circVAPA-rich small extracellular vesicles derived from gastric cancer promote neural invasion by inhibiting SLIT2 expression in neuronal cells.

Gastric cancer (GC) is one of the most common cancer worldwide. Neural invasion (NI) is considered as the symbiotic interaction between nerves and cancers, which strongly affects the prognosis of GC patients. Small extracellular vesicles (sEVs) play a key role in intercellular communication. However, whether sEVs mediate GC-NI remains unexplored. In this study, sEVs release inhibitor reduces the NI potential of GC cells. Muscarinic receptor M3 on GC-derived sEVs regulates their absorption by neuronal cells. The enrichment of sEV-circVAPA in NI-positive patients' serum is validated by serum high throughput sEV-circRNA sequencing and clinical samples. sEV-circVAPA promotes GC-NI in vitro and in vivo. Mechanistically, sEV-circVAPA decreases SLIT2 transcription by miR-548p/TGIF2 and inhibits SLIT2 translation via binding to eIF4G1, thereby downregulates SLIT2 expression in neuronal cells and finally induces GC-NI. Together, this work identifies the preferential absorption mechanism of GC-derived sEVs by neuronal cells and demonstrates a previously undefined role of GC-derived sEV-circRNA in GC-NI, which provides new insight into sEV-circRNA based diagnostic and therapeutic strategies for NI-positive GC patients.

PEG modification increases thermostability and inhibitor resistance of Bst DNA polymerase.

Polyethylene glycol modification (PEGylation) is a widely used strategy to improve the physicochemical properties of various macromolecules, especially protein drugs. However, its application in enhancing the performance of enzymes for molecular biology remains underexplored. This study explored the PEGylation of Bst DNA polymerase, determining optimal modification reaction conditions. In comparison to the unmodified wild-type counterpart, the modified Bst DNA polymerase exhibited significantly improved of activity, thermal stability and inhibitor tolerance during loop-mediated isothermal amplification (LAMP). When applied for the detection of Salmonella in crude samples, the modified enzyme demonstrated a notably accelerated reaction rate. Therefore, PEGylation emerges as a viable strategy for refining DNA polymerases, helping in the development of novel molecular diagnostic reagents.

MOTS-c is an effective target for treating streptozotocin induced painful diabetic neuropathy through induction of AMPK/PGC-1α -mediated mitochondrial biogenesis.

Painful Diabetic Neuropathy (PDN) is a common diabetes complication that frequently causes severe hyperalgesia and allodynia and presents treatment challenges. MOTS-c, a novel mitochondrial-derived peptide, has been shown to regulate glucose metabolism, insulin sensitivity, and inflammatory responses. This study aimed to evaluate the effects of MOTS-c in streptozocin (STZ)-induced PDN model and investigate the putative underlying mechanisms. We found that endogenous MOTS-c levels in plasma and spinal dorsal horn were significantly lower in STZ-treated mice than in control animals. Accordingly, MOTS-c treatment significantly improves STZ-induced weight loss, elevation of blood glucose, mechanical allodynia, and thermal hyperalgesia; however, these effects were blocked by dorsomorphin, an AMPK inhibitor. In addition, MOTS-c treatment significantly enhanced AMPKα1/2 phosphorylation and PGC-1α expression in the lumbar spinal cord of PDN mice. Mechanistic studies indicated that MOTS-c significantly restored mitochondrial biogenesis, inhibited microglia activation, and decreased the production of pro-inflammatory factors, which contributed to the alleviation of pain. Moreover, MOTS-c decreased STZ-induced pain hypersensitivity in PDN mice by activating AMPK/PGC-1α signaling pathway. This provides the pharmacological and biological evidence for developing mitochondrial peptide-based therapeutic agents for PDN.

Interlayer-Coupling-Driven High-Temperature Superconductivity in La_{3}Ni_{2}O_{7} under Pressure.

