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We have demonstrated a single‐crystal‐to‐single‐crystal (SCSC) transformation from a two‐dimensional noninterpenetrated layer to a microporous three‐dimensional fourfold interpenetrated MOF. The centrosymmetric [Co2(μ2‐OH)(EIBA)3]n (SNUT‐25) transforms into a microporous [Co(EIBA)2]n (SNUT‐26), which is triggered by the reaction time with DMF that acts as a structure‐directing agent (HEIBA = 4‐(2‐ethyl‐1H‐imidazol‐1‐yl)benzoic acid; DMF = N,N′‐dimethylformamide). Despite the distinct structure and coordination arrangements of SNUT‐25 in contrast to SNUT‐26, both Co‐MOFs were synthesized using the same ligand. Fascinatingly, upon introducing a specific quantity of DMF combined with a negligible proportion of nitric acid, SNUT‐25 will progressively and completely transform into SNUT‐26. Under the synergistic induction of solvent molecules and temperature, SNUT‐25 changed from the original two‐dimensional layered structure to the three‐dimensional pore structure of SNUT‐26. In addition, SNUT‐25 and SNUT‐26 are efficient photocatalysts for the degradation of organic dye methyl blue (MB) under visible light irradiation. Surprisingly, the degradation rates of both SNUT‐25 and SNUT‐26 can reach over 96%. In addition, SNUT‐25 and SNUT‐26 also exhibited high electrocatalytic oxygen evolution reaction. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies, with a notoriously dismal prognosis. As a competitive inhibitor of DNA synthesis, gemcitabine is the cornerstone drug for treating PDAC at all stages. The therapeutic effect of gemcitabine, however, is often hindered by drug resistance, and the underlying mechanisms remain largely unknown. It is unclear whether their response to chemotherapeutics is regulated by endocrine regulators, despite the association between PDAC risk and endocrine deregulation. Here, we show that prolactin receptor (PRLR) synergizes with gemcitabine in both in vitro and in vivo treatment of PDAC. Interestingly, PRLR promotes the expression of miR‐4763‐3p and miR‐3663‐5p, two novel miRNAs whose functions are unknown. Furthermore, the analysis of transcriptome sequencing data of tumors from lactating mouse models enriches the PPP pathway, a multifunctional metabolic pathway. In addition to providing energy, the PPP pathway mainly provides a variety of raw materials for anabolism. We demonstrate that two key enzymes of the pentose phosphate pathway (PPP), G6PD and TKT, are directly targeted by miR‐4763‐3p and miR‐3663‐5p. Notably, miR‐4763‐3p and miR‐3663‐5p diminish the nucleotide synthesis of the PPP pathway, thereby increasing gemcitabine sensitivity. As a result, PRLR harnesses these two miRNAs to suppress PPP and nucleotide synthesis, subsequently elevating the gemcitabine sensitivity of PDAC cells. Also, PDAC tissues and tumors from LSL‐KrasG12D/+, LSL‐Trp53R172H/+, and PDX1‐cre (KPC) mice exhibit downregulation of PRLR. Bisulfite sequencing of PDAC tissues revealed that PRLR downregulation is due to epigenetic methylation. In this study, we show for the first time that the endocrine receptor PRLR improves the effects of gemcitabine by boosting two new miRNAs that block the PPP pathway and nucleotide synthesis by inhibiting two essential enzymes concurrently. The PRLR‐miRNAs‐PPP axis may serve as a possible therapeutic target to supplement chemotherapy advantages in PDAC. [ABSTRACT FROM AUTHOR]

AbstractThis study compared the effects of megestrol acetate (MA) prophylactic (p-MA) versus reactive (r-MA) use for critical body-weight loss (>5% from baseline) during concurrent chemoradiotherapy (CCRT) in patients with advanced pharyngolaryngeal squamous cell carcinoma (PLSCC).Patients receiving CCRT alone in two phase-II trials were included for analyses. Both the p-MA and r-MA cohorts received the same treatment protocol at the same institution, and the critical body-weight loss, survival, and adverse event profiles were compared.The mean (SD) weight loss was 5.1% (4.7%) in the p-MA cohort (n = 54) vs. 8.1% (4.6%) in the r-MA cohort (n = 50) (p = .001). The percentage of subjects with body-weight loss >5% was 42.6% in the p-MA cohort vs. 68.0% in the r-MA cohort (p = .011). Tube feeding was needed in 22.2% of p-MA vs. 62.0% of r-MA patients (p < .001). Less neutropenia (26.0% vs. 70.0% [p < .001]) and a shorter duration of grade 3-4 mucositis (2.4 ± 1.4 vs. 3.6 ± 2.0 wk [p = .009]) were observed with p-MA treatment. Disease-specific survival, locoregional control, or distant metastasis-free survival did not differ. Less competing mortality from secondary primary cancer resulted in a better overall survival trend in the p-MA cohort.p-MA may reduce body-weight loss and improve adverse event profiles during CCRT for patients with PLSCC. [ABSTRACT FROM AUTHOR]

Identifying a means of effectively separating and adsorbing the harmful constituents from flue gas emissions is always crucial for the protection of human health and the environment. All-atom molecular dynamics were employed to analyze the dynamic behaviour of flue gas molecules in Au nanopores. The influences of various system temperatures, gas concentrations, and pore sizes on the adsorption conformation, diffusion coefficient, average adsorption energy, and adsorption probability of the flue gases inside an Au nanopore were examined. Results showed that when the temperature rose to 300∼400 K, the gaseous H2S constituent in the flue gas was swiftly adsorbed to the nanopore walls due to the strong H2S-Au interactions, enabling an effective separation of H2S from the flue gas. In addition, increases in pore size (d ≥ 40 Å) reduced the adsorption probability of CO2 and CO on the nanopore surfaces, which also promoted constituent separations of H2S from the flue gas. When the concentration of flue gas exceeded 6.6 mol/L, hydrogen bonds of H2O clusters and their networks entangled, impeding molecular diffusion and thereby reducing the functionality of nanopore-trapping molecules. The results presented in this paper provide a valuable reference for filter material design for flue gas depuration. [ABSTRACT FROM AUTHOR]

Extensive genome structure variations, such as copy number variations (CNVs) and presence/absence variations, are the basis for the remarkable genetic diversity of maize; however, the effect of CNVs on maize herbivory defense remains largely underexplored. Here, we report that the naturally occurring duplication of the maize 9-lipoxygenase gene ZmLOX5 leads to increased resistance of maize to herbivory by fall armyworms (FAWs). Previously, we showed that ZmLOX5-derived oxylipins are required for defense against chewing insect herbivores and identified several inbred lines, including Yu796, that contained duplicated CNVs of ZmLOX5, referred to as Yu796-2×LOX5. To test whether introgression of the Yu796-2×LOX5 locus into a herbivore-susceptible B73 background that contains a single ZmLOX5 gene is a feasible approach to increase resistance, we generated a series of near-isogenic lines that contained either two, one, or zero copies of the Yu796-2×LOX5 locus in the B73 background via six backcrosses (BC6). Droplet digital PCR (ddPCR) confirmed the successful introgression of the Yu796-2×LOX5 locus in B73. The resulting B73-2×LOX5 inbred line displayed increased resistance against FAW, associated with increased expression of ZmLOX5, increased wound-induced production of its primary oxylipin product, the α-ketol, 9-hydroxy-10-oxo-12(Z),15(Z)-octadecadienoic acid (9,10-KODA), and the downstream defense hormones regulated by this molecule, 12-oxo-phytodienoic acid (12-OPDA) and abscisic acid (ABA). Surprisingly, wound-induced JA-Ile production was not increased in B73-2×LOX5, resulting from the increased JA catabolism. Furthermore, B73-2×LOX5 displayed reduced water loss in response to drought stress, likely due to increased ABA and 12-OPDA content. Taken together, this study revealed that the duplicated CNV of ZmLOX5 quantitively contributes to maize antiherbivore defense and presents proof-of-concept evidence that the introgression of naturally occurring duplicated CNVs of a defensive gene into productive but susceptible crop varieties is a feasible breeding approach for enhancing plant resistance to herbivory and tolerance to abiotic stress. [ABSTRACT FROM AUTHOR]

