival (OS) and cancer-specific survival (CSS). In total, 580 patients were enrolled in our study, including 151 patients who underwent surgery and 429 patients who did not. The median survival time of surgical patients was longer than non-surgical patients (OS: 25 months vs. 8 months, p < 0.001; CSS: 40 months vs. 25 months, p < 0.001). Similarly, the 5-year survival rate in the surgery group was significantly higher than those in the non-surgery group (5-year OS rate: 12.91% vs. 0%; p < 0.001; 5-year CSS rate:26.91% vs. 0%; p < 0.001). Multivariate Cox analysis showed that the OS (HR:0.299, 95% CI: 0.229–0.390, p < 0.001) and CSS (HR:0.305, 95% CI:0.222–0.419, p < 0.001) of patients undergoing surgical resection were significantly improved. Meanwhile, after propensity score matching (PSM) of the original data, we come to the same conclusion.

Phase-change material (PCM) can enhance the efficiency of photovoltaic (PV) modules by reducing their temperature and is widely studied for thermal management. However, their performance varies due to differences in local solar radiation and climate conditions. Previous studies have mainly focused on the thermal properties of PCM, but practical evaluation should consider specific local conditions. To investigate the thermal-management performance of PCMs in different zones and obtain optimal design parameters, this study investigated the temperature-control effect of PCMs on PV systems across different regions through experiments. The results revealed that the temperature-control performance of PCM was limited in cold regions. Furthermore, the study developed a PCM-PV model and employed response surface methodology along with an NSGA-II to analyze the temperature-control effectiveness of the PCM-PV system in nine regions of China. Pareto solutions were obtained for nine regions in China, balancing annual power generation and system costs. PCM effectiveness is limited in colder regions like Naqu, where it increases power generation by only 0.5%, while in other regions, it improves annual power generation by 1.4% to 3%, especially in areas with high temperatures and abundant solar resources. However, when considering life-cycle gains and initial investment, PCM technology may not always be economically efficient, highlighting the need for region-specific evaluations.

The synergistic effects of pyrolysis byproduct, biochar (BC) on heavy metal consolidation, and H 2 S removal during and after from microwave pyrolysis of municipal sludge were studied in this paper. The results showed that above 80% of heavy metals (Zn and Pb) were enriched in the biochar and the leaching toxicity of both heavy metals was lower than the national emission standards. The chemical specification analysis found the sum of acid-soluble/exchangeable fraction (F1) and reducible fraction (F2) for Pb and Zn metals decreased by 26 and 40%; however, the residual fraction (F4) increased 33 and 46%, which contributed to the good stabilization of heavy metals in biochar. Besides, biochar achieved high H 2 S removal efficiency of 78.4% compared with the commercial activated carbon (AC). Furthermore, the biochar prepared by microwave pyrolysis had excellent adsorption performance, which was attributed to its larger specific surface area of 476.87m 2 /g under nitrogen atmosphere at 650 o C compared with traditional pyrolysis. The mechanism analysis showed that microwave pyrolysis resulted in the high alkaline condition and formation of a large number of microparticles containing large metal elements on the biochar surface, which mainly contributed to the stabilization of heavy metals. The metal oxides adsorbed on the surface of biochar can catalyze the oxidation of H 2 S absorption, which will change the pH atmosphere of biochar reducing the leaching behavior of heavy metals. This study provided the good application potential of solid waste (biochar) for simultaneous heavy metal stabilization and H 2 S capture.

