Human Neonatal Fc Receptor Is the Cellular Uncoating Receptor for Enterovirus B.

Enterovirus B (EV-B), a major proportion of the genus Enterovirus in the family Picornaviridae, is the causative agent of severe human infectious diseases. Although cellular receptors for coxsackievirus B in EV-B have been identified, receptors mediating virus entry, especially the uncoating process of echovirus and other EV-B remain obscure. Here, we found that human neonatal Fc receptor (FcRn) is the uncoating receptor for major EV-B. FcRn binds to the virus particles in the "canyon" through its FCGRT subunit. By obtaining multiple cryo-electron microscopy structures at different stages of virus entry at atomic or near-atomic resolution, we deciphered the underlying mechanisms of enterovirus attachment and uncoating. These structures revealed that different from the attachment receptor CD55, binding of FcRn to the virions induces efficient release of "pocket factor" under acidic conditions and initiates the conformational changes in viral particle, providing a structural basis for understanding the mechanisms of enterovirus entry.

The nearby atomic environment effect on an Fe-N-C catalyst for the oxygen reduction reaction: a density functional theory-based study.

Fe-N-C materials have emerged as highly promising non-noble metal catalysts for oxygen reduction reactions (ORRs) in polymer electrolyte membrane fuel cells. However, they still encounter several challenges that need to be addressed. One of these challenges is establishing an atomic environment near the Fe-N4 site, which can significantly affect catalyst activity. To investigate this, herein, we employed density functional theory (DFT). According to our computational analysis of the Gibbs free energy of the reaction based on the computational hydrogen electrode (CHE) model, we successfully determined two C-O-C structures near the Fe-N4 site (referred to as str-11) with the highest limiting potential (0.813 V). Specifically, in the case of O-doped structures, the neighboring eight carbon (C) atoms around nitrogen (N) can be categorized into two distinct types: four C atoms (type A) exhibiting high sensitivity to the limiting potential and the remaining four C atoms (type B) displaying inert behavior. Electronic structure analysis further elucidated that a structure will have strong activity if the valence band maximum (VBM) around its gamma point is mainly contributed by dxz, dyz or dz2 orbitals of Fe atoms. Constant-potential calculations showed that str-11 is suitable for the ORR under both acidic and alkaline conditions with a limiting potential of 0.695 V at pH = 1 and 0.926 V at pH = 14, respectively. Additionally, microkinetic simulations indicated the possibility of str-11 as the active site for the ORR under working potential at pH = 14.

The Evaluation of Outcomes after Thoracic Endovascular Aortic Repair for Type B Aortic Dissection in Mainland China.

BACKGROUND: To assess the mortality and outcomes after thoracic endovascular aortic repair (TEVAR) in patients with type B aortic dissection (TBAD) in mainland China, and to compare these outcomes with data from Western countries, while analyzing the potential reasons for differences among different countries. METHODS: An extensive literature search spanning from January 1999 to October 2023 was conducted using PubMed, Cochrane Library, and Embase databases for studies on endovascular treatment for TBAD. This systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Data extraction and analysis followed the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Primary outcomes were in-hospital mortality and mid-term (< 5 years) mortality. RESULTS: Based on 25 publications (3,080 patients), pooled estimate for in-hospital mortality was 2.2% (95% confidence interval, 1.6%-2.9%). Major perioperative complications included stroke (2.4% [1.8%-3.3%]), spinal cord ischemia (1.4% [1.0%-2.2%]), retrograde type A aortic dissection (1.2% [0.8%-1.8%]), type I endoleak (5.6% [3.6%-8.6%]), visceral ischemia (1.0% [0.5%-2.1%]), and acute renal failure (2.8% [2.0%-3.8%]). Mid-term mortality was 5.1% (3.6%-7.3%), and secondary intervention rate was 4.9% (4.0%-6.0%) with 1.7% (1.0%-2.9%) conversion rate to open surgery. In subgroup analysis based on uncomplicated TBAD, in-hospital and mid-term mortality was 0.5% (0.2%-1.5%) and 0.6% (0.2-1.7%), respectively. Compared with data from Western countries, mainland Chinese patients had a lower mortality. CONCLUSIONS: In mainland China, the outcomes of endovascular treatment for TBAD are comparable to those of Western countries. The large number of patients undergoing TEVAR in mainland China and its good performance support the use of TEVAR in uncomplicated TBAD.