Background: Little is known about the impact of the COVID-19 pandemic on patients with Parkinson's disease (PD) at different stages of the pandemic. This study aims to assess the lives and disease status of PD patients during the zero-COVID policy period and after ending the zero-COVID policy. Methods: This multicenter cross-sectional study included two online surveys among PD patients in China, from May 30 to June 30 in 2022 and from January 1 to February 28 in 2023, respectively. The survey questionnaires contained four sections: (1) status of COVID-19 infection; (2) impact on motor and non-motor symptoms; (3) impact on daily and social lives; and (4) impact on PD disease management. Results: A total of 1764 PD patients participated in the first online survey, with 200 patients having lockdown experience and 3 being COVID-19-positive (0.17%). In addition, 537 patients participated in the second online survey, with 467 patients having COVID-19 infection (86.96%). (1) During zero-COVID, all of the COVID-19-positive patients had mild symptoms of COVID-19 and no death was reported. After zero-COVID, 83.51% of the COVID-19-positive patients had mild symptoms. The overall death rate and inpatient mortality rate of COVID-19-positive PD patients were 3.21% and 30.00%, respectively. (2) During zero-COVID, 49.43% of PD patients reported worsening of PD-related symptoms (lockdown vs. unlockdown, 60.50% vs. 48.02%, P = 0.0009). After zero-COVID, 54.93% of PD patients reported worsening of PD-related symptoms (COVID-19 positive vs. COVID-19 negative, 59.31% vs. 25.71%, P < 0.0001). (3) During zero-COVID, 62.36% of patients felt worried, and 'limited outdoor activities' (55.39%) was the top reason for mental health problems. After zero-COVID, 59.03% of patients felt worried, with 'poor health' (58.10%) being the top reason. The PD patients tended to change their daily activities from offline to online, and their economic and caregiver burdens increased both during and after zero-COVID. (4) Most PD patients would like to choose online rehabilitation during (69.56%) and after zero-COVID (69.27%). The demand for online medication purchasing also increased during (47.00%) and after zero-COVID (26.63%). Conclusions: The COVID-19 pandemic aggravated the motor and non-motor symptoms of PD patients either during or after the zero-COVID policy period. The PD patients also experienced prominent mental health problems, changes in daily activities, and increases in economic and caregiver burdens. The COVID-19 pandemic has changed ways of PD management with increasing demands for online medication purchasing and rehabilitation. [ABSTRACT FROM AUTHOR]

Many active hydrogen recovery systems have been proposed for medium-to-large scale proton exchange membrane fuel cells (PEMFCs). However, relatively few passive solutions for hydrogen recovery in PEMFC systems of such size are available. Accordingly, the present study proposes a novel passive hydrogen recovery system incorporating two vacuum ejectors (one high-flow rate and one low-flow rate) for a 10 kW PEMFC. MATLAB/Simulink models are constructed of the PEMFC system and all its major components. The validity of the simulation model is confirmed via a comparison with the experimental data reported in the literature. Further simulations are then performed to investigate the effects of the fuel stack active area and working temperature on the hydrogen recirculation performance and hydrogen stoichiometric ratio. Overall, the results show that the proposed dual vacuum ejector system increases the fuel cell efficiency to 52.16% and maintains the average fuel cell efficiency at 52.12%. • Under a high flow rate of the secondary hydrogen gas stream, the recovery ratio increases with a lower active area of the PEMFC. • Hydrogen stoichiometric ratio both increase with an increasing temperature of the primary flow working fluid. • The dual passive hydrogen recovery system results in a maximum system efficiency of 52.16%. [ABSTRACT FROM AUTHOR]

The lifetime performance index is a process capability index that is commonly used for the evaluation of the durability of products in life testing and reliability analysis. In the context of multiple production lines, we introduce an overall lifetime performance index and explore the relationship between this comprehensive index and individual lifetime performance indices. For products with lifespans following the Rayleigh distribution in the ith production line, we delve into the maximum likelihood estimator and asymptotic distribution to derive both the individual and overall lifetime performance indices. By establishing a predetermined target for the overall lifetime performance index, we can determine the corresponding target for each individual lifetime performance index. The testing algorithmic procedure is proposed to ascertain whether the overall lifetime performance index has reached its target value based on the maximum likelihood estimator, accompanied by figures illustrating the analysis of test power. We found that there is a monotonic relationship for the test power with various structures of parameters. Finally, a practical illustration with one numeral example is presented to demonstrate how the testing procedure is employed to evaluate the capabilities of multiple production lines. [ABSTRACT FROM AUTHOR]

Although the asymmetric catalysis has made a spurt of progress, the use of chiral auxiliaries remains crucial in asymmetric synthesis due to both the reliability and versatility of the methods, and the predictability of stereochemistry of the reactions. Up to date, Evans' chiral non‐racemic oxazolidinone‐based asymmetric synthetic methodology is still widely used in asymmetric synthesis. More importantly, the Evans asymmetric synthetic methodology turned out to be a fruitful source of inspiration for the development of related asymmetric synthetic methodologies. However, although reviews on the application of Evans' asymmetric synthetic methodology in both organic synthesis and medicinal chemistry continually to appear in the literature, a comprehensive review dedicating to the extensions of Evans' chiral non‐racemic oxazolidinone‐based asymmetric methodology remains elusive. In this review, we summarize the extensions of the Evans asymmetric methodology, which cover: (1) the modification of the chiral oxazolidinone auxiliaries; (2) the extension of the Evans' asymmetric aldol reaction from Evans' syn‐aldol to other diastereomeric aldol adducts; (3) the extension of the asymmetric reaction types; (4) the extension of chiral imide‐type substrates to N‐alkenyl, N‐allenenyl and N‐alkynyl oxazolidinones; (5) the achiral oxazolidinone‐based asymmetric catalysis; (6) the catalytic transformation of Evans' products; and (7) the straightforward transformations of Evans' chiral products to other classes of compounds than the chiral carboxylic acids, esters, alcohols, and Weinreb amides. [ABSTRACT FROM AUTHOR]

Although cytarabine (AraC) has greatly contributed to improving the prognosis of patients with acute myeloid leukemia (AML), many patients developed drug resistance and eventually succumbed to AML. Thus, resistance to AraC is a major obstacle to improve the efficacy of chemotherapy in AML. Hence, this study aimed to demonstrate that artesunate (ART) can reliably induce cell death in vitro and block AraC resistance. AML cell lines resistant to AraC were first constructed by repeated dosing for 5 months. Further, we analyzed whether ART intervention affected the sensitivity of AraC-resistant cells to AraC by cell function experiments, mainly including CCK-8 to assess cell viability, flow cytometry to examine apoptosis, and Western blotting to measure the Janus kinase (JAK)/signal transducers and activators of transcription 3 (STAT3) pathway protein expression. Furthermore, whether JAK/STAT3 pathway knockdown has a blocking effect on the efficacy of ART was also assessed. Co-treatment of ART and AraC increased the sensitivity of AML cells to AraC. Also, it effectively reversed the resistance of AML cells to AraC that is shown by the significantly reduced proliferation and increased apoptosis rates. ART intervention suppressed the activation of the JAK/STAT3 signaling pathway in AraC-resistant AML cells, suggesting that the function of ART in reversing AraC resistance is indeed dependent on the JAK/STAT3 signaling pathway. In summary, ART enhanced the sensitivity of AML/AraC-resistant cells to AraC by modulating the JAK/STAT3 pathway. [ABSTRACT FROM AUTHOR]

During glycolysis, the muscle isoform of pyruvate kinase PKM2 produces ATP in exchange for dephosphorylation of phosphoenolpyruvate (PEP) into pyruvate. PKM2 has been considered as a tumor-promoting factor in most cancers, whereas the regulatory role of PKM2 during head and neck carcinogenesis remained to be delineated. PKM2 mRNA and protein expression was examined in head and neck tumorous specimens. The role of PKM2 in controlling cellular malignancy was determined in shRNA-mediated PKM2-deficient head and neck squamous cell carcinoma (HNSC) cells. In agreement with the results in other cancers, PKM2 expression is enriched in both mouse and human HNSC tissues. Nevertheless, PKM2 mRNA expression reversely correlated with tumor stage, and greater recurrence-free survival rates are evident in the PKM2high HNSC population, arguing that PKM2 may be tumor-suppressive. Multifaceted analyses showed a greater in vivo xenografic tumor growth and an enhanced cisplatin resistance in response to PKM2 loss, whereas PKM2 silencing led to reduced cell motility. At the molecular level, metabolic shifts towards mitochondrial metabolism and activation of oncogenic Protein kinase B (PKB/Akt) and extracellular signal-regulated kinase (ERK) signals were detected in PKM2-silencing HNSC cells. In sum, our findings demonstrated that PKM2 differentially modulated head and neck tumorigenicity via metabolic reprogramming. [ABSTRACT FROM AUTHOR]

