Clinical significance of positive resection margin for patients with rectal neuroendocrine tumors within 20 mm following initial endoscopic resection: A multi-center study.

BACKGROUND: The incidence of rectal neuroendocrine tumors (RNETs) has witnessed a significant surge, with a notable proportion being amenable to endoscopic removal. However, the clinical significance of positive resection margin for RNETs patients following endoscopic resection remain unknown, resulting in a lack of consensus regarding the appropriateness of implementing salvage treatment. METHODS: In this large, multicenter, retrospective cohort study, we analyzed the medical records of individuals who underwent endoscopic resection for RNETs and classified them into two groups: the positive resection margin and the negative resection margin group. The overall survival (OS) and disease-free survival (DFS) were compared among two group. The independent variables were identified using univariate and multivariate logistic regression analyses to predict positive resection margin. Then, the model was established to predict the patients with positive resection margin using multivariate logistic regression. RESULTS: 181 RNETs patients (34.3 %) represented positive margin after endoscopic resection. Following a median follow-up period of 72 months, tumor recurrence manifested in 12 out of 527 patients (2.2 %) and the presence of positive resection margin was associated with worse DFS. Independent factors correlating with positive resection margin included endoscopic resection method choice, RNETs located in the low rectum, NLR >4.44 and tumor size exceeding 14.89 mm. A prediction model was therefore established with high predictive accuracy and excellent clinical applicability determined by calibration curves and DCA curve. Among RNETs patients with positive margin following endoscopic resection, implementing salvage treatment was beneficial for improving DFS and salvage endoscopic resection offer equal efficiency compared with salvage radical resection. CONCLUSIONS: Positive resection margin following endoscopic resection may indicate negative prognosis. Salvage treatment can improve the prognosis of RNETs patients with positive resection margin. Notably, salvage local resection exhibited similar efficacy compared with radical surgery in term of survival benefit.

Psychometric evaluation of the Chinese version of the resilience scale for parents of children with cancer.

Background: Pediatric cancer ranks among the leading causes of mortality in children globally. While serving as primary caregivers, certain parents may experience anxiety, depression, and other related challenges. However, not all parents succumb to such psychological distress. Resilience emerges as a potential protective factor. Assessing parental resilience holds paramount importance for healthcare professionals in identifying issues and offering tailored interventions. Yet, mainland China lacks adequate tools for this assessment. Hence, this study endeavors to translate the Resilience Scale for Parents of Children with Cancer (RSP-CC) into Chinese and scrutinize its psychometric properties. Methods: From April 2023 to January 2024, a methodological study was conducted in Chengdu, Chongqing, and Jinzhou, China, recruiting 377 eligible parents via convenience sampling for a multicenter cross-sectional survey. The translation process of the RSP-CC adhered rigorously to the Brislin model, involving forward and back-translation, followed by necessary modifications. Item analysis was assessed using the critical ratio and the item-total correlation coefficient. Validity evaluation encompassed content and internal validity assessments. Scale reliability was determined through Cronbach's α coefficient, retest reliability, and split-half reliability coefficients. Results: The Chinese version of the RSP-CC comprises 4 dimensions and 24 items, explaining a cumulative variance contribution of 63.58%. In this investigation, the content validity index attained a score of 0.97. Exploratory factor analysis (EFA) yielded four factors consistent with the original scale, while confirmatory factor analysis (CFA) indicated satisfactory fit indices. Both Cronbach's α coefficient and retest reliability stood at 0.95, with a split-half reliability coefficient of 0.82. Conclusion: After rigorous translation and verification, the RSP-CC was adapted in China, demonstrating favorable psychometric characteristics. It stands as an effective instrument for parents of children diagnosed with cancer in China. Additionally, this scale could serve as a crucial tool for clinical staff in formulating specific interventions.

Individualized regimen of Posaconazole oral suspension in Chinese HSCT patients based on population pharmacokinetic model.

