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Background: The frequent occurrence of pressure injuries despite their preventability raises important questions about our understanding of the barriers to care. This study explores the lived experience of nurses and caregivers in Singapore to establish a conceptual framework for better understanding of pressure injuries arising in the community. Methods: A multicenter qualitative study was conducted utilizing semistructured interviews and focused group discussions of nurses and caregivers of patients with pressure injuries. Data were collected with a narrative inquiry approach and analyzed with grounded theory. An iterative cycle of interviewing, coding, discussion, and reflection was conducted until theoretical saturation. Results: Ten inpatient nurses and 10 caregivers from the community were recruited. Analysis identified cognitive (awareness and caregiver training), emotional (motivation and empowerment), resource (human and infrastructural), and biomedical factors which collectively impacted the effectiveness of prevention. Additionally, constructs of learning and sustainability of caregiving played a crucial role in long term prevention. Limitation: The derived framework requires further validation with quantitative data and may not be generalizable to other cultural and economic populations. Conclusion: Multiple constructs have been identified to have a synergistic effect in prevention. Targeted measures should be implemented by healthcare institutions to better equip caregivers in prevention.

Thirteen rhizobial strains isolated from New ZealandCarmichaeliaspp.,Clianthus puniceus,Montigena novae-zelandiae(Montigena) andSophoraspp. and the AustralianSwainsona galegifoliain the current or previous studies were tested for their ability to nodulateMontigena. Only rhizobial strains isolated fromCarmichaeliaspp., and those fromClianthus puniceusthat produced functional nodules on their original host, and strains fromMontigenaproduced functional nodules onMontigena. Strains that produced functional nodules onSophoraspp. orSwainsona galegifoliadid not nodulateMontigena. Strains that nodulatedMontigena, identified here or previously asMesorhizobiumspp., had variable 16S ribosomal RNA,recAandglnIIbut specificnifH,nodAandnodCgenes. Results indicate thatMontigenashares rhizobia with its closely relatedCarmichaeliaandClianthusbut notSophoraspp. orSwainsona galegifoliaand that the ability of different rhizobial strains to produce functional nodules onMontigena,CarmichaeliaandClianthus puniceusis likely to be dependent on specific symbiosis genes. [ABSTRACT FROM PUBLISHER]

Ringkasan. Pembusukan pada udang adalah suatu akibat kerdja enzima2 hidrolitik berasal dari udang sendiri dan djuga dari bakter2 jang ada pada udang. Hasil penelitian menjatakan bahwa aktivitas spesifik SH-protease udang ber-angsur2 menurun selama proses pembusukan, sehingga sifat ini baik untuk dipakai sebagai kriteria pembusukan udang. Aktivitas enzima ditentukan pada 37oC selama 20 menit dengan 1% kasein dalam 0,1 M buffer fostat pH 8 sebagai substrat dan siteina (0,02 M) sebagai activator. Sebagai larutan enzima dipakai homogenat udang dalam 0,1 M buffer fosfat pH 8. Berdasarkan atas sifat penurunan aktivitas spesifik SH-protase dan kenaikan pH dan kadar trimetilamina udang pada proses pembusukan, maka dapatlah disusun suatu penggolongan deradjat kesegaran udang. Hal ini dapat penting untuk keperluan2 dalam praktek. Abstract. Spoilage of shrimps is largely caused by enzyme action especially by shrimp proteases in addition to microbial action which is also enzymatic in nature. It was found that when spoilage is in progress the specific activity of the shrimp SH-proteases is remarkably decreased. It appeared that this is a suitable criterion for the determination of the degree of spoilage. Enzyme activity determinations were carried out at 37°C with 1% of casein in 0.1 M phosphate buffer of pH S as the substrate and cysteine (0.02 W as the activator). Shrimp homogenate was used as the enzyme solution which was prepared in 0.1 M phosphate buffer of pH 8 at 0-4°C. Based on the decrease of SH-protease activity and on the increase of pH and volatile base (trimethylamine etc.) content a classification of the freshness of shrimps can be made, which might be useful for practical purposes.

Purpose: Rotator cuff tears (RCTs) occur commonly, especially among certain groups of individuals. In this meta-analysis, we aim to identify risk factors for RCTs. Methods: We searched MEDLINE for 210 articles. Seventeen articles were selected for systematic review, of which 10 were eligible for meta-analysis. Data was analysed with Review Manager 5.3, using Mantel–Haenszel statistics and random effect models. Results: A total of 6653 individuals were analysed. The odds of sustaining a RCT on the dominant hand was 2.30 times more than the non-dominant hand (95% confidence interval (CI): 1.01–5.25, Z = 1.99, p = 0.05; Heterogenity: τ 2 = 0.38, χ 2 = 8.84, df = 2 ( p = 0.01), I 2 = 77%). The odds of an individual aged 60 years and above sustaining a RCT was 5.07 times higher than an individual less than 60 years old (95% CI: 2.45–10.51, Z = 4.37, p < 0.001; Heterogenity: τ 2 = 0.47, χ 2 = 25.24, df = 3 ( p < 0.001), I 2 = 88%). Female gender was not a significant association, with an odds ratio of 0.98 when compared to the male gender (95% CI: 0.66–1.45, Z = 0.09, p = 0.93; Heterogenity: τ 2 = 0.20, χ 2 = 44.24, df = 5 ( p < 0.001), I 2 = 89%). Conclusions: Hand dominance and older age are associated with RCTs. More studies are required for further assessment of associations and risk factors of RCTs.

Abstract Background Chromophobe renal cell carcinoma (chRCC) and renal oncocytoma are two distinct but closely related entities with strong morphologic and genetic similarities. While chRCC is a malignant tumor, oncocytoma is usually regarded as a benign entity. The overlapping characteristics are best explained by a common cellular origin, and the biologic differences between chRCC and oncocytoma are therefore of considerable interest in terms of carcinogenesis, diagnosis and clinical management. Previous studies have been relatively limited in terms of examining the differences between oncocytoma and chromophobe RCC. Methods Gene expression profiling using the Affymetrix HGU133Plus2 platform was applied on chRCC (n = 15) and oncocytoma specimens (n = 15). Supervised analysis was applied to identify a discriminatory gene signature, as well as differentially expressed genes. High throughput single-nucleotide polymorphism (SNP) genotyping was performed on independent samples (n = 14) using Affymetrix GeneChip Mapping 100 K arrays to assess correlation between expression and gene copy number. Immunohistochemical validation was performed in an independent set of tumors. Results A novel 14 probe-set signature was developed to classify the tumors internally with 93% accuracy, and this was successfully validated on an external data-set with 94% accuracy. Pathway analysis highlighted clinically relevant dysregulated pathways of c-erbB2 and mammalian target of rapamycin (mTOR) signaling in chRCC, but no significant differences in p-AKT or extracellular HER2 expression was identified on immunohistochemistry. Loss of chromosome 1p, reflected in both cytogenetic and expression analysis, is common to both entities, implying this may be an early event in histogenesis. Multiple regional areas of cytogenetic alterations and corresponding expression biases differentiating the two entities were identified. Parafibromin, aquaporin 6, and synaptogyrin 3 were novel immunohistochemical markers effectively discriminating the two pathologic entities. Conclusions Gene expression profiles, high-throughput SNP genotyping, and pathway analysis effectively distinguish chRCC from oncocytoma. We have generated a novel transcript predictor that is able to discriminate between the two entities accurately, and which has been validated both in an internal and an independent data-set, implying generalizability. A cytogenetic alteration, loss of chromosome 1p, common to renal oncocytoma and chRCC has been identified, providing the opportunities for identifying novel tumor suppressor genes and we have identified a series of immunohistochemical markers that are clinically useful in discriminating chRCC and oncocytoma.