A new zinc(II) metal organic framework has been obtained from the solvothermal assembly of 1,3,5-benzene tricarboxylate and 1,3-bis(imidazole)propane with zinc nitrate in DMAc–H2O (DMAc is N,N -dimethylacetamide), namely {[Zn2 (μ2-OH)(1,3-BIP)(BTC)]·DMAc·2H2O}n (SNUT-6). The product is characterized by single-crystal and powder X-ray diffraction, infrared spectroscopy, thermogravimetric analysis, and elemental analysis. The single-crystal X-ray diffraction reveals that SNUT-6 exhibits a 3D→3D two-fold interpenetrating framework. Furthermore, SNUT-6 demonstrates a highly efficient turn-off fluorescent detection ability for aniline in methanol and shows high sensitivity with a K sv value of 4.771 × 104 M−1. It also shows excellent photocatalytic degradation performance for a three-dye molecular model: rhodamine b, methyl orange, and methyl blue. [ABSTRACT FROM AUTHOR]

The high local electron density and efficient charge carrier separation are two important factors to affect photocatalytic activity, especially for the CO2 photoreduction reaction. However, the systematic studies on the structure‐functional relationship regarding the above two factors based on precisely structure model are rarely reported. Herein, as a proof‐of‐concept, we developed a new strategy on the evaluation of local electron density by controlling the relative electron‐deficient (ED) and electron‐rich (ER) intensity of monomer at a molecular level based on three rational‐designed vinylene‐linked sp2 carbon‐covalent organic frameworks (COFs). As expected, the as‐prepared vinylene‐linked sp2 carbon‐conjugated metal‐covalent organic framework (MCOFs) (VL‐MCOF‐1) with molecular junction exhibited excellent activities for CO2‐to‐HCOOH conversion (283.41 μmol g−1 h−1) and high selectivity of 97.1 %, much higher than the VL‐MCOF‐2 and g‐C34N6‐COF, which is due to the synergistic effect of the multi‐electronic metal clusters (Cu3(PyCA)3) (PyCA=pyrazolate‐4‐carboxaldehyde) as strong ER roles and cyanopyridine units as ED roles and active sites, as well as the boosted photo‐induced charge separation efficiency of vinyl connection and increased light utilization ability. These results not only provide a strategy for regulating the electron‐density distribution of photocatalysts at the molecular level but also offers profound insights for metal clusters‐based COFs to effective CO2 conversion. [ABSTRACT FROM AUTHOR]

The high local electron density and efficient charge carrier separation are two important factors to affect photocatalytic activity, especially for the CO2 photoreduction reaction. However, the systematic studies on the structure‐functional relationship regarding the above two factors based on precisely structure model are rarely reported. Herein, as a proof‐of‐concept, we developed a new strategy on the evaluation of local electron density by controlling the relative electron‐deficient (ED) and electron‐rich (ER) intensity of monomer at a molecular level based on three rational‐designed vinylene‐linked sp2 carbon‐covalent organic frameworks (COFs). As expected, the as‐prepared vinylene‐linked sp2 carbon‐conjugated metal‐covalent organic framework (MCOFs) (VL‐MCOF‐1) with molecular junction exhibited excellent activities for CO2‐to‐HCOOH conversion (283.41 μmol g−1 h−1) and high selectivity of 97.1 %, much higher than the VL‐MCOF‐2 and g‐C34N6‐COF, which is due to the synergistic effect of the multi‐electronic metal clusters (Cu3(PyCA)3) (PyCA=pyrazolate‐4‐carboxaldehyde) as strong ER roles and cyanopyridine units as ED roles and active sites, as well as the boosted photo‐induced charge separation efficiency of vinyl connection and increased light utilization ability. These results not only provide a strategy for regulating the electron‐density distribution of photocatalysts at the molecular level but also offers profound insights for metal clusters‐based COFs to effective CO2 conversion. [ABSTRACT FROM AUTHOR]

Four previously undescribed terpenoid glucosides, including one sesquiterpenoid di-glucoside (1), two new iridoid glucosides (2, 3), and a new triterpenoid tri-glucoside (4), were isolated from a 70% ethanol extract of the root of Gentiana macrophylla (Gentianaceae), along with eight known terpenoids. Their structures were determined by spectroscopic techniques, including 1D, 2D NMR, and HRMS (ESI), as well as chemical methods. The absolute configuration of compound 1 was determined by quantum chemical calculation of its theoretical electronic circular dichroism (ECD) spectrum. The sugar moieties of all the new compounds were confirmed to be D-glucose by GC analysis after acid hydrolysis and acetylation. Anti-pulmonary inflammation activity of the iridoids were evaluated on a TNF-α induced inflammation model in A549 cells. Compound 2 could significantly alleviate the release of proinflammatory cytokines IL-1β and IL-8 and increase the expression of anti-inflammatory cytokine IL-10. [ABSTRACT FROM AUTHOR]

Background: Nocturnal symptoms have a significant effect on the quality of life in Parkinson's disease (PD) patients. Objective: This study aimed to investigate the prevalence and associated factors of nocturnal symptoms in Chinese PD patients. Methods: This multicenter cross-sectional study included 1,500 patients with primary PD from 18 centers in China was carried out between February 2019 and February 2020. Questionnaires including Parkinson's disease sleep scale 2 (PDSS-2), Parkinson's disease questionnaire 8 (PDQ-8), Beck depression inventory (BDI), and generalized anxiety disorder scale 7 (GAD-7) were used to assess nocturnal symptoms, quality of life, depression, and anxiety. Results: Among 1,500 Chinese PD patients, 576 (38.4%) reported nocturnal symptoms. Of them, 59.2% were older than 65 years. The PDQ-8 total score was higher in patients with nocturnal symptoms (p < 0.01). Moderate and severe depression was reported more often in patients with nocturnal symptoms (p < 0.01), and the occurrence and severity of anxiety were higher as well (p < 0.01). Longer disease duration and higher Hoehn-Yahr (HY) stage were independently associated with nocturnal symptoms (p < 0.01). Education level, depression, disease course, HY stage, and nocturnal symptoms were related to the quality of life in Chinese PD patients (p < 0.01). Conclusion: Our study found that 38.4% of Chinese PD patients have nocturnal symptoms, even in early and mid-stage PD. Nocturnal symptoms were associated with worse quality of life and higher incidences of depression and anxiety. Nocturnal symptoms should be included in the assessment and care plan, especially in patients with longer disease courses and higher HY stages. [ABSTRACT FROM AUTHOR]

Foliage-feeding fall armyworm (FAW; Spodoptera frugiperda) and root-feeding western corn rootworm (WCR; Diabrotica virgifera virgifera) are maize (Zea mays L.) pests that cause significant yield losses. Jasmonic acid (JA) plays a pivotal defense role against insects. 12-oxo-phytodienoic acid (12-OPDA) is converted into JA by peroxisome-localized OPDA reductases (OPR). However, little is known about the physiological functions of cytoplasmic OPRs. Here, we show that disruption of ZmOPR2 reduced wound-induced JA production and defense against FAW while accumulating more JA catabolites. Overexpression of ZmOPR2 in Arabidopsis enhanced JA production and defense against beet armyworm (BAW; Spodoptera exigua). In addition, lox10opr2 double mutants were more susceptible than either single mutant, suggesting that ZmOPR2 and ZmLOX10 uniquely and additively contributed to defense. In contrast to the defensive roles of ZmOPR2 and ZmLOX10 in leaves, single mutants did not display any alteration in root herbivory defense against WCR. Feeding on lox10opr2 double mutants resulted in increased WCR mortality associated with greater herbivory-induced production of insecticidal death acids and ketols. Thus, ZmOPR2 and ZmLOX10 cooperatively inhibit the synthesis of these metabolites during herbivory by WCR. We conclude that ZmOPR2 and ZmLOX10 regulate JA-mediated resistance in leaves against FAW while suppressing insecticidal oxylipin synthesis in roots during WCR infestation. [ABSTRACT FROM AUTHOR]