Coil embolization of asymptomatic left gastric artery aneurysm: Case report and literature review.

Patients with visceral artery aneurysms are rare, and the reported incidence of left gastric aneurysm (LGA) is only 4%. At present, although there is little knowledge about such disease, it is generally believed that appropriate treatment should be planned to prevent some dangerous aneurysms from rupturing. We introduced a case of 83-year-old patient with LGA who underwent endovascular aneurysm repair. The 6-month follow-up computed tomography angiography showed complete thrombosis in the aneurysm lumen. In addition, to insight the management strategy on LGAs deeply, a literature review concerning this entity published in recent 35 years was performed.

The Role of Location, Length, and Thickness of the Intimal Flap in the Propagation of Stanford Type B Aortic Dissection Based on Ex Vivo Porcine Aorta Models.

PURPOSE: To explore the role of location, length, and thickness of the intimal flap in the propagation of Stanford type B aortic dissection (TBAD) based on ex vivo porcine aorta models based on ex vivo porcine aorta models. MATERIALS AND METHODS: The porcine aortas were harvested and randomly divided into 6 groups to create various TBAD aortic models. We constructed intimal flaps for different locations (group A [entry tear on outer curvature] and group B [entry tear on inner curvature]), lengths (group C [long] and group D [short]), and thicknesses (group E [thick] and group F [thin]). For the ex vivo perfusion experiments conducted on model aortas, an experimental circulation loop (ECL) was employed. The pressure in false lumen (FL) was constantly monitored. A comparison was made between the morphological data collected before and after the experiment to quantify the changes in the FL after the experiment. RESULTS: Compared the results with group B, the mean peak pressures of the FL in group A were lower (106.87±15.55 vs. 124.01±22.75 mm Hg, p=0.028). The mean axial propagation length in group A was shown to be shorter than that of group B (88.14±33.38 vs. 197.43±41.65 mm, p<0.001). The mean peak pressure was higher in group C than in group D (144.04±19.37 vs. 92.51±26.70 mm Hg, p<0.001). The mean peak pressure of group E was higher than that of group F (160.83±32.83 vs. 109.33±15.62 mm Hg, p<0.001), as was the mean axial propagation length of group E (143.11±39.73 vs. 100.45±35.44 mm, p=0.021). According to the results of multivariable linear regression, axial propagation length=45.873-0.703×length of initial FL+0.863× peak pressure (p<0.001). CONCLUSION: There was a relationship between FL propagation and the location, length, and thickness of the intimal flap. The axial propagation length was related to the length of the intimal flap and the peak pressure of propagation. It may be helpful to evaluate the risk of propagation in patients with TBAD. CLINICAL IMPACT: This study found that the locations, lengths, and thickness of the intimal flap significantly contributed to propagation pressure of FL. Using dissection flap characteristics, a physician can predict FL development in a patient and formulate a treatment plan.The purpose was to investigate the relationship between the dissection flap characteristics (location, length, and thickness) and the propagation of the FL, which is not clear at present. This study employed porcine models to create an experimental circulation loop. The perfusion experiment was conducted using a FL without distal re-entry and a non-pulsating flow.

Risk Factors Associated with Poor Prognosis in Patients with Stanford Type B Aortic Dissection after Thoracic Endovascular Aortic Repair.

