Short-term effect of low-dose roxadustat combined with erythropoiesis-stimulating agent treatment for erythropoietin-resistant anemia in patients undergoing maintenance hemodialysis.

Background: Erythropoietin resistance is present in some patients with chronic kidney disease, especially in those undergoing hemodialysis, and is often treated using roxadustat rather than iron supplements and erythropoiesis-stimulating agents (ESAs). However, some patients cannot afford full doses of roxadustat. This retrospective study investigated the efficacy of low-dose roxadustat combined with recombinant human erythropoietin (rhuEPO) therapy in 39 patients with erythropoietin-resistant renal anemia undergoing maintenance hemodialysis (3-4 sessions/week). Methods: The ability of the combination of low-dose roxadustat and rhuEPO to increase the hemoglobin concentration over 12 weeks was assessed. Markers of iron metabolism were evaluated. Eligible adults received 50-60% of the recommended dose of roxadustat and higher doses of rhuEPO. Results: The mean hemoglobin level increased from 77.67 ± 11.18 g/dL to 92.0 ± 8.35 g/dL after treatment, and the hemoglobin response rate increased to 72%. The mean hematocrit level significantly increased from 24.26 ± 3.99% to 30.04 ± 3.69%. The soluble transferrin receptor level increased (27.29 ± 13.60 mg/L to 38.09 ± 12.78 mg/L), while the total iron binding capacity (49.22 ± 11.29 mg/L to 43.91 ± 12.88 mg/L) and ferritin level (171.05 ± 54.75 ng/mL to 140.83 ± 42.03 ng/mL) decreased. Conclusion: Therefore, in patients with ESA-resistant anemia who are undergoing hemodialysis, the combination of low-dose roxadustat and rhuEPO effectively improves renal anemia and iron metabolism.

Mfsd2a regulates the blood-labyrinth-barrier formation and function through tight junctions and transcytosis.

The Blood-Labyrinth Barrier (BLB) is pivotal for the maintenance of lymphatic homeostasis within the inner ear, yet the intricacies of its development and function are inadequately understood. The present investigation delves into the contribution of the Mfsd2a molecule, integral to the structural and functional integrity of the Blood-Brain Barrier (BBB), to the ontogeny and sustenance of the BLB. Our empirical findings delineate that the maturation of the BLB in murine models is not realized until approximately two weeks post-birth, with preceding stages characterized by notable permeability. Transcriptomic analysis elucidates a marked augmentation in Mfsd2a expression within the lateral wall of the cochlea in specimens exhibiting an intact BLB. Moreover, both in vitro and in vivo assays substantiate that a diminution in Mfsd2a expression detrimentally impacts BLB permeability and structural integrity, principally via the attenuation of tight junction protein expression and the enhancement of endothelial cell transcytosis. These insights underscore the indispensable role of Mfsd2a in ensuring BLB integrity and propose it as a viable target for therapeutic interventions aimed at the amelioration of hearing loss.

ZBP1-mediated apoptosis and inflammation exacerbate steatotic liver ischemia/reperfusion injury.

Steatotic donor livers are becoming more and more common in liver transplantation. However, the current use of steatotic grafts is less acceptable than normal grafts due to their higher susceptibility to ischemia/reperfusion (I/R) injury. To investigate the mechanism underlying the susceptibility of steatotic liver to I/R injury, we detected cell death markers and inflammation in clinical donor livers and animal models. We found that caspase-8-mediated hepatic apoptosis is activated in steatotic liver I/R injury. However, ablation of caspase-8 only slightly mitigated steatotic liver I/R injury without affecting inflammation. We further demonstrated that RIPK1 kinase induces both caspase-8-mediated apoptosis and cell death-independent inflammation. Inhibition of RIPK1 kinase significantly protects against steatotic liver I/R injury by alleviating both hepatic apoptosis and inflammation. Additionally, we found that RIPK1 activation is induced by Z-DNA binding protein 1 (ZBP1) but not the canonical TNF-α pathway during steatotic liver I/R injury. Deletion of ZBP1 substantially decreases the steatotic liver I/R injury. Mechanistically, ZBP1 is amplified by palmitic acid-activated JNK pathway in steatotic livers. Upon I/R injury, excessive reactive oxygen species trigger ZBP1 activation by inducing its aggregation independent of the Z-nucleic acids sensing action in steatotic livers, leading to the kinase activation of RIPK1 and the subsequent aggravation of liver injury. Thus, ZBP1-mediated RIPK1-driven apoptosis and inflammation exacerbate steatotic liver I/R injury, which could be targeted to protect steatotic donor livers during transplantation.