Background: Resveratrol (RSVL) is a plant-derived polyhydroxyphenolic compound with excellent anticancer properties, alone or in combination with other chemotherapeutic drugs. However, the anticancer mechanism of RSVL is diverse and high concentrations are often required for RSVL to exert its anticancer effect, which would also adversely affect normal cells., Purpose: The main objective of this study is to investigate the molecular mechanism of how non-cytotoxic concentrations of RSVL enhance the anticancer effect of cisplatin involving a newly identified RSVL-binding protein., Methods: Cell viability of cell lines from three cancer types exposed to RSVL and/or cisplatin was measured by NBB staining assay. RSVL-binding proteins were identified using RSVL-bound CNBr-activated Sepharose 4B beads coupled with LC-MS/MS, and the binding between RSVL and novel RSVL-binding protein was further confirmed with an in vitro pull-down assay. The expression of proteins was examined by immunoblot analysis, and the activity of methyltransferase was evaluated by in vitro methylation assay. The methylation level of H3R17 in the gene promoter was investigated using ChIP-qPCR. Bioinformatics analysis was conducted to identify pathway enrichment of genes, predict drug sensitivity, and analyze the survival of cancer patients., Results: Low doses of RSVL might promote cancer cell growth whereas high doses of RSVL showed cytotoxic effects on normal cells. When co-treated with a lower cisplatin dose, non-cytotoxic RSVL levels showed synergistic anticancer effects. Here, coactivator-associated arginine methyltransferase 1 (CARM1) was identified as a novel RSVL-binding protein, and we showed that the upregulation of CARM1 increased the sensitivity of cancer cells to RSVL. Interestingly, we found that CARM1 was essential in the RSVL-induced sensitivity of cisplatin. Further molecular mechanistic studies revealed that RSVL could stabilize CARM1 protein, resulting in the upregulation and increased methyltransferase activity of CARM1. Additionally, we showed that the methylation levels of H3R17 in the promoter of p21, a downstream gene of CARM1 involving cell cycle arrest, were significantly increased after RSVL treatment. Finally, data from our bioinformatics analysis suggested that CARM1 could be utilized as a potential biomarker for chemotherapeutic drug sensitivity and prognosis in cancers., Conclusions: This study identified CARM1 as a RSVL-binding protein for the first time and elucidated the potential roles of CARM1 in enhancing the efficacy of cisplatin by low doses of RSVL, which could have important clinical implications., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: The electrocardiogram-based algorithm for predicting paraseptal atrial tachycardia (PSAT) is limited by the significant overlaps in P-wave morphology originating from various paraseptal sites., Objectives: The goals of this study were to investigate the endocardial activation characteristics of PSAT and to seek an endocardial activation-derived predictor for the ablation site., Methods: Forty-four patients [11 men (25%); mean age 62.6 ± 14.7 years] with PSAT ablation in 4 tertiary medical centers were assigned to 3 groups according to the ablation site: right atrial (RA) para-Hisian region (group 1, n = 10), noncoronary cusp (NCC) (group 2, n = 13), and left atrial (LA) paraseptal area (group 3, n = 21). Multiple-chamber activation mapping was performed guided by a 3-dimensional navigation system. The discrepancies in the earliest activation time between 2 of 3 chambers (ΔRA-LA, ΔRA-NCC, and ΔLA-NCC) were calculated in each group and used for pairwise comparisons., Results: There was a significant difference in ΔRA-LA, ΔRA-NCC, and ΔLA-NCC among the 3 groups. ΔRA-LA was the only parameter that could consistently predict the ablation site of PSAT with good accuracy (area under the curve 1.000, sensitivity 100% and specificity 100%, and cutoff value 7 ms for predicting right para-Hisian or NCC ablation; area under the curve 0.974, sensitivity 92.3% and specificity 95.2%, and cutoff value -4 ms for predicting NCC or left paraseptal ablation). Based on 2 cutoff values, a 2-step algorithm was developed to predict the ablation site of PSAT with a positive predictive value of 95.4% and a negative predictive value of 97.0%., Conclusion: ΔRA-LA is a useful endocardial activation-derived parameter for predicting the successful ablation site of PSAT., Competing Interests: Disclosures The authors declare that they have no competing interests., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Heavy metal ions and organic pollutants discharged into various water bodies have caused serious water pollution, and the efficient removal of these contaminants remains a challenge. Here, we report a novel MXene/poly-melamine-formaldehyde (PMF) composite membrane, in which the PMF particles serve as spacers, and the -NH 2 groups of PMF and the hydroxyl groups of MXene nanosheets have a synergistic effect on the adsorption of pollutants, and the crosslinking of glutaraldehyde inhibits the swelling of the composite membrane. The MXene/PMF composite membrane with 83.7% PMF particle loading displays a water permeability of 381.2 L m -2 h -1 bar -1 (405% that of MXene membrane) and excellent adsorption ability. In static adsorption, the removal rates of Zn 2+ , Pb 2+ , phenol, and crystal violet reach 96.2%, 91.7%, 99.1%, and 96.4% respectively, 20∼100% higher than those of MXene membranes. In dynamic adsorption, the breakthrough volumes of the membrane for 2 ppm p-nitrophenol solution and methyl blue solution reach 75 mL (about 8500 times membrane volume) and 350 mL (about 39800 times membrane volume), and the saturation volumes are 1500 mL and 5000 mL, respectively. After cyclic adsorption/desorption for four times, the removal rate of the membranes still maintains above 90%. This work provides an efficient composite membrane for removing pollutants from wastewater., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Extracellular vesicles (EVs) are small vesicles that are naturally released by cells and play a crucial role in cell-to-cell communication, tissue repair and regeneration. As naturally secreted EVs are limited, liposomes with different physicochemical properties, such as 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) and linoleic acid (LA) with modifications have been formulated to improve EVs secretion for in vitro wound healing. Various analyses, including dynamic light scattering (DLS) and transmission electron microscopy (TEM) were performed to monitor the successful preparation of different types of liposomes. The results showed that cholesterol-LA liposomes significantly improved the secretion of EVs from immortalized adipose-derived mesenchymal stem cells (AD-MSCs) by 1.5-fold. Based on the cell migration effects obtained from scratch assay, both LA liposomal-induced EVs and cholesterol-LA liposomal-induced EVs significantly enhanced the migration of human keratinocytes (HaCaT) cell line. These findings suggested that LA and cholesterol-LA liposomes that enhance EVs secretion are potentially useful and can be extended for various tissue regeneration applications.