Integrated land-sea development and protection are important for the sustainable development of coastal areas. To promote the transition from separate land-sea management to integrated land-sea governance, the scientific delineation of the integrated spatial zoning units of coastal watershed-nearshore waters is an important tool for integrated land-sea management. From the perspective of physical geography, this study uses digital hydrological analysis based on DEM data to determine the coastal basin range and generate multilevel watersheds and river networks using different thresholds, and establishes spatial correspondence among physical geospatial spaces, such as watershed zones, coastlines, and nearshore waters, after considering the boundaries of major estuaries and bays. On this basis, the coastal zone is divided into several integrated spatial zoning units of coastal watershed-nearshore waters, and a physical geography-based integrated spatial zoning method is developed to form a physical geography-based land-sea integrated spatial zoning scheme. This study conducted spatial heterogeneity research of the integrated spatial zoning units, from the perspectives of topography analysis, land use analysis, socioeconomic analysis of the watershed, sea use analysis, seawater quality analysis of the nearshore waters, and load pressure analysis of the watershed-nearshore waters. The elemental differences of zoning units are studied in detail, which can provide a data reference for establishing the relationship between watersheds and nearshore waters. Applying this research method to the Guangxi Zhuang Autonomous Region in China, where the land-sea linkage pattern is forming, can provide a spatial reference and scientific basis for land-sea integrated management for ecological protection and sustainable resource utilization in the coastal zone. [ABSTRACT FROM AUTHOR]

Peroxisome‐localized oxo‐phytodienoic acid (OPDA) reductases (OPR) are enzymes converting 12‐OPDA into jasmonic acid (JA). However, the biochemical and physiological functions of the cytoplasmic non‐JA producing OPRs remain largely unknown. Here, we generated Mutator‐insertional mutants of the maize OPR2 gene and tested its role in resistance to pathogens with distinct lifestyles. Functional analyses showed that the opr2 mutants were more susceptible to the (hemi)biotrophic pathogens Colletotrichum graminicola and Ustilago maydis, but were more resistant to the necrotrophic fungus Cochliobolus heterostrophus. Hormone profiling revealed that increased susceptibility to C. graminicola was associated with decreased salicylic acid (SA) but increased JA levels. Mutation of the JA‐producing lipoxygenase 10 (LOX10) reversed this phenotype in the opr2 mutant background, corroborating the notion that JA promotes susceptibility to this pathogen. Exogenous SA did not rescue normal resistance levels in opr2 mutants, suggesting that this SA‐inducible gene is the key downstream component of the SA‐mediated defences against C. graminicola. Disease assays of the single and double opr2 and lox10 mutants and the JA‐deficient opr7opr8 mutants showed that OPR2 negatively regulates JA biosynthesis, and that JA is required for resistance against C. heterostrophus. Overall, this study uncovers a novel function of a non‐JA producing OPR as a major negative regulator of JA biosynthesis during pathogen infection, a function that leads to its contrasting contribution to either resistance or susceptibility depending on pathogen lifestyle. [ABSTRACT FROM AUTHOR]

The prognostic value of the left atrial function index (LAFI) in acute ST segment elevation myocardial infarction (STEMI) patients treated with percutaneous coronary intervention (PCI) is unknown. This study sought to determine whether the LAFI predicts prognosis in STEMI patients treated with PCI. Patients with newly diagnosed STEMI who were treated with PCI in Hunan Provincial People's Hospital from March 2020 to October 2020 were prospectively enrolled. All patients underwent transthoracic echocardiography at baseline and follow-up. The endpoint events included rehospitalization due to unstable angina, nonfatal myocardial infarction, rehospitalization due to heart failure and cardiovascular death. A total of 156 STEMI patients treated with PCI were studied with a median follow-up of 14 months. Forty-eight patients had endpoint events. The LAFI had the highest area under the receiver operating characteristic curve (AUC) predicting the endpoint events, with an AUC of 0.90 (95% CI 0.84–0.94). Multivariate Cox analysis demonstrated that only the LAFI (HR: 0.91, 95% CI 0.87–0.96, P < 0.0001) was independently predictive of endpoint events. Kaplan‒Meier survival curves showed that patients with an LAFI ≤ 42.25 cm/cc/m2 had more events than patients with an LAFI > 42.25 cm/cc/m2 (HR: 19.15, 95% CI 8.90–41.21, P < 0.001). The LAFI is a strong and independent predictor of events in STEMI patients treated with PCI. [ABSTRACT FROM AUTHOR]

Simulations are performed to examine the performance of a vacuum ejector in the hydrogen recovery loop of a 10-kW PEMFC system. The simulations commence by examining the effects of the primary flow fluid pressure and secondary flow temperature on the recirculation ratio and hydrogen stoichiometric ratio. Further simulations are then performed to investigate the temperature, pressure, velocity and Mach number distributions within the ejector for various values of the primary flow inlet pressure and temperature. A prototype ejector is fabricated using a 3D printing technique. Experiments are performed to evaluate the gas tightness and gas recovery performance of the ejector under realistic operating conditions. The simulation results show that the recirculation ratio and hydrogen stoichiometric ratio increase with a decreasing primary flow inlet pressure and secondary flow inlet temperature. As the primary flow inlet pressure increases, the pressure, velocity, and Mach number in the mixing chamber increase, and the hydrogen recovery performance decreases. Furthermore, as the temperature of the primary fluid flow increases, the stability of the isentropic flow condition within the ejector is enhanced. The experimental results show that the prototype vacuum ejector has a maximum gas leakage of just 0.7 psi and a minimum hydrogen recirculation rate of 59.3%. Consequently, it has significant potential for passive hydrogen recovery in large-scale fuel cell systems. • The recirculation ratio and hydrogen stoichiometric ratio have values of 79.2% and 1.43. • Hydrogen stoichiometric ratio increase as the temperature of the secondary gas flow increases. • A lower primary fluid inlet pressure results in a more stable isentropic flow condition within the mixing chamber. • The maximum gas leakage of the prototype SS316L vacuum ejector is 0.7 psi. [ABSTRACT FROM AUTHOR]

Background: Rabies, caused by the rabies virus (RABV), is an ancient and neglected zoonotic disease posing a large public health threat to humans and animals in developing countries. Immunization of animals with a rabies vaccine is the most effective way to control the epidemic and the occurrence of the disease in humans. Therefore, the development of cost-effective and efficient rabies vaccines is urgently needed. The activation of dendritic cells (DCs) is known to play an important role in improving the host immune response induced by rabies vaccines. Methodology/Principal findings: In this study, we constructed a recombinant virus, rCVS11-MAB2560, based on the reverse genetic system of the RABV CVS11 strain. The MAB2560 protein (a DC-targeting molecular) was chimeric expressed on the surface of the viral particles to help target and activate the DCs when this virus was used as inactivated vaccine. Our results demonstrated that inactivated rCVS11-MAB2560 was able to promote the recruitment and/or proliferation of DC cells, T cells and B cells in mice, and induce good immune memory after two immunizations. Moreover, the inactivated recombinant virus rCVS11-MAB2560 could produce higher levels of virus-neutralizing antibodies (VNAs) in both mice and dogs more quickly than rCVS11 post immunization. Conclusions/Significance: In summary, the recombinant virus rCVS11-MAB2560 chimeric-expressing the molecular adjuvant MAB2560 can stimulate high levels of humoral and cellular immune responses in vivo and can be used as an effective inactivated rabies vaccine candidate. Author summary: Due to the lack of effective treatments and drugs, rabies is still an important zoonotic disease, posing a great risk to animals and human public health in developing countries. Vaccines, especially inactivated vaccines, are currently the most effective way to prevent and control the rabies epidemic. Here, we constructed a recombinant virus rCVS11-MAB2560 chimeric-expressed MAB2560 protein (a DC-targeting molecular) on the surface of the RABV particles to promote its immunogenicity in vivo by activating the dendritic cells (DCs) and enhancing antigen uptake. Our results showed that inactivated rCVS11-MAB2560 was able to promote the recruitment and/or proliferation of DC cells, T cells and B cells in mice, and induce good immune memory after two immunizations. Moreover, compared with rCVS11, the inactivated recombinant virus rCVS11-MAB2560 could induce higher level of virus-neutralizing antibodies (VNAs) in mice and dogs more quickly post immunization. rCVS11-MAB2560 thus has potential to be used as a promising candidate for an effective inactivated rabies vaccine. [ABSTRACT FROM AUTHOR]

