Single-nucleus RNA-sequencing of orbitofrontal cortex in rat model of methamphetamine-induced sensitization.

The behavioral sensitization, characterized by escalated behavioral responses triggered by recurrent exposure to psychostimulants, involves neurobiological mechanisms that are brain-region and cell-type specific. Enduring neuroadaptive changes have been observed in response to methamphetamine (METH) within the orbitofrontal cortex (OFC), the cell-type specific transcriptional alterations in response to METH sensitization remain understudied. In this study, we utilized Single-nucleus RNA-sequencing (snRNA-seq) to profile the gene expression changes in the OFC of a rat METH sensitization model. The analyses of differentially expressed genes (DEGs) unveiled cell-type specific transcriptional reactions associated with METH sensitization, with the most significant alterations documented in microglial cells. Bioinformatic investigations revealed that distinct functional and signaling pathways enriched in microglia-specific DEGs majorly involved in macroautophagy processes and the activation of N-methyl-D-aspartate ionotropic glutamate receptors (NMDAR). To validate the translational relevance of our findings, we analyzed our snRNA-seq data in conjunction with a transcriptomic study of individuals with opioid use disorder (OUD) and a large-scale Genome-Wide Association Studies (GWAS) from multiple externalizing phenotypes related to drug addiction. The validation analysis confirmed the consistent expression changes of key microglial DEGs in human METH addiction. Moreover, the integration with GWAS data revealed associations between addiction risk genes and the DEGs observed in specific cell types, particularly microglia and excitatory neurons. Our study highlights the importance of cell-type specific transcriptional alterations in the OFC in the context of METH sensitization and their potential translational relevance to human drug addiction.

Engineering of stepwise-targeting chitosan oligosaccharide conjugate for the treatment of acute kidney injury.

Acute kidney injury (AKI) is a common and serious clinical syndrome of acute renal dysfunction in a short period. One of therapeutic interventions for AKI is to reduce ROS massively generated in the mitochondria and then ameliorate cell damage and apoptosis induced by oxidative stress. In this study, stepwise-targeting chitosan oligosaccharide, triphenyl phosphine-low molecular weight chitosan-curcumin (TPP-LMWC-CUR, TLC), was constructed for sepsis-induced AKI via removing excessive ROS in renal tubular epithelial cells. Benefiting from good water solubility and low molecular weight, TLC was rapidly and preferentially distributed in the renal tissues and then specifically internalized by tubular epithelium cells via interaction between Megalin receptor and LMWC. The intracellular TLC could further delivery CUR to mitochondria due to high buffering capacity of LMWC and delocalized positive charges of TPP. Both in vitro and in vivo pharmacodynamic results demonstrated the enhanced therapeutic effect of TLC in the treatment of AKI.

Effect of Electropulsing Treatment on Microstructure and Mechanical Properties of a Deformed ZrTiAlV Alloy.

In contrast to conventional heat treatment processes, electropulsing not only heats an alloy, but also exerts some other positive effects during the heating process. In this paper, the microstructural evolution and mechanical properties of a deformed Zr40Ti5Al4V alloy after electropulsing treatment were investigated. The results showed that when the charging voltage was 2 kV, there was a slight decrease in dislocation density due to the electron wind which softened the alloy even though the highest temperature of the specimen during the treatment was only 86 °C. Increasing the charging voltage to 6 kV not only further increased the heating temperature, but accelerated the phase transformation process of α″ → ß â†’ α. The presence of the α phase strengthened the alloy but notably deteriorated its ductility. A full and refined ß phase microstructure could be obtained when the charging voltage was increased to 8 kV. This simultaneously increased the strength and ductility of the alloy.

Novel zirconium complexes with constrained cyclic ß-enaminoketonato ligands: improved catalytic capability toward ethylene polymerization.

Novel Zr(iv) and Hf(iv) complexes bearing two constrained bulky ß-enaminoketonato ligands {[ArN[double bond, length as m-dash]CH-C8H3(CH2)n(R)O]2MBn2, M = Zr or Hf; n = 1, 2 or 3; R = H or C6H5; Ar = C6H5 or C6F5} were synthesized and clearly characterized. X-ray crystal structure analysis reveals that these complexes adopt a distorted octahedral geometry. Compared with non-constrained analogues, the Zr(iv) complexes with a cyclic skeleton exhibited high catalytic activities (up to 16.4 kgPE mmolZr(-1) h(-1)) toward ethylene polymerization at ambient pressure and elevated temperatures. Moreover, the catalytic properties of these complexes could be governed exquisitely by appropriate variation of the N-aryl substituents and the size of the benzocyclane. The Zr(iv) complexes bearing a non-fluorinated N-aryl group yielded oligomers, while the fluorinated analogues bearing a five-membered or six-membered cyclane group produced high molecular weight polyethylenes (33.4-306 kg mol(-1)) under similar conditions on account of the suppression effects on ß-H elimination. The Zr(iv) complexes are more active toward ethylene polymerization than the Hf(iv) analogues, and the resulting polymers exhibited higher molecular weight and narrower molecular weight distribution.

