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Dietary therapies are recommended for the treatment of pediatrics with functional abdominal pain disorders (FAPDs), but the comparative effectiveness among them is unclear. Therefore, the main aim of this systematic review and meta-analysis was to compare the effectiveness of differential dietary therapies in pediatrics with functional abdominal pain disorders. We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials databases from inception to February 28, 2023. Randomized clinical trials of dietary treatments for pediatric patients with functional abdominal pain disorders were included. The primary outcome was the improvement in abdominal pain. The secondary outcomes were changes in pain intensity and pain frequency. Thirty-one studies after screening 8695 retrieved articles were included, and 29 studies were available for network meta-analysis. Compared with placebo, fiber (RR, 4.86; 95%CI, 1.77 to 13.32; P-score = 0.84), synbiotics (RR, 3.92; 95%CI, 1.65 to 9.28; P-score = 0.75), and probiotics (RR, 2.18; 95%CI, 1.46 to 3.26; P-score = 0.46) had significantly larger effect on the improvement in abdominal pain, the three treatments had larger effect than placebo but statistically insignificant in difference in improving pain frequency and intensity. Similarly, there were no significant differences between the dietary treatments after indirect comparisons of the three outcomes. Conclusion: Fiber supplements, synbiotics, and probiotics were efficacious in improving abdominal pain of FAPDs in children, suggested by very low or low evidence. The evidence of the efficacy of probiotics is more convincing than fiber and synbiotics when sample size and statistical power were considered. No difference in the efficacy of the three treatments. High-quality trials are needed to further investigate the efficacy of dietary interventions. What is Known: • Multiple dietary treatment options are available for functional abdominal pain disorders in the pediatric population, of which the most beneficial one is currently unknown. What is New: • This NMA found very low to low certainty of the evidence suggesting that fiber, synbiotics, and probiotics might be more efficacious in improving abdominal pain of FAPDs in children than the other dietary treatments. • There were no significant differences between active dietary treatments for changes in abdominal pain intensity. [ABSTRACT FROM AUTHOR]

Flower-like phosphorus-doped nickel oxide (P-NiO) is proposed as a counter electrode (CE) for dye-sensitized solar cells (DSSCs). The flower-like nickel oxide essentially serves as the matrix for the CE, which is expected to promote a two-dimensional electron transport pathway. The phosphorus is intended to improve the catalytic ability by creating more active sites in the NiO for the catalysis of triiodide ions (I3−) to iodide ions (I−) on the surface of the CE. The P-NiO is controlled by a sequencing of precursor concentration, which allows the P-NiO to possess different features. The debris aggregation occurs in the P-NiO-1, while the P-NiO-0.75 leads to the incomplete flower-like nanosheets. The complete flower-like morphology can be observed in the P-NiO-0.5, P-NiO-0.25 and P-NiO-0.1 catalytic electrodes. The DSSC with the P-NiO-0.5 CE achieves a power conversion efficiency (η) of 9.05%, which is better than that of the DSSC using a Pt CE (η = 8.51%); it also performs better than that with the Pt CE, even under rear illumination and dim light conditions. The results indicate the promising potential of the P-NiO CE to replace the expensive Pt CE. [ABSTRACT FROM AUTHOR]

Lyme disease, caused by Lyme Borrelia spirochetes, is the most common vector-borne illness in the United States. Despite its global significance, with an estimated 14.5 % seroprevalence, there is currently no licensed vaccine. Previously, we demonstrated that CspZ-YA protein conferred protection against Lyme Borrelia infection, making it a promising vaccine candidate. However, such a protein was tagged with hexahistidine, and thus not preferred for vaccine development; furthermore, the formulation to stabilize the protein was understudied. In this work, we developed a two-step purification process for tag-free E. coli -expressed recombinant CspZ-YA. We further utilized various bioassays to analyze the protein and determine the suitable buffer system for long-term storage and formulation as a vaccine immunogen. The results indicated that a buffer with a pH between 6.5 and 8.5 stabilized CspZ-YA by reducing its surface hydrophobicity and colloidal interactions. Additionally, low pH values induced a change in local spatial conformation and resulted in a decrease in α-helix content. Lastly, an optimal salinity of 22–400 mM at pH 7.5 was found to be important for its stability. Collectively, this study provides a fundamental biochemical and biophysical understanding and insights into the ideal stabilizing conditions to produce CspZ-YA recombinant protein for use in vaccine formulation and development. [ABSTRACT FROM AUTHOR]

Background Objective Materials and methods Results Conclusions A large number of studies have shown that leptin plays an important role in the regulation of fertility via the hypothalamus‐pituitary‐gonad axis. However, its peripheral function in epididymis was still elusive.The purpose of this study was to determine the pro‐secretion effect of leptin on the rat epididymal epithelium.In the present study, real‐time quantitative polymerase chain reaction, western blot, and immunohistochemical analysis were employed to detect the expression pattern of leptin receptors in rat epididymis. The pro‐secretion effect of leptin on epididymal epithelial cells was measured by short‐circuit current, and the prostaglandin E2 and cyclic adenosine monophosphate level was evaluated by enzyme‐linked immunosorbent assay.We verified that the leptin receptor was located on the epididymal epithelium, with a relatively high expression level in corpus and cauda epididymis. Ussing chamber experiments showed that leptin stimulated a significant rise of the short‐circuit current in rat epididymal epithelial cells, which could be abolished by the specific leptin receptor antagonist peptide Allo‐aca, or by removing the ambient Cl− and HCO3−. Furthermore, the leptin‐stimulated short‐circuit current response could be abrogated by blocking the apical cystic fibrosis transmembrane regulator or the basolateral Na+‐K+‐2Cl− cotransporter. Our pharmacological experiments manifested that interfering with the prostaglandin H synthase‐2‐prostaglandin E2‐EP2/EP4‐adenylate cyclase pathways could significantly blunt the cystic fibrosis transmembrane regulator‐mediated anion secretion induced by leptin. The enzyme‐linked immunosorbent assay demonstrated that leptin could induce a substantial increase in prostaglandin E2 release and cyclic adenosine monophosphate synthesis of primary cultured rat cauda epididymal epithelial cells. Our data also suggested that JAK2, ERK, and PI3K‐dependent phosphorylation may be involved in the activation of prostaglandin H synthase‐2 and the subsequent prostaglandin E2 production.The present study demonstrated the pro‐secretion function of leptin in rat epididymal epithelium via the activation of cystic fibrosis transmembrane regulator and Na+‐K+‐2Cl− cotransporter, which was dependent on the paracrine/autocrine prostaglandin E2 stimulated EP2/EP4‐adenylate cyclase pathways, and thus contributed to the formation of an appropriate microenvironment essential for sperm maturation. [ABSTRACT FROM AUTHOR]

