Ultrathin zigzag-surface copper nanowire assembled hierarchical microspheres to enhance oxygen reduction catalysis.

Ultrathin catalysts predominantly expose surface active atoms to deliver promising applications in oxygen reduction reactions (ORRs). However, they are commonly synthesized at high reaction temperatures, with tedious chemical routes involved. Herein, we report a low temperature (273 K) electric field driven route to synthesize zigzag-surface ultrathin copper nanowires. Interestingly, the ultrathin copper nanowires assemble into three-dimensional microspheres, which exhibit hydrophobic-aerophilic features, eventually resulting in good ORR activities. The aerophilicity and hydrophobicity of copper nanowires are related to their Cu2O active sites and hierarchical protuberances, respectively. Our findings open a new door to grow ultrathin catalysts for new energy storage systems.

Pyridine-borane complex-catalysed thioesterification: the direct conversion of carboxylic acids to thioesters.

Thioesters are a common class of biologically active fragments and synthetically useful building blocks. An attractive synthetic approach would be to use simple and bench-stable carboxylic acids as a coupling partner. Herein, we present a 4-bromo pyridine-borane complex as a catalyst for the direct coupling of carboxylic acids with thiols. A wide range of thioesters with good functional group compatibility could be prepared via this metal-free approach. The merit of this strategy is exemplified by the modification of carboxylic acid-containing drugs.

Natural products in atherosclerosis therapy by targeting PPARs: a review focusing on lipid metabolism and inflammation.

Inflammation and dyslipidemia are critical inducing factors of atherosclerosis. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors and control the expression of multiple genes that are involved in lipid metabolism and inflammatory responses. However, synthesized PPAR agonists exhibit contrary therapeutic effects and various side effects in atherosclerosis therapy. Natural products are structural diversity and have a good safety. Recent studies find that natural herbs and compounds exhibit attractive therapeutic effects on atherosclerosis by alleviating hyperlipidemia and inflammation through modulation of PPARs. Importantly, the preparation of natural products generally causes significantly lower environmental pollution compared to that of synthesized chemical compounds. Therefore, it is interesting to discover novel PPAR modulator and develop alternative strategies for atherosclerosis therapy based on natural herbs and compounds. This article reviews recent findings, mainly from the year of 2020 to present, about the roles of natural herbs and compounds in regulation of PPARs and their therapeutic effects on atherosclerosis. This article provides alternative strategies and theoretical basis for atherosclerosis therapy using natural herbs and compounds by targeting PPARs, and offers valuable information for researchers that are interested in developing novel PPAR modulators.

Enhancing Multi-Spectral Fingerprint Sensing for Trace Explosive Molecules with All-Silicon Metasurfaces.

Spectroscopy is a powerful tool to identify the specific fingerprints of analytes in a label-free way. However, conventional sensing methods face unavoidable barriers in analyzing trace-amount target molecules due to the difficulties of enhancing the broadband molecular absorption. Here, we propose a sensing scheme to achieve strong fingerprint absorption based on the angular-scanning strategy on an all-silicon metasurface. By integrating the mid-infrared and terahertz sensing units into a single metasurface, the sensor can efficiently identify 2,4-DNT with high sensitivity. The results reveal that the fingerprint peak in the enhanced fingerprint spectrum is formed by the linked envelope. It exhibits a significant enhancement factor exceeding 64-fold in the terahertz region and more than 55-fold in the mid-infrared region. Particularly, the corresponding identification limit of 2,4-DNT is 1.32 µg cm-2, respectively. Our study will provide a novel research idea in identifying trace-amount explosives and advance practical applications of absorption spectroscopy enhancement identification in civil and military security industries.

Synaptotagmins family affect glucose transport in retinal pigment epithelial cells through their ubiquitination-mediated degradation and glucose transporter-1 regulation.

