Tumor-Targeting Multiple Metabolic Regulations for Bursting Antitumor Efficacy of Chemodynamic Therapy.

Interfering with intratumoral metabolic processes is proven to effectively sensitize different antitumor treatments. Here, a tumor-targeting catalytic nanoplatform (CQ@MIL-GOX@PB) loading with autophagy inhibitor (chloroquine, CQ) and glucose oxidase (GOX) is fabricated to interfere with the metabolisms of tumor cells and tumor-associated macrophages (TAMs), then realizing effective antitumor chemodynamic therapy (CDT). Once accumulating in the tumor site with the navigation of external biotin, CQ@MIL-GOX@PB will release Fe ions and CQ in the acid lysosomes of tumor cells, the latter can sensitize Fe ions-involved antitumor CDT by blocking the autophagy-dependent cell repair. Meanwhile, the GOX component will consume glucose, which not only generates many H2O2 for CDT but also once again decelerates the tumor repair process by reducing energy metabolism. What is more, the release of CQ can also drive the NO anabolism of TAMs to further sensitize CDT. This strategy of multiple metabolic regulations is evidenced to significantly improve the antitumor effect of traditional CDT nanoagents and might provide a new sight to overcome the bottlenecks of different antitumor treatments.

Transcription factors MdMYC2 and MdMYB85 interact with ester aroma synthesis gene MdAAT1 in apple.

Volatile esters in apple (Malus domestica) fruit are the critical aroma components determining apple flavor quality. While the exact molecular regulatory mechanism remains unknown, jasmonic acid (JA) plays a crucial role in stimulating the synthesis of ester aromas in apples. In our study, we investigated the effects of methyl jasmonate (MeJA) on the production of ester aroma in apples. MeJA treatment significantly increased ester aroma synthesis, accompanied by the upregulation of several genes involved in the jasmonate pathway transduction. Specifically, expression of the gene MdMYC2, which encodes a transcription factor associated with the jasmonate pathway, and the R2R3-MYB transcription factor gene MdMYB85 increased upon MeJA treatment. Furthermore, the essential gene ALCOHOL ACYLTRANSFERASE 1 (MdAAT1), encoding an enzyme responsible for ester aroma synthesis, showed increased expression levels as well. Our investigation revealed that MdMYC2 and MdMYB85 directly interacted with the promoter region of MdAAT1, thereby enhancing its transcriptional activity. In addition, MdMYC2 and MdMYB85 directly bind their promoters and activate transcription. Notably, the interaction between MdMYC2 and MdMYB85 proteins further amplified the regulatory effect of MdMYB85 on MdMYC2 and MdAAT1, as well as that of MdMYC2 on MdMYB85 and MdAAT1. Collectively, our findings elucidate the role of the gene module consisting of MdMYC2, MdMYB85, and MdAAT1 in mediating the effects of JA and promoting ester aroma synthesis in apples.

Reductive Coupling of P(O)-H Compounds and Aldehydes for the General Synthesis of Phosphines and Phosphine Oxides.

A novel strategy for the selective construction of a C(sp3)-P(III) or -P(V) bond from >P(O)-H compounds and aldehydes is disclosed. By using the H3PO3/I2 system, various secondary phosphine oxides could react with both aromatic and aliphatic aldehydes to afford valuable phosphines (isolated as sulfides) and phosphine oxides in good yields. This method features a wide substrate scope and simple reaction conditions and avoids the use of toxic halides and metals.

Molecular characterization, expression analysis and function identification of Pf_IL-12p35, Pf_IL-23p19 and Pf_IL-12p40 genes in yellow catfish (Pelteobagrus fulvidraco).

