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Background: Percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) has been reported to be safe and effective at midterm follow-up to treat drug-refractory hypertrophic obstructive cardiomyopathy in a single center. However, data from other centers are lacking. This retrospective cohort study aimed to investigate the efficacy and safety of PIMSRA from another independent center., Methods and Results: PIMSRA was performed in 76 patients with hypertrophic obstructive cardiomyopathy in our center from April 2020 to June 2023. The primary outcome was the reduction of left ventricular outflow tract gradient after 6 months or more post-PIMSRA. Secondary outcomes were periprocedural major adverse clinical events. Sixty-one patients returned to the hospital for follow-up 6 to 30 (median, 14) months after the procedure. At the last follow-up of the 61 patients, the maximum septal thickness decreased from a median of 23.6 (interquartile range, 20.5-26.4) to 19.1 (interquartile range, 16.0-22.1) mm ( P <0.001) and the left ventricular outflow tract peak gradient at rest decreased from a median of 70.0 (interquartile range, 29.1-107.5) to 20.0 (interquartile range, 10.8-48.8) mm Hg ( P <0.001). The percentage of patients with symptoms of New York Heart Association functional class III/IV decreased from 51% to 0%. Of all 76 patients, there was no in-hospital or 30-day death, no right or left branch block, and no permanent pacemaker implantation. Six (8%) patients had pericardial effusion, with 1 experiencing cardiac tamponade and ventricular fibrillation, and 1 (1%) patient developed septal branch aneurysm that was treated with coil occlusion., Conclusions: PIMSRA allows for the reduction in the left ventricular outflow tract gradient and enhances symptomatic improvement, with a limited incidence of adverse events and complications among patients with hypertrophic obstructive cardiomyopathy.

The rapid emergence of drug resistance severely reduces the clinical response of human immunodeficiency virus-1 (HIV-1) to non-nucleoside reverse transcriptase inhibitors (NNRTIs). Herein, a series of 2,4,6-trisubstituted pyrimidine derivatives was designed and synthesized, with the aim to identify novel anti-HIV-1 agents with improved drug resistance profiles. The antiviral activity results demonstrated that all compounds showed excellent potency to wild-type (WT) HIV-1 strain (EC 50  = 3.61-15.5 nM). Moreover, 13c was proved to be the most potent inhibitor against the whole tested viral panel, with EC 50 ranging from 4.68 to 229 nM. In addition, 13c yielded moderate HIV-1 RT inhibition with IC 50 value of 0.231 μM, which demonstrated it was a classical NNRTI. Molecular docking was further conducted to illustrate its binding mode with HIV-1 RT. These encouraging results indicated that 13c can be used as a lead compound for further study., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

A vast and painful price has been paid in the battle against viruses in global health [...].

HIV-1 reverse transcriptase (RT) has received great attention as an attractive therapeutic target for acquired immune deficiency syndrome (AIDS), but the inevitable drug resistance and side effects have always been major challenges faced by non-nucleoside reverse transcriptase inhibitors (NNRTIs). This work aimed to identify novel chemotypes of anti-HIV-1 agents with improved drug-resistance profiles, reduced toxicity, and excellent druggability. A series of diarylpyrimidine (DAPY) derivatives were prepared via structural modifications of the leads K-5a2 and 25a . Among them, 15a with dimethylphosphine oxide moiety showed the most prominent antiviral potency against all of the tested viral panel, being 1.6-fold (WT, EC 50  = 1.75 nmol/L), 3.0-fold (L100I, EC 50  = 2.84 nmol/L), 2.4-fold (K103N, EC 50  = 1.27 nmol/L), 3.3-fold (Y181C, EC 50  = 5.38 nmol/L), 2.9-fold (Y188L, EC 50  = 7.96 nmol/L), 2.5-fold (E138K, EC 50  = 4.28 nmol/L), 4.8-fold (F227L/V106A, EC 50  = 3.76 nmol/L) and 5.3-fold (RES056, EC 50  = 15.8 nmol/L) more effective than that of the marketed drug ETR. Molecular docking results illustrated the detailed interactions formed by compound 15a and WT, F227L/V106A, and RES056 RT. Moreover, 15a ·HCl carried outstanding pharmacokinetic ( t 1/2  = 1.32 h, F  = 40.8%) and safety profiles (LD 50  > 2000 mg/kg), which demonstrated that 15a HCl is a potential anti-HIV-1 drug candidate., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors.)