To establish a population pharmacokinetic (PopPK) model of posaconazole suspension in Chinese hematopoietic stem cell transplantation (HSCT) patients and to recommend an optimal dosing regimen. A single-center, retrospective, model-based study was conducted in 62 Chinese patients, including 103 with posaconazole plasma concentrations. PopPK analysis using NONMEM software. A one-compartment model of first-order elimination and absorption was in good agreement with the experimental data. Analysis of covariance showed that body weight (WT), creatinine clearance (CCR), and proton pump inhibitor (PPI) had a significant effect on the pharmacokinetics of posaconazole. The dose simulation results show that patients with CCR ≥ 90 mL/min require at least 3 mg/kg TID and 7 mg/kg BID dosing regimens for prevention and treatment, respectively. However, when combined with PPI, at least 5 mg/kg BID and 5 mg/kg TID dosing regimens are required for prevention and treatment, respectively. Regardless of whether it is used in combination with PPI or not, patients with a CCR of 60-90 mL/min can achieve PTA goals by using a 4 mg/kg BID and 4 mg/kg TID regimen for prevention and treatment, respectively. A dosing regimen of 3 mg/kg BID in patients with a CCR of 30-60 mL/min is sufficient to meet the PTA goal of prophylaxis, and the dose needs to be elevated to 4 mg/kg BID for the treatment of fungal infections, and there is no need to change the dose according to the coadministration of PPI. When the patient's CCR is less than 30 mL/min, whether or not combined with PPI, the administration regimen of 2 mg/kg BID and 3 mg/kg BID can meet the PTA goals for prevention and treatment, respectively.

Accurate construction of monolayer, bilayer, sandwich bilayer, four-layer, multi-layer and chiral bilayer 2D pillararene-type supramolecular networks.

The accurate construction of mono-, bi- and multi-layer networks has been an important challenge, especially for bi- and multi-layer networks. Monolayer, bilayer, sandwich bilayer, four-layer, and multi-layer two-dimensional pillararene-type metal-organic coordination networks have been constructed from functionalized pillar[5]arene and pillar[6]arene by utilizing the coordination interaction of cobalt and copper ions and combining with temperature control and guest induction. These two-dimensional coordination networks exhibit the excellent plasticity of pillararenes and structural variety, which are characterized by X-ray single crystal diffraction and PXRD, confirming that pillararenes units can function as excellent tunable scaffolds for structural regulation. Two-dimensional chiral double-layer structure products are also constructed from R- and S-pillar[6]arene, which are obtained by high-performance liquid chromatography. Atomic force microscopic imaging confirms the thicknesses of these networks. Moreover, these networks also exhibit high iodine adsorption capacity in aqueous environments at ambient temperature. The monolayer, bilayer, sandwich bilayer, four-layer and multi-layer structures of the pillararene-type networks represent a new facile supramolecular self-assembly strategy and platform for designing more mono-, bi- and multi-layer two-dimensional nanomaterials and chiral two-dimensional double-layer structures provide a new method for the construction of more two-dimensional chiral polymers.

BEROLECMI: a novel prediction method to infer circRNA-miRNA interaction from the role definition of molecular attributes and biological networks.

Circular RNA (CircRNA)-microRNA (miRNA) interaction (CMI) is an important model for the regulation of biological processes by non-coding RNA (ncRNA), which provides a new perspective for the study of human complex diseases. However, the existing CMI prediction models mainly rely on the nearest neighbor structure in the biological network, ignoring the molecular network topology, so it is difficult to improve the prediction performance. In this paper, we proposed a new CMI prediction method, BEROLECMI, which uses molecular sequence attributes, molecular self-similarity, and biological network topology to define the specific role feature representation for molecules to infer the new CMI. BEROLECMI effectively makes up for the lack of network topology in the CMI prediction model and achieves the highest prediction performance in three commonly used data sets. In the case study, 14 of the 15 pairs of unknown CMIs were correctly predicted.