The interleukin-12 (IL-12) family is a class of heterodimeric cytokines that play crucial roles in pro-inflammatory and pro-stimulatory responses. Although some IL-12 and IL-23 paralogues have been found in fish, their functional activity in fish remains poorly understood. In this study, Pf_IL-12p35a/b, Pf_IL-23p19 and Pf_IL-12p40a/b/c genes were cloned from yellow catfish (Pelteobagrus fulvidraco), four α-helices were found in Pf_IL-12p35a/b and Pf_IL-23p19. The transcripts of these six genes were relatively high in mucus and immune tissues of healthy individuals, and in gill leukocytes. Following Edwardsiella ictaluri infection, Pf_IL-12p35a/b and Pf_IL-23p19 mRNAs were induced in brain and kidney (or head kidney), Pf_IL-12p40a mRNA was induced in gill, and Pf_IL-12p40b/c mRNAs were induced in brain and liver (or skin). The mRNA expression of these genes in PBLs was induced by phytohaemagglutinin (PHA) and polyinosinic-polycytidylic acid (poly I:C), while lipopolysaccharides (LPS) induced the mRNA expression of Pf_IL-12p35a and Pf_IL-12p40b/c in PBLs. After stimulation with recombinant (r) Pf_IL-12 and rPf_IL-23 subunit proteins, either alone or in combination, mRNA expression patterns of genes related to T helper cell development exhibited distinct differences. The results suggest that Pf_IL-12 and Pf_IL-23 subunits may play important roles in regulating immune responses to pathogens and T helper cell development.

Chronic Alcohol Exposure Alters the Levels and Assembly of the Actin Cytoskeleton and Microtubules in the Adult Mouse Hippocampus.

BACKGROUND: Alcohol abuse, a prevalent global health issue, is associated with the onset of cognitive impairment and neurodegeneration. Actin filaments (F-actin) and microtubules (MTs) polymerized from monomeric globular actin (G-actin) and tubulin form the structural basis of the neuronal cytoskeleton. Precise regulation of the assembly and disassembly of these cytoskeletal proteins, and their dynamic balance, play a pivotal role in regulating neuronal morphology and function. Nevertheless, the effect of prolonged alcohol exposure on cytoskeleton dynamics is not fully understood. This study investigates the chronic effects of alcohol on cognitive ability, neuronal morphology and cytoskeleton dynamics in the mouse hippocampus. METHODS: Mice were provided ad libitum access to 5% (v/v) alcohol in drinking water and were intragastrically administered 30% (v/v, 6.0 g/kg/day) alcohol for six weeks during adulthood. Cognitive functions were then evaluated using the Y maze, novel object recognition and Morris water maze tests. Hippocampal histomorphology was assessed through hematoxylin-eosin (HE) and Nissl staining. The polymerized and depolymerized states of actin cytoskeleton and microtubules were separated using two commercial assay kits and quantified by Western blot analysis. RESULTS: Mice chronically exposed to alcohol exhibited significant deficits in spatial and recognition memory as evidenced by behavioral tests. Histological analysis revealed notable hippocampal damage and neuronal loss. Decreased ratios of F-actin/G-actin and MT/tubulin, along with reduced levels of polymerized F-actin and MTs, were found in the hippocampus of alcohol-treated mice. CONCLUSIONS: Our findings suggest that chronic alcohol consumption disrupted the assembly of the actin cytoskeleton and MTs in the hippocampus, potentially contributing to the cognitive deficits and pathological injury induced by chronic alcohol intoxication.

Spatially and temporally understanding dynamic solid-electrolyte interfaces in carbon dioxide electroreduction.

The ubiquity of solid-liquid interfaces in nature and the significant role of their atomic-scale structure in determining interfacial properties have led to intensive research. Particularly in electrocatalysis, however, a molecular-level picture that clearly describes the dynamic interfacial structures and organizations with their correlation to preferred reaction pathways in electrochemical reactions remains poorly understood. In this review, CO2 electroreduction reaction (CO2RR) is spatially and temporally understood as a result of intricate interactions at the interface, in which the interfacial features are highly relevant. We start with the discussion of current understandings and model development associated with the charged electrochemical interface as well as its dynamic landscape. We further highlight the interactive dynamics from the interfacial field, catalyst surface charges and various gradients in electrolyte and interfacial water structures at interfaces under CO2RR working conditions, with emphasis on the interfacial-structure dependence of catalytic reactivity/selectivity. Significantly, a probing energy-dependent "in situ characterization map" for dynamic interfaces based on various complementary in situ/operando techniques is proposed, aiming to present a comprehensive picture of interfacial electrocatalysis and to provide a more unified research framework. Moreover, recent milestones in both experimental and theoretical aspects to establish the correct profile of electrochemical interfaces are stressed. Finally, we present key scientific challenges with related perspectives toward future opportunities for this exciting frontier.

