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Application programming interface (API) recommendation plays a crucial role in facilitating smart contract development by providing developers with a ranked list of candidate APIs for specific recommendation points. Deep learning‐based approaches have shown promising results in this field. However, existing approaches mainly rely on token sequences or abstract syntax trees (ASTs) for learning recommendation point‐related features, which may overlook the essential knowledge implied in the relations between or within statements and may include task‐irrelevant components during feature learning. To address these limitations, we propose a novel code graph called pruned and augmented AST (pa‐AST). Our approach enhances the AST by incorporating additional knowledge derived from the control and data flow relations between and within statements in the smart contract code. Through this augmentation, the pa‐AST can better represent the semantic features of the code. Furthermore, we conduct AST pruning to eliminate task‐irrelevant components based on the identified flow relations. This step helps mitigate the interference caused by these irrelevant parts during the model feature learning process. Additionally, we extract the API sequence surrounding the recommendation point to provide supplementary knowledge for the model learning. The experimental results demonstrate our proposed approach achieving an average mean reciprocal rank (MRR) of 68.02%, outperforming the baselines' performance. Furthermore, through ablation experiments, we explore the effectiveness of our proposed code representation approach. The results indicate that combining pa‐AST with the API sequence yields improved performance compared with using them individually. Moreover, our AST augmentation and pruning techniques significantly contribute to the overall results. [ABSTRACT FROM AUTHOR]

Objective: Numerous methods and materials are available for vertical partial laryngectomy. In this study, the reparative effects of the platysma myocutaneous flap (PMF) and ribbon myocutaneous flap (RMF) on the postoperative voice quality of patients were compared to provide a reference for selecting a method conducive to improving postoperative voice quality. Methods: A retrospective analysis was performed on patients with unilateral T2‐3 glottic carcinoma. Following vertical partial laryngectomy, the defect was repaired with a PMF or simple RMF. Twelve months after surgery, voice quality was assessed according to voice acoustics, aerodynamics, and subjective perceptual evaluation, and glottic morphology was recorded using a laryngeal stroboscopy. Results: A total of 70 patients were identified, including 54 in the PMF group and 16 in the RMF group. The PMF group was superior to the RMF group in terms of voice quality assessed by voice acoustics, aerodynamics, and subjective perceptual evaluation. In the PMF group, 72.2% of patients performed phonation with their vocal cords, and approximately 27.8% of patients were affected by supraglottic compression. In the RMF group, 81.3% of patients were affected by supraglottic compression. No significant difference was found in the 5‐year survival rate between the two groups. Conclusion: For defect repair following vertical partial laryngectomy, a PMF can allow better postoperative voice quality to be achieved than an RMF because a PMF can provide more tissue (including strap muscle under the flap) for padding, which enables the glottic portion corresponding to the vocal cord to close well. Level of Evidence: 3 Laryngoscope, 134:3181–3186, 2024 [ABSTRACT FROM AUTHOR]

Paraquat (PQ), is characterized by neurotoxicity, which increases the potential risk of Parkinson's disease (PD) exposure in the long‐term and low doses. Triggering microglia activation and neuroinflammation is deemed an early event resulting in PD. However, the underlying pathogenesis of PD by PQ is not clear yet. In this article, C57BL/6J mice treated with PQ could successfully act out Parkinson‐like. In addition, we observed the fluorescence intensity enhancement of Iba‐1 activated microglia with released pro‐inflammatory, all ahead of both the damage of dopaminergic neurons in the substantia nigra and corpus striatum of the brain. Surprisingly, the injection of minocycline before PQ for many hours not only can effectively improve the neurobehavioral symptoms of mice but inhibit the activation of microglia and the release of pro‐inflammatory substances, even controlling the gradual damage and loss of neurons. A further mechanism of minocycline hampered the expression levels of key signaling proteins PI3K, PDK1, p‐AKT, and CD11b (the receptor of microglia membrane recognition), while a large number of inflammatory factors. Our results suggested that the CD11b/PI3K/NOX2 pathway may be a clue that microglia‐mediated inflammatory responses and neuronal damage in a PQ‐induced abnormal behavior Parkinson‐like mouse. [ABSTRACT FROM AUTHOR]

The synthesis and application of magnetic photocatalysts have become a critical topic in organic waste treatment. In this study, SrFe12O19 powder, SrFe12O19/SiO2 particles and SrFe12O19/SiO2/TiO2 photocatalysts were successfully produced using coprecipitation technique, Stöber process and solvothermal method, respectively. The degradation of methylene blue dye and simulated petroleum wastewater under simulated sunlight and ultraviolet light was used to assess the photocatalytic activity of the SrFe12O19/SiO2/TiO2 composites. Results showed the high photocatalytic performance of the produced SrFe12O19/SiO2/TiO2 photocatalysts with a 1 : 4 mass ratio of SrFe12O19 to TiO2 synthesized at 170 °C, whose surface has more hydroxyl groups as the active center. At 120 min of irradiation, the photodegradation rates of methylene blue and simulated petroleum wastewater were 83.94 % and 60.77 %, respectively. The photocatalytic activity of the Fe12O19/SiO2/TiO2 with ferrite semiconductor/insulator/semiconductor structure was improved by the action of the magnetic field of SrFe12O19. The SrFe12O19/SiO2/TiO2 composite particles can be recycled easily under an external magnetic field and show good application prospects in organic wastewater degradation. [ABSTRACT FROM AUTHOR]

