A Composite Hydrogel Functionalized by Borosilicate Bioactive Glasses and VEGF for Critical-Size Bone Regeneration.

Critical-size bone defects pose a formidable challenge in clinical treatment, prompting extensive research efforts to address this problem. In this study, an inorganic-organic multifunctional composite hydrogel denoted as PLG-g-TA/VEGF/Sr-BGNPs is developed, engineered for the synergistic management of bone defects. The composite hydrogel demonstrated the capacity for mineralization, hydroxyapatite formation, and gradual release of essential functional ions and vascular endothelial growth factor (VEGF) and also maintained an alkaline microenvironment. The composite hydrogel promoted the proliferation and osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs), as indicated by increased expression of osteogenesis-related genes and proteins in vitro. Moreover, the composite hydrogel significantly enhanced the tube-forming capability of human umbilical vein endothelial cells (HUVECs) and effectively inhibited the process of osteoblastic differentiation of nuclear factor kappa-B ligand (RANKL)-induced Raw264.7 cells and osteoclast bone resorption. After the implantation of the composite hydrogel into rat cranial bone defects, the expression of osteogenic and angiogenic biomarkers increased, substantiating its efficacy in promoting bone defect repair in vivo. The commendable attributes of the multifunctional composite hydrogel underscore its pivotal role in expediting hydrogel-associated bone growth and repairing critical bone defects, positioning it as a promising adjuvant therapy candidate for large-segment bone defects.

Causal association between low vitamin D and polycystic ovary syndrome: a bidirectional mendelian randomization study.

BACKGROUND: Recent studies have revealed the correlation between serum vitamin D (VD) level and polycystic ovary syndrome (PCOS), but the causality and specific mechanisms remain uncertain. OBJECTIVE: We aimed to investigate the cause-effect relationship between serum VD and PCOS, and the role of testosterone in the related pathological mechanisms. METHODS: We assessed the causality between serum VD and PCOS by using genome-wide association studies (GWAS) data in a bidirectional two-sample Mendelian randomization (TS-MR) analysis. Subsequently, a MR mediation analysis was conducted to examine the mediating action of testosterone in the causality between serum VD and PCOS. Ultimately, we integrated GWAS data with cis-expression quantitative loci (cis-eQTLs) data for gene annotation, and used the potentially related genes for functional enrichment analysis to assess the involvement of testosterone and the potential mechanisms. RESULTS: TS-MR analysis showed that individuals with lower level of serum VD were more likely to develop PCOS (OR = 0.750, 95% CI: 0.587-0.959, P = 0.022). MR mediation analysis uncovered indirect causal effect of serum VD level on the risk of PCOS via testosterone (OR = 0.983, 95% CI: 0.968-0.998, P = 0.025). Functional enrichment analysis showed that several pathways may be involved in the VD-testosterone-PCOS axis, such as steroid hormone biosynthesis and autophagy process. CONCLUSION: Our findings suggest that genetically predicted lower serum VD level may cause a higher risk of developing PCOS, which may be mediated by increased testosterone production.

Fluorinated Organic Polymers for Cancer Drug Delivery.

In the realm of cancer therapy, the spotlight is on nanoscale pharmaceutical delivery systems, especially polymer-based nanoparticles, for their enhanced drug dissolution, extended presence in the bloodstream, and precision targeting achieved via surface engineering. Leveraging the amplified permeation and retention phenomenon, these systems concentrate therapeutic agents within tumor tissues. Nonetheless, the hurdles of systemic toxicity, biological barriers, and compatibility with living systems persist. Fluorinated polymers, distinguished by their chemical idiosyncrasies, are poised for extensive biomedical applications, notably in stabilizing drug metabolism, augmenting lipophilicity, and optimizing bioavailability. Material science heralds the advent of fluorinated polymers that, by integrating fluorine atoms, unveil a suite of drug delivery merits: the hydrophobic traits of fluorinated alkyl chains ward off lipid or protein disruption, the carbon-fluorine bond's stability extends the drug's lifecycle in the system, and a lower alkalinity coupled with a diminished ionic charge bolsters the drug's ability to traverse cellular membranes. This comprehensive review delves into the utilization of fluorinated polymers for oncological pharmacotherapy, elucidating their molecular architecture, synthetic pathways, and functional attributes, alongside an exploration of their empirical strengths and the quandaries they encounter in both experimental and clinical settings.