Regioselective Tip-Enhanced Raman Spectroscopy of Lipid Membranes with Sub-Nanometer Axial Resolution.

Noninvasive and label-free analysis of cell membranes at the nanoscale is essential to comprehend vital cellular processes. However, conventional analytical tools generally fail to meet this challenge due to the lack of required sensitivity and/or spatial resolution. Herein, we demonstrate that tip-enhanced Raman spectroscopy (TERS) is a powerful nanoanalytical tool to analyze dipalmitoylphosphatidylcholine (DPPC) bilayers and human cell membranes with submolecular resolution in the vertical direction. Unlike the far-field Raman measurements, TERS spectra of the DPPC bilayers reproducibly exhibited a uniquely shaped C-H band. These unique spectral features were also reproducibly observed in the TERS spectrum of human pancreatic cancer cells. Spectral deconvolution and DFT simulations confirmed that the TERS signal primarily originated from vibrations of the CH3 groups in the choline headgroup of the lipids. The reproducible TERS results obtained in this study unequivocally demonstrate the ultrahigh sensitivity of TERS for nanoanalysis of lipid membranes under ambient conditions.

A retrospective study of occlusal reconstruction in patients with old jaw fractures and dentition defects.

PURPOSE: This study evaluated the methods and clinical effects of multidisciplinary collaborative treatment for occlusal reconstruction in patients with old jaw fractures and dentition defects. METHODS: Patients with old jaw fractures and dentition defects who underwent occlusal reconstruction at the Third Affiliated Hospital of Air Force Military Medical University from January 2018 to December 2022 were enrolled. Clinical treatment was classified into 3 phases. In phase I, techniques such as orthognathic surgery, microsurgery, and distraction osteogenesis were employed to reconstruct the correct three-dimensional (3D) jaw position relationship. In phase II, bone augmentation and soft tissue management techniques were utilized to address insufficient alveolar bone mass and poor gingival soft tissue conditions. In phase III, implant-supported overdentures or fixed dentures were used for occlusal reconstruction. A summary of treatment methods, clinical efficacy evaluation, comparative analysis of imageological examinations, and satisfaction questionnaire survey were utilized to evaluate the therapeutic efficacy in patients with traumatic old jaw fractures and dentition defects. All data are summarized using the arithmetic mean and standard deviation and compared using independent sample t-tests. RESULTS: In 15 patients with old jaw fractures and dentition defects (an average age of 32 years, ranging from 18 to 53 years), there were 7 cases of malocclusion of single maxillary fracture, 6 of malocclusion of single mandible fracture, and 2 of malocclusion of both maxillary and mandible fractures. There were 5 patients with single maxillary dentition defects, 2 with single mandibular dentition defects, and 8 with both maxillary and mandibular dentition defects. To reconstruct the correct 3D jaw positional relationship, 5 patients underwent Le Fort I osteotomy of the maxilla, 3 underwent bilateral sagittal split ramus osteotomy of the mandible, 4 underwent open reduction and internal fixation for old jaw fractures, 3 underwent temporomandibular joint surgery, and 4 underwent distraction osteogenesis. All patients underwent jawbone augmentation, of whom 4 patients underwent a free composite vascularized bone flap (26.66%) and the remaining patients underwent local alveolar bone augmentation. Free gingival graft and connective tissue graft were the main methods for soft tissue augmentation (73.33%). The 15 patients received 81 implants, of whom 11 patients received implant-supported fixed dentures and 4 received implant-supported removable dentures. The survival rate of all implants was 93.82%. The final imageological examination of 15 patients confirmed that the malocclusion was corrected, and the clinical treatment ultimately achieved occlusal function reconstruction. The patient satisfaction questionnaire survey showed that they were satisfied with the efficacy, phonetics, aesthetics, and comfort after treatment. CONCLUSION: Occlusal reconstruction of old jaw fractures and dentition defects requires a phased sequential comprehensive treatment, consisting of 3D spatial jaw correction, alveolar bone augmentation and soft tissue augmentation, and implant-supported occlusal reconstruction, achieving satisfactory clinical therapeutic efficacy.

