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Vision transformers (ViTs) are increasingly utilized for HSI classification due to their outstanding performance. However, ViTs encounter challenges in capturing global dependencies among objects of varying sizes, and fail to effectively exploit the spatial–spectral information inherent in HSI. In response to this limitation, we propose a novel solution: the multi-scale spatial–spectral transformer (MSST). Within the MSST framework, we introduce a spatial–spectral token generator (SSTG) and a token fusion self-attention (TFSA) module. Serving as the feature extractor for the MSST, the SSTG incorporates a dual-branch multi-dimensional convolutional structure, enabling the extraction of semantic characteristics that encompass spatial–spectral information from HSI and subsequently tokenizing them. TFSA is a multi-head attention module with the ability to encode attention to features across various scales. We integrated TFSA with cross-covariance attention (CCA) to construct the transformer encoder (TE) for the MSST. Utilizing this TE to perform attention modeling on tokens derived from the SSTG, the network effectively simulates global dependencies among multi-scale features in the data, concurrently making optimal use of spatial–spectral information in HSI. Finally, the output of the TE is fed into a linear mapping layer to obtain the classification results. Experiments conducted on three popular public datasets demonstrate that the MSST method achieved higher classification accuracy compared to state-of-the-art (SOTA) methods. [ABSTRACT FROM AUTHOR]

The poor prognosis of immunotherapy in patients with colorectal cancer (CRC) necessitates a comprehensive understanding of the immunosuppressive mechanisms within tumor microenvironment (TME). Undoubtedly, the anti‐tumor immune cells play an indispensable role in immune tolerance. Therefore, it is imperative to investigate novel immune‐related factors that have the capacity to enhance anti‐tumor immunity. Here, we employed bioinformatic analysis using R and Cytoscape to identify the hub gene chemokine (C‐X‐C motif) ligand 8 (CXCL8), which is overexpressed in CRC, in the malignant progression of CRC. However, its specific role of CXCL8 in CRC immunity remains to be elucidated. For this purpose, we evaluated how tumor‐derived CXCL8 promotes M2 macrophage infiltration by in vivo and in vitro, which can be triggered by IL‐1β within TME. Mechanistically, CXCL8‐induced polarization of M2 macrophages depends on the activation of the STAT3 signaling. Finally, immunohistochemistry and multiplexed immunohistochemistry analysis identified that CXCL8 not only enhances PD‐L1+ M2 macrophage infiltration but also attenuates the recruitment of PD‐1+CD8+ T cells in murine CRC models. Together, these findings emphasize the critical role for CXCL8 in promoting M2 macrophage polarization and inhibiting CD8+ T cell infiltration, thereby links CXCL8 to the emergency of immunosuppressive microenvironment facilitating tumor evasion. Overall, these findings may provide novel strategy for CRC immunotherapy. [ABSTRACT FROM AUTHOR]

Objectives: Non-suicidal self-injury (NSSI) behavior is a severe public health issue in adolescents. This study investigated the possible impact of the coronavirus disease 2019 (COVID-19) and analyzed psychological risk factors on adolescent NSSI. Methods: A one-year follow-up study was conducted in September 2019 (Time 1) and September 2020 (Time 2) among 3588 high school students. The completed follow-up participants (N = 2527) were classified into no NSSI (negative at both time points), emerging NSSI (negative at Time 1 but positive at Time 2), and sustained NSSI (positive at both time points) subgroups according to their NSSI behaviors before and during the COVID-19 pandemic. Perceived family functioning, perceived school climate, negative life events, personality traits (neuroticism, impulsivity, and self-control) were assessed using self-report scales. Results: The data indicated an increase (10.3%) in the incidence of NSSI. Compared to no NSSI subjects, the emerging NSSI and sustained NSSI subgroups had lower perceived family functioning, higher neuroticism, higher impulse-system but lower self-control scores, and more negative life events. Logistic regressions revealed that after controlling for demographics, neuroticism and impulse-system levels at Time 1 positively predicted emerging NSSI behavior, and similarly, higher neuroticism and impulsivity and lower self-control at Time 1 predicted sustained NSSI behavior. Conclusions: These findings highlighted the aggravated impact of the COVID-19 on NSSI, and suggested that individual neuroticism, impulsivity, and self-control traits might be crucial for the development of NSSI behavior among adolescent students. [ABSTRACT FROM AUTHOR]

To investigate the efficacy of direct computed tomography venography (CTV) in early and accurate detection of lower extremity venous (LEV) abnormalities. Cross-sectional research was conducted in Hebei General Hospital of China. A total of 211 CTV reports of both lower extremities from January 2017 to September 2019, 75 color Doppler ultrasound (DUS) examinations, and eight intravascular angiography records of these patients over the same period were collected from the hospital. Comparisons were made for the reported number and percentage of LEV abnormalities (thrombosis, stenosis including severe stenosis, and varicosities). Chi-square test and t-test were applied to compare the rates and means, respectively. Significance level α was 0.05. Individual interviews were performed to understand the perceptions of medical staff and patients on the application of CTV, and the interview results were analyzed. Of the 75 cases with both CTV and DUS reports, 159 abnormalities occurring in the lower extremity deep veins (LEDV) were reported, among which 125 (79%) and 18 (11%) were reported by CTV and DUS on a single basis, respectively, whereas 16 (10%) were reported by CTV and DUS simultaneously. A statistically significant greater number of abnormalities in LEDV were identified by CTV than DUS in both males and females (χ2males = 78.449, χ2females = 27.574, χ2total = 104.164, p <.05). In the 211 CTV reports, among the 383 abnormalities reported in total, the common iliac vein (CIV) had the highest number of reported abnormalities (132, 34.5%), followed by the femoral vein (93, 24.3%). The ratios between LEDV abnormality and patient numbers were 1.055 and 0.688 for left and right sides in males, and 0.892 and 0.461 for left and right sides in females, respectively, with that for the left side statistically significantly higher than the right one (tmale = 2.896, tfemale = 4.347, p <.05). The incidence of thrombosis was 10.9% (95% CI = 6.7 ∼ 15.1%). Reported abnormities in CIV by CTV were in agreement with those by intravascular angiography. The medical staff believed that CTV could guide the performance of surgeries for LEV and the patients perceived CTV acceptable. Application of CTV for early and accurate detection of LEDV abnormalities including thrombosis has been proven to be efficient. Corresponding benefit in early intervention and reduction of severe complications of such abnormalities is of important value. CTV earned good recognition from medical staff and patients. Hence, it could be considered as part of global health assistance cooperation with developing countries to facilitate enhanced medical services. [ABSTRACT FROM AUTHOR]

This paper investigates two flow shop scheduling problems with two machines A and B , and a single transporter V. In the first problem, the transporter V is located at machine A initially, each job has to be processed first on A , then transported to B for further processing. While in the second problem, the transporter V is located at machine B initially, each job needs to be processed first on A , then on B , finally transported to the destination. In both problems, the transporter V can carry up to c (where c is a constant and c ≥ 1) jobs at a time and the objective is to minimize the makespan. For the former problem, the best approximation algorithm guarantees a worst-case ratio bound of (5 3 + ε) , while for the latter one, the best approximation algorithm provides a worst-case ratio bound of 2. For each problem, we design a polynomial-time approximation scheme (PTAS). [ABSTRACT FROM AUTHOR]