The newly discovered high-temperature superconductivity in La_{3}Ni_{2}O_{7} under pressure has attracted a great deal of attention. The essential ingredient characterizing the electronic properties is the bilayer NiO_{2} planes coupled by the interlayer bonding of 3d_{z^{2}} orbitals through the intermediate oxygen atoms. In the strong coupling limit, the low-energy physics is described by an intralayer antiferromagnetic spin-exchange interaction J_{∥} between 3d_{x^{2}-y^{2}} orbitals and an interlayer one J_{⊥} between 3d_{z^{2}} orbitals. Taking into account Hund's rule on each site and integrating out the 3d_{z^{2}} spin degree of freedom, the system reduces to a single-orbital bilayer t-J model based on the 3d_{x^{2}-y^{2}} orbital. By employing the slave-boson approach, the self-consistent equations for the bonding and pairing order parameters are solved. Near the physically relevant 1/4-filling regime (doping δ=0.3∼0.5), the interlayer coupling J_{⊥} tunes the conventional single-layer d-wave superconducting state to the s-wave one. A strong J_{⊥} could enhance the interlayer superconducting order, leading to a dramatically increased T_{c}. Interestingly, there could exist a finite regime in which an s+id state emerges.

Coordination polymer derived Fe-N-C electrocatalysts with high performance for the oxygen reduction reaction in Zn-air batteries.

Developing high performance noble-metal-free electrocatalysts as an alternative to Pt-based catalysts for the oxygen reduction reaction (ORR) in energy conversion devices is highly desirable. We report herein the preparation of a coordination-polymer (CP)-derived Fe/CP/C composite as an electrocatalyst for the ORR with excellent activity and stability both in solution and in Zn-air batteries. The Fe/CP/C catalyst was obtained from the pyrolysis of an iron porphyrin Fe(TPP)Cl (5,10,15,20-tetraphenyl-21H,23H-porphyrin iron(III) chloride) grafted Zn-coordination polymer with dangling functional groups 4,4'-oxybisbenzoic acid and 4,4'-bipyridine ligands. The Fe/CP/C catalyst showed much higher ORR activity with a half-wave potential (E1/2) of 0.90 V (vs. RHE) than the Fe/C catalyst (E1/2 = 0.85 V) derived from the carbon-black-supported Fe porphyrins in 0.1 M KOH solution. When Fe/CP/C was used as the cathode electrocatalyst in Zn-air batteries (ZABs), the ZABs achieved a significantly higher open circuit voltage (OCV = 1.43 V) and maximum power density (Pmax = 142.8 mW cm-2) compared with Fe/C (OCV = 1.38 V, Pmax = 104.5 mW cm-2) and commercial 20 wt% Pt/C (OCV = 1.41 V, Pmax = 117.6 mW cm-2). Using dangling functional groups in CP to increase the loading efficiency of iron porphyrins offered a facile method to prepare high-performance noble-metal-free electrocatalysts for the ORR, which may provide promising applications to energy conversion devices.

One-year results of the flowdynamics dense mesh stent for residual dissection after proximal repair of stanford type a or type b aortic dissection: a multicenter, prospective and randomized study.

OBJECTIVE: Negative remodeling of the distal aorta following proximal repair for acute aortic dissection has garnered growing attention. This clinical scenario has spurred the development of techniques and devices. A multicenter, prospective, and randomized controlled study was conducted with the aim of confirming the safety and effectiveness of a newly-designed flowdynamics dense mesh stent for the treatment of residual dissection after proximal repair. METHODS: Patients with nonchronic residual dissection affecting visceral branches were prospectively enrolled at three centers and randomly allocated to either the FDMS group or the control group. Primary endpoints encompassed all-cause and aortic-related mortality, while the patency of branch arteries is indeed a key focal metric. Morphological changes (diameter, area, and volume) were analyzed to demonstrate the therapeutic effect. RESULTS: 112 patients were recruited in the clinical trial, and 103 patients completed the 12-month follow-up. The rate of freedom from all-cause and aortic-related death in the FDMS group was 94.64% and 100%, respectively. All visceral branches remained patent. The FDMS group exhibited a substantial expansion in TL and a notable shrinkage in FL at the planes below renal arteries (ΔArea TL: FDMS vs. Control, 0.74±0.46 vs. 0.34±0.66 cm2, P<0.001; ΔArea FL: FDMS vs. Control, -0.72±1.26 vs. -0.12±0.86 cm, P = 0.01) and 5 cm below renal arteries (ΔArea TL: FDMS vs. Control, 1.06±0.75 vs. 0.16±0.63 cm2, P<0.001; ΔArea FL: FDMS vs. Control, -0.53±1.43 vs. -0.25±1.00 cm, P = 0.27). Meanwhile, the FDMS group demonstrated an increase of 22.55±11.14 cm3 in TL (P<0.001) and a corresponding reduction of 21.94±11.77 cm3 in FL (P=0.08). CONCLUSIONS: This newly-designed FDMS for endovascular repair of residual dissection following the proximal repair is demonstrated to be safe and effective at 12 months.