The development of a self‐powered photodetector capable of functioning without an external power source has generated significant interest among researchers due to the growing demand for miniaturization and portability. In this study, a p‐Te/n‐WSe2 van der Waals heterojunction with a distinct rectification ratio exceeding 104, an ultralow reverse current of 10−11 A, and a light on/off ratio of up to 5657 under 405 nm light illumination is fabricated. Additionally, the Te/WSe2 heterojunction displayed a fast response speed of 18 µs and a broadband detection capability from 405 to 1550 nm. Furthermore, the Te/WSe2 heterojunction demonstrated a competitive self‐powered photodetector, exhibiting a light on/off ratio above 5 × 104, a photovoltaic responsivity of 196 mA W−1, and a photovoltaic detectivity of 7.5 × 1011 Jones. This study highlights the promising potential of Te/WSe2 vdWH for ultrasensitive self‐powered photodetection applications. [ABSTRACT FROM AUTHOR]

We have previously reported that Gypenoside LXXV (GP‐75), a novel natural PPARγ agonist isolated from Gynostemma pentaphyllum, ameliorated cognitive deficits in db/db mice. In this study, we further investigated the beneficial effects on cognitive impairment in APP/PS1 mice and a mouse model of diabetic AD (APP/PS1xdb/db mice). Interestingly, intragastric administration of GP‐75 (40 mg/kg/day) for 3 months significantly attenuated cognitive deficits in APP/PS1 and APP/PS1xdb/db mice. GP‐75 treatment markedly reduced the levels of glucose, HbA1c and insulin in serum and improved glucose tolerance and insulin sensitivity in APP/PS1xdb/db mice. Notably, GP‐75 treatment decreased the β‐amyloid (Aβ) burden, as measured by 11C‐PIB PET imaging. Importantly, GP‐75 treatment increased brain glucose uptake as measured by 18F‐FDG PET imaging. Moreover, GP‐75 treatment upregulated PPARγ and increased phosphorylation of Akt (Ser473) and GLUT4 expression levels but decreased phosphorylation of IRS‐1 (Ser616) in the hippocampi of both APP/PS1 and APP/PS1xdb/db mice. Furthermore, GP‐75‐induced increases in GLUT4 membrane translocation in primary hippocampal neurons from APP/PS1xdb/db mice was abolished by cotreatment with the selective PPARγ antagonist GW9662 or the PI3K inhibitor LY294002. In summary, GP‐75 ameliorated cognitive deficits in APP/PS1 and APP/PS1xdb/db mice by enhancing glucose uptake via activation of the PPARγ/Akt/GLUT4 signaling pathways. [ABSTRACT FROM AUTHOR]

Aim: To review and analyse the evidence on the efficacy and safety of non‐pharmacological interventions for preterm infants to relieve endotracheal suctioning (ES) pain. Design: A systematic review per the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines. Methods: Six databases were searched with a retrieval strategy. Parallel and crossover randomized controlled trials reporting non‐pharmacological interventions for relieving ES pain in preterm infants were identified from inception to 1 September 2021. The protocol was published in PROSPERO (CRD42021276058). Results: Ten studies were retrieved, including nine different non‐pharmacological interventions. Seven studies reported that non‐pharmacological interventions in relieving pain were more effective than conventional care during ES, and three trials reported its safety. Due to the heterogeneity of pain assessment tools, time of assessment and population, only Facilitated tucking had sufficient evidence that it is a safe and effective non‐pharmacological intervention. [ABSTRACT FROM AUTHOR]

Background: The therapeutic value of targeted therapies in patients with lung cancer is reduced when tumours acquire secondary resistance after an initial period of successful treatment. However, the molecular events behind the resistance to targeted therapies in lung cancer remain largely unknown. Aims: To discover the important role and mechanism of lncRNA BC in promoting tumor metastasis and influencing clinical prognosis of LUAD. Materials & Methods: Microarrays were used to screen a comprehensive set of lncRNAs with differential expression profiles in lung cancer cells. The functional role and mechanism of lncRNA were further investigated by gain‐ and loss‐of‐function assays. RNA pull‐down, protein assays, and mass spectrometry were used to identify proteins that interacted with lncRNA. TaqMan PCR was used to measure lncRNA in lung adenocarcinoma and adjacent nontumor tissues from 428 patients. The clinical significance of lncRNA identified was statistically confirmed in this cohort of patients. Results: In this study, we show that the long non‐coding RNA BC009639 (BC) is involved in acquired resistance to EGFR‐targeted therapies. Among the 235 long non‐coding RNAs that were differentially expressed in lung cancer cell lines, with different metastatic potentials, BC promoted growth, invasion, metastasis, and resistance to EGFR‐tyrosine kinase inhibitors (EGFR‐TKIs), both in vitro and in vivo. BC was highly expressed in 428 patients with lung adenocarcinoma (LUAD) and high BC expression correlated with reduced efficacy of EGFR‐TKI therapy. To uncover the molecular mechanism of BC‐mediated EGFR‐TKI resistance in lung cancer, we screened and identified nucleolin and hnRNPK that interact with BC. BC formed the splicing complex with nucleolin and hnRNPK to facilitate the production of a non‐protein‐coding inositol monophosphatase domain containing 1 (IMPAD1) splice variant, instead of the protein‐coding variant. The BC‐mediated alternative splicing (AS) of IMPAD1 resulted in the induction of the epithelial–mesenchymal transition and resistance to EGFR‐TKI in lung cancer. High BC expression correlated with clinical progress and poor survival among 402 patients with LUAD. Disscussion: Through alternative splicing, BC boosted the non‐coding IMPAD1‐203 transcript variant while suppressing the IMPAD1‐201 variant. In order to control the processing of pre‐mRNA, BC not only attracted RNA binding proteins (NCL, IGF2BP1) or splicing factors (hnRNPK), but also controlled the formation of the splicing‐regulator complex by creating RNA‐RNA‐duplexes. Conclusion: Our results reveal an important role for BC in mediating resistance to EGFR‐targeted therapy in LUAD through IMPAD1 AS and in implication for the targeted therapy resistance. [ABSTRACT FROM AUTHOR]