In this study, a microcosm experiment was conducted to investigate the effects of Na 2 S 2 O 8 preoxidation combined with biostimulation on petroleum-contaminated soil remediation. The response of microbial community during this process was explored using BIOLOG ECO microplate carbon utilization method and 16 s rDNA high-throughput sequencing. The results showed that use of 10 mg/g Na 2 S 2 O 8 removed 19.8 % of the petroleum hydrocarbons, reduced soil biotoxicity and did not affect soil microbial activity compared to other concentrations. Therefore, sodium persulfate of ca. 10 mg/g was used to oxidize petroleum in soil before the biostimulation experiment with organic and inorganic fertilizers. Our finding showed that the content of total petroleum hydrocarbons (TPHs) in soil was reduced by 43.3 % in inorganic fertilizer treatment after 60 days. The results of BIOLOG ECO microplate carbon utilization analysis and 16 S rDNA high-throughput sequencing further confirmed that biostimulation quickly restored the microbial activities in oxidant treated soil. The main marker bacteria in chemical oxidation combined with biostimulation remediation were Arthrobacter and Paenarthrobacter, and their relative abundances were both significantly negatively correlated with the content of petroleum hydrocarbons in soil., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Weeds present a significant challenge to agricultural productivity, and acetyl-CoA carboxylase (ACCase)-inhibiting herbicides have proven to be effective in managing weed populations in rice fields. To develop ACCase-inhibiting herbicide-resistant rice, we generated mutants of rice ACCase (OsACC) featuring Ile-1792-Leu or Gly-2107-Ser substitutions through ethyl methyl sulfonate (EMS) mutagenesis. The Ile-1792-Leu mutant displayed cross-resistance to aryloxyphenoxypropionate (APP) and phenylpyrazoline (DEN) herbicides, whereas the Gly-2107-Ser mutants primarily exhibited cross-resistance to APP herbicides with diminished resistance to the DEN herbicide. In vitro assays of the OsACC activity revealed an increase in resistance to haloxyfop and quizalofop, ranging from 4.84- to 29-fold in the mutants compared to that in wild-type. Structural modeling revealed that both mutations likely reduce the binding affinity between OsACC and ACCase inhibitors, thereby imparting resistance. This study offers insights into two target-site mutations, contributing to the breeding of herbicide-resistant rice and presenting alternative weed management strategies in rice cultivation.

Saline and alkaline stresses limit plant growth and reduce crop yield. Soil salinization and alkalization seriously threaten the sustainable development of agriculture and the virtuous cycle of ecology. Biofertilizers made from plant growth-promoting rhizobacteria (PGPR) not only enhance plant growth and stress tolerance, but also are environmentally friendly and cost-effective. There have been many studies on the mechanisms underlying PGPRs enhancing plant salt resistance. However, there is limited knowledge about the interaction between PGPR and plants under alkaline-sodic stress. To clarify the mechanisms underlying PGPR's improvement of plants' tolerance to alkaline-sodic stress, we screened PGPR from the rhizosphere microorganisms of local plants growing in alkaline-sodic land and selected an efficient strain, Bacillus altitudinis AD13-4, as the research object. Our results indicate that the strain AD13-4 can produce various growth-promoting substances to regulate plant endogenous hormone levels, cell division and differentiation, photosynthesis, antioxidant capacity, etc. Transcriptome analysis revealed that the strain AD13-4 significantly affected metabolism and secondary metabolism, signal transduction, photosynthesis, redox processes, and plant-pathogen interactions. Under alkaline-sodic conditions, inoculation of the strain AD13-4 significantly improved plant biomass and the contents of metabolites (e.g., soluble proteins and sugars) as well as secondary metabolites (e.g., phenols, flavonoids, and terpenoids). The 16S rRNA gene sequencing results indicated that the strain AD13-4 significantly affected the abundance and composition of the rhizospheric microbiota and improved soil activities and physiochemical properties. Our study provides theoretical support for the optimization of saline-alkali-tolerant PGPR and valuable information for elucidating the mechanism of plant alkaline-sodic tolerance.

Background: Indigenous chickens were developed through a combination of natural and artificial selection; essentially, changes in genomes led to the formation of these modern breeds via admixture events. However, their confusing genetic backgrounds include a genomic footprint regulating complex traits, which is not conducive to modern animal breeding., Results: To better evaluate the candidate regions under domestication in indigenous chickens, we considered both runs of homozygosity (ROHs) and selective signatures in 13 indigenous chickens. The genomes of Silkie feather chickens presented the highest heterozygosity, whereas the highest inbreeding status and ROH number were found in Luhua chickens. Short ROH (< 1 Mb), were the principal type in all chickens. A total of 291 ROH islands were detected, and QTLdb mapping results indicated that body weight and carcass traits were the most important traits. An ROH on chromosome 2 covering VSTM2A gene was detected in 12 populations. Combined analysis with the Tajima's D index revealed that 18 genes (e.g., VSTM2A, BBOX1, and RYR2) were under selection and covered by ROH islands. Transcriptional analysis results showed that RYR2 and BBOX1 were specifically expressed in the heart and muscle tissue, respectively., Conclusion: Based on genome-wide scanning for ROH and selective signatures, we evaluated the genomic characteristics and detected significant candidate genes covered by ROH islands and selective signatures. The findings in this study facilitated the understanding of genetic diversity and provided valuable insights for chicken breeding and conservation strategies., (© 2024. The Author(s).)