Important soil microbiota's effects on plants and soils: a comprehensive 30-year systematic literature review.

Clarifying the relationship between soil microorganisms and the plant-soil system is crucial for encouraging the sustainable development of ecosystems, as soil microorganisms serve a variety of functional roles in the plant-soil system. In this work, the influence mechanisms of significant soil microbial groups on the plant-soil system and their applications in environmental remediation over the previous 30 years were reviewed using a systematic literature review (SLR) methodology. The findings demonstrated that: (1) There has been a general upward trend in the number of publications on significant microorganisms, including bacteria, fungi, and archaea. (2) Bacteria and fungi influence soil development and plant growth through organic matter decomposition, nitrogen, phosphorus, and potassium element dissolution, symbiotic relationships, plant growth hormone production, pathogen inhibition, and plant resistance induction. Archaea aid in the growth of plants by breaking down low-molecular-weight organic matter, participating in element cycles, producing plant growth hormones, and suppressing infections. (3) Microorganism principles are utilized in soil remediation, biofertilizer production, denitrification, and phosphorus removal, effectively reducing environmental pollution, preventing soil pathogen invasion, protecting vegetation health, and promoting plant growth. The three important microbial groups collectively regulate the plant-soil ecosystem and help maintain its relative stability. This work systematically summarizes the principles of important microbial groups influence plant-soil systems, providing a theoretical reference for how to control soil microbes in order to restore damaged ecosystems and enhance ecosystem resilience in the future.

Toward Enhancing Performance of Electromagnetic Wave Absorption for Conductive Metal-Organic Frameworks: Nanostructure Engineering or Crystal Morphology Controlling.

Conductive metal-organic frameworks (cMOFs), which have high porosity and intrinsic electron conductivity, are regarded as ideal candidates for electromagnetic wave (EMW) absorption materials. Controlling the nanostructure of absorbers may be one of the effective strategies to improve the electromagnetic wave (EMW) absorption performance. Herein, a series of conductive Cu-HHTP MOFs (HHTP = 2,3,6,7,10,11-hexahydroxytriphenyl hydrates) with different nanostructures or crystal morphologies were successfully synthesized by using different structural inducers to regulate the changes in the morphology, thereby improving the EMW absorption performance. Specifically, when ammonia was used as an inducer, the obtained A-Cu-HHTP with a nanosheet structure exhibited excellent EMW absorption performance. The minimum reflection loss (RLmin) can reach -51.08 dB at 7.25 GHz with a thickness of 4.4 mm, and the maximum effective absorption bandwidth (EAB) can cover 5.73 GHz at 2.5 mm. The influence of the nanostructures of the cMOFs on the dielectric and EMW absorption performance was clarified. The nanosheet structure of A-Cu-HHTP increases its specific surface area, which expands multiple scattering and reflection paths of incident EMW; Meanwhile, the unique structure facilitates the formation of more heterogeneous interfaces, optimizing impedance matching. The significant improvement in EMW performance is mainly attributed to multiple reflections and scattering as well as impedance matching. This work not only provides a simple and effective strategy for improving electromagnetic wave absorption performance but also offers guidelines for preparing morphology functional cMOF materials.

Dynamic prediction of goal location by coordinated representation of prefrontal-hippocampal theta sequences.