The Arabidopsis RTH plays an important role in regulation of iron (Fe) absorption and transport.

KEY MESSAGE: RTH may activate Fe assimilation related genes to promote Fe absorption, transport and accumulation in Arabidopsis. Iron (Fe) is an important nutrient element. The Fe absorption and transport in plants are well investigated over the past decade. Our previous work indicated that RTE1-HOMOLOG (RTH), the homologous gene of reversion-to-ethylene sensitivity 1 (RTE1), plays a role in ethylene signaling pathway. However, its function in Fe absorption and transport is largely unknown. In the present study, we found that RTH was expressed in absorptive tissue and conducting tissue, including root hairs, root vascular bundle, and leaf veins. Under high Fe concentration, the seedling growth of rth-1 mutant was better, while the RTH overexpression lines were retarded compared to the wild type (Col-0). When treated with EDTA-Fe3+ (400 µM), the chlorophyll content and ion leakage rate were higher and lower in rth-1 than those of Col-0, respectively. By contrast, the chlorophyll contents and ion leakage rates of RTH overexpression lines were decreased and hastened compared with Col-0, respectively. Fe measurement indicated that the Fe contents of rth-1 were lower than those of Col-0, whereas those of RTH overexpression lines were comparably higher. Gene expression analysis revealed that Fe absorption and transport genes AHA2, IRT1, FIT, FPN1, and YSL1 decreased in rth-1 but increased in RTH overexpression lines compared with Col-0. Additionally, Y2H (yeast two-hybrid) and BiFC (bimolecular fluorescence complementation) assays showed that RTH can physically interact with hemoglobin 1 (HB1) and HB2. All these findings suggest that RTH may play an important role in regulation of Fe absorption, transport, and accumulation in Arabidopsis.

Enhancing intercropping sustainability: Manipulating soybean rhizosphere microbiome through cropping patterns.

Understanding the responses of soybean rhizosphere and functional microbiomes in intercropping scenarios holds promise for optimizing nitrogen utilization in legume-based intercropping systems. This study investigated three cropping layouts under film mulching: sole soybean (S), soybean-maize intercropping in one row (IS), and soybean-maize intercropping in two rows (IIS), each subjected to two nitrogen levels: 110 kg N ha-1 (N110) and 180 kg N ha-1 (N180). Our findings reveal that cropping patterns alter bacterial and nifh communities, with approximately 5 % of soybean rhizosphere bacterial amplicon sequence variants (ASVs) and 42 % of rhizosphere nifh ASVs exhibiting altered abundances (termed sensitive ASVs). Root traits and soil properties shape these communities, with root traits exerting greater influence. Sensitive ASVs drive microbial co-occurrence networks and deterministic processes, predicting 85 % of yield variance and 78 % of partial factor productivity of nitrogen, respectively. These alterations impact bacterial and nifh diversity, complexity, stability, and deterministic processes in legume-based intercropping systems, enhancing performance in terms of yield, nitrogen utilization efficiency, land equivalent ratio, root nodule count, and nodule dry weight under IIS patterns with N110 compared to other treatments. Our findings underscore the importance of field management practices in shaping rhizosphere-sensitive ASVs, thereby altering microbial functions and ultimately impacting the productivity of legume-based intercropping systems. This mechanistic understanding of soybean rhizosphere microbial responses to intercropping patterns offers insights for sustainable intercropping enhancements through microbial manipulation.

Simulation training of laparoscopic biliary-enteric anastomosis with a three-dimensional-printed model leads to better skill transfer: a randomized controlled trial.