Approximately 5–7% of non–small cell lung cancer (NSCLC) cases harbor an anaplastic lymphoma kinase (ALK) fusion gene and may benefit from ALK inhibitor therapy. To detect ALK fusion genes, we developed a novel test using reverse transcription polymerase chain reaction (RT-PCR) for the ALK kinase domain (KD). Since ALK expression is mostly silenced in the adult with the exception of neuronal tissue, the normal lung tissue, mesothelial lining, and inflammatory cells are devoid of ALK transcript, making ALK KD RT-PCR an ideal surrogate test for ALK fusion transcripts in lung or pleural effusion. The test was designed with a short PCR product (197 bp) to work for both malignant pleural effusion (MPE) and formalin-fixed, paraffin-embedded (FFPE) NSCLC samples. Using ALK IHC as a reference, the sensitivity of the test was 100% for both MPE and FFPE. The specificity was 97.6% for MPE and 97.4% for FFPE. Two false positive cases were found. One was a metastatic brain lesion which should be avoided in the future due to intrinsic ALK expression in the neuronal tissue. The other one resulted from ALK gene amplification. Due to potential false positivity, subsequent confirmation tests such as fluorescence in situ hybridization or multiplex PCR would be preferable. Nevertheless, the test is simple and inexpensive with no false negativity, making it a desirable screening test. It also offers an advantage over multiplex RT-PCR with the capability to detect novel ALK fusions. Indeed through the screening test, we found a novel ALK fusion partner (sperm antigen with calponin homology and coiled-coil domains 1 like gene, SPECC1L) with increased sensitivity to crizotinib in vitro. In summary, a novel RNA-based ALK KD analysis was developed for ALK rearrangement screening in MPE and FFPE specimens of NSCLC. This simple inexpensive test can be implemented as routine diagnostics. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are the first-line regimen for the treatment of non-small cell lung cancer (NSCLC) patients with EGFR mutations. However, false-negative results are occasionally observed, even with FDA-approved molecular tests. Such examples in have been reported in our pilot study showing a slightly upward-shifted amplification curve using commercial reverse transcription-quantitative (RT-q)PCR. Verification using peptide nucleic acid (PNA) clamping-sequencing, which has a sensitivity of ~0.1%, may allow better prediction of which patients will benefit from EGFR-TKI therapy. To confirm this hypothesis, samples were prospectively collected from 1,783 lung cancer cases diagnosed in National Cheng Kung University Hospital between 2012–2018. An independent lung cancer cohort of 1,944 cases was also recruited from other hospitals. The clinical significance of mutant-enriched PCR with PNA-sequencing was analyzed and patient outcomes were followed. A total of 17 of 34 cases (50%) were found to harbor EGFR mutations by PNA-sequencing. A total of 22 cases were discovered in the independent lung cancer cohort, and 14 of these (63.6%) cases had EGFR mutations. TKIs were administered to 14 of the 17 mutation-positive patients, and a partial response was observed in 4 cases and stable disease in 10 cases. Patients with EGFR mutations receiving a TKI regimen had a longer overall survival (OS) (median: 40.0 vs. 10.0 months) compared with those without treatment. The difference in OS was not significant. Based on the results of the present study, combining RT-qPCR with PNA-sequencing may be a practical supplementary technology in a clinical molecular laboratory for a subset of lung cancer patients in selection of EGFR TKI therapy. [ABSTRACT FROM AUTHOR]

This work aimed to investigate miR‐93‐5p expression in tumor tissue and its in vitro effects in colorectal cancer (CRC) by targeting programmed death ligand‐1 (PD‐L1). MiR‐93‐5p and PD‐L1 expression was detected in CRC and adjacent normal tissues by quantitative real‐time polymerase chain reaction and immunohistochemistry. The correlation between miR‐93‐5p and PD‐L1 was validated by a dual‐luciferase reporter assay. HCT116 and SW480 cells were divided into blank, miR‐NC, miR‐93‐5p mimics, miR‐93‐5p inhibitor, PD‐L1 small interfering RNA (siRNA) and miR‐93‐5p inhibitor + PD‐L1 siRNA groups, and wound‐healing and transwell assays were performed to detect cell migration and invasion, respectively. Protein expression was measured by western blotting. The secretion of cytokines was detected in the CRC cell/T coculture models. MiR‐93‐5p was downregulated in CRC tissues with upregulated PD‐L1. In PD‐L1‐negative patients, miR‐93‐5p expression was increased compared with that in PD‐L1‐positive patients. MiR‐93‐5p and PD‐L1 expression levels were associated with the tumor differentiation, lymphatic metastasis, TNM, Duke's stage, and prognosis of CRC. PD‐L1 siRNA weakened the migration and invasion abilities via decreased expression of matrix metalloproteinase‐1 (MMP‐1), ‐2, and ‐9, and these effects were abolished by the miR‐93‐5p inhibitor. Additionally, anti‐PD‐L1 upregulated the expressions of interleukin‐2 (IL‐2), tumor necrosis factor‐α (TNF‐α), and interferon γ (IFN‐γ) in the coculture of T cells with CRC cells, but downregulated the expressions of IL‐1β, IL‐10, and TGF‐β. However, these changes were partially reversed by miR‐93‐5p inhibition. miR‐93‐5p is expected to be a novel target for CRC treatment since it decreases the migration and invasion, as well as the immune evasion, of CRC cells via targeting PD‐L1. [ABSTRACT FROM AUTHOR]

Light attenuation and antioxidation are the main mechanisms of photoprotection by anthocyanin under high light (HL) stress. Anthocyanin synthase (ANS) is the key enzyme in the downstream portion of anthocyanin synthetic pathways. To explore the role of ANS in photoprotection by anthocyanin under HL stress, homozygous ANS -deficient Arabidopsis mutants were screened from SALK_073183 and SALK_028793. Here, we obtained two deficient mutants, ans - 1 and ans - 2 , which had ANS gene expression levels equal to 5.9 and 32.9% of that of Col respectively. By analysing their physiological and biochemical responses to HL stress, we found that there were positive correlations among ANS expression level, anthocyanin content and resistance to HL. The line with the lowest ANS expression level, ans - 1 , was also the most sensitive to HL, showing the lowest anthocyanin content, chlorophyll content, F v/ F m ratio, and Rubisco content and the highest O2•− accumulation and membrane leakage rate, although it also had the highest antioxidant capacity. Experimental evidence suggests that ANS mainly regulated the light-attenuating function of anthocyanin in photoprotection under HL. Blocking excess light is an important function of anthocyanin that protects plants from HL stress, and a high antioxidant capacity cannot compensate for the absence of the light-shielding function of anthocyanin. Upon high light stress, light-shielding and antioxidation are the main mechanisms of photoprotection by anthocyanin, the final key enzyme in whose synthetic pathways is anthocyanin synthase (ANS). This investigation tackled the role of ANS in photoprotection: ANS mainly regulates the light-shielding of anthocyanin in photoprotection. Additionally, we found that light-shielding is the important function in photoprotection of anthocyanins, and high antioxidant capacity cannot compensate for the absence of the light-shielding. [ABSTRACT FROM AUTHOR]

Little is known about the link between child abuse and health risk behaviors among Chinese college students. This cross-sectional study examined the prevalence of child abuse and its relations with individual and clusters of health risk behaviors among Chinese college students. A total of 507 students participated in this survey. The prevalence of child abuse from the highest to the lowest was emotional neglect (53.9%), physical neglect (49.0%), emotional abuse (21.8%), physical abuse (18.3%), and sexual abuse (18.1%), respectively. Males were more likely to report child abuse than females ( p < 0.01). For males, emotional abuse was associated with internet addiction [OR = 2.28; 95%CI (1.00, 5.20)] and suicidal behavior [OR = 12.47, 95%CI (2.61, 59.54)]; while sexual abuse was associated with internet addiction [OR = 2.30, 95%CI (1.14, 4.66)]. For females, emotional abuse was significantly associated with increased risks for self-harm behavior [OR = 15.03, 95%CI (3.59, 63.07)] and suicidal behavior [OR = 5.16, 95%CI (1.63, 16.40)]. Physical abuse was related to risks for internet addiction [OR = 2.50, 95%CI (1.03, 6.04)] significantly. Two-step cluster analysis showed that participants in clusters with more health risk behaviors reported higher scores of child abuse. These findings suggest that child abuse was associated with both individual and clustering of health risk behaviors among Chinese college students. [ABSTRACT FROM AUTHOR]

Formation of amyloid fibrils has been associated with at least 30 different protein aggregation diseases. The 129-residue polypeptide hen lysozyme, which is structurally homologous to human lysozyme, has been demonstrated to exhibit amyloid fibril-forming propensity in vitro . This study is aimed at exploring the influence of erythrosine B on the in vitro amyloid fibril formation of hen lysozyme at pH 2.0 and 55 °C using ThT binding assay, transmission electron microscopy, far-UV circular dichroism absorption spectroscopy, 1-anilinonaphthalene-8-sulfonic acid fluorescence spectroscopy, and synchronous fluorescence study. We found that lysozyme fibrillogenesis was dose-dependently suppressed by erythrosine B. In addition, our far-UV CD and ANS fluorescence data showed that, as compared with the untreated lysozyme control, the α-to-ß transition and exposure of hydrophobic clusters in lysozyme were reduced upon treatment with erythrosine B. Moreover, it could be inferred that the binding of erythrosine B occurred in the vicinity of the tryptophan residues. Finally, molecular docking and molecular dynamics simulations were further employed to gain some insights into the possible binding site(s) and interactions between lysozyme and erythrosine B. We believe the results obtained here may contribute to the development of potential strategies/approaches for the suppression of amyloid fibrillogenesis, which is implicated in amyloid pathology. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 45-year-old multiparous woman who was presented to the emergency department with a right lower abdominal pain, vomiting, diarrhea and fever and was diagnosed with Uterine leiomyomas. Topics mention including the abdominal examination, detection of right pelvic mass and histopathologic examination.