Background: The immune profile in primary resected hypopharyngeal squamous cell carcinoma (HPSCC) and its prognostic value remain to be defined. Methods: We enrolled 100 patients with HPSCC underwent primary surgical resection at our department. HPSCC samples were examined using immunohistochemistry for the expressions of CD8, Foxp3, CD163, CD66B, programmed death ligand‐1 (PD‐L1), and interferon (IFN)‐γ. The immune pattern of the tumor microenvironment (TME) was discriminated into inflamed and non‐inflamed tumors based on the presence or absence of parenchymal CD8+ T cells. Results: We found that 74% of HPSCC cases in our cohort were characterized by an immune‐inflamed TME. Immune‐inflamed patterns demonstrated an inferior survival with a significantly increased density of CD163+ tumor‐associated macrophages and Foxp3+ regulatory T cells. Additionally, the inflamed tumor showed increased expression of PD‐L1, without IFN‐γ upregulation. Conclusions: The immune‐inflamed pattern is the predominant preexisting immune phenotype in HPSCC and demonstrates immunosuppressive immune cell recruitment. [ABSTRACT FROM AUTHOR]

Background: Given malignant ascites with a terrible prognosis and a unique immune microenvironment, our purpose is to evaluate whether oncolytic herpes simplex virus type 2(OH2) is able to safely eliminate ascites of colon cancer and through which specific mechanism it exerts antitumor immunity. Methods: We established an ascites mice model through intraperitoneal injection of CT26 cells and obtained an appropriate dose range for in vivo tests. Efficacy and safety of OH2 were detected by weight of ascites, blood routine analysis, histopathological examination, and the survival time of mice. The specific mechanism underlying antitumor immunity was analyzed by cytometric bead array, flow cytometry, and single‐cell RNA sequencing. Furthermore, anti‐interleukin (IL)‐6R antibody tocilizumab was synchronously or sequentially delivered with OH2 to explore the role of the regional cytokine storm, mainly IL‐6 hypersecretion. Results: OH2 was able to eliminate ascites and significantly prolong the survival of mice‐bearing CT26 tumor cells by intraperitoneal injection, without obvious systemic damage to the main organs even though a regional cytokine storm. Hypersecretion of pro‐inflammatory cytokines, mainly IL‐6, and increased infiltration of CD4+ and CD8+ T cells were observed in ascites mice treated by OH2, compared with those treated by 5‐fluorouracil or nonresponders. Furthermore, the initial‐stage blocking of the IL‐6 pathway was able to considerably suppress antitumor immune responses driven by OH2. Surprisingly, we discovered upregulations of the immune checkpoint genes such as Cd274 and Pdcd1 by single‐cell RNA sequencing. Conclusions: OH2 could safely eliminate malignant ascites of colon cancer and convert the cold immune microenvironment by inducing a remarkably regional cytokine storm in ascites, mainly IL‐6, in the early stage of antitumor immune responses beyond directed oncolytic virotherapy. [ABSTRACT FROM AUTHOR]

Spiro[azetidine‐indolines] are important scaffolds in diverse bioactive compounds. Current efforts to synthesize spiro[azetidine‐indolines] are limited to chiral spiro[azetidine‐2,3′‐indolines]. Asymmetric synthesis of structurally similar chiral spiro[azetidine‐3,3′‐indolines] remains unexplored. In this work, the first copper(I)‐catalyzed asymmetric Kinugasa/aryl C−C coupling cascade reaction is described. This provides a straightforward access to densely functionalized chiral spiro[azetidine‐3,3′‐indoline]‐2,2′‐diones in good yields and with high enantioselectivity. [ABSTRACT FROM AUTHOR]

The advantages of urgent‐start peritoneal dialysis (PD) vis‐à‐vis urgent‐start hemodialysis (HD) are not clear. We performed a systematic review and meta‐analysis of studies comparing the two modalities. Databases of PubMed, Embase, Ovoid, and Google Scholar were searched up to November 1, 2020. The primary outcome was mortality, and secondary outcomes were dialysis‐related infectious complications and mechanical complications. Risk ratios (RRs) were calculated for all outcomes. Seven studies were included. The pooled analysis revealed a statistically significant reduced risk of all‐cause mortality in patients undergoing urgent‐start PD as compared to urgent‐start HD (RR: 0.61, 95% confidence interval [CI] [0.40, 0.94], I2 = 56.34%). A meta‐analysis of dialysis‐related infectious complications indicated no statistically significant difference between the two modalities (RR: 0.66, 95% CI [0.29, 1.50], I2 = 69.62%). Our analysis revealed a statistically significant reduced risk of mechanical complications in patients undergoing urgent‐start PD (RR: 0.54, 95% CI [0.40, 0.73], I2 = 0%). To conclude, unadjusted data from observational studies are indicative of lower mortality and lower risk of mechanical complications with urgent‐start PD versus urgent‐start HD. The risk of infectious complications was not different between the two groups. Further studies with a larger sample size using propensity‐matched cohorts are needed to strengthen current evidence. [ABSTRACT FROM AUTHOR]