Azobenzene-bridged Covalent Organic Frameworks Boosting Photocatalytic Hydrogen Peroxide Production from Alkaline Water: One Atom Makes a Significant Improvement.

Covalent organic frameworks (COFs) have been demonstrated as promising photocatalysts for hydrogen peroxide (H2O2) production. However, the construction of COFs with new active sites, high photoactivity, and wide-range light absorption for efficient H2O2 production remains challenging. Herein, we present the synthesis of a novel azobenzene-bridged 2D COF (COF-TPT-Azo) with excellent performance on photocatalytic H2O2 production under alkaline conditions. Notably, although COF-TPT-Azo differs by only one atom (-N=N- vs. -C=N-) from its corresponding imine-linked counterpart (COF-TPT-TPA), the COF-TPT-Azo exhibits a significantly narrower band gap, enhanced charge transport, and prompted photoactivity. Remarkably, when employed as a metal-free photocatalyst, COF-TPT-Azo achieves a high photocatalytic H2O2 production rate up to 1498 µmol g-1 h-1 at pH =11, which is 7.9 times higher than that of COF-TPT-TPA. Further density functional theory (DFT) calculations reveal that the -N=N- linkages are the active sites for photocatalysis. This work provides new prospects for developing high-performance COF-based photocatalysts.

Nickel-catalyzed regiodivergent hydrosilylation of α-(fluoroalkyl)styrenes without defluorination.

The fluoroalkyl-containing organic molecules are widely used in drug discovery and material science. Herein, we report ligand regulated nickel(0)-catalyzed regiodivergent hydrosilylation of α-(fluoroalkyl)styrenes without defluorination, providing an atom- and step-economical synthesis route of two types of fluoroalkyl substituted silanes with exclusive regioselectivity. The anti-Markovnikov addition products (ß-fluoroalkyl substituted silanes) are formed with monodentate phosphine ligand. Noteworthy, the bidentate phosphine ligand promote the generation of the more challenging Markovnikov products (α-fluoroalkyl substituted silanes) with tetrasubstituted saturated carbon centers. This protocol features with easy available starting materials and commercially available nickel catalysis, a wide range of substrates and excellent regioselectivity. The structure divergent products undergo a variety of transformations. Comprehensive mechanistic studies including the inverse kinetic isotope effects demonstrate the regioselectivity controlled by ligand structure through α-CF3 nickel intermediate. DFT calculations reveal a distinctive mechanism involving an open-shell singlet state, which is crucial for generating intricate tetra-substituted Markovnikov products.

Six-Cyclic Crown Ether-Type Pillar[5]Arene: Enhanced Binding Ability to Bispyridinium Derivatives.

A six-cyclic crown ether-type pillar[5]arene was synthesized, and the five ethylene oxide loops were located outside the cavity and not affected by temperature changes which was confirmed by variable-temperature NMR experiment in DMSO-d6 and CDCl3 and 2D 1H-1H NOESY experiment in CDCl3. The six-cyclic pillar[5]-crown also showed greater binding ability of host-guest with bis(pyridinium) derivatives than conventional alkoxy pillar[5]arenes that illustrated through 1H NMR titration spectroscopic experiment in acetone-d6/CDCl3 (1 : 1) and UV-vis titration experiments in CHCl3 at room temperature. The five benzocrown ethers at the periphery were able to bind metal cations by 1H NMR titration spectroscopic experiment in CD2Cl2/methanol-d4(9 : 1).

Correlation between bone mineral density and type 2 diabetes mellitus in elderly men and postmenopausal women.

