Comprehensive Analysis of Bufadienolide and Protein Profiles of Gland Secretions from Medicinal Bufo Species.

Toad Venom (TV) is the dried product of toxic secretions from Bufo bufo gargarizans Cantor (BgC) or B. melanostictus Schneider (BmS). Given the increasing medical demand and the severe depletion of wild toads, a number of counterfeit TVs appeared on the market, posing challenges to its quality control. In order to develop an efficient, feasible, and comprehensive approach to evaluate TV quality, a thorough analysis and comparison of chemical compounds among legal species BgC and BmS, as well as the main confusion species B. andrewsi Schmidt (BaS) and B. raddei Strauch (BrS), were conducted by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS), high performance liquid chromatography (HPLC), sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and Nano LC-MS/MS analyses. We identified 126 compounds, including free or conjugated bufadienolides, indole alkaloids and amino acids, among the four Bufo species. The content of main bufadienolides, such as gamabufotalin, bufotalin, bufalin, cinobufagin, and resibufogenin, and the total protein contents varied widely among 28 batches of TV due to their origin species. The sum of the five bufadienolides within the BgC, BmS, BaS, and BrS samples were 8.15-15.93%, 2.45-4.14%, 11.15-13.50%, and 13.21-14.68%, respectively. The total protein content of BgC (6.9-24.4%) and BaS (19.1-20.6%) samples were higher than that of BmS (4.8-20.4%) and BrS (10.1-13.7%) samples. Additionally, a total of 1357 proteins were identified. There were differences between the protein compositions among the samples of the four Bufo species. The results indicated that BgC TV is of the highest quality; BaS and BrS TV could serve as alternative resources, whereas BmS TV performed poorly overall. This research provides evidence for developing approaches to evaluate TV quality and selecting the proper Bufo species as the origin source of TV listed in the Chinese pharmacopoeia.

Autophagy-related biomarkers in preeclampsia: the underlying mechanism, correlation to the immune microenvironment and drug screening.

BACKGROUND: Preeclampsia is a life-threatening disease of pregnancy that lacks effective pharmaceuticals which can target its pathogenesis. Since preeclampsia involves complex pathological processes, including autophagy, this study aims to explore autophagy-related mechanisms of preeclampsia and to screen potential drugs. METHODS: Firstly, the datasets GSE75010, GSE24129, GSE66273, and autophagic genes lists were downloaded from public databases. Then, a weighted gene co-expression network analysis (WGCNA) was applied to filter autophagic-related hub genes of preeclampsia. The differential expression levels of the hub genes were validated with datasets GSE24129 and GSE66273. Next, the GO and KEGG enrichment, protein-protein interacting (PPI) network, as well as the downstream pathways was analyzed via the starBase, STRING and Cytoscape to determine the functions and regulatory network of the hub genes. Additionally, the immune microenvironment of preeclampsia was investigated by the CIBERSORTX database. Finally, three herb ingredients, berberine, baicalein, and luteolin were screened by molecular docking in comparison to pravastatin, metformin, and aspirin, to predict potential drugs for treating preeclampsia. RESULTS: A total of 54 autophagy-related genes were filtered by WGCNA. After filtering with |GS| > 0.5 and |MM| > 0.8, three hub genes, namely PKM, LEP, and HK2, were identified and validated. Among these genes, PKM and LEP were overexpressed in women older than 35 years old ( p<0.05; p<0.05); the expression of PKM, LEP, and HK2 differed remarkably in women with different BMI (all p<0.05); PKM overexpressed in women with hypertension (p<0.05). The regulatory network of hub genes demonstrated that they were mainly enriched in metabolic pathways, including the AMPK signaling pathway, glucagon signaling pathway, adipocytokine signaling pathway, and central carbon metabolism. Then, immune microenvironment analysis turned out that M2 macrophages were reduced in preeclampsia women (p<0.0001) and were negatively correlated with the expression of PKM (r=-0.2, p<0.05), LEP (r=-0.4, p<0.0001), and HK2 (r=-0.3, p<0.001). Lastly, molecular docking showed baicalein and luteolin could bind intimately to hub genes. CONCLUSION: PKM, LEP, and HK2 could be promising biomarkers for preeclampsia, which might regulate the pathogenesis of preeclampsia via metabolism pathways and immune microenvironment. Baicalein and luteolin could be potential therapeutics for preeclampsia.

