Protein disulfide isomerase family member 4 promotes triple-negative breast cancer tumorigenesis and radiotherapy resistance through JNK pathway.

BACKGROUND: Despite radiotherapy ability to significantly improve treatment outcomes and survival in triple-negative breast cancer (TNBC) patients, acquired resistance to radiotherapy poses a serious clinical challenge. Protein disulfide isomerase exists in endoplasmic reticulum and plays an important role in promoting protein folding and post-translational modification. However, little is known about the role of protein disulfide isomerase family member 4 (PDIA4) in TNBC, especially in the context of radiotherapy resistance. METHODS: We detected the presence of PDIA4 in TNBC tissues and paracancerous tissues, then examined the proliferation and apoptosis of TNBC cells with/without radiotherapy. As part of the validation process, xenograft tumor mouse model was used. Mass spectrometry and western blot analysis were used to identify PDIA4-mediated molecular signaling pathway. RESULTS: Based on paired clinical specimens of TNBC patients, we found that PDIA4 expression was significantly higher in tumor tissues compared to adjacent normal tissues. In vitro, PDIA4 knockdown not only increased apoptosis of tumor cells with/without radiotherapy, but also decreased the ability of proliferation. In contrast, overexpression of PDIA4 induced the opposite effects on apoptosis and proliferation. According to Co-IP/MS results, PDIA4 prevented Tax1 binding protein 1 (TAX1BP1) degradation by binding to TAX1BP1, which inhibited c-Jun N-terminal kinase (JNK) activation. Moreover, PDIA4 knockdown suppressed tumor growth xenograft model in vivo, which was accompanied by an increase in apoptosis and promoted tumor growth inhibition after radiotherapy. CONCLUSIONS: The results of this study indicate that PDIA4 is an oncoprotein that promotes TNBC progression, and targeted therapy may represent a new and effective anti-tumor strategy, especially for patients with radiotherapy resistance.

Manipulating 2D Membrane Interlayer Channels with Accelerated Mass-Transfer Behavior to Boost Solar Desalination.

The scarcity of fresh water necessitates sustainable and efficient water desalination strategies. Solar-driven steam generation (SSG), which employs solar energy for water evaporation, has emerged as a promising approach. Graphene oxide (GO)-based membranes possess advantages like capillary action and Marangoni effect, but their stacking defects and dead zones of flexible flakes hinders efficient water transportation, thus the evaporation rate lag behind unobstructed-porous 3D evaporators. Therefore, fundamental mass-transfer approach for optimizing SSG evaporators offers new horizons. Herein, a universal multi-force-fields-based method is presented to regularize membrane channels, which can mechanically eliminate inherent interlayer stackings and defects. Both characterization and simulation demonstrate the effectiveness of this approach across different scales and explain the intrinsic mechanism of mass-transfer enhancement. When combined with a structurally optimized substrate, the 4Laponite@GO-1 achieves evaporation rate of 2.782 kg m-2 h-1 with 94.48% evaporation efficiency, which is comparable with most 3D evaporators. Moreover, the optimized membrane exhibits excellent cycling stability (10 days) and tolerance to extreme conditions (pH 1-14, salinity 1%-15%), verifies the robust structural stability of regularized channels. This optimization strategy provides simple but efficient way to enhance the SSG performance of GO-based membranes, facilitating their extensive application in sustainable water purification technologies.

Comparison of the dimensional and morphological accuracy of three-dimensional digital dental casts digitized using different methods.