The relationship between bone mineral density and type 2 diabetes is still controversial. The aim of this study is to investigate the relationship between type 2 diabetes mellitus (T2DM) and bone mineral density (BMD) in elderly men and postmenopausal women. The participants in this study included 692 postmenopausal women and older men aged ≥ 50 years, who were divided into the T2DM group and non-T2DM control group according to whether or not they had T2DM. The data of participants in the two groups were collected from the inpatient medical record system and physical examination center systems, respectively, of the Tertiary Class A Hospital. All data analysis is performed in SPSS Software. Compared with all T2DM group, the BMD and T scores of lumbar spines 1-4 (L1-L4), left femoral neck (LFN) and all left hip joints (LHJ) in the non-T2DM group were significantly lower than those in the T2DM group (P < 0.05), and the probability of major osteoporotic fracture in the next 10 years (PMOF) was significantly higher than that in T2DM group (P < 0.001). However, with the prolongation of the course of T2DM, the BMD significantly decreased, while fracture risk and the prevalence of osteoporosis significantly increased (P < 0.05). We also found that the BMD of L1-4, LFN and LHJ were negatively correlated with homeostatic model assessment-insulin resistance (HOMA-IR) (P = 0.028, P = 0.01 and P = 0.047, respectively). The results also showed that the BMD of LHJ was positively correlated with indirect bilirubin (IBIL) (P = 0.018). Although the BMD was lower in the non-T2DM group than in the T2DM group, the prolongation of the course of T2DM associated with the lower BMD. And the higher prevalence of osteoporosis and fracture risk significantly associated with the prolongation of the course of T2DM. In addition, BMD was significantly associated with insulin resistance (IR) and bilirubin levels in T2DM patients.Registration number: China Clinical Trials Registry: MR-51-23-051741; https://www.medicalresearch.org.cn/search/research/researchView?id=c0e5f868-eca9-4c68-af58-d73460c34028 .

Clinical significance of TROAP in endometrial cancer and the antiproliferative and proapoptotic effects of TROAP knockdown in endometrial cancer cells: integrated utilization of bioinformatic analysis and in vitro test verification.

Trophinin-associated protein (TROAP), a cytoplasmic protein essential for spindle assembly and centrosome integrity during mitosis, has been reported to serve as an oncogene in various tumors. However, its role in endometrial cancer (EC) progression is still undefined. TROAP expression in EC was analyzed via GEPIA and HPA databases. The diagnostic and prognostic values of TROAP were examined by ROC curve analysis and Kaplan-Meier plotter, respectively. Cell proliferation was evaluated using CCK-8 and EdU incorporation assays. Apoptosis was assessed using TUNEL and flow cytometry assays. GSEA was performed to explore TROAP-related pathways in EC. Expression of TROAP, proliferating cell nuclear antigen (PCNA), Ki-67, cleaved-caspase-3 (cl-caspase-3), caspase-3, active ß-catenin, and total ß-catenin was detected using western blot analysis. TROAP was upregulated in EC. TROAP served as a potential diagnostic and prognostic marker in EC patients. TROAP silencing suppressed proliferation and enhanced apoptosis in EC cells. GSEA revealed that EC and Wnt signaling pathways were related to the expression of TROAP. We further demonstrated that TROAP knockout repressed the Wnt/ß-catenin pathway in EC cells. Moreover, SKL2001, a Wnt/ß-catenin activator, partially abrogated the effects of TROAP silencing on EC cell proliferation and apoptosis, while the signaling inhibitor XAV-939 had the opposite effect. In conclusion, TROAP knockout retarded proliferation and elicited apoptosis in EC cells by blocking the Wnt/ß-catenin pathway.

Tuning interfacial fluidity and colloidal stability of membranized coacervate protocells.

The cell membrane not only serves as the boundary between the cell's interior and the external environment but also plays a crucial role in regulating fundamental cellular behaviours. Interfacial membranization of membraneless coacervates, formed through liquid-liquid phase separation (LLPS), represents a reliable approach to constructing hierarchical cell-like entities known as protocells. In this study, we demonstrate the capability to modulate the interfacial membrane fluidity and thickness of dextran-bound coacervate protocells by adjusting the molecular weight of dextran or utilizing dextranase-catalyzed hydrolysis. This modulation allows for rational control over colloidal stability, interfacial molecular transport and cell-protocell interactions. Our work opens a new avenue for surface engineering of coacervate protocells, enabling the establishment of cell-mimicking structures and behaviours.