BACKGROUND: Synaptotagmins (SYTs) are a family of 17 membrane transporters that function as calcium ion sensors during the release of Ca2+-dependent neurotransmitters and hormones. However, few studies have reported whether members of the SYT family play a role in glucose uptake in diabetic retinopathy (DR) through Ca2+/glucose transporter-1 (GLUT1) and the possible regulatory mechanism of SYTs. AIM: To elucidate the role of the SYT family in the regulation of glucose transport in retinal pigment epithelial cells and explore its potential as a therapeutic target for the clinical management of DR. METHODS: DR was induced by streptozotocin in C57BL/6J mice and by high glucose medium in human retinal pigment epithelial cells (ARPE-19). Bioinformatics analysis, reverse transcriptase-polymerase chain reaction, Western blot, flow cytometry, ELISA, HE staining, and TUNEL staining were used for analysis. RESULTS: Six differentially expressed proteins (SYT2, SYT3, SYT4, SYT7, SYT11, and SYT13) were found between the DR and control groups, and SYT4 was highly expressed. Hyperglycemia induces SYT4 overexpression, manipulates Ca2+ influx to induce GLUT1 fusion with the plasma membrane, promotes abnormal expression of the glucose transporter GLUT1 and excessive glucose uptake, induces ARPE-19 cell apoptosis, and promotes DR progression. Parkin deficiency inhibits the proteasomal degradation of SYT4 in DR, resulting in SYT4 accumulation and enhanced GLUT1 fusion with the plasma membrane, and these effects were blocked by oe-Parkin treatment. Moreover, dysregulation of the myelin transcription factor 1 (Myt1)-induced transcription of SYT4 in DR further activated the SYT4-mediated stimulus-secretion coupling process, and this process was inhibited in the oe-MYT1-treated group. CONCLUSION: Our study reveals the key role of SYT4 in regulating glucose transport in retinal pigment epithelial cells during the pathogenesis of DR and the underlying mechanism and suggests potential therapeutic targets for clinical DR.

Efficacy and safety of novel multifunctional M10 CAR-T cells in HIV-1-infected patients: a phase I, multicenter, single-arm, open-label study.

Chimeric antigen receptor T (CAR-T) cells have been proposed for HIV-1 treatment but have not yet demonstrated desirable therapeutic efficacy. Here, we report newly developed anti-HIV-1 CAR-T cells armed with endogenic broadly neutralizing antibodies (bNAbs) and the follicle-homing receptor CXCR5, termed M10 cells. M10 cells were designed to exercise three-fold biological functions, including broad cytotoxic effects on HIV-infected cells, neutralization of cell-free viruses produced after latency reversal, and B-cell follicle homing. After demonstrating the three-fold biological activities, M10 cells were administered to treat 18 HIV-1 patients via a regimen of two allogenic M10 cell infusions with an interval of 30 days, with each M10 cell infusion followed by two chidamide stimulations for HIV-1 reservoir activation. Consequently, 74.3% of M10 cell infusions resulted in significant suppression of viral rebound, with viral loads declining by an average of 67.1%, and 10 patients showed persistently reduced cell-associated HIV-1 RNA levels (average decrease of 1.15 log10) over the 150-day observation period. M10 cells were also found to impose selective pressure on the latent viral reservoir. No significant treatment-related adverse effects were observed. Overall, our study supported the potential of M10 CAR-T cells as a novel, safe, and effective therapeutic option for the functional cure of HIV-1/AIDS.

Signal enhancement ratio of multi-phase contrast-enhanced MRI: an imaging biomarker for survival in pancreatic adenocarcinoma.