NNRTI is an important component of the highly active antiretroviral therapy (HAART), but the rapid emergence of drug resistance and poor pharmacokinetics limited their clinical application. Herein, a series of novel aryl triazolone dihydropyridines (ATDPs) were designed by structure-guided design with the aim of improving drug resistance profiles and pharmacokinetic profiles. Compound 10n (EC 50 = 0.009-17.7 μM) exhibited the most active potency, being superior to or comparable to that of doravirine (DOR) against the whole tested viral panel. Molecular docking was performed to clarify the reason for its higher resistance profiles. Moreover, 10n demonstrated excellent pharmacokinetic profile ( T 1/2 = 5.09 h, F = 108.96%) compared that of DOR ( T 1/2 = 4.4 h, F = 57%). Additionally, 10n was also verified to have no in vivo acute or subacute toxicity (LD 50 > 2000 mg/kg), suggesting that 10n is worth further investigation as a novel oral NNRTIs for HIV-1 therapy.

The existing available antipsychotics have failed to manage the cognitive impairment of schizophrenia and induced a number of seriously undesirable effects. Trace amine-associated receptor 1 (TAAR1) has emerged as an ideal target for the design of antischizophrenia drugs, with the ability to mediate multiple psychological functions by sensing endogenous amine-containing metabolites without the side effects of catalepsy. In this work, a series of novel TAAR1 agonists were designed based on the structural analysis of the TAAR1 activation pocket. Among them, 6e displayed a potent TAAR1-G s /G q dual-pathway activation property, being different from that of the clinical drug candidate SEP-363856 with only TAAR1-G s pathway activation. In rodent models, 6e significantly alleviated MK-801-induced schizophrenia-like cognitive phenotypes without inducing catalepsy. Furthermore, 6e·HCl exhibited favorable pharmacokinetic ( T 1/2 = 2.31 h, F = 39%) and safety properties. All these demonstrated that 6e·HCl may be used as a novel drug candidate for schizophrenia treatment.

Compared to commercial chickens, local breeds exhibit better in meat quality and flavour, but the productivity (e.g., growth rate, body weight) of local chicken breeds is rather low. Genetic analysis based on whole-genome sequencing contributes to elucidating the genetic markers or putative candidate genes related to some economic traits, facilitating the improvement of production performance, the acceleration of breeding progress, and the conservation of genetic resources. Here, a total of 209 local chickens from 13 breeds were investigated, and the observation of approximately 91.4% high-quality sequences (Q30 > 90%) and a mapping rate over 99% for each individual indicated good results of this study, as confirmed by a genome coverage of 97.6%. Over 19 million single nucleotide polymorphisms (SNPs) and 1.98 million insertion-deletions (InDels) were identified using the reference genome (GRCg7b), further contributing to the public database. This dataset provides valuable resources for studying genetic diversity and adaptation and for the cultivation of new chicken breeds/lines., (© 2024. The Author(s).)