Analyzing EGFR mutations and detecting ALK gene fusion are indispensable when planning to treat pulmonary adenocarcinoma. Malignant pleural effusion (MPE) is a devastating complication of lung cancer and sometimes the only source for mutation analysis. The percentage of tumor cells in the pleural effusion may be low; therefore, mutant enrichment is required for a successful analysis. The EGFR mutation status in MPE was determined using three methods: (1) PCR sequencing of genomic DNA (direct sequencing), (2) mutant-enriched PCR sequencing of genomic DNA using peptide nucleic acid (PNA-sequencing), and (3) PCR sequencing of cDNA after reverse transcription for cellular RNA (RNA-sequencing). RT-PCR was also used to test cases for ALK gene fusion. PNA-sequencing and RNA-sequencing had similar analytical sensitivities (< 1%), which indicates similar enrichment capabilities. The clinical sensitivity in 133 cases when detecting the common EGFR exon 19 and exon 21 mutations was 56.4% (75/133) for direct sequencing, 63.2% (84/133) for PNA-sequencing, and 65.4% (87/133) for RNA-sequencing. RT-PCR and sequencing showed 5 cases (3.8%) with ALK gene fusion. All had wild-type EGFR. For EGFR analysis of MPE, RNA-sequencing is at least as sensitive as PNA-sequencing but not limited to specific mutations. Detecting ALK fusion can be incorporated in the same RNA workflow. Therefore, RNA is a better source for comprehensive molecular diagnoses in MPE. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Chinese herbal products (CHPs) are commonly prescribed for sleep disorder and major depressive disorder (MDD). The aim of this study was to investigate the prescription patterns of CHPs and Western medicine for patients with these disorders in Taiwan, and analyze the frequency of using single herbs (SHs) and herbal formulas (HFs). Materials and methods In this retrospective population-based study secondary data analysis was performed using data from Taiwan’s Longitudinal Health Insurance Database (LHID) between January 2007 and December 2011. In total, 1000,000 beneficiaries from the LHID were randomly selected from the 2010 registry for beneficiaries of the National Health Insurance Research Database. Patients with sleep disorder and MDD according to the International Classification of Diseases, Ninth Revision, Clinical Modification codes 307.40 and 311, respectively. Results Among a total of 11,030 patients with sleep disorder, 9619 used Western medicine, 1334 used CHPs, and 77 used both, Among a total of 11,571 patients with MDD, 11,389 used Western medicine, 131 used CHPs, and 51 used both. Regardless of disorder type, women were predominant The majority of the patients were aged 22–44 years, had a monthly income of NT$17,281–NT$22,800, and lived in an area with Level 1 and Level 2 urbanization. Of the patients with sleep disorder, 1411 had used CHPs and visited a clinic 5298 times on average. Of the patients with MDD, 182 had used CHPs and visited a clinic 755 times on average. The three most commonly used SHs and HFs were Ziziphi Spinosae Semen, Polygoni Multiflori Caulis, and Polygalae Radix, and Jia-Wei-Xiao-Yao-San, Suan-Zao-Ren-Tang, and Chai-Hu-Chia-Lung-Ku-Mu-Li-Tang, respectively. Conclusion Chinese herbal products including SHs and HFs are prescribed for patients with sleep disorder and MDD. However, the efficacy and safety of CHPs for sleep disorder and MDD need to be further evaluated. [ABSTRACT FROM AUTHOR]

Inspired by the debate about character between situationism and virtue ethics, I argue that John Doris's idea, 'local trait', offers a fresh insight into contemporary character education. Its positive variant, 'local virtue', signals an inescapable relay station of the gradual development of virtue, and serves as a promising point of departure for advanced growth. The idea of converting local virtues to more global ones is accordingly proposed to represent an empirically more realistic way of conceiving how to approach the ethical ideal of global virtues. It helps to direct our gaze to the great intermediate developmental stages of virtue, which mark out a whole spectrum of virtues of varying degrees that fall short of full virtue. This new notion works together with the traditional Aristotelian account to provide a full account of how to effectively undertake the age-old educational business of the inculcation of virtues. [ABSTRACT FROM AUTHOR]

Highlights: [•] Heat insulation solar glass (HISG) is a type of multifunction PV module. [•] HISG has a considerably low shading coefficient and U value. [•] HISG can reduce air conditioning and heating energy consumption in buildings. [•] HISG can replace any type of glass installed in a building. [•] HISG is a safe construction material. [ABSTRACT FROM AUTHOR]

In order to study the compositional change of residual gas during different desorption stages, refined desorption experiments of nine freshly anthracite samples, collected from the drilling wells and coal mines in Zhina, Guizhou, were carried out, and the gas compositions were determined by gas chromatography(model SP-3400). It was found that the desorbed gas volume is largest at crushed desorption stages, indicating that most of the residual gas is trapped in closed coal pores. Methane, carbon monoxide, carbon dioxide and ethane concentrations show a V-type change and are lowest at crushed desorption stage, whereas nitrogen concentration gives anti-V type trend and is highest. A remarkable compositional fractionation of each component occurs during heated desorption after crushing, showing the progressive enrichment of carbon monoxide, carbon dioxide and ethane, and relatively depletion of methane and nitrogen. It was suggested that the fractionation effect is derived from the differences of adsorption temperature and adsorption capacity, resulting in more retention of the gas components with higher adsorption capacity in micropores after desorption at the room temperature, and then desorption at the higer temperature 90-95 °C of water bath heating. [ABSTRACT FROM AUTHOR]

Mounting observational records demonstrate human‐caused faunal decline in recent decades, while accumulating archaeological evidence suggests an early biodiversity impact of human activities during the Holocene. A fundamental question arises concerning whether modern wildlife population declines began during early human disturbance. Here, we performed a population genomic analysis of six common forest birds in East Asia to address this question. For five of them, demographic history inference based on 25–33 genomes of each species revealed dramatic population declines by 4‐ to 48‐fold over millennia (e.g. 2000–5000 thousand years ago). Nevertheless, summary statistics detected nonsignificant correlations between these population size trajectories and Holocene temperature variations, and ecological niche models explicitly predicted extensive range persistence during the Holocene, implying limited demographic consequence of Holocene climate change. Further analyses suggest high negative correlations between the reconstructed population declines and human disturbance intensities and indicate a potential driver of human activities. These findings provide a deep‐time and large‐scale insight into the recently recognized avifaunal decline and support an early origin hypothesis of human effects on biodiversity. Overall, our study sheds light on the current biodiversity crisis in the context of long‐term human–environment interactions and offers a multi‐evidential framework for quantitatively assessing the ecological consequences of human disturbance. [ABSTRACT FROM AUTHOR]

The different sorts of virtuous people who display various virtues to a remarkable degree have brought the issue of individualisation of moral character to the forefront. It signals a more personal dimension of character development which is notoriously ignored in the current discourse on character education. The case is made that since in practice, the individualisation of moral character must, by necessity, advance side by side with the cultivation of virtues, a full account of character education needs to give consideration to both concerns. After analysing the specific ways which temperament, social roles, and occupations respectively contribute to the individualisation of moral character, some practical implications are drawn to shed new light on the common practice of the inculcation of virtues. Firstly, since the varieties of moral personality is the norm, it is appropriate to encourage the educated to become virtuous people of different sorts. Secondly, given the influence that temperament may exert on virtue, having good knowledge of each child's temperament, identifying the specific difficulties possibly confronting him/her accordingly, and then providing more opportunities to strengthen the cultivation of the related virtues are crucial. Thirdly, since children with different temperaments are inclined to identify with different sorts of moral exemplars, it is valuable to present them a great variety of moral models, from which they can choose the kind of virtuous people they would want to emulate. Lastly, since assuming different occupations and social roles is liable to result in various moral characters, character formation cannot be confined to the family or school. Among others, workplaces and communities are also important variables. [ABSTRACT FROM AUTHOR]