Background This study examined the relationship between maternal preeclampsia (PE) and gut microbiota colonization in preterm infants and analyzed the effects of prenatal Bifidobacterium supplementation. Methods This observational study included 45 preterm infants categorized according to their mothers’ exposure status during pregnancy. Group A (healthy controls, n  = 15) included infants born to healthy mothers who received no supplementation; Group B (PE+Bifidobacterium, n  = 15) included infants whose mothers had PE and received Bifidobacterium supplementation as part of routine clinical management; and Group C (PE only, n  = 15) included infants born to mothers with PE who did not receive Bifidobacterium supplementation. All enrolled infants were followed from birth for subsequent analyses. The initial postnatal fecal samples of the infants were collected and analyzed using 16S rRNA gene sequencing. Microbial diversity within the intestinal microbiota was evaluated using alpha diversity (within-sample) and beta diversity (between-sample) analyses. To identify taxon-specific differences among groups, we performed linear discriminant analysis effect size and differential abundance analysis, with statistical significance set at p  < 0.05. The functional potential of the gut microbiota was inferred based on Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways via the PICRUSt2 algorithm. Results Alpha diversity analysis revealed significantly greater microbial diversity in the fecal microbiota of preterm infants born to healthy mothers (Group A) than in those delivered by mothers with PE, regardless of prenatal Bifidobacterium exposure. Taxonomic profiling revealed distinct microbial community structures across groups: Group A exhibited significant enrichment of Bacteroides at all taxonomic levels, along with an elevated abundance of Clostridium at the class and order levels. Group B showed a markedly greater relative abundance of Actinobacteria at the phylum level and Rothia at the genus level, whereas Group C was dominated by Proteobacteria (phylum level) and Streptococcus (genus level). All intergroup differences were statistically significant following Benjamini‒Hochberg correction (q < 0.05). A functional analysis of the gut microbiota revealed 53 KEGG pathways with significant overall group differences ( p  < 0.05), among which 23 pathways were significantly different in at least two groups (q < 0.05). Notably, the activity of the LPS biosynthesis pathway was significantly upregulated in Group C compared with Group A (q = 0.001). Although LPS biosynthesis activity was reduced in Group B relative to Group C (q = 0.018), it remained elevated compared to Group A (q = 0.001), suggesting incomplete mitigation of endotoxin risk. Additionally, glycolytic activity was significantly impaired in Group C relative to Group A (q = 0.003) but was partially restored in Group B compared to Group C (q = 0.022). Conclusions Maternal PE impaired early-life gut microbiota establishment in preterm infants, manifesting in reduced microbial diversity, enrichment of pathogenic Proteobacteria and Streptococcus, and consequent functional dysbiosis characterized by elevated endotoxin biosynthesis potential and compromised energy metabolism. Although prenatal supplementation with Bifidobacterium partially restored the microbial compositional balance, promoting beneficial bacteria, reducing LPS synthesis activity, and partially improving glycolytic function, it failed to fully reverse endotoxin-related risks, indicating the need to develop more effective microbiota-targeted strategies to comprehensively optimize metabolic and immune homeostasis.

Background Premature infants are more prone to brain injuries owing to incomplete nervous system development and poor adaptation outside the mother’s body. Without timely intervention, premature infants with brain injuries often develop intellectual disabilities, causing significant burdens on families and the society. Multiple studies have shown that gut dysbiosis can affect the nervous system, and vice versa. This study aimed to explore the changes in gut microbiota of typical premature infants and those with brain injuries on the third and seventh days after birth using 16 S rRNA technology. Methods Fecal samples from typical premature infants (non-brain injury group, n  = 17) and those with brain injuries (brain injury group, n  = 21) were collected on days 1, 3, and 7 after birth for 16 S rRNA sequencing. Alpha diversity analysis was used to evaluate the diversity of gut microbiome. LEfSe and DESeq2 were used to analyze of the microorganisms’ characteristics and differentiate the microorganisms between the two groups. Results At the phylum level, Firmicutes, Proteobacteria, and Actinobacteria were the dominant flora in both groups. At the genus level, the proportion of Enterococcus in fecal samples of the brain injury group was higher than that of the non-brain injury group on day three after birth; however, the opposite was observed on day seven. Rothia and Lactobacillales were characteristic bacteria of the non-brain injury group on days three and seven after birth, whereas Enterococcus and Bifidobacteria were characteristic bacteria of the brain injury group on days three and seven after birth, respectively. Three days after birth, the Shannon and Simpson indices of the non-brain injury group were significantly higher than those of the brain injury group. Conclusion Premature infants with brain injuries have a unique gut microbiota that is different from that of typical premature infants, indicating correlation between brain injuries and gut microbiota.