Introduction: To investigate the efficacy and safety of preprocedural simethicone (S) and pronase (P) for optimal mucosal visualization during esophagogastroduodenoscopy with sedation. The effect of postural change combined with premedication on mucosal visibility was also examined., Methods: The study randomized 496 patients into 8 groups based on the type of premedication provided and whether a postural change occurred. The premedication in the control group was 100 mL of normal saline solution (NS). The remaining 3 intervention groups were administered 100 mL of simethicone alone (S), pronase solution alone (P), and simethicone plus pronase solution (S + P). Each group was classified into subgroups according to whether there was a postural change (PC). The mucosal visibility score (MVS), total mucosal visibility score (TVS), procedure time, water consumption for mucosal cleansing, and proportion of patients with diminutive lesions <5 mm were recorded., Results: The P and S groups had a significantly better TVS than the NS group (11.86 ± 3.36 in group P vs 14.52 ± 2.57 in group NS, P < 0.001; 12.36 ± 2.93 in group S vs 14.52 ± 2.57 in group NS, P = 0.006). The TVS was better in the P group than in the S group (11.86 ± 3.36 vs 12.36 ± 2.93, P = 0.037). The MVS was significantly better in the esophagus and duodenum and worse in the upper and lower gastric body in the S group than in the P group. The P + S group had a significantly better TVS than the P and S groups (9.81 ± 2.90 in group P + S vs 11.86 ± 3.36 in group P and 12.36 ± 2.93 in group S, respectively, P < 0.001),\ and had a reduced amount of flushing water during the procedure (0 [interquartile range [IQR]: 0-33] mL in group P + S vs 40 [IQR: 0-70] mL in group P, P < 0.01; 0 [IQR: 0-33] mL in group P + S vs 50 [IQR: 20-98] mL in group S, P < 0.001). The TVS was significantly better in the P + S + PC group than in the P + S group (8.44 ± 2.10 vs 9.81 ± 2.90, P = 0.003). The MVS was significantly better in the gastric antrum, fundus, and upper and lower gastric body in the P + S + PC group than in the P + S group. There was no significant difference in the detection rate of diminutive lesions among the different groups during an endoscopic examination ( P > 0.05)., Discussion: The combination of preprocedural administration with simethicone and pronase achieved superior mucosal visualization compared with saline, simethicone, or pronase alone in patients receiving upper endoscopy. Postural change maneuvers performed before endoscopy further improved the mucosal visibility in most parts of the stomach when used with preprocedural simethicone and pronase., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Circadian rhythm disorders pose major risks to human health and animal production activity, and the hypothalamus is the center of circadian rhythm regulation. However, the epigenetic regulation of circadian rhythm based on farm animal models has been poorly investigated. We collected chicken hypothalamus samples at seven time points in one light/dark cycle and performed long noncoding RNA (lncRNA), circular RNA (circRNA), and mRNA sequencing to detect biomarkers associated with circadian rhythm. We enhanced the comprehensive expression profiling of ncRNAs and mRNAs in the hypothalamus and found two gene sets (circadian rhythm and retinal metabolism) associated with the light/dark cycle. Noncoding RNA networks with circadian expression patterns were identified by differential expression and circadian analysis was provided that included 38 lncRNAs, 15 circRNAs, and 200 candidate genes. Three lncRNAs (ENSGALT00000098661, ENSGALT00000100816, and MSTRG.16980.1) and one circRNA (novel&#95;circ&#95;010168) in the ncRNA-mRNA regulatory network were identified as key molecules influencing circadian rhythm by regulating AOX1 in retinal metabolism. These ncRNAs were predicted to be related to pernicious anemia, gonadal, eye disease and other disorders in humans. Together, the findings of this study provide insights into the epigenetic mechanisms of circadian rhythm and reveal AOX1 as a promising target of circadian rhythm regulation.

In vitro 3D models are advanced biological tools that have been established to overcome the shortcomings of oversimplified 2D cultures and mouse models. Various in vitro 3D immuno-oncology models have been developed to mimic and recapitulate the cancer-immunity cycle, evaluate immunotherapy regimens, and explore options for optimizing current immunotherapies, including for individual patient tumours. Here, we review recent developments in this field. We focus, first, on the limitations of existing immunotherapies for solid tumours, secondly, on how in vitro 3D immuno-oncology models are established using various technologies - including scaffolds, organoids, microfluidics and 3D bioprinting - and thirdly, on the applications of these 3D models for comprehending the cancer-immunity cycle as well as for assessing and improving immunotherapies for solid tumours., (© 2023. Springer Nature Limited.)