[Research progress in quality control of Bufonis Venenum in preparations].

Bufonis Venenum, an animal medicinal material, is widely used for treating cardiovascular diseases and pain induced by rheumatics or malignant tumors. In view of the high activity and high toxicity, it is of great significance to pay attention to the quality control of Bufonis Venenum to ensure the safety and effectiveness of its preparations. China's drug standards involve 102 preparations(474 batch numbers) containing Bufonis Venenum approved for sale, including 14 preparations in the Chinese Pharmacopoeia(2020 edition) and 68 preparations in the standards issued by the Ministry of Health Drug Standard of the People's Republic of China. Bufonis Venenum is mostly used in pill and powder preparations in the form of raw powder, with the main functions of clearing heat, removing toxin, relieving swelling and pain, replenishing qi, activating blood, opening orifice, and awakening brain. Except the high level of quality control for Bufonis Venenum in the preparations in the Chinese Pharmacopoeia(2020 edition), the quality control standards of Bufonis Venenum in other preparations are low or even absent. Therefore, it is urgent to conduct research on the improvement of quality standards for the preparations containing Bufonis Venenum. This study retrieved the reports focusing on the quality evaluation and quality control of the preparations containing Bufonis Venenum from CNKI, PubMed, and Web of Science. Qualitative and quantitative analysis methods for 64 preparations containing Bufonis Venenum have been reported, mainly including thin-layer chromatography, HPLC fingerprint, and multi-component content determination. The index components mainly involved bufadienolides, such as gamabufalin, arenobufagin, bufotalin, bufalin, cinobufagin, and resibufogenin. According to the literature information, this paper suggests that attention should be paid to the correlations between the analysis methods and detection indexes of medicinal materials, decoction pieces and preparations, the monitoring of indole alkaloids, and the content uniformity inspection for further improving the quality standards for the preparations containing Bufonis Venenum.

The interplay between PEGylated nanoparticles and blood immune system.

During the last two decades, an increasing number of reports have pointed out that the immunogenicity of polyethylene glycol (PEG) may trigger accelerated blood clearance (ABC) and hypersensitivity reaction (HSR) to PEGylated nanoparticles, which could make PEG modification counterproductive. These phenomena would be detrimental to the efficacy of the load and even life-threatening to patients. Consequently, further elucidation of the interplay between PEGylated nanoparticles and the blood immune system will be beneficial to developing and applying related formulations. Many groups have worked to unveil the relevance of structural factors, dosing schedule, and other factors to the ABC phenomenon and hypersensitivity reaction. Interestingly, the results of some reports seem to be difficult to interpret or contradict with other reports. In this review, we summarize the physiological mechanisms of PEG-specific immune response. Moreover, we speculate on the potential relationship between the induction phase and the effectuation phase to explain the divergent results in published reports. In addition, the role of nanoparticle-associated factors is discussed based on the classification of the action phase. This review may help researchers to develop PEGylated nanoparticles to avoid unfavorable immune responses based on the underlying mechanism.

Comparison of High-Flow Nasal Cannula with Conventional Oxygen Therapy in Patients with Hypercapnic Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.