BACKGROUND: The aim of the study was to analyze the clinical characteristics of patients with Stanford type B aortic dissection (TBAD) and risk factors for poor prognosis after thoracic endovascular aortic repair (TEVAR). METHODS: Clinical records for patients with TBAD presenting to a medical center between March 1, 2012 and July 31, 2020 were reviewed. Clinical data including demographics, comorbidities, and postoperative complications were obtained from electronic medical records. Comparative analysis and subgroup analysis were performed. A logistic regression model was used to analyze prognostic factors in patients with TBAD after TEVAR. RESULTS: TEVAR was performed on all 170 patients with TBAD, and poor prognosis was identified in 28.2% (48/170) of cases. Patients with a poor prognosis were younger (38.5 [32.0, 53.8] years vs. 55.0 [48.0, 62.0] years, P < 0.001), had higher systolic blood pressure (SBP) (138.5 [127.8, 152.8] mm Hg vs. 132.0 [120.8, 145.3] mm Hg, P = 0.013) and more complicated aortic dissection patients (19 [60.4] vs. 71 [41.8], P = 0.029) than those without a poor prognosis. According to the results of binary logic regression analysis, the possibility of a poor prognosis after TEVAR decreased with each 10 years increase in age (odds ratio: 0.464, 95% confidence interval: 0.327-0.658, P < 0.001). CONCLUSIONS: There is an association between younger age and a poor prognosis after TEVAR in patients with TBAD, with the condition that those with poor prognoses have higher SBP and more complicated cases. In younger patients, postoperative follow-up should be more frequent, and complications should be managed in time.

Evolution of Stabilized 1T-MoS2 by Atomic-Interface Engineering of 2H-MoS2 /Fe-Nx towards Enhanced Sodium Ion Storage.

Metallic conductive 1T phase molybdenum sulfide (MoS2 ) has been identified as promising anode for sodium ion (Na+ ) batteries, but its metastable feature makes it difficult to obtain and its restacking during the charge/discharge processing result in part capacity reversibility. Herein, a synergetic effect of atomic-interface engineering is employed for constructing 2H-MoS2 layers assembled on single atomically dispersed Fe-N-C (SA Fe-N-C) anode material that boosts its reversible capacity. The work-function-driven-electron transfer occurs from SA Fe-N-C to 2H-MoS2 via the Fe-S bonds, which enhances the adsorption of Na+ by 2H-MoS2 , and lays the foundation for the sodiation process. A phase transfer from 2H to 1T/2H MoS2 with the ferromagnetic spin-polarization of SA Fe-N-C occurs during the sodiation/desodiation process, which significantly enhances the Na+ storage kinetics, and thus the 1T/2H MoS2 /SA Fe-N-C display a high electronic conductivity and a fast Na+ diffusion rate.

Poly (ADP-ribose) polymerase 1-mediated defective mitophagy contributes to painful diabetic neuropathy in the db/db model.

Studies have shown that poly (ADP-ribose) polymerase 1 (PARP1) is involved in the pathological process of diabetes. Mitophagy is widely acknowledged to be a key regulatory process in maintaining reactive oxygen species homeostasis via lysosome degradation of damaged mitochondria. However, the regulatory role of PARP1 in mitophagy-related mitochondrial oxidative injury and progression of painful diabetic neuropathy (PDN) is unclear. In this study, we studied the in vitro and in vivo mechanisms of PARP1-mediated mitophagy blockade in a leptin gene-mutation (db/db) mouse model of PDN. Db/db mice models of PDN were established by assessing the sciatic nerve conduction velocity (SNCV), mechanical withdrawal threshold (MWT), and thermal withdrawal latency (TWL). The results showed that PARP1 activity and mitochondrial injury of dorsal root ganglion (DRG) neurons were increased, and mitophagy was impaired in PDN mice. PARP1 was found to mediate the impairment of mitophagy in DRG neurons isolated from PDN mice. PARP1 inhibitors (PJ34 or AG14361) attenuated diabetes-induced peripheral nerve hyperalgesia, restored DRG neuron mitophagy function and decreased mitochondrial oxidative injury. Mitophagy impairment induced by lysosome deacidificant (DC661) aggravated diabetes-induced DRG neuron mitochondrial oxidative stress and injury. Taken together, our data revealed that PARP1-induced defective mitophagy of DRG neurons is a key mechanism in diabetes-induced peripheral neuropathic injury. Inhibition of PARP1 and restoration of mitophagy function are potential therapeutic targets for PDN.