Targeting the PPARγ might be a potential therapeutic strategy for diabetes‐associated cognitive decline (DACD). In this study, Gypenoside LXXV (GP‐75), a dammarane‐type triterpene compound isolated from Gynostemma pentaphyllum, was found to be a novel PPARγ agonist using a dual‐luciferase reporter assay system. However, whether GP‐75 has protective effects against DACD remains unknown. Interestingly, intragastric administration of GP‐75 (40 mg/kg/day) for 12 weeks significantly attenuated the cognitive deficit in db/db mice. GP‐75 treatment significantly improved the glucose tolerance and lipid metabolism, and suppressed neuroinflammation. Notably, GP‐75 treatment dramatically increased the uptake of glucose by the brain, as detected by 18F‐FDG PET. Incubation of primary cortical neurons with GP‐75 significantly increased 2‐deoxyglucose uptake. In addition, GP‐75 treatment markedly increased the p‐Akt (Ser 473)/total Akt levels and the expression levels of PPARγ and GLUT4, while decreasing the levels of p‐IRS‐1 (Ser 616)/total IRS‐1. Importantly, all of these protective effects mediated by GP‐75 were abolished by cotreatment with the PPARγ antagonist, GW9662. However, GP‐75‐mediated PPARγ upregulation was not affected by coincubation with the phosphatidylinositol 3‐kinase inhibitor, LY294002. Collectively, GP‐75 might be a novel PPARγ agonist that ameliorates cognitive deficit by enhancing brain glucose uptake via the activation of Akt/GLUT4 signaling in db/db mice. [ABSTRACT FROM AUTHOR]

Enhancing glucagon‐like peptide 1 (GLP‐1) signaling with a dipeptidyl peptidase IV (DPP‐4) inhibitor might exert protective effects on Alzheimer's disease (AD). We found that intragastric administration of Gramcyclin A (10, 20 and 40 mg/kg), a novel DPP‐4 inhibitor, for 3 months significantly reversed cognitive decline in APP/PS1/tau triple transgenic mice in a dose‐dependent manner. Gramcyclin A treatment markedly reduced Aβ plaques as well as the insoluble and soluble forms of Aβ40 and Aβ42 in the hippocampus of APP/PS1/tau mice. Treatment with Gramcyclin A remarkedly decreased the level of microglia and suppressed neuroinflammation in the hippocampus of APP/PS1/tau mice. Moreover, Gramcyclin A treatment could increase brain glucose uptake in APP/PS1/tau mice, as detected by 18‐fluoro‐2‐deoxyglucose (18F‐FDG) micro‐positron emission tomography (micro‐PET) imaging. Furthermore, Gramcyclin A significantly increased expression of glucagon‐like peptide‐1 (GLP‐1), GLP‐1R, proliferator‐activated receptor gamma coactivator (PGC)‐1α and glucose transporter 4 (GLUT4), and inhibited insulin receptor (IRS)‐1 phosphorylation and tau hyperphosphorylation in the hippocampus of APP/PS1/tau mice. Collectively, Gramcyclin A conferred protective effects against AD via enhancing brain GLP‐1‐dependent glucose uptake. The DPP‐4 inhibitor Gramcyclin A might be a potential therapeutic drug for AD. [ABSTRACT FROM AUTHOR]

Background: The histological grade of bladder cancer (BCa) is an important factor associated with the treatment and prognosis. However, accurate determination of the preoperative histological grade of BCa remains a challenge. Purpose: To investigate the diagnostic potential of synthetic MRI (SyMRI) in evaluating the histological grade of BCa. Study Type: Prospective. Subjects: Sixty patients (48 men and 12 women; mean age, 65 ± 11 years) with pathologically confirmed BCa (33 with high‐grade BCa and 27 with low‐grade BCa) were enrolled. Field Strength/Sequence: Diffusion‐weighted imaging (DWI) acquired by a single‐shot echo‐planar sequence and SyMRI acquired by a multidynamic multiecho (MDME) sequence at 3.0 T. Assessment: Preoperative quantitative longitudinal relaxation time (T1), transverse relaxation time (T2), proton density (PD), and apparent diffusion coefficient (ADC) values of BCa were independently measured by two radiologists. Statistical Tests: Interclass correlation coefficient (ICC), independent sample t‐test, Mann–Whitney U test, Delong test, and receiver operating characteristic curve (ROC) analysis were used. Results: Significant differences were found in the mean of all the T1, T2, PD, and ADC values between high‐ and low‐grade BCa. The best diagnostic performance was found for the mean ADC value with an area under the ROC curve (AUC) of 0.869, while the AUC values of the mean PD, T1, and T2 values were 0.755, 0.740, and 0.723, respectively. Data Conclusion: SyMRI may be a potential noninvasive technique for evaluating the histological grade of BCa. However, the overall diagnostic performance of SyMRI‐derived parameters was inferior to the ADC value. Levels of Evidence: 2. Technical Efficacy Stage: 2. [ABSTRACT FROM AUTHOR]

A copper‐catalyzed [3+2] cylcoaddition/ alkenyl C−N coupling tandem reaction was demonstrated. It provided a method for the formation of triazolopiperidine skeletons. [ABSTRACT FROM AUTHOR]

A synthesis of spiroindolinone‐isoindolinone skeletons is presented. The protocol is through a Ugi four‐component reaction followed by highly efficient and mild copper‐catalyzed intramolecular tandem C−N/C−C coupling process. Control experiments demonstrated that the formation of C−C bond is a copper catalyzed coupling process rather than base promoted nucleophilic aromatic substitution pathway which proposed in Prof. Van der Eycken's palladium catalyst system previously. [ABSTRACT FROM AUTHOR]