Thermal noise-driven resonant sensors.

MEMS/NEMS resonant sensors hold promise for minute mass and force sensing. However, one major challenge is that conventional externally driven sensors inevitably encounter undesired intrinsic noise, which imposes a fundamental limitation upon their signal-to-noise ratio (SNR) and, consequently, the resolution. Particularly, this restriction becomes increasingly pronounced as sensors shrink to the nanoscale. In this work, we propose a counterintuitive paradigm shift that turns intrinsic thermal noise from an impediment to a constituent of the sensor by harvesting it as the driving force, obviating the need for external actuation and realizing 'noise-driven' sensors. Those sensors employ the dynamically amplified response to thermal noise at resonances for stimulus detection. We demonstrate that lightly damped and highly compliant nano-structures with high aspect ratios are promising candidates for this class of sensors. To overcome the phase incoherence of the drive force, three noise-enabled quantitative sensing mechanisms are developed. We validated our sensor paradigm by experimental demonstrating noise-driven pressure and temperature sensors. Noise-driven sensors offer a new opportunity for delivering practical NEMS sensors that can function at room temperature and under ambient pressure, and a development that suggests a path to cheaper, simpler, and low-power-consumption sensors.

Identification of two-dimensional covalent organic frameworks with mcm topology and their application in photocatalytic hydrogen evolution.

Covalent organic frameworks have attracted considerable attention in recent years as a distinct class of crystalline porous organic materials. Their functional properties are inherently linked to their structural characteristics. Although hundreds of COFs have been reported so far, the types of their topologic structure are still limited. In this article, we report the identification of mcm topology for three porphyrin-based two-dimensional COFs, which are constructed from [4 + 4] imine condensation reactions. The mcm net is generated by pentagonal tiling, which has not been identified for COFs before. The structure of the COFs is elucidated by a variety of experimental characterization and structural simulations, by which their reticular frameworks exclusively composed of pentagonal pores have been confirmed. Moreover, the COFs exhibit high performance in photocatalytic hydrogen evolution from water, with the best one up to 10.0 mmol g-1 h-1 after depositing 0.76 wt% Pt as a co-catalyst. This study identifies mcm topology for COFs for the first time and highlights the potential of these COFs as promising photocatalysts for sustainable hydrogen production from water.

Promotion of direct electron transfer between Shewanella putrefaciens CN32 and carbon fiber electrodes via in situ growth of α-Fe2O3 nanoarray.

The iron transport system plays a crucial role in the extracellular electron transfer process of Shewanella sp. In this study, we fabricated a vertically oriented α-Fe2O3 nanoarray on carbon cloth to enhance interfacial electron transfer in Shewanella putrefaciens CN32 microbial fuel cells. The incorporation of the α-Fe2O3 nanoarray not only resulted in a slight increase in flavin content but also significantly enhanced biofilm loading, leading to an eight-fold higher maximum power density compared to plain carbon cloth. Through expression level analyses of electron transfer-related genes in the outer membrane and core genes in the iron transport system, we propose that the α-Fe2O3 nanoarray can serve as an electron mediator, facilitating direct electron transfer between the bacteria and electrodes. This finding provides important insights into the potential application of iron-containing oxide electrodes in the design of microbial fuel cells and other bioelectrochemical systems, highlighting the role of α-Fe2O3 in promoting direct electron transfer.

Seipin deficiency-induced lipid dysregulation leads to hypomyelination-associated cognitive deficits via compromising oligodendrocyte precursor cell differentiation.