Pharyngocutaneous fistula after total laryngectomy: A systematic review and meta-analysis of risk factors.

OBJECTIVE: The pharyngocutaneous fistula (PCF) is the troublesome complication after total laryngectomy. Despite a large number of investigations having been performed, there is still controversy about which factors are most significant for PCF. The objective of the present meta-analysis was to analyze the potential risk factors for PCF after total laryngectomy. DATA SOURCES: Published English-language literature. REVIEW METHODS: PubMed, Ovid, Cochrane, and Web of Science databases were systematically searched using multiple search terms. Twenty-one studies with 3832 patients were identified. The quality of evidence was assessed by The National Institute for Health and Clinical Excellence. RESULTS: Sixteen studies involving 2598 patients were included for the meta-analysis. The results showed that, tumor subsite (RR=0.64, 95% CI 0.47-0.88, P<0.01), T stage (RR=0.70, 95% CI 0.51-0.96, P=0.03), previous radiotherapy (RR=0.62, 95% CI 0.46-0.84, P<0.01), postoperative hemoglobin <12.5g/L (RR=0.46, 95% CI 0.27-0.76, P<0.01), and surgical margin (RR=0.41, 95% CI 0.22-0.74, P<0.01) were the risk factors associated with the development of PCF. CONCLUSIONS: From the results of our study, several significant risk factors for PCF are identified. Methodologically high-quality comparative studies are needed for further evaluation.

[Histopathological study on the regularity of pyriform sinus carcinoma invading adjacent tissue and structure].

OBJECTIVE: To explore the regularity invading adjacent tissue of pyriform sinus carcinoma. METHODS: The whole organ serial section of 68 total or partial laryngectomy and hypopharyngectomy specimen of pyriform sinus carcinoma were histopathologically studied. RESULTS: In 68 pyriform sinus carcinoma, invaded ventricular and paraglottic spaces was 63 and 38 cases respectively, the difference of invasive frequency of both spaces was significantly marked (chi2 = 21.37, P < 0.01). Thyroid cartilage had the most invaded frequency of 92.6% (63/68). The all touching and pressing invasion of laryngeal cartilage was 89 times, and infiltrating invasion was 51 times. The invasive frequency of lateral cricoarytenoid muscle, posterior cricoarytenoid one, thyroarytenoid and interarytenoid ones were 63.2% (43/68), 57.4% (39/68), 55.9% (38/68), 51.5% (35/68) respectively. The invasive frequency of cricoarytenoid and cricothyroid joints were 30.9% (21/68), 17.6% (12/68) respectively. The invasive frequency of superior laryngeal nerve was 67.7% (44/65) , and more than that of recurrent laryngeal nerve (18/65, 27.7%). The pyriform sinus medial wall carcinoma was 14 cases, lateral wall carcinoma 18 cases, medial and lateral wall carcinoma 36 cases. The invaded pyriform sinus apex was 34 cases, normal its apex was 26 ones, submucous invasion of its apex was 8 ones. Light lymphocytic invasion was 66.2% (45/68) and seen most in pyriform sinus carcinoma. Submucous and leaping invasion of pyriform sinus carcinoma were 24 and 8 cases. CONCLUSIONS: Intralaryngeal invasion of pyriform sinus carcinoma arose through paraglottic space first. Laryngeal cartilage membrane and their cartilage were anatomical obstacle against cancerous invasion. Lateral cricoarytenoid muscle, posterior cricoarytenoid one, thyroarytenoid and interarytenoid ones were often invaded. Pyriform sinus medial wall carcinoma invaded intralaryngeal structure easily, its lateral wall carcinoma may invade upward, downward and outward along thyroid cartilage interior wall, medial and lateral wall carcinoma may invade intralaryngeal and extralaryngeal structure, and was the most serious lesion. The invasion of pyriform sinus apex is an important sign of pyriform sinus carcinoma spreading downward to inferior and peripheral tissues of hypopharynx.