Aspirin boosts the synergistic effect of EGFR/p53 inhibitors on lung cancer cells by regulating AKT/mTOR and p53 pathways.

The regimen of afatinib and vinorelbine has been used to treat breast or lung cancer cells with some limitations. Aspirin alone or in combination with other agents has shown unique efficacy in the treatment of cancer. We designed a preclinical study to investigate whether the triple therapy of aspirin, afatinib, and vinorelbine could synergistically inhibit the growth of p53 wild-type nonsmall cell lung cancer (NSCLC) cells. Three NSCLC cells A549, H460, and H1975 were selected to study the effect of triple therapy on cell proliferation and apoptosis. Compared to single agents, triple therapy synergistically inhibited the proliferation of lung cancer cells with combination index <1. Meanwhile, the therapeutic index of triple therapy was superior to that of single agents, indicating a balance between efficacy and safety in the combination of three agents. Mechanistic studies showed that triple therapy significantly induced apoptosis by decreasing mitochondrial membrane potential, increasing reactive oxygen species, and regulating mitochondria-related proteins. Moreover, epidermal growth factor receptor (EGFR) downstream signaling proteins including JNK, AKT, and mTOR were dramatically suppressed and p53 was substantially increased after NSCLC cells were exposed to the triple therapy. We provided evidence that the triple therapy of aspirin, afatinib and vinorelbine synergistically inhibited lung cancer cell growth through inactivation of the EGFR/AKT/mTOR pathway and accumulation of p53, providing a new treatment strategy for patients with p53 wild-type NSCLC.

Different Agglomeration Processes Induced by the Varied Interaction of Fe-Fe Analogues with Differently Charged Surfactants.

The catalytic activity of Prussian blue analogues (PBAs) is mainly tuned via the control of material sizes and morphologies. However, the shapes and sizes of many PBAs are difficult to control. In this work, a facile approach is demonstrated using differently charged surfactants to tune the catalytic activity of PBAs. Fe-Fe PBAs prepared with non-ionic P123, cationic cetyltrimethylammonium bromide, and anionic sodium dodecyl sulfate are chosen to study the effect of surfactant charges on the catalytic activity. The transesterification of propylene carbonate to dimethyl carbonate by methanol is selected as a model reaction. Owing to the different agglomeration processes of PB particles after modified with differently charged surfactants, significantly varied shapes and sizes were observed. Accordingly, the catalytic activity is greatly varied by adding surfactants. The different catalytic activities may arise from the different behaviors of agglomeration of PB particles after surfactant modification as well as the material size and shape changes. Besides, apparent activation energies for PBs adding different surfactants were derived. Finally, the agglomeration mechanism of PB particles in the presence of differently charged surfactants was proposed.

Recent Advances on Synthesis of CoCO3 with Controlled Morphologies.

Cobalt carbonates and derivatives represent most promising cost-effective materials for energy storage, conversion and upgrading. Morphology determines the performances, as size, shape and electronic configuration are key factors for tunable properties in the area of batteries, catalysis, magnetics and plasmonics. However, there is lack of insights in literature on morphological control of cobalt carbonates during hydrothermal and solvothermal conditions. Therefore, this review provides detailed discussion on synthesis, formation mechanism and morphological control of nanosheets, wires, spheres and cubes of cobalt carbonates. Furthermore, the influence of experimental conditions and plausible mechanism which govern the growing processes were further discussed in details. The outcome of this short review will offer insights into rational design of inexpensive metal carbonates for numerous other energy and environment applications.

The relationship between bladder storage function and frequent micturition after TURP.