A new protocol for the direct transformation of secondary amides (N -acyl- o -xenylamines) to phenanthridines under mild conditions is reported. The method features trifluoromethanesulfonic anhydride (Tf2 O)/2-fluoropyridine as the efficient amide activation system and MeCN or CH2 Cl2 as the solvent. For some substrates, MeCN participated in the reaction, which affords a mild access to polysubstituted quinazolines. By employing a Tf2 O/2,4,6-tri- tert -butylpyrimidine (TTBP) combination, the method was extended to an N -formyl- o -xenylamine, which represents a recalcitrant amide substrate type for the dehydrative cyclization reaction. More importantly, a one-pot method was established for the direct and divergent synthesis of four types of phenanthridinoids from o -xenylamines, which features both a tert - N -formyl- o -xenylamine and phenanthridinium salt as key and versatile intermediates. The investigation has resulted in one of the shortest and the most efficient total syntheses of the three natural products trisphaeridine, 5,6-dihydrobicolorine, and N -methylcrinasiadine, and in the formal total syntheses of three other ones: 3-hydroxytrisphaeridine, bicolorine, and zephycandidine A. [ABSTRACT FROM AUTHOR]

To investigate the impact of an electronic medical record management system (EMRMS) on disease activity and the frequency of outpatient visits among patients with ankylosing spondylitis (AS). We identified 652 patients with AS who were followed up for at least 1 year before and after the first Ankylosing Spondylitis Disease Activity Score (ASDAS) assessment and compared the number of outpatient visits and average visit time within 1 year before and after the initial ASDAS assessment. Finally, we analyzed 201 patients with AS who had complete data and received ≥ 3 continuous ASDAS assessments at an interval of 3 months, and we compared the results of the second and third ASDAS assessments with those of the first. The number of annual outpatient visits increased after ASDAS assessment (4.0 (4.0, 7.0) vs. 4.0 (4.0, 8.0), p < 0.001), particularly among those with a high initial disease activity. The average visit time was reduced within 1 year after ASDAS assessment (6.4 (8.5, 11.2) vs. 6.3 (8.3, 10.8) min, p = 0.073), especially among patients whose with an inactive disease activity was < 1.3 (ASDAS C-reactive protein (CRP) 6.7 (8.8, 11.1) vs. 6.1 (8.0, 10.3) min, p = 0.033; ASDAS erythrocyte sedimentation rate (ESR) 6.4 (8.7, 11.1) vs. 6.1 (8.1, 10.0) min, p = 0.027). Among patients who received at least three ASDAS assessments, the third ASDAS-CRP tended to be lower than the first (1.5 (0.9, 2.1) vs. 1.4 (0.8, 1.9), p = 0.058). The use of an EMRMS increased the frequency of ambulatory visits among AS patients with high and very high disease activity and reduced the visit time among those with an inactive disease. Continual ASDAS assessments may help control the disease activity of patients with AS. [ABSTRACT FROM AUTHOR]

The development of quick and precise detection technologies for active compounds in vivo is critical for disease prevention, diagnosis and pathological investigation. The fluorescence signal of the fluorophore usually defines the probe's sensitivity to the chemical being examined. Many natural compounds containing flavone and isoflavone scaffolds exhibit a certain amount fluorescence, albeit with poor fluorescence quantum yields. Therefore, we used density functional theory (DFT) and time-dependent density functional theory (TDDFT) calculations to investigate the fluorescence characteristics of chromium-derived fluorophores in more depth. Different substituents are introduced at different positions of the chromone. As weak electron donor groups, alkyl and aromatic groups were discovered to have varying quantum yields on the fluorophore scaffold, and longer alkyl chains are favorable to enhance fluorescence quantum yield. In comparison to the amino group, substituted amino group can avoid group rotation, and the introduction of cyclic amines such as pyrrolidine and heterocyclic amines can improve optical characteristics. The electron-donating methoxy group at position 6 helps to increase the fluorescence quantum yield. [ABSTRACT FROM AUTHOR]

The visualization and identification of the deep cerebellar nuclei (DCN) (dentate [DN], interposed [IN] and fastigial nuclei [FN]) are particularly challenging. We aimed to visualize the DCN using quantitative susceptibility mapping (QSM), predict the contrast differences between QSM and T2* weighted imaging, and compare the DCN volume and susceptibility in movement disorder populations and healthy controls (HCs). Seventy‐one Parkinson's disease (PD) patients, 39 essential tremor patients, and 80 HCs were enrolled. The PD patients were subdivided into tremor dominant (TD) and postural instability/gait difficulty (PIGD) groups. A 3D strategically acquired gradient echo MR imaging protocol was used for each subject to obtain the QSM data. Regions of interest were drawn manually on the QSM data to calculate the volume and susceptibility. Correlation analysis between the susceptibility and either age or volume was performed and the intergroup differences of the volume and magnetic susceptibility in all the DCN structures were evaluated. For the most part, all the DCN structures were clearly visualized on the QSM data. The susceptibility increased as a function of volume for both the HC group and disease groups in the DN and IN (p <.001) but not the FN (p =.74). Only the volume of the FN in the TD‐PD group was higher than that in the HCs (p =.012), otherwise, the volume and susceptibility among these four groups did not differ significantly. In conclusion, QSM provides clear visualization of the DCN structures. The results for the volume and susceptibility of the DCN can be used as baseline references in future studies of movement disorders. [ABSTRACT FROM AUTHOR]

Light-emitting diodes (LEDs), particularly in the blue waveform range, are regarded as a major source of circadian rhythm dysregulation. A circadian rhythm dysregulation induced by blue LEDs is associated with non-alcoholic fatty liver disease (NAFLD). Hepatocellular accumulation of lipids is a key event in the early stages of NAFLD. Kupffer cells (KCs) have been reported to be lost in the early onset of NAFLD followed by an inflammatory reaction that alters the liver response to lipid overload. This study focused on the detection of the initial stages (subpathological stages) of LED light-triggered NAFLD. Mice were exposed to either blue or white LED irradiation for 44 weeks. Synchrotron radiation-based Fourier-transform infrared microspectroscopy (SR-FTIRM) and wax physisorption kinetic-Fourier transform infrared (WPK-FTIR) imaging were used to evaluate the ratio of lipid to protein and the glycosylation of glycoprotein, respectively. Immunohistopathological studies on KCs and circadian-related proteins were performed. Although liver biopsy showed normal pathology, an SR-FTIRM study revealed a high hepatic lipid-to-protein ratio after receiving LED illumination. The results of WPK-FTIR demonstrated that a high inflammation index was found in the high irradiance of the blue LED illumnation group. These groups showed a decrease in KC number and an increase in Bmal1 and Reverbα circadian protein expression. These findings provide explanations for the reduction of KCs without subsequent inflammation. A significant reduction of Per2 and Cry1 expression is correlated with the findings of WPK-FTIR imaging. WPK-FTIR is a sensitive method for detecting initiative stages of NAFLD induced by long-term blue LED illumination. [ABSTRACT FROM AUTHOR]

Aims/Introduction: Fatty acid desaturase (FADS) genetic polymorphisms are strongly correlated with the risk of dyslipidemia and cardiovascular disease. In this study, we examined the impact of FADS1 and FADS2 genetic variants on plasma lipid status, and assessed interactions between FADS genetic polymorphisms and plasma n‐3/n‐6 fatty acids regarding lipid status within a population of 816 Taiwanese patients with type 2 diabetes. Materials and Methods: Selected tag single‐nucleotide polymorphisms (FADS1 rs174546 [T/C]; FADS2 rs174602 [A/G] and rs2072114 [A/G]) were genotyped (n = 816). Results: The distribution of genotypes were compared with reports publicly available in the Genome Aggregation Database for East Asian populations (https://gnomad.broadinstitute.org). In the subgroup of patients not taking lipid‐lowering medications (n = 192), we observed that the G allele of FADS2 rs174602 was statistically significantly correlated with lower low‐density lipoprotein cholesterol (LDL‐C) concentrations (P = 0.001), whereas the G allele of rs2072114 was marginally associated with LDL‐C concentrations (P = 0.091). Using a general linear model adjusted for confounding factors, statistically significant interactions (P = 0.016) between single‐nucleotide polymorphisms in rs2072114 and a low alpha‐linolenic acid (18:3n‐3)/linoleic acid (18:2n‐6) ratio; the G allele correlated with lower LDL‐C levels among individuals with a low alpha‐linolenic acid/linoleic acid ratio. Interaction between rs174602 single‐nucleotide polymorphisms and low alpha‐linolenic acid/linoleic acid values on LDL‐C was only marginally significant (P = 0.063). Conclusions: Our results show the role of n‐3/n‐6 dietary polyunsaturated fatty acids in modifying the effects of genetic susceptibility on lipoprotein concentrations in patients with type 2 diabetes. Our findings highlight the potential of interventions with dietary polyunsaturated fatty acids regarding developing individualized prevention strategies for type 2 diabetes presenting with co‐occurring dyslipidemia and cardiovascular diseases. [ABSTRACT FROM AUTHOR]