Pancreatic β-cell dysfunction plays a vital role in the development of diabetes. IL-33 exerts anti-diabetic effects via its anti-inflammatory properties and has been demonstrated to increase insulin secretion in animal models. However, IL-33, as a pleiotropic cytokine, may also exert a deleterious effect on β-cells, which has not been rigorously studied. In the present study, we found that IL-33 promoted cell survival and insulin secretion in MIN6 (a mouse pancreatic β-cell line) cells under diabetogenic conditions. IL-33 increased the expression of its receptor ST2 and the transcription factor PPARγ, whereas PPARγ inhibition impaired IL-33-mediated β-cell survival and insulin release. IL-33 did not repress the expression of pro-inflammatory mediators, including Tf , Icam1 , Cxcl10 , and Il1b , whereas it significantly reduced the expression of Ccl2. IL-33 decreased TNF-α secretion and increased IL-10 secretion; these effects were completely reversed by PPARγ inhibition. IL-33 increased glucose uptake and expression of Glut2. It upregulated the expression of glycolytic enzyme genes, namely, Pkm2, Hk2, Gpi1 , and Tpi , and downregulated the expression of Gck, Ldha, and Mct4. However, it did not alter hexokinase activity. Moreover, IL-33 increased the number and activity of mitochondria, accompanied by increased ATP production and reduced accumulation of ROS. IL-33 upregulated the expression of PGC-1α and cytochrome c , and mitochondrial fission- and fusion-associated genes, including Mfn1 , Mfn2 , and Dnm1l. IL-33-mediated mitochondrial homeostasis was partially reversed by PPARγ inhibition. Altogether, IL-33 protects β-cell survival and insulin secretion that could be partially driven via PPARγ, which regulates glucose uptake and promotes mitochondrial function and anti-inflammatory responses. [ABSTRACT FROM AUTHOR]

• The coating-substrate pull-off strength increased by up to 112.2% with carbonation curing. • Interfacial debonding was altered to substrate failure after ACC treatment. • Pure physical adhesion had limited contribution to the strength rises. • Pillar-like CaCO 3 nano-crystals provided the crystals anchoring adhesion. Strong coating-substrate adhesion is crucial for ensuring long-term durability and performance of protective coatings in various applications. The growth of nano crystals on the substrate may be a preferable way to enhance the coating-substrate interactions. Here, an accelerated carbonation curing (ACC) scheme (0.5 MPa CO 2 gas pressure) was designed to grow calcium carbonate (CaCO 3) nano-crystals on a mortar substrate at early age before coated with a waterborne epoxy resin (WER). Microstructures of the ACC-treated mortar specimens and the coating-substrate interfaces were characterized by multiple microscopic tests, and the compressive strength of the carbonated substrate and the pull-off coating-substrate strength were measured. Results showed that the ACC treatment not only increased the mortar strength (by up to 17%), but also greatly improved the pull-off strength (by up to 112.2%). Substrate failure took place in the mortars after the ACC treatment. The mechanisms of physical adhesion, surface roughness, and crystals anchoring caused by the growth of pillar-like CaCO 3 nano-crystals may account for the largely raised pull-off strength. The findings would deepen the understandings of interfacial adhesion mechanisms between polymer coatings and cement-based substrates and provide new insights into developing stronger coating-substrate adhesions. [ABSTRACT FROM AUTHOR]

Repetitive transcranial magnetic stimulation (rTMS) has attracted considerable attention because of its non-invasiveness, minimal side effects, and treatment efficacy. Despite an adequate duration of rTMS treatment, some patients with post-stroke depression (PSD) do not achieve full symptom response or remission. This was a prospective randomized controlled trial. Participants receiving rTMS were randomly assigned to the ventromedial prefrontal cortex (VMPFC), left dorsolateral prefrontal cortex (DLPFC), or contralateral motor area (M1) groups in a ratio of 1:1:1. Enrollment assessments and data collection were performed in weeks 0, 2, 4, and 8. The impact of depressive symptom dimensions on treatment outcomes were tested using a linear mixed-effects model fitted with maximum likelihood. Univariate analysis of variance (ANOVA) and back-testing were used to analyze the differences between the groups. In total, 276 patients were included in the analysis. Comparisons across groups showed that 17-item Hamilton Rating Scale for Depression (HAMD-17) scores of the DLPFC group significantly differed from those of the VMPFC and M1 groups at 2, 4, and 8 weeks after treatment (p < 0.05). A higher observed mood score (β = −0.44, 95% confidence interval [CI]: −0.85–0.04, p = 0.030) could predict a greater improvement in depressive symptoms in the DLPFC group. Higher neurovegetative scores (β = 0.60, 95% CI: 0.25–0.96, p = 0.001) could predict less improvement of depressive symptoms in the DLPFC group. Stimulation of the left DLPFC by high-frequency rTMS (HF-rTMS) could significantly improve depressive symptoms in the subacute period of subcortical ischemic stroke, and the dimension of depressive symptoms at admission might predict the treatment effect. • PSD is one of the most common complications after stroke. • rTMS is noninvasiveness, minimal side effects and treatment efficacy. • Stimulation of left DLPFC by HF-rTMS could improve depressive symptoms after stroke. • The dimension of depressive symptoms could predict treatment effect of rTMS on PSD. [ABSTRACT FROM AUTHOR]

Background: Kawasaki disease (KD) is a systemic form of self-limited vasculitis in children less than five years old, and the main complication is coronary artery injury. However, the etiology of KD remains unclear. The IL-1B polymorphisms rs16944 GG and rs1143627 AA and their diplotype GA/GA have been associated with significantly increased risk of intravenous immunoglobulin (IVIG) resistance in a Taiwanese population, but the relationship between rs16944 A/G and rs1143627 G/A and coronary artery lesions (CALs) in patients with KD has not been investigated. The present study is aimed at investigating whether the rs16944 A/G and rs1143627 G/A polymorphisms in IL-1B were associated with KD susceptibility and CALs in a southern Chinese population.Methods and Results: We recruited 719 patients with KD and 1401 healthy children. Multiplex PCR was used to assess the genotypes of single nucleotide polymorphisms (SNPs), including two SNPs of IL-1B, rs16944 A/G and rs1143627 G/A. According to the results, no significant association was observed between the IL-1B (rs16944 and rs1143627) polymorphisms and KD risk in the patients compared with the healthy controls in our southern Chinese population. However, in further stratified analysis, we found that children younger than 12 months with the rs16944 GG and rs1143627 AA genotypes of IL-1B had a higher risk of CALs than those with the AA/AG genotypes of rs16944 and GG/AG genotypes of rs1143627 (OR = 2.28, 95% CI = 1.32-3.95, P = 0.0032, adjusted OR = 2.33, 95% CI = 1.34-4.04, P = 0.0027).Conclusions: Our results indicated that there was no association between the rs16944 A/G and rs1143627 G/A gene polymorphisms and KD susceptibility. However, the rs16944 GG and rs1143627 AA genotypes of IL-1B may significantly impact the risk of CAL formation in children younger than 12 months, which may contribute to the pathogenesis of KD. These findings need further validation in multicenter studies with larger sample sizes. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Shale gas microscopic seepage mechanism under supercritical CO 2 condition is reviewed. • Adsorption potential theory provides a method for predicting shale gas production. • Desorption model needs to be considered simultaneously due to the hysteresis. • The diffusion between CO 2 and CH 4 should be considered in supercritical CO 2 mining. • Multi-component and multi-field coupling is a challenge for further research. Abstract Shale gas exploitation with supercritical CO 2 is a promising technology that not only improve gas recovery but also achieve geological storage of CO 2. This paper presents the research status of shale gas seepage mechanism under supercritical CO 2 conditions from several aspects including the adsorption and desorption of gas, the competitive adsorption of CO 2 and CH 4 , the multi-scale spatial gas mass transfer process and the shale gas seepage mechanism under multi-field coupling. Adsorption potential theory provides a method for predicting the real shale reservoir adsorption capacity under supercritical conditions. The desorption model needs to be considered simultaneously due to the existence of hysteresis. The adsorption selectivity of CO 2 /CH 4 is always greater than 1, and there is an optimal selectivity coefficient to optimize the in-situ process conditions. For the competitive adsorption mechanism, the reason why CO 2 adsorption capacity of shale is stronger than that of CH 4 is explained in terms of kinetic diameter, critical temperature, molecular polarity and diffusion rate. The interaction between CO 2 and CH 4 will make the shale gas seepage mechanism more complex, so further research is needed on the mass transfer process involving multi-component gas. The changes in reservoir physical properties after supercritical CO 2 fracturing, the mathematical model of multi-field fully coupled gas microscopic seepage and the universal stress-sensitive model are the focus of future research. [ABSTRACT FROM AUTHOR]