ß-C-H Allylation of Trialkylamines with Allenes Promoted by Synergistic Borane/Palladium Catalysis.

Functionalization of the C(sp3 )-H bonds of trialkylamines is challenging, especially for reactions at positions other than the α position. Herein, we report a method for ß-C(sp3 )-H allylation of trialkylamines. In these reactions, which involve synergistic borane/palladium catalysis, an enamine intermediate is first generated from the amine via α,ß-dehydrogenation promoted by B(C6 F5 )3 and a base, and then the enamine undergoes palladium-catalyzed reaction with an allene to give the allylation product. Because the hydride and the proton resulting from the initial dehydrogenation are ultimately shuttled to the product by B(C6 F5 )3 and the palladium catalyst, respectively, these reactions show excellent atom economy. The establishment of this method paves the way for future studies of C-H functionalization of trialkylamines by means of synergistic borane/transition-metal catalysis.

Mechanistic Understanding of Oxygen Activation on Bulk Au(111) Surface Using Tip-Enhanced Raman Spectroscopy.

Gaining mechanistic understanding of oxygen activation on metal surfaces is a topical area of research in surface science. However, direct investigation of on-surface oxidation processes at the nanoscale and the empirical validation of oxygen activation pathways remain challenging for the conventional analytical tools. In this study, we applied tip-enhanced Raman spectroscopy (TERS) to gain mechanistic insights into oxygen activation on bulk Au(111) surface. Specifically, oxidation of 4-aminothiophenol (4-ATP) to 4-nitrothiophenol (4-NTP) on Au(111) surface was investigated using hyperspectral TERS imaging. Nanoscale TERS images revealed a markedly higher oxidation efficiency in disordered 4-ATP adlayers compared to the ordered adlayers signifying that the oxidation of 4-ATP molecules proceeds via interaction with the on-surface oxidative species. These results were further validated via direct oxidation of the 4-ATP adlayers with H2O2 solution. Finally, TERS measurements of oxidized 4-ATP adlayers in the presence of H2O18 provided the first empirical evidence for the generation of oxidative species on bulk Au(111) surface via water-mediated activation of molecular oxygen. This study expands our mechanistic understanding of oxidation chemistry on bulk Au surface by elucidating the oxygen activation pathway.

Bimetallic Single Atom/Nanoparticle Ensemble for Efficient Photochemical Cascade Synthesis of Ethylene from Methane.

Light-driven photoredox catalysis presents a promising approach for the activation and conversion of methane (CH4) into high value-added chemicals under ambient conditions. However, the high C-H bond dissociation energy of CH4 and the absence of well-defined C-H activation sites on catalysts significantly limit the highly efficient conversion of CH4 toward multicarbon (C2+) hydrocarbons, particularly ethylene (C2H4). Herein, we demonstrate a bimetallic design of Ag nanoparticles (NPs) and Pd single atoms (SAs) on ZnO for the cascade conversion of CH4 into C2H4 with the highest production rate compared with previous works. Mechanistic studies reveal that the synergistic effect of Ag NPs and Pd SAs, upon effecting key bond-breaking and -forming events, lowers the overall energy barrier of the activation process of both CH4 and the resulting C2H6, constituting a truly synergistic catalytic system to facilitate the C2H4 generation. This work offers a novel perspective on the advancement of photocatalytic directional CH4 conversion toward high value-added C2+ hydrocarbons through the subtle design of bimetallic cascade catalyst strategy.

Efficient Homolytic Cleavage of H2O2 on Hydroxyl-Enriched Spinel CuFe2O4 with Dual Lewis Acid Sites.