The purpose of this study was to compare the accuracy of digital dental casts from plaster cast scanning (PCS), impression scanning (IPS), intraoral scanning (IOS), and cone-beam computed tomography (CBCT) scanning (CCS) methods. The maxillary and mandibular dental casts of 15 patients who needed CBCT scans for oral examination or treatment were digitized via four methods. 12 linear distance measurements of all digital dental casts were selected and acquired with software and compared to those of the reference plaster cast to evaluate the dimensional accuracy. Three-dimensional deviation analysis of the IPS, IOS and CCS groups with respect to the reference PCS group was performed to evaluate the morphological accuracy. The discrepancy in linear distances between the digital dental casts and reference plaster casts was statistically significant (p < 0.01). The dimensional accuracies of the PCS (0.06 ± 0.12 mm) and IPS (0.03 ± 0.05 mm) casts were better than those of the IOS (0.37 ± 0.30 mm) and CCS (0.54 ± 0.40 mm) casts. The one-sample t test showed that there were statistically significant differences between the discrepancies in 8 of the linear distances for the PCS group and 9 of the linear distances for the IPS group between the digital dental casts and reference plaster casts, with an ideal error of 0.00 (p < 0.05). The sequence of morphological accuracy from good to poor was maxillary and mandibular IPS, mandibular IOS; maxillary IOS; and maxillary and mandibular CCS. The accuracy of the digital dental casts from the PCS and IPS methods was greater than that of IOS and CCS methods. Although accuracy of the digital dental cast from IOS was low, it satisfied the clinical requirements for fixed restorations in small units. The accuracy of the digital dental cast from CCS was poorest and could only be used for procedures with lower accuracy requirements.

Comparison of the accuracy (trueness and precision) of virtual dentofacial patients digitized by three different methods based on 3D facial and dental images.

STATEMENT OF PROBLEM: The accuracy of virtual dentofacial patients has been explored, but the accuracy of virtual patients established by using a straightforward and reliable method and the accuracy of different virtual patients are unclear. PURPOSE: The purpose of this clinical study was to compare the accuracy of virtual dentofacial patients digitized by using registered-block impression, exposed anterior teeth, and cone beam computed tomography (CBCT) reconstruction methods based on 3-dimensional (3D) facial and dental images. MATERIAL AND METHODS: From the 15 selected participants who needed CBCT scanning, 3 kinds of virtual dentofacial patients were established by using 3 registration methods based on digital dental casts: 3D facial images, CBCT data, and registered-block impression. Compared with actual measurement, 25 linear distances of all virtual dentofacial patients were selected and measured by using a software program, and 3 separate measurements were calculated by the same person. The 1-way analysis of variance (ANOVA) was used to compare the deviations among 3 kinds of virtual dentofacial patients (trueness) and the deviations within groups (precision). The 1-sample t test was used to compare the difference between the deviation and the ideal error of 0.00 (α=.05). RESULTS: Compared with the actual measurement, the trueness of the average deviations for registered-block impression (1.02 ±1.24 mm) was better than that of exposed anterior teeth (2.35 ±1.71 mm) and CBCT reconstruction (2.86 ±1.61 mm). The precision of the average deviations for registered-block impression (1.29 ±1.43 mm) was better than that of exposed anterior teeth (2.00 ±1.72 mm) and CBCT reconstruction (2.12 ±1.94 mm). Significant differences in trueness and precision were found among the 3 groups of virtual dentofacial patients (P<.01). Significant differences among the deviations of all linear distances and the ideal error of 0.00 were observed for all groups of virtual dentofacial patients (P<.05). CONCLUSIONS: The accuracy of registered-block impression was better than that of the exposed anterior teeth and CBCT reconstruction. The accuracy of exposed anterior teeth was lower than that of the other methods but could satisfy the requirements of clinical diagnostics and scientific methods. The accuracy of CBCT reconstruction was poor and could only be used for special situations that permitted low accuracy.

KIF15 promotes the evolution of gastric cancer cells through inhibition of reactive oxygen species-mediated apoptosis.