Objectives: To develop and validate a prognostic model of integrating whole-tumour apparent diffusion coefficient (ADC) from pretreatment diffusion-weighted (DW) magnetic resonance (MR) imaging with human papillomavirus (HPV) genotyping in predicting the overall survival (OS) and disease-free survival (DFS) for women with stage IB-IV cervical cancer following concurrent chemoradiotherapy (CCRT).Methods: We retrospectively analysed three prospectively collected cohorts comprising 300 patients with stage IB-IV cervical cancer treated with CCRT in 2007-2014 and filtered 134 female patients who underwent MR imaging at 3.0 T for final analysis (age, 24-92 years; median, 54 years). Univariate and multivariate Cox regression analyses were used to evaluate the whole-tumour ADC histogram parameters, HPV genotyping and relevant clinical variables in predicting OS and DFS. The dataset was randomly split into training (n = 88) and testing (n = 46) datasets for construction and independent bootstrap validation of the models.Results: The median follow-up time for surviving patients was 69 months (range, 9-126 months). Non-squamous cell type, ADC10 <0.77 × 10-3 mm2/s, T3-4, M1 stage and high-risk HPV status were selected to generate a model, in which the OS and DFS for the low, intermediate and high-risk groups were significantly stratified (p < 0.0001). The prognostic model improved the prediction significantly compared with the International Federation of Gynaecology and Obstetrics (FIGO) stage for both the training and independent testing datasets (p < 0.0001).Conclusions: The prognostic model based on integrated clinical and imaging data could be a useful clinical biomarker to predict OS and DFS in patients with stage IB-IV cervical cancer treated with CCRT.Key Points: • ADC 10 is the best prognostic factor among ADC parameters in cervical cancer treated with CCRT • A novel prognostic model was built based on histology, ADC 10 , T and M stage and HPV status • The prognostic model outperforms FIGO stage in the survival prediction. [ABSTRACT FROM AUTHOR]

Focal adhesion kinase (FAK) is a non‑receptor tyrosine kinase involved in the development and progression of cancer. However, the regulatory role of FAK in cell migration remains unclear. The aim of the present study was to investigate the mechanism underlying the regulation of melanoma cell migration by FAK. The effect of FAK knockdown on gene expression in B16F10 cells was examined by gene chip analysis. The expression levels of coiled‑coil domain containing 80 (CCDC80) and epithelial (E)‑cadherin were analyzed by reverse transcription quantitative polymerase chain reaction and western blotting. Wound healing and transwell assays were used to monitor B16F10 cell migration. It was identified that the knockdown of FAK increased the expression levels of CCDC80 and E‑cadherin, while the overexpression of CCDC80 elevated E‑cadherin expression. Concurrently, upregulation of CCDC80 inhibited the migration of B16F10 cells, and downregulation of CCDC80 promoted the migration of B16F10 cells. The clinical data from the Oncomine database also revealed that the mRNA level of FAK was increased while the mRNA levels of CCDC80 and E‑cadherin were decreased in patients with melanoma compared with normal controls. Taken together, the results of the present study suggest that the regulation of B16F10 melanoma cell migration by FAK is potentially mediated by CCDC80. [ABSTRACT FROM AUTHOR]

Purpose: This study is a retrospective analysis evaluating the efficacy and toxicity of combination chemotherapy with Paclitaxel (PTX) and Oxaliplatin (OXA) as first-line treatment for patients with advanced gastric cancer (AGC).Methods: One hundred and seven patients with locally advanced or metastatic gastric adenocarcinoma received intravenous infusions of PTX at 135 mg/m2 and OXA at 85 mg/m2 on day 1 every 14 days.Results: Among 107 patients enrolled, 9 patients could not be evaluated for a response because of the absence of any measurable lesions. Assessment of the response of 98 patients was made. The overall objective response rate was 42.9% (95% CI 32.9-52.8%), with two complete responses and 40 partial responses. The disease control was 79.6% (95% CI 71.5-87.7%). With 29 months of the median time of follow-up, the median progression-free survival was 5.8 months (95% CI 4.30-7.30 months) and the median overall survival was 11.5 months (95% CI 9.08-13.9 months). The 1-year survival rate was 48.0%. The most common grades 3 and 4 toxicities included neutropenia (32.7%), leucopenia (17.8%), fatigue (5.61%), and anemia (4.67%). Peripheral neuropathy occurred in 23.4% patients and grade 2 or higher peripheral neuropathy occurred in 12.1% of the patients.Conclusions: Combination chemotherapy with PTX and OXA offers a new, effective and safe regimen for patients with advanced gastric cancer. [ABSTRACT FROM AUTHOR]

The package delivery industry has become one of the more prominent industries worldwide, one which is indispensable to many people’s daily lives. Clients expect their packages to be delivered as promptly as possible, and to this end, leading delivery agencies like Amazon and DHL have begun to use drones for package delivery. Drones are aircraft or flying machines either controlled by trained pilots or which autonomously follow a pre-programmed route. However, companies using drones for deliveries have experienced several problems. In particular, package delivery time and tardiness must be minimized. This paper therefore focuses of the problem of minimizing delivery time and tardiness, proposing a Hybrid block-based edge recombination algorithm (HBERA) to solve the package delivery problem. The performance results of the proposed algorithm were compared with those of the edge recombination algorithm (ERX), showing that the proposed methodology’s computational result showed a clearly optimal group of solutions. In addition, HBERA also can be proved to be able to solve the multiple-objective problems. [ABSTRACT FROM AUTHOR]

Background: Cytotoxic T lymphocyte-mediated (CTL-mediated) severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), are rare but life-threatening adverse reactions commonly induced by drugs. Although high levels of CTL-associated cytokines, chemokines, or cytotoxic proteins, including TNF-α and granulysin, were observed in SJS-TEN patients in recent studies, the optimal treatment for these diseases remains controversial. We aimed to evaluate the efficacy, safety, and therapeutic mechanism of a TNF-α antagonist in CTL-mediated SCARs.Methods: We enrolled 96 patients with SJS-TEN in a randomized trial to compare the effects of the TNF-α antagonist etanercept versus traditional corticosteroids.Results: Etanercept improved clinical outcomes in patients with SJS-TEN. Etanercept decreased the SCORTEN-based predicted mortality rate (predicted and observed rates, 17.7% and 8.3%, respectively). Compared with corticosteroids, etanercept further reduced the skin-healing time in moderate-to-severe SJS-TEN patients (median time for skin healing was 14 and 19 days for etanercept and corticosteroids, respectively; P = 0.010), with a lower incidence of gastrointestinal hemorrhage in all SJS-TEN patients (2.6% for etanercept and 18.2% for corticosteroids; P = 0.03). In the therapeutic mechanism study, etanercept decreased the TNF-α and granulysin secretions in blister fluids and plasma (45.7%-62.5% decrease after treatment; all P < 0.05) and increased the Treg population (2-fold percentage increase after treatment; P = 0.002), which was related to mortality in severe SJS-TEN.Conclusions: The anti-TNF-α biologic agent etanercept serves as an effective alternative for the treatment of CTL-mediated SCARs.Trial Registration: ClinicalTrials.gov NCT01276314.Funding: Ministry of Science and Technology of Taiwan. [ABSTRACT FROM AUTHOR]

Osteosarcoma (OS) is the third most frequent type of cancer in adolescents and represents >56% of all bone tumors. In addition, metastatic OS frequently demonstrates resistance to conventional chemotherapy; thus, the development of novel therapeutic agents for the treatment of patients with metastatic OS is warranted. In the present study, the metabolic mechanisms underlying OS metastasis were investigated using a subpathway analysis method and lead to the identification of candidate drugs for the treatment of metastatic OS. Using the GSE14827 microarray dataset from the Gene Expression Omnibus database, 546 differentially expressed genes were identified between samples from patients with OS who did or did not develop metastatic OS. Furthermore, nine significantly enriched metabolic subpathways were identified, which may be involved in OS metastasis. Finally, using an integrated analysis of metastatic OS-associated subpathways and drug-affected subpathways, 98 small molecule drug candidates capable of targeting the metastatic OS-associated subpathways were identified. This method identified existing anti-cancer drugs, including semustine, in addition to predicting potential drugs, such as lansoprazole, for the treatment of metastatic OS. Transwell and wound healing assays demonstrated that lansoprazole reduced the invasiveness and migration of U2OS cells. These small molecule drug candidates identified through a bioinformatics approach may provide insights into novel therapy options for the treatment of patients with metastatic OS. [ABSTRACT FROM AUTHOR]