Determining the mechanism of gene function is greatly enhanced using conditional mutagenesis. However, generating engineered conditional alleles is inefficient and has only been widely used in mice. Importantly, multiplex conditional mutagenesis requires extensive breeding. Here we demonstrate a system for one-generation multiplex conditional mutagenesis in zebrafish (Danio rerio) using transgenic expression of both cas9 and multiple single guide RNAs (sgRNAs). We describe five distinct zebrafish U6 promoters for sgRNA expression and demonstrate efficient multiplex biallelic inactivation of tyrosinase and insulin receptor a and b, resulting in defects in pigmentation and glucose homeostasis. Furthermore, we demonstrate temporal and tissue-specific mutagenesis using transgenic expression of Cas9. Heat-shock-inducible expression of cas9 allows temporal control of tyr mutagenesis. Liver-specific expression of cas9 disrupts insulin receptor a and b, causing fasting hypoglycemia and postprandial hyperglycemia. We also show that delivery of sgRNAs targeting ascl1a into the eye leads to impaired damage-induced photoreceptor regeneration. Our findings suggest that CRISPR/Cas9-based conditional mutagenesis in zebrafish is not only feasible but rapid and straightforward.

Background Gestational diabetes mellitus has a long-term effect on pregnant women. Walnut ( Juglans regia L.) oil-derived polyunsaturated fatty acid (PUFA) possesses multifarious pharmacological activities. This study investigated the beneficial effects of walnut oil-derived PUFA on glucose metabolism, pregnancy outcomes, oxidative stress, and lipid metabolism in gestational diabetes mellitus. Methods The GDM rat model was generated by intraperitoneal injection of streptozotocin (40 mg/kg) on gestational day (GD) 6, GD7 and GD8. The differences between groups were estimated using one-way ANOVA followed by the Tukey’s multiple comparison test for post-hoc analysis. Results The results indicated that PUFA could mitigate GDM in pregnant diabetic rats, as embodied by the decrease of fasting blood glucose and the increase of plasma insulin and hepatic glycogen levels. Also, PUFA could suppress oxidative stress in pregnant diabetic rats, as reflected by the decrease of malondialdehyde content, an increase of superoxide dismutase, catalase and gutathione peroxidase activities. PUFA could also mitigate the abnormal changes of lipid profiles in plasma and hepatic tissue. Moreover, the relative mRNA expression of sterol regulatory element-binding transcription factor-1, stearoyl-CoA desaturase-1, fatty acid synthase, and acetyl-coenzyme A carboxylase, was suppressed by PUFA in pregnant diabetic rats. Conclusions These results suggested that PUFA supplementation during pregnancy is beneficial in preventing diabetic complications in pregnant rats.

Background and aimsWith the development of endoscopic technology, endoscopic treatment has been widely used in Gastrointestinal stromal tumors (GISTs). However, population-based studies comparing the long-term results of patients who received endoscopic treatment vs. Surgery are lacking. We used the Surveillance, Epidemiology, and End Results (SEER) database to analyze the long-term survival of colorectal or gastric GISTs who underwent primary tumor resection (endoscopic therapy or surgery) in the USA.MethodsPatients with colorectal or gastric GISTs were selected from the SEER database between 2010 and 2015. Kaplan–Meier analyses and log-rank tests were used to evaluate the difference in the long-term survival between the endoscopic therapy group and the surgery group. We examined the association between different treatments and survival after using the multivariate cox proportional hazards model to adjust the relevant covariates. Besides, we used Propensity score matching (PSM) to overcome the different distributions of covariates between the two groups and then further compare the survival difference.ResultsIn total, 2355 patients were enrolled in our study, of which 1999 (84.9%) received surgical treatment and 356 (15.1%) received endoscopic treatment. There was no significant difference in overall survival (OS) between the two groups before PSM. The median OS (73.5 months vs. 72.2 months) and 5-year OS rate (85.7% vs. 81.5%) of endoscopic therapy were similar to surgical patients (P = 0.34). The median Cancer-specific survival (CSS) and 5-year CSS rate in the endoscopic treatment group were higher than the surgical group before PSM, with 81.3 months, 97.1% versus 78.8 months, 92.7% (P = 0.011). After adjusting for other clinical factors and PSM, the long-term OS and CSS did not significantly differ between those treated surgically and treated endoscopically.ConclusionBased on the American population, we preliminarily found that the long-term OS and CSS did not differ between patients undergoing endoscopic therapy and surgery.