Enhanced osteogenesis and physicochemical properties of PMMA bone cement with SrBG/HA porous core-shell microspheres.

Artificial bone graft with osteoconductivity, angiogenesis, and immunomodulation is promising clinical therapeutics for the reluctant healing process of bone defects. Among various osteogenic substitutes, polymethyl methacrylate (PMMA) bone cement is a quit competitive platform due to its easy deployment to the bone defects with irregular shape and biomimetic mechanical properties. However, the biologically inert essence of PMMA is reliant on the passive osseointegration and cannot provide sufficient biologic cues to induce fast bone repair. Bioactive glass could serve as an efficient platform for the active osteogenesis of PMMA via ionic therapy and construction of alkaline microenvironment. However, the direct of deployment of bioactive glass into PMMA may trigger additional cytotoxicity and hinder cell growth on its surface. Hence we incorporated ionic therapy as osteogenic cue into the PMMA to enhance the biomedical properties. Specifically, we synthesized core-shell microspheres with a strontium-doped bioactive glass (SrBG) core and hydroxyapatite (HA) shell, and then composited them with PMMA to introduce multifunctional effects of HA incorporation, alkaline microenvironment construction, and functional ion release by adding microsphere. We preparedxSrBG@HA/PMMA cements (x= 30, 40, 50) with varied microsphere content and evaluated impacts on mechanical/handling properties, ion release, and investigated the impacts of different composite cements on proliferation, osteogenic differentiation, angiogenic potential, and macrophage polarization. These findings provide new perspectives and methodologies for developing advanced bone biomaterials to promote tissue regeneration.

Granulomatosis with polyangiitis.

A 30-year-old man presented to otolaryngology department complaining of nasal congestion and runny nose for six months, with repeated fever, and shortness of breath.The weight loss in the past 20 days was about 5 kg. At first, he was diagnosed with respiratory infection and was treated with antibiotics, but it didn't work. Nasopharynx CT scan showed soft tissue thickening without bone destruction, with obvious inhomogeneous enhancement. Chest CT scan revealed multiple patchy clouding nodules and ground-glass opacity with poorly-defined border. Urine test showed urine microalbumin ≥ 150 mg per liter (reference range, 0-20), white-cell count of 11.0 cells per microliter (reference range, 0-5). Histology of nasopharynx biopsy showed small-medium-vessel necrotizing vasulitis.Although nasopharyngeal histopathology didn't reveal peri- and extravascular granulomatosis and antineutrophilic cytoplasmic antibodies (ANCA) was negtive, he had ENT signs, lung nodules, and kidney involvement and condition developed fast and biopsy showed small- and- medium-vessel vasculitis. Therefore, the patient met the classification criteria for GPA and his symptoms were disappeared 1 week after starting GPA treatment, the chest CT showed ground-glass opacity decreased and CRP、ESR became normal. He was treated with rituximab combined with glucocorticoids for 4 weeks, after which he was discharged.

Bio-Inspired Electrodes with Rational Spatiotemporal Management for Lithium-Ion Batteries.

Lithium-ion batteries (LIBs) are currently the predominant energy storage power source. However, the urgent issues of enhancing electrochemical performance, prolonging lifetime, preventing thermal runaway-caused fires, and intelligent application are obstacles to their applications. Herein, bio-inspired electrodes owning spatiotemporal management of self-healing, fast ion transport, fire-extinguishing, thermoresponsive switching, recycling, and flexibility are overviewed comprehensively, showing great promising potentials in practical application due to the significantly enhanced durability and thermal safety of LIBs. Taking advantage of the self-healing core-shell structures, binders, capsules, or liquid metal alloys, these electrodes can maintain the mechanical integrity during the lithiation-delithiation cycling. After the incorporation of fire-extinguishing binders, current collectors, or capsules, flame retardants can be released spatiotemporally during thermal runaway to ensure safety. Thermoresponsive switching electrodes are also constructed though adding thermally responsive components, which can rapidly switch LIB off under abnormal conditions and resume their functions quickly when normal operating conditions return. Finally, the challenges of bio-inspired electrode designs are presented to optimize the spatiotemporal management of LIBs. It is anticipated that the proposed electrodes with spatiotemporal management will not only promote industrial application, but also strengthen the fundamental research of bionics in energy storage.

Flooding Length Mediates Fencing and Grazing Effects on Soil Respiration in Meadow Steppe.