Kinesin family member 15 (KIF15) is a member of the kinesin superfamily of proteins, which promotes cell mitosis, participates in the transport of intracellular materials, and helps structural assembly and cell signaling pathways transduction. However, its biological role and molecular mechanisms of action in the development of gastric cancer (GC) remain unclear. In the present study, an integrated analysis of The Cancer Genome Atlas (TCGA), Gene Expression Omnibus database, and Kaplan-Meier plotter database was performed to predict the expression and prognostic value of KIF15 in GC patients. Detection of KIF15 expression in GC cells and tissues was performed by a quantitative polymerase chain reaction. In vitro cell proliferation, viability, colony formation ability and flow cytometry assays, and in vivo tumorigenicity assay, were performed to evaluate the effects of KIF15 knockdown on GC cell phenotype. It was demonstrated that the expression of KIF15 messenger RNA in GC tissues was significantly higher compared with that in adjacent tissues, and was closely associated with larger tumor size and poor patient prognosis. In addition, functional studies demonstrated that, due to the increase in reactive oxygen species (ROS) generation, the interference with the expression of KIF15 not only decreased cell proliferation but also increased cell apoptosis and induced cell cycle arrest. ROS-mediated activation of c-Jun N-terminal kinase/c-Jun signaling reduced cell proliferation by regulating the GC cell cycle and increasing apoptosis. Taken together, the results of the present study indicate that KIF15 is an oncoprotein contributing to GC progression, and is expected to help identify novel biomarkers and treatment targets in GC.

Synthesis and Catalytic Properties of Porous Metal Silica Materials Templated and Functionalized by Extended Coordination Cages.

A practically applicable strategy is developed to rationally immobilize easily accessed and highly dispersed redox-active metal oxides into porous metal silica (PMS) materials templated and functionalized by porous metal-ligand moieties. On the basis of this strategy, the highly active porous catalyst PMS-1 is successfully targeted for aerobic oxidation of cyclohexane with conversion up to 14.6%, which is much superior to the current industrially adopted catalysts (less than 4% cyclohexane conversion) that use harsh conditions. This promising approach to explore highly active heterogeneous catalysts for inert C-H bond activation should lead to the further discovery of numerous industrially useful catalysts for the oxidation of inert hydrocarbon raw materials.

Facile Fluorescence Dopamine Detection Strategy Based on Acid Phosphatase (ACP) Enzymatic Oxidation Dopamine to Polydopamine.

Facile and effective detection of dopamine (DA) plays a significant role in current clinical applications. Substantially, special optical nanomaterials are important for fabricating easy-to-control, cheap, selective, and portable fluorescence DA sensors with superior performance. Herein, carbon dots (CDs) prepared from melting method were applied as signal to establish a simple but effective fluorescence strategy for DA determination based on the enzymatic activity of acid phosphatase (ACP), which induces DA to form polydopamine (pDA). The formed pDA caused by the enzymatic oxidization of ACP toward DA can interact with CDs through the inner filter effect. Such behavior effectively quenched the CDs' fluorescence. The degree of fluorescence quenching of CDs was positively correlated with the DA content. Under the optimized reaction conditions, the proposed fluorescence method exhibited a comparable analytical performance with other DA sensors with good selectivity. Furthermore, this method has been successfully applied to detect DA in DA hydrochloride injection and human serum samples. It shows that this method features potential practical application value and is expected to be used in clinical research.

A novel small-molecule compound disrupts influenza A virus PB2 cap-binding and inhibits viral replication.

OBJECTIVES: The conserved residues 318-483 in the PB2 subunit of influenza A polymerase is an independently folded cap-binding domain (PB2cap) that exhibits a distinct binding mode from other host cap-binding proteins, which suggests that PB2cap might be an ideal drug target. This study aimed to identify a new class of anti-influenza inhibitors that specifically disrupts the interaction between PB2cap and host cap structures. METHODS: An innovative fluorescence polarization assay was established for primary screening, followed by cap-binding inhibitory activity, antiviral efficacy and cytotoxicity evaluations of the selected compounds. The best compound was characterized by multi-cycle virus growth assay, cross-protection test, synergism evaluation, mini-replicon assay, binding affinity analysis, docking simulation and mouse study. RESULTS: Several PB2 cap-binding inhibitors were discovered. The compound 7-(4-hydroxy-2-oxo-2H-chromen-3-yl)-6H,7H,8H-chromeno[3',4':5,6]pyrano[3,2-c]chromene-6,8-dione, designated PB2-39, was identified as a potent inhibitor of replication of multiple subtypes of influenza A virus, including H1N1, H3N2, H5N1, H7N7, H7N9 and H9N2 in vitro and H1N1, H5N1 and H7N9 in vivo. Combinational treatment with the influenza virus release inhibitor zanamivir and PB2-39 exerted a synergistic anti-influenza effect. Mechanistic experiments supported that PB2-39 suppressed viral polymerase activity. Docking and binding affinity analyses demonstrated that PB2-39 interacted with the PB2 cap-binding pocket, suggesting its role as a cap-binding competitor. CONCLUSIONS: Our study provides new insights for the strategic development of novel cap-binding inhibitors of influenza A viruses.