PURPOSE: To investigate the relationship between preoperative bladder function and frequent micturition after transurethral resection of prostate in patients with benign prostatic hyperplasia. METHODS: We retrospectively included 80 eligible patients aged 54-87 years (mean age 69.8 years) who underwent transurethral resection of the prostate at our hospital from January 2019 to October 2021. Patients were divided into detrusor overactivity positive and negative groups, and according to bladder compliance, they were divided into: low (G1), normal (G2), and high (G3) bladder compliance groups. RESULTS: The incidence and score of postoperative frequent micturition in the detrusor overactivity positive group were higher than those in the detrusor overactivity negative group. The incidence and score of postoperative frequent micturition in the low bladder compliance group were higher than those in the normal and high bladder compliance groups. There was no significant difference in the score of frequent micturition between the normal and high bladder compliance groups. Multivariate logistic regression analysis indicated that frequent micturition was significantly correlated with detrusor overactivity, bladder compliance, maximum cystometric capacity, and maximum flow rate. CONCLUSION: This study confirmed that patients with abnormal bladder storage functions (detrusor instability and low bladder compliance) before transurethral resection of the prostate were likely to have frequent and severe urination after transurethral resection of the prostate. Therefore, preoperative urodynamic examination to evaluate the urinary storage function of patients with benign prostatic hyperplasia is of great significance to predict the occurrence and degree of postoperative frequent micturition.

Perioperative factors influencing the difficulty of retroperitoneal laparoscopic adrenalectomy: a single-center retrospective study.

PURPOSE: Identifying patients in whom adrenalectomy may be more difficult can help with surgical decision-making. This study investigated the perioperative factors affecting the difficulty of retroperitoneal laparoscopic adrenalectomy (RLA). METHODS: Sixty-eight patients who underwent RLA at our hospital between December 1, 2020 and May 1, 2021 were included. The difficulty of RLA was assessed by operating time and intraoperative blood loss. We analyzed the relationship between surgical difficulty and patient sex, age, and body mass index, pathological type, tumor side, tumor size, distance from the lower pole of the adrenal tumor to the upper pole of the kidney (DAK), and distance from the lower pole of the adrenal tumor to the renal pedicle (DARP). RESULTS: Mean operating time was 105.38 ± 33.31 min and mean intraoperative blood loss was 32.28 ± 22.88 ml. Univariate linear regression analysis showed that age (P = 0.047), tumor size (P = 0.002), DAK (P = 0.002), and DARP (P < 0.001) were significantly correlated with a longer operating time. Univariate logistic regression analysis showed that DARP (P = 0.001), DAK (P = 0.001), tumor size (P = 0.002), and age (P = 0.033) were significantly correlated with a longer operating time. Multivariate logistic regression indicated that DARP (OR 5.341; 95% CI 1.704-16.739; P = 0.004), and tumor size (OR 4.433; 95% CI 1.434-13.709; P = 0.010) were independent predictors of operating time. CONCLUSION: Age, tumor size, DAK, and DARP were predictors of the difficulty of RLA. Older age, lower DARP and DAK, and a larger tumor size were associated with a longer operating time. DARP and tumor size were independent predictors of surgical difficulty.

Genome-wide identification of CLE gene family and their potential roles in bolting and fruit bearing in cucumber (Cucumis sativus L.).