Prefrontal (PFC) and hippocampal (HPC) sequences of neuronal firing modulated by theta rhythms could represent upcoming choices during spatial memory-guided decision-making. How the PFC-HPC network dynamically coordinates theta sequences to predict specific goal locations and how it is interrupted in memory impairments induced by amyloid beta (Aß) remain unclear. Here, we detected theta sequences of firing activities of PFC neurons and HPC place cells during goal-directed spatial memory tasks. We found that PFC ensembles exhibited predictive representation of the specific goal location since the starting phase of memory retrieval, earlier than the hippocampus. High predictive accuracy of PFC theta sequences existed during successful memory retrieval and positively correlated with memory performance. Coordinated PFC-HPC sequences showed PFC-dominant prediction of goal locations during successful memory retrieval. Furthermore, we found that theta sequences of both regions still existed under Aß accumulation, whereas their predictive representation of goal locations was weakened with disrupted spatial representation of HPC place cells and PFC neurons. These findings highlight the essential role of coordinated PFC-HPC sequences in successful memory retrieval of a precise goal location.

The efficacy of articaine in pain management during endodontic procedures in pediatric patients.

OBJECTIVE: This trial aimed to study the efficacy of articaine in pain management during endodontic procedures in pediatric patients. METHODS: Ninety-eight children who received endodontic painless treatment were collected and randomly divided into the control group and observation group, with 49 cases in each group. The control group received infiltration anesthesia with lidocaine, and the observation group received infiltration anesthesia with articaine. Anesthesia effect, anesthesia onset time, sensory recovery time, duration of anesthesia, pain intensity, blood pressure, heart rate, and adverse reactions were compared. RESULTS: The effective rate of anesthesia in the observation group was higher than that in the control group. The anesthesia onset time and sensory recovery time were shorter, the duration of anesthesia was longer, and the VAS score and facial expression score were lower in the observation group than in the control group. The heart rate of the observation group was lower, and diastolic blood pressure was higher than those of the control group. The total incidence of adverse reactions in the observation group was lower than that in the control group. CONCLUSION: In the treatment of dental pulp diseases in children, the use of articaine can achieve better anesthesia effect and rapid onset of anesthesia and has less impact on the patient's blood pressure and heart rate, but it also can relieve pain and has good safety after the use of medication. It is worthy of clinical application.

I Treated the Way You Treated Me: The Effect of Leader Hypocrisy on Employees' Voice Behavior.

Purpose: In recent years, due to the increasingly prominent role of voice behavior in leader decision-making and organizational performance, such behavior has become a central topic for scholars. A majority of studies explore the "uphold" effects of multiple leader behavior toward the voice behavior; nonetheless, our study revealed the "undo" effect --- leader hypocrisy on voice behavior. Drawing on social cognitive theory, we investigated the relationship between leader hypocrisy and voice behavior, examined the mediating effects of cognition-based trust and affect-based trust, and the moderating effect of moral identity. Patients and Methods: We conducted a three-wave survey in a large Chinese corporation to test the hypothesized model. We collected 562 employees to participate in this survey. Results: The results show that leader hypocrisy negatively impacts employees' cognition-based and affect-based trust, and both types of trust mediate the relationship between leader hypocrisy and voice behavior, respectively. In the meantime, moral identity manifested the negative effect of leader hypocrisy on cognition-based and affect-based trust. Conclusion: Our research not only enriches the related research on leader hypocrisy and voice behavior but also uncovers the underlying mechanism through which leader hypocrisy affects voice behavior and the boundary conditions of this effect. Meanwhile, our research provides a theoretical reference for increasing employees' voice behavior and promoting the healthy development of enterprises.

Overexpression of circulating CD38+ NK cells in colorectal cancer was associated with lymph node metastasis and poor prognosis.

Introduction: Lymph node metastasis (LNM) is a critical prognostic factor for colorectal cancer (CRC). Due to the potential influence of immune system on CRC progression, investigation into lymphocyte subsets as clinical markers has gained attention. The objective of this study was to assess the capability of lymphocyte subsets in evaluating the lymph node status and prognosis of CRC. Methods: Lymphocyte subsets, including T cells (CD3+), natural killer cells (NK, CD3- CD56+), natural killer-like T cells (NK-like T, CD3+ CD56+), CD38+ NK cells (CD3- CD56+ CD38+) and CD38+ NK-like T cells (CD3+ CD56+ CD38+), were detected by flow cytometry. Univariate and multivariate analyses were used to assess the risk factors of LNM. The prognostic role of parameters was evaluated by survival analysis. Results: The proportion of CD38+ NK cells within the NK cell population was significantly higher in LNM-positive patients (p <0.0001). However, no significant differences were observed in the proportions of other lymphocyte subsets. Poorer histologic grade (odds ratio [OR] =4.76, p =0.03), lymphovascular invasion (LVI) (OR =22.38, p <0.01), and CD38+ NK cells (high) (OR =4.54, p <0.01) were identified as independent risk factors for LNM. Furthermore, high proportion of CD38+ NK cells was associated with poor prognosis of CRC patients (HR=2.37, p =0.03). Conclusions: It was demonstrated that the proportion of CD38+ NK cells was a marker overexpressed in LNM-positive patients compared with LNM-negative patients. Moreover, an elevated proportion of CD38+ NK cells is a risk factor for LNM and poor prognosis in CRC.