Abstract: Due to its malignancy, the development of effective therapeutic strategies for hepatocellular carcinoma (HCC) is of urgent needs. Natural antimicrobial peptides (AMPs), also known as host defense peptides (HDPs), not only act as direct antimicrobial agents, but also represent important regulators of the innate immune system. It has been reported that cationic AMPs may exhibit cancer-selective toxicity. We have designed a series of novel AMPs with potent antimicrobial activity against a broad spectrum of bacterial pathogens. In the current study, we evaluate the antitumor potency of these AMPs toward HCC cell lines J5, Huh7, and Hep3B. Selected AMPs inhibit the viability of HCC cells in a dose-dependent fashion, while the normal 3T3 cells were significantly less susceptible to these AMPs. GW-H1 treatment (20μM) of J5 cells for 24–72h resulted in the induction of apoptosis, as revealed by flow cytometry (increased sub-G1 populations), and western blot analysis for the appearance of activated caspase-3, -7 and -9 cleavages. Two-dimensional gel electrophoresis was applied to further analyze the AMP-responsive protein profiles of HCC, down-regulation of Hsp27, phophoglycerate kinase 1 and triosephosphate isomerase indicated that GW-H1 may induce apoptosis, and further inhibit progression and metastasis of J5 HCC cells. FITC-labeled GW-H1 was found to attach to cell membrane initially, then translocated into the cytoplasm, and eventually membranous organelles or nucleus. GW-H1 induced a marked growth suppression of J5 xenografts in nude mice in a dose dependent manner. These findings provided support for future application of GW-H1 as potential therapeutic agent for HCC. [Copyright &y& Elsevier]

Monoclonal expansions of immunoglobulin (Ig) and T-cell receptor (TCR) genes are, respectively, important markers for B- and T-cell malignancies. We used BIOMED-2 protocols to detect clonality of these genes in B- (BCL) and T-cell lymphoma (TCL) in southern Taiwan. Heteroduplex analysis was used after PCR reactions. Ig/TCR clonality rates were 95% (22 in 23 cases) for BCL and 76% (19 in 25 cases) for TCL. These results reveal overall satisfactory detection rates for both BCL and TCL. None of the four natural killer (NK)/T-cell lymphomas detected showed TCR gene clonality, which suggested that BIOMED-2 protocols distinguished the NK/T-cell lymphoma from TCL. In addition, three of the five tested precursor T-cell lymphoblastic lymphomas showed no TCR gene clonality, probably because the immature T-cells in this type of TCL had not undergone TCR gene rearrangements. We conclude that BIOMED-2 protocols are suitable for detecting Ig and TCR clonalities in B- and T-cell malignancies in southern Taiwan. [ABSTRACT FROM AUTHOR]

The natural compound n-butylidenephthalide (BP), which is isolated from the chloroform extract of Angelica sinensis, has been investigated for its antitumoral effects on glioblastoma multiform (GBM) brain tumors both in vitro and in vivo. To determine the mechanism of BP-induced growth arrest and apoptosis, we examined BP-induced changes in gene expression by microarray screening using human GBM brain tumor cells. This analysis identified several BP-inducible genes, including the nuclear receptors NOR-1, Nurr1, and Nur77. Among these genes, Nur77 is particularly interesting because it plays an important role in the apoptotic processes in various tumor cell lines. BP was able to increase Nur77 mRNA and protein expression in a time-dependent manner. After BP treatment in GBM 8401 cells, Nur77 translocated from the nucleus to the cytoplasm, the cytochrome c was released from the mitochondria, and caspase 3 became activated. Furthermore, using Nur77 promoter-luciferase assay, BP increased Nur77 was AP1 related. Inhibition of BP-induced Nur77 expression by Nur77 short interfering RNA blocked BP-induced apoptosis in GBM 8401 cells, suggesting that the induction of Nur77 negatively affected GBM 8401 cell survival. In summary, our results suggest that up-regulation of Nur77 may explain the antitumoral activity of BP in brain tumor cells. [ABSTRACT FROM AUTHOR]

The naturally-occurring compound, n-butylidenephthalide (BP), which is isolated from the chloroform extract of Angelica sinensis (AS-C), has been investigated with respect to the treatment of angina. In this study, we have examined the anti-tumor effects of n-butylidenephthalide on glioblastoma multiforme (GBM) brain tumors both in vitro and in vivo. In vitro, GBM cells were treated with BP, and the effects of proliferation, cell cycle and apoptosis were determined. In vivo, DBTRG-05MG, the human GBM tumor, and RG2, the rat GBM tumor, were injected subcutaneously or intracerebrally with BP. The effects on tumor growth were determined by tumor volumes, magnetic resonance imaging and survival rate. Here, we report on the potency of BP in suppressing growth of malignant brain tumor cells without simultaneous fibroblast cytotocixity. BP up-regulated the expression of Cyclin Kinase Inhibitor (CKI), including p21 and p27, to decrease phosphorylation of Rb proteins, and down-regulated the cell-cycle regulators, resulting in cell arrest at the G0/G1 phase for DBTRG-05MG and RG2 cells, respectively. The apoptosis-associated proteins were dramatically increased and activated by BP in DBTRG-05MG cells and RG2 cells, but RG2 cells did not express p53 protein. In vitro results showed that BP triggered both p53-dependent and independent pathways for apoptosis. In vivo, BP not only suppressed growth of subcutaneous rat and human brain tumors but also, reduced the volume of GBM tumors in situ, significantly prolonging survival rate. These in vitro and in vivo anti-cancer effects indicate that BP could serve as a new anti-brain tumor drug. [ABSTRACT FROM AUTHOR]

Abstract: We previously demonstrated that the crude acetone extract of Bupleurum scorzonerifolium (BS-AE) 60μg/ml has anti-proliferation activity and apoptotic effects on A549 non-small cell lung cancer (NSCLC). A novel lignan, isochaihulactone (4-benzo[1,3]dioxol-5-ylmethyl-3(3,4,5-trimethoxyl-benzylidene)-dihydro-furan-2-one), was isolated from BS-AE and identified from spectral evidence (1H NMR, 13C NMR, IR, and MS) and by comparison with authentic synthetic standards. Isochaihulactone was cytotoxic (IC50 =10–50μM) in a variety of human tumor cell lines. In in vitro and in vivo microtubule assembly assays, it inhibited tubulin polymerization in a concentration-dependent manner. As determined by flow cytometry, isochaihulactone caused G2/M phase arrest and apoptosis in a time- and concentration-dependent manner. G2/M arrest was correlated with increased p21/WAF1 levels, downregulation of the checkpoint proteins cyclin B1/cdc2 and mobility shift of cdc25C. Moreover, isochaihulactone (30 and 50mg/kg) inhibited the growth of non-small cell lung carcinoma A549 xenograft in nude mice. These findings indicate isochaihulactone is a promising new antimitotic anticancer compound with potential for clinical application in the future. [Copyright &y& Elsevier]

Abstract: We previously demonstrated that the crude acetone extract of Bupleurum scorzonerifolium (AE-BS) 60 μg/ml has anti-proliferation activity and apoptosis effects to A549 human lung cancer cells. They can also cause tumor cell arrest in G2/M phase. To better understand its target protein in A549 cell, two-dimensional electrophoresis and liquid chromatography-tandem mass spectrometry were applied. The modification of keratin 8 was identified. By immunoblot, the expression of phosphorylated keratin 8 at Ser-73 was increased from 2.0 to 3.0-fold after AE-BS treatment 24 to 48 hr respectively as compared with untreated A549 control cells. Furthermore, the A549 cells were pretreated with 50 μM PD98059, a specific inhibitor of the upstream regulator of ERK1/2, or with the p38 kinase inhibitor 20 μM SB203580 or JNK inhibitor 20 μM SP600125 for 30 min, followed by 24 h of incubation with AE-BS, PD98059 can inhibit K8-Ser-73 hyperphosphorylation and prevented cell apoptosis which was induced by AE-BS significantly. By immunoblot, AE-BS also can induce ERK 1/2 phosphorylation. In conclusion, our data indicate that the AE-BS induced tumor apoptosis in A549 cells was related to ERK 1/2 activation. The molecular mechanism of hyperphosphorylation of K8 on Ser-73 was associated with ERK 1/2 activation rather than JNK and p38 kinase. The apoptosis induced by AE-BS may be related to K8 phosphorylation. [Copyright &y& Elsevier]