In this paper we study a flow shop problem F 2 → D | v = 1 , c ≥ 1 | C max with two machines and one transporter: machines A , B and a transporter V which is initially located at machine B . There are a set of jobs needed to be processed on machine A first, then on machine B , and transported to the destination by V finally. Transporter V can carry at most c jobs in one batch where c ≥ 1 . The objective is to minimize the completion time when all the jobs are transported to the destination. Problem F 2 → D | v = 1 , c = 2 | C max has been proved to be binary NP-hard in EJOR2007 [20] when c = 2 , we solve the open question in [20] and prove it is strongly NP-hard, i.e., there is no FPTAS for the problem. [ABSTRACT FROM AUTHOR]

A new trinuclear Cu(II) cryptate ( 1 ) was synthesized and characterized by Infrared (IR) spectroscopy, single-crystal, powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), UV–Vis spectra and electrospray mass spectra (ES-MS). Interestingly, there is one bidentate carbonate group formed by fixation of atmosphere CO 2 in the trinuclear unit. The magnetic susceptibility measurements of the sample indicated strong antiferromagnetic coupling between the Cu(II) centers mediated by the bridging hydroxyl groups in the cryptate. [ABSTRACT FROM AUTHOR]

The electrically conductive nanocomposites composing of different concentrations (0.05–1.5 wt%) of reduced graphene oxide (RGO) in the thermoplastic polyurethane/polypropylene (TPU/PP, 55/40) matrix with a fine co-continuous structure were fabricated by solution-flocculation and melt-mixing process using a micron twin-screw extruder. Both thermodynamic and kinetic theoretical analysis predicated the preferential location of RGO in the TPU rather than PP phase. Both optical microscope and field emission scanning electron microscopy (FESEM) observations verified this theoretical dispersion predication. The homogeneous dispersion of RGO in the TPU matrix is confirmed by wide-angle X-ray diffraction (WAXD) patterns and transmission electron microscope (TEM) observation. A very low percolation threshold of 0.054 wt% was achieved owing to high conductivity of RGO and favorable double percolation effect. The tensile strength and elongation at break of the composites with RGO content of only 0.5 wt% were improved by 341.9% and 354.3%, respectively. The present work provides a guideline for an efficient, facile fabrication technique of graphene based conductive polymer nanocomposites with high electrical conductivity and improved mechanical properties. [ABSTRACT FROM AUTHOR]

Background: Apolipoprotein E (ApoE) is a major lipid carrier that supports lipid transport and injury repair in the brain. The APOE ϵ4 allele is associated with depression, mild cognitive impairment (MCI) and dementia; however, the precise molecular mechanism through which ApoE4 influences the risk of disease development remains unknown. To address this gap in knowledge, we investigated the potential effects of chronic unpredictable mild stress (CUMS) on ApoE3 and ApoE4 target replacement (ApoE3-TR and ApoE4-TR) mice. Results: All ApoE-TR mice exposed to CUMS at 3 months old recovered from a depression-like state by the age of 12 months. Of note, ApoE4-TR mice, unlike age-matched ApoE3-TR mice, displayed impaired spatial cognitive abilities, loss of GABAergic neurons, decreased expression of Reelin, PSD95, SYN and Fyn, and reduced phosphorylation of NMDAR2B and CREB. Conclusion: These results suggest that early-life stress may mediate cognitive impairment in middle-age ApoE4-TR mice through sustained reduction of GABAergic neurons and Reelin expression, which might further diminish the activation of the Fyn/NMDAR2B signaling pathway. [ABSTRACT FROM AUTHOR]

To ensure correct DNA replication, eukaryotes have signaling pathways that respond to replication-associated DNA damage and trigger repair. In both Saccharomyces cerevisiae and Schizosaccharomyces pombe, a complex of proteins, including the cullin protein Rtt101p and two adapter proteins Mms22p and Mms1p, is important for proper response to replication stress. We have investigated this system in Candida albicans. In this pathogen, Mms22p is important for recovery from DNA replication damage induced by agents including methylmethane sulfonate, camptothecin, and ionizing radiation. Although no clear ortholog of Mms1p has been identified in C. albicans, loss of either Mms22p or Rtt101p generates similar damage sensitivity, consistent with a common function. In S. cerevisiae, the Mrc1p2Csm3p2Tof1p complex stabilizes stalled replication forks and activates a replication checkpoint and interacts withMms22p. A similar complex in S. pombe, consisting of the Tof1p and Csm3p orthologs Swi1p and Swi3p, along with the fission yeast Mrc1p, genetically also interacts with Mms22p. Intriguingly in C. albicans only Mrc1p and Csm3p appear involved in damage repair, and Mms22p is required for responding to DNA damage agents in MRC1 or CSM3 conditional mutants. In C. albicans, although the loss of RAD57 greatly impairs response in the pathogen to many DNA-damaging agents, lethality due to camptothecin damage requires concomitant loss of Rad57p and Mms22p, suggesting that Mms22p is only essential for homologous recombination induced by camptothecin. These results establish that although C. albicans uses conserved cellular modules to respond to DNA damage and replication blocks, the specific details of these modules differ significantly from the S. cerevisiae model. [ABSTRACT FROM AUTHOR]

Resistivity–temperature characteristics of conductive multi-walled carbon nanotubes (MWCNT)/epoxy (EP) composite were studied during a heating-cooling run (HCR) with different top test temperatures. The values of R e (room-temperature resistance at the end of a HCR) decrease with increasing the top test temperature. The fluctuation-induced tunneling conduction (FITC) and the hysteresis effect developing in MWCNT/EP composite are responsible for this fascinating phenomenon. In order to understand this result further, resistivity–temperature characteristic at different cooling rates was studied. The values of R e also decrease with rising the cooling rate. This paper provides an effective approach to acquire a tunable temperature sensor. [ABSTRACT FROM AUTHOR]

Denitrification is an important process of nitrogen removal in lake ecosystems. However, the importance of denitrification across the entire soil-depth gradients including subsurface layers remains poorly understood. This study aims to determine the spatial pattern of soil denitrification enzyme activity (DEA) and its environmental determinants across the entire soil depth gradients in the raised fields in Baiyang Lake, North China. In two different zones of the raised fields (i.e., water boundary vs. main body of the raised fields), the soil samples from −1.0 m to 1.1 m depth were collected, and the DEA and following environmental determinants were quantified: soil moisture, pH, total nitrogen (TN), ammonia nitrogen (NH-N), nitrate nitrogen (NO-N), total organic carbon (TOC), and rhizome biomass of Phragmites australis. The results showed that the soil DEA and environmental factors had a striking zonal distribution across the entire soil depth gradients. The soil DEA reached two peak values in the upper and middle soil layers, indicating that denitrification are important in both topsoil and subsurface of the raised fields. The correlation analysis showed that the DEA is negatively correlated with the soil depth ( p < 0.05). However, this phenomenon did not occur in the distance to the water edge, except in the upper layers (from 0.2 m to 0.7 m) of the boundary zone of the raised fields. In the main body of the raised fields, the DEA level remained high; however, it showed no significant relationship with the distance to the water edge. The linear regression analysis showed significant positive correlation of the DEA with the soil TN, NO-N, NH-N, and TOC; whereas it showed negative correlation with soil pH. No significant correlations with soil moisture and temperature were observed. A positive correlation was also found between the DEA and rhizome biomass of P. australis. [ABSTRACT FROM AUTHOR]