Gelatin-Encapsulated Tetrahedral DNA Nanostructure Enhances Cellular Internalization for Treating Noise-Induced Hearing Loss.

Nanoparticle-based drug delivery strategies have emerged as a crucial avenue for comprehensive sensorineural hearing loss treatment. Nevertheless, developing therapy vectors crossing both biological and cellular barriers has encountered significant challenges deriving from various external factors. Herein, the rational integration of gelatin nanoparticles (GNPs) with tetrahedral DNA nanostructures (TDNs) to engineer a distinct drug-delivery nanosystem (designed as TDN@GNP) efficiently enhances the biological permeability and cellular internalization, further resolving the dilemma of noise-induced hearing loss via loading epigallocatechin gallate (EGCG) with anti-lipid peroxidation property. Rationally engineering of TDN@GNP demonstrates dramatic alterations in the physicochemical key parameters of TDNs that are pivotal in cell-particle interactions and promote cellular uptake through multiple endocytic pathways. Furthermore, the EGCG-loaded nanosystem (TDN-EGCG@GNP) facilitates efficient inner ear drug delivery by superior permeability through the biological barrier (round window membrane), maintaining high drug concentration within the inner ear. The TDN-EGCG@GNP actively overcomes the cell membrane, exhibiting hearing protection from noise insults via reduced lipid peroxidation in outer hair cells and spiral ganglion neurons. This work exemplifies how integrating diverse vector functionalities can overcome biological and cellular barriers in the inner ear, offering promising applications for inner ear disorders.

Personalized Porous Gelatin Methacryloyl Sustained-Release Nicotinamide Protects Against Noise-Induced Hearing Loss.

There are no Food and Drug Administration-approved drugs for treating noise-induced hearing loss (NIHL), reflecting the absence of clear specific therapeutic targets and effective delivery strategies. Noise trauma is demonstrated results in nicotinamide adenine dinucleotide (NAD+) downregulation and mitochondrial dysfunction in cochlear hair cells (HCs) and spiral ganglion neurons (SGNs) in mice, and NAD+ boosted by nicotinamide (NAM) supplementation maintains cochlear mitochondrial homeostasis and prevents neuroexcitatory toxic injury in vitro and ex vivo, also significantly ameliorated NIHL in vivo. To tackle the limited drug delivery efficiency due to sophisticated anatomical barriers and unique clearance pathway in ear, personalized NAM-encapsulated porous gelatin methacryloyl (PGMA@NAM) are developed based on anatomy topography of murine temporal bone by micro-computed tomography and reconstruction of round window (RW) niche, realizing hydrogel in situ implantation completely, NAM sustained-release and long-term auditory preservation in mice. This study strongly supports personalized PGMA@NAM as NIHL protection drug with effective inner ear delivery, providing new inspiration for drug-based treatment of NIHL.

Sound conditioning strategy promoting paracellular permeability of the blood-labyrinth-barrier benefits inner ear drug delivery.