The impact of coronavirus disease 2019 (COVID-19) pandemic on patients with neurodegenerative diseases and the specific neurological manifestations of COVID-19 have aroused great interest. However, there are still many issues of concern to be clarified. Therefore, we review the current literature on the complex relationship between COVID-19 and neurodegenerative diseases with an emphasis on Parkinson's disease (PD) and Alzheimer's disease (AD). We summarize the impact of COVID-19 infection on symptom severity, disease progression, and mortality rate of PD and AD, and discuss whether COVID-19 infection could trigger PD and AD. In addition, the susceptibility to and the prognosis of COVID-19 in PD patients and AD patients are also included. In order to achieve better management of PD and AD patients, modifications of care strategies, specific drug therapies, and vaccines during the pandemic are also listed. At last, mechanisms underlying the link of COVID-19 with PD and AD are reviewed. [ABSTRACT FROM AUTHOR]

Rabies is a fatal neurological zoonotic disease caused by the rabies virus (RABV), and the approved post‐exposure prophylaxis (PEP) procedure remains unavailable in areas with inadequate medical systems. Although strategies have been proposed for PEP and postinfection treatment (PIT), because of the complexity of the treatment procedures and the limited curative outcome, developing an effective treatment strategy remains a holy grail in rabies research. Herein, a facile approach is proposed involving photothermal therapy (PTT) and photothermally triggered immunological effects to realize effective PEP and PIT simultaneously. The designed photothermal agent (N+TT‐mCB nanoparticles) featured positively charged functional groups and high photo‐to‐heat efficiency, which are favorable for virus targeting and inactivation. The level of the virus at the site of infection in mice is significantly decreased upon treatment with orthotopic PTT, and the transfer of the virus to the brain is significantly inhibited. Furthermore, the survival ratio of the mice three days postinfection is increased by intracranial injection of N+TT‐mCB and laser irradiation. Overall, this work provides a platform for the effective treatment of RABV and opens a new avenue for future antiviral studies. [ABSTRACT FROM AUTHOR]

The vibrational and electronic structures of diruthenium nickel and copper complexes [Ru2Ni(dpa)4Cl2]0,1+ and [Ru2Cu(dpa)4Cl2]0,1+ were studied by using temperature‐controlled Raman spectroscopy and density functional theory (DFT) calculations. In the neutral species, the Ru−Ru stretching mode νRu−Ru was assigned to the 333/325 cm−1 band for the diruthenium Ni/Cu complexes, and this band greatly red shifted to 317/321 cm−1 at high temperatures. In contrast, this νRu−Ru band showed no shift in the oxidized forms. The time‐dependent DFT (TD‐DFT) calculations yielded that these complexes in the neutral form, have [Ru2]5+[M]1+ cores with [Ru2] moiety configuration (π*)2(δ*)1 and two low‐lying electronic excited states with [Ru2]4+[M]2+ cores and [Ru2] configurations of (π*)2(δ*)2 and (π*)3(δ*)1, respectively. The significant red shift of νRu−Ru band was explained to thermally access to these two excited states which have [Ru2]4+ cores and weak Ru−Ru bonding. These two states were resulted from metal‐to‐metal intramolecular charge transfer processes from [Ru2]5+[Ni/Cu]1+ to [Ru2]4+[Ni/Cu]2+. This charge transfer reaction is prohibited in the oxidized form. [ABSTRACT FROM AUTHOR]

We aim to investigate the alteration in disease activity of ankylosing spondylitis (AS) individuals before, during, and after the COVID-19 wave in Taiwan by using electronic medical-record management system (EMRMS). We identified 126 AS individuals from the single center, and gathered data of the three disease activities (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI], Ankylosing Spondylitis Disease Activity Score with erythrocyte sedimentation rate [ASDAS-ESR], and Ankylosing Spondylitis Disease Activity Score with C-Reactive Protein [ASDAS-CRP]) by using EMRMS before (7 February to 1 May, 2021), during (2 May to 24 July, 2021), and after the COVID-19 wave (25 July to 16 October, 2021). We compared the disease activity measures of the three phases through a paired t test. Among the 126 individuals, CRP was significantly higher during the COVID-19 wave (0.2 (0.1, 0.5) mg/dl, p = 0.001) than before the wave (0.2 (0.1, 0.4) mg/dl), ESR (8.0 (4.0, 15.0) mm/h, p = 0.003) and ASDAS-ESR (1.4 (1.0, 1.9), p = 0.032) were significantly higher after the wave than during the wave (6.0 (3.0, 12.0) mm/h and 1.2 (0.9, 1.8) mm/h) e. ESR, CRP, ASDAS-ESR and ASDAS-CRP were all significant higher after COVID-19 wave than before. The disease activities of AS individuals in Taiwan worsened after 2021 COVID-19 wave in Taiwan. [ABSTRACT FROM AUTHOR]

Aim: To investigate the role of RAD54B in the proliferation of inflamed human dental pulp cells (hDPCs) induced by lipopolysaccharide (LPS). Methodology: Normal, carious and pulpitic human dental pulp tissues were collected. Total RNA was subjected to RNA‐sequencing (seq) and gene expression profiles were studied by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Differentially expressed genes (DEGs) in homologous recombination repair (HRR) were validated with qRT‐PCR. The expression of RAD54B and TNF‐α in human dental pulp tissues was detected using immunohistochemistry. HDPCs were cultured and RAD54B level in hDPCs was detected after LPS stimulation using western blot. CCK‐8 was used to investigate the proliferation of hDPCs transfected with negative control (Nc) small interfering RNA (siRNA), RAD54B siRNA, P53 siRNA or both siRNAs with or without LPS stimulation. Flow cytometry was used to detect the cell cycle distribution, and western blot and immunofluorescence were used to analyse the expression of RAD54B, P53 and P21 under the above treatments. One‐way and two‐way anova followed by least significant difference posttest were used for statistical analysis. Results: RNA‐seq results identified DEGs amongst the three groups. KEGG pathway analysis revealed enrichment of DEGs in the replication and repair pathway. HRR and non‐homologous end joining (NHEJ) components were further verified and qRT‐PCR results were basically consistent with the sequencing data. RAD54B, an HRR accessory factor highly expressed in carious and pulpitic tissues as compared to that in normal pulps, was chosen as our gene of interest. High RAD54B expression was confirmed in inflamed human dental pulp tissues and LPS‐stimulated hDPCs. Upon RAD54B knockdown, P53 and P21 expressions in hDPCs were upregulated whereas the proliferation was significantly downregulated, accompanied by increased G2/M phase arrest. After inhibiting P53 expression in RAD54B‐knockdown hDPCs, P21 expression and cell proliferation were reversed. Conclusions: Gene expression profiles of normal, carious and pulpitic human dental pulp tissues were revealed. HRR components were elucidated to function in dental pulp inflammation. Amongst the DEGs in HRR, RAD54B regulated the proliferation of inflamed hDPCs via P53/P21 signalling. This research deepens our understanding of dental pulp inflammation and provides new insight to clarify the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Machine learning (ML) techniques discover knowledge from large amounts of data. Modeling in ML is becoming essential to software systems in practice. The accuracy and efficiency of ML models have been focused on ML research communities, while there is less attention on validating the qualities of ML models. Validating ML applications is a challenging and time-consuming process for developers since prediction accuracy heavily relies on generated models. ML applications are written by relatively more data-driven programming based on the black box of ML frameworks. All of the datasets and the ML application need to be individually investigated. Thus, the ML validation tasks take a lot of time and effort. To address this limitation, we present a novel quality validation technique that increases the reliability for ML models and applications, called MLVal. Our approach helps developers inspect the training data and the generated features for the ML model. A data validation technique is important and beneficial to software quality since the quality of the input data affects speed and accuracy for training and inference. Inspired by software debugging/validation for reproducing the potential reported bugs, MLVal takes as input an ML application and its training datasets to build the ML models, helping ML application developers easily reproduce and understand anomalies in the ML application. We have implemented an Eclipse plugin for MLVal that allows developers to validate the prediction behavior of their ML applications, the ML model, and the training data on the Eclipse IDE. In our evaluation, we used 23,500 documents in the bioengineering research domain. We assessed the ability of the MLVal validation technique to effectively help ML application developers: (1) investigate the connection between the produced features and the labels in the training model, and (2) detect errors early to secure the quality of models from better data. Our approach reduces the cost of engineering efforts to validate problems, improving data-centric workflows of the ML application development. [ABSTRACT FROM AUTHOR]