Voice banking involves recording an inventory of sentences produced via natural speech. The recordings are used to create a synthetic text-to-speech voice that can be installed on speech-generating devices. This study highlights a minimally researched, clinically relevant issue surrounding the development and evaluation of Singaporean-accented English synthetic voices that were created using readily available voice banking software and hardware. Processes used to create seven unique synthetic voices that produce Singaporean-accented English, and the development of a custom Singaporean Colloquial English (SCE) recording inventory, are reviewed. The perspectives of adults who spoke SCE and banked their voices for this project are summarized and were generally positive. Finally, 100 adults familiar with SCE participated in an experiment that evaluated the intelligibility and naturalness of the Singaporean-accented synthetic voices, as well as the effect of the SCE custom inventory on listener preferences. The addition of the custom SCE inventory did not affect intelligibility or naturalness of the synthetic speech, and listeners tended to prefer the voice created with the SCE inventory when the stimulus was an SCE passage. The procedures used in this project may be helpful for interventionists who wish to create synthetic voices with accents that are not commercially available.

A 51-year-old male with a history of chronic alcoholism presented to the emergency department with an abrupt onset of complete bilateral blindness lasting for one hour. Funduscopic examination yielded unremarkable findings. Systemic evaluations revealed the presence of severe ketoacidosis. The patient spontaneously regained light perception after experiencing total blindness for 3 hours; however, he subsequently developed hypothermia and entered a state of shock. Following treatment with sodium bicarbonate and aggressive fluid resuscitation, his condition stabilized, and there was a rapid improvement in his visual acuity. The diagnosis of alcoholic ketoacidosis was established based on the patient's history of chronic alcohol abuse, physical examination findings, and blood analysis results.

The catalytic mechanisms for the wild-type and the mutated Cu-only superoxide dismutase were studied using the hybrid density functional B3LYP and a quantum chemical cluster approach. Optimal protonation states of the active site were examined for each stage of the catalytic cycle. For both the reductive and the oxidative half-reactions, the arrival of the substrate O 2 • - was found to be accompanied by a charge-compensating H + with exergonicities of -15.4 kcal·mol and -4.7 kcal·mol, respectively. The second-sphere Glu-110 and first-sphere His-93 were suggested to be the transient protonation site for the reductive and the oxidative half-reactions, respectively, which collaborates with the hydrogen bonding water chain to position the substrate near the redox-active copper center. For the reductive half-reaction, the rate-limiting step was found to be the inner-sphere electron transfer from the partially coordinated O 2 • - to Cu II with a barrier of 8.1 kcal·mol. The formed O 2 is released from the active site with an exergonicity of -14.9 kcal·mol. For the oxidative half-reaction, the inner-sphere electron transfer from Cu I to the partially coordinated O 2 • - was found to be accompanied by the proton transfer from the protonated His-93 and barrierless. The rate-limiting step was found to be the second proton transfer from the protonated Glu-110 to H O 2 - with a barrier of 7.3 kcal·mol. The barriers are reasonably consistent with experimental activities, and a proton-transfer rate-limiting step in the oxidative half-reaction could explain the experimentally observed pH-dependence. For the E110Q CuSOD, Asp-113 was suggested to be likely to serve as the transient protonation site in the reductive half-reaction. The rate-limiting barriers were found to be 8.0 and 8.6 kcal·mol, respectively, which could explain the slightly lower performance of E110X mutants. The results were found to be stable, with respect to the percentage of exact exchange in B3LYP.

Luminescent Zn(II) complexes that respond to external stimuli are of wide interest due to their potential applications. Schiff base with O,N,O-hydrazone shows excellent luminescence properties with multi-coordination sites for different coordination modes. In this work, three salicylaldehyde hydrazone Zn(II) complexes ( 1 , 2a , 2b ) were synthesized and their stimuli-responsive behaviors in different states were explored. Only complex 1 exhibits reversible and self-recoverable photochromic and photoluminescence properties in solution. This may be due to the configuration eversion and the excited-state intramolecular proton transfer (ESIPT) process. In the solid state, 2a has obvious mechanochromic luminescence property, which is caused by the destruction of intermolecular interactions and the transformation from crystalline state to amorphous state. 2a and 2b have delayed fluorescence properties due to effective halogen bond interactions in structures. 2a could undergo crystal-phase transformation into its polymorphous 2b by force/vapor stimulation. Interestingly, 2b shows photochromic property, which can be attributed to the electron transfer and generation of radicals induced by UV irradiation. Due to different conformations and coordination modes, the three Zn(II) complexes show different stimuli-responsive properties. This work presents the multi-stimuli-responsive behaviors of salicylaldehyde hydrazone Zn(II) complexes in different states and discusses the response mechanism in detail, which may provide new insights into the design of multi-stimuli-responsive materials.

An in-depth understanding of structure-property relationships and the construction of multifunctional stimuli-responsive materials are still difficult challenges. Herein, we discovered a 4,4'-bipyridinium derivative with both photochromism and dynamic afterglow at 77 K for the first time. A one-dimensional (1D) Cd(II) coordination polymer ( 1 ) assembled by only a 4,4'-bipyridinium derivative and cadmium chloride showed photochromism, room-temperature phosphorescence (RTP), and electrochromism. Interestingly, we found that 1 underwent single-crystal-to-single-crystal transformation during the anion exchange process, and the color of the crystal changed from colorless to yellow ( 1-SCN - ) within 10 min. Complex 1 exhibited photochromism, whereas 1-SCN - did not. The difference in the photochromic behavior between the two complexes was ascribed to the electron transfer pathway between the carboxylate groups and viologen. The DFT calculation based on the crystal structure of 1-SCN - indicated that the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) were mainly located on bipyridine and cadmium atoms, eliminating the possibility of electron transfer, whereas for complex 1 , electron transfer was probable from O and Cl atoms to pyridinium N atoms in viologen as demonstrated by density of states (DOS) calculations. In addition, complex 1 was successfully made into test paper for the rapid detection of I - and SCN - and displayed potential applications in inkless printing, multiple encryption, and anticounterfeiting.

