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Standardized guidelines for optimal tunnel length in tunneled peripherally inserted central catheters (PICCs) are lacking. The objective of this study was to evaluate the real-world impact of tunnel length on clinical outcomes. This retrospective cohort study included 207 cancer patients who received tunneled PICCs, categorized into a control group (tunnel length > 4 cm, n = 134) and an observation group (tunnel length ≤ 4 cm, n = 73). Propensity score matching (PSM) was used to address baseline heterogeneity. Cox regression analyses were used to assess the risk of complication during a 120-day follow-up. Compared to the control group (tunnel length > 4 cm), the observation group (tunnel length ≤ 4 cm) had a significantly higher adjusted overall complication risk (HR = 2.92, 95% CI: 1.07-7.94, P = 0.036) and unplanned catheter removal rate (4.4% vs. 0.0%, P = 0.027), confirming the safety of longer tunnels despite comparable comfort levels between groups. After PSM, Cox regression analysis showed results consistent with those from the unmatched cohort. Subgroup analyses revealed a reduced risk of complications with longer tunnels in patients with BMI ≤ 25 kg/m² (HR = 0.29, 95% CI: 0.11-0.82), without hypertension (HR = 0.36, 95% CI: 0.13-1.00), without diabetes (HR = 0.38, 95% CI: 0.15-0.97), and with solid tumors (HR = 0.31, 95% CI: 0.11-0.85). The results show that tunnel lengths > 4 cm reduce overall complications and prolong catheter retention, supporting the implementation of standardized protocols while advocating for personalized adjustments based on BMI, comorbidities, and cancer type.

Background Previous genome-wide association studies (GWAS) have identified numerous risk genes for lacunar stroke, but it is challenging to decipher how they confer risk for the disease. We employed an integrative analytical pipeline to efficiently transform genetic associations to identify novel proteins for lacunar stroke. Methods We systematically integrated lacunar stroke genome-wide association study (GWAS) ( N =7338) with human brain proteomes ( N =376) to perform proteome-wide association studies (PWAS), Mendelian randomization (MR), and Bayesian colocalization. We also used an independent human brain proteomic dataset ( N =152) to annotate the new genes. Results We found that the protein abundance of seven genes ( ICA1L , CAND2 , ALDH2 , MADD , MRVI1 , CSPG4 , and PTPN11 ) in the brain was associated with lacunar stroke. These seven genes were mainly expressed on the surface of glutamatergic neurons, GABAergic neurons, and astrocytes. Three genes ( ICA1L , CAND2 , ALDH2 ) were causal in lacunar stroke ( P < 0.05/proteins identified for PWAS; posterior probability of hypothesis 4 ≥ 75 % for Bayesian colocalization), and they were linked with lacunar stroke in confirmatory PWAS and independent MR. We also found that ICA1L is related to lacunar stroke at the brain transcriptome level. Conclusions Our present proteomic findings have identified ICA1L , CAND2 , and ALDH2 as compelling genes that may give key hints for future functional research and possible therapeutic targets for lacunar stroke.

Recent studies reveal that glycerol monolaurate (GML) is regarded as an effective feed supplement in the production of broilers; however, the underlying mechanism remains unknown. The current study aimed to investigate how GML affected production performance and meat quality in yellow-feathered broilers. A total of 528 chicks were randomly assigned into four groups for a 56-day feeding trial. The control group received a basal diet, and the treated groups fed basal diet containing 300 (GML300), 450 (GML450), and 600 (GML600) mg/kg GML. Results revealed that dietary GML notably increased the average daily feed intake (p < 0.05) and body weight in broilers during 28–56 days of age and improved the duodenum and jejunum morphology. Dietary GML increased the total cholesterol in broilers (p < 0.05), but the hepatic, abdominal, and muscular fat deposition, as well as muscle fatty acids, were not affected. The flavor amino acids and total amino acids in muscle of GML300 and GML 450 groups were notably (p < 0.05) increased. GML supplementation selectively increased the colonization of an unclassified genus of Lachnospiraceae family and Bifidobacteriaceae, which were significantly (p < 0.05) correlated with the increase of muscle amino acids. Meanwhile, dietary GML notably increased short chain fatty acids content and the microbial DNA abundance of carbohydrate, amino acids and lipid metabolism pathway in cecum. These findings demonstrated that dietary GML improved performance, intestinal morphology, and muscle amino acids in broilers mainly by manipulating community, function and metabolites of gut microbiota.Key points• GML improves performance, muscle composition, and feed efficiency in broilers.• GML alters gut microbiota community, function, and microbial metabolites in broilers.• Improvements of broilers by GML closely associated with gut microbiota alteration.