A new risk model based on a 11-m6A-related lncRNA signature for predicting prognosis and monitoring immunotherapy for gastric cancer.

OBJECTIVE: N6-methyladenosine (m6A) mRNA modification triggers malignant behaviors of tumor cells and thereby drives malignant progression in gastric cancer (GC). However, data regarding the prognostic values of m6A RNA methylation-related long non-coding RNAs (lncRNAs) in GC are very limited in the literature. We aimed to investigate the prognostic potential of m6A-related lncRNAs in predicting prognosis and monitoring immunotherapy efficacy in GC patients. METHODS: Transcriptome and clinical data were obtained from GC biopsies from Cancer Genome Atlas (TCGA). M6A-related lncRNAs associated with GC were identified by constructing a co-expression network, and the gene pairs differentially expressed in GC were selected using univariate analysis. We constructed a risk model based on prognosis-related lncRNA pairs selected using the LASSO algorithm and quantified the best cutoff by comparing the area under the curve (AUC) for risk stratification. A risk model with the optimal discrimination between high- and low-risk GC patients was established. Its feasibility for overall survival prediction and discrimination of clinicopathological features, tumor-infiltrating immune cells, and biomarkers of immune checkpoint inhibitors between high- and low-risk groups were assessed. RESULTS: Finally, we identified 11 m6A-related lncRNA pairs associated with GC prognosis based on transcriptome analysis of 375 GC specimens and 32 normal tissues. A risk model was constructed with an AUC of 0.8790. We stratified GC patients into high- and low-risk groups at a cutoff of 1.442. As expected, patients in the low-risk group had longer overall survival versus the high-risk group. Infiltration of cancer-associated fibroblasts, endothelial cells, macrophages, particularly M2 macrophages, and monocytes was more severe in high-risk patients than low-risk individuals, who exhibited high CD4+ Th1 cell infiltration in GC. Altered expressions of immune-related genes were observed in both groups. PD-1 and LAG3 expressions were found higher in low-risk patients than high-risk patients. Immunotherapy, either single or combined use of PD-1 or CTLA4 inhibitors, had better efficacy in low-risk patients than high-risk patients. CONCLUSION: The new risk model based on a 11-m6A-related lncRNA signature can serve as an independent predictor for GC prognosis prediction and may aid in the development of personalized immunotherapy strategies for patients.

In Vitro and In Vivo Dendritic Cell Immune Stimulation Effect of Low Molecular Weight Fucoidan from New Zealand Undaria pinnatifida.

Low molecular weight fucoidan (LMWF) has been reported to have immunomodulation effects through the increase of the activation and function of macrophages. In this study, the regulating effect of LMWF from Undaria pinnatifida grown in New Zealand on dendritic cells (DCs) was investigated. We discovered that LMWF could stimulate DCs' maturation and migration, as well as CD4+ and CD8+ T cells' proliferation in vitro. We proved that this immune promoting activity is activated through TLR4 and its downstream MAPK and NF-κB signaling pathways. Further in vivo (mouse model) investigation showed that LMWF has a strong immunological boosting effect, such as facilitating the proliferation of immune cells and increasing the index of immune organs. These findings suggest that LMWF has a positive immunomodulatory effect and is a promising candidate to supplement cancer immunotherapy.

High-throughput screening of a CRISPR/Cas9 library for functional genomics in human cells.

Targeted genome editing technologies are powerful tools for studying biology and disease, and have a broad range of research applications. In contrast to the rapid development of toolkits to manipulate individual genes, large-scale screening methods based on the complete loss of gene expression are only now beginning to be developed. Here we report the development of a focused CRISPR/Cas-based (clustered regularly interspaced short palindromic repeats/CRISPR-associated) lentiviral library in human cells and a method of gene identification based on functional screening and high-throughput sequencing analysis. Using knockout library screens, we successfully identified the host genes essential for the intoxication of cells by anthrax and diphtheria toxins, which were confirmed by functional validation. The broad application of this powerful genetic screening strategy will not only facilitate the rapid identification of genes important for bacterial toxicity but will also enable the discovery of genes that participate in other biological processes.