Purpose: This study aimed to evaluate the clinical outcomes of high-flow nasal cannula (HFNC) compared with conventional oxygen therapy (COT) in patients with hypercapnic chronic obstructive pulmonary disease (COPD), including arterial partial pressure of carbon dioxide (PaCO2), arterial partial pressure of oxygen (PaO2), respiratory rate (RR), treatment failure, exacerbation rates, adverse events and comfort evaluation. Patients and Methods: PubMed, EMBASE and the Cochrane Library were retrieved from inception to September 30, 2022. Eligible trials were randomized controlled trials and crossover studies comparing HFNC and COT in hypercapnic COPD patients. Continuous variables were reported as mean and standard derivation and calculated by weighted mean differences (MD), while dichotomous variables were shown as frequency and proportion and calculated by odds ratio (OR), with the 95% confidence intervals (Cl). Statistical analysis was performed using RevMan 5.4 software. Results: Eight studies were included, five with acute hypercapnia and three with chronic hypercapnia. In acute hypercapnic COPD, short-term HFNC reduced PaCO2 (MD -1.55, 95% CI: -2.85 to -0.25, I² = 0%, p <0.05) and treatment failure (OR 0.54, 95% CI: 0.33 to 0.88, I² = 0%, p<0.05), but there were no significant differences in PaO2 (MD -0.36, 95% CI: -2.23 to 1.52, I² = 45%, p=0.71) and RR (MD -1.07, 95% CI: -2.44 to 0.29, I² = 72%, p=0.12). In chronic hypercapnic COPD, HFNC may reduce COPD exacerbation rates, but there was no advantage in improving PaCO2 (MD -1.21, 95% CI: -3.81 to 1.39, I² = 0%, p=0.36) and PaO2 (MD 2.81, 95% CI: -1.39 to 7.02, I² = 0%, p=0.19). Conclusion: Compared with COT, short-term HFNC reduced PaCO2 and the need for escalating respiratory support in acute hypercapnic COPD, whereas long-term HFNC reduced COPD exacerbations rates in chronic hypercapnia. HFNC has great potential for treating hypercapnic COPD.

Chronic exposure to IQOS results in impaired pulmonary function and lung tissue damage in mice.

The use of IQOS brand heated tobacco products (HTPs) is increasing worldwide; however, little is known about the long-term effects of HTPs aerosol exposure on the lungs. Herein, we exposed C57BL/6 J mice for 24 weeks to clean air, IQOS aerosol, or cigarette smoke, and determined pulmonary function, lung tissue pathology, inflammation, and oxidative stress. Compared with the control group mice, IQOS group mice showed substantially decreased weight and lung function. Levels of IL-6 and TNF-a, as well as oxidative stress markers, were comparable to those found in the cigarette group. In addition, hematoxylin and eosin staining showed that the alveolar space was enlarged and that emphysema had formed in the IQOS group. Masson staining showed that collagen deposition areas were substantially increased in the airway walls in the IQOS group than in the control group. Immunohistochemical staining showed epithelial-mesenchymal transition in the airways of mice in the IQOS group. In conclusion, chronic exposure to IQOS aerosol results in impaired pulmonary function and lung tissue damage; hence, concern should be raised regarding the long-term safety of this product.

Efficient direct conversion of methane into methanol on CuZn hetero-diatomic catalysts with certain coordination spheres: a DFT study.

The oxidation of methane to a high-value-added chemical, methanol, is a major challenge in catalysis, requiring high energy input to overcome the CH3-H bond activation energy barrier. Based on density functional theory (DFT) calculations, methane oxidation to methanol is catalyzed by hetero-diatomic catalysts (CuZn-NG) with different coordination spheres (CSs). Valence band maximum (VBM), atomic charge and d-band center are selected as analysis methods for the pathway selection and activity of catalysis. The VBM plays a vital role in the catalytic pathway selection, CuZn-NG catalyzes the direct conversion of methane into methanol without side reactions. Alarmingly, the most important reaction step, CH3-H bond activation, is a spontaneously exothermic reaction (releasing 0.06 eV) with CuZn-NPAG as the catalyst, in contrast to most other endothermic reactions in the same activation. By analyzing the atomic charge of the Cu center and O atom, the special electronic phenomenon for this important step is summarized as the "bow-release effect". The CS affects the electronic properties of the active center and further affects the methane oxidation activity. This work provides a useful guide to understand the catalytic selectivity and activity of hetero-diatomic catalysts.