The efficacy of cisplatin in treating advanced non-small cell lung cancer is limited mainly because of insensitivity and/or acquired resistance. MAPK15, previously shown by us to enhance the sensitivity of the anti-cancer drug arsenic trioxide, could also enhance the sensitivity of other anti-cancer drugs. Here, we explore the potential role of MAPK15 in chemosensitivity to cisplatin in human lung cancer cells. Our results indicated that the expression level of MAPK15 was positively correlated with cisplatin sensitivity through affecting the DNA repair capacity of cisplatin-treated cells. The expression of MAPK15 was transcriptionally regulated by the TNF-α-activated NF-κB signaling pathway, and TNF-α synergized with cisplatin, in a MAPK15-dependent manner, to exert cytotoxicity in vitro and in vivo . Therefore, levels of TNF-α dictate the responsiveness/sensitivity of lung cancer cells to cisplatin by transcriptionally upregulating MAPK15 to enhance chemosensitivity, suggesting manipulation of MAPK15 as a strategy to improve the therapeutic efficacy of chemotherapeutic drugs., Competing Interests: The authors declare no conflicts of interest., (© 2022 The Author(s).)

Several electrocardiographic algorithms have been proposed to identify the site of origin for the ventricular arrhythmias (VAs) from the left ventricular outflow tract (LVOT) versus right ventricular outflow tract. However, the electrocardiographic criteria for distinguishing VAs originated from the different sites of LVOT is lacking. We aimed to develop a simple and efficient ECG algorithm to differentiate LVOT VAs originated from the aortic root, AMC and LV summit. We analyzed 12-lead ECG characteristics of 68 consecutive patients who underwent successful radiofrequency catheter ablation of symptomatic VAs from LVOT. Patients were divided into RCC (right coronary cusp) group (n = 8), the L-RCC (the junction between the LCC and RCC) group (n = 21), the LCC (left coronary cusp) group (n = 24), the aortomitral continuity (AMC) group (n = 9) and the LV summit group (n = 6) according to the final ablation sites. Measurements with the highest diagnostic performance were modeled into a 4-stepwise algorithm to discriminate LVOT VAs. The performance of this novel algorithm was prospectively tested in a validation cohort of 43 consecutive patients undergoing LVOT VAs ablation. Based on the accuracy of AUC, a 4-stepwise ECG algorithm was developed. First, the QS duration in aVL > 134 ms was used to distinguish VAs from AMC, LV summit and VAs from aortic root (80% sensitivity and 76% specificity). Second, the R duration in II > 155 ms was used to differentiate VAs from LV summit and VAs from AMC (67% sensitivity and 56% specificity). Third, the ratio of III/II < 0.9 was used to discriminate VAs from RCC and VAs from LCC, L-RCC (82% sensitivity and 63% specificity). Fourth, the QS duration of aVR > 130 ms was used to discern VAs from LCC and VAs from L-RCC (75% sensitivity and 62% specificity). In the prospective evaluation, our 4-stepwise ECG algorithm exhibited a good predictive value. We have developed a novel and simple 4-stepwise ECG algorithm with good predictive value to discriminate the AVs from different sites of LVOT.

Human transmembrane protein metal cation symporter ZIP8 (SLC39A8) is a member of the solute carrier gene family responsible for intracellular transportation of essential micronutrients, including manganese, selenium, and zinc. Previously, we established a ZIP8-knockout (KO) human cell model using the CRISPR/Cas9 system and explored how the expression of ZIP8 could possibly contribute to a wide range of human diseases. To further assess the biophysiological role of ZIP8, in the current study, we employed isobaric tags for relative and absolute quantitation (iTRAQ) and detected the changes of the proteome in ZIP8-KO cells (proteomic data are available via ProteomeXchange with identifier PXD036680). A total of 286 differentially expressed proteins (206 downregulated and 80 upregulated proteins) were detected in the ZIP8-KO cell model, and subsequent bioinformatics analyses (GO, KEGG, KOG, and PPI) were performed on these proteins. Interestingly, four "uncharacterized" proteins (proteins with unknown biological function) were identified in the differentially expressed proteins: C1orf198, C9orf85, C17orf75, and CXorf38-all of which were under-expressed in the ZIP8-KO cells. Notably, C9orf85 and CXorf38 were amongst the top-10 most downregulated proteins, and their expressions could be selectively induced by essential micronutrients. Furthermore, clinical-based bioinformatic analysis indicated that positive correlations between the gene expressions of ZIP8 and C9orf85 or CXorf38 were observed in multiple cancer types. Overall, this study reveals the proteomic landscape of cells with impaired ZIP8 and uncovers the potential relationships between essential micronutrients and uncharacterized proteins C9orf85 and CXorf38. The differentially expressed proteins identified in ZIP8-KO cells could be the potential targets for diagnosing and/or treating human ZIP8-associated diseases, including but not limited to malnutrition, viral infection, and cancers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tan, Xu, Liang, Cai, Wu and Lau.)

Introduction: A sample size justification is required for all studies and should give the minimum number of subjects to be recruited for the study to achieve its primary objective. The aim of this review is to describe sample sizes from agreement studies with continuous or categorical endpoints and different methods of assessing agreement, and to determine whether sample size justification was provided., Methods: Data were gathered from the PubMed repository with a time interval of 28 th September 2018 to 28 th September 2020. The search returned 5257 studies of which 82 studies were eligible for final assessment after duplicates and ineligible studies were excluded., Results: We observed a wide range of sample sizes. Forty-six studies (56%) used a continuous outcome measure, 28 (34%) used categorical and eight (10%) used both. Median sample sizes were 50 (IQR 25 to 100) for continuous endpoints and 119 (IQR 50 to 271) for categorical endpoints. Bland-Altman limits of agreement (median sample size 65; IQR 35 to 124) were the most common method of statistical analysis for continuous variables and Kappa coefficients for categorical variables (median sample size 71; IQR 50 to 233). Of the 82 studies assessed, only 27 (33%) gave justification for their sample size., Conclusions: Despite the importance of a sample size justification, we found that two-thirds of agreement studies did not provide one. We recommend that all agreement studies provide rationale for their sample size even if they do not include a formal sample size calculation., (© 2022. The Author(s).)