Aims. This umbrella review aims to comprehensively synthesize and analyze the findings of available systematic reviews on the effectiveness of individual-based strategies for reducing nurse burnout occurring in hospital-based settings. Methods. Following JBI guidelines, an umbrella review was conducted to integrate the effectiveness of various strategies to reduce burnout. Systematic reviews were searched in the Embase, MEDLINE (Ovid), Cochrane Library, CINAHL (EBSCO), Scopus, and WOS databases. Inclusion criteria included studies published in any language from database inception to April 2023. Eligibility assessment involved two independent reviewers who evaluated titles, abstracts, and full texts. The systematic reviews were critically evaluated using JBI SUMARI. The results were narratively synthesized and grouped by strategy. Results. Eleven systematic reviews were included, covering the years 2012 to 2021. The appraisal tools varied, though all included reviews were of high quality. The strategies were categorized into three domains: mental health (51%), physical activities (26%), and professional competence (13%). The interventions most identified were mindfulness-based stress reduction for mental health, yoga for physical activities, and professional competence education. These individual-based strategies were shown to effectively eliminate emotional exhaustion (72.7%), depersonalization (44%), and occupational stress (78%) among nurses in hospital-based settings. Conclusion. Mental health, physical activities, and professional competence are strategies to reduce nurse burnout. Implementing these approaches in healthcare settings can improve emotional exhaustion, depersonalization, and occupational stress of nurses. [ABSTRACT FROM AUTHOR]

Langerhans cell histiocytosis is a rare disease and is lethal in premature neonates. A male premature neonate born at gestational 33 weeks presented with generalized vesicles, hydrops fetalis with pleural effusion, bilateral cataracts, and severe respiratory distress syndrome complicated with persistent pulmonary hypertension. Skin biopsy confirmed the diagnosis of Langerhans cell histiocytosis. [ABSTRACT FROM AUTHOR]

Induction of DNA damage response (DDR) to ensure accurate duplication of genetic information is crucial for maintaining genome integrity during DNA replication. Cellular senescence is a DDR mechanism that prevents the proliferation of cells with damaged DNA to avoid mitotic anomalies and inheritance of the damage over cell generations. Human WWOX gene resides within a common fragile site FRA16D that is preferentially prone to form breaks on metaphase chromosome upon replication stress. We report here that primary Wwox knockout (Wwox−/−) mouse embryonic fibroblasts (MEFs) and WWOX-knockdown human dermal fibroblasts failed to undergo replication-induced cellular senescence after multiple passages in vitro. Strikingly, by greater than 20 passages, accelerated cell cycle progression and increased apoptosis occurred in these late-passage Wwox−/− MEFs. These cells exhibited γH2AX upregulation and microsatellite instability, indicating massive accumulation of nuclear DNA lesions. Ultraviolet radiation-induced premature senescence was also blocked by WWOX knockdown in human HEK293T cells. Mechanistically, overproduction of cytosolic reactive oxygen species caused p16Ink4a promoter hypermethylation, aberrant p53/p21Cip1/Waf1 signaling axis and accelerated p27Kip1 protein degradation, thereby leading to the failure of senescence induction in Wwox-deficient cells after serial passage in culture. We determined that significantly reduced protein stability or loss-of-function A135P/V213G mutations in the DNA-binding domain of p53 caused defective induction of p21Cip1/Waf1 in late-passage Wwox−/− MEFs. Treatment of N-acetyl-l-cysteine prevented downregulation of cyclin-dependent kinase inhibitors and induced senescence in Wwox−/− MEFs. Our findings support an important role for fragile WWOX gene in inducing cellular senescence for maintaining genome integrity during DDR through alleviating oxidative stress. [ABSTRACT FROM AUTHOR]

Deep sequencing of T-cell receptor (TCR) genes is powerful at profiling immune repertoire. To prepare a TCR sequencing library, multiplex polymerase chain reaction (mPCR) is widely applied and is highly efficient. That is, most mPCR products contain the region critical for antigen recognition, which also indicates regular V(D)J recombination. Multiplex PCR, however, may suffer from primer bias. A promising alternative is 5'-RACE, which avoids primer bias by applying only one primer pair. In 5'-RACE data, however, non-regular V(D)J recombination (e.g., TCR sequences without a V gene segment) has been observed and the frequency varies (30–80%) between studies. This suggests that the cause of or how to reduce non-regular TCR sequences is not yet well known by the science community. Although it is possible to speculate the cause by comparing the 5'-RACE protocols, careful experimental confirmation is needed and such a systematic study is still not available. Here, we examined the 5'-RACE protocol of a commercial kit and demonstrated how a modification increased the fraction of regular TCR-β sequences to >85%. We also found a strong linear correlation between the fraction of short DNA fragments and the percentage of non-regular TCR-β sequences, indicating that the presence of short DNA fragments in the library was the main cause of non-regular TCR-β sequences. Therefore, thorough removal of short DNA fragments from a 5'-RACE library is the key to high data efficiency. We highly recommend conducting a fragment length analysis before sequencing, and the fraction of short DNA fragments can be used to estimate the percentage of non-regular TCR sequences. As deep sequencing of TCR genes is still relatively expensive, good quality control should be valuable. [ABSTRACT FROM AUTHOR]

We investigate the instability of threshold voltage in D-mode MIS-HEMT with in-situ SiN as gate dielectric under different negative gate stresses. The complex non-monotonic evolution of threshold voltage under the negative stress and during the recovery process is induced by the combination effect of two mechanisms. The effect of trapping behavior of interface state at SiN/AlGaN interface and the effect of zener traps in AlGaN barrier layer on the threshold voltage instability are opposite to each other. The threshold voltage shifts negatively under the negative stress due to the detrapping of the electrons at SiN/AlGaN interface, and shifts positively due to zener trapping in AlGaN barrier layer. As the stress is removed, the threshold voltage shifts positively for the retrapping of interface states and negatively for the thermal detrapping in AlGaN. However, it is the trapping behavior in the AlGaN rather than the interface state that results in the change of transconductance in the D-mode MIS-HEMT. [ABSTRACT FROM AUTHOR]

Background: Osimertinib yields significant tumor responses and durations of progression‐free survival (PFS) in patients with acquired T790M mutations. However, the evidence supporting liquid biopsy‐guided treatment is still limited. This study examined the real‐world benefits of osimertinib in patients with tissue or plasma T790M mutations. Methods: From January 2016 to June 2018, a total of 183 non‐small‐cell lung cancer patients were enrolled. The presence of the T790M mutation was assessed by either tissue or plasma. The PFS, overall survival, and tumor response rates of the patients were calculated and compared with those of previous clinical trials. Results: T790M mutations were detected in 51.5% of the patients, including 64 of 140 (45.7%) who underwent liquid biopsies and 23 of 29 (79.3%) who underwent tumor biopsies. After excluding those in clinical trials, 46 patients received osimertinib, including 33 with positive plasma and 13 with positive tissue results for T790M mutations. The median PFS was 11.3 months (interquartile range: 5.2‐NR) in all the T790M‐positive patients and 10.1 months (interquartile range: 5.9‐NR) in the plasma T790M‐positive patients. The overall survival, meanwhile, was not reached, whereas the one‐year survival rate was 66.1% in all the patients and 61.4% in those who were plasma T790M‐positive. The objective response rate and disease control rate were 37.8% and 91.9% in all the patients and 34.6% and 92.3% in the plasma T790M‐positive group, respectively. Using a Cox proportional hazards regression, we determined that male gender was a poor prognostic factor for PFS. Conclusions: In this retrospective real‐world analysis, it was determined that both tissue and plasma T790M mutations can be used to guide treatment with osimertinib. Similar disease control rates and survival durations were observed in comparison to those of phase 3 clinical trials. [ABSTRACT FROM AUTHOR]

Microsatellite instability (MSI) is the primary predictive biomarker for therapeutic efficacies of cancer immunotherapies. Establishment of the MSI detection methods with high sensitivity and accessibility is important. Because MSI is mainly caused by defects in DNA mismatch repair (MMR), immunohistochemical (IHC) staining for the MMR proteins has been widely employed to predict the responses to immunotherapies. Thus, due to the high sensitivity of PCR, the MSI-PCR analysis has also been recommended as the primary approach as MMR IHC. This study aimed to develop a sensitive and convenient platform for daily MSI-PCR services. The routine workflow used a non-labeling QIAxcel capillary electrophoresis system which did not need the fluorescence labeling of the DNA products or usage of a multi-color fluorescence reader. Furthermore, the 15 and 1000 bp size alignment markers were used to precisely detect the size of the DNA product. A cohort of 336 CRC cases was examined by MSI-PCR on the five mononucleotide MSI markers recommended by ESMO. The PCR products were analyzed in the screening gels, followed by high-resolution gel electrophoresis for confirmation if needed. In the MSI-PCR tests, 90.1% (303/336) cases showed clear major shift patterns in the screening gels, and only 33 cases had to be re-examined using the high-resolution gels. The cohort was also analyzed by MMR IHC is, which revealed 98.5% (331/336) concordance with MSI-PCR. In the five discordant cases, 4 (3 MSI-L and 1 MSS) showed MSH6 loss. Besides, one case exhibited MSI-H but no loss in the MMR IHC. Further NGS analysis, in this case, found that missense and frameshift mutations in the PMS2 and MSH6 genes occurred, respectively. In conclusion, the non-labeling MSI-PCR capillary electrophoresis revealed high concordance with the MMR IHC analysis and is cost- and time-effective. Therefore, it shall be highly applicable in clinical laboratories. [ABSTRACT FROM AUTHOR]