BackgroundWith the rapid advances in endoscopic technology, endoscopic therapy (ET) is increasingly applied to the treatment of small (≤ 20 mm) colorectal neuroendocrine tumors (NETs). However, long-term data comparing ET and surgery for management of T1N0M0 colorectal NETs are lacking. The purpose of this work was to compare overall survival (OS) and cancer-specific survival (CSS) of such patients with ET or surgery.MethodsPatients with T1N0M0 colorectal NETs were identified within the Surveillance Epidemiology and End Results (SEER) database (2004–2016). Demographics, tumor characteristics, therapeutic methods, and survival were compared. Propensity score matching (PSM) was used 1:3 and among this cohort, Cox proportional hazards regression models were performed to evaluate correlation between treatment and outcomes.ResultsOf 4487 patients with T1N0M0 colorectal NETs, 1125 were identified in the matched cohort, among whom 819 (72.8%) underwent ET and 306 (27.2%) underwent surgery. There was no difference in the 5-year and 10-year OS and CSS rates between the 2 treatment modalities. Likewise, analyses stratified by tumor size and site showed that patients did not benefit more from surgery compared with ET. Moreover, multivariate analyses found no significant differences in OS [Hazard Ratio (HR) = 0.857, 95% Confidence Interval (CI): 0.513–1.431, P = 0.555] and CSS (HR = 0.925, 95% CI: 0.282–3.040, P = 0.898) between the 2 groups. Similar results were observed when comparisons were limited to patients with different tumor size and site.ConclusionsIn this population-based study, patients with lesions < 10 mm treated endoscopically had comparable long-term survival compared with those treated surgically, which demonstrates ET as an alternative to surgery in T1N0M0 colorectal NETs of < 10 mm. Further high-quality prospective studies are warranted to comprehensively evaluate the role of ET in patients with tumors 10 to 20 mm.

Water kefir grains are complex probiotic granules that can efficiently ferment fruit and vegetable juices and significantly improve product flavor. However, the mechanisms of flavor formation remain unclear, which limits the process optimization of this technology. This study investigated the mechanisms involved in flavor formation during the fermentation of strawberry juice with water kefir grains. The results showed that as fermentation progressed, the total acidity increased, whereas the pH value and soluble solids content decreased. Additionally, the contents of citric acid and malic acid gradually decreased with fermentation, while the contents of lactic, acetic, and succinic acid increased, and three soluble sugars showed reduced levels. A total of 218 volatile compounds were identified. Eight dominant bacterial genera and one dominant yeast species were detected. Significant correlations between some key microorganisms and flavor compounds were observed. Specifically, Lactiplantibacillus was positively correlated with hexyl acetate. Meanwhile, Gluconobacter and Acetobacter were positively correlated with methyl (Z,Z)-9,12-octadecadienoate, isoamyl acetate, etc. In contrast, LAB such as Lacticaseibacillus and Schleiferilactobacillus showed the opposite correlations with these key flavor compounds. Saccharomyces showed a positive correlation with ethyl palmitate, ethyl propionate, phenylsuccinic acid, and 1-pentanol. The main flavor compound metabolic pathways were predicted and they were significantly related with yeasts, acetic acid bacteria, and lactic acid bacteria. Overall, this study offers a theoretical basis for the directional regulation and optimization of the flavor quality of strawberry juice fermented with water kefir.