OBJECTIVES: To evaluate signal enhancement ratio (SER) for tissue characterization and prognosis stratification in pancreatic adenocarcinoma (PDAC), with quantitative histopathological analysis (QHA) as the reference standard. METHODS: This retrospective study included 277 PDAC patients who underwent multi-phase contrast-enhanced (CE) MRI and whole-slide imaging (WSI) from three centers (2015-2021). SER is defined as (SIlt - SIpre)/(SIea - SIpre), where SIpre, SIea, and SIlt represent the signal intensity of the tumor in pre-contrast, early-, and late post-contrast images, respectively. Deep-learning algorithms were implemented to quantify the stroma, epithelium, and lumen of PDAC on WSIs. Correlation, regression, and Bland-Altman analyses were utilized to investigate the associations between SER and QHA. The prognostic significance of SER on overall survival (OS) was evaluated using Cox regression analysis and Kaplan-Meier curves. RESULTS: The internal dataset comprised 159 patients, which was further divided into training, validation, and internal test datasets (n = 60, 41, and 58, respectively). Sixty-five and 53 patients were included in two external test datasets. Excluding lumen, SER demonstrated significant correlations with stroma (r = 0.29-0.74, all p < 0.001) and epithelium (r = -0.23 to -0.71, all p < 0.001) across a wide post-injection time window (range, 25-300 s). Bland-Altman analysis revealed a small bias between SER and QHA for quantifying stroma/epithelium in individual training, validation (all within ± 2%), and three test datasets (all within ± 4%). Moreover, SER-predicted low stromal proportion was independently associated with worse OS (HR = 1.84 (1.17-2.91), p = 0.009) in training and validation datasets, which remained significant across three combined test datasets (HR = 1.73 (1.25-2.41), p = 0.001). CONCLUSION: SER of multi-phase CE-MRI allows for tissue characterization and prognosis stratification in PDAC. CLINICAL RELEVANCE STATEMENT: The signal enhancement ratio of multi-phase CE-MRI can serve as a novel imaging biomarker for characterizing tissue composition and holds the potential for improving patient stratification and therapy in PDAC. KEY POINTS: Imaging biomarkers are needed to better characterize tumor tissue in pancreatic adenocarcinoma. Signal enhancement ratio (SER)-predicted stromal/epithelial proportion showed good agreement with histopathology measurements across three distinct centers. Signal enhancement ratio (SER)-predicted stromal proportion was demonstrated to be an independent prognostic factor for OS in PDAC.

Effort-reward imbalance and sleep quality in railway locomotive stewards: a cross-sectional study.

OBJECTIVE: To assess the correlation between the effort-reward imbalance (ERI) and sleep quality among railway locomotive stewards. DESIGN: Cross-sectional study. SETTING: Lanzhou Bureau Group, China Railway, between July and August 2022. PARTICIPANTS: Railway locomotive stewards. PRIMARY AND SECONDARY OUTCOME MEASURES: Sleep quality was assessed using the Pittsburgh Sleep Quality Index Scale (PSQI), categorising scores of >14 as poor, 8-14 as fair and <8 as good. RESULTS: A total of 5738 valid questionnaires (mean age of 30.85±6.91 years and 5730 males) were included. The response rate was 92.27%. The PSQI score was 11.52±3.95; 2304 (40.15%) respondents had good sleep quality, 1590 (27.71%) had fair sleep quality and 1844 (32.14%) had poor sleep quality. Stepwise multivariable logistic regression analysis showed that, compared with poor sleep quality, Jiayuguan Locomotive Depot workers (OR 0.775, 95% CI 0.587 to 0.971, p=0.028), electric locomotive drivers (OR 0.499, 95% CI 0.316 to 0.786, p=0.003), passenger train locomotive drivers (OR 0.209, 95% CI 1.313 to 3.337, p=0.002), working <40 hours weekly (OR 2.291, 95% CI 1.686 to 3.112, p<0.001), working 40-50 hours weekly (OR 1.602, 95% CI 1.299 to 1.977, p<0.001), senior titles (OR 0.727, 95% CI 0.570 to 0.928, p=0.010), high effort/low reward (OR 2.812, 95% CI 2.218 to 3.564, p<0.001) and low overcommitment (OR 5.848, 95% CI 4.710 to 7.261, p<0.001) were independently associated with fair sleep quality. Electric locomotive drivers (OR 0.535, 95% CI 0.364 to 0.787, p=0.001), diesel locomotive drivers (OR 0.567, 95% CI 0.348 to 0.924, p=0.023), passenger train locomotive drivers (OR 1.471, 95% CI 1.005 to 2.155, p=0.047), working <40 hours weekly (OR 1.549, 95% CI 1.196 to 2.006, p=0.001), working 40-50 hours weekly (OR 1.340, 95% CI 1.141 to 1.574, p<0.001), high school diploma or less (OR 1.448, 95% CI 1.062 to 1.975, p=0.019), high effort/low reward (OR 1.237, 95% CI 1.006 to 1.521, p=0.044), balanced effort-reward (OR 0.653, 95% CI 0.478 to 0.892, p=0.007) and low overcommitment (OR 2.553, 95% CI 2.224 to 2.931, p<0.001) were independently associated with good sleep quality. CONCLUSION: The results revealed an acceptable ERI and poor sleep quality among railway stewards. ERI was correlated with sleep quality. Health education, lifestyle changes and improved work schedules may help boost sleep quality and well-being among railway locomotive stewards.