Epidemic status of Swine influenza virus in china.

As one of the most significant swine diseases, in recent years, swine influenza (SI) has had an immense impact on public health and has raised extensive public concerns in China. Swine are predisposed to both avian and human influenza virus infections, between that and/or swine influenza viruses, genetic reassortment could occur. This analysis aims at introducing the history of swine influenza virus, the serological epidemiology of swine influenza virus infection, the clinical details of swine influenza, the development of vaccines against swine influenza and controlling the situation of swine influenza in China. Considering the elaborate nature of swine influenza, a more methodical surveillance should be further implemented.

An "all-in-one" treatment and imaging nanoplatform for breast cancer with photothermal nanoparticles.

Drug delivery systems based on nanoparticles still face challenges of low efficacy and an inability to track treatment effects in tumor therapy due to biological barriers. This limitation hinders clinicians' ability to determine treatment effects and proper drug dosages, thus, ultimately impeding the further application and transformation of nanoplatforms. To address this challenge, an all-in-one nanoplatform for therapy and imaging is proposed. The nanoplatform is constructed by using nanoparticles through the co-encapsulation of the photothermal therapeutic agent IR780, the passively targeted drug OA@Fe3O4, and the chemotherapeutic drug paclitaxel. Under the guidance of magnetic navigation, the nanoparticles can enhance local enrichment of the drug, while the luminescence properties of IR780 enable drug tracking at the same time. Remarkably, the nanoparticles exhibit improved photothermal-chemotherapy synergy under magnetic targeting guidance, demonstrating antitumor effects in both in vitro and in vivo experiments. It is demonstrated that the use of these polymeric nanoparticles has significant potential for future biomedical applications and clinical decisions.

Precision targeting of CuET overload to disrupt mitochondrial unfolded protein response by integrated liposome.

Mitochondria in breast cancer play a critical role in survival and adaptation to dynamic environments. Thus, targeting mitochondria emerges as a promising therapeutic strategy for breast cancer. However, the adaptive unfolded protein response in mitochondria (UPRmt) due to mitochondrial unspecific distribution might contribute to diminished therapeutic outcomes. Herein, mitochondrial targeting liposome agents (CTPP-Lipid) are constructed and adopted for delivering the copper ion (CuET-DSF), which is especially sensitive for mitochondria-abundant breast tumors. In brief, the CTPP-Lipid@CuET achieves the goal of Cu2+ overloading by mitochondria targeting delivery. This rapidly increases ROS production, disrupts mitochondrial structure, and avoids the adaptive UPRmt formation, finally leading to apoptosis of breast cancer cells. In general, the Cu2+ overloading at mitochondria by CTPP-Lipid@CuET is a potential strategy for antitumor therapy, providing new insights into breast tumor therapy.

Genetic characterization of IncI2 plasmids carrying blaCTX-M-55 spreading in both pets and food animals in China.

pHN1122-1 carrying bla(CTX-M-55), from an Escherichia coli isolate from a dog, was completely sequenced. pHN1122-1 has an IncI2 replicon and typical IncI2-associated genetic modules, including mok/hok-finO-yafA/B, nikABC, and two transfer regions, tra and pil, as well as a shufflon. bla(CTX-M-55) is found within a 3.084-kb ISEcp1 transposition unit that includes a fragment of IncA/C plasmid backbone. pHN1122-1 and closely related plasmids were identified in other E. coli isolates from animals in China.