Traditional H2O2 cleavage mediated by macroscopic electron transfer (MET) not only has low utilization of H2O2, but also sacrifices the stability of catalysts. We present a non-redox hydroxyl-enriched spinel (CuFe2O4) catalyst with dual Lewis acid sites to realize the homolytic cleavage of H2O2. The results of systematic experiments, in situ characterizations, and theoretical calculations confirm that tetrahedral Cu sites with optimal Lewis acidity and strong electron delocalization can synergistically elongate the O-O bonds (1.47 Š→ 1.87 Å) in collaboration with adjacent bridging hydroxyl (another Lewis acid site). As a result, the free energy of H2O2 homolytic cleavage is decreased (1.28 eV → 0.98 eV). H2O2 can be efficiently split into ⋅OH induced by hydroxyl-enriched CuFe2O4 without MET, which greatly improves the catalyst stability and the H2O2 utilization (65.2 %, nearly 2 times than traditional catalysts). The system assembled with hydroxyl-enriched CuFe2O4 and H2O2 affords exceptional performance for organic pollutant elimination. The scale-up experiment using a continuous flow reactor realizes long-term stability (up to 600 mL), confirming the tremendous potential of hydroxyl-enriched CuFe2O4 for practical applications.

Interface Synergy of Exposed Oxygen Vacancy and Pd Lewis Acid Sites Enabling Superior Cooperative Photoredox Synthesis.

Photo-driven cross-coupling of o-arylenediamines and alcohols has emerged as an alternative for the synthesis of bio-active benzimidazoles. However, tackling the key problem related to efficient adsorption and activation of both coupling partners over photocatalysts towards activity enhancement remains a challenge. Here, we demonstrate an efficient interface synergy strategy by coupling exposed oxygen vacancies (VO) and Pd Lewis acid sites for benzimidazole and hydrogen (H2) coproduction over Pd-loaded TiO2 nanospheres with the highest photoredox activity compared to previous works so far. The results show that the introduction of VO optimizes the energy band structure and supplies coordinatively unsaturated sites for adsorbing and activating ethanol molecules, affording acetaldehyde active intermediates. Pd acts as a Lewis acid site, enhancing the adsorption of alkaline amine moleculesvia Lewis acid-base pair interactions and driving the condensation process. Furthermore, VO and Pd synergistically promote interfacial charge transfer and separation. This work offers new insightful guidance for the rational design of semiconductor-based photocatalysts with interface synergy at the molecular level towards the high-performance coproduction of renewable fuels and value-added feedstocks.

Cooperative Coupling of Oxidative Organic Synthesis and Hydrogen Production over Semiconductor-Based Photocatalysts.

Merging hydrogen (H2) evolution with oxidative organic synthesis in a semiconductor-mediated photoredox reaction is extremely attractive because the clean H2 fuel and high-value chemicals can be coproduced under mild conditions using light as the sole energy input. Following this dual-functional photocatalytic strategy, a dreamlike reaction pathway for constructing C-C/C-X (X = C, N, O, S) bonds from abundant and readily available X-H bond-containing compounds with concomitant release of H2 can be readily fulfilled without the need of external chemical reagents, thus offering a green and fascinating organic synthetic strategy. In this review, we begin by presenting a concise overview on the general background of traditional photocatalytic H2 production and then focus on the fundamental principles of cooperative photoredox coupling of selective organic synthesis and H2 production by simultaneous utilization of photoexcited electrons and holes over semiconductor-based catalysts to meet the economic and sustainability goal. Thereafter, we put dedicated emphasis on recent key progress of cooperative photoredox coupling of H2 production and various selective organic transformations, including selective alcohol oxidation, selective methane conversion, amines oxidative coupling, oxidative cross-coupling, cyclic alkanes dehydrogenation, reforming of lignocellulosic biomass, and so on. Finally, the remaining challenges and future perspectives in this flourishing area have been critically discussed. It is anticipated that this review will provide enlightening guidance on the rational design of such dual-functional photoredox reaction system, thereby stimulating the development of economical and environmentally benign solar fuel generation and organic synthesis of value-added fine chemicals.

Linear Segmented Arc-Shaped Piezoelectric Branch Beam Energy Harvester for Ultra-Low Frequency Vibrations.