DNA methylation markers in esophageal cancer.

Background: Esophageal cancer (EC) is a prevalent malignancy characterized by a low 5-year survival rate, primarily attributed to delayed diagnosis and limited therapeutic options. Currently, early detection of EC heavily relies on endoscopy and pathological examination, which pose challenges due to their invasiveness and high costs, leading to low patient compliance. The detection of DNA methylation offers a non-endoscopic, cost-effective, and secure approach that holds promising prospects for early EC detection. Methods: To identify improved methylation markers for early EC detection, we conducted a comprehensive review of relevant literature, summarized the performance of DNA methylation markers based on different input samples and analytical methods in EC early detection and screening. Findings: This review reveals that blood cell free DNA methylation-based method is an effective non-invasive method for early detection of EC, although there is still a need to improve its sensitivity and specificity. Another highly sensitive and specific non-endoscopic approach for early detection of EC is the esophageal exfoliated cells based-DNA methylation analysis. However, while there are substantial studies in esophageal adenocarcinoma, further more validation is required in esophageal squamous cell carcinoma. Conclusion: In conclusion, DNA methylation detection holds significant potential as an early detection and screening technology for EC.

The salt sensitivity of Drd4-null mice is associated with the upregulations of sodium transporters in kidneys.

To explore the mechanism of the hypertension in dopamine receptor-4 (Drd4) null mice, we determined the salt sensitivity and renal sodium transport proteins in Drd4-/- and Drd4+/+ mice with varied salt diets. On normal NaCl diet (NS), mean arterial pressures (MAP, telemetry) were higher in Drd4-/- than Drd4+/+; Low NaCl diet (LS) tended to decrease MAP in both strains; high NaCl diet (HS) elevated MAP with sodium excretion decreased and pressure-natriuresis curve shifted to right in Drd4-/- relative to Drd4+/+ mice. Drd4-/- mice exhibited increased renal sodium-hydrogen exchanger 3 (NHE3), sodium-potassium-2-chloride cotransporter (NKCC2), sodium-chloride cotransporter (NCC), and outer medullary α-epithelial sodium channel (αENaC) on NS, decreased NKCC2, NCC, αENaC, and αNa+-K+-ATPase on LS, and increased αENaC on HS. NKCC2, NCC, αENaC, and αNa+-K+-ATPase in plasma membrane were greater in Drd4-/- than in Drd4+/+ mice with HS. D4R was expressed in proximal and distal convoluted tubules, thick ascending limbs, and outer medullary collecting ducts and colocalized with NKCC2 and NCC. The phosphorylation of NKCC2 was enhanced but ubiquitination was reduced in the KO mice. There were no differences between the mouse strains in serum aldosterone concentrations and urinary dopamine excretions despite their changes with diets. The mRNA expressions of renal NHE3, NKCC2, NCC, and αENaC on NS were not altered in Drd4-/- mice. Thus, increased protein expressions of NHE3, NKCC2, NCC and αENaC are associated with hypertension in Drd4-/- mice; increased plasma membrane protein expression of NKCC2, NCC, αENaC, and αNa+-K+-ATPase may mediate the salt sensitivity of Drd4-/- mice.