HIV-1 reverse transcriptase (RT) is considered as one of the most significant targets for the anti-HIV-1 drug design due to their determined mechanism and well-decoded crystal structure. As a part of our continuous efforts towards the development of potent HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) by exploiting the tolerant region I of NNRTIs binding pocket (NNIBP), the miniaturized parallel synthesis via CuAAC click chemistry reaction followed by in situ biological screening have been performed in this work. The in situ enzyme inhibition screening results showed that 14 compounds exhibited higher or equivalent inhibitory activity compared to the lead K-5a2 and ETR. Anti-HIV-1 activity results indicated that C1N51 displayed the most potent activity (EC 50  = 0.01-0.26 μM) against wild-type and a panel of NNRTIs-resistant strains. Moreover, the molecular simulation demonstrated that the newly introduced triazole ring could develop new hydrogen bonds with Lys103 and Pro236, which explained the feasibility of introducing triazole in the tolerant region I of the RT binding pocket., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Improving high-temperature tolerance of microalgae is crucial to enhance the robustness and economy of microalgae industrial production. Herein, a continuous adaptive laboratory evolution (ALE) system was developed to generate the thermotolerant strain of Chlorella sorokiniana. The resulting thermotolerant strain TR42 exhibited excellent cell growth and biomass production at 42 °C, the temperature that the original strain (OS) could not survive. The high-temperature resistant mechanism of TR42 was investigated by integrating the physiology, transcriptome, proteome and metabolome analyses, which involved enhancing antioxidant capacity, maintaining protein homeostasis, remodeling photosynthetic metabolism, and regulating the synthesis of heat-stress related metabolites. The proof-of-concept high-temperature outdoor cultivation demonstrated that TR42 exhibited 1.15- to 5.72-fold increases in biomass production and 1.62- to 7.04-fold increases in lipid productivity compared to those of OS, respectively, which provided a promising platform for microalgae industrial production. Thus, the multi-system thermotolerant mechanism of TR42 offered potential targets for enhancing high-temperature tolerance of microalgae., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Trace amine-associated receptor 1 (TAAR1) senses a spectrum of endogenous amine-containing metabolites (EAMs) to mediate diverse psychological functions and is useful for schizophrenia treatment without the side effects of catalepsy. Here, we systematically profiled the signaling properties of TAAR1 activation and present nine structures of TAAR1-Gs/Gq in complex with EAMs, clinical drugs, and synthetic compounds. These structures not only revealed the primary amine recognition pocket (PARP) harboring the conserved acidic D 3.32 for conserved amine recognition and "twin" toggle switch for receptor activation but also elucidated that targeting specific residues in the second binding pocket (SBP) allowed modulation of signaling preference. In addition to traditional drug-induced Gs signaling, Gq activation by EAM or synthetic compounds is beneficial to schizophrenia treatment. Our results provided a structural and signaling framework for molecular recognition by TAAR1, which afforded structural templates and signal clues for TAAR1-targeted candidate compounds design., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Ultra-low molecular weight (ULMW) CO 2 -polyols with well-defined hydroxyl end groups represent useful soft segments for the preparation of high-performance polyurethane foams. However, owing to the poor proton tolerance of catalysts towards CO 2 /epoxide telomerization, it remains challenging to synthesize ULMW yet colorless CO 2 -polyols. Herein, we propose an immobilization strategy of constructing supported catalysts by chemical anchoring of aluminum porphyrin on Merrifield resin. The resulting supported catalyst displays both extremely high proton tolerance (≈8000 times the equivalents of metal centers) and independence of cocatalyst, affording CO 2 -polyols with ULMW (580 g mol -1 ) and high polymer selectivity (>99 %). Moreover, the ULMW CO 2 -polyols with various architectures (tri-, quadra-, and hexa-arm) can be obtained, suggesting the wide proton universality of supported catalysts. Notably, benefiting from the heterogeneous nature of the supported catalyst, colorless products can be facilely achieved by simple filtration. The present strategy provides a platform for the synthesis of colorless ULMW polyols derived from not only CO 2 /epoxides, but also lactone, anhydrides etc. or their combinations., (© 2023 Wiley-VCH GmbH.)

Ultraviolet C (UVC) sterilization has the advantages of high efficiency, broad spectrum, and no secondary pollution. However, the emission wavelength of UVC phosphors still suffers from a large deviation from the golden sterilization wavelength of 265 nm and a low luminescence intensity. Herein, we report UVC emission near the golden sterilization wavelength as well as a long afterglow through crystal field engineering, which can lead to 100% sterilization efficiency. Combined with theoretical calculation and experimental studies, substitution of Ca 2+ with large-sized Sr 2+ could obtain slight expansion and distortion of cationic sites, resulting in a decrease in crystal field intensity and blue shift of Ca 1.5 Sr 0.5 Al 2 SiO 7 :1%Pr 3+ , and produce near golden UVC emission. Ca 1.5 Sr 0.5 Al 2 SiO 7 :1%Pr 3+ phosphor can effectively inactivate Staphylococcus aureus within 10 min, showing more efficiency than the traditional mercury lamp. This work provides an effective solution for the design and preparation of UVC phosphors using crystal field engineering toward near golden UVC emission.

Mining salt tolerance genes is significant for breeding high-quality salt-tolerant rice varieties in order to improve the utilization of saline-alkaline land. In this study, 173 rice accessions were measured for their germination potential (GP), germination rate (GR), seedling length (SL), root length (RL), germination potential relative to salt damage rate (GPR), germination rate relative to salt damage rate (GRR), seedling length relative to salt damage rate (SLR), relative salt damage rate at the germination stage (RSD) and comprehensive relative salt damage rate in the early seedling stage (CRS) under normal and salt stress conditions. Genome-wide association analysis was performed with 1,322,884 high-quality SNPs obtained by resequencing. Eight quantitative trait loci (QTLs) related to salt tolerance traits at the germination stage were detected in 2020 and 2021. They were related to the GPR ( qGPR2 ) and SLR ( qSLR9 ), which were newly discovered in this study. Three genes were predicted as salt tolerance candidate genes: LOC&#95;Os02g40664, LOC&#95;Os02g40810 , and LOC&#95;Os09g28310 . At present, marker-assisted selection (MAS) and gene-edited breeding are becoming more widespread. Our discovery of candidate genes provides a reference for research in this field. The elite alleles identified in this study may provide a molecular basis for cultivating salt-tolerant rice varieties.