BACKGROUND: Signal peptides are essential for plant growth and development. In plants, biological processes including cell-cell communication, cellular proliferation and differentiation, cellular determination of self-incompatibility, and defensive responses, all depend heavily on peptide-signaling networks such as CLE (CLAVATA3/Embryo surrounding region-related). The CLEs are indispensable in different periods of plant growth and development, especially in maintaining the balance between proliferation and differentiation of stem cells in various meristematic tissues. The working system of CLE genes in cucumber, an important economical vegetable (Cucumis sativus L.), has not been fully studied yet. The distributional patterns of chromosome-level genome assembly in cucumber provide a fundamental basis for a genome-wide comparative analysis of CLE genes in such plants. RESULTS: A total of 26 individual CLE genes were identified in Chinese long '9930' cucumber, the majority of which belong to unstable short alkaline and hydrophilic peptides. A comparative analysis showed a close relationship in the development of CLE genes among Arabidopsis thaliana, melon, and cucumber. Half of the exon-intron structures of all CsCLEs genes are single-exon genes, and motif 1, a typical CLE domain near the C-terminal functioning in signal pathways, is found in all cucumber CLE proteins but CsCLE9. The analysis of CREs (Cis-Regulatory Elements) in the upstream region of the 26 cucumber CLE genes indicates a possible relationship between CsCLE genes and certain functions of hormone response elements. Cucumber resulted closely related to Arabidopsis and melon, having seven and 15 orthologous CLE genes in Arabidopsis and melon, respectively. Additionally, the calculative analysis of a pair of orthologous genes in cucumber showed that as a part of the evolutionary process, CLE genes are undergoing a positive selection process which leads to functional differentiation. The specific expression of these genes was vigorous at the growth and development period and tissues. Cucumber gene CLV3 was overexpressed in Arabidopsis, more than half of the transformed plants in T1 generation showed the phenomena of obvious weakness of the development of growing point, no bolting, and a decreased ability of plant growth. Only two bolted strains showed that either the pod did not develop or the pod was short, and its development was significantly inferior to that in the wild type. CONCLUSIONS: In this study, 26 CLE genes were identified in Chinese long '9930' cucumber genome. The CLE genes were mainly composed of alkaline hydrophilic unstable proteins. The genes of the CLE family were divided into seven classes, and shared close relationships with their homologs in Arabidopsis and melon. The specific expression of these genes was evaluated in different periods of growth and tissue development, and CLV3, which the representative gene of the family, was overexpressed in Arabidopsis, suggesting that it has a role in bolting and fruit bearing in cucumber.

Catalytic Deoxygenation of Xylitol to Renewable Chemicals: Advances on Catalyst Design and Mechanistic Studies.

Xylitol is commonly known as one of the top platform intermediates for biomass conversion. Catalytic deoxygenation of xylitol provides an atomic and energetic efficient way to produce a variety of renewable chemicals including ethylene glycol, 1,2-propanediol, lactic acid and 1,4-anhydroxylitol. Despite a few initial attempts in converting xylitol into those products, improving catalyst selectivity towards C-O and C-C cleavage reactions remains a grand challenge in this area. To our best knowledge, there is lack of comprehensive review to summarize the most recent advances on catalyst design and mechanisms in deoxygenation of xylitol, offering important perspective into future development of xylitol transformation technologies. Therefore, in this mini-review, we have critically discussed the conversion routes involved in xylitol deoxygenation over solid catalyst materials, the nanostructures of supported metal catalysts for C-H, C-C and C-O bond cleavage reactions, and mechanistic investigation for xylitol conversion. The outcome of this work provides new insights into rational design of effective deoxygenation catalyst materials for upgrading of xylitol and future process development in converting hemicellulosic biomass.

Recent Advances in Facile Liquid Phase Epoxidation of Light Olefins over Heterogeneous Molybdenum Catalysts.

Molybdenum complexes are versatile and efficient for liquid phase olefin epoxidation reactions. Rational design of catalysts is critical to achieve high atom efficiency during epoxidation processes. Although liquid phase epoxidation has been a popular topic for decades, three key issues, (a) rational control of morphology of molybdenum nanoparticles, (b) manipulating metal-support interaction and (c) altering electronic configuration at molybdenum center remains unsolved in this area. Therefore, in this paper, we have critically revised recent research progress on heterogeneous molybdenum catalysts for facile liquid phase olefin epoxidation in terms of catalyst synthesis, surface characterization, catalytic performance and structure-function relationship. Furthermore, plausible reaction mechanisms will be systematically discussed with the aim to provide insights into fundamental understanding on novel epoxidation chemistry.

Double-grating with multiple diffractions enabled small angle measurement.

We demonstrate a small angle measurement setup enabled by the double-grating configuration, where the multiple diffractions are used to magnify the deflection angle of the optical beam. Such small angle measurement setup has characteristics of high sensitivity and compact size. The use of two unparallel blazed gratings with a special included angle can realize multiple diffractions for the incident light, leading to the realization of deflection angle amplification. Experimental results verify that small angle can be accurately characterized and the angular resolution of measurement can be improved more than 40 times by inserting the double-grating configuration into the conventional auto-collimation angle measurement setup. Therefore, the micro-radian angle can be accurately measured with our proposed compact characterization setup.