Down-regulation of KLRB1 is associated with increased cell growth, metastasis, poor prognosis, as well as a dysfunctional immune microenvironment in LUAD.

Killer cell lectin-like receptor B1 (KLRB1) is implicated in cancer progression and immunity. In this study, we aimed to evaluate the expression levels of KLRB1 in lung adenocarcinoma (LUAD) and analyze the relationship between KLRB1 expression levels, LUAD progression, and the tumor immune microenvironment. KLRB1 levels in LUAD were analyzed using data from the TCGA and XENA databases. Additionally, the diagnostic values of KLRB1 were analyzed in patients with LUAD. Survival and meta-analyses were employed to investigate the relationship between KLRB1 levels and other prognostic factors in patients with LUAD. Bioinformatics and cellular experiments were used to understand the functions and mechanisms of KLRB1. In addition, correlation analysis was used to investigate the relationship between KLRB1 levels and the immune microenvironment in LUAD. Reduced KLRB1 expression in LUAD was found to positively correlate with tumor size, distant metastasis, pathological stage, age, overall survival, diagnostic value, and disease-specific survival in patients with LUAD (P < 0.05). Conversely, increased KLRB1 expression was found to positively correlate with the overall survival and disease-specific survival in patients with LUAD (P < 0.05). We also found that the overexpression of KLRB1 can inhibit the proliferation, migration, and invasion of LUAD cells and promote apoptosis. KLRB1 was involved in immune cell differentiation, NF-kB, PD-L1, and PD-1 checkpoint pathways and others. Additionally, KLRB1 expression was linked to tumor purity, stromal, immune, and estimate scores, the levels of immune cells including B cells, CD8+ T cells, and CD4+ T cells, and immune cell markers in LUAD. Reduced KLRB1 expression has a significant positive correlation with diagnosis, poor prognosis, and immunity to cancer in patients with LUAD. KLRB1 inhibited cell proliferation and migration in patients with LUAD. These results suggest that KLRB1 may serve as a potential therapeutic target in patients with LUAD.

Clinical analysis of colistin sulfate in the treatment of pneumonia caused by carbapenem-resistant Gram-negative bacteria.