The development of effective drug-loaded dressings has been considered a hot research topic for biomedical therapeutics, including the use of botanical compounds. For wound healing, adequate dressings can provide a good microenvironment for drug release, such as lidocaine. Biological macromolecular materials such as alginate show excellent properties in wound management. This study involves the preparation and evaluation of biocompatible multilayered-structure microspheres composed of chitosan, porous gelatin, and calcium alginate microspheres. The multilayered structure microspheres were named chitosan@ porous gelatin@ calcium alginate microspheres (CPAMs) and the drugs were rapidly released by the volume expansion of the calcium alginate microspheres. The in vitro release curve revealed that the peak release of lidocaine from CPAMs was reached within 18 min. After 21 min, the remaining lidocaine was then slowly released, and the active drug release was converted to a passive drug release phase. The initial release effect of lidocaine was much better than that reported in the published studies. Additionally, blood coagulation experiments showed that CPAMs coagulated blood in 60 s, and the blood liquidity of the CPAMs group was worse than that of the woundplast group. Therefore, the coagulation characteristics of CPAMs were superior to the commonly used woundplast containing lidocaine healing gel. These study outcomes indicated that the CPAMs acted as fast-release dressings for faster pain control and better coagulation properties. [ABSTRACT FROM AUTHOR]

In this work, a high linearity AlGaN/GaN HEMT integrated dual threshold coupling (DT) technology and Schottky–Ohmic drain (SOD) were fabricated and analyzed. Since the architecture of DT synthesized planar- and recess-HEMT periodically along the gate width, SOD alleviated the peak electric field (E-field) around the gate region and the peak transconductance (Gm-max) of 248 mS/mm with the associated transconductance plateau of ∼4.0 V at Vds = 28 V was obtained, which is evidently flatter than that of HEMT without the SOD structure. Attributed to the improved Gm linearity at high E-field, the DT-SOD HEMT exhibits the predicted linearity figure of merit of 5–13 dB when biased at class AB operation, which is ∼10 dB higher than that of DT-HEMT. Moreover, the fabricated device yields a nearly constant fT/fmax of 47/118 GHz over a wide gate voltage, and load-pull measurements at 30 GHz reveal that these devices deliver output power density (Pout) of 7.8 W/mm with the associated 1-dB compression point (P1dB) of 28.5 dBm at Vds = 28 V. The experimental results indicate that the employment of DT technology and SOD structure is an attractive approach to enhance the linearity at high E-field for millimeter wave devices. [ABSTRACT FROM AUTHOR]

The CCNB1 and CDK1 genes encode the proteins of CyclinB1 and CDK1 respectively, which interact with each other and are involved in cell cycle regulation, centrosome duplication and chromosome segregation. This study aimed to investigate whether the genetic variants in these two genes may affect breast cancer (BC) susceptibility, progression, and survival in Chinese Han population using haplotype-based analysis. A total of ten tSNPs spanning from 2kb upstream to 2kb downstream of these genes were genotyped in 1204 cases and 1204 age-matched cancer-free controls. The haplotype blocks were determined according to our genotyping data and linkage disequilibrium (LD) status of these SNPs. For CCNB1, rs2069429 was significantly associated with increased BC susceptibility under recessive model (OR=2.352, 95%CI=1.480-3.737), so was the diplotype TAGT/TAGT (OR=1.947 95%CI=1.154-3.284, P=0.013). In addition, rs164390 was associated with Her2-negative BC. For CDK1, rs2448343 and rs1871446 were significantly associated with decreased BC risk under dominant models, so was the haplotype ATATT. These two SNPs also showed a dose-dependent effect on BC susceptibility. Using stratified association analysis, we found that women with the heterozygotes or minor allele homozygotes of rs2448343 had much less BC susceptibility among women with BMI<23. In CDK1, three closely located SNPs, rs2448343, rs3213048 and rs3213067, were significantly associated with tumor’s PR status: the heterozygotes of rs2448343 were associated with PR-positive tumors, while the minor allele homozygotes of rs3213048 and heterozygotes of rs3213067 were associated with PR-negative BC tumors. In survival analysis, rs1871446 was associated with unfavorable event-free survival under recessive model, so was the CDK1 diplotype ATATG/ATATG, which carried the minor allele homozygote of rs1871446. Our study indicates that genetic polymorphisms of CCNB1 and CDK1 are related to BC susceptibility, progression, and survival in Chinese Han women. Further studies need to be performed in other populations as an independent replication to verify these results. [ABSTRACT FROM AUTHOR]

The classification and part segmentation of point cloud models are the basic tasks of 3D point cloud data processing, and the core is to obtain point cloud features that can effectively represent 3D models. This paper proposes a 3D point cloud feature learning network that introduces attention mechanisms. The network adopts a hierarchical point cloud feature extraction method. In the process of hierarchical feature extraction, the feature channel attention mechanism is adopted to obtain the correlation among channels, and the key channel information is enhanced. The spatial position attention mechanism is adopted to obtain the attention weight of each point based on the spatial information of the points. The enhanced point cloud feature is obtained by combining two or more attention mechanisms. Based on this feature, multi-level feature extraction is performed to obtain the final point cloud features for downstream tasks. Shape classification and part segmentation experiments are performed on Model- Net40 and ShapeNet datasets, respectively. The experimental results show that the proposed method can achieve high-precision and robust 3D point cloud shape classification and segmentation. [ABSTRACT FROM AUTHOR]

In recent years, many investigations have found that artificial sunscreen additives not only have allergic and endocrine disruption problems, but also found that these additives affect aquatic organisms such as corals. Therefore, finding alternative additives to satisfy the needs of users while ensuring environmental and ecological safety has become an important issue today. Natural sunscreen additives with low toxicity, low allergenicity and high environmental friendliness have become the focus of development of new sunscreens. It is known from previous studies that the renewable parts of Garcinia subelliptica are rich in benzophenones, biflavonoids and xanthonoids, indicating potential for application in sun protection. Hence, this study evaluated the potential of the renewable parts (branches, leaves and fruits) of G. subelliptica , and combined the concept of the circular economy to make natural sunscreen additives with environment-friendly value. The results showed that the phenolic compounds and flavonoids in the renewable parts of G. subelliptica are rich, endowing them with good sun protection efficacies and antioxidant ability via absorption of ultraviolet light and scavenging of free radicals, especially the biflavonoids in the leaves. These results indicated that the extract of G. subelliptica leaves has the most potential for development as natural sunscreen additives. The active ingredients in these leaves are worth further investigate. Future research can also combine urban forestry or community forestry policies to develop the renewable parts of G. subelliptica into environmentally friendly raw materials for natural sunscreen additives with multiple functions such as sunscreen and antioxidant, enhancing the utilization values. • Leaf extract from Garcinia subelliptica has the potential to develop as sunscreens. • Biflavonoids in G. subelliptica leaves contributes the sun protection capabilities. • G. subelliptica can be applied as a new industrial crop in cosmetic field. [ABSTRACT FROM AUTHOR]

Galectin-3, a member of the β-galactoside-binding lectin family, expresses in many different immune cells and modulates broad biological functions including cell adhesion, cell activation, cell growth, apoptosis, and inflammation. However, the role of galectin-3 in mucosal immunity or inflammatory bowel diseases is still not clear. We demonstrate here that galectin-3 knockout mice have more severe disease activity in the dextran sulfate sodium (DSS)-induced colitis model, indicating that galectin-3 may protect from inflammation in DSS-induced colitis. Furthermore, treating with galectin-3 reduced body weight loss, shortened colonic length, and ameliorated mucosal inflammation in mice having DSS-induced colitis. However, the protective effects of galectin-3 were eliminated by the administration of anti-CD25 mAb. In addition, primary T cells treated with galectin-3 ex vivo induced the expression of FOXP3, ICOS, and PD-1 with a Treg cell phenotype having a suppression function. Moreover, adoptive transfer of galectin-3-treated T cells reduced bowel inflammation and colitis in the T cell transfer colitis model. In conclusion, our results indicate that galectin-3 inhibited colonic mucosa inflammation and reduced disease severity by inducing regulatory T cells, suggesting that it is a potential therapeutic approach in inflammatory bowel disease. Key messages: [ABSTRACT FROM AUTHOR]