• Three novel Supramolecular complexes were constructed by solvothermal method. • (DFT) calculations were carried out to ascertain the optimum geometry structures. • The fluorescent properties of three complexes were investigated. • Hirshfeld surface analysis and molecular docking had been investigated. • Antibacterial properties also had been investigated. Three supramolecular complexes of Co(II), Zn(II) and Mn(II) based on a pyridazine dicarboxylic derivative, namely, {M(H 2 O) 2 [H(4-CPCA)] 2 }·2H 2 O (M = Co (SNUT-16), Zn (SNUT-17), Mn (SNUT-18), H 2 (4-CPCA) = 1-(4-carboxyphenyl)-4-oxo-1,4-dihydropyridazine-3-carboxylic acid, have been successfully obtained by the solvothermal method. Single crystal X-ray crystallography reveals that SNUT-16, SNUT-17 and SNUT-18 are isostructural, which exhibit same 3D supramolecular network. Density Functional Theory (DFT) calculations were carried out to ascertain the optimum geometry structures of three complexes with the DFT/B3LYP method at the 6–311Gcomputational level and the calculated HOMO and LUMO energies were presented. Theoretical modeling on the electronic structure properties was performed, quantitative analysis of intermolecular interactions in crystal structures has been conducted using Hirshfeld surface analysis. In addition, the fluorescence, molecular docking and antibacterial properties also had been investigated at room temperature. Three 0D isomorphic complexes (SNUT-16, SNUT-17 and SNUT-18) were successfully synthesized and their structures were verified through DFT calculations. In addition, their inhibitory concentrations against E.coli and P.aeruginosa has been tested, and molecular docking confirmed the interaction between them. [Display omitted] [ABSTRACT FROM AUTHOR]

SO2 is not only a new potential gas signaling molecule, but also an antioxidant and antioxidant metabolite, which plays an important role in biophysiological and pathological processes. However, excessive intake of it can lead to serious complications of various diseases. Indole–iodide conjugated double bonds are often used as a sensitive response site for SO2, but the fluorescence of the system is often quenched after the nucleophilic addition of SO2. In this work, we introduced sulfur and nitrogen electron donors into a fluorophore, which rescued the trend of fluorescence quenching and enabled the system to develop a ratiometric fluorescence response for more accurate detection of SO32−. In addition, this probe can target mitochondria. The probe has good selectivity, sensitivity, a fast response (200 s) and a limit of detection (LOD) of 0.17 μM. Furthermore, the probe was successfully applied to visualize both endogenous and exogenous SO32− in Hela cells and zebrafish. [ABSTRACT FROM AUTHOR]

Intracellular redox homeostasis exerts a tremendous influence on pathophysiological fields. In order to maintain the homeostasis of intracellular redox state, reactive oxygen species (ROS) and reactive sulfur species (RSS) react and transform with each other, and their levels also directly reflect the degree of oxidative stress and disease. To understand the correlation and pathophysiological effects of these two signaling molecules in oxidative stress, unique fluorescence imaging tools are required. Fluorescent probes have become an indispensable detection tool in modern scientific research and disease diagnosis. Currently, there are many fluorescent probes for detecting ROS or RSS. However, the cellular environment is extremely complex. Dual detection fluorescent probes that can monitor more than one species in a biological environment cause our attention. This review describes dual detection fluorescent probes that can detect ROS and RSS simultaneously or sequentially. This will provide strong support for the study of redox homeostasis. [ABSTRACT FROM AUTHOR]

Syndiotactic poly(4-methyl-1-pentene) (sP4M1P)-based stereoregular diblock copolymers, namely sP4M1P-b-polystyrene and sP4M1P-b-polymethylmethacrylate, were prepared from an α-bromoester-capped sP4M1P macroinitiator, which was chain extended with styrene and methyl methacrylate, respectively, via the atom transfer radical polymerization reaction. The α-bromoester-capped sP4M1P was generated by the esterification of hydroxyl-capped sP4M1P with α-bromoisobutyryl bromide. The hydroxyl-capped sP4M1P was synthesized by inducing a selective chain transfer reaction to aluminum during the syndiospecific polymerization of 4-methyl-1-pentene in the presence of a syndiospecific metallocene catalyst. As stereoregular diblock copolymers are difficult to prepare using existing methods, the current study offers an effective process for the preparation of sP4M1P-based stereoregular diblock copolymers. These copolymers were found to have well-defined architectures and they can undergo molecular self-assembly into ordered nanostructures, as evidenced by small-angle X-ray scattering analyses. [ABSTRACT FROM AUTHOR]

This study analyzes the characteristic numerical analysis of membrane electrode assembly in Proton Exchange Membrane Fuel Cell (PEMFC) with bipolar plate, flow channel, gas diffusion electrode, and proton exchange membrane. The numerical solution focuses on discussing the effects of different parameters, including permeability, porosity, and operation voltage, on various mass fractions, current-voltage curve, and power-voltage curve. The results show that as the porous medium with high gas permeability is an important factor that affects the mass fraction of hydrogen. Regarding the analyses of various porosities, the fuel cell performance can be effectively promoted with larger ratio of porosity and permeability. However, increasing the porosity will affect the electrical conductivity and increase the flooding of water, which will block the flow channel and reduce efficiency. • Increasing the permeability will improve PEMFC performance. • High porosity can be effectively associated and allow the gas to flow through. • High voltages will increase the hydrogen mass fraction and affect the electrochemical reaction. [ABSTRACT FROM AUTHOR]

Neuroendocrine neoplasm (NEN) is a common gastrointestinal (GI) tract tumor divided into the neuroendocrine tumor (NET) and neuroendocrine carcinoma (NEC) according to mitosis and Ki-67 index. However, the objective discordance between interobserver may cause unsuitable diagnosis and misleading treatment. Nowadays, aberrant glycosylation of glycoconjugates inducing further populations of elongated complex oligosaccharide covalent attached to glycoconjugates anchored in the cell membrane by neo-synthesis of cancer-associated alteration of carbohydrate determinants were observed during cancer development. This study aimed to demonstrate the wax physisorption kinetics coupled with Fourier transform infrared (WPK-FTIR) imaging between NET and NEC in the rectum, colon, and stomach by utilizing two wax reagents (beeswax and paraplast) as glycan adsorbents for physical binding glycans of glycoconjugates based on dipole-induced dipole interaction. Results showed greater physisorption with beeswax than that of paraplast, suggesting highly populated elongated glycans of glycoconjugates adhering onto the tumor surfaces of NETs than that of adjacent benign mucosa in the rectum and colon. Besides, the WPK results of gastric NEN tissue sections showed a higher infrared absorbance ratio of beeswax-remnant to paraplast-remnant remains onto the tissue sections referring to a higher population of elongated glycans in gastric NET as compared with that of gastric NEC. Based on our findings, different anatomical locations could share similar phenomena with minor variance. In conclusion, WPK-FTIR imaging may have the potential to be employed as an alternative diagnostic method in GI NENs in the future. [ABSTRACT FROM AUTHOR]