Associative analysis of multi-omics data indicates that acetylation modification is widely involved in cigarette smoke-induced chronic obstructive pulmonary disease.

We aimed to study the molecular mechanisms of chronic obstructive pulmonary disease (COPD) caused by cigarette smoke more comprehensively and systematically through different perspectives and aspects and to explore the role of protein acetylation modification in COPD. We established the COPD model by exposing C57BL/6J mice to cigarette smoke for 24 weeks, then analyzed the transcriptomics, proteomics, and acetylomics data of mouse lung tissue by RNA sequencing (RNA-seq) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), and associated these omics data through unique algorithms. This study demonstrated that the differentially expressed proteins and acetylation modification in the lung tissue of COPD mice were co-enriched in pathways such as oxidative phosphorylation (OXPHOS) and fatty acid degradation. A total of 19 genes, namely, ENO3, PFKM, ALDOA, ACTN2, FGG, MYH1, MYH3, MYH8, MYL1, MYLPF, TTN, ACTA1, ATP2A1, CKM, CORO1A, EEF1A2, AKR1B8, MB, and STAT1, were significantly and differentially expressed at all the three levels of transcription, protein, and acetylation modification simultaneously. Then, we assessed the distribution and expression in different cell subpopulations of these 19 genes in the lung tissues of patients with COPD by analyzing data from single-cell RNA sequencing (scRNA-seq). Finally, we carried out the in vivo experimental verification using mouse lung tissue through quantitative real-time PCR (qRT-PCR), Western blotting (WB), immunofluorescence (IF), and immunoprecipitation (IP). The results showed that the differential acetylation modifications of mouse lung tissue are widely involved in cigarette smoke-induced COPD. ALDOA is significantly downregulated and hyperacetylated in the lung tissues of humans and mice with COPD, which might be a potential biomarker for the diagnosis and/or treatment of COPD.

Electronic properties of double-atom catalysts for electrocatalytic oxygen evolution reaction in alkaline solution: a DFT study.

In alkaline solution, the electrocatalytic oxygen evolution reaction (OER) of dual transition metal atom (2TM) nitrogen-decorated graphene as a double-atom catalyst (DAC) has received special attention. Here, using density functional theory (DFT) calculations, the OER electrocatalysis of 2TM-pyridine/amino-nitrogen-decorated graphene (2TM-NPAG and 2TM-NPG. 2TM represents FeCo, FeNi, Conti) is studied. The electrocatalytic OER mechanism is that 2TM-NPG acts as the pre-catalyst, while the real catalysts are 2TM-NPAG and 2TM-NPG-O. In particular, CoNi-NPAG and CoNi-NPG-O exhibit higher OER activity compared to state-of-the-art RuO2 at pH = 14. It is confirmed that the potential-determining step is also the rate-determining step. Amino-nitrogen is the main accepter of electrons from CoNi atoms and pyridine-nitrogen is the main acceptor of electrons from nearby C atoms. The role of different N coordination continues to influence the entire electrocatalytic OER process of CoNi-NG. Simultaneously, the overpotential of CoNi-NG is in a volcano-shaped relationship with the electronic properties (oxidation state or d-band center) of the catalytic site of Co. Moreover, CoNi-NPAG and CoNi-NPG-O are the closest to the center of the OER overpotential (a function of the d-band center and oxidation state) contour plot, implying that they exhibit the best catalytic activity among all the CoNi-NG materials. The optimal electronic properties of CoNi-NPAG and CoNi-NPG-O contribute towards their excellent OER performance, and provide a new breakthrough in developing high-performance DACs.

Prognostic Value of Leucocyte to High-Density Lipoprotein-Cholesterol Ratios in COVID-19 Patients and the Diabetes Subgroup.