Modeling and correction for the optical axis pointing error of an airborne electro-optical platform.

Optical axis pointing accuracy is an important index of airborne electro-optical (EO) platforms. In this work, we aim to correct the optical axis pointing angle of an airborne EO platform by digital compensation. First, a basic parameter model (BPM) of pointing error with clear physical significance is established by analyzing the physical structure and error source of the EO platform. Then, to suppress the nonlinear factors in the error, we propose an improved algorithm of a semi-parametric regression model based on the BPM. Numerical simulation analysis shows that the improved algorithm inherits the advantages of the BPM, such as fewer model parameters and clear physical significance, and can improve the correction effect. Finally, experimental results show that the mean square error of the azimuth angle is reduced from more than 110'' to less than 4'', and that of the elevation angle is reduced from more than 75'' to less than 3''. According to the results obtained, the proposed correction model can improve the optical axis pointing accuracy of an airborne EO platform quickly and effectively, which has significant application value.

Cistanche tubulosa phenylethanoid glycosides induce apoptosis in H22 hepatocellular carcinoma cells through both extrinsic and intrinsic signaling pathways.

BACKGROUND: Cistanche tubulosa (Schenk) R. Wight is a traditional Chinese medicine that parasitizes the roots of the Tamarix plant and has been used to treat male impotence, sterility, body weakness, and as a tonic. However, its antitumor effect on hepatocellular carcinoma is still elusive. Here, we investigated the antitumor effect of C. tubulosa phenylethanoid glycosides (CTPG) on H22 hepatocellular carcinoma cells both in vitro and in vivo and its mechanisms. METHODS: The morphology, viability, apoptosis, cell cycle and mitochondrial membrane potential (Δψm) of H22 cells were analyzed by inverted microscopy, MTT assay and flow cytometry, respectively. The expression and activation of proteins in apoptosis pathway were detected by Western blot. The in vivo antitumor effect was evaluated in tumor mouse model established using male Kunming mice. RESULTS: CTPG treatment significantly suppressed H22 cell growth in a dose- and time-dependent manner, which was correlated with the increased apoptosis and cell cycle arrest at G0/G1 and G2/M phases. Moreover, the chromosomal condensation was observed in CTPG-treated H22 cells. CTPG treatment significantly increased Bax/Bcl-2 ratio, reduced Δψm and enhanced the release of cytochrome c. The levels of cleaved caspase-8 and caspase-9 in both extrinsic and intrinsic signaling pathways were significantly increased that sequentially activated caspase-7 and -3 to cleave PARP. Finally, CTPG inhibited the growth of H22 cells in mice and improved the survival rate of tumor mice. CONCLUSIONS: These results suggested that CTPG suppressed H22 cell growth through both extrinsic and intrinsic apoptosis pathways.

Enantioselective Hydroamidation of Enals by Trapping of a Transient Acyl Species.

An enantioselective synthesis of ß-chiral amides through asymmetric and redox-neutral hydroamidation of enals is reported. In this reaction, a chiral N-heterocyclic carbene (NHC) catalyst reacts with enals to generate the homoenolate intermediate. Upon highly enantioselective ß-protonation through proton-shuttle catalysis, the resulting azolium intermediate reacts with imidazole to yield the key ß-chiral acyl species. This transient intermediate provides access to diversified ß-chiral carbonyl derivatives, such as amides, hydrazides, acids, esters, and thioesters. In particular, ß-chiral amides can be prepared in excellent yield and ee (40 chiral amides, up to 95 % yield and 99 % ee). This modular strategy overcomes the challenge of disruption of the highly selective proton-shuttling process by basic amines.

Enantioselective ß-Protonation of Enals via a Shuttling Strategy.