Grassland management affects soil respiration (Rs, consists of heterotrophic respiration and autotrophic respiration) through soil micro-ecological processes, such as hydrothermal, plant root, organic carbon decomposition and microbial activity. Flooding, an irregular phenomenon in grasslands, may strongly regulate the response of soil respiration and its components to grassland management, but the regulatory mechanism remains unclear. We conducted a 3-year experiment by grassland management (fencing and grazing) and flooding conditions (no flooding (NF), short-term flooding (STF) and long-term flooding (LTF)) to study their effects on Rs and its components in a meadow steppe in the Hui River basin of Hulunbuir. We found differences in the patterns of Rs and its components under grassland management and flooding conditions. In 2021-2023, the temporal trends of Rs, heterotrophic respiration (Rh) and autotrophic respiration (Ra) were generally consistent, with peaks occurring on days 190-220, and the peaks of grazing were higher than that of fencing. In NF, Rs of grazed grassland was significantly higher than that of fenced grassland in 2021-2022 (p < 0.05). In STF and LTF, there was no significant difference in Rs between fenced and grazed grassland (p > 0.05). The dependence of Rs on soil temperature (ST) decreased with increasing flooding duration, and the dependence of Rs on ST of grazed grassland was higher than fenced grassland under NF and STF, but there was no difference between fenced grassland and grazed grassland under LTF. In addition, Rh was more sensitive to ST than Ra. This may be due to the different pathways of ST effects on Rs under grazing in different flooding conditions. Our study indicates that the effect of flooding on Rs is the key to the rational use of grassland under future climate change. To reduce regional carbon emissions, we recommend grazing on flooding grassland and fencing on no-flooding grassland.

Enhanced ·OH-Scavenging Activity of Cu-CeOx Nanozyme via Resurrecting Macrophage Nrf2 Transcriptional Activity Facilitates Diabetic Wound Healing.

Diabetic wounds are a prevalent and devastating complication of diabetes, which may impede their healing and regeneration. In diabetic wounds, excess reactive oxygen species (ROS) activate the nuclear factor kappa-B pathway, leading to transcriptional silencing of nuclear factor erythroid 2-related factor 2 (Nrf2), resulting in a vicious cycle of oxidative stress and inflammation. Conventional nanozymes have limitations in preventing the continuous production of ROS, including the most oxidizing reactive hydroxyl radical (·OH), although they can remove pre-existing ROS. Herein, a novel antioxidant nanoplatform addresses this challenge by incorporating JSH-23 into the mesoporous of cupric-doped cerium oxide nanozymes. Additionally, for rapid wound adaptability and durable tissue adhesion, a nanozyme hydrogel spray consisting of oxidized sodium alginate and methacrylate gelatin is constructed, named OG@CCJs. This platform resurrects Nrf2 transcriptional activity of macrophages in vitro, curbing the production of ROS at its source, particularly ·OH, while enabling the nanozymes to scavenge previously generated ROS. OG@CCJs significantly alleviate oxidative stress in diabetic wounds in vivo, promoting wound healing. Overall, the proposed nanozyme-hydrogel spray with enhanced ·OH-scavenging activity uses a "two-track" antioxidant strategy to rebuild the antioxidant defense barrier of macrophages. This pioneering approach highlights the tremendous potential of OG@CCJs for facilitating diabetic wound healing.

Nanocrystals Incorporated with Mordenite Zeolite Composites with Enhanced Upconversion Emission for Cu2+ Detection.

In this research, upconversion nanocrystals incorporated with MOR zeolite composites were synthesized using the desilicated MOR zeolite as a host for the in situ growth of NaREF4 (RE = Y, Gd) Yb/Er nanocrystals. The structure and morphology of the composites were studied with XRD, XPS, and TEM measurements, and the spectral studies indicated that the subsequent thermal treatment can effectively improve the upconversion emission intensity of Er3+. By using the NaYF4:Yb/Er@DSi1.0MOR-HT composite that holds the strongest upconversion emission, a probe of UCNC@DSiMOR/BPEI was constructed with the modification of branched poly ethylenimine for the detection of Cu2+. It was indicated that the integrated emission intensity of Er3+ shows a linear dependence with the logarithm value of the Cu2+ concentration ranging from 0.1 to 10 µM. This study offered a feasible method for the construction of UCNC@zeolite composites with enhanced upconversion emission, which may have a potential application as fluorescent probes for the detection of various metal ions by adjusting the doping luminescent center.