The key parameter to determine whether jadeitite can be named gem grade jadeitite 'jadeite jade' or not is the content (the mass fraction) of jadeite in jadeitite. So far, most methods to determine the mass fraction of mineral in rock are destructive, which is not suitable in gem detection. Based on the changes of mineral composition and mass fraction of mineral in jadeitite, a non-destructive method by measuring the relative density of jadeitite was established in order to get the mass fraction of jadeite. By Static Water Density Method, 186 pieces of jadeitite samples with relative densities of 3.30 -2.88 were divided into groups according to different densities. The main mineral composition and mass fraction of minerals in jadeitite were analyzed by X-ray Powder Diffraction, Manual Heavy-sand Analysis, Electron Probe Microanalysis, Infrared Spectrometry and Raman Spectrometry. The linear relationship between the mass fraction of jadeite and the relative density of jadeitite was statisticstically analyzed. Results show that the main minerals in jadeitite are e'adeite, albite, and analcite. As the mass fraction (wA) of jadeite decreases, those of albite and analcime increase, and the measured specific gravities (SG) of jadeitite change accordingly. The relationship between them is wA =1. 3454 SG -3. 4531 (r =0. 9814), showing a good linear dependence relation. Because the measured specific gravity of jadeitite is approximately equal to the theoretical one, mass fraction of jadeite is obtained by measuring the specific gravity of jadeitite. This nondestructive method applies to jadeitite with a specific gravity of 3. 3 -3.0, jadeite content of 95% -60%, and sum mass fractions of jadeite and albite of 90%-97%. [ABSTRACT FROM AUTHOR]

In recent years, quantitative evaluation for biosimilarity has been taken seriously due to the development of biosimilar products. The concept for assessment of biological products is very different from that of small-molecule drug products because of the variability with respect to the manufacturing process and environmental factors of the biological products. In this article, we propose an estimate method for a biosimilar index and the related lower bound based on the concept of reproducibility probability by assessing power. In addition, some approximations are proposed and compared in regard to simplicity and accuracy. [ABSTRACT FROM AUTHOR]

In this paper we study an online minimum makespan scheduling problem with a reordering buffer. We obtain the following results: (i) for m > 51 identical machines, we give a 1.5-competitive online algorithm with a buffer of size ⌈1.5m⌉; (ii) for three identical machines, we give an optimal online algorithm with a buffer size six, better than the previous nine; (iii) for m uniform machines, using a buffer of size m, we improve the competitive ratio from 2 + ε to 2 − 1/m+ ε, where ε > 0 is sufficiently small and m is a constant. [ABSTRACT FROM AUTHOR]

The area of fall-planted cover crop in China is quite low in paddy field, and multiple cropping index declines yearly, resulting in tremendous waste of soil resources. This reduction in fall-planted cover crop can lead to decrease in soil fertility. Most paddy field in southern China is suitable for growing winter green manure because of abundant light and heat resources. Winter green manure in general contains 15% - 20% of the organic matter. It can be used to improve soil nutrients cycling and facilitate the mineralization of soil organic matter. Comprehensive evaluation of green manures in different crop rotations in paddy fields of southern China region is needed in order to develop sustainable multiple cropping systems. The objective of this study was to determine the effect of green manure on different cropping systems (A: fallow-early rice-late rice→fallow-early rice-late rice (CK); B: milk vetch- rice- rice→rapeseed/peanut-rice; C: rapeseed/peanut- rice→ potato/maize+ soybean- rice; D: potato/maize+soybean- rice→vegetable/peanut+maize- rice; E: vegetable/peanut+maize- rice→milk vetch- ricerice) on soil nutrients, soil organic carbon, and carbon pool management indexes in southern China where two rice crops per year were common. The experiment was conducted during September 2011 - November 2013. Soil samples (at depths of 10-20 cm) were taken after rice was harvested in 2013 for analysis. The results showed that compared with CK, green manure rotation treatments had significantly (P<0.05) improved organic matter, alkaline hydrolytic nitrogen and available potassium by 8.73%-15.59%, 11.79%-19.64%, and 5.80%-37.19%, respectively. Soil organic of green manure rotation treatments of B and C were 15.59% and 11.19% higher (P<0.05) than CK. Soil active organic carbon of all green manure rotation treatments was 29.03%, 19.96%, 16.67% and 21.75% respectively higher (P<0.05) than CK. Compared with CK, the soil carbon pool index significantly (P<0.05) increased by 15.70% for the treatment B, and soil carbon management index significantly (P<0.05) increased by 32.07 for the treatment B, 21.98 for the treatment C, 18.64 for the treatment D and 24.47 for the treatment E, respectively. Among the treatments, milk vetch- rice- rice→rapeseed/peanut- rice had the highest values for the soil carbon pool index and soil carbon management index. The soil organic matter and total nitrogen, available phosphorus, total organic carbon, active organic carbon, and carbon pool management index were highly significantly (P<0.01) correlated. Soil total nitrogen, alkaline hydrolytic nitrogen, and available phosphorus had a significant (P<0.05) correlation with carbon pool management index. In addition, soil organic carbon was significantly (P<0.05) positively correlated with active organic carbon and carbon pool management indexes. Therefore, green manure rotation, especially milk vetch- rice- rice→rapeseed/peanut- rice could increase soil organic carbon contents and soil carbon pool management index, improve soil quality and soil fertility under the local soil fertility conditions, and was important for promoting sustainable development of agriculture. [ABSTRACT FROM AUTHOR]

Abstract: Systemic lupus erythematosus (SLE) is one of the common autoimmune diseases, with complex genetic components. Interleukin-21 (IL-21) is the most recently discovered member of the type-I cytokine family, which has a variety of effects on the immune system, including B cell activation, plasma cell differentiation, and immunoglobulin production. Previous studies have identified that IL-21 was associated with different autoimmune and inflammatory diseases, such as rheumatoid arthritis, multiple sclerosis and SLE. Variations in the DNA sequence in the IL-21 gene may lead to altered IL-21 production and/or activity, and thus this can modulate an individual's susceptibility to SLE. To test this hypothesis, we investigated the association of the IL-21 polymorphisms and its serum levels with the risk of SLE in a Chinese population. We analyzed three single nucleotide polymorphisms of IL-21 gene rs907715 C/T, rs2221903 T/C and rs2055979 C/A in 175 patients with SLE and 190 age- and sex-matched controls, using Snapshot SNP genotyping assays and DNA sequencing method. Soluble IL-21 (sIL-21) levels were measured by ELISA. There were significant differences in the genotype and allele frequencies of IL-21 gene rs2055979 C/A polymorphism between the group of patients with SLE and the control group (P <0.05). sIL-21 levels were increased in patients with SLE compared with controls (P <0.01). Moreover, genotypes carrying the IL-21 rs2055979 A variant allele were associated with increased IL-21 levels compared to the homozygous wild-type genotype in patients with SLE. The rs2055979 C/A polymorphism of IL-21 and its sIL-21 levels were associated with SLE in the Chinese population. Our data suggests that IL-21 gene may play a role in the development of SLE. [Copyright &y& Elsevier]

Abstract: In this paper, we study a two-dimensional knapsack problem: packing squares as many as possible into a unit square. Our results are the following: [(i)] we propose an algorithm called IHS (Increasing Height Shelf), and prove that the packing is optimal if in an optimal packing there are at most 5 squares, and this upper bound is sharp; [(ii)] if all the squares have side length at most , we propose a simple and fast algorithm with an approximation ratio in time ; [(iii)] we give an EPTAS for the problem, where the previous result in Jansen and Solis-Oba (2008) [16] is a PTAS, not an EPTAS. However our approach does not work on the previous model of Jansen and Solis-Oba (2008) [16], where each square has an arbitrary weight. [Copyright &y& Elsevier]