Background: Blood parameters, such as neutrophil-to-lymphocyte ratio, have been identified as reliable inflammatory markers with diagnostic and predictive value for the coronavirus disease 2019 (COVID-19). However, novel hematological parameters derived from high-density lipoprotein-cholesterol (HDL-C) have rarely been studied as indicators for the risk of poor outcomes in patients with severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infection. Here, we aimed to assess the prognostic value of these novel biomarkers in COVID-19 patients and the diabetes subgroup. Methods: We conducted a multicenter retrospective cohort study involving all hospitalized patients with COVID-19 from January to March 2020 in five hospitals in Wuhan, China. Demographics, clinical and laboratory findings, and outcomes were recorded. Neutrophil to HDL-C ratio (NHR), monocyte to HDL-C ratio (MHR), lymphocyte to HDL-C ratio (LHR), and platelet to HDL-C ratio (PHR) were investigated and compared in both the overall population and the subgroup with diabetes. The associations between blood parameters at admission with primary composite end-point events (including mechanical ventilation, admission to the intensive care unit, or death) were analyzed using Cox proportional hazards regression models. Receiver operating characteristic curves were used to compare the utility of different blood parameters. Results: Of 440 patients with COVID-19, 67 (15.2%) were critically ill. On admission, HDL-C concentration was decreased while NHR was high in patients with critical compared with non-critical COVID-19, and were independently associated with poor outcome as continuous variables in the overall population (HR: 0.213, 95% CI 0.090-0.507; HR: 1.066, 95% CI 1.030-1.103, respectively) after adjusting for confounding factors. Additionally, when HDL-C and NHR were examined as categorical variables, the HRs and 95% CIs for tertile 3 vs. tertile 1 were 0.280 (0.128-0.612) and 4.458 (1.817-10.938), respectively. Similar results were observed in the diabetes subgroup. ROC curves showed that the NHR had good performance in predicting worse outcomes. The cutoff point of the NHR was 5.50. However, the data in our present study could not confirm the possible predictive effect of LHR, MHR, and PHR on COVID-19 severity. Conclusion: Lower HDL-C concentrations and higher NHR at admission were observed in patients with critical COVID-19 than in those with noncritical COVID-19, and were significantly associated with a poor prognosis in COVID-19 patients as well as in the diabetes subgroup.

Impaired Fasting Glucose and Diabetes Are Related to Higher Risks of Complications and Mortality Among Patients With Coronavirus Disease 2019.

Background: Diabetes correlates with poor prognosis in patients with COVID-19, but very few studies have evaluated whether impaired fasting glucose (IFG) is also a risk factor for the poor outcomes of patients with COVID-19. Here we aimed to examine the associations between IFG and diabetes at admission with risks of complications and mortality among patients with COVID-19. Methods: In this multicenter retrospective cohort study, we enrolled 312 hospitalized patients with COVID-19 from 5 hospitals in Wuhan from Jan 1 to Mar 17, 2020. Clinical information, laboratory findings, complications, treatment regimens, and mortality status were collected. The associations between hyperglycemia and diabetes status at admission with primary composite end-point events (including mechanical ventilation, admission to intensive care unit, or death) were analyzed by Cox proportional hazards regression models. Results: The median age of the patients was 57 years (interquartile range 38-66), and 172 (55%) were women. At the time of hospital admission, 84 (27%) had diabetes (and 36 were new-diagnosed), 62 (20%) had IFG, and 166 (53%) had normal fasting glucose (NFG) levels. Compared to patients with NFG, patients with IFG and diabetes developed more primary composite end-point events (9 [5%], 11 [18%], 26 [31%]), including receiving mechanical ventilation (5 [3%], 6 [10%], 21 [25%]), and death (4 [2%], 9 [15%], 20 [24%]). Multivariable Cox regression analyses showed diabetes was associated increased risks of primary composite end-point events (hazard ratio 3.53; 95% confidence interval 1.48-8.40) and mortality (6.25; 1.91-20.45), and IFG was associated with an increased risk of mortality (4.11; 1.15-14.74), after adjusting for age, sex, hospitals and comorbidities. Conclusion: IFG and diabetes at admission were associated with higher risks of adverse outcomes among patients with COVID-19.