Background: Many factors have an aberrant effect on the overall survival of lung cancer (LC) patients. In recent years, remarkable progress has been made in immunotherapy, targeted treatment, and promising biomarkers. However, the available treatments and diagnostic methods are not specific for all patients., Aim: To establish a system for predicting poor survival in patients with LC., Methods: The expression matrix and clinical information for this study were obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases. After the differential analysis of all screened genes, weighted gene coexpression network analysis was performed to analyze hub genes related to patient survival. A logistic regression model was used to construct the scoring system. The expression of the hub genes was verified by performing quantitative reverse transcription-polymerase chain reaction., Results: A total of 5007 differentially expressed genes were selected for the Weighted Gene Co-expression Network Analysis algorithm. We found that the turquoise module showed the highest correlation with patient prognosis. The gene module with the greatest positive correlation with patient survival was located in the turquoise area. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses performed for the genes contained in the turquoise module indicated the potential roles of the selected genes in the regulation of LC development. In addition, protein-protein interaction analysis was performed to screen hub genes, which identified 100 hub genes located in the core area of the network. We then intersected the 100 hub genes with 75 key genes sorted by module members to identify real hub genes associated with prognosis. Forty-one genes were finally selected. We then used a logistic regression model to determine 11 independent risk genes, namely CCNB2 , CDC20 , CENPO , FOXM1 , HJURP , NEK2 , OIP5 , PLK1 , PRC1 , SKA1 , UBE2C and SPARC ., Conclusion: We constructed a predictive model based on 11 independent risk genes to establish a system predicting the survival status of patients with non-small-cell lung carcinoma., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Chilo sacchariphagus Bojer is an important sugarcane pest globally. Along with genetic modification strategies, the sterile insect technique (SIT) has gained more attention as an environment-friendly method for pest control. The identification of key genes associated with sex determination and differentiation will provide important basic information for this control strategy. As such, the transcriptome sequencing of female and male adults was conducted in order to understand the sex-biased gene expression and molecular basis of sex determination and differentiation in this species. A total of 60,429 unigenes were obtained; among them, 34,847 genes were annotated. Furthermore, 11,121 deferentially expressed genes (DEGs) were identified, of which 8986 were male-biased and 2135 were female-biased genes. The male-biased genes were enriched for carbon metabolism, peptidase activity and transmembrane transport, while the female-biased genes were enriched for the cell cycle, DNA replication, and the MAPK signaling pathway. In addition, 102 genes related to sex-determination and differentiation were identified, including the protein toll , ejaculatory bulb-specific protein , fruitless , transformer-2 , sex-lethal , beta-Catenin , sox , gata4 , beta-tubulin , cytosol aminopeptidase , seminal fluid , and wnt4 . Furthermore, transcription factors such as myb , bhlh and homeobox were also found to be potentially related to sex determination and differentiation in this species. Our data provide new insights into the genetic elements associated with sex determination and differentiation in Chilo sacchariphagus , and identified potential candidate genes to develop pest-control strategies.

Exosomes and liposomes are vesicular nanoparticles that can encapsulate functional cargo. The chemical similarities between naturally occurring exosomes and synthetic liposomes have accelerated the development of exosome mimetics as a therapeutic drug delivery platform under physiological and pathological environments. To maximise the applications of exosomes and liposomes in the clinical setting, it is essential to look into their basic chemical properties and utilise these characteristics to optimise the preparation, loading, modification and hybridisation. This review summarises the chemical and biological properties of both exosomal and liposomal systems as well as some of the challenges related to their production and application. This article concludes with a discussion on potential perspectives for the integration of exosomal and liposomal technologies in mapping better approaches for their biomedical use, especially in therapeutics., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

A triphenylamine (TPA)-based 2 H -quinazoline Zn(II) complex ( Q-TPA-Zn ) exhibiting dual fluorescence and phosphorescence emission in the solid state was designed and prepared. It possesses mechanochromic luminescence and thermochromic luminescence properties. In the solid state, the white afterglow luminescence could be observed at 77 K (CIE xy : 0.27, 0.33) while cyan luminescence could be observed at 297 K. After thermolysis at 300 °C, Q-TPA-Zn could be transformed into Schiff base complex S-TPA-Zn with white fluorescence in the powder state (CIE xy : 0.32, 0.38), in methanol (CIE xy : 0.32, 0.39), and in dimethylformamide (CIE xy : 0.26, 0.32) at room temperature. This arises from dual emission of normal* emission and tautomeric* emission induced by excited-state intramolecular proton transfer (ESIPT) from the benzimidazole NH group to the Schiff base N atom. Q-TPA-Zn could also be transformed into its isomeric form, S-TPA-Zn , through photochemical ring-opening reaction upon irradiation under 365 nm in the solution, exhibiting high-contrast photochromic luminescence. Interestingly, S-TPA-Zn could further be transformed into its zwitterionic isomer after continuous irradiation. The same ring-opening reaction could also take place for the orgainc compound Q-TPA via heating or 365 nm irradiation. The ring-opening reaction mechanism and ESIPT emission were interpreted via theoretical calculation.

Objectives: The Integrated Care for Advanced REspiratory Disorders (ICARE) service is a stay-in, post-acute care program for hospitalized patients with chronic, nonmalignant lung diseases. It provides palliative rehabilitation-a novel model integrating functional rehabilitation with early palliative care. We compare reduction of health care utilization among ICARE participants vs matched controls receiving usual care., Design: This is a prospective, propensity score-matched study. Primary outcomes were reduction in hospital readmissions and length of stay and emergency department (ED) visits, comparing the period 6 months before and after ICARE, or 6 months before and after hospital discharge (for controls). Secondary outcomes included 6-minute walking distance (6MWD) and Modified Barthel Index (MBI)., Setting: Participants were matched 1:1 to controls by age, respiratory diagnosis, socioeconomic strata, index hospitalization length of stay, frailty, and recent admissions into intensive care unit or noninvasive ventilation units., Methods: Multidisciplinary interventions focused on symptom relief, functional rehabilitation, targeted comorbidity management, and postdischarge care coordination., Results: One hundred pairs of patients were matched. Participants were older adults (mean age 73.9 ± 8.2 years) with prolonged index hospitalization (median 12.0 days; interquartile range 7-18). Overall, 57% had high Hospital Frailty Risk Scores and 71% had overlapping respiratory diagnoses, the most common commonest being COPD (89%), followed by interstitial lung disease (54%) and bronchiectasis (28%). Small reductions in health care utilization were observed among controls. ICARE was associated with a further 9.1 ± 19.9 days' reduction in hospitalization length of stay (P < .001), 0.8 ± 1.9 lesser admission (P < .001), and 0.6 ± 2.2 fewer ED visits (P < .02). Participants with longest index hospitalization were observed to have greatest reduction in length of stay. 6MWD and MBI scores improved by 41.0 ± 60.2 m and 12.3 ± 11.6 points, respectively (both P < .001). Greater improvement was observed in patients with lower baseline 6MWD and MBI scores. Prescription of slow-release opioids rose from 9% to 49%. Treatment for anxiety and depression rose from 5% to 19%., Conclusions and Implications: Integrating palliative care with postexacerbation functional rehabilitation was associated with short-term reduction in health care utilization, improved functional capacity, and increased treatment of dyspnea, anxiety, and depression., (Copyright © 2021 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: The outbreak of the newly discovered human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has disrupted the normal life of almost every civilization worldwide. Studies have shown that the coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 can affect multiple human organs and physiological systems, but the respiratory system remains the primary location for viral infection., Areas Covered: We summarize how omics technologies are used in SARS-CoV-2 research and specifically review the current knowledge of COVID-19 from the aspect of human bronchial-pulmonary proteomics. Also, knowledge gaps in COVID-19 that can be fulfilled by proteomics are discussed., Expert Opinion: Overall, human bronchial-pulmonary proteomics plays an important role in revealing the dynamics, functions, tropism, and pathogenicity of SARS-CoV-2, which is crucial for COVID-19 biomarker and therapeutic target discoveries. To more fully understand the impact of COVID-19, research from various angles using multi-omics approaches should also be conducted on the lungs as well as other organs.