AIM: A new simulation model and training curriculum for laparoscopic bilioenteric anastomosis has been developed. Currently, this concept lacks evidence for the transfer of skills from simulation to clinical settings. This study was conducted to determine whether training with a three-dimensional (3D) bilioenteric anastomosis model result in greater transfer of skills than traditional training methods involving video observation and a general suture model. METHODS: Fifteen general surgeons with no prior experience in laparoscopic biliary-enteric anastomosis were included in this study and randomised into three training groups: video observation only, practice using a general suture model, and practice using a 3D-printed biliary-enteric anastomosis model. Following five training sessions, each surgeon was asked to perform a laparoscopic biliary-enteric anastomosis procedure on an isolated swine organ model. The operative time and performance scores of the procedure were recorded and compared among the three training groups. RESULTS: The operation time in the 3D-printed model group was significantly shorter than the suture and video observation groups ( P =0.040). Furthermore, the performance score of the 3D-printed model group was significantly higher than those of the suture and video observation groups ( P =0.001). Finally, the goal score for laparoscopic biliary-enteric anastomosis in the isolated swine organ model was significantly higher in the 3D model group than in the suture and video observation groups ( P =0.004). CONCLUSIONS: The utilisation of a novel 3D-printed model for simulation training in laparoscopic biliary-enteric anastomosis facilitates improved skill acquisition and transferability to an animal setting compared with traditional training techniques.

Double-branched stent graft and four-stage deployment in total arch repair: safety and feasibility evaluation in porcine models.

OBJECTIVES: The primary objective of this research was to evaluate the safety and feasibility of an innovative double-branched stent graft system employing four-stage deployment technology for aortic arch repair in porcine models. METHODS: The double-branched stent graft system consisted of a proximal polyester artificial blood vessel, the main and double-branched stent grafts and a delivery system. We utilized 12 healthy pigs as experimental animals (6 per group). Postimplantation, samples were collected at 90 and 180 days after the operations. Preoperative and postoperative imaging and intraoperative arterial blood gas analyses were performed. After the pigs were euthanized, the implanted product, surrounding tissue and major organs were collected for pathological analysis. RESULTS: The technical success rate of the stent graft implants was 100% (12/12). All animals survived to the experimental end point. Perioperative assessments showed intact stent grafts, and imaging features at the end of the follow-up period revealed neither endoleak nor device migration. No major adverse cardiovascular events were observed during the postoperative follow-up period. Pathological examinations confirmed the satisfactory biocompatibility of the stent graft. CONCLUSIONS: This innovative double-branched stent graft system with four-stage deployment technology was affirmed as a safe and feasible option for aortic arch repair in accordance with our preclinical evaluation with porcine models.

Evaluation of the prognostic performance of different cutoff values of lymph node ratio staging system for stage III colorectal cancer.

This study attempted to compare the prognostic performance of lymph node ratio (LNR) staging system with different cutoff values relative to American Joint Committee on Cancer (AJCC) pN staging system in stage III colorectal cancer (CRC). Overall, 45,069 patients from the SEER dataset and 69 patients from the Second Affiliated Hospital of Nanjing Medical University (the External set) who underwent surgical resection of the primary tumor and were diagnosed with stage III CRC by postoperative pathology were included. Patients were divided into three subgroups based on the LNR cutoff used in previous studies, Kaplan-Meier curves were plotted, and log-rank test was used to compare the differences among groups in terms of cancer-specific survival (CSS). Cox regression model was applied for survival analysis. To evaluate the discriminatory power of different lymph node staging systems, Harrell's C statistic(C-index) and Akaike's Information Criterion (AIC) were applied. A set of optimal cutoff values (0.11; 0.36; 0.66) of LNR staging system with the most considerable discriminatory power to the prognosis in patients with stage III CRC (SEER set: C-index = 0.714; AIC = 58,942.46, External set: C-index = 0.809; AIC = 164.36) were obtained, and both were superior to the AJCC pN staging system (SEER set: C-index = 0.708; AIC = 59,071.20, External set: C-index = 0.788; AIC = 167.06). For evaluating the prognostic efficacy of patients with stage III colorectal cancer, the cutoff value (0.11; 0.36; 0.66) of LNR staging system had the best discrimination and prognostic ability, which was superior to LNR staging system under other cutoff values and AJCC pN staging system.

Rapid Screening of 34 Emerging Contaminants in Surface Water by UHPLC-Q-TOF-MS.