Remote asymmetric protonation is a longstanding challenge due to the small size of protons. Reactions involving electron-deficient olefins pose a further difficulty due to the electrophilic nature of these substrates. We report a shuttling system that delivers a proton in a highly enantioselective manner to the ß-carbon of enals using a chiral N-heterocyclic carbene (NHC) catalyst. Choices of a Brønsted base shuttle and a Brønsted acid cocatalyst are critical for highly stereoselective ß-protonation of the homoenolate intermediate and regeneration of the NHC catalyst results in functionalization of the carbonyl group. Thioesters with a ß-chiral center were prepared in a redox-neutral transformation with an excellent yield and ee.

SAP-regulated T Cell-APC adhesion and ligation-dependent and -independent Ly108-CD3ζ interactions.

The germinal center response requires cooperation between Ag-specific T and B lymphocytes, which takes the form of long-lasting cell-cell conjugation in vivo. Signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) is required for stable cognate T-B cell conjugation, whereas SLAM family transmembrane (TM) receptor Ly108 may negatively regulate this process. We show that, other than phosphotyrosine-binding, SAP does not harbor motifs that recruit additional signaling intermediates to stabilize T-B adhesion. Ly108 dampens T cell adhesion to not only Ag-presenting B cells, but also dendritic cells by inhibiting CD3ζ phosphorylation through two levels of regulated Ly108-CD3ζ interactions. Constitutively associated with Src homology 2 domain-containing tyrosine phosphatase-1 even in SAP-competent cells, Ly108 is codistributed with the CD3 complex within a length scale of 100-200 nm on quiescent cells and can reduce CD3ζ phosphorylation in the absence of overt TCR stimulation or Ly108 ligation. When Ly108 is engaged in trans during cell-cell interactions, Ly108-CD3ζ interactions are promoted in a manner that uniquely depends on Ly108 TM domain, leading to more efficient CD3ζ dephosphorylation. Whereas replacement of the Ly108 TM domain still allows the constitutive, colocalization-dependent inhibition of CD3ζ phosphorylation, it abrogates the ligation-dependent Ly108-CD3ζ interactions and CD3ζ dephosphorylation, and it abolishes the suppression on Ag-triggered T-B adhesion. These results offer new insights into how SAP and Ly108 antagonistically modulate the strength of proximal TCR signaling and thereby control cognate T cell-APC interactions.

Electronic and optical properties of quaternary alloy GaAsBiN lattice-matched to GaAs.

Employing first-principles combined with hybrid functional calculations, the electronic and optical properties of GaAs alloyed with isovalent impurities Bi and N are investigated. As GaAsBiN alloy is a quaternary alloy, the band gap and the lattice constant of the alloy can be individually tuned. Both impurities are important to the valence band and conduction band of the alloy, with the band gap of the alloy being dramatically reduced by Bi 6p states and N localized 2s states. Interestingly, the calculated optical properties of the quaternary alloy are similar to those of undoped GaAs except that the absorption edge has a redshift toward lower energy. These results suggest potential interest in the long-wavelength applications of GaAsBiN alloy.

Nanomedicine-based cancer immunotherapy: a bibliometric analysis of research progress and prospects.

Despite the increasing number of studies on nanomedicine-based cancer immunotherapy, the overall research trends in this field remain inadequately characterized. This study aims to evaluate the research trends and hotspots in nanomedicine-based cancer immunotherapy through a bibliometric analysis. As of March 31, 2024, relevant publications were retrieved from the Web of Science Core Collection. Analytical tools including VOSviewer, CiteSpace, and an online bibliometric analysis platform were employed. A total of 5,180 publications were analyzed. The study reveals geographical disparities in research output, with China and the United States being the leading contributors. Institutionally, the Chinese Academy of Sciences, University of Chinese Academy of Sciences, and Sichuan University are prominent contributors. Authorship analysis identifies key researchers, with Liu Zhuang being the most prolific author. "ACS Nano" and the "Journal of Controlled Release and Biomaterials" are identified as the leading journals in the field. Frequently occurring keywords include "cancer immunotherapy" and "drug delivery." Emerging frontiers in the field, such as "mRNA vaccine," "sonodynamic therapy," "oral squamous cell carcinoma," "STING pathway,"and "cGAS-STING pathway," are experiencing rapid growth. This study aims to provide new insights to advance scientific research and clinical applications in nanomedicine-based cancer immunotherapy.