Objectives: The postoperative outcomes of patients with oral cavity squamous cell carcinoma (OCSCC) vary greatly. To improve risk stratification, we sought to identify genetic biosignatures by whole-exome sequencing (WES).Materials and Methods: We retrieved patients with OCSCC patients with paired freshly frozen malignant and non-malignant tissue specimens and performed WES by Illumina HiSeq4000 platform. We further applied a tree-based method to analyze copy number variations and obtain signature classification and driver-gene identification. We further confirmed the prognostic impact of the WES biosignature in an external independent validation set.Results: We examined 168 paired samples from patients with surgically treated OCSCC. Similar to the literature, the most commonly mutated genes were TP53 (66%), FAT1 (32%), and NOTCH1 (24%). The signatures 13 (APOBEC Cytidine deaminase [C > G]), 1 (spontaneous deamination of 5-methylcytosine), and 7 (UV exposure) showed the highest concordance rates. Using the MutSigCV, MuSiC, 20/20+, OncodriveFML, e-Driver, OncodriveCLUST, and tree-based methods, we identified a nine-gene OCSCC panel (RYR1, HLA-B, TSHZ2, PCDH17, DNAH17, GRID1, SBNO2, KSR2, and GCN1L1) predicting survival outcomes in our sample. We used the TCGA database to validate the prognostic value of the panel independently. Furthermore, gene-gene covariance analysis confirmed the coexistence of several gene alterations.Conclusion: We identified and independently validated a WES biosignature that predicts outcomes in surgically treated OCSCC in Taiwan, a betel-quid-chewing-prevent area. We proposed that the panel might help clinical trial designation for adjuvant therapy based on the risk stratification from the novel gene panel and identify targets for liquid biopsy monitoring during surveillance. [ABSTRACT FROM AUTHOR]

Background: Post-stroke depression (PSD) is one of the most common neuropsychiatric complications after stroke. The occurrence, development and prognosis of PSD have long been different between males and females. The main purpose of this study was to explore the influencing factors of PSD at 3 months in males and females, and construct random forest (RF) models to rank the influencing factors. Methods: This is a prospective multicenter cohort study (Registration number: ChiCTR-ROC-17013993). Stroke patients hospitalized in the department of Neurology of three hospitals in Wuhan were enrolled from May 2018 to August 2019. Scale assessments were performed 24 hours after admission and 3 months after stroke onset. Binary logistic regression analysis was used for univariate and multivariate (stepwise backward method) analysis, when p was less than 0.05, the difference between groups was considered statistically significant. Lastly, the RF models were constructed according to the results of multivariate regression analysis. Results: This study found that several baseline variables were associated with PSD at 3 months in males and females. RF model ranked them as stroke severity (OR [odds ratio] =1.17, p < 0.001, 95%CI [confidence interval]:1.11–1.24), neuroticism dimension (OR = 1.06, p = 0.002, 95%CI:1.02–1.10), physical exercise (OR = 0.62, p = 0.007, 95%CI:0.44–0.88), sleeping time < 5 h (OR = 1.91, p = 0.006, 95% CI:1.20–3.04) and atrial fibrillation (OR = 4.18, p = 0.012, 95%CI:1.38–12.68) in males. In females, RF model ranked them as psychological resilience (OR = 0.98, p = 0.015, 95%CI:0.96–1.00), ability of daily living (OR = 0.98, p = 0.001, 95%CI:0.97–0.99), neuroticism dimension (OR = 1.11, p = 0.002, 95%CI:1.04–1.18) and subjective support (OR = 1.11, p < 0.001, 95%CI:1.05–1.78). Conclusion: The study found influencing factors of PSD at 3 months were different in males and females, and construct RF models to rank them according to their importance. This suggests that clinicians should focus their interventions on sex-specific influencing factors in order to improve the prognosis of PSD patients. Trial registration: ChiCTR-ROC-17013993. [ABSTRACT FROM AUTHOR]

Unlike traditional small molecule (chemical) drug products, the development of biologic products is very different and variable with respect to the manufacturing process and environmental factors such as light and temperature. The complexity and heterogeneity of the molecular structure, complicated manufacturing process, different analytical methods, and possibility of severe immunogenicity reactions make quantitative evaluation of follow-on biologics a great challenge to both scientific community and regulatory agencies. In this article, we propose a general approach for development of a biosimilarity index based on the concept of reproducibility probability for quantitative evaluation of biosimilarity and interchangeability. The proposed method is robust regardless the biosimilarity criteria used and/or study design employed. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

In this work, we demonstrate the capability of controllingthe crystallographic orientation of ZnO nanostructure arrays grownalong nonpolar [11̅00] orientation. The Au catalyst was usedto initiate and guide the growth of ZnO nanostructures on (100) γ-LiAlO2substrate. The morphology, structure, and optical propertiesof the as-synthesized ZnO nanostructures were characterized by fieldemission scanning electron microscopy, X-ray diffraction, field emissiontransmission electron microscope, monochromatic cathodoluminescenceimage, and photoluminescence spectroscopy. The ZnO nanostructure arraysexhibited special shape and were aligned vertically on the (100) γ-LiAlO2substrate. A cooperative of Au-catalyzed VLS vertebral columngrowth along [11̅00] orientation, zinc-self-catalyzed VLS growthalong [0001], and ZnO VS lateral expansion growth process was proposedfor the special ZnO nanostructures. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, we consider an online non-preemptive scheduling problem on two related machines, where at most jobs are allowed to be rearranged, but only after all jobs have been revealed and (temporarily) scheduled. We minimize the makespan, and we call the problem as Online scheduling with bounded rearrangement at the end (BRE), which is a semi-online problem. Jobs arrive one by one over list. After all the jobs have been arrived and scheduled, we are informed that the input sequence is over; then at most already scheduled jobs can be reassigned. With respect to the worst case ratio, we close the gap between the lower bound and upper bound, improving the previous result as well. Especially, for the lower bound, (i) for an improved lower bound is obtained, which is better than (Liu et al. (2009) ); (ii) for , an improved lower bound is obtained, which is better than (Liu et al. (2009) ). For the upper bound, (i) for and , a new upper bound is obtained, which is optimal and better than the one in Liu et al. (2009) ; (ii) for and , an upper bound is proposed, which is optimal and better than the previous one in Liu et al. (2009) ; (iii) for and , an upper bound is obtained, which is also optimal and better than the previous one in Liu et al. (2009) . [Copyright &y& Elsevier]

Abstract: An experimental plasma chemical reactor, equipped with a novel water plasma torch, was used for reforming methane and carbon dioxide mixture to produce synthesis gas (syngas). Water plasma is generated by the torch at atmospheric pressure, in the absence of carrier gases, water cooling system and special steam supply system. The influence of the ratio of CO2 to CH4 and total feed gas rate on syngas production, composition and energy conversion efficiency were investigated. Compared to other plasma technologies, the higher reaction performance was obtained by the novel water plasma process. The results show that, under optimum experimental conditions, the energy conversion efficiency reaches up to maximum value of 1.87 mmol/kJ and the highest energy efficiency of 74.63% is achieved, which is higher than that of other plasma processes. Furthermore, the obtained syngas with high mole ratio of H2 to CO (close to 2) is suitable for the direct industrial application. [Copyright &y& Elsevier]

Three new phenylpropanoid compounds, named nervolans A–C 1–3, resp., together with two other known phenylpropanoids, coniferyl diangelate and sinapyl diangelate, were isolated from the aerial parts of Inula nervosaWall. Asteraceae, a traditional Chinese medicinal plant. The structures of 1–3were elucidated by detailed spectroscopic analyses, including HRESIMS data and 2DNMR spectroscopy. Compounds 1–5exhibited mild inhibitory effects against NO production in LPSstimulated RAW264.7 cells. [ABSTRACT FROM AUTHOR]

Arsenic (As) contaminated soils and waters are becoming major global environmental and human health risks. The identification of natural hyperaccumulators of As opens the door for phytoremediation of the arsenic contaminant. Pteris vittata is the first identified naturally evolving As hyperaccumulator. More than a decade after its discovery, we have made great progress in understanding the uptake, transport, and detoxification of As in the fern. The molecular mechanisms controlling As accumulation in P. vittata are now beginning to be recognized. In this review, we will try to summarize what we have learned about this As accumulator, with particular emphasis on the current knowledge of the physiological and molecular mechanisms of arsenic phytoremediation. We also discuss the potential strategies to further enhance phytoextraction abilities of P. vittata. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the effect of Candida albicans mitochondrial respiratory status on antifungal azole susceptibility. [ABSTRACT FROM PUBLISHER]