AMPK α1 Downregulates ROS Levels Through Regulating Trx Leading to Dysfunction of Apoptosis in Non-Small Cell Lung Cancer.

PURPOSE: AMP-activated protein kinase α1 (AMPK α1) associates closely with cancers. However, the relationship between AMPK α1 and non-small cell lung cancer (NSCLC) is not fully understood. In this study, we aim to explore the role and mechanism of AMPK α1 in NSCLC initiation and progression. MATERIALS AND METHODS: A total of 165 clinical NSCLC specimens were included in the formalin-fixed and paraffin-embedded (FFPE) lung cancer tissue arrays. The expression levels of AMPK α1 and thioredoxin (Trx) in NSCLC cancer tissues and adjacent non-tumor lung tissues were measured through using immunohistochemistry. MTT assay was used to detect cell proliferation. Intracellular ROS levels were measured by using H2DCFDA reagent. Lentiviruses including LV-PRKAA1-RNAi, LV-PRKAA1 and a negative LV-control were used to infect A549 cells to modulate AMPK α1 expression in vitro. Immunoblotting was used to determine the modulation relationship between AMPK α1 and Trx. Log rank test and Kaplan-Meier survival analysis were performed to evaluate the significances of AMPK α1 and Trx expression levels on NSCLC patients' prognoses. RESULTS: AMPK α1 was highly expressed in NSCLC cancer tissues and correlated with poor prognosis in patients with NSCLC. In A549 cells, overexpression of AMPK α1 promoted proliferation, suppressed ROS levels and inhibited apoptosis. Moreover, inhibition of AMPK α1 expression achieved the opposite effects. Trx was significantly overexpressed in NSCLC cancer tissues; furthermore, Trx expressed much more in cytoplasm when compared with cell nucleus. Trx expression levels were positively correlated with AMPK α1 expression levels in NSCLC tissues. AMPK α1 could regulate Trx in A549 cells. No significant correlations were observed between Trx expression variances and prognoses in NSCLC patients. Combination of AMPK α1 and Trx had no advantage in predicting prognoses of NSCLC patients. CONCLUSION: These results suggest that AMPK α1 serves a carcinogenic role at least in part through the regulation of Trx expression, and thus represents a potential treatment target in patients with NSCLC.

Rare cause of repeated pulmonary embolism: a case of primary pleural squamous cell carcinoma and literature review.

BACKGROUND: Malignant tumors are risk factors for a pulmonary embolism (PE), and a PE caused by a tumor is not uncommon. Primary pleural squamous cell carcinoma (PPSCC) is a rare malignancy; thus, a related PE is extremely rare. CASE PRESENTATION: A previously healthy 49-year-old female patient was admitted to Northern Jiangsu People's Hospital owing to chest tightness, cough, and breathing difficulty that persisted for 3 days. Following admission, a computed tomography (CT) pulmonary angiography revealed an embolism in the main pulmonary artery, upper and lower pulmonary artery branch. The patient was treated with alteplase, warfarin, and antibiotics. Over the following year, she experienced recurrent chest pain and tightness and breathing difficulty, with multiple CT pulmonary angiography revealing thrombosis in the right and left main pulmonary artery. No abnormalities were observed in surrogate markers of autoimmune diseases, tumor antigen testing, or ultrasonography; thus, the cause of recurrent PE was not identified. Subsequently, a positron emission tomography-computed tomography (PET-CT) examination revealed diffuse heterogeneous thickening of the right pleura and substantially increased glucose metabolism. A CT-guided pleural biopsy was performed, and histopathological examination of the pleura eventually revealed a diagnosis of PPSCC. CONCLUSIONS: PPSCC is a rare tumor that lacks specific clinical manifestations and is difficult to detect with imaging techniques. The occurrence of PE as the primary manifesting symptom in a patient with PPSCC is extremely rare. Thus, malignant tumors should be considered in patients with no risk factors for PE and/or in those with recurrent PE. An immediate diagnosis and adequate intervention can be achieved with increased awareness of this diagnosis and subsequent related examinations.