Defective autophagy contributes to bupivacaine-induced aggravation of painful diabetic neuropathy in db/db mice.

Current evidence suggests that hyperactivated or impaired autophagy can lead to neuronal death. The effect of local anesthetics on painful diabetic neuropathy (PDN) and the role of autophagy in the above pathological process remain unclear, warranting further studies. So, PDN models were established by assessing the paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) in leptin gene-mutation (db/db) mice. Wild type (WT) and PDN mice received intrathecal 0.75% bupivacaine or/with intraperitoneal drug treatment (rapamycin or bafilomycin A1). Subsequently, the PWT and PWL were measured to assess hyperalgesia at 6 h, 24 h, 30 h, and 48 h after intrathecal bupivacaine. Also, sensory nerve conduction velocity (SNCV) and motor nerve conduction velocity (MNCV) were measured before and 48 h after intrathecal bupivacaine treatment. The spinal cord tissue of L4-L6 segments and serum were harvested to evaluate the change of autophagy, oxidative stress, oxidative injury, and apoptosis. We found that bupivacaine induced the activation of autophagy but did not affect the pain threshold, SNCV and MNCV in WT mice at predefined time points. Conversely, bupivacaine lowered autophagosome generation and degradation, slowed SNCV and aggravated spinal dorsal horn neuron oxidative injury and hyperalgesia in PDN mice. The autophagy activator (rapamycin) could decrease spinal dorsal horn neuron oxidative injury, alleviate the alterations in SNCV and hyperalgesia in bupivacaine-treated PDN mice. Meanwhile, the autophagy inhibitor (bafilomycin A1) could exacerbate spinal dorsal horn neuron oxidative injury, the alterations in SNCV and hyperalgesia in bupivacaine-treated PDN mice. Our results showed that bupivacaine could induce defective autophagy, slowed SNCV and aggravate spinal dorsal horn neuron oxidative injury and hyperalgesia in PDN mice. Restoring autophagy may represent a potential therapeutic approach against nerve injury in PDN patients with local anesthesia and analgesia.

Contribution of PKS+ Escherichia coli to colon carcinogenesis through the inhibition of exosomal miR-885-5p.

Objectives: About 90 % of all colorectal cancer (CRC) fatalities are caused by the metastatic spread of primary tumors, which is closely correlated with patient survival and spreads by circulating tumor cells (CTCs). The epithelial-mesenchymal transition (EMT) that characterizes CTCs is associated with a poor prognosis. Organotropic metastasis is dictated by the transmission of miRNAs by cancer-derived exosomes. The purpose of this research is to examine PKS + E's function. Coli in CRC metastases and exosomal miR-885-5p suppression. Methods: A cohort of 100 patients (50 CRC, 50 healthy) underwent colonoscopy screenings from February 2018 to August 2021. Exosomes were isolated using ultracentrifugation, and exosomal miRNA was analyzed using sequencing and qPCR. Results: Among the patients, 40 tested positive for E. coli (12 CRC, 23 healthy). Serotyping revealed that 68.57 % harbored the PKS gene. Exosomal miR-885-5p levels were significantly altered in CRC patients with PKS + E. coli. Intriguingly, our findings indicate that exosomes derived from EMT-CRC cells did not affect miR-885-5p synthesis in HUVECs. Moreover, we observed that the levels of miR-885-5p in both exosomes and the total CRC-conditioned medium were comparable upon isolation of exosomes from CRC cells. What's more, an increased expression of miR-558-5p within the tumors, and the group that received exosome treatment, as well as the EMT-HCT116 group, exhibited a higher occurrence of distant metastasis. Conclusion: PKS + E. By inhibiting exosomal miR-885-5p, coli is linked to CRC metastases, offering a possible target for therapeutic intervention.