Abstract: A great deal of research has been done on production planning and sourcing problems, most of which concern deterministic or stochastic demand and cost situations and single period systems. In this paper, we consider a new class of multi-period production planning and sourcing problem with credibility service levels, in which a manufacturer has a number of plants and subcontractors and has to meet the product demand according to the credibility service levels set by its customers. In the proposed problem, demands and costs are uncertain and assumed to be fuzzy variables with known possibility distributions. The objective of the problem is to minimize the total expected cost, including the expected value of the sum of the inventory holding and production cost in the planning horizon. Because the proposed problem is too complex to apply conventional optimization algorithms, we suggest an approximation approach (AA) to evaluate the objective function. After that, two algorithms are designed to solve the proposed production planning problem. The first is a PSO algorithm combining the AA, and the second is a hybrid PSO algorithm integrating the AA, neural network (NN) and PSO. Finally, one numerical example is provided to compare the effectiveness of the proposed two algorithms. [Copyright &y& Elsevier]

Abstract: Quality by design (QbD) principles were explored to maximize the understanding of the unit operation of microfluidization, for the preparation of nanosuspensions using indomethacin as a model drug. The effects of key formulation and process variables (drug concentration, stabilizer type, stabilizer concentration, temperature, milling time and microfluidization pressure) were investigated by executing a 2(5−1) factorial design. Particle size, zeta potential and the physical form of the drug constituted the critical quality attributes (CQAs). Multiple linear regression analysis and ANOVA were employed to identify and estimate the effect of important parameters, establish their relationship with CQAs, create design space and model the process of microfluidization for predictive purposes. In order of importance, milling time, microfluidization pressure, stabilizer type, temperature and stabilizer concentration were identified as critical parameters affecting the formation and stability of nanosuspensions. Interaction between homogenization pressure, temperature and milling time also significantly affected the nanosuspension particle size. No correlation was found between the zeta potential and the storage stability. No change in the physical form of indomethacin was observed on storage for 28 days at 4°C and 25°C. This research highlights the level of understanding that can be accomplished through a well designed study based on the philosophy of QbD. [Copyright &y& Elsevier]

Localized radiotherapy (RT) induces an immunogenic antitumor response that is in part counterbalanced by activation of immune evasive and tissue remodeling processes, e.g., via upregulation of programmed cell death-ligand 1 (PD-L1) and transforming growth factor β (TGF-β). We report that a bifunctional fusion protein that simultaneously inhibits TGF-β and PD-L1, bintrafusp alfa (BA), effectively synergizes with radiotherapy, leading to superior survival in multiple therapy-resistant murine tumor models with poor immune infiltration. The BA + RT (BART) combination increases tumor-infiltrating leukocytes, reprograms the tumor microenvironment, and attenuates RT-induced fibrosis, leading to reconstitution of tumor immunity and regression of spontaneous lung metastases. Consistently, the beneficial effects of BART are in part reversed by depletion of cytotoxic CD8+ T cells. Intriguingly, targeting of the TGF-β trap to PD-L1+ endothelium and the M2/lipofibroblast-like cell compartment by BA attenuated late-stage RT-induced lung fibrosis. Together, the results suggest that the BART combination has the potential to eradicate therapy-resistant tumors while sparing normal tissue, further supporting its clinical translation. [Display omitted] • BA synergizes with RT to overcome tumor immune evasion via TME reprogramming • Reconstitution of tumor immunosurveillance by BART induces abscopal effects • In fibrotic lungs, PD-L1+ endothelial cells and M2-like lipofibroblasts express TGF-β • BA attenuates lung fibrosis by neutralizing TGF-β in the relevant PD-L1+ compartments Lan et al. demonstrate that tumor microenvironment reprogramming and immune activation via bintrafusp alfa (BA; targeting PD-L1 and TGF-β) and radiation therapy (RT) synergize to eradicate therapy-resistant tumors. Moreover, BA ameliorates RT-induced lung fibrosis. Clinical translation of BART may overcome inherent and acquired tumor resistance while sparing normal tissue from late toxicities. [ABSTRACT FROM AUTHOR]

Abstract: The photolysis of simulating low concentration of hydrogen sulfide malodorous gas was studied under UV irradiation emitted by self-made microwave discharge electrodeless lamps (i.e. microwave UV electrodeless mercury lamp (185/253.7nm) and iodine lamp (178.3/180.1/183/184.4/187.6/206.2nm)). Experiments results showed that the removal efficiency () of hydrogen sulfide was decreased with increasing initial H2S concentration and increased slightly with gas residence time; H2S removal efficiency was decreased dramatically with enlarged pipe diameter. Under the experimental conditions with pipe diameter of 36mm, gas flow rate of 0.42standardls−1, was 52% with initial H2S concentration of 19.5mgm−3 by microwave mercury lamp, the absolute removal amount (ARA) was 4.30μgs−1, and energy yield (EY) was 77.3mgkWh−1; was 56% with initial H2S concentration of 18.9mgm−3 by microwave iodine lamp, the ARA was 4.48μgs−1, and the EY was 80.5mg kWh−1. The main photolysis product was confirmed to be with IC. [Copyright &y& Elsevier]

Safe incineration of harvested hyperaccumulators containing high content of heavy metals to avoid secondary environmental pollution is a problem for popularizing phytoremediation technology. The As volatilization behavior and its mechanism during incineration of Pteris vittata, an As-hyperaccumulator, was investigated. Incineration results reveal that 24% of total As accumulated by P. vittata (H-As) containing high As content (1170 mg/kg) is emitted at 800 °C, of which 62.5% of the total emitted As is volatilized below 400 °C. A study of the extended X-ray absorption fine structure (EXAFS) shows that part of As(III) was identified in the thermal decomposition residue of dried P. vittata (H-As), As2O5 + P. vittata (L-As) containing low As content (14.7 mg/kg), and As2O5 + charcoal (C) at 200 °C, suggesting that carbon originating from biomass incineration might catalyze As(V) reduction. This speculation was tested through thermogravimetric experiments, in which either C or P. vittata (L-As) markedly catalyzed the volatilization of pure As2O5 at low temperature. Therefore, the reduction of As(V) to As(III) is responsible for As volatilization during incineration of P. vittata below 400 °C. This study provides important insights into As behavior during incineration of As-hyperaccumulators, which is helpful to safely dispose harvested biomass with high As content. [ABSTRACT FROM AUTHOR]

Abstract: The cytokine interleukin-8 (IL-8) may play a role in the pathogenesis of nasopharyngeal carcinoma (NPC) through the modulation of tumor immune response or enhanced angiogenesis. Polymorphism of IL-8 gene, which may affect the production level of cytokine, has been inversely associated with a number of cancers. To test this hypothesis, we investigated the relationship of IL-8 gene polymorphisms and NPC in a Chinese population. We analyzed single nucleotide polymorphisms (SNPs) of IL-8 gene −845 T/C, −738 T/A, −353 A/T, −251 A/T and +678 T/C in 280 patients with NPC and 290 age and sex matched controls, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and polymerase chain reaction-sequence specific primers method (PCR-SSP). There were significant differences in the genotype and allele distribution of −251 A/T polymorphism of the IL-8 gene among cases and controls. The −251 AA and AT genotypes were associated with a significantly increased risk of NPC as compared with the −251 TT genotypes (OR=1.820, 95% CI, 1.120–2.959, P =0.015 and OR=1.590, 95% CI, 1.104–2.290, P =0.013, respectively). Haplotype analysis revealed that the homozygosity of the AAT haplotype (defined by SNPs at positions −353, −251 and +678) of IL-8 gene conveys the highest risk for NPC compared with the homozygosity for the TTC haplotype (OR=1.396; 95% CI, 1.064–1.831; P =0.016). The −251 A/T polymorphism of IL-8 and its haplotype are associated with NPC in a Chinese population. Our data suggests that IL-8 gene may play a role in the development of NPC. [Copyright &y& Elsevier]