BACKGROUND: Multidrug-resistant Gram-negative bacteria, exacerbated by excessive use of antimicrobials and immunosuppressants, are a major health threat. AIM: To study the clinical efficacy and safety of colistin sulfate in the treatment of carbapenem-resistant Gram-negative bacilli-induced pneumonia, and to provide theoretical reference for clinical diagnosis and treatment. METHODS: This retrospective analysis involved 54 patients with Gram-negative bacilli pneumonia admitted to intensive care unit of The General Hospital of the Northern Theater Command of the People's Liberation Army of China from August 2020 to June 2022. After bacteriological culture, the patients' airway secretions were collected to confirm the presence of Gram-negative bacilli. The patients were divided into the experimental and control groups according to the medication used. The research group consisted of 28 patients who received polymyxin sulfate combined with other drugs through intravenous, nebulization, or intravenous combined with nebulization, with a daily dosage of 1.5-3.0 million units. The control group consisted of 26 patients who received standard dosages of other antibiotics (including sulbactam sodium for injection, cefoperazone sodium sulbactam for injection, tigecycline, meropenem, or vaborbactam). RESULTS: Of the 28 patients included in the research group, 26 patients showed improvement, treatment was ineffective for two patients, and one patient died, with the treatment efficacy rate of 92.82%. Of the 26 patients in the control group, 18 patients improved, treatment was ineffective for eight patients, and two patients died, with the treatment efficacy rate of 54.9%; significant difference was observed between the two groups (P < 0.05). The levels of white blood cell (WBC), procalcitonin (PCT), and C-reactive protein (CRP) in both groups were significantly lower after treatment than before treatment (P < 0.05), and the levels of WBC, PCT, and CRP in the research group were significantly lower than those in the control group (P < 0.05). Compared with before treatment, there were no significant changes in aspartate aminotransferase, creatinine, and glomerular filtration rate in both groups, while total bilirubin and alanine aminotransferase decreased after treatment (P < 0.05) with no difference between the groups. In patients with good clinical outcomes, the sequential organ failure assessment (SOFA) score was low when treated with inhaled polymyxin sulfate, and specific antibiotic treatment did not improve the outcome. Sepsis and septic shock as well as a low SOFA score were independent factors associated with good clinical outcomes. CONCLUSION: Polymyxin sulfate has a significant effect on the treatment of patients with multiple drug-resistant Gram-negative bacilli pneumonia and other infections in the lungs and is safe and reliable. Moreover, the administration route of low-dose intravenous injection combined with nebulization shows better therapeutic effects and lower adverse reactions, providing new ideas for clinical administration.

A Terahertz Metasurface Sensor Based on Quasi-BIC for Detection of Additives in Infant Formula.

Prohibited additives in infant formula severely affect the health of infants. Terahertz (THz) spectroscopy has enormous application potential in analyte detection due to its rich fingerprint information content. However, there is limited research on the mixtures of multiple analytes. In this study, we propose a split ring metasurface that supports magnetic dipole bound states in the continuum (BIC). By breaking the symmetry, quasi-BIC with a high quality (Q) factor can be generated. Utilizing an angle-scanning strategy, the frequency of the resonance dip can be shifted, resulting in the plotting of an envelope curve which can reflect the molecular fingerprint of the analytes. Two prohibited additives found in infant formula, melamine and vanillin, can be identified in different proportions. Furthermore, a metric similar to the resolution in chromatographic analysis is introduced and calculated to be 0.61, indicating that these two additives can be detected simultaneously. Our research provides a new solution for detecting additives in infant formula.

[Feasibility of non-invasive prenatal testing for the detection of fetal chromosomal copy number variants].

OBJECTIVE: To explore the feasibility of non-invasive prenatal testing (NIPT) for detecting fetal chromosomal copy number variants (CNV). METHODS: A retrospective analysis was carried out on NIPT positive samples in Suzhou Municipal Hospital from January 1, 2019 to December 31, 2021. The effect of NIPT on fetal CNV detection was assessed by comparison with the results of karyotype analysis and/or chromosomal microarray analysis (CMA). RESULTS: Among the 525 NIPT positive samples, 146 were CNV cases, of which 84 were further verified by karyotyping and/or CMA, 29 (34.5%) were true positive. Among them, 12 cases were pathogenic variants, 2 cases were likely pathogenic variants and 15 cases were variants of uncertain significance. CONCLUSION: NIPT could detect CNV with high accuracy, and to combine CNV detection and chromosomal aneuploidy detection has great significance to improve the prenatal and postnatal care.

Tea Polysaccharide Ameliorates High-Fat Diet-Induced Renal Tubular Ectopic Lipid Deposition via Regulating the Dynamic Balance of Lipogenesis and Lipolysis.