Obesity and associated metabolic disorders are worldwide public health issues. The gut microbiota plays a key role in the pathophysiology of diet-induced obesity. Glycerol monolaurate (GML) is a widely consumed food emulsifier with antibacterial properties. Here, we explore the anti-obesity effect of GML (1,600 mg/kg of body weight) in high-fat diet (HFD)-fed mice. HFD-fed mice were treated with 1,600 mg/kg GML. Integrated microbiome, metabolome, and transcriptome analyses were used to systematically investigate the metabolic effects of GML, and antibiotic treatment was used to assess the effects of GML on the gut microbiota. Obesity and associated metabolic disorders are worldwide public health issues. The gut microbiota plays a key role in the pathophysiology of diet-induced obesity. Glycerol monolaurate (GML) is a widely consumed food emulsifier with antibacterial properties. Here, we explore the anti-obesity effect of GML (1,600 mg/kg of body weight) in high-fat diet (HFD)-fed mice. HFD-fed mice were treated with 1,600 mg/kg GML. Integrated microbiome, metabolome, and transcriptome analyses were used to systematically investigate the metabolic effects of GML, and antibiotic treatment was used to assess the effects of GML on the gut microbiota. Our data indicated that GML significantly reduced body weight and visceral fat deposition, improved hyperlipidemia and hepatic lipid metabolism, and ameliorated glucose homeostasis and inflammation in HFD-fed mice. Importantly, GML modulated HFD-induced gut microbiota dysbiosis and selectively increased the abundance of Bifidobacterium pseudolongum . Antibiotic treatment abolished all the GML-mediated metabolic improvements. A multiomics (microbiome, metabolome, and transcriptome) association study showed that GML significantly modulated glycerophospholipid metabolism, and the abundance of Bifidobacterium pseudolongum strongly correlated with the metabolites and genes that participated in glycerophospholipid metabolism. Our results indicated that GML may be provided for obesity prevention by targeting the gut microbiota and regulating glycerophospholipid metabolism.

The gut microbiota, which can be highly and dynamically affected by dietary components, is closely related to IBD pathogenesis. Here, we demonstrated that food-grade glycerol monolaurate (GML)-mediated enhancement of Bifidobacterium and fecal SCFAs could be responsible for the anticolitis effect. Inflammatory bowel disease (IBD) is a type of immune-mediated chronic and relapsing inflammatory gastrointestinal symptoms. IBD cannot be completely cured because of the complex pathogenesis. Glycerol monolaurate (GML), naturally found in breast milk and coconut oil, has excellent antimicrobial, anti-inflammatory, and immunoregulatory functions. Here, the protective effect of GML on dextran sodium sulfate (DSS)-induced mouse colitis and the underlying gut microbiota-dependent mechanism were assessed in C57BL/6 mice pretreated or cotreated with GML and in antibiotic-treated mice transplanted with GML-modulated microbiota. Results showed that GML pretreatment has an advantage over GML cotreatment in alleviating weight loss and reducing disease activity index (DAI), colonic histological scores, and proinflammatory responses. Moreover, the amounts of Lactobacillus and Bifidobacterium and fecal propionic acid and butyric acid were elevated only in mice pretreated with GML upon DSS induction. Of note, fecal microbiota transplantation (FMT) from GML-pretreated mice achieved faster and more significant remission of DSS-induced colitis, manifested as reduced DAI, longer colon, decreased histological scores, and enhanced colonic Foxp3 + regulatory T cells (Tregs) and ratio of serum anti-inflammatory/proinflammatory cytokines, as well as the reconstruction of microbial communities, including elevated Helicobacter ganmani and decreased pathogenic microbes. In conclusion, GML-mediated enhancement of Bifidobacterium and fecal short-chain fatty acids (SCFAs) could be responsible for the anticolitis effect. FMT assay confirmed that gut microbiota modulated by GML was more resistant to DSS-induced colitis via elevating beneficial H. ganmani and establishing Treg tolerant phenotype. Importantly, colitis remission induced by GML is associated with novel gut microbiota patterns, even though different microbial contexts were involved. IMPORTANCE The gut microbiota, which can be highly and dynamically affected by dietary components, is closely related to IBD pathogenesis. Here, we demonstrated that food-grade glycerol monolaurate (GML)-mediated enhancement of Bifidobacterium and fecal SCFAs could be responsible for the anticolitis effect. FMT assay confirmed that gut microbiota modulated by GML was more resistant to DSS-induced colitis via elevating beneficial H. ganmani and establishing Treg tolerant phenotype. Collectively, colitis remission induced by GML is associated with novel gut microbiota patterns, even though different microbial contexts were involved, which further provided a perspective to identify specific microbial members and those responsible for the anticolitis effect, such as Bifidobacterium and Helicobacter .

In order to solve the problems of low thermal conductivity and local heat accumulation of phase change materials (PCM) in battery heat dissipation applications, in this study, expanded graphite (EG) and olefin block copolymers (OBCs) were compounded by melt blending method using paraffin (PA) as the matrix, and flexible shaped composite phase change materials (FSPCM) with shape stability and high thermal conductivity were successfully prepared. The effects of EG doping on the latent heat properties and heat dissipation properties of PA/OBCs matrix materials were mainly explored. The results show that EG significantly improves the thermal conductivity of the material, but its enhancement effect changes nonlinearly with the increase of content, and the comprehensive performance of the composite is the best when the EG content is 2.5%. In addition, the introduction of copper foam can improve the temperature homogeneity of phase change materials, reducing the temperature difference between the upper and lower surfaces by 27.5%.