Nanostructured Metal Catalysts for Selective Hydrogenation and Oxidation of Cellulosic Biomass to Chemicals.

Conversion of biomass to chemicals provides essential products to human society from renewable resources. In this context, achieving atom-economical and energy-efficient conversion with high selectivity towards target products remains a key challenge. Recent developments in nanostructured catalysts address this challenge reporting remarkable performances in shape and morphology dependent catalysis by metals on nano scale in energy and environmental applications. In this review, most recent advances in synthesis of heterogeneous nanomaterials, surface characterization and catalytic performances for hydrogenation and oxidation for biorenewables with plausible mechanism have been discussed. The perspectives obtained from this review paper will provide insights into rational design of active, selective and stable catalytic materials for sustainable production of value-added chemicals from biomass resources.

Suppressed expression of Cbl-b by NF-κB mediates icotinib resistance in EGFR-mutant non-small-cell lung cancer.

Although epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) could greatly improve the prognosis of NSCLC patients harboring activating EGFR mutations, drug resistance still remains a major obstacle to successful treatment. Our previous study found that the EGFR-TKI icotinib could upregulate the expression of Casitas-B-lineage lymphoma protein-B (Cbl-b), an E3 ubiquitin ligase. In the present study, we aimed to clarify the potential role of Cbl-b in the resistance to icotinib, and the underlying mechanisms using EGFR-mutant cell lines. We found that icotinib inhibited the proliferation of mutant-EGFR NSCLC cells (PC9 and HCC827), and upregulated the expression of Cbl-b at both the protein and mRNA levels. Cbl-b knockdown decreased the sensitivity of PC9 and HCC827 cells to icotinib, and partially restored icotinib-inhibited AKT activation in PC9 cells. On the contrary, Cbl-b overexpression could partly reverse the drug resistance in PC9 icotinib-resistant cells (PC9/IcoR). Moreover, overexpressing p65, the main member of transcription factor NF-κB family, reversed the icotinib-mediated upregulation of Cbl-b. Collectively, these data suggest that icotinib could upregulate Cbl-b mediated by NF-κB inhibition, and Cbl-b contribute to the icotinib sensitivity in EGFR-mutant NSCLC cells. This study highlights that low expression of Cbl-b might be the key obstacles in the efficacy of icotinib therapy.

Liquid crystal-optical phased arrays (LC-OPA)-based optical beam steering with microradian resolution enabled by double gratings.

We demonstrate an optical beam steering setup based on a liquid crystal-optical phased array (LC-OPA) with high angular resolution and low beam divergence, due to the use of double-grating configuration to enhance the corresponding angular resolution of LC-OPA. The introduction of two nonparallel blazed gratings with a special included angle can achieve multiple diffractions for the incident light, leading to the realization of angular compression. Numerical simulation results show the angular compression ratio can be optimized by selecting the appropriate grating constant and the included angle of double-grating. Experimental results verify that the steered angle of the incident light can be compressed so that the angular resolution of the steered beam can correspondingly be improved more than six times. In addition, when the beam is multiply diffracted within the double-grating configuration, the divergence angle becomes smaller as the beam size is enlarged. Therefore, both the microradian steering resolution and the narrow beam divergence can be simultaneously obtained with our proposed setup. The efficiency of the steering where the beam diffracted four times within the double-grating configuration is 80%.

Tyrosine kinase inhibitor-induced IL-6/STAT3 activation decreases sensitivity of EGFR-mutant non-small cell lung cancer to icotinib.