Genetic characterization of avian-origin H3N2 canine influenza viruses isolated from Guangdong during 2006-2012.

Canine influenza virus (CIV) is an emerging pathogen that causes severe and acute respiratory disease in dogs. In 2006, the H3N2 canine influenza virus was first identified in dogs from Guangdong province in China. Up to now, nine CIVs have been isolated from different populations in Guangdong. The nine isolates were grouped together with the canine H3N2 viruses isolated from dogs and felines in Korea, when the eight phylogenetic trees constructed were compared. These findings emphasize the importance of CIV surveillance in this region for understanding the genesis of this virus, and it is important to remain aware of the potential of H3N2 CIV to be transmitted from dogs to the human population.

Ankle biomechanics of the three-step layup in a basketball player with chronic ankle instability.

At present, the effects of chronic ankle instability (CAI) on the biomechanics of the ankle joint in the three-step layup of basketball players are not clear. This work aims to thoroughly investigate the impact of CAI on the biomechanical characteristics of the ankle during the execution of a three-step layup in basketball players. Thirty male basketball players were stratified into distinct groups-namely, a CAI group and a non-CAI group-comprising 15 individuals each, based on the presence or absence of CAI. Demographic attributes, including age, weight, height, and the Cumberland Ankle Instability Tool (CAIT) score, were subjected to rigorous statistical examination within both athlete cohorts. The research employed four Whistler 9281CA 3D force measuring platforms (Switzerland), recording at 1000 Hz, in conjunction with eight camera motion analysis systems (USA), functioning at a frequency of 200 Hz. The study recorded maximal plantarflexion angle, inversion angle, dorsiflexion angle, and peak ankle dorsiflexion moment across the subjects during the distinct phases of push-off, landing, and the ensuing landing period. The findings notably exhibited that within the context of the one-foot push-off phase, the maximum ankle inversion angle was notably diminished in the CAI group as contrasted with the non-CAI group, demonstrating statistical significance (t = - 3.006, P < 0.01). The CAI group exhibited a lesser alteration in ankle inversion angle compared to the non-CAI group. Notably, during the one-foot landing period, the CAI group demonstrated a significantly greater maximum ankle inversion angle in contrast to the non-CAI group (t = 8.802, P < 0.001). Furthermore, the CAI group displayed a substantially larger maximum dorsiflexion angle at the ankle joint compared to the non-CAI group (t = 2.265, P < 0.05). Additionally, the CAI group exhibited a prolonged peak time for ankle dorsiflexion moment as compared to the non-CAI group (t = - 2.428, P < 0.05). Collectively, the findings elucidated a reduction in the maximum ankle joint inversion angle during the one-foot push-off phase in individuals with CAI. Furthermore, increased maximum inversion angle and maximum dorsiflexion angle of the ankle joint were observed during the one-foot landing period, alongside a lengthening of the peak time of ankle dorsiflexion moment. These results contribute valuable insights into the selection of training methodologies for basketball players afflicted by CAI.

[Effectiveness of TiRobot-assisted and free-hand percutaneous kyphoplasty via pedicle of vertebra in treatment of osteoporotic vertebral compression fracture of thoracic vertebra].