In this work, ultrathin barrier (∼6 nm) AlGaN/GaN high-electron-mobility transistors (HEMTs) with in situ SiN gate dielectric and slant-field plate (SFP) T-gates were fabricated and analyzed. Since the proposed scheme of gate dielectric and SFP effectively suppresses the gate leakage and alleviates the peak electric field (E-field) around gate region, the maximum breakdown voltage (VBK) was improved to 92 V, which is 54 V higher than that of the conventional device. The fabricated ultrathin AlGaN/GaN HEMT with 60-nm SFP-T-gate exhibited the peak fT of 177 GHz and peak fmax of 393 GHz, yielding high figure-of-merits of fT · VBK = 16 THz V and fmax·VBK = 36 THz V. Moreover, load-pull measurements at 30 GHz reveal that these devices deliver output power density (Pout) of 4.6 W/mm at Vds = 20 V and high power-added efficiency up to 52.5% at Vds = 10 V. Essentially, the experimental results indicate that the employment of SFP and in situ SiN gate dielectric is an attractive approach to balance the breakdown and speed for millimeter wave devices. [ABSTRACT FROM AUTHOR]

Neoadjuvant immunotherapy and chemotherapy have improved the major pathological response (MPR) in patients with early-stage operable non-small cell lung cancer (NSCLC). This study aimed to assess whether the presence of targetable driver mutations affects the efficacy of the combination of immunotherapy and chemotherapy. We enrolled patients with early-stage operable NSCLC who received preoperative neoadjuvant therapy between January 1, 2017, and December 30, 2020. Neoadjuvant therapy was delivered with platinum-doublet chemotherapy; moreover, pembrolizumab was added at the attending physician's discretion based on patient's request. Pathological responses were assessed; moreover, disease-free survival was estimated. Next-generation sequencing was performed in case sufficient preoperative biopsy specimens were obtained. We included 23 patients; among them, 11 received a combination of neoadjuvant immunotherapy and chemotherapy while 12 received neoadjuvant chemotherapy alone. The MPR and pathological complete response rates were 54.5% and 27.3%, respectively, in patients who received a combination of neoadjuvant immunotherapy and chemotherapy. These rates were significantly higher than those in patients who only received neoadjuvant chemotherapy. Three patients in the combination group experienced disease recurrence during the follow-up period even though two of them showed an MPR. These three patients had targetable driver mutations, including an EGFR exon 20 insertion, EGFR exon 21 L858R substitution, and MET exon 14 skipping. Only one patient who remained disease-free had a targetable driver mutation. Among patients with early-stage operable NSCLC requiring neoadjuvant therapy, comprehensive genomic profiling is crucial before the administration of the combination of neoadjuvant immunotherapy and chemotherapy. [ABSTRACT FROM AUTHOR]

Carbonaceous fuel combustion has increased such that approximately 80% of current global Hg emissions originate from anthropogenic sources, particularly from coal-fired plants and incinerators. Accordingly, the development of effective Hg scrubbing methods that enable cleaner industrial processes is of great significance to human health. Because of the weak physical adsorption of Hg at ambient temperatures, numerous sorbents are required for its removal via processes such as electrostatic precipitation, selective catalytic reduction, flue gas desulfurization, and activated carbon injection. Alternatively, capturing Hg at elevated temperatures has numerous advantages such as high capacity and the avoidance of the diffusion of Hg species throughout the process. Herein, we report the preparation of a novel sorbent with a layered structure, (Mg3-x, Mx)-Al-CO3, via the coprecipitation of Mg2+, M2+, and Al3+ in an alkaline solution of NaOH/Na2CO3, where M2+ = Cu2+ or Zn2+. In a fixed-bed reactor, the Hg removal rate R notably increased at elevated temperatures (200-300 °C) and was enhanced by a factor of 10 via the incorporation of M2+ in Mg-Al-CO3. These results demonstrate the potential of such synthetic Hg sorbents under medium-high temperature conditions. [ABSTRACT FROM AUTHOR]

Abstract: Exfoliated TiNbO5 nanosheets were obtained by delaminating a layered compound KTiNbO5. Employing a layer-by-layer electrostatic deposition technology, the exfoliated nanosheets were deposited into a multilayer composite film with polyethylenimine as the linker, confirmed by UV–vis absorption spectra and X-ray diffraction. The polymer-free TiNbO5 nanosheet multilayer film was achieved through the subsequent ultraviolet light exposure. The cyclic voltammogram of the resulting TiNbO5 nanosheet multilayer film electrode exhibited a reversible reduction–oxidation process of Ti3+/Ti4+, accompanying with the insertion/deinsertion of Li+ ions into/from the nanosheet galleries. The bandgap energy and flatband potential of TiNbO5 nanosheet were observed to be 3.47eV and −1.01V vs. Ag/AgCl, respectively. The investigation on the photoelectrocatalytic degradation of Rhodamine B with the TiNbO5 nanosheet electrodes revealed that both the oxygen anionic radicals and the dye cationic radical are essential for the mineralization of the dye under visible light-driven photocatalytic conditions, and that the electron separation under an anode bias can suppress the rapid recombination of the photogenerated charge carriers under ultraviolet light irradiation. It is the first time to investigate the mechanism of photoelectrocatalysis for TiNbO5 nanosheet electrode. [Copyright &y& Elsevier]

Primary effusion lymphoma, a human herpesvirus 8 (HHV8)-associated lymphoma, is uncommon, and it is usually seen in human immunodeficiency virus (HIV)-infected patients. It presents as a body cavity-based lymphomatous effusion, but several cases of the so-called solid primary effusion lymphoma presenting as solid tumors without associated lymphomatous effusion have been reported. They have similar clinical, histopathological and immunophenotypical features. Most of them have a B-cell genotype. This suggests the solid variant may represent a clinicopathological spectrum of primary effusion lymphoma. We report a case of HHV8-associated lymphoma histopathologically and immunophenotypically mimicking cutaneous anaplastic large cell lymphoma. The patient was a 31-year-old HIV-seropositive man presenting with skin nodules over his right thigh. Biopsy of the nodules showed anaplastic large cells infiltrating the dermis. These malignant cells strongly expressed CD3, CD30 and CD43. Cutaneous anaplastic large T-cell lymphoma was initially diagnosed, but further tests, including immunoreactivity for HHV8 protein and clonal rearrangements of immunoglobulin genes, confirmed the diagnosis of HHV8-associated B-cell lymphoma with aberrant T-cell marker expression. This case provides an example of solid primary effusion lymphoma mimicking cutaneous anaplastic large T-cell lymphoma and highlights the importance of HHV8 immunohistochemistry and molecular tests in the diagnosis of HHV8-associated lymphoma with a cutaneous presentation. Li M-F, Hsiao C-H, Chen Y-L, Huang W-Y, Lee Y-H, Huang H-N, Lien H-C. Human herpesvirus 8-associated lymphoma mimicking cutaneous anaplastic large T-cell lymphoma in a patient with human immunodeficiency virus infection. [ABSTRACT FROM AUTHOR]

Abstract: Fe-doped cesium titanate was obtained by a solid state reaction with a mixture of Cs2CO3, TiO2, and Fe2O3. ZnO-pillared doped titanate nanocomposite was successfully fabricated by exfoliating doped titanate and restacking its nanosheets with ZnO nanoparticles. The resulting nanocomposite was characterized by powder X-ray diffraction, scanning electron microscope, X-ray photoelectron spectroscopy, N2 adsorption–desorption measurement, thermogravimetric analysis and UV–vis spectroscopy. It was revealed that the present nanocomposite exhibits greatly increased specific surface area with mesoporous texture and that there exists an electronic coupling between the host sheets and the guest nanoparticles in the pillared system. The results of degradation of methylene blue under visible light radiation suggest that doping iron ions improves the material spectral response region and that hybridizing with ZnO nanopillars can suppress the recombination of photogenerated electron–hole pairs. [Copyright &y& Elsevier]