OBJECTIVES: To establish a rapid screening method for 34 emerging contaminants in surface water by ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry (UHPLC-Q-TOF-MS). METHODS: The pretreatment conditions of solid phase extraction (SPE) were optimized by orthogonal experimental design and the surface water samples were concentrated and extracted by Oasis® HLB and Oasis® MCX SPE columns in series. The extracts were separated by Kinetex® EVO C18 column, with gradient elution of 0.1% formic acid aqueous solution and 0.1% formic acid methanol solution. Q-TOF-MS 'fullscan' and 'targeted MS/MS' modes were used to detect 34 emerging contaminants and to establish a database with 34 emerging contaminants precursor ion, product ion and retention times. RESULTS: The 34 emerging contaminants exhibited good linearity in the concentration range respectively and the correlation coefficients (r) were higher than 0.97. The limit of detection was 0.2-10 ng/L and the recoveries were 81.2%-119.2%. The intra-day precision was 0.78%-18.70%. The method was applied to analyze multiple surface water samples and 6 emerging contaminants were detected, with a concentration range of 1.93-157.71 ng/L. CONCLUSIONS: The method is simple and rapid for screening various emerging contaminants at the trace level in surface water.

Function and mechanism of exosomes derived from different cells as communication mediators in colorectal cancer metastasis.

Colorectal cancer (CRC) ranks as the second leading cause of cancer-related mortality, with metastasis being the primary determinant of poor prognosis in patients. Investigating the molecular mechanisms underlying CRC metastasis is currently a prominent and challenging area of research. Exosomes, as crucial intercellular communication mediators, facilitate the transfer of metabolic and genetic information from cells of origin to recipient cells. Their roles in mediating information exchange between CRC cells and immune cells, fibroblasts, and other cell types are pivotal in reshaping the tumor microenvironment, regulating key biological processes such as invasion, migration, and formation of pre-metastatic niche. This article comprehensively examines the communication function and mechanism of exosomes derived from different cells in cancer metastasis, while also presenting an outlook on current research advancements and future application prospects. The aim is to offer a distinctive perspective that contributes to accurate diagnosis and rational treatment strategies for CRC.

Nomogram predicting the efficacy of transurethral surgery in benign prostatic hyperplasia patients.

PURPOSE: This study aimed to develop and validate a nomogram for predicting the efficacy of transurethral surgery in benign prostatic hyperplasia (BPH) patients. METHODS: Patients with BPH who underwent transurethral surgery in the West China Hospital and West China Shang Jin Hospital were enrolled. Patients were retrospectively involved as the training group and were prospectively recruited as the validation group for the nomogram. Logistic regression analysis was utilized to generate nomogram for predicting the efficacy of transurethral surgery. The discrimination of the nomogram was assessed using the area under the receiver operating characteristic curve (AUC) and calibration plots were applied to evaluate the calibration of the nomogram. RESULTS: A total of 426 patients with BPH who underwent transurethral surgery were included in the study, and they were further divided into a training group (n = 245) and a validation group (n = 181). Age (OR 1.07, 95% CI 1.02-1.15, P < 0.01), the compliance of the bladder (OR 2.37, 95% CI 1.20-4.67, P < 0.01), the function of the detrusor (OR 5.92, 95% CI 2.10-16.6, P < 0.01), and the bladder outlet obstruction (OR 2.21, 95% CI 1.07-4.54, P < 0.01) were incorporated in the nomogram. The AUC of the nomogram was 0.825 in the training group, and 0.785 in the validation group, respectively. CONCLUSION: The nomogram we developed included age, the compliance of the bladder, the function of the detrusor, and the severity of bladder outlet obstruction. The discrimination and calibration of the nomogram were confirmed by internal and external validation.

Interfacial Engineering of P2-Type Ni/Mn-Based Layered Oxides by a Facile Water-Washing Method for Superior Sodium-Ion Batteries.