The difference between the surface and the bulk shell of CexPr1-xO2-mixed oxides was studied by Raman spectroscopy with four different excitation lasers. Two Raman peaks appear at 465 and 570 cm-1under all of the four lasers. The former is attributed to the Raman active F2gmode of CeO2, while the latter is attributed to oxygen vacancy. On the basis of the fact that the laser with shorter wavelength is closer to the electronic adsorption of samples, it is found that the Raman information detected by excitation laser with shorter wavelength is more sensitive to the surface region of samples. An inflection is observed in the relationship of the value I570/I465to the Ce content in CexPr1-xO2-. With the increase in the wavelength of excitation laser, the Ce content corresponding to the inflection decreases. Combined with the surface concentration obtained by XPS, it can be deduced that the composition of CexPr1-xO2-mixed oxide particles in the surface region and the bulk shell are different, the former is enrichment of Pr component and the latter is enrichment of Ce component. The thickness of the surface layer with rich Pr component decreases with the increase in the Ce content. [ABSTRACT FROM AUTHOR]

Abstract: Diglycidyl ether of 4,4′-dihydroxybiphenol (BPDGE) is a liquid crystalline epoxy. The biphenyl epoxy (diglycidyl ether of 3,3′,5,5′-tetramethyl-4,4′-biphenyl, TMBPDGE) has found great applications in plastic encapsulated semiconductor packaging. Phenol novolac (PN) was used as curing agent. The reaction kinetics of BPDGE/PN and TMBPDGE/PN systems in the presence of triphenylphosphine (TPP) were characterized by an isoconversional method under dynamic conditions using differential scanning calorimetry (DSC) measurements. The results showed that the curing of epoxy resins involves different reaction stages and the values of activation energy are dependent on the degree of conversion. The effects of curing temperature on their phase structure have been investigated with polarized optical microscopy and Wide-angle X-ray diffraction. With proper curing process, BPDGE showed a nematic phase when cured with PN. [Copyright &y& Elsevier]

In flowering plants, penetration of the pollen tube through stigma, style, and transmitting tract is essential for delivery of sperm nuclei to the egg cells embedded deeply within female tissues. Despite its importance in plant reproduction, little is known about the underlying molecular mechanisms that regulate the navigation of the pollen tube through the stigma, style, and transmitting tract. Here, we report the identification and characterization of an Arabidopsis thaliana gene, VANGUARD1 (VGD1) that encodes a pectin methylesterase (PME)-homologous protein of 595 amino acids and is required for enhancing the growth of pollen tubes in the style and transmitting tract tissues. VGD1 was expressed specifically in pollen grain and the pollen tube. The VGD1 protein was distributed throughout the pollen grain and pollen tube, including the plasma membrane and cell wall. Functional interruption of VGD1 reduced PME activity in the pollen to 82% of the wild type and greatly retarded the growth of the pollen tube in the style and transmitting tract, resulting in a significant reduction of male fertility. In addition, the vgd1 pollen tubes were unstable and burst more frequently when germinated and grown on in vitro culture medium, compared with wild-type pollen tubes. Our study suggests that the VGD1 product is required for growth of the pollen tube, possibly via modifying the cell wall and enhancing the interaction of the pollen tube with the female style and transmitting tract tissues. [ABSTRACT FROM AUTHOR]

Background: Post-stroke depression (PSD) is one of the most common neuropsychiatric complications after stroke. Studies on the underlying mechanisms and biological markers of sex differences in PSD are of great significance, but there are still few such studies. Therefore, the main objective of this study was to investigate the association of biomarkers with PSD at 3 months after minor stroke in men and women. Methods: This was a prospective multicenter cohort study that enrolled 530 patients with minor stroke (males, 415; females, 115). Demographic information and blood samples of patients were collected within 24 h of admission, and followed up at 3 months after stroke onset. PSD was defined as a depressive disorder due to another medical condition with depressive features, major depressive-like episode, or mixed-mood features according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-V). Univariate analysis was performed using the chi-square test, Mann–Whitney U test, or t-test. Partial least-squares discriminant analysis (PLS-DA) was used to distinguish between patients with and without PSD. Factors with variable importance for projection (VIP) > 1.0 were classified as the most important factors in the model segregation. Results: The PLS-DA model mainly included component 1 and component 2 for males and females. For males, the model could explain 13% and 16.9% of the variables, respectively, and 29.9% of the variables in total; the most meaningful predictors were exercise habit and fibrinogen level. For females, the model could explain 15.7% and 10.5% of the variables, respectively, and 26.2% of the variables in total; the most meaningful predictors in the model were brain-derived neurotrophic factor (BDNF), magnesium and free T3. Fibrinogen was positively correlated with the Hamilton Depression Scale-17 items (HAMD-17) score. BDNF, magnesium, and free T3 levels were negatively correlated with the HAMD-17 score. Conclusions: This was a prospective cohort study. The most important markers found to be affecting PSD at 3 months were fibrinogen in males, and free T3, magnesium, and BDNF in females. Trial registration: ChiCTR-ROC-17013993. [ABSTRACT FROM AUTHOR]

Simple Summary: A comprehensive analysis based on mutational signatures and oncogenic signaling pathways to identify a specific subgroup of patients that had a significantly negative impact on both disease-free and overall survival in oral cavity squamous cell carcinoma (OCSCC) from whole exome-sequencing data. This analysis has revealed a variety of biologically relevant candidate target genes. Thirty percent of 165 tumors had multiple targetable alterations in multiple pathways. This suggests the complex interplay and crosstalk of oncogenic signaling pathways play an important role on the outcome of patients with OCSCC, and the candidate genes and pathways identified may include prognostic genetic biomarkers or therapeutic targets for OCSCC. Mutational profiling of patients' tumors has suggested that the development of oral cavity squamous cell carcinoma (OCSCC) is driven by multiple genes in multiple pathways. This study aimed to examine the association between genomic alterations and clinical outcomes in patients with advanced stages OCSCC to facilitate prognostic stratification. We re-analyzed our previous whole-exome sequencing data from 165 long-term follow-ups of stages III and IV patients with OCSCC. Their frequent mutations were mapped to 10 oncogenic signaling pathways. Clinicopathological risk factors, relapse, and survival were analyzed to identify the genetic factors associated with advanced OCSCC. Frequent genetic alterations included point mutations in TP53, FAT1, NOTCH1, CASP8, CDKN2A, HRAS, PIK3CA, KMT2B (also known as MLL4), and LINC00273; amplified segments in CCND1, EGFR, CTTN, and FGFR1; and lost segments in CDKN2A, ADAM3A, and CFHR1/CFHR4. Comprehensive analysis of genetic alterations revealed that subgroups based on mutational signatures had a significant negative impact on disease-free survival (p = 0.0005) and overall survival (p = 0.0024). Several important signaling pathways were identified to be frequently genetically altered in our cohort. A specific subgroup of patients with alterations in NOTCH, RTK/RAS/MAPK, and TGF-beta pathways that had a significantly negative impact on disease-free survival (p = 0.0009). Thirty percent of samples had multiple targetable mutations in multiple pathways, indicating opportunities for novel therapy. [ABSTRACT FROM AUTHOR]

Background: Failure of immunotherapy in high-grade serous ovarian cancer (HGSC) may be due to high levels of transforming growth factor-β (TGF-β) in ascites or tumour immune microenvironment (TIME). Here, we test whether coordinated blockade of TGF-β and PD-L1 with bintrafusp alfa (BA) can provoke anti-tumour immune responses in preclinical HGSC models. Methods: BA is a first-in-class bifunctional inhibitor of TGF-β and PD-L1, and was tested for effects on overall survival and altered TIME in syngeneic HGSC models. Results: Using a mouse ID8-derived HGSC syngeneic model with IFNγ-inducible PD-L1 expression, BA treatments significantly reduced ascites development and tumour burden. BA treatments depleted TGF-β and VEGF in ascites, and skewed the TIME towards cytotoxicity compared to control. In the BR5 HGSC syngeneic model, BA treatments increased tumour-infiltrating CD8 T cells with effector memory and cytotoxic markers, as well as cytolytic NK cells. Extended BA treatments in the BR5 model produced ∼50% BA-cured mice that were protected from re-challenge. These BA-cured mice had increased peritoneal T-effector memory and NK cells compared to controls. Conclusions: Our preclinical studies of BA in advanced ovarian cancer models support further testing of BA as an improved immunotherapy option for patients with advanced ovarian cancer. [ABSTRACT FROM AUTHOR]