Excessive nitrogen (N) fertilization in croplands results in environmental problems, such as soil quality deterioration, water contamination, and biodiversity losses, which threaten the sustainable development of soil ecosystems. The soil nematode food web plays key roles in soil organic matter decomposition and nutrient cycling, and thus the sustainable development of cropland ecosystems. However, how the negative impact from the excessive N fertilization on the nematode food web is effectively alleviated remains uncertain. This study aimed to explore the effects of different N fertilization management practices (N fertilizer reduction or organic material addition) on alleviating the negative effects on the nematode food web in croplands. Four treatments/ management practices were examined: conventional fertilization (N control), N fertilizer reduction of 100% (N0), N fertilizer reduction of 50% (N1), and conventional fertilization with organic material addition (N+S). The results showed that the abundance of nematodes and microbial phospholipid fatty acids (PLFAs) both increased in the treatments of N0, N1, and N+S compared with N. Besides, N+S also increased the nematodes' biomass, diversity, and metabolic footprint, which correspondingly strengthened the nutrient turnover through the nematode food web. Overall, two management practices 1)N fertilizer reduction and 2) organic material addition, differ in the abiotic or biotic process in alleviating the negative effects of N fertilization on the nematode food web. The reducing N fertilization can directly alleviate the negative effect of fertilizer on soil acidification and then benefit for the growth of microorganisms and nematodes. The exogenous carbon input from organic material addition might promote carbon flowing and immobilization into nematode food web, and ultimately enhance the stability of soil food web. [ABSTRACT FROM AUTHOR]

Numerous studies have suggested that urothelial cancer‐associated 1 (UCA1) acts as a suppressor gene affecting cell proliferation and migration. However, the biological role and the potential mechanism of UCA1 in the progression of pre‐eclampsia (PE) remains unclear. The UCA1 level was markedly upregulated in PE pregnancies relative to non‐PE ones in GSE75010 and tissues. A higher body mass index (BMI), maximum systolic blood pressure (BP), and maximum diastolic BP were observed in PE pregnancies, whereas the newborn weight z‐score was lower compared with those of non‐PE pregnancies. Knockdown of UCA1 accelerated the proliferative migratory abilities and cell cycle progression, but inhibited apoptosis of HTR‐8/SVneo and JAR cells. Then, we found that Janus kinases 2 (JAK2) was negatively correlated with UCA1. In addition, JAK2 was downregulated in the placenta of PE pregnancies and was negatively regulated by UCA1. UCA1 was mainly enriched in the nucleus. Knockdown of UCA1 reduced the occupancies of the enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) and H3K27me3 on the Janus kinase 2 (JAK2) promoter regions. Finally, rescue experiments found that transfection of short‐hairpin JAK2 attenuated proliferative and migratory abilities of trophoblasts, which were partially reversed after UCA1 knockdown. In short, UCA1 is upregulated in the trophocytes of PE pregnancies and accelerates trophoblast cell invasion and proliferation by downregulating JAK2. [ABSTRACT FROM AUTHOR]

Synaptic mitochondria are particularly vulnerable to physiological insults, and defects in synaptic mitochondria are linked to early pathophysiology of Alzheimer's disease (AD). Mitophagy, a cargo‐specific autophagy for elimination of dysfunctional mitochondria, constitutes a key quality control mechanism. However, how mitophagy ensures synaptic mitochondrial integrity remains largely unknown. Here, we reveal Rheb and Snapin as key players regulating mitochondrial homeostasis at synapses. Rheb initiates mitophagy to target damaged mitochondria for autophagy, whereas dynein–Snapin‐mediated retrograde transport promotes clearance of mitophagosomes from synaptic terminals. We demonstrate that synaptic accumulation of mitophagosomes is a feature in AD‐related mutant hAPP mouse brains, which is attributed to increased mitophagy initiation coupled with impaired removal of mitophagosomes from AD synapses due to defective retrograde transport. Furthermore, while deficiency in dynein–Snapin‐mediated retrograde transport recapitulates synaptic mitophagy stress and induces synaptic degeneration, elevated Snapin expression attenuates mitochondrial defects and ameliorates synapse loss in AD mouse brains. Taken together, our study provides new insights into mitophagy regulation of synaptic mitochondrial integrity, establishing a foundation for mitigating AD‐associated mitochondria deficits and synaptic damage through mitophagy enhancement. Synopsis: The integrity of synaptic mitochondria is maintained by a coordination of Rheb‐dependent mitophagy and dynein‐Snapin‐mediated retrograde transport. Rheb targets damaged mitochondria for autophagy in distal axons, whereas dynein‐Snapin‐mediated retrograde transport promotes removal of mitophagosomes from synaptic terminals.Increased mitophagy initiation coupled with impaired retrograde transport of mitophagosomes induces mitophagy stress at Alzheimer's disease (AD) synapses.Elevated Snapin expression rescues such mitophagy failure and attenuates synaptic mitochondrial deficits, thereby ameliorating AD‐linked synaptic degeneration. [ABSTRACT FROM AUTHOR]

The platysma skin flap was used for laryngeal reconstruction after vertical partial laryngectomy to improve the postoperative voice quality of patients with T2 and T3 glottic laryngeal carcinoma. Sixty‐nine patients with unilateral T2 and T3 glottic laryngeal carcinoma were included. Forty‐six patients received vertical partial laryngectomy, and a platysma skin flap was used for laryngeal reconstruction. The other 23 patients underwent transoral laser microsurgery. Subjective and objective examinations were performed to evaluate laryngeal morphology after the surgery. Acceptable voice quality was achieved for 46 patients who underwent vertical partial laryngectomy. Flap vibrational waves occurred in 19 cases (41.3%). The platysma skin flap is an ideal tissue for the reconstruction of articulation structure in open surgery of T2 and T3 unilateral glottic laryngeal carcinoma. [ABSTRACT FROM AUTHOR]