Tyrosine kinase Inhibitors (TKIs) of epidermal growth factor receptor (EGFR) has considerably benefited for non-small cell lung carcinomas (NSCLC) harbor mutations in EGFR. However, the factors attenuating EGFR-TKI efficiency are obstacles to inhibit the proliferation of EGFR-mutant NSCLC cells successfully. Clarifying the insensitivity mechanisms of EGFR-TKI would help to develop new treatment strategy. In this study, the sensitivity of EGFR-mutant NSCLC cell lines, PC9 and HCC827, to icotinib was detected. Similar with other EGFR-TKIs such as gefitinib and erlortinib in previous research, the proliferation of two cell lines was apparently inhibited. However, we surprisingly found that contrast with the suppression of EGFR-AKT/ERK pathway, STAT3 was significantly activated in PC9 cells with the treatment of icotinib, but not in HCC827 cells. Further study confirmed that icotinib concomitantly induced IL-6 secretion and src activation in PC9 cells. Moreover, with the treatment of IL-6 neutralizing antibody or src inhibitor, dasatinib, icotinib-induced phosphorylation of STAT3 was reduced, as well as the sensitivity of PC9 to icotinib was also partially increased. Our results suggest that Src/IL-6/STAT3 bypass pathway is activated to maintain cell survival when the EGFR pathway was inhibited by TKIs, even in some EGFR-mutant NSCLC cells sensitive to TKIs. This finding provides a groundwork for potential combinatorial treatment with TKIs and Src or STAT3 inhibitor to improve icotinib sensitivity.

Age-period-cohort analysis of suicide mortality by gender among white and black Americans, 1983-2012.

BACKGROUND: Previous studies suggested that the racial differences in U.S. suicide rates are decreasing, particularly for African Americans, but the cause behind the temporal variations has yet to be determined. This study aims to investigate the long-term trends in suicide mortality in the U.S. between 1983 and 2012 and to examine age-, period-, and cohort-specific effects by gender and race. METHOD: Suicide mortality data were collected from the Web-based Injury Statistics Query and Reporting System (WISQARS) and analyzed with the Joinpoint regression and age-period-cohort (APC) analysis. RESULTS: We found that although age-standardized rate of suicide in white males, white females, black males, and black females all changed at different degrees, the overall situation almost has not changed since these changes offset each other. By APC analysis, while the age effect on suicide demonstrate an obvious difference between white males and females (with the peak at 75 to 79 for white males and 45 to 54 for white females), young black people are predominantly susceptible to suicide (risk peaks in early 20s for black males and late 20s for black females). Cohort effects all showed a descending trend, except that in white males and females which showed an obvious increase peaked in around cohort 1960. There was a similar period effect trend between different genders in the same race group, but between the races, differences were found in the period before 1990 and after 2000. CONCLUSION: We confirmed that the distinction in age-specific suicide rate patterns does exist by gender and by race after controlling for period and cohort effects, which suggested that minorities' age patterns of suicide may have been masked up by the white people in the whole population. The differences of period effects and cohort effects between white and black Americans were likely to be mainly explained by the difference in race susceptibility to economic depression.

Unraveling the Molecular Size Effect on Surface Engineering of Perovskite Solar Cells.

Surface engineering in perovskite solar cells, especially for the upper surface of perovskite, is widely studied. However, most of these studies have primarily focused on the interaction between additive functional groups and perovskite point defects, neglecting the influence of other parts of additive molecules. Herein, additives with -NH3 + functional group are introduced at the perovskite surface to suppress surface defects. The chain lengths of these additives vary to conduct a detailed investigation into the impact of molecular size. The results indicate that the propane-1,3-diamine dihydroiodide (PDAI2 ), which possesses the most suitable size, exhibited obvious optimization effects. Whereas the molecules, methylenediamine dihydroiodide (MDAI2 ) and pentane-1,5-diamine dihydroiodide (PentDAI2 ) with unsuitable size, lead to a deterioration in device performance. The PDAI2 -treated devices achieved a certified power conversion efficiency (PCE) of 25.81% and the unencapsulated devices retained over 80% of their initial PCE after 600 h AM1.5 illumination.

Corrigendum: Resilience and caregiving ability among caregivers of people with stroke: the mediating role of uncertainty in illness.

[This corrects the article DOI: 10.3389/fpsyt.2022.788737.].

Polyureas from diamines and carbon dioxide: synthesis, structures and properties.