Recent advances in tumor microenvironment (TME) modeling as well as its applications to cancer therapy has brought various dramatical changes in multiple malignancies management. Understanding the mechanisms of response and resistance to cancer therapy requires a clear elucidation of the intricate interactions between TME cells, the surrounding stroma, and distant affected tissues or organs. To address this demand, various three-dimensional (3D) cell culture techniques have been developed in order to recapitulate and understand cancer biology over the past decade. This review summarizes some saliant progresses in in vitro 3D TME modeling, including the cell-based, matrix-based, and vessel-based dynamic 3D modeling techniques and their applications in investigating tumor-stroma interactions and responses to cancer therapies. The review also discusses the limitations of current TME modeling approaches and proposes some new thoughts on the construction of more clinically relevant models., (© 2023 IOP Publishing Ltd.)

Bi 4 Ge 3 O 12 (BGO) is a traditional scintillator, widely used in high-energy physics and nuclear medicine. However, it not only suffers from low scintillation intensity but also tends to be damaged by high-energy rays. Herein, we prepare pure-phase BGO materials enriched with Bi vacancies by rationally reduced Bi content, showing significantly enhanced luminescence intensity and irradiation resistance ability. The optimized Bi 3.6 Ge 3 O 12 shows 178% of luminescence intensity compared to BGO. After 50 h of ultraviolet irradiation, Bi 3.6 Ge 3 O 12 possesses ∼80% of original luminescence intensity, much superior to the 60% for BGO. The existence of the Bi vacancy is identified by advanced experimental and theoretical studies. The mechanism studies show the Bi vacancies could cause the symmetry destruction of the local field around the Bi 3+ ion. It enhances scintillation luminescence by increasing the probability of radiative transition while resisting nonradiative relaxation caused by irradiation damage. This study initiates vacancy-induced performance enhancement for inorganic scintillators.

Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

This study presents proof of concept for designing a novel HIV-1 covalent inhibitor targeting the highly conserved Tyr318 in the HIV-1 non-nucleoside reverse transcriptase inhibitors binding pocket to improve the drug resistance profiles. The target inhibitor ZA-2 with a fluorosulfate warhead in the structure was found to be a potent inhibitor (EC 50 = 11-246 nM) against HIV-1 IIIB and a panel of NNRTIs-resistant strains, being far superior to those of NVP and EFV. Moreover, ZA-2 was demonstrated with lower cytotoxicity (CC 50 = 125 µM). In the reverse transcriptase inhibitory assay, ZA-2 exhibited an IC 50 value of 0.057 µM with the ELISA method, and the MALDI-TOF MS data demonstrated the covalent binding mode of ZA-2 with the enzyme. Additionally, the molecular simulations have also demonstrated that compounds can form covalent binding to the Tyr318.

Eu 3+ -doped GdAlO 3 (Eu:GAP) and Gd 0.5 La 0.5 AlO 3 (Eu:GLAP) perovskite single crystals were successfully grown using the optical floating zone (OFZ) method. The microstructure, optical, photoluminescence (PL) and radioluminescence (under X-ray excitation, XEL) were investigated. Under the PL excitation of 275 nm, obvious emission bands peaking at 556 nm, 592 nm, 617 nm, 625 nm, 655 nm, and 706 nm were demonstrated, which correspond to the 5D 0 → 7F j (j = 0-4) transitions of Eu 3+ . The grown Eu:GAP single crystal showed a stronger PL intensity compared with that of Eu:GLAP in the red light region. After annealing at 1000 °C for 4 h in weak reductive atmosphere (Ar + 5% H 2 ), a slight redshift and dramatic enhancement of PL and XEL intensity occurred. In addition, Eu:GLAP show a more intense XEL emission than that of Eu:GAP. Considering their different densities, these two kinds of red luminescence phosphors are proposed to be promising in a wide field of X-ray imaging, warm white, or plant lighting, respectively.

Ce 3+ , Pr 3+ co-doped Lu 3 Al 5 O 12 (Ce, Pr:LuAG) single crystals and ceramics were prepared using the optical floating zone (OFZ) and reactive vacuum sintering methods, respectively. The microstructure, photo- (λ ex = 450 nm), and radio-luminescence (under X-ray excitation) performance, as well as scintillation light yield (LY, under γ-ray, 137 Cs source) of both materials, were investigated and compared. Ce, Pr:LuAG ceramics had an in-line transmittance of approximately 20% in the visible light range, while the analogous crystals were more transparent (~65%). The X-ray excited luminescent (XEL) spectra showed the characteristic Ce 3+ and Pr 3+ emissions located at 310 nm, 380 nm, and 510 nm. The highest LY of the Ce, Pr:LuAG ceramics reached 34,112 pho/MeV at 2 μs time gate, which is higher than that of a single crystal. The ratio of LY values (LY2/LY0.75) between shaping times of 0.75 μs and 2 μs indicated a faster scintillation decay of ceramics regarding single crystals. It was ascribed to the lower effective concentration of luminescent activators in single crystals because of the coefficient segregation effect.