The metal cation symporter ZIP8 (SLC39A8) is a transmembrane protein that imports the essential micronutrients iron, manganese, and zinc, as well as heavy toxic metal cadmium (Cd). It has been recently suggested that selenium (Se), another essential micronutrient that has long been known for its role in human health and cancer risk, may also be transported by the ZIP8 protein. Several mutations in the ZIP8 gene are associated with the aberrant ion homeostasis of cells and can lead to human diseases. However, the intricate relationships between ZIP8 mutations, cellular Se homeostasis, and human diseases (including cancers and illnesses associated with Cd exposure) have not been explored. To further verify if ZIP8 is involved in cellular Se transportation, we first knockout (KO) the endogenous expression of ZIP8 in the HeLa cells using the CRISPR/Cas9 system. The elimination of ZIP8 expression was examined by PCR, DNA sequencing, immunoblot, and immunofluorescence analyses. Inductively coupled plasma mass spectrometry indicated that reduced uptake of Se, along with other micronutrients and Cd, was observed in the ZIP8-KO cells. In contrast, when ZIP8 was overexpressed, increased Se uptake could be detected in the ZIP8-overexpressing cells. Additionally, we found that ZIP8 with disease-associated single-point mutations G38R, G204C, and S335T, but not C113S, showed reduced Se transport ability. We then evaluated the potential of Se on Cd cytotoxicity prevention and therapy of cancers. Results indicated that Se could suppress Cd-induced cytotoxicity via decreasing the intracellular Cd transported by ZIP8, and Se exhibited excellent anticancer activity against not all but only selected cancer cell lines, under restricted experimental conditions. Moreover, clinical-based bioinformatic analyses revealed that up-regulated ZIP8 gene expression was common across multiple cancer types, and selenoproteins that were significantly co-expressed with ZIP8 in these cancers had been identified. Taken together, this study concludes that ZIP8 is an important protein in modulating cellular Se levels and provides insights into the roles of ZIP8 and Se in disease prevention and therapy.

Purpose: The main tendon of the extensor hallucis longus (EHL) muscle attaches to the dorsal aspect of the distal phalanx of the great toe. One or multiple accessory tendons of the EHL have been reported in several ethnic/regional groups, except Taiwan. This study aimed to investigate the incidence, length, and insertion of the accessory tendon of the EHL in Taiwanese people., Methods: Anatomical dissection was performed on 48 feet of 24 formalin-embalmed cadavers. The occurrence and morphological characteristics of the accessory tendon of the EHL were recorded and analyzed., Results: The accessory tendon of the EHL was found in 97.92% (47/48) of the legs that were dissected. In one male cadaver, an independent muscle belly was identified in each leg, whereas all the other accessory tendons originated from the main tendon of the EHL. In this study, the insertion of the accessory tendon were classified into four patterns. The most common insertion sites were the first metatarsophalangeal (MTP) joint capsule and proximal phalanx of the great toe. The length of the accessory tendons did not correlate with age or with sex when the two tendons with independent muscle belly were excluded., Conclusions: The accessory tendon of the EHL appears to be a regular feature in Taiwanese people. Most accessory tendons of the EHL (85.7%) attached on the first MTP joint capsule may play a role in the prevention of capsular impingement during great toe extension., (© 2021. The Author(s), under exclusive licence to Springer-Verlag France SAS part of Springer Nature.)

Objective: Atrial fibrillation (AF) and sinus node dysfunction (SND) have common underlying pathophysiological mechanisms. As an index of SND, corrected sinus node recovery time (CSNRT) may also reflect atrial function. The aim of the present study was to determine whether CSNRT predicts AF recurrence in patients undergoing AF ablation., Methods: Consecutive patients with paroxysmal atrial fibrillation (PAF) who underwent radiofrequency catheter ablation between January 2017 and December 2018 were enrolled. Clinical data, CSNRT, and other electrophysiology indices were collected and analysed between patients with or without AF recurrence., Results: A total of 159 patients with PAF who underwent the same radiofrequency catheter ablation procedure were enrolled, including 25 patients with SND. During the one-year follow-up period, 22 patients experienced AF recurrence. Patients with recurrence had a significantly longer CSNRT and a larger left atrial volume index (LAVI) than patients without AF recurrence. SND (CSNRT > 550 ms) and a larger LAVI were independently associated with AF recurrence after ablation. A statistically significant CSNRT cut-off value of 550 ms predicted AF recurrence with 73% sensitivity and 85% specificity., Conclusion: CSNRT and LAVI are independent predictors of PAF recurrence following ablation.

Lung cancer is the leading cause of cancer-related deaths worldwide, in which angiogenesis is highly required for lung cancer cell growth and metastasis. Genetic regulation of this multistep process is being studied extensively, however, relatively less is known about the epigenetic regulation of angiogenesis in lung cancer. Several epigenetic alterations contribute to regulating angiogenesis, such as epimodifications of DNA, posttranslational modification of histones, and expression of noncoding RNAs. Here, we review the current knowledge of the epigenetic regulation of angiogenesis and discuss the potential clinical applications of epigenetic-based anticancer therapy in lung cancer. Overall, epigenetic-based therapy will likely emerge as a prominent approach to treat lung cancer in the future., (© 2020 Wiley Periodicals LLC.)

Organically-derived biofertilizers and biostimulants, developed from harvested materials such as seaweed and waste from animal and fish processing, are currently the subject of much fundamental and applied research. These products have significant potential in reducing synthetic fertilizer inputs to horticultural, arable, and pasture-based agricultural systems, although there is frequently some ambiguity over the magnitude and consistency of any positive effects these products may have on plant performance. This study examined the effects of organically-derived plant growth promoters (PGPs) available in New Zealand on the early vegetative growth of 16 plant species maintained under glasshouse conditions. When applied as a root drench to low nutrient potting mix, the effects of the PGPs on seedling shoot growth were strongly related to the NPK contents of the applied solutions. Any positive effects on shoot growth were, on average, reduced when the seedlings were maintained in higher nutrient growing media. Applying the PGPs at concentrations twice, and four times, the recommended concentration, only caused further growth responses when the PGPs contained high levels of nutrients. Applying the PGPs as a foliar spray had negligible effects on shoot growth. Overall, the results of these trials suggest that the positive effects of applying some organically-derived PGPs on seedling growth are a function of the PGP nutrient content, and not due to any indirect effects related to phytohormone pathways or modification of rhizosphere microorganisms.