Recent progress in functional metal-organic frameworks for bio-medical application.

Metal-organic frameworks (MOFs) have a high specific surface area, adjustable pores and can be used to obtain functional porous materials with diverse and well-ordered structures through coordination and self-assembly, which has intrigued wide interest in a broad range of disciplines. In the arena of biomedical engineering, the functionalized modification of MOFs has produced drug carriers with excellent dispersion and functionalities such as target delivery and response release, with promising applications in bio-detection, disease therapy, tissue healing, and other areas. This review summarizes the present state of research on the functionalization of MOFs by physical binding or chemical cross-linking of small molecules, polymers, biomacromolecules, and hydrogels and evaluates the role and approach of MOFs functionalization in boosting the reactivity of materials. On this basis, research on the application of functionalized MOFs composites in biomedical engineering fields such as drug delivery, tissue repair, disease treatment, bio-detection and imaging is surveyed, and the development trend and application prospects of functionalized MOFs as an important new class of biomedical materials in the biomedical field are anticipated, which may provide some inspiration and reference for further development of MOF for bio-medical applications.

Nerve growth factor (Ngf) gene-driven semaphorin 3a (Sema3a) expression exacerbates thoracic aortic aneurysm dissection in mice.

Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening disease and currently there is no pharmacological therapy. Sympathetic nerve overactivity plays an important role in the development of TAAD. Sympathetic innervation is mainly controlled by nerve growth factor (NGF, a key neural chemoattractant) and semaphoring 3A (Sema3A, a key neural chemorepellent), while the roles of these two factors in aortic sympathetic innervation and especially TAAD are unknown. We hypothesized that genetically manipulating the NGF/Sema3A ratio by the Ngf -driven Sema3a expression approach may reduce aortic sympathetic nerve innervation and mitigate TAAD progression. A mouse strain of Ngf gene-driven Sema3a expression (namely NgfSema3a/Sema3a mouse) was established by inserting the 2A-Sema3A expression frame to the Ngf terminating codon using CRISPR/Cas9 technology. TAAD was induced by ß-aminopropionitrile monofumarate (BAPN) both in NgfSema3a/Sema3a mice and wild type (WT) littermates. Contrary to our expectation, the BAPN-induced TAAD was severer in NgfSema3a/Sema3a mice than in wild-type (WT) mice. In addition, NgfSema3a/Sema3a mice showed higher aortic sympathetic innervation, inflammation and extracellular matrix degradation than the WT mice after BAPN treatment. The aortic vascular smooth muscle cells isolated from NgfSema3a/Sema3a mice and pretreated with BAPN in vivo for two weeks showed stronger capabilities of proliferation and migration than that from the WT mice. We conclude that the strategy of Ngf -driven Sema3a expression cannot suppress but worsens the BAPN-induced TAAD. By investigating the aortic phenotype of NgfSema3a/Sema3a mouse strain, we unexpectedly find a path to exacerbate BAPN-induced TAAD which might be useful in future TAAD studies.

Corrigendum to "Crystal structure of RNA helicase from Saint Louis encephalitis virus and discovery of its inhibitors" [Genes Dis 10 (2023) 389-392].

[This corrects the article DOI: 10.1016/j.gendis.2022.07.001.].

Endoplasmic reticulum stress caused by traumatic injury promotes cardiomyocyte apoptosis through acetylation modification of GRP78.

Cardiomyocyte apoptosis is an important cause of trauma-induced secondary cardiac injury (TISCI), in which the endoplasmic reticulum stress (ERS)-mediated apoptosis signaling pathway is known to be first activated, but the mechanism remains unclear. In this study, rat models of traumatic injury are established by using the Noble-Collip trauma device. The expression of glucose-regulating protein 78 (GRP78, a molecular chaperone of the cardiomyocyte ER), acetylation modification of GRP78 and apoptosis of cardiomyocytes are determined. The results show that ERS-induced GRP78 elevation does not induce cardiomyocyte apoptosis in the early stage of trauma. However, with prolonged ERS, the GRP78 acetylation level is elevated, and the apoptosis of cardiomyocytes also increases significantly. In addition, in the early stage of trauma, the expression of histone acetyl-transferase (HAT) P300 is increased and that of histone deacetylase 6 (HDAC6) is decreased in cardiomyocytes. Inhibition of HDAC function could induce the apoptosis of traumatic cardiomyocytes by increasing the acetylation level of GRP78. Our present study demonstrates for the first time that post-traumatic protracted ERS can promote cardiomyocyte apoptosis by increasing the acetylation level of GRP78, which may provide an experimental basis for seeking early molecular events of TISCI.