Renal tubular ectopic lipid deposition (ELD) plays a significant role in the development of chronic kidney disease, posing a great threat to human health. The present work aimed to explore the intervention effect and potential molecular mechanism of a purified tea polysaccharide (TPS3A) on renal tubular ELD. The results demonstrated that TPS3A effectively improved kidney function and slowed the progression of tubulointerstitial fibrosis in high-fat-diet (HFD)-exposed ApoE-/- mice. Additionally, TPS3A notably suppressed lipogenesis and enhanced lipolysis, as shown by the downregulation of lipogenesis markers (SREBP-1 and FAS) and the upregulation of lipolysis markers (HSL and ATGL), thereby reducing renal tubular ELD in HFD-fed ApoE-/- mice and palmitic-acid-stimulated HK-2 cells. The AMPK-SIRT1-FoxO1 axis is a core signal pathway in regulating lipid deposition. Consistently, TPS3A significantly increased the levels of phosphorylated-AMPK, SIRT1, and deacetylation of Ac-FoxO1. However, these effects of TPS3A on lipogenesis and lipolysis were abolished by AMPK siRNA, SIRT1 siRNA, and FoxO1 inhibitor, resulting in exacerbated lipid deposition. Taken together, TPS3A shows promise in ameliorating renal tubular ELD by inhibiting lipogenesis and promoting lipolysis through the AMPK-SIRT1-FoxO1 signaling pathway.

A comparative study of the hypolipidemic effects and mechanisms of action of Laminaria japonica- and Ascophyllum nodosum-derived fucoidans in apolipoprotein E-deficient mice.

The structural characteristics of fucoidans exhibit species and regional diversity. Previous studies have demonstrated that Laminaria japonica- and Ascophyllum nodosum-derived fucoidans have type I and type II fucosyl chains, respectively. These chemical differences may contribute to distinct hypolipidemic effects and mechanisms of action. Chemical analysis demonstrated that the percentage contents of sulfate, glucuronic acid, and galactose were higher in L. japonica-derived fucoidans than those of A. nodosum-derived fucoidans. In hyperlipidemic apolipoprotein E-deficient mice, both A. nodosum- and L. japonica-derived fucoidans significantly decreased the plasma and hepatic levels of total cholesterol and triglyceride, leading to the reduction of atherosclerotic plaques. Western blotting experiments demonstrated that these fucoidans significantly enhanced the expression and levels of scavenger receptor B type 1, cholesterol 7 alpha-hydroxylase A1, and peroxisome proliferator-activated receptor (PPAR)-α, contributing to circulating lipoprotein clearance and fatty acid degradation, respectively. Differentially, L. japonica-derived fucoidan significantly increased the LXR/ATP-binding cassette G8 signaling pathway in the small intestine, as revealed by real-time quantitative PCR, which may lead to further cholesterol and other lipid excretion. Collectively, these data are useful for understanding the hypolipidemic mechanisms of action of seaweed-derived fucoidans, and their potential application for the prevention and/or treatment of atherosclerotic cardiovascular diseases.

The function of brown adipose tissue at different sites of the body in Brandt's voles during cold acclimation.

Ambient temperatures have great impacts on thermoregulation of small mammals. Brown adipose tissue (BAT), an obligative thermogenic tissue for small mammals, is localized not only in the interscapular depot (iBAT), but also in supraclavicular, infra/subscapular, cervical, paravertebral, and periaortic depots. The iBAT is known for its cold-induced thermogenesis, however, less has been paid attention to the function of BAT at other sites. Here, we investigated the function of BAT at different sites of the body during cold acclimation in a small rodent species. As expected, Brandt's voles (Lasiopodomys brandtii) consumed more food and reduced the body mass gain when they were exposed to cold. The voles increased resting metabolic rate and maintained a relatively lower body temperature in the cold (36.5 ± 0.27 °C) compared to those in the warm condition (37.1 ± 0.36 °C). During cold acclimation, the uncoupling protein 1 (UCP1) increased in aBAT (axillary), cBAT (anterior cervical), iBAT (interscapular), nBAT (supraclavicular), and sBAT (suprascapular). The levels of proliferating cell nuclear antigen (PCNA), a marker for cell proliferation, were higher in cBAT and iBAT in the cold than in the warm group. The pAMPK/AMPK and pCREB/CREB were increased in cBAT and iBAT during cold acclimation, respectively. These data indicate that these different sites of BAT play the cold-induced thermogenic function for small mammals.