Summary: Copper‐catalyzed cross‐couplings of aryl halides and nucleophiles, traditionally called Ullmann‐type coupling reactions, were initially reported by Ullmann et al. from 1901—1929. A seminal report in 1998 by Ma et al. from Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences revealed an accelerating effect caused by amino acids, which brought Ullmann‐type coupling reactions into a ligand‐accelerating era. From 1999 to the first 10 years of 2000s, the first‐generation ligands were developed by many researchers and promoted Ullmann‐type coupling reactions of aryl iodides and bromides under relatively mild conditions. Amino acid ligands, developed by Ma and coworkers, are one class of the most important first‐generation ligands. In the second 10 years of 2000s, Ma et al. led the discovery of second‐generation ligands for copper‐catalyzed cross‐coupling reactions. Two great breakthroughs have been realized by using second‐generation oxalic diamide and related amide ligands, with aryl chlorides as general coupling partner and with low catalyst loadings. Now copper‐catalyzed cross coupling reactions of aryl halides and nucleophiles with amino acids or oxalic diamides and related amides as ligands are recognized as Ullmann‐Ma reactions and have found extensive applications in organic synthesis. [ABSTRACT FROM AUTHOR]

Summary: Copper‐catalyzed cross‐couplings of aryl halides and nucleophiles, traditionally called Ullmann‐type coupling reactions, were initially reported by Ullmann et al. from 1901—1929. A seminal report in 1998 by Ma et al. from Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences revealed an accelerating effect caused by amino acids, which brought Ullmann‐type coupling reactions into a ligand‐accelerating era. From 1999 to the first 10 years of 2000s, the first‐generation ligands were developed by many researchers and promoted Ullmann‐type coupling reactions of aryl iodides and bromides under relatively mild conditions. Amino acid ligands, developed by Ma and coworkers, are one class of the most important first‐generation ligands. In the second 10 years of 2000s, Ma et al. led the discovery of second‐generation ligands for copper‐catalyzed cross‐coupling reactions. Two great breakthroughs have been realized by using second‐generation oxalic diamide and related amide ligands, with aryl chlorides as general coupling partner and with low catalyst loadings. Now copper‐catalyzed cross coupling reactions of aryl halides and nucleophiles with amino acids or oxalic diamides and related amides as ligands are recognized as Ullmann‐Ma reactions and have found extensive applications in organic synthesis. [ABSTRACT FROM AUTHOR]

The objective of the present study was to explore the effects of environmental chemicals, such as methyl mercury, paraquat, and bisphenol A, on cell proliferation and apoptosis, as well as the expression levels of neuronal differentiation‐related genes in neural stem cells (NSCs). NSCs originated from human umbilical cord blood (HUCB‐NSCs) were used as cell models in the current study. CCK‐8 and flow cytometry experiments were performed to assess the effects of methyl mercury, paraquat, and bisphenol A on the proliferation and apoptosis of HUCB‐NSCs at different processes, including proliferation and differentiation stages. The expressions of neuronal differentiation‐related genes were determined by reverse transcription‐polymerase chain reaction and western blot analysis. The results showed that methyl mercury, paraquat, and bisphenol A treatments significantly inhibited cell proliferation and induced cell apoptosis in HUCB‐NSCs, as well as decreased the expressions of Oct4, Gdf3, and Sox1, whereas increased Pax6 and Ngn1 expressions at both mRNA and protein levels. In conclusion, this study demonstrates that environmental chemicals can impair the proliferation and differentiation of NSCs, which may cause abnormal development of the nervous system. [ABSTRACT FROM AUTHOR]

Tumor complexity makes the development of highly sensitive tumor imaging probes an arduous task. Here, we construct a peptide‐based near‐infrared probe that is responsive to fibroblast activation protein‐α (FAP‐α), and specifically forms nanofibers on the surface of cancer‐associated fibroblasts (CAFs) in situ. The assembly/aggregation‐induced retention (AIR) effect results in enhanced accumulation and retention of the probe around the tumor, resulting in a 5.5‐fold signal enhancement in the tumor 48 h after administration compared to that of a control molecule that does not aggregate. The probe provides a prolonged detectable window of 48 h for tumor diagnosis. The selective assembly of the probe results in a signal intensity over four‐ and fivefold higher in tumor than in the liver and kidney, respectively. With enhanced tumor imaging capability, this probe can visualize small tumors around 2 mm in diameter. [ABSTRACT FROM AUTHOR]