The therapeutic effects of pharmaceuticals depend on their drug concentrations in the cochlea. Efficient drug delivery from the systemic circulation into the inner ear is limited by the blood-labyrinth-barrier (BLB). This study investigated a novel noninvasive sound conditioning (SC) strategy (90 dB SPL, 8-16 kHz, 2 h sound exposure) to temporally enhance BLB permeability in a controllable way, contributing to maximizing the penetration of pharmaceuticals from blood circulation into the cochlea. Trafficking of Fluorescein Isothiocyanate conjugated dextran and bovine serum albumin (FITC-dextran and FITC-BSA) demonstrated that paracellular leakage of BLB sustained for 6 h after SC, providing a controllable time window for systemic administration. Cochlear concentrations of dexamethasone (DEX) and dexamethasone phosphate (DEX-P), respectively transported by transcellular and paracellular pathways, showed a higher content of the latter one after SC, further confirming the key role of paracellular pathway in the SC-induced hyperpermeability. Results of high-throughput RNA-sequencing identified a series of tight junction (TJ)-associated genes after SC. The expressions of TJ (ZO-1) were reduced and irregular rearrangements of the junction were observed by transmission electron microscopy after SC. We further determined the inhibiting role of Rab13 in the recruitment of ZO-1 and later in the regulation of cellular permeability. Meanwhile, no significant change in the quantifications of endothelial caveolae vesicles after SC indicated that cellular transcytosis accounted little for the temporary hyperpermeability after SC. Based on these results, SC enhances the BLB permeability within 6 h and allows systemically applied drugs which tend to be transported by paracellular pathway to readily enter the inner ear, contributing to guiding the clinical medications on hearing loss.

Impact of Cooperative Innovation on the Technological Innovation Performance of High-Tech Firms: A Dual Moderating Effect Model of Big Data Capabilities and Policy Support.

The mechanism of cooperative innovation (CI) for high-tech firms aims to improve their technological innovation performance. It is the effective integration of the internal and external innovation resources of these firms, along with the simultaneous reduction in the uncertainty of technological innovation and the maintenance of the comparative advantage of the firms in the competition. This study used 322 high-tech firms as our sample, which were located in 33 national innovation demonstration bases identified by the Chinese government. We implemented a multiple linear regression to test the impact of CI conducted by these high-tech firms at the level of their technological innovation performance. In addition, the study further examined the moderating effect of two boundary conditions-big data capabilities and policy support (PS)-on the main hypotheses. Our study found that high-tech firms carrying out CI can effectively improve their technological innovation performance, with big data capabilities and PS significantly enhancing the degree of this influence. The study reveals the intrinsic mechanism of the impact of CI on the technological innovation performance of high-tech firms, which, to a certain extent, expands the application context of CI and enriches the research perspective on the impact of CI on the innovation performance of firms. At the same time, the findings provide insight for how high-tech firms in the digital era can make reasonable use of data empowerment in the process of CI to achieve improved technological innovation performance.

What happens to regulatory T cells in multiple myeloma.

Abnormal tumor microenvironment and immune escape in multiple myeloma (MM) are associated with regulatory T cells (Tregs), which play an important role in maintaining self-tolerance and regulating the overall immune response to infection or tumor cells. In patients with MM, there are abnormalities in the number, function and distribution of Tregs, and these abnormalities may be related to the disease stage, risk grade and prognosis of patients. During the treatment, Tregs have different responses to various treatment regiments, thus affecting the therapeutic effect of MM. It is also possible to predict the therapeutic response by observing the changes of Tregs. In addition to the above, we reviewed the application of Tregs in the treatment of MM. In conclusion, there is still much room for research on the mechanism and application of Tregs in MM.

FN1 and TGFBI are key biomarkers of macrophage immune injury in diabetic kidney disease.

The pathogenesis of diabetic kidney disease (DKD) is complex, and the existing treatment methods cannot control disease progression well. Macrophages play an important role in the development of DKD. This study aimed to search for biomarkers involved in immune injury induced by macrophages in DKD. The GSE96804 dataset was downloaded and analyzed by the CIBERSORT algorithm to understand the differential infiltration of macrophages between DKD and normal controls. Weighted gene co-expression network analysis was used to explore the correlation between gene expression modules and macrophages in renal tissue of DKD patients. Protein-protein interaction network and machine learning algorithm were used to screen the hub genes in the key modules. Subsequently, the GSE30528 dataset was used to further validate the expression of hub genes and analyze the diagnostic effect by the receiver operating characteristic curve. The clinical data were applied to explore the prognostic significance of hub genes. CIBERSORT analysis showed that macrophages increased significantly in DKD renal tissue samples. A total of ten modules were generated by weighted gene co-expression network analysis, of which the blue module was closely associated with macrophages. The blue module mainly played an important role in biological processes such as immune response and fibrosis. Fibronectin 1 (FN1) and transforming growth factor beta induced (TGFBI) were identified as hub genes of DKD patients. Receiver operating characteristic curve analysis was performed in the test cohort: FN1 and TGFBI had larger area under the curve values (0.99 and 0.88, respectively). Clinical validation showed that 2 hub genes were negatively correlated with the estimated glomerular filtration rate in DKD patients. In addition, FN1 and TGFBI showed a strong positive correlation with macrophage alternative activation. FN1 and TGFBI are promising biomarkers for the diagnosis and treatment of DKD patients, which may participate in immune response and fibrosis induced by macrophages.