Spatially Confined π-Complexation within Pore-Space-Partitioned Metal-Organic Frameworks for Enhanced Light Hydrocarbon Separation and Purification.

Ultramicroporous metal-organic frameworks (MOFs) are demonstrated to be advantageous for the separation and purification of light hydrocarbons such as C2H2, C2H4, and CH4. The introduction of transition metal sites with strong π-complexation affinity into MOFs is more effective than other adsorption sites for the selective adsorption of π-electron-rich unsaturated hydrocarbon gases from their mixtures. However, lower coordination numbers make it challenging to produce robust MOFs directly utilizing metal ions with π-coordination activity, such as Cu+, Ag+, and Pd2+. Herein, a series of novel π-complexing MOFs (SNNU-33s) with a pore size of 4.6 Å are precisely constructed by cleverly introducing symmetrically matched C3-type [Cu(pyz)3] (pyz = pyrazine) coordinated fragments into 1D hexagonal channels of MIL-88 prototype frameworks. Benifit from the spatial confinement combined with π-complex-active Cu+ of [Cu(pyz)3], pore-space-partitioned SNNU-33 MOFs all present excellent C2H2/CH4, C2H4/CH4, and CO2/CH4 separation ability. Notably, the optimized SNNU-33b adsorbent demonstrates top-level IAST selectivity values for C2H2/CH4 (597.4) and C2H4/CH4 (69.8), as well as excellent breakthrough performance. Theoretical calculations further reveal that such benchmark light hydrocarbon separation and purification ability is mainly ascribed to the extra-strong binding affinity between Cu+ and π-electron donor molecules via a spatially confined π-complexation process.

Long-term outcomes of intraoperative chemotherapy with 5-FU for colorectal cancer patients receiving curative resection (IOCCRC): a randomized, multicenter, prospective, phase III trial.

BACKGROUND: We aimed to compare combined intraoperative chemotherapy and surgical resection with curative surgical resection alone in colorectal cancer patients. METHODS: We performed a multicenter, open-label, randomized, phase III trial. All eligible patients were randomized and assigned to intraoperative chemotherapy and curative surgical resection or curative surgical resection alone (1:1). Survival actualization after long-term follow-up was performed in patients analyzed on an intention-to-treat basis. RESULTS: From January 2011 to January 2016, 696 colorectal cancer patients were enrolled and randomly assigned to intraoperative chemotherapy and radical surgical resection (n=341) or curative surgical resection alone (n=344). Intraoperative chemotherapy with surgical resection showed no significant survival benefit over surgical resection alone in colorectal cancer patients (3-year DFS: 91.1% vs. 90.0%, P=0.328; 3-year OS: 94.4% vs. 95.9%, P=0.756). However, colon cancer patients benefitted from intraoperative chemotherapy, with a relative 4% reduction in liver and peritoneal metastasis (HR=0.336, 95% CI: 0.148-0.759, P=0.015) and a 6.5% improvement in 3-year DFS (HR=0.579, 95% CI: 0.353-0.949, P=0.032). Meanwhile, patients with colon cancer and abnormal pretreatment CEA levels achieved significant survival benefits from intraoperative chemotherapy (DFS: HR=0.464, 95% CI: 0.233-0.921, P=0.029 and OS: (HR=0.476, 95% CI: 0.223-1.017, P=0.049). CONCLUSIONS: Intraoperative chemotherapy showed no significant extra prognostic benefit in total colorectal cancer patients who underwent radical surgical resection; however, in colon cancer patients with abnormal pretreatment serum CEA levels (> 5 ng/ml), intraoperative chemotherapy could improve long-term survival.