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) represent an indispensable part of anti-HIV-1 therapy. To discover novel HIV-1 NNRTIs with increased drug resistance profiles and improved pharmacokinetic (PK) properties, a series of novel diarylpyrimidine derivatives were generated via the cocrystal structure-based drug design strategy. Among them, 36a exhibited outstanding antiviral activity against HIV-1 IIIB and a panel of mutant strains (L100I, K103N, Y181C, Y188L, E138K, F227L + V106A, and RES056), with EC 50 ranging from 2.22 to 53.3 nM. Besides, 36a was identified with higher binding affinity ( K D = 2.50 μM) and inhibitory activity (IC 50 = 0.03 μM) to HIV-1 RT. Molecular docking and molecular dynamics simulation were performed to rationalize the design and the improved drug resistance of these novel inhibitors. Additionally, 36a·HCl exhibited favorable PK ( T 1/2 = 5.12 h, F = 12.1%) and safety properties (LD 50 > 2000 mg/kg). All these suggested that 36a·HCl may serve as a novel drug candidate anti-HIV-1 therapy.

Environmental problem caused by carbon emission is of widespread concern. Involving CO 2 as C 1 resource into chemical synthesis is one of the most attractive ways for carbon recycling. Herein, the first example of host-guest composites featuring metal-organic framework (MOF)-encapsulated binuclear N-heterocyclic carbene (NHC) complex, Co 2 @MIL101, was developed with the molecularly dispersed [Co(IPr)Br] 2 (μ-Br) 2 (Co 2 ) loading in the cage of MIL-101(Cr) via a "ligand-in-dimer-trap" strategy, which was comprehensively investigated through various techniques including synchrotron X-ray absorption, electron microscopy, X-ray diffraction, solid-state nuclear magnetic resonance spectroscopy, and others. The noble-metal-free double-sites catalyst Co 2 @MIL101 exhibited promising stability, activity, efficiency, reusability, and substrate adaptability for converting CO 2 into various formamides with amines and hydrosilanes and achieved the best performance for one of the most useful formamides, N-methyl-N-phenylformamide (MFA), among the recyclable catalysts at ambient conditions, providing a reliable approach to successfully unify the advantages of both homo- and heterogeneous catalysts. Density functional theory calculations were applied to illustrate the superior activity of the binuclear NHC complex center as double-sites catalyst toward the activation of CO 2 ., (© 2022 Wiley-VCH GmbH.)

Organizational resilience is vital to the survival and thriving of enterprises, especially during the COVID-19 pandemic. Although there has been an increasing interest in organizational resilience, the effects from the entrepreneur perspective receive scant attention. Based on upper echelons theory (UET) and personality psychology, we propose a model in which entrepreneurial mindfulness and entrepreneurial resilience could influence organizational resilience of SMEs. We empirically analyzed a sample of 180 entrepreneurs managing small- and medium-sized enterprises (SMEs) in China during the COVID-19 pandemic, using SmartPLS software. The research findings indicated that entrepreneurial mindfulness is positively associated with organizational resilience and such relationship is partially mediated by entrepreneurial resilience. These findings convey important theoretical implications in this field of research as well as practical implications for SMEs in China or other countries with similar nature., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Wu, Wang and Zhou.)

Uniquely, thiourea dioxide not only can reduce carbonyl compounds but also generate an oxidant to trigger luminol chemiluminescence. Herein, derivatization-free carbonyl compound detection using bifunctional chemiluminescence coreactant thiourea dioxide has been developed for the first time with the second most crucial flavor benzaldehyde as a representative.

For high-throughput anti-cancer drug screening, microwell arrays may serve as an effective tool to generate uniform and scalable tumor spheroids. However, microwell arrays are commonly anchored in non-oxygen-permeable culture plates, leading to limited oxygen supply for avascular spheroids. Herein, a polydimethylsiloxane (PDMS)-based oxygen-permeable microwell device is introduced for generating highly viable and functional hepatocellular carcinoma (HCC) spheroids. The PDMS sheets at the bottom of the microwell device provide a high flux of oxygen like in vivo neighboring hepatic sinusoids. Owing to the better oxygen supply, the generated HepG2 spheroids are larger in size and exhibit higher viability and proliferation with less cell apoptosis and necrosis. These spheroids also exhibit lower levels of anaerobic cellular respiration and express higher levels of liver-related functions. In anti-cancer drug testing, spheroids cultured in PDMS plates show a significantly stronger resistance against doxorubicin because of the stronger stem-cell and multidrug resistance phenotype. Moreover, higher expression of vascular endothelial growth factor-A produces a stronger angiogenesis capability of the spheroids. Overall, compared to the spheroids cultured in conventional non-oxygen-permeable plates, these spheroids can be used as a more favorable model for early-stage HCCs and be applied in high-throughput anti-cancer drug screening., (© 2022 Wiley-VCH GmbH.)