Inorganic Polysulfide Chemistries for Better Energy Storage Systems.

ConspectusSulfur-based cathode materials have become a research hot spot as one of the most promising candidates for next-generation, high-energy lithium batteries. However, the insulating nature of elemental sulfur or organosulfides has become the biggest challenge that leads to dramatic degradation and hinders their practical application. The disadvantage is more obvious for all-solid-state battery systems, which require both high electronic and ionic migration at the same sites to realize a complete electrochemical reaction. In addition to adding conductive components into the cathode composites, another effective way to realize high-reversibility sulfur-based cathodes is by optimizing the inherent nature of sulfur-based materials to make them "conductive". Inorganic polysulfide materials including polysulfide molecules, selenium-sulfur solid solutions, and (lithium) metal polysulfides are promising, as they have different structures that can make them intrinsically conductive or becoming conductive during lithiation. They all contain at least one -S-S- bridged bond, which is the intrinsic structural characteristic and the source of the chemical properties of these polysulfide compounds. For example, by balancing the conductivity and reversible capacity, researchers in the US National Aeronautics and Space Administration (NASA) have shown that 500 Wh/kg solid-state Li-Se/S batteries can power cars and even electric aircraft.We have long been focusing on the inorganic polysulfide component, reported the selenium-sulfur solid solutions, the first sulfur-rich phosphorus polysulfide molecules, and followed the research of metal polysulfide components. The proposed Account summarizes our current knowledge of the fundamental aspects of inorganic polysulfides in energy storage systems based on state-of-the-art publications on this topic. Both fast electron and ion migrations within the electrode materials are vital to achieving high-energy batteries. We begin by illustrating effective approaches to enhance the electronic/ionic conductivity of sulfur-based electrode materials. We then present some basic observations and properties (especially the intrinsic high conductivities) of the inorganic polysulfide electrode materials. The key chemical and structural factors dictating their conductive and electrochemical behaviors will be discussed. Finally, we show the advantages and broad applications of inorganic polysulfides in energy storage areas. The proposed Account will provide an insightful perspective on the current knowledge of inorganic polysulfide materials, as well as their future research directions and development potential, serving as a keynote reference for researchers in the field of energy storage.

Synaptotagmin 1 Suppresses Colorectal Cancer Metastasis by Inhibiting ERK/MAPK Signaling-Mediated Tumor Cell Pseudopodial Formation and Migration.

Although synaptotagmin 1 (SYT1) has been identified participating in a variety of cancers, its role in colorectal cancer (CRC) remains an enigma. This study aimed to demonstrate the effect of SYT1 on CRC metastasis and the underlying mechanism. We first found that SYT1 expressions in CRC tissues were lower than in normal colorectal tissues from the CRC database and collected CRC patients. In addition to this, SYT1 expression was also lower in CRC cell lines than in the normal colorectal cell line. SYT1 expression was downregulated by TGF-ß (an EMT mediator) in CRC cell lines. In vitro, SYT1 overexpression repressed pseudopodial formation and reduced cell migration and invasion of CRC cells. SYT1 overexpression also suppressed CRC metastasis in tumor-bearing nude mice in vivo. Moreover, SYT1 overexpression promoted the dephosphorylation of ERK1/2 and downregulated the expressions of Slug and Vimentin, two proteins tightly associated with EMT in tumor metastasis. In conclusion, SYT1 expression is downregulated in CRC. Overexpression of SYT1 suppresses CRC cell migration, invasion, and metastasis by inhibiting ERK/MAPK signaling-mediated CRC cell pseudopodial formation. The study suggests that SYT1 is a suppressor of CRC and may have the potential to be a therapeutic target for CRC.

Crystal structure of mRNA cap (guanine-N7) methyltransferase E12 subunit from monkeypox virus and discovery of its inhibitors.