RNA base editing therapy cures hearing loss induced by OTOF gene mutation.

Otoferlin (OTOF) gene mutations represent the primary cause of hearing impairment and deafness in auditory neuropathy. The c.2485C>T (p. Q829X) mutation variant is responsible for approximately 3% of recessive prelingual deafness cases within the Spanish population. Previous studies have used two recombinant AAV vectors to overexpress OTOF, albeit with limited efficacy. In this study, we introduce an enhanced mini-dCas13X RNA base editor (emxABE) delivered via an AAV9 variant, achieving nearly 100% transfection efficiency in inner hair cells. This approach is aimed at treating OTOFQ829X, resulting in an approximately 80% adenosine-to-inosine conversion efficiency in humanized OtofQ829X/Q829X mice. Following a single scala media injection of emxABE targeting OTOFQ829X (emxABE-T) administered during the postnatal day 0-3 period in OtofQ829X/Q829X mice, we observed OTOF expression restoration in nearly 100% of inner hair cells. Moreover, auditory function was significantly improved, reaching similar levels as in wild-type mice. This enhancement persisted for at least 7 months. We also investigated P5-P7 and P30 OtofQ829X/Q829X mice, achieving auditory function restoration through round window injection of emxABE-T. These findings not only highlight an effective therapeutic strategy for potentially addressing OTOFQ829X-induced hearing loss but also underscore emxABE as a versatile toolkit for treating other monogenic diseases characterized by premature termination codons.

Discovery of zolinium TSG1180 as a novel agonist of transgelin-2 for treating asthma.

Asthma is a complex and heterogeneous respiratory disease that causes serious social and economic burdens. Current drugs such as ß2-agonists cannot fully control asthma. Our previous study found that Transgelin-2 is a potential target for treating asthmatic pulmonary resistance. Herein, we discovered a zolinium compound, TSG1180, that showed a strong interaction with Transgelin-2. The equilibrium dissociation constants (KD) of TSG1180 to Transgelin-2 were determined to be 5.363 × 10-6 and 9.81 × 10-6 M by surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC). Cellular thermal shift assay (CETSA) results showed that the thermal stability of Transgelin-2 increased after coincubation of TSG1180 with lysates of airway smooth muscle cells (ASMCs). Molecular docking showed that Arg39 may be the key residue for the binding. Then, the SPR result showed that the binding affinity of TSG1180 to Transgelin-2 mutant (R39E) was decreased by 1.69-fold. Real time cell analysis (RTCA) showed that TSG1180 treatment could relax ASMCs by 19 % (P < 0.05). Once Transgelin-2 was inhibited, TSG1180 cannot induce a relaxation effect, suggesting that the relaxation effect was specifically mediated by Transgelin-2. In vivo study showed TSG1180 effectively reduced pulmonary resistance by 64 % in methacholine-induced mice model (P < 0.05). Furthermore, the phosphorylation of Ezrin at T567 was increased by 8.06-fold, the phosphorylation of ROCK at Y722 was reduced by 38 % and the phosphorylation of RhoA at S188 was increased by 52 % after TSG1180 treatment. These results suggested that TSG1180 could be a Transgelin-2 agonist for further optimization and development as an anti-asthma drug.

High serum mannose in colorectal cancer: a novel biomarker of lymph node metastasis and poor prognosis.