Owing to the strong basicity and reactivity, residual sodium compounds (RSCs) on the surface of Na-based layered oxides for sodium-ion batteries (SIBs) cause the deterioration of the electrochemical performance and processability of the oxide cathode materials. Herein, considering P2-type Na0.66Ni0.26Zn0.07Mn0.67O2 as the model material, the water-washing treatment is proven to be a facile, economic, and highly efficient method to improve the electrochemical performance of P2-type Ni/Mn-based layered oxides. Experimental results show that RSCs on material surfaces can be effectively removed by water washing without causing severe damage to the bulk structure. Notably, water washing triggers the formation of an ultrathin (2-3 nm thick) Na-poor disordered interfacial layer on the surface of Na0.66Ni0.26Zn0.07Mn0.67O2. This layer plays a passivating role in further enhancing the material's resistance to water and reduces the reactivity of the material surface with the electrolyte. These compositional and structural optimizations for P2-type Na0.66Ni0.26Zn0.07Mn0.67O2 effectively suppress the release of gaseous CO2, formation of thick cathode-electrolyte interphase films, and consumption of active Na+, enabling good Na+ transport kinetics during cycling. The water-washed Na0.66Ni0.26Zn0.07Mn0.67O2 exhibits significantly improved cycling stability with a capacity retention of 89.1% at 100 mA g-1 after 100 cycles and rate capability with a discharge capacity of 76.3 mA g-1 at 2000 mA g-1; these values are higher than those of the unwashed Na0.66Ni0.26Zn0.07Mn0.67O2 (83.3%, 71.4 mA h g-1). This work provides fundamental insights into the detrimental effect of RSCs on the electrochemical performance of layered oxides and highlights the importance of regulating interfacial compositions for developing high-performance layered-oxide cathode materials for SIBs.

Therapeutic Application of Dendrobium fimbriatum Hook for Retinopathy Caused by Ultraviolet Radiation and Chemotherapy Using ARPE-19 Cells and Mouse Retina.

Retinopathy caused by ultraviolet radiation and cancer chemotherapy has increased dramatically in humans due to rapid environmental and social changes. Therefore, it is very important to develop therapeutic strategies to effectively alleviate retinopathy. In China, people often choose dendrobium to improve their eyesight. In this study, we explored how Dendrobium fimbriatum extract (DFE) protects ARPE-19 cells and mouse retinal tissue from damage of ultraviolet (UV) radiation and chemotherapy. We evaluated the antioxidant capacity of DFE using the 1,1-diphenyl-2-trinitophenylhydrazine (DPPH) assay. The protective effects of DEF from UV- and oxaliplatin (OXA)-induced damage were examined in ARPE-19 cells using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and immunofluorescence (IF) stains, and in mouse retinal tissue using immunohistochemistry (IHC) stains. Our results show that DFE has excellent antioxidant capacity. The ARPE-19 cell viability was decreased and the F-actin cytoskeleton structure was damaged by UV radiation and OXA chemotherapy, but both were alleviated after the DFE treatment. Furthermore, DFE treatment can alleviate OXA chemotherapy-induced reduced expressions of rhodopsin and SOD2 and increased expressions of TNF-α and caspase 3 in mouse retinal tissue. Thus, we suggest that DFE can act as suitable treatment for retinopathy through reducing oxidative stress, inflammation, and apoptosis.

Regulation of PDGFRα+ cells and ICC in progesterone-mediated slow colon transit in pregnant mice.

Background: Progesterone can inhibit intestinal smooth muscle contraction; however, the specific mechanism remains unclear. Besides smooth muscle cells, smooth muscle has two important mesenchymal cells, namely interstitial cells of Cajal (ICC) and PDGFRα+ cells, which induce the contraction and relaxation of smooth muscles. We aimed to explore the regulation of PDGFRα+ cells and ICC in progesterone-mediated colon slow transit in pregnant mice. Methods: Colon transit experiments were performed in vivo and in vitro to observe slow colon transit. The expression of PDGFRα and c-KIT was detected by Western blot, RT-PCR, and immunofluorescence. An isometric tension experiment was performed to investigate smooth muscle contractions. Results: The colon transit time in pregnant mice was longer than that in non-pregnant mice. Progesterone significantly blocks colonic smooth muscle contractions. However, when the relaxation and contraction of PDGFRα+ cells and ICC are blocked, progesterone cannot inhibit smooth muscle contraction. When the function of only PDGFRα+ cells are blocked, progesterone has a more obvious inhibitory effect on smooth muscle in the non-pregnant group than that in the pregnant group. However, when ICC alone was blocked, progesterone inhibited smooth muscle contractions more clearly in pregnant mice. The protein and mRNA expression of PDGFRα was higher and c-KIT was lower in pregnant mice. PDGFRα+ cells and ICC from smooth muscle all co-localize progesterone receptors. Conclusions: Under the regulation of progesterone, the relaxation function of PDGFRα+ cells is enhanced and the contraction function of ICC is weakened, leading to the slow colon transit of pregnant mice.