Piezoelectric energy harvesting systems have been drawing the attention of the research community over recent years due to their potential for recharging/replacing batteries embedded in low-power-consuming smart electronic devices and wireless sensor networks. However, conventional linear piezoelectric energy harvesters (PEH) are often not a viable solution in such advanced practices, as they suffer from a narrow operating bandwidth, having a single resonance peak present in the frequency spectrum and very low voltage generation, which limits their ability to function as a standalone energy harvester. Generally, the most common PEH is the conventional cantilever beam harvester (CBH) attached with a piezoelectric patch and a proof mass. This study investigated a novel multimode harvester design named the arc-shaped branch beam harvester (ASBBH), which combined the concepts of the curved beam and branch beam to improve the energy-harvesting capability of PEH in ultra-low-frequency applications, in particular, human motion. The key objectives of the study were to broaden the operating bandwidth and enhance the harvester's effectiveness in terms of voltage and power generation. The ASBBH was first studied using the finite element method (FEM) to understand the operating bandwidth of the harvester. Then, the ASBBH was experimentally assessed using a mechanical shaker and real-life human motion as excitation sources. It was found that ASBBH achieved six natural frequencies within the ultra-low frequency range (<10 Hz), in comparison with only one natural frequency achieved by CBH within the same frequency range. The proposed design significantly broadened the operating bandwidth, favouring ultra-low-frequency-based human motion applications. In addition, the proposed harvester achieved an average output power of 427 µW at its first resonance frequency under 0.5 g acceleration. The overall results of the study demonstrated that the ASBBH design can achieve a broader operating bandwidth and significantly higher effectiveness, in comparison with CBH.

Longitudinal association of edentulism with cognitive impairment, sarcopenia and all-cause mortality among older Chinese adults.

BACKGROUND: Tooth loss may be a surrogate for systemic health and aging. However, no previous studies have systematically assessed multiple outcomes relevant to aging trajectory in this area, and many important confounders were not adjusted in most previous studies. This study aims to prospectively evaluate the associations of complete tooth loss (edentulism) with broad markers of sarcopenia, cognitive impairment and mortality. METHODS: Data were derived from the China Health and Retirement Longitudinal Study, a nationally representative household study of the Chinese population aged 45 years and older. Multivariate Weibull proportional hazards regression was used to assess the association between edentulism with sarcopenia and all-cause mortality. Average changes in cognitive function by edentulism was estimated by mixed-effects linear regression models. RESULTS: During the 5-year follow-up, the prevalence of edentulism among adults aged 45 and over was 15.4%. Participants with edentulism had a greater decline in cognitive function compared to those without (ß=-0.70, 95%CI:-1.09, -0.31, P < 0.001). The association of edentulism and all-cause mortality for 45-64 age group (HR = 7.50, 95%CI: 1.99, 28.23, P = 0.003), but not statistically significant for the ≥ 65 age group (HR = 2.37, 95%CI: 0.97, 5.80, P = 0.057). Effects of edentulism on sarcopenia are statistically significant for all age groups (45-64 age group: HR = 2.15, 95%CI: 1.27, 3.66, P = 0.005; ≥65 age group: HR = 2.15, 95%CI: 1.27, 3.66, P = 0.002). CONCLUSIONS: These findings could have important clinical and public health implications, as tooth loss is a quick and reproducible measurement that could be used in clinical practice for identifying persons at risk of accelerated aging and shortened longevity, and who may benefit most from intervention if causality is established.

Evaluation and influencing factors of the tourism industry efficiency under carbon emission constraints in China.

A significant industrial transformation in China's tourism sector is currently taking place in response to carbon peak and carbon neutrality targets. This paper applies the data envelopment analysis (DEA) model to calculate the efficiency of the tourism industry under carbon emission constraints and further investigates its influencing factors through the Tobit regression. The results are as follows: (1) The tourism efficiency under carbon emission constraints of China from 2000 to 2019 showed a trend of first rising and then declining, and there were obvious regional differences; (2) from 2000 to 2019, the total factor productivity of tourism in China increased significantly, while the contributions of technical progress, pure technical efficiency, and scale efficiency decreased sequentially; (3) the factors of industrial structure, transportation convenience, economic development level, degree of opening to the outside world, and the level of scientific and technological development have varying degrees of influence on tourism efficiency. Based on the analysis results, this paper puts forward several policy suggestions on tourism efficiency and low-carbon development. The findings of this paper have some bearing on developing nations' efforts to boost tourism efficiency and realize high-quality industry growth within the framework of sustainable development.