Mutation Analysis of Three Infantile Cases of X-linked Severe Combined Immunodeficiency.

BACKGROUND: Mutations in the IL2RG gene are known to cause X linked severe combined immunodeficiency (XSCID). More than 250 unique variants of the IL2RG gene have been reported to be identified in SCID patients so far, while many of them are of unknown significance which complicate the interpretation of mutation analysis results; furthermore, there are still many novel variants seen in clinical practice. METHODS: In this study we reviewed the testing results in three unrelated SCID families. All three probands had very severe immunodeficiency phenotypes and died in infancy. Next generation sequencing methods based on either SCID gene panel or exome sequencing were applied in causal variant screening for three probands. Sanger sequencing was used for verification of the variants of interest and carrier status study for the family members. STR analysis using the GoldeneyeTM DNA ID system (PeopleSpot Inc., China) was applied to verify the kinship of the family members when a de novo mutation was identified. RESULTS: Causal mutations were identified in all three SCID male probands, among which one was novel (c.557dupT), one was reported to be identified in a common variable immunodeficiency patient in literature (Leu87Pro), and one was a "hot-spot-mutation" (Arg226Cys). The patient with the missense mutation Leu87Pro in this study had much more severe infection phenotypes compared with the reported case in literature. CONCLUSIONS: Combining our findings and the published evidence together, Leu87Pro can be classified as a pathogenic variant following the ACMG guidelines. Correct and undoubted classification of the variants is of great importance for clinical gene testing.

Perfect Spin Filtering in Homobimetallic Ni Complex with High Tolerance to Structural Changes.

In the theory of ligand fields, depending on the nature and field strength of the surrounding ligands, the central metal ion may exhibit different electronic configurations, low spin (LS) or high spin (HS). Realizing stable spin polarization is one of the main challenges in the field of molecular spintronic devices because of spin switching triggered by an external stimulus. Here, an asymmetric homobimetallic complex has been investigated using the nonequilibrium Green's function and spin density functional theory. Our calculations indicate that the homobimetallic complex can achieve negative differential resistance, rectification effect, and perfect spin filtering transport on the level of an individual molecule. Strikingly, when the molecule is stretched by 0.45 Å, the HS state is still the most stable because of the weak magnetic Ni-Ni interaction. Although its conductivity decreases by 30%, the efficiency of spin filtering remains 100%. These obtained theoretical findings suggest that the homobimetallic complexes hold great potential in molecular spintronics.

Mixed-Metal-Cluster Strategy for Boosting Electrocatalytic Oxygen Evolution Reaction of Robust Metal-Organic Frameworks.

Rational construction of mixed metal-organic frameworks (MOFs) has been proved to be an effective way to heighten the electrocatalytic performance for MOFs, while the function of mixed metal clusters in MOFs to the electrocatalytic activity has not been known. For the first time, we present a mixed-metal-cluster strategy to boost electrocatalytic oxygen evolution reaction (OER) performance for MOFs. Heterometal clusters (Fe2M(µ3-O) (CH3COO)6(H2O)3, denoted as Fe2M (M: Co or Ni)), were chosen as the metal source to construct two bimetal PCN-250-Fe2M. Then, we further mixed Fe2Co and Fe2Ni clusters to construct mixed-metal-cluster PCN-Fe2Co-Fe2Ni by the in situ solvothermal reaction. Consequently, the OER activity of PCN-Fe2Co-Fe2Ni shows a dramatic enhancement compared with that of the parent bimetal MOFs. The PCN-Fe2Co-Fe2Ni displays a lower overpotential of 271 mV (η10), small Tafel slope (67.7 mV dec-1), and good linear sweep voltammetry cycle stability for the OER. Combination of DFT calculation and experiment results show that the improved electrocatalytic activity of PCN-Fe2Co-Fe2Ni is ascribed to the increased electron density of Co and Ni active centers and electrochemically active areas.