The mid-depth ocean circulation is critically linked to actual changes in the long-term global climate system. However, in the past few decades, predictions based on ocean circulation models highlight the lack of data, knowledge, and long-term implications in climate change assessment. Here, using 842,421 observations produced by Argo floats from 2001-2020, and Lagrangian simulations, we show that only 3.8% of the mid-depth oceans, including part of the equatorial Pacific Ocean and the Antarctic Circumpolar Current, can be regarded as accurately modelled, while other regions exhibit significant underestimations in mean current velocity. Knowledge of ocean circulation is generally more complete in the low-latitude oceans but is especially poor in high latitude regions. Accordingly, we propose improvements in forecasting, model representation of stochasticity, and enhancement of observations of ocean currents. The study demonstrates that knowledge and model representations of global circulation are substantially compromised by inaccuracies of significant magnitude and direction, with important implications for modelled predictions of currents, temperature, carbon dioxide sequestration, and sea-level rise trends. Analysis of big Argo data reveals that model representation of global ocean circulation near 1000-m depth is substantially compromised by inaccuracies. Only 3.8% of the mid-depth ocean circulation can be considered accurately modelled.

Ferroptosis is a newly discovered programmed cell death that plays a vital role in the occurrence and development of tumors. However, little is known about its prognostic value of ferroptosis-related genes (FRGs) in colorectal cancer (CRC). This study was to investigate the clinical significance of FRGs on overall survival (OS) of patients with CRC. The mRNA expression profiles and corresponding clinical data of CRC patients were downloaded from public databases. Least absolute shrinkage and selection operator (LASSO) Cox regression was applied to identify hub FRGs and establish a novel ferroptosis-related gene signature in predicting OS in training cohort, and assessed in the validation cohort. Then, the genomic-clinicopathologic nomogram integrating risk scores and clinicopathological features were established. Thirteen FRGs were identified to be most significantly related to the OS of CRC patients. Based on the LASSO Cox regression algorithm, we selected 10 genes from 13 FRGs to establish a prognostic risk signature. The log-rank test and Kaplan–Meier analysis confirmed the predictive value of the risk scores for OS in CRC patients. The time-dependent receiver operating characteristic (tdROC) of signature indicates the showed powerful prediction ability in both training cohort and validation cohort. Then, a genomic-clinicopathologic nomogram integrating age, stage, and risk scores was established and demonstrated high predictive accuracy and clinical value, which was validated through tdROC and calibration curves. The ferroptosis-related gene signature and genomic-clinicopathologic nomogram could be used to predict the prognosis of CRC patients and might also be potential therapeutic targets.

N6-methyladenosine (m6A) is enriched in 3′untranslated region (3′UTR) and near stop codon of mature polyadenylated mRNAs in mammalian systems and has regulatory roles in eukaryotic mRNA transcriptome switch. Significantly, the mechanism for this modification preference remains unknown, however. Herein we report a characterization of the full m6A methyltransferase complex in HeLa cells identifying METTL3/METTL14/WTAP/VIRMA/HAKAI/ZC3H13 as the key components, and we show that VIRMA mediates preferential mRNA methylation in 3′UTR and near stop codon. Biochemical studies reveal that VIRMA recruits the catalytic core components METTL3/METTL14/WTAP to guide region-selective methylations. Around 60% of VIRMA mRNA immunoprecipitation targets manifest strong m6A enrichment in 3′UTR. Depletions of VIRMA and METTL3 induce 3′UTR lengthening of several hundred mRNAs with over 50% targets in common. VIRMA associates with polyadenylation cleavage factors CPSF5 and CPSF6 in an RNA-dependent manner. Depletion of CPSF5 leads to significant shortening of 3′UTR of over 2800 mRNAs, 84% of which are modified with m6A and have increased m6A peak density in 3′UTR and near stop codon after CPSF5 knockdown. Together, our studies provide insights into m6A deposition specificity in 3′UTR and its correlation with alternative polyadenylation.

Side-blown smelting technology has been widely adopted in the copper smelting process. In this study, the stirring uniformity of molten bath and the smelting efficiency of the copper smelting process was improved by a computational fluid dynamics method. Simulation of the gas–slag–matte three-phase flow in the furnace was performed by the volume of a fraction multiphase model coupled to a realizable k–ε turbulence model. The flow field can be divided into five zones, high-speed injection, strong-loop, weak-loop, gas overflow and separation, and settlement zones. Three improved gas injection modes, including oblique, horizontal staggered, and vertical staggered, have been proposed to improve the flow field of the weak-loop zone in the center of the molten bath. Of these methods, the oblique injection mode showed the best improvement effect. The stirring intensity and the slag splashing amount were nearly twice and only one-quarter of the original condition, respectively.