Background: To investigate whether the relative computed tomography (CT) value (rCT) of adjacent pancreatic parenchyma can distinguish focal‐type autoimmune pancreatitis (fAIP) from pancreatic ductal adenocarcinoma (PDAC). Methods: A total of 13 patients with fAIP and 20 patients with PDAC were included in this study. The rCT was calculated as the ratio of the CT value of adjacent pancreatic parenchyma to that of muscle. The diagnostic performance of rCT for discriminating fAIP from PDAC was evaluated using receiver operating characteristic (ROC) analysis. Results: Both fAIP and PDAC presented hyper‐fibrosis histologically and delayed enhancement on CT examination. Moreover, the pancreatic parenchyma of fAIP presented serious inflammation. The mean rCT of the parenchyma was significantly lower in fAIP than in PDAC in all phases. The best diagnostic performance of the rCT value was found in the pancreatic phase, with an area under the ROC curve of 0.912, while the areas under the ROC curve of the portal and delayed phases were 0.812 and 0.754, respectively. The optimal cut‐off value for distinguishing fAIP from PDAC was 1.62 in the pancreatic phase. Conclusions: The rCT of the pancreatic parenchyma during the pancreatic phase may be a feasible CT feature for differentiating fAIP from PDAC. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of paraquat (PQ) exposure on gene expression in neural stem cells as well as structures and functions of vascular endothelial cells. Methods: RNA‐Seq was used to explore the differentially expressed genes in human umbilical cord blood‐neural stem cells (HUCB‐NSCs) at different stages (eg, proliferation, early and late differentiation) in the presence of PQ. The effects of PQ on human umbilical vein endothelial cells (HUVECs), including cell proliferation, apoptosis, cytokines secretion, and expression of tight junction proteins, were assessed with CCK‐8, flow cytometry, ELISA, and western blot analysis, individually. Results: A total of 53 genes were up‐regulated and 61 genes were down‐regulated in PQ treated HUCB‐NSCs, including seven genes associated with the differentiation of neural stem cells, for example, Gfap, S100B, Oct4, Gdf3, Sox1, Pax6, and Ngn1. PQ treatment significantly reduced the proliferation of HUVECs, inhibited cytokines secretion (VEGF, BFGF) and expressions of tight junction‐associated protein (Claudin 1, Occludin, ZO‐1), as well as induced significant apoptosis. Conclusion: Our study suggests that PQ impairs the development of nervous system by regulating the expression of genes associated with neural stem cell differentiation, as well as the structure and function of vascular endothelial cells, which together lead to abnormality in the nervous system. [ABSTRACT FROM AUTHOR]

A copper‐catalysed double O‐aylation for enantioselective formation of chiral oxa‐spirocycles is described. The method is based on a stepwise process and afforded chiral oxa‐spirocycles with good yields and moderate to high enantioselectivities. [ABSTRACT FROM AUTHOR]

2,4‐Dihydro‐3H‐1,2,4‐triazol‐3‐ones are a class of biologically important heterocycles. A novel and simple synthesis of such structures is developed. The method is through a base‐promoted Boulton‐Katritzky‐type rearrangement of 1‐(isoxazol‐3‐yl)ureas and is highly efficient for the formation of 2,4‐dihydro‐3H‐1,2,4‐triazol‐3‐ones. [ABSTRACT FROM AUTHOR]

Abstract: Background: Thyroglossal duct cysts (TDCs) are usually resected through an incision over the entire protruding zone. The resulting scar is aesthetically displeasing, so we explored the use of endoscope‐assisted excision of TDCs via a submaxillary vestibular approach. The purpose of this study was to demonstrate the feasibility, validity, and safety of this approach and to evaluate the follow‐up results. Methods: From January 2007 to August 2015, 16 patients with TDCs underwent surgical resection using a submaxillary vestibular approach. Results: All procedures were successfully performed using endoscope‐assisted surgery via a submaxillary vestibular approach. There were no postoperative complications and no conversions of the operation. The average follow‐up period was 73 months (range 14‐117 months) without recurrence. All patients and their families were satisfied with the cosmetic results. Conclusion: Endoscope‐assisted excision of TDCs using a submaxillary vestibular approach is feasible and can be applied effectively and safely with good cosmetic results. Therefore, this method should be considered a viable alternative approach for these patients. [ABSTRACT FROM AUTHOR]

An efficient and practical approach to 3a-azidofuroindolines and -pyrroloindolines involving an iodine-catalyzed azidation/cyclization cascade of tryptophols and tryptamines with NaN3 was developed. Further transformation of the C3-azidated product provided a key intermediate for the total synthesis of psychotriasine. [ABSTRACT FROM AUTHOR]

Molybdenum sulfide (MoS2) has emerged as a promising electrocatalyst for hydrogen evolution reaction (HER) owing to its high activity and stability during the reaction. However, the efficiency of hydrogen production is limited by the number of active sites in MoS2. In this work, a simple method of fabricating polycrystalline multilayer MoS2 on Mo foil for efficient hydrogen evolution is demonstrated by controlling the sulfur (S) vacancy concentration, which can introduce new bands and lower the hydrogen adsorption free energy (Δ GH). For the first time, theoretical and experimental results show that the HER performance of synthesized MoS2 with S vacancy can be further enhanced by the very small amount of platinum (Pt) decoration, which can introduce new gap states and more catalytic sites in real space with suitable free energy. The fabricated hybrid electrocatalyst exhibits significantly smaller Tafel slope of 38 mV dec−1 and better HER electrocatalytic activity compared to previous works. This approach provides a simple pathway to design low-cost, efficient and sizable hydrogen-evolving electrode by simultaneously tuning the MoS2 band structure and active sites. [ABSTRACT FROM AUTHOR]

Angioimmunoblastic T-cell lymphomas ( AITLs) frequently carry mutations in the TET2 and IDH2 genes. TET2 mutations represent early genetic lesions as they had already been detected in haematopoietic precursor cells of AITL patients. We show by analysis of whole-tissue sections and microdissected PD1+ cells that the frequency of TET2-mutated AITL is presumably even higher than reported (12/13 cases in our collection; 92%). In two-thirds of informative AITLs (6/9), a fraction of B cells was also TET2-mutated. Investigation of four AITLs by TET2 and IGHV gene sequencing of single microdissected B cells showed that between 10% and 60% of polyclonal B cells in AITL lymph nodes harboured the identical TET2 mutations of the respective T-cell lymphoma clone. Thus, TET2-mutated haematopoietic precursor cells in AITL patients not only give rise to the T-cell lymphoma but also generate a large population of mutated mature B cells. Future studies will show whether this is a reason why AITL patients frequently also develop B-cell lymphomas. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