Effect of Conjugation Mode on Intramolecular Charge Transfer in Fabricating Acid-Responsive Fluorophores.

Solid-state acid-responsive materials are promising for the tunability of their intrinsic properties. However, the relationship between molecular structure and emission shift as a response to acid stimuli has not been systematically studied. Herein, we report the effect of protonation and subsequent intramolecular hydrogen bonding on the photophysical properties of compounds (MPP-s, MPP-d, and MPP-d-CN) with different conjugation modes between the electron-donating dimethoxyl phenyl and the electron-withdrawing benzothiazole ring. The results established that the stronger the intramolecular charge transfer feature of the compound, the smaller is the emission shift after acid stimuli. Our studies also indicated that the conjugation mode significantly affected the solid-state packing mode: MPP-s and MPP-d tended to form dimers, while MPP-d-CN exhibited the strongest aggregation-induced emission enhancement (AIEE). The exploration of structure-property relationship would provide experimental and theoretical guidance in designing acid-responsive molecular switches and developing high-performance AIEE-active luminogens.

The clinical responses of TNIP2-ALK fusion variants to crizotinib in ALK-rearranged lung adenocarcinoma.

OBJECTIVES: Anaplastic lymphoma kinase (ALK) has been proven to be another driver oncogene that accounts for 3%-7% of non-small-cell lung cancer, and it is more common in young patients and nonsmokers. ALK rearrangements have been previously identified in about 5.1% of lung adenocarcinoma, including EML4-ALK fusion variants, KIF5B-ALK and TFG-ALK. However, a TNIP2-ALK fusion has not been reported in lung adenocarcinoma. Herein, we described a rare case of ALK-rearranged lung adenocarcinoma responding to crizotinib. MATERIALS AND METHODS: Immunohistochemistry (IHC) assay and comprehensive next-generation sequencing (NGS) were performed on the aspirated biopsied tumor tissue. RESULTS: The IHC analysis revealed an ALK-positive tumor, while NGS detected a TNIP2-ALK fusion. The patient achieved continuous remission after treatment with crizotinib (250 mg, twice a day). CONCLUSION: This case provides valuable information on the response to crizotinib of patients with TNIP2-ALK fusion and better understanding of ALK-TKI applications in the future. NGS is a new method that can offer effective detection of gene fusion and gene mutations.

The demographic and treatment options for patients with large cell neuroendocrine carcinoma of the lung.

INTRODUCTION: Lung large cell neuroendocrine carcinoma (L-LCNEC) is a rare, aggressive tumor, for which the optimal treatment strategies for LCNEC have not yet been established. In order to explore how to improve the outcome of prognosis for patients with LCNEC, this study investigated the effect of different treatments based on the data obtained from the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: A total of 2594 LCNEC cases with conditional information were extracted from SEER database. Propensity Score Matching (PSM) method was conducted to reduce possible bias between groups. One-way ANOVA was used to test the differences of characteristics between groups. Univariate and multivariate Cox proportional hazard models were applied to identify prognostic factors. RESULTS: Clinicopathologic characteristics including gender, age, TNM stage, T stage, N stage, and M stage were all identified as independent prognostic factors. Surgery benefited stage I, II, and III LCNEC patients' prognoses. The combination treatment that surgery combining with chemotherapy was the optimal treatment for stage I, II, and III LCENC patients. Compared with palliative treatment, stage IV patients obtained better prognoses with the treatment of radiation, chemotherapy, or chemoradiation. When comparing the effect of the three treatments (radiation, chemotherapy, and chemoradiation) in achieving better prognosis for stage IV patients, chemotherapy alone was better than the other treatments. CONCLUSION: Surgery combining with chemotherapy was the optimal treatment for stage I, II, and III LCNEC patients; chemotherapy alone achieves more benefit than the other treatments for stage IV patients.