In the fight against COVID-19, the Pfizer and BioNTech vaccine announcement marked a significant turning point. Analysing the topics discussed surrounding the announcement is critical to shed light on how people respond to the vaccination against COVID-19. Specifically, since the COVID-19 vaccine was developed at unprecedented speed, different segments of the public with a different understanding of the issues may react and respond differently. We analysed Twitter tweets to uncover the issues surrounding people's discussion of the vaccination against COVID-19. Through the use of Latent Dirichlet Allocation (LDA), nine topics were identified pertaining to vaccine-related tweets. We analysed the temporal differences in the nine topics, prior and after the official vaccine announcement., (84th Annual Meeting of the Association for Information Science & Technology | Oct. 29 – Nov. 3, 2021 | Salt Lake City, UT. Author(s) retain copyright, but ASIS&T receives an exclusive publication license.)

Coronavirus (CoV) disease 2019 (COVID-19) is an ongoing pandemic caused by severe acute respiratory syndrome CoV 2 (SARS-CoV-2). The highly contagious SARS-CoV-2 belongs to the genus Betacoronavirus, and it is phylogenetically closely related to SARS-CoV, a human CoV that caused an outbreak back in 2002 to 2003. Both SARS-CoV-2 and SARS-CoV enter human cells via the interactions between viral crown-like spike protein and human angiotensin-converting enzyme 2 (ACE2) receptor. Here, we aim to review the involvement of ACE2 in human CoV infections by discussing the roles of ACE2 in CoV evolution, cross-species transmissibility, and COVID-19 susceptibility. We also provide our perspectives on COVID-19 treatment and prevention., (© 2020 John Wiley & Sons, Ltd.)

Coilin is the main component of Cajal body (CB), a membraneless organelle that is involved in the biogenesis of ribonucleoproteins and telomerase, cell cycle, and cell growth. The disruption of CBs is linked to neurodegenerative diseases and potentially cancers. The coilin gene ( COIL ) contains two nonsynonymous SNPs: rs116022828 (E121K) and rs61731978 (V145I). Here, we investigated for the first time the functional impacts of these coilin SNPs on CB formation, coilin subcellular localization, microtubule formation, cell growth, and coilin expression and protein structure. We revealed that both E121K and V145I mutants could disrupt CB formation and result in various patterns of subcellular localization with survival motor neuron protein. Noteworthy, many of the E121K cells showed nucleolar coilin accumulation. The microtubule regrowth and cell cycle assays indicated that the E121K cells appeared to be trapped in the S and G2/M phases of cell cycle, resulting in reduced cell proliferation. In silico protein structure prediction suggested that the E121K mutation caused greater destabilization on the coilin structure than the V145I mutation. Additionally, clinical bioinformatic analysis indicated that coilin expression levels could be a risk factor for cancer, depending on the cancer types and races.

Objective: To investigate the pharmacokinetics (PK) and pharmacodynamics (PD) of a rapid-acting insulin analog-insulin aspart (the tested formulation) which was manufactured by The United Laboratories and to evaluate the bioequiavailability to the reference formulation (NovoRapid ® ) produced by Novo Nordisk in Chinese healthy volunteers., Methods: A total of 24 male healthy volunteers were recruited from February to April 2016 to participant in this before-after, single dose, and randomized crossover study. And the experimental observation was conducted on 2 test days respectively with a between-period from 7 to10 d. According to a random number table, the volunteers were divided into group A or B, group A was administrated with tested insulin aspart (IAsp) for the first time and reference NovoRapid ® for the second time and group B had the revered order differed from group A. The PK/PD of these insulin analogs were estimated by euglycemic clamp study., Results: The relative biological effectiveness (reflecting gloucose-lowing effect) and bioavailability on behalf of plasma-drug concentration were 98.3±18.8% and 97.3%±8.3% respectively. For PK parameters, the 90% confidence interval ( CI ) of peak plasma insulin concentration ( C max ) and area under the curve of insulin aspart concentration from 0 to 10 hours ( AUC IAsp, 0-10 h ) of IAsp were 88.8%-106% (equivalent range 70%-143%) and 94.0%-100% (equivalent range 80%-125%) respectively; for PD parameters, the 90% CI of the maximum glucose infusion rate ( GIR max ) and AUC GIR, 0-10 h were 95.5%-113% (equivalent range 70%-143%) and 89.9%-104% (equivalent range 80%-125%) respectively, which indicated that IAsp and NovoRapid® was bioequivalent. One of the subjects discovered hyperuricemia without clinical symptoms and the rest had no clinically significant abnormalities in the safety indexes before and after the tests. No hypoglycemic events, allergic reactions, or local injection adverse reaction occurred in this trial., Conclusion: The tested IAsp has comparable relative bioavailability to the reference NovoRapid ® ., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).)

The synergistic anticancer effect of gemcitabine (GEM) and resveratrol (RSVL) has been noted in certain cancer types. However, whether the same phenomenon would occur in lung cancer is unclear. Here, we uncovered the molecular mechanism by which RSVL enhances the anticancer effect of GEM against lung cancer cells both in vitro and in vivo. We established human lung adenocarcinoma HCC827 xenografts in nude mice and treated them with GEM and RSVL to detect their synergistic effect in vivo. Tumor tissue sections from nude mice were subjected to hematoxylin and eosin staining for blood vessel morphological observation, and immunohistochemistry was conducted to detect CD31-positive staining blood vessels. We also established the HCC827-human umbilical vein endothelial cell (HUVEC) co-culture model to observe the tubule network formation. Human angiogenesis antibody array was used to screen the angiogenesis-related proteins in RSVL-treated HCC827. RSVL suppressed the expression of endoglin (ENG) and increased tumor microvessel growth and blood perfusion into tumor. Co-treatment of RSVL and GEM led to more tumor growth suppression than treatment of GEM alone. Mechanistically, using the HCC827-HUVEC co-culture model, we showed that RSVL-suppressed ENG expression was accompanied with augmented levels of phosphorylated extracellular signal-regulated kinase (ERK) 1/2 and increased tubule network formation, which may explain why RSVL promoted tumor microvessel growth in vivo. RSVL promoted tumor microvessel growth via ENG and ERK and enhanced the anticancer efficacy of GEM. Our results suggest that intake of RSVL may be beneficial during lung cancer chemotherapy.