ABSTRACT Epithelial-mesenchymal transition (EMT) is believed to be involved in lung fibrosis process induced by paraquat (PQ); however, the molecular mechanism of this process has not been clearly established. The present study investigated the potential involvement of EMT after PQ poisoning. The expressions of EMT markers, such as E-cadherin and α-smooth muscle actin (α-SMA), at multiple time points after exposure to different concentrations of PQ were evaluated by western blot analysis. Following PQ treatment, EMT induction was observed under microscopy. Related fibrosis genes, including Matrix metalloproteinase 2 (MMP-2), Matrix metalloproteinase 9 (MMP-9), collagens type I (COL I), and type III (COL III), were also evaluated by measuring their mRNA levels using RT-PCR analysis. Signaling pathways were analyzed using selective pharmacological inhibitors for MAPK. Cell migration ability was evaluated by scratch wound and Transwell assays. The data showed that PQ-induced epithelial RLE-6NT cells to develop mesenchymal cell characteristics, as indicated by a significant decrease in the epithelial marker E-cadherin and a significant increase in the extracellular matrix (ECM) marker α-smooth muscle actin in a dose and time-dependent manner. Moreover, PQ-treated RLE-6NT cells had an EMT-like phenotype with elevated expression of MMP-2, MMP-9, and COL I and COL III and enhanced migration ability. Signal pathway analysis revealed that PQ-induced EMT led to ERK-1 and Smad2 phosphorylation through activation of the MAPK pathway. The results of the current study indicate that PQ-induced pulmonary fibrosis occurs via EMT, which is mediated by the MAPK pathway. This implies that the MAPK pathway is a promising therapeutic target in alveolar epithelial cells. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1407-1414, 2016. [ABSTRACT FROM AUTHOR]

POEMS syndrome is a rare plasma cell dyscrasia. Serum concentrations of the monoclonal protein in this disorder are typically low, and inapplicable to monitor disease activity in most cases, resulting in limited practical and prognostic values. Novel immunoassays measuring isotype-specific heavy/light chain ( HLC) pairs showed its utility in disease monitoring and outcome prediction in several plasma cell dyscrasias. We report results of HLC measurements in 90 patients with POEMS syndrome. Sixty-six patients (73%; 95% confidence interval, 63-82%) had an abnormal HLC ratio at baseline. It could stratify the risk of disease relapse and was strongly associated with worse progression-free survival in a multivariate analysis ( P = 0.021; hazard ratio [ HR] 6.89, 95% CI 1.34-35.43). After therapy, HLC ratios improved, with 43 patients (48%) remaining abnormal. The post-therapeutic HLC ratio, if abnormal, also remained as an independent prognostic factor associated with worse progression-free survival ( P = 0.019; HR 4.30, 95% CI 1.27-14.56). These results suggest the prognostic utility of HLC ratios in clinical management of POEMS patients. [ABSTRACT FROM AUTHOR]

Although autologous stem cell transplantation or melphalan-based chemotherapy has significantly improved the prognosis of POEMS syndrome, a few patients will relapse or be refractory to primary therapy, and there is a lack of studies regarding these patients. In this study, we used low-dose lenalidomide (10 mg daily) and dexamethasone (40 mg, once weekly) to treat twelve patients with relapsed ( n = 8) or refractory ( n = 4) POEMS syndrome. After a median follow-up time of 20 months, the overall hematologic response rate was 77% with 44% having a complete response. Eight (67%) patients had neurological response, and the median overall neuropathy limitation scale score was reduced from 3 (range, 1-9) to 2 (range, 0-6). Serum vascular endothelial growth factor response rate was 91% and 46% of patients had normal serum VEGF levels. One patient had progression of the disease 3 months after the end of treatment and subsequently died from the disease. Therefore, the estimated 2 year overall survival and progression-free survival were 92%. The low-dose lenalidomide and dexamethasone regimen was well tolerated, with no treatment-related death or any grade 3 or 4 toxicity. In conclusion, low-dose lenalidomide plus dexamethasone therapy is an effective and safe regimen for patients with relapsed or refractory POEMS syndrome. [ABSTRACT FROM AUTHOR]

Spirobicyclic structures are versatile building blocks for functional chiral molecules. An enantioselective synthesis of chiral spirobilactams via a copper-catalyzed double N-arylation was developed. Amplification of solution ee by in situ precipitation of the racemate was observed with this method and enantioenriched spirobilactams were obtained with excellent ee values through simple solid-solution phase separation. [ABSTRACT FROM AUTHOR]

O-Heterocyclic structures such as 2,3-dihydrobenzofurans are key motifs in many natural compounds and pharmaceuticals. Enantioselective formation of chiral dihydrobenzofurans and analogues was achieved through a copper-catalyzed desymmetrization strategy with a chiral cyclic 1,2-diamine. A broad range of substrates are compatible with this CuI-diamine catalytic system and afford the desired coupling products with chiral tertiary or quaternary carbon centers in high yields and good to excellent enantioselectivities under mild conditions. [ABSTRACT FROM AUTHOR]

The enantioselective construction of all-carbon quaternary stereocenters is one of the most challenging fields in asymmetric synthesis. An asymmetric desymmetrization strategy offers an indirect and efficient method for the formation of all-carbon stereocenters. An enantioselective formation of cyano-bearing all-carbon quaternary stereocenters in 1,2,3,4,-tetrahydroquinolines and 2,3,4,5-tetrahydro-1H-benzo[ b]azepines by copper-catalyzed desymmetric N-arylation is demonstrated. The cyano group at the prochiral center plays a key role for the high enantioselectivity and works as an important functional group for further transformations. DFT studies provide a model which successfully accounts for the origin of enantioselectivity. [ABSTRACT FROM AUTHOR]