Seipin is one key mediator of lipid metabolism that is highly expressed in adipose tissues as well as in the brain. Lack of Seipin gene, Bscl2, leads to not only severe lipid metabolic disorders but also cognitive impairments and motor disabilities. Myelin, composed mainly of lipids, facilitates nerve transmission and is important for motor coordination and learning. Whether Seipin deficiency-leaded defects in learning and motor coordination is underlined by lipid dysregulation and its consequent myelin abnormalities remains to be elucidated. In the present study, we verified the expression of Seipin in oligodendrocytes (OLs) and their precursors, oligodendrocyte precursor cells (OPCs), and demonstrated that Seipin deficiency compromised OPC differentiation, which led to decreased OL numbers, myelin protein, myelinated fiber proportion and thickness of myelin. Deficiency of Seipin resulted in impaired spatial cognition and motor coordination in mice. Mechanistically, Seipin deficiency suppressed sphingolipid metabolism-related genes in OPCs and caused morphological abnormalities in lipid droplets (LDs), which markedly impeded OPC differentiation. Importantly, rosiglitazone, one agonist of PPAR-gamma, substantially restored phenotypes resulting from Seipin deficiency, such as aberrant LDs, reduced sphingolipids, obstructed OPC differentiation, and neurobehavioral defects. Collectively, the present study elucidated how Seipin deficiency-induced lipid dysregulation leads to neurobehavioral deficits via impairing myelination, which may pave the way for developing novel intervention strategy for treating metabolism-involved neurological disorders.

Recovering from prolonged cardiac arrest induced by electric shock: A case report.

BACKGROUND: Cardiac arrest (CA) induced by electric shock is a rare occurrence, particularly in cases of prolonged CA. Currently, there is limited literature on similar incidents, and we present a relevant case report. CASE SUMMARY: A 27-year-old Asian male man, experiencing respiratory CA due to electric shock, was successfully restored to sinus rhythm after 50 min of cardiopulmonary resuscitation and 8 electrical defibrillation sessions. In the subsequent stages, the patient received multiple organ function protection measures, leading to a successful recovery and eventual discharge from the hospital. CONCLUSION: Prolonging resuscitation time can enhance the chances of survival for patients, this study provide valuable insights into the management of electric shock-induced CA.

Targeting Interactions between Fibroblasts and Macrophages to Treat Cardiac Fibrosis.

Excessive extracellular matrix (ECM) deposition is a defining feature of cardiac fibrosis. Most notably, it is characterized by a significant change in the concentration and volume fraction of collagen I, a disproportionate deposition of collagen subtypes, and a disturbed ECM network arrangement, which directly affect the systolic and diastolic functions of the heart. Immune cells that reside within or infiltrate the myocardium, including macrophages, play important roles in fibroblast activation and consequent ECM remodeling. Through both direct and indirect connections to fibroblasts, monocyte-derived macrophages and resident cardiac macrophages play complex, bidirectional, regulatory roles in cardiac fibrosis. In this review, we discuss emerging interactions between fibroblasts and macrophages in physiology and pathologic conditions, providing insights for future research aimed at targeting macrophages to combat cardiac fibrosis.

Structural, elastic, mechanical, electronic, and optical properties of cubic K2Pb2O3 from first-principle study.

CONTEXT: Based on first principles, the structure, elasticity, mechanics, electronics, and optical properties of cubic K2Pb2O3 were studied. The structural parameters calculated by this method are close to the previous theoretical results. The elastic constant, bulk modulus, shear modulus, Young's modulus, Poisson's ratio, and mechanical stability are studied, and it is shown that cubic K2Pb2O3 is mechanically stable, isotropic, and brittleness. The electrical conductivity and chemical bonding of cubic K2Pb2O3 were analyzed based on the calculated band structure, density of states (DOS), and bond populations. The dispersion of optical functions, including the dielectric function, refractive index, extinction coefficient, reflectivity, absorption coefficient, and loss function, is displayed and analyzed. METHODS: All computations have been carried out based on density functional theory (DFT) as implemented in the CASTEP code. The norm conservation pseudopotential method is used to exchange correlation functionals within the generalized gradient approximation (GGA).