Objective: To compare the effectiveness of TiRobot-assisted and C-arm X-ray fluoroscopy assisted percutaneous kyphoplasty (PKP) via pedicle of vertebra in the treatment of osteoporotic vertebral compression fracture (OVCF) of thoracic vertebrae. Methods: The clinical data of 85 patients with OVCF of thoracic vertebrae who were admitted between January 2020 and March 2023 and met the selection criteria was retrospectively analyzed including 40 patients (50 vertebrae) undergoing PKP assisted by TiRobot (group A) and 45 patients (50 vertebrae) undergoing PKP assisted by C-arm X-ray fluoroscopy (group B). There was no significant difference in the comparison of baseline data such as gender, age, body mass index, bone mineral density T-value, fracture segment, trauma history, and preoperative numerical rating scale (NRS) score, Oswestry disability index (ODI), and Cobb angle of injured vertebra between the two groups ( P>0.05). The effectiveness evaluation indexes of the two groups, including the operation time, the volume of injected cement, the times of fluoroscopies, the length of hospital stay, and the occurrence of postoperative complications were collected and compared. Anteroposterior and lateral X-ray films and CT of the injured vertebra were reviewed at 1 day after operation to observe whether there was cement leakage and to evaluate the distribution of cement in the injured vertebra. Before and after operation, pain was assessed using the NRS score, dysfunction was assessed using the ODI, and vertebral height recovery was assessed by measuring the Cobb angle of the injured vertebrae by X-ray films. Results: Both groups of patients successfully completed the operation, the operation time, the volume of injected cement, the times of fluoroscopies, and the length of hospital stay in group A were significantly less than those in group B ( P<0.05). The patients in two groups were followed up 4-12 months (mean, 9.6 months). Bone cement leakage occurred in 5 vertebrae in group A and 15 vertebrae in group B after operation, all of which leaked to the intervertebral space and around the vertebral body, and the patients had no obvious clinical symptoms. The difference of bone cement leakage between the two groups was significant ( P<0.05). No severe complication such as intraspinal leakage, infection, or vascular embolism was found in the two groups. At 1 day after operation, the distribution index of bone cement in group A was mostly grade Ⅴ, which was well dispersed; while in group B, it was mostly grade Ⅱ and grade Ⅴ; the difference of bone cement distribution index between the two groups was significant ( P<0.05). The NRS score, ODI, and Cobb angle of injured vertebra in both groups were significantly improved at 1 day after operation when compared with preoperative ones ( P<0.05). There was no significant difference in the difference of the above indexes between the two groups before and after operation ( P>0.05). Conclusion: TiRobot-assisted unilateral PKP in the treatment of OVCF of thoracic vertebrae is safe and effective, which can reduce the X-ray transmission times during operation, shorten the operation time, reduce the volume of bone cement injection, and thus decrease incidence of bone cement leakage.

Loss of erm(B)-Mediated rRNA Dimethylation and Restoration of Erythromycin Susceptibility in Erythromycin-Resistant Enterococci Following Induced Linezolid Resistance.

Linezolid has been reported to restore erythromycin susceptibility in erythromycin-resistant Staphylococcus aureus. This phenomenon has not been reported in enterococci and the mechanisms involved therein are still unknown. The purpose of this study was to investigate the mechanisms involved and the effect of combining linezolid with erythromycin on erythromycin-resistant enterococci. Checkerboard techniques were used to determine drug interactions, and 12 of 14 isolates showed a synergistic effect between erythromycin and linezolid (fractional inhibitory concentration <0.5). We observed that the erm(B) gene, which encodes a dimethyltransferase responsible for erythromycin resistance, was expressed from transposon Tn1545 in the tested erythromycin-resistant enterococci. After exposure to linezolid, erm(B)-mediated rRNA dimethylation at A2071 could not be detected, and the erm(B) gene was lost following acquisition of erythromycin susceptibility. Thus, in conclusion, linezolid combined with erythromycin exerts a synergistic effect against erythromycin-resistant enterococci. Linezolid treatment suppressed erm(B)-mediated rRNA dimethylation at A2071, which could lead to loss of the erm(B) gene.

Thyroid endocrine disruption and neurotoxicity of gestodene in adult female mosquitofish (Gambusia affinis).