Abstract: Mesoporous α-Fe2O3-pillared titanate nanocomposites have been successfully synthesized through an exfoliation−restacking route. Powder X-ray diffraction and N2 adsorption–desorption isotherms revealed that the α-Fe2O3 pillared titanate has an interlayer distance of 3.27nm, a specific surface area of 66m2/g and an average pore size of 7.6nm, suggesting the formation of a mesoporous pillared structure. UV–vis diffuse reflectance spectra show a red shift, indicative of a narrow band gap energy of ∼2.1eV compared to the host layered titanate, which is essential in creating a visible light photocatalytic activity. The results of degradation of rhodamine B reveal that the present pillared mesoporous composites exhibit better photocatalytic activities than those of the pristine materials under visible irradiation, based on the band gap excitement and the dye-sensitized path, originated from their high surface area, mesoporosity and the electronic coupling between the host and the guest components. [Copyright &y& Elsevier]

Phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3), the mammalian ortholog of yeast vesicular protein sorting 34 (Vps34), belongs to the phosphoinositide 3-kinase (PI3K) family. PIK3C3 can phosphorylate phosphatidylinositol (PtdIns) to generate phosphatidylinositol 3-phosphate (PI3P), a phospholipid central to autophagy. Inhibition of PIK3C3 successfully inhibits autophagy. Autophagy maintains cell survival when modifications occur in the cellular environment and helps tumor cells resist metabolic stress and cancer treatment. In addition, PIK3C3 could induce oncogenic transformation and enhance tumor cell proliferation, growth, and invasion through mechanisms independent of autophagy. This review addresses the structural and functional features, tissue distribution, and expression pattern of PIK3C3 in a variety of human tumors and highlights the underlying mechanisms involved in carcinogenesis. The implications in cancer biology, patient prognosis prediction, and cancer therapy are discussed. Altogether, the discovery of pharmacological inhibitors of PIK3C3 could reveal novel strategies for improving treatment outcomes for PIK3C3-mediated human diseases. [ABSTRACT FROM AUTHOR]

Microsatellite instability (MSI) is reflective of a deficient mismatch repair (dMMR) system, which is mostly associated with the methylation of mismatch repair (MMR) genes and BRAF mutations in sporadic colorectal cancers (CRCs). We performed a retrospective study to analyze the clinicopathological features of dMMR CRCs and their association with the BRAF V600E mutation. The incidence of dMMR CRCs in our cohort was 7.4 % (118/1603). Immunohistochemistry (IHC) revealed four common dMMR IHC patterns in 116 dMMR CRCs from 110 patients. dMMR type 1 (MLH1-/PMS2-) CRCs were the most frequent pattern, usually showing typical proximal location and MSI histology. The BRAF V600E mutation was almost exclusively observed in dMMR type 1 (32 of 72) and dMMR type 2 (PMS- only, 7 of 18) CRCs (p = 0.001). Patients with dMMR type 3 (MSH2-/MSH6-) CRCs were usually diagnosed at younger ages (p < 0.001) and had the strongest family history of Lynch syndrome-associated tumors (p = 0.002). dMMR type 3 CRCs frequently presented at advanced stages (p = 0.005) with perineural invasion (p = 0.021). We also found a significant positive association of dMMR type 1 and type 3 with advanced stages of CRC, whereas dMMR types 2 and 4 (MSH6- only) were usually diagnosed at early stages of CRC (p < 0.001). In conclusion, BRAF V600E mutations almost exclusively occurred in dMMR type 1 and 2 CRCs. Patterns of MMR protein expression display distinct associations with tumor staging and age at diagnosis. [ABSTRACT FROM AUTHOR]

Background: Illumina sequencing of a marker gene is popular in metagenomic studies. However, Illumina paired-end (PE) reads sometimes cannot be merged into single reads for subsequent analysis. When mergeable PE reads are limited, one can simply use only first reads for taxonomy annotation, but that wastes information in the second reads. Presumably, including second reads should improve taxonomy annotation. However, a rigorous investigation of how best to do this and how much can be gained has not been reported. Results: We evaluated two methods of joining as opposed to merging PE reads into single reads for taxonomy annotation using simulated data with sequencing errors. Our rigorous evaluation involved several top classifiers (RDP classifier, SINTAX, and two alignment-based methods) and realistic benchmark datasets. For most classifiers, read joining ameliorated the impact of sequencing errors and improved the accuracy of taxonomy predictions. For alignment-based top-hit classifiers, rearranging the reference sequences is recommended to avoid improper alignments of joined reads. For word-counting classifiers, joined reads could be compared to the original reference for classification. We also applied read joining to our own real MiSeq PE data of nasal microbiota of asthmatic children. Before joining, trimming low quality bases was necessary for optimizing taxonomy annotation and sequence clustering. We then showed that read joining increased the amount of effective data for taxonomy annotation. Using these joined trimmed reads, we were able to identify two promising bacterial genera that might be associated with asthma exacerbation. Conclusions: When mergeable PE reads are limited, joining them into single reads for taxonomy annotation is always recommended. Reference sequences may need to be rearranged accordingly depending on the classifier. Read joining also relaxes the constraint on primer selection, and thus may unleash the full capacity of Illumina PE data for taxonomy annotation. Our work provides guidance for fully utilizing PE data of a marker gene when mergeable reads are limited. [ABSTRACT FROM AUTHOR]

Abstract: Traditional medicines provide a fertile ground to explore potent lead compounds, yet their transformation into modern drugs is fraught with challenges in deciphering the target that is mechanistically valid for its biological activity. Herein we reveal that (Z)‐(+)‐isochaihulactone (1) exhibited significant inhibition against multiple‐drug‐resistant (MDR) cancer cell lines and mice xenografts. NMR spectroscopy showed that 1 resisted an off‐target thiolate, thus indicating that 1 was a target covalent inhibitor (TCI). By identifying the pharmacophore of 1 (α,β‐unsaturated moiety), a probe derived from 1 was designed and synthesized for TCI‐oriented activity‐based proteome profiling. By MS/MS and computer‐guided molecular biology approaches, an affinity‐driven Michael addition of the noncatalytic C247 residue of GAPDH was found to control the “ON/OFF” switch of apoptosis through non‐canonically nuclear GAPDH translocation, which bypasses the common apoptosis‐resistant route of MDR cancers. [ABSTRACT FROM AUTHOR]

Abstract: Traditional medicines provide a fertile ground to explore potent lead compounds, yet their transformation into modern drugs is fraught with challenges in deciphering the target that is mechanistically valid for its biological activity. Herein we reveal that (Z)‐(+)‐isochaihulactone (1) exhibited significant inhibition against multiple‐drug‐resistant (MDR) cancer cell lines and mice xenografts. NMR spectroscopy showed that 1 resisted an off‐target thiolate, thus indicating that 1 was a target covalent inhibitor (TCI). By identifying the pharmacophore of 1 (α,β‐unsaturated moiety), a probe derived from 1 was designed and synthesized for TCI‐oriented activity‐based proteome profiling. By MS/MS and computer‐guided molecular biology approaches, an affinity‐driven Michael addition of the noncatalytic C247 residue of GAPDH was found to control the “ON/OFF” switch of apoptosis through non‐canonically nuclear GAPDH translocation, which bypasses the common apoptosis‐resistant route of MDR cancers. [ABSTRACT FROM AUTHOR]

A series of 1-aroylindoline-hydroxamic acids have been synthesized in the present study. The results of the biological evaluation led to the identification of compound 12 as dual HDAC6/HSP90 inhibitor. Compound 12 displayed striking inhibitory effects towards the HDAC6 isoform and HSP 90 protein with IC 50 values of 1.15 nM (HDAC6) and 46.3 nM (HSP90). Compound 12 also exhibited 113, 139 and 246 fold higher selectivity for HDAC6 over HDAC 1, HDAC 3 and HDAC 8 isoforms and was endowed with significant cytotoxic effects with GI 50 values ranging 1.04–1.61 μM against lung A549, colorectal HCT116, leukemia HL60, and EGFR T790M mutant lung H1975 cell lines. Another interesting finding of the study was substantial cytotoxic effects of compounds particularly against lung H1975 (NSCLC) cell lines with IC 50  = 0.26 μM which may be mediated through HSP90 inhibition. Compound 8 as such was devoid of HDAC inhibitory activity. [ABSTRACT FROM AUTHOR]