Polyureas were synthesized from diamines and carbon dioxide in the absence of any catalyst or solvent, analogous to the synthesis of urea from condensation of ammonia with carbon dioxide. The method used carbon dioxide as a carbonyl source to substitute highly toxic isocyanates for the synthesis of polyureas. FTIR and DFT calculations confirmed that strong bidentate hydrogen bonds were formed between urea motifs, and XRD patterns showed that the PUas were highly crystalline and formed a network structure through hydrogen bonds, which served as physical cross-links. The long chain PUas presented a microphase separated morphology as characterized by SAXS and showed a high melting temperature above 200 °C. The PUas showed high resistance to solvents and excellent thermal stability, which benefitted from their special network structures. The PUas synthesized by this method are a new kind of functional material and could serve some areas where their analogues with similar functional groups could not be applied.

Resilience and caregiving ability among caregivers of people with stroke: The mediating role of uncertainty in illness.

Background: In China, stroke survivors are usually cared for by their family members. However, the caregiving ability of these informal caregivers remain inadequate during the hospitalization of their family members following a sudden onset of a stroke, and this sudden need for care overwhelms caregivers even after the hospital discharge. Therefore, research is required to identify predictors of caregiving ability that could be targeted in future interventions aimed at improving caregiving skills and reducing the burden on caregivers who care for stroke survivors. Materials and methods: From August 2019 to February 2020, stroke survivors were hospitalized for the first time, and their family caregivers were registered via convenience sampling. Caregiver demographic information, resilience status, uncertainty in illness, caregiving ability, and patients' severity of stroke were measured using standardized questionnaires. Structural equation modeling was used to test the proposed model, where caregiver resilience and stroke severity predicted caregiving ability directly, and uncertainty in illness mediated the association between caregiver resilience and caregiving ability. Results: A total of 306 dyads were included in the study. The tested model fit the data well (χ2 = 118.2, df = 64, RMSEA = 0.053, CFI = 0.946, TLI = 0.923). Statistically significant pathways linked caregivers' resilience status to uncertainty in illness (ß = -0.558, S.E. = 0.022, P < 0.01), caregivers' resilience to the status of caregiving ability (ß = -0.269, S.E. = 0.013, P < 0.01) and caregivers' uncertainty about the illness to caregiving ability (ß = 0.687, S.E. = 0.051, P < 0.01). We also found that caregivers' uncertainty in illness mediated the association between caregivers' resilience and caregiving ability (ß = -0.384, S.E. = 0.061, P < 0.01). Conclusions: Our structural equation modeling result identified resilience and uncertainty about the illness as predictors of the caregiving ability of informal family caregivers who suffered from care burdens. Supporting family caregivers to build their resilience and reduce illness uncertainty may improve caregiving for stroke survivors.

Integrating physiology, genetics, and transcriptome to decipher a new thermo-sensitive and light-sensitive virescent leaf gene mutant in cucumber.

Chloroplasts are the material basis of photosynthesis, and temperature and light severely affect chloroplast development and thus influence photosynthetic efficiency. This study identified a spontaneous virescent leaf mutant, SC311Y, whose cotyledons and true leaves were yellow and gradually turned green. However, temperature and light affected the process of turning green. In addition, this mutant (except at the seedling stage) had ruffled leaves with white stripes, sterile males, and poorly fertile female flowers. Genetic characteristics analysis revealed that the recessive gene controlled the virescent leaf. Two F2 populations mapped v-3 to the interval of 33.54-35.66 Mb on chromosome 3. In this interval, BSA-Seq, RNA-Seq, and cDNA sequence analyses revealed only one nonsynonymous mutation in the Csa3G042730 gene, which encoded the RNA exosome supercomplex subunit resurrection1 (RST1). Csa3G042730 was predicted to be the candidate gene controlling the virescent leaf, and the candidate gene may regulate chloroplast development by regulating plastid division2 (PDV2). A transcriptome analysis showed that different factors caused the reduced chlorophyll and carotenoid content in the mutants. To our knowledge, this study is the first report of map-based cloning related to virescent leaf, male-sterile, and chloroplast RNA regulation in cucumber. The results could accelerate the study of the RNA exosome supercomplex for the dynamic regulation of chloroplast RNA.