Tumor necrosis factor α-induced protein 8-like-2 controls microglia phenotype via metabolic reprogramming in BV2 microglial cells and responses to neuropathic pain.

Microglial are major players in neuroinflammation that have recently emerged as potential therapeutic targets for neuropathic pain. Glucose metabolic programming has been linked to differential activation state and function in microglia. Tumor necrosis factor α-induced protein 8-like-2 (TNFAIP8L2) is an important component in regulating the anti-inflammatory response. However, the role of TNFAIP8L2 in microglia differential state during neuropathic pain and its interplay with glucose metabolic reprogramming in microglia has not yet been determined. Thus, we aimed to investigate the role of TNFAIP8L2 in the status of microglia in vitro and in vivo. BV2 microglial cells were treated with lipopolysaccharides plus interferon-gamma (LPS/IFNγ) or interleukin-4 (IL-4) to induce the two different phenotypes of microglia in vitro. In vivo experiments were conducted by chronic constriction injury of the sciatic nerve (CCI). We investigated whether TNFAIP8L2 regulates glucose metabolic programming in BV2 microglial cells. The data in vitro showed that TNFAIP8L2 lowers glycolysis and increases mitochondrial oxidative phosphorylation (OXPHOS) in inflammatory microglia. Blockade of glycolytic pathway abolished TNFAIP8L2-mediated differential activation of microglia. TNFAIP8L2 suppresses inflammatory microglial activation and promotes restorative microglial activation in BV2 microglial cells and in spinal cord microglia after neuropathic pain. Furthermore, TNFAIP8L2 controls differential activation of microglia and glucose metabolic reprogramming through the MAPK/mTOR/HIF-1α signaling axis. This study reveals that TNFAIP8L2 plays a critical role in neuropathic pain, providing important insights into glucose metabolic reprogramming and microglial phenotypic transition, which indicates that TNFAIP8L2 may be used as a potential drug target for the prevention of neuropathic pain.

CPXM1 correlates to poor prognosis and immune cell infiltration in gastric cancer.

Background: Gastric cancer (GC) is the fourth most common cause of cancer-related death and the fifth most frequent malignant cancer, especially advanced GC. Carboxypeptidase X member 1 (CPXM1) is an epigenetic factor involved in many physiological processes, including osteoclast differentiation and adipogenesis. Several studies have shown the association of CPXM1 with multiple tumors; however, the mechanism of CPXM1 involvement in the progression of GC is yet to be characterized. Method: CPXM1 expression data were obtained from the Tumor Immune Estimation Resource. The Cancer Genome Atlas and the Gene Expression Omnibus databases were used to obtain patient-matched clinicopathological information, and the Kaplan-Meier plot database was utilized for the prognosis analysis of GC patients. The Catalog of Somatic Mutations in Cancer and cBioportal databases were adopted to study CPXM1 mutations in tumors. Next, we utilized the Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis for mechanism research. Furthermore, we performed tumor microenvironment and immune infiltration analysis based on CPXM1. Finally, we predicted sensitivity to several targeted drugs in GC patients based on CPXM1.CPXM1 is upregulated in GC and is correlated with poor prognosis, gender, and tumor stage in GC patients. Gene enrichment analysis suggested that CPXM1 may regulate the occurrence and progression of GC via the PI3K-AKT and TGF-ß pathway. Moreover, CPXM1 expression results in an increase in the proportion of immune and stromal cells. Additionally, the proportion of plasma cells was inversely related to the expression of CPXM1, whereas macrophage M2 expression was proportionate to CPXM1 expression. Finally, six small-molecule drugs that showed notable variations in IC50 between two groups were screened. Conclusion: These results suggested that CPXM1 regulates the progression of GC and may represent a novel target for the detection and treatment of GC.