In July 2022, the World Health Organization announced monkeypox as a public health emergency of international concern (PHEIC), and over 85,000 global cases have been reported currently. However, preventive and therapeutic treatments for the monkeypox virus (MPXV) remain limited. MPXV mRNA cap N7 methyltransferase (MTase) is composed of two subunits (E1 C-terminal domain (E1CTD) and E12) which are essential for the replication of MPXV. Here, we solved a 2.16 Å crystal structure of E12. We also docked the D1CTD of the vaccinia virus (VACV) corresponding to the E1CTD in MPXV with E12 and found critical residues at their interface. These residues were further used for drug screening. After virtual screening, the top 347 compounds were screened out and a list of top 20 potential MPXV E12 inhibitors were discovered, including Rutin, Quercitrin, Epigallocatechin, Rosuvastatin, 5-hydroxy-L-Tryptophan, and Deferasirox, etc., which were potential E12 inhibitors. Taking the advantage of the previously unrecognized special structure of MPXV MTase composing of E1CTD and E12 heterodimer, we screened for inhibitors targeting MTase for the first time based on the interface between the heterodimer of MPXV MTase. Our study may provide insights into the development of anti-MPXV drugs.

Identification, structural, and biophysical characterization of a positive modulator of human Kv3.1 channels.

Voltage-gated potassium channels (Kv) are tetrameric membrane proteins that provide a highly selective pathway for potassium ions (K+) to diffuse across a hydrophobic cell membrane. These unique voltage-gated cation channels detect changes in membrane potential and, upon activation, help to return the depolarized cell to a resting state during the repolarization stage of each action potential. The Kv3 family of potassium channels is characterized by a high activation potential and rapid kinetics, which play a crucial role for the fast-spiking neuronal phenotype. Mutations in the Kv3.1 channel have been shown to have implications in various neurological diseases like epilepsy and Alzheimer's disease. Moreover, disruptions in neuronal circuitry involving Kv3.1 have been correlated with negative symptoms of schizophrenia. Here, we report the discovery of a novel positive modulator of Kv3.1, investigate its biophysical properties, and determine the cryo-EM structure of the compound in complex with Kv3.1. Structural analysis reveals the molecular determinants of positive modulation in Kv3.1 channels by this class of compounds and provides additional opportunities for rational drug design for the treatment of associated neurological disorders.

Hypoxic Microenvironment Reconstruction with Synergistic Biofunctional Ions Promotes Diabetic Wound Healing.

Chronic hypoxia and ischemia make diabetic wounds non-healing. Cellular functions of diabetic chronic wounds are inhibited under a pathological environment. Therefore, this work develops a composite hydrogel system to promote diabetic wound healing. The composite hydrogel system consists of ε-poly-lysine (EPL), calcium peroxide (CP), and borosilicate glass (BG). The hydrogel supplies continuous dissolved oxygen molecules to the wound that can penetrate the skin tissue to restore normal cellular function and promote vascular regeneration. Biofunctional ions released from BGs can recruit more macrophages through neovascularization and modulate macrophage phenotypic transformation. Combining oxygen-mediated vascular regeneration and ion-mediated inflammatory regulation significantly accelerated diabetic wound healing. These findings indicate that this composite hydrogel system holds promise as a novel tissue engineering material.

Expression signature and prognostic value of CREC gene family in human colorectal cancer.

Colorectal cancer (CRC) is one of the malignant tumors with the highest morbidity and mortality and poor prognosis. The mammalian gene family of Cab45/reticulocalbin/ERC-45/calumenin (CREC) consists of RCN1, RCN2, RCN3, SDF4 and CALU. Although CREC family members have been associated with CRC, the expression pattern, prognostic value, and the role of CREC family in CRC remain unclear. In this study, the expression, survival and biological functions of CREC family in CRC were determined via bioinformatic datasets analysis and experimental verification on clinical CRC specimen. Bioinformatic analysis showed that the expression levels of most CREC family genes were higher in CRC tissues than in normal colorectal tissues. The qPCR and western blot results also revealed that the transcriptional and protein levels of CREC family were elevated in CRC tissues compared with adjacent tissues. Besides, CREC family was significantly correlated with advanced tumor stage and poor prognosis of CRC patients. The expression levels of CREC family had correlations with genomic mutation and methylation, and with the infiltration levels of CD4 + T cells, macrophages, neutrophils, and dendritic cells in the microenvironment of CRC. Functional networks enrichment analysis indicated that the genes of CREC family were essential factors for CRC metastasis. Collectively, these findings suggest that CREC family might be potential targets for the treatment of CRC and candidate prognostic markers for CRC patients.