Abstract: An adaptive nonhydrostatic atmospheric dynamical core was developed on a Cartesian grid and extended to spherical geometry with the application of a cubed‐sphere grid. To assure a practical Courant‐Friedrichs‐Lewy number for stability, a horizontally explicit and vertically implicit algorithm was applied in this model through a third‐order implicit–explicit Runge–Kutta scheme. A two‐dimensional adaptive grid was applied in the horizontal directions to generate the computational meshes, with variable resolutions according to the evolution of the predicted variables during the simulations, while the vertical grid is fixed considering the characteristics of atmospheric flows and the computational efficiency in practical applications. The Berger–Oliger block‐structured adaptive algorithm was adopted in this study. Blocks with different resolutions can be constructed straightforwardly on each patch of the cubed sphere and an algorithm to exchange both solution and block information between adjacent patches was designed in order to implement a global model. The nonhydrostatic governing equations are solved by a three‐point multimoment constrained finite‐volume scheme. Using the compact stencil for spatial reconstructions, the interpolation operations between coarse–fine blocks can be implemented efficiently and the local‐based scheme is also helpful to suppress the computational modes around the coarse–fine interfaces due to the abrupt change of grid resolution. Additionally, flux corrections were conducted along the block boundaries and the resulting dynamical core is rigorously conservative. The proposed model was evaluated by calculating several idealized benchmark tests, and the effectiveness of the adaptive model in saving computational costs was verified in this study. [ABSTRACT FROM AUTHOR]

In Mainland China and Hong Kong, health authorities utilize Agkistrodon halys antivenom in the treatment of patients who sustained bites from green pit vipers. However, the treatment benefit of Agkistrodon halys antivenom among such patients is still controversial. The purpose of this study is to evaluate the coagulation parameters normalization time of Agkistrodon halys antivenom in patients who sustained green pit viper bites and explore independent risk factors of patient prognosis. Data were extracted from the Donghua Hospital Information System. Comparison of the two groups of patients – who used antivenom (GPUA) and who did not use antivenom (GPNUA) were performed using stratified analysis, univariate and multivariate ordered logistic regression models to evaluate the coagulation parameters normalization time. Univariate and multivariate ordered logistic regression models were used to explore independent risk factors of patient prognosis. Between the GPUA and GPNUA groups, there is no significant difference in the coagulation parameters normalization time with the treatment of Agkistrodon halys antivenom. GPNUA consumed more cryoprecipitate and platelets and had a lower cost. The patient's severity of the bite, first coagulation profile, and dosages of fresh frozen plasma, platelet, and red cell suspension was found to be risk factors for the normalization time of coagulation parameters. The therapeutic effect of Agkistrodon halys antivenom in green pit vipers bite patients is not quite satisfying. In addition, more attention should be paid to the first coagulation profile, blood clotting factors indices, platelet count (PLT), and hemoglobin when treating such patients. [ABSTRACT FROM AUTHOR]

Although locus coeruleus (LC) has been demonstrated to play a critical role in the cognitive function of Parkinson's disease (PD), the underlying mechanism has not been elucidated. The objective was to investigate the relationship among LC degeneration, cognitive performance, and the glymphatic function in PD. In this retrospective study, 71 PD subjects (21 with normal cognition; 29 with cognitive impairment (PD-MCI); 21 with dementia (PDD)) and 26 healthy controls were included. All participants underwent neuromelanin-sensitive magnetic resonance imaging (NM-MRI) and diffusion tensor image scanning on a 3.0 T scanner. The brain glymphatic function was measured using diffusion along the perivascular space (ALPS) index, while LC degeneration was estimated using the NM contrast-to-noise ratio of LC (CNR LC). The ALPS index was significantly lower in both the whole PD group (P = 0.04) and the PDD subgroup (P = 0.02) when compared to the controls. Similarly, the CNR LC was lower in the whole PD group (P < 0.001) compared to the controls. In the PD group, a positive correlation was found between the ALPS index and both the Montreal Cognitive Assessment (MoCA) score (r = 0.36; P = 0.002) and CNR LC (r = 0.26; P = 0.03). Mediation analysis demonstrated that the ALPS index acted as a significant mediator between CNR LC and the MoCA score in PD subjects. The ALPS index, a neuroimaging marker of glymphatic function, serves as a mediator between LC degeneration and cognitive function in PD. • Exploring the path of locus coeruleus (LC) affects cognitive function. • Multimodal MRI imaging address the function of glymphatic system and LC. • LC degeneration is related to cognition in Parkinson's disease (PD). • Impaired glymphatic function as a mediator in this relationship in PD. [ABSTRACT FROM AUTHOR]

Modified (core) θ-Al 2 O 3 @ (shell) polyethylene glycol (PEG) technology was used to prepare α-Al 2 O 3 green compacts composed of <100-nm α-Al 2 O 3 crystallites using θ-Al 2 O 3 as the starting material. The preparation process has two steps. In the first step, θ-Al 2 O 3 compacts in which alumina crystallites were apart individually after the removal of PEG were made. In the second step, the θ-Al 2 O 3 was transformed into α-Al 2 O 3.The compact showed phase purity of >85% α-Al 2 O 3 with crystallites sizes ranging from 50 to 100 nm and the compact density was >60% of the theoretical value. [ABSTRACT FROM AUTHOR]

Two new neolignans jatrolignans, C (1) and D (2), a pair of epimers, were isolated from the whole plants of Jatropha curcas L. (Euphorbiaceae). Their structures were determined with HRESIMS, IR, and NMR data analysis, and electronic circular dichroism (ECD) experiments via a comparison of the experimental and the calculated ECD spectra. Their antichlamydial activity was evaluated in Chlamydia abortus. They both showed dose-dependent antichlamydial effects. Significant growth inhibitory effects were observed at a minimum concentration of 40 μM. [ABSTRACT FROM AUTHOR]

Purpose: To identify factors associated with posttraumatic growth (PTG) of head-and-neck cancer squamous cancer (HNC) patients with oncologic emergencies (OE) within the first six months post-treatment.Methods: We conducted a cross-sectional study of HNC patients in Taiwan from May 2019 to April 2021 using patient-reported outcomes. Patients were assessed for symptom distress, anxiety, fear of recurrence (FCR), and PTG. Multiple regression analysis was conducted to identify factors associated with PTG. The independent-samples t-test was used to compare PTG and its five specific domains in patients with low FCR, high FCR, low anxiety, and high anxiety.Results: Of the 114 patients surveyed, 46.5% reported little-to-no PTG, and 53.5% had moderate-to-high PTG. Greater PTG was associated with greater FCR, longer time since OE, less anxiety, having a cancer recurrence, and greater educational attainment. These factors explained 38.6% of the variance in PTG.Conclusion: A notable proportion of HNC patients with OE-reported PTG but almost half-reported little-to-no PTG. PTG occurred most in the domain of appreciation of life. The study results also suggest that training patients in coping skills and inviting them to group growth experiences can help them increase PTG and cope with cancer-related psychological threats related to OE. [ABSTRACT FROM AUTHOR]

Background: Demoralization is a common problem in oral cancer patients owing to the chronic and severe nature of their affliction. However, the association between demoralization and the patient's spiritual needs, quality of life, and suicidal ideation remains unclear. This study aims to provide insights into possible links between demoralization among oral cancer patients and its effects on the patient's spiritual needs, quality of life, and suicidal ideation.Methods: We examined 155 Taiwanese oral cancer inpatients in Taichung Veterans General Hospital, Taiwan, using the following three rating scales: (a) Demoralization Scale Mandarin Version (DS-MV), (b) Spiritual Interests Related to Illness Tool, and (c) The Taiwan Chinese versions of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. Suicidal ideation was established if at least one of the two suicide-related items on the DS-MV scale were checked. We divided the participants into high- and low-demoralization groups, per the cutoff score of 30. We then explored group associations with sociodemographic features, quality of life, and spiritual needs. Logistic regression and receiver operating characteristic (ROC) curves were used to determine demoralization and its association between these variables.Results: Fifty-five (35.5%) patients were categorized as having high demoralization (DS-MV scale score > 30), with scores for DS-MV for all patients being 27.2 ± 16.8. The rates of suicidal ideation were 29.1% (16/55) in the high-demoralization group and 2% (2/100) in the low-demoralization group, with an odds ratio (95% confidence interval) of 20.10 (4.41-91.55). Logistic regression analysis revealed significant effects of spiritual needs and global health status on the DS-MV scores (p < 0.001). Multivariate analyses further confirmed that only overall quality of life scores < 62.5 and spiritual needs < 3.7 significantly predicted the occurrence of high demoralization.Conclusion: High demoralization is associated with low satisfaction with spiritual needs, poor quality of life, and high risk of suicidal ideation. DS-MV may potentially be an effective tool for achieving holistic health care among oral cancer patients. [ABSTRACT FROM AUTHOR]