Background: Lymph node status is an important prognostic indicator and it significantly influences treatment decisions for colorectal cancer (CRC). The objective of this study was to evaluate the ability of serum monosaccharides in predicting lymph node metastasis (LNM) and prognosis. Methods: High performance anion exchange chromatography coupled with pulsed amperometric detector (HPAEC-PAD) was used to quantify serum monosaccharides from 252 CRC patients. Receiver operating characteristic (ROC) curves were used to evaluate predictive performance of parameters. Predictors of LNM were evaluated by univariate and multivariate analyses. The prognostic role of the factors was evaluated by survival analysis. Results: The levels of serum mannose (Man) and galactose (Gal) were significantly increased in patients with LNM (p <0.0001, p =0.0017, respectively). The area under the curves (AUCs) of Man was 0.8140, which was higher than carcinoembryonic antigen (CEA) (AUC =0.6523). Univariate and multivariate analyses demonstrated histologic grade (G3) (odds ratio [OR] =2.60, p =0.043), histologic grade (mucin-producing subtype) (odds ratio [OR] =3.38, p =0.032), lymphovascular invasion (LVI) (OR =2.42, p <0.01), CEA (>5ng/ml) (OR =1.85, p =0.042) and high Man (OR =2.65, p =0.006) to be independent risk factors of LNM. The survival analysis showed that the high serum Man was independent risk factor for poor prognosis in CRC patients (HR=1.75, p =0.004). Conclusions: The Man is superior to CEA in prediction of LNM for CRC patients. Man is expected to be a predictor for LNM in CRC. High serum Man is associated with poor prognosis of CRC patients.

A Mini Review of Ceramic-Based MOF Membranes for Water Treatment.

Ceramic membranes have been increasingly employed in water treatment owing to their merits such as high-stability, anti-oxidation, long lifespan and environmental friendliness. The application of ceramic membranes mainly focuses on microfiltration and ultrafiltration processes, and some precise separation can be achieved by introducing novel porous materials with superior selectivity. Recently, metal-organic frameworks (MOFs) have developed a wide spectrum of applications in the fields of the environment, energy, water treatment and gas separation due to the diversity and tunable advantages of metal clusters and organic ligands. Although the issue of water stability in MOF materials inhibits the development of MOF membranes in water treatment, researchers still overcome many obstacles to advance the application of MOF membranes in water treatment processes. To the best of our knowledge, there is still a lack of a reviews on the development process and prospects of ceramic-based MOF membranes for water treatment. Therefore, in this review, we mainly summarize the fabrication method for ceramic-based MOF membranes and their application in water treatment, such as water/salt separation, pollutant separation, heavy metal separation, etc. Following this, based on the high structural, thermal and chemical stability of ceramic substrates, and the high controllability of MOF materials, the superiority and insufficient use of ceramic-based MOF membranes in the field of water treatment are critically discussed.

Adiponectin inhibits TGF-ß1-induced skin fibroblast proliferation and phenotype transformation via the p38 MAPK signaling pathway.

The aim of this study was to investigate the effects of adiponectin (APN) on the proliferation and phenotypic transformation of human skin fibroblasts (HSFs) induced by TGF-ß1. Primary fibroblast cultures were collected from prepuce surgery, and the cell viability and proliferative activity of HSFs were detected by Cell Counting Kit-8 and EdU assays. In addition, cell migration was detected by Transwell assay. The protein levels of related genes in HSF were detected by Western blotting. The results showed that the proliferation and migration abilities of HSF in the TGF-ß1 group were significantly improved, and the relative protein expression levels of PCNA, α-SMA, and Collagen I in the TGF-ß1 group were greatly increased. Furthermore, TGF-ß1 stimulated the phosphorylation of p38 in HSF, while APN pretreatment significantly inhibited the TGF-ß1-induced phosphorylation of p38. Additionally, blocking the p38 MAPK signaling pathway relieved the injury in the HSF induced by TGF-ß1 and enhanced the therapeutic effect of APN in the TGF-ß1-treated HSF. In conclusion, APN inhibits TGF-ß1-induced HSF proliferation and myofibroblast phenotypic transformation by activating the p38 MAPK signaling pathway. APN is expected to become a potential target for preventing and treating skin fibrosis and pathological scars.