The frequent detection of progestins in various aquatic environments and their potential endocrine disruptive effects in fish have attracted increasing attention worldwide. However, data on their effects on thyroid function and neurotoxicity in fish are limited, and the underlying mechanisms remain unclear. Here, the effects of gestodene (GES, a common progestin) on the thyroid endocrine and nervous systems of mosquitofish (Gambusia affinis) were studied. Adult female fish were exposed to GES at environmentally relevant concentrations (4.4-378.7 ng/L) for 60 days. The results showed that exposure to 378.7 ng/L GES caused a significant decrease in fish growth compared with the control and a marked reduction in the total distance traveled (50.6%) and swimming velocity (40.1-61.9%). The triiodothyronine (T3) levels were significantly increased by GES in a dose-dependent manner, whereas those of tetraiodothyronine (T4) were significantly decreased only at the G500 concentration. The acetylcholinesterase (AChE) activity was decreased significantly in the 4.42 ng/L GES treatments, but increased significantly at 378.67 ng/L. In the brain, a strong increase in the transcriptional levels of bdnf, trh, and dio2 was observed in fish after the 378.7 ng/L treatment. In addition, chronic exposure to GES caused colloid depletion with a concentration-dependent manner in the thyroid, and angiectasis, congestion, and vacuolar necrosis in the brain. These findings provide a better understanding of the effects of GES and associated underlying mechanisms in G. affinis.

A shear-thinning, ROS-scavenging hydrogel combined with dental pulp stem cells promotes spinal cord repair by inhibiting ferroptosis.

Spinal cord injury (SCI) is a serious clinical disease. Due to the deformability and fragility of the spinal cord, overly rigid hydrogels cannot be used to treat SCI. Hence, we used TPA and Laponite to develop a hydrogel with shear-thinning ability. This hydrogel exhibits good deformation, allowing it to match the physical properties of the spinal cord; additionally, this hydrogel scavenges ROS well, allowing it to inhibit the lipid peroxidation caused by ferroptosis. According to the in vivo studies, the TPA@Laponite hydrogel could synergistically inhibit ferroptosis by improving vascular function and regulating iron metabolism. In addition, dental pulp stem cells (DPSCs) were introduced into the TPA@Laponite hydrogel to regulate the ratios of excitatory and inhibitory synapses. It was shown that this combination biomaterial effectively reduced muscle spasms and promoted recovery from SCI.

Stabilization of IGF2BP1 by USP10 promotes breast cancer metastasis via CPT1A in an m6A-dependent manner.

Metastasis leads to the vast majority of breast cancer mortality. Increasing evidence has shown that N6-methyladenosine (m6A) modification and its associated regulators play a pivotal role in breast cancer metastasis. Here, we showed that overexpression of the m6A reader IGF2BP1 was clinically correlated with metastasis in breast cancer patients. Moreover, IGF2BP1 promoted distant metastasis in vitro and in vivo. Mechanistically, we first identified USP10 as the IGF2BP1 deubiquitinase. USP10 can bind to, deubiquitinate, and stabilize IGF2BP1, resulting in its higher expression level in breast cancer. Furthermore, by MeRIP-seq and experimental verification, we found that IGF2BP1 directly recognized and bound to the m6A sites on CPT1A mRNA and enhanced its stability, which ultimately mediated IGF2BP1-induced breast cancer metastasis. In clinical samples, USP10 levels correlated with IGF2BP1 and CPT1A levels, and breast cancer patients with high levels of USP10, IGF2BP1, and CPT1A had the worst outcome. Therefore, these findings suggest that the USP10/IGF2BP1/CPT1A axis facilitates breast cancer metastasis, and this axis may be a promising prognostic biomarker and therapeutic target for breast cancer.

Sprayable hydrogel for biomedical applications.

Polymeric hydrogels have extraordinary potential to be utilized for biomedical applications. Recently, sprayable hydrogels have received increasing attention for their biocompatibility, degradability, tunable mechanical properties and rapid spray-filming abilities. In this review, hydrogel-based biomaterials, especially those based on natural polymers, such as polysaccharides and proteins, have been explained. The focus of this review lies on illuminating recent advances in sprayable hydrogel systems and highlighting the properties and applications of sprayable hydrogels, such as wound management, postoperative adhesion and cancer therapeutics. In addition, future research directions and challenges are also discussed.