[Penile cancer with perineural invasion is more prone to postoperative recurrence].

OBJECTIVE: To explore the correlation between perineural invasion and postoperative recurrence in patients surgically treated for penile cancer. METHODS: We conducted a retrospective analysis of the clinical data on 18 penile cancer patients surgically treated in our hospital from January 2018 to December 2021, 8 with postoperative recurrence (the recurrence group) and the other 10 without (the non-recurrence control group). We compared the two groups of patients in the age of onset, tumor-node-metastasis (TNM) stages, American Joint Committee on Cancer (AJCC) prognosis stages, surgical methods, perineural invasion and recurrence time. We analyzed the differences in postoperative recurrence using the Kaplan Meier plotted survival curve and in independent risk factors in predicting postoperative recurrence using the ROC curve. RESULTS: Compared with the non-recurrence controls, the patients in the recurrence group had a significantly older age of onset (P=0.0411) and severer perineural invasion (P<0.001), and those with perineural invasion had a shorter recurrence time (P<0.001), which was an independent risk factor for postoperative recurrence. The areas under the ROC curves for perineural invasion and age were 0.885 and 0.213, respectively. CONCLUSION: Penile cancer with perineural invasion is more prone to and perineural invasion is an independent risk factor for postoperative recurrence of the malignancy.

[Periplaneta americana extract Câ ¡-3 induces senescence of leukemia K562 cells via SIRT1/mTOR signaling pathway].

This study aims to investigate the role of slient mating-type information regulation 2 homolog 1(SIRT1)/tuberous sclerosis complex 2(TSC2)/mammalian target of rapamycin(mTOR) signaling pathways in the Periplaneta americana extract CⅡ-3-induced senescence of human leukemia K562 cells. K562 cells were cultured in vitro and treated with 0(control), 5, 10, 20, 40, 80, and 160 µg·mL~(-1) of P. americana extract CⅡ-3. Cell counting kit-8(CCK-8) and flow cytometry were employed to examine the proliferation and cell cycle of the K562 cells. Senescence-associated ß-galactosidase stain kit(SA-ß-gal) was used to detect the positive rate of senescent cells. Mitochondrial membrane potential was detected by flow cytometry. The relative mRNA level of telomerase reverse transcriptase(TERT) was determined by fluorescence quantitative PCR. The mRNA and protein levels of SIRT1, TSC2, and mTOR were determined by fluorescence quantitative PCR and Western blot, respectively. The results showed that CⅡ-3 significantly inhibited the proliferation of K562 cells and the treatment with 80 µg·mL~(-1) CⅡ-3 for 72 h had the highest inhibition rate. Therefore, 80 µg·mL~(-1) CⅡ-3 treatment for 72 h was selected as the standard for subsequent experiments. Compared with the control group, CⅡ-3 increased the proportion of cells arrested in G_0/G_1 phase, decreased the proportion of cells in S phase, increased the positive rate of SA-ß-Gal staining, elevated the mitochondrial membrane potential and down-regulated the mRNA expression of TERT. Furthermore, the mRNA expression of SIRT1 and TSC2 was down-regulated, while the mRNA expression of mTOR was up-regulated. The protein expression of SIRT1 and p-TSC2 was down-regulated, while the protein expression of p-mTOR was up-regulated. The results indicated that P. americana extract CⅡ-3 induced the senescence of K562 cells via the SIRT1/mTOR signaling pathway.

C3-Cyanation of Pyridines: Constraints on Electrophiles and Determinants of Regioselectivity.

Methods for C-H cyanation of pyridines are rare. Here, we report a method for C3-selective cyanation of pyridines by a tandem process with the reaction of an in situ generated dihydropyridine with a cyano electrophile as the key step. The method is suitable for late-stage functionalization of pyridine drugs. The low reduction potential of the electrophile and effective transfer of the nitrile group were found to be essential for the success of this method. We studied the reaction mechanism in detail by means of control experiments and theoretical calculations and found that a combination of electronic and steric factors determined the regioselectivity of reactions involving C2-substituted pyridines.