3D printing enables on-demand solutions for a wide spectrum of needs ranging from personal protection equipment to medical devices and isolation wards. This versatile technology is suited to address supply-demand imbalances caused by socio-economic trends and disruptions in supply chains., Competing Interests: Competing interestsThe authors declare no competing interests., (© Springer Nature Limited 2020.)

For every ton of biodiesel produced, about 100 kg of glycerol is also generated as a by-product. The traditional method of removing glycerol is mainly by gravity separation or centrifugation. This method generates crude glycerol, which may still contain impurities such as methanol, oil, soap, salt, and other organic materials at ppm levels. The effective usage of crude glycerol is important to improve the economic sustainability of the biodiesel industry while reducing the environmental impacts caused by the generated waste. The application and value of crude glycerol can be enhanced if these impurities are removed or minimized. Thus, it is important to develop a method which can increase the economic and applicable value of crude glycerol. Therefore, in the present study, the dual step purification method comprised of acidification and ion exchange techniques has been used to purify the crude glycerol and convert it into higher-value products. The acidification process started with the pH adjustment of the crude glycerol, using phosphoric acid to convert soap into fatty acid and salts. Then, the pretreated glycerol was further purified by ion exchange with a strong cation H + resin. Gas chromatography (GC) was used to analyze both crude and purified glycerol and expressed as the weight percentage of glycerol content. A maximum glycerol purity of 98.2% was obtained after the dual step purification method at the optimized conditions of 60% of solvent, the flow rate of 15 mL/min and 40 g of resin. Further, the glycerol content measured being within the accepted amount of BS 2621:1979. Therefore, this study has proven that the proposed crude glycerol purification process is effective in improving the glycerol purity and could enhance the applicability of glycerol in producing value-added products which bring new revenue to the biodiesel industry., (Copyright © 2019 Abdul Raman, Tan and Buthiyappan.)

Background: To identify thyroid dose-volume thresholds for radiotherapy (RT)-related hypothyroidism (HT) in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated RT (IMRT). In this way, we desired to guide the design of treatment plans and, finally, lower HT prevalence., Methods: In total, 345 NPC patients treated with IMRT were evaluated retrospectively during a median follow-up of 45.2 (range, 11.3-64.9) months. Serum-based assessments of thyroid function before and after IMRT were monitored periodically. Thyroid dose-volume parameters were analyzed for their association with HT risk., Results: In total, 44.1% of patients (152/345) developed primary HT. Analyses of thyroid dose-volume parameters identified a stringent dose-volume histogram (DVH) threshold defined by V 25Gy (the percentage thyroid volume that receives >25 Gy, not the absolute volume) ≤60%, V 35Gy  ≤ 55%, and V 45Gy  ≤ 45%. Patients whose thyroid DVHs satisfied these constraints had a lower prevalence of 2-year HT compared with the overall prevalence (13.2% vs 25.8%, P < .001). Another DVH was defined by V 25Gy  > 95%, V 35Gy  > 90%, and V 45Gy  > 75%, and patients whose thyroid DVHs satisfied with these constraints had a higher prevalence of 2-year HT than the overall incidence (36.0% vs 25.8%, P < .001)., Conclusion: We recommend V 25Gy  ≤ 60%, V 35Gy  ≤ 55%, and V 45Gy  ≤ 45% as the "stringent" DVH line, and V 25Gy  > 95%, V 35Gy  > 90%, and V 45Gy  > 75% as the "inhibition" DVH line, under the precondition of not compromising the target coverage. These findings could help in the design of individual treatment plans and, eventually, to lowering of HT prevalence., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Quantum dots (QDs) are luminescent nanoparticles with superior versatility. In this regard, cadmium telluride (CdTe) QDs have been widely used for various bioimaging applications. Although these nano-Cd containing particles can be capped with shells to reduce their cytotoxicity, these shells would be gradually disintegrated after a certain period of time, thereby inevitably exerting nanotoxicity. Previously, we showed that treatment of human bronchial epithelial BEAS-2B cells with uncapped CdTe QDs (520Q, 580Q and 730Q with emission maximum at 520, 580 and 730 nm, respectively) elicited dose-dependent cytotoxicity for 520Q and 580Q (<5 nm), while 730Q (>5 nm) elicited negligible cytotoxicity. In order to gain a more global perspective on the action mechanism of these nano-Cd particles, here, we further characterized the proteome response of BEAS-2B when challenged with the above QDs. Interestingly, among the three nano-Cd particles, we observed that 520Q and 580Q treatment altered the BEAS-2B proteome significantly in a very similar magnitude while 730Q has no obvious impact at all, as compared with the untreated control. Notably, the treatment of BEAS-2B with glutathione before nano-Cd particles abrogated the induction/repression of differentially expressed proteins and prevented cell death. Taken together, our findings show that uncapped CdTe nanoparticles (520Q and 580Q) induce oxidative stress in human bronchial epithelial cells, and the similarly altered protein signatures also suggest potential mitotoxicity and common cellular and detoxification responses upon exposure of lung cells to these two QDs. On the other hand, 730Q may exert a more noticeable effect after long-term exposure, but not upon transient exposure., (This journal is © The Royal Society of Chemistry 2019.)

Accumulating evidence illustrates the significance of cell plasticity in the molecular biology of liver cancer. Reprogramming of mature parenchymal cells to a less differentiated state by key molecular targets contributes to the pathogenesis of hepatocellular carcinoma (HCC). Hereby, we investigated the role of GATA6, a transcription factor implicated in hepatocyte lineage specification, in HCC. Our results demonstrated a lower expression of GATA6 in HCC tissues compared to the corresponding nontumoral liver tissues. Moreover, GATA6 underexpression, as observed in about 50% cases in our clinical cohort, was associated with a poorer degree of tumor cell differentiation and worse disease-free survival outcome. In vitro, silencing of GATA6 in HCC cells augmented cell migration and invasion abilities of HCC cells by activating epithelial-mesenchymal transition. Self-renewal was also enhanced in vitro. Consistently, in vivo tumorigenicity and self-renewal was promoted upon GATA6 knockdown. Notably, suppression of GATA6 converts HCC cells to a metabolic phenotype recapitulating stem-cell state. Expression of glycolytic markers was elevated in GATA6-knockdown clones accompanied by increased glucose uptake; while overexpression of GATA6 resulted in opposite effects. Further to this, we identified that GATA6 bound to the promoter region of PKM gene and regulated PKM2 transcription. Taken together, downregulation of GATA6 directs HCC cells to glycolytic metabolism and fosters tumorigenicity, self-renewal and metastasis. GATA6 is a transcriptional regulator and a genetic switch that converts the phenotypic reprogramming of HCC cells. It is a potential prognostic biomarker and therapeutic target for liver cancer., (© 2019 UICC.)