Carbonic anhydrase XIV (Car14) is highly expressed in the hepatocyte, with predominance in the canalicular membrane and its active site in the extracellular milieu. The aim of this study is to determine the physiological relevance of Car14 for biliary fluid and acid/base output, as well as its role in the maintenance of hepatocellular and cholangiocyte integrity. The common bile duct of anesthetized car14 -/- and car14 +/+ mice was cannulated and hepatic HCO 3 - output was measured by microtitration and bile flow gravimetrically before and during stimulation with intravenously applied tauroursodeoxycholic acid (TUDCA). Morphological alterations and hepatic damage were assessed histologically and immunohistochemically in liver tissue from 3- to 52-week-old car14 -/- and car14 +/+ mice, and gene and/or protein expression was measured for pro-inflammatory cytokines, fibrosis, and cholangiocyte markers. Biliary basal and more so TUDCA-stimulated HCO 3 - output were significantly reduced in car14 -/- mice of all age groups, whereas bile flow and hepatic and ductular morphology were normal at young age. Car14 -/- mice developed fibrotic and proliferative changes in the small bile ducts at advanced age, which was accompanied by a reduction in bile flow, and an upregulation of hepatic cytokeratin 19 mRNA and protein expression. Membrane-bound Car14 is essential for biliary HCO 3 - output, and its loss results in gradual development of small bile duct disease and hepatic fibrosis. Bile flow is not compromised in young adulthood, suggesting that Car14-deficient mice may be a model to study the protective role of biliary canalicular HCO 3 - against luminal noxi to the cholangiocyte., (© 2022. The Author(s).)

To obtain a deeper understand of the energy transfer mechanism between Ce 3+ and Tb 3+ ions in the aluminum garnet hosts, (Ce, Tb, Gd) 3 Ga 2 Al 3 O 12 (GGAG:Ce, Tb) single crystals grown by the optical floating zone (OFZ) method were investigated systematically in a wide range of Tb 3+ doping concentration (1-66 at.%). Among those, crystal with 7 at.% Tb reached a single garnet phase while the crystals with other Tb 3+ concentrations are mixed phases of garnet and perovskite. Obvious Ce and Ga loss can be observed by an energy dispersive X-ray spectroscope (EDS) technology. The absorption bands belonging to both Ce 3+ and Tb 3+ ions can be observed in all crystals. Photoluminescence (PL) spectra show the presence of an efficient energy transfer from the Tb 3+ to Ce 3+ and the gradually quenching effect with increasing of Tb 3+ concentration. GGAG: 1% Ce 3+ , 7% Tb 3+ crystal was found to possess the highest PL intensity under excitation of 450 nm. The maximum light yield (LY) reaches 18,941 pho/MeV. The improved luminescent and scintillation characteristics indicate that the cation engineering of Tb 3+ can optimize the photoconversion performance of GGAG:Ce.

Rice leaf angle is an important agronomic trait determining plant architecture and crop yield. Brassinosteroids (BRs) play crucial roles in controlling rice leaf angle, thus an increasing number of researches were focused on the BR signaling pathway in rice. However, the orthologs of some important components in Arabidopsis BR signaling have not yet been characterized in rice. In this study, we identified a rice bHLH transcription factor named OsBIM1, as the closest rice homolog of AtBIM1 (BES1-Interacting MYC-like Protein1). Overexpression of OsBIM1 significantly increases rice leaf angles, whereas the T-DNA knock-out mutant osbim1 and wide type (WT) showed similar leaf inclination. OsBIM1 overexpression enhances the sensitivity and response to BR treatment in rice. Gene expression analysis showed that the overexpression of OsBIM1 significantly increased the transcripts of INCREASED LEAF INCLINATION1 (OsILI1) that functions as a key transcription factor promoting BR signaling and response. Meanwhile, OsBIM1 inhibited the expression of DWARF2 (OsD2, a key enzyme in BR biosynthesis pathway). OsBIM1 can bind with OsILI1 promoter and enhance OsILI1 expression in response to BR treatment. The promoting effect of OsBIM1 overexpression on leaf angle can still be observed at harvest stage, but overexpression of OsBIM1 resulted in smaller grain size and reduced yield. These results indicate that OsBIM1 functions as a positive regulator in BR signaling, and its overexpression increases rice lamina inclination by promoting BR sensitivity and response., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Gastric cancer is the one of the most lethal malignancies of digestive system. Identifying molecular biomarkers is invaluable in help predicting clinical outcomes and developing targeted chemotherapies. GINS complex subunit 2 (GINS2) plays an essential role in the initiation and elongation of DNA replication. Although there have been studies revealing the prognostic significance of GINS2 in breast cancer and lung cancer, its involvement and function in gastric cancer need to be elucidated. We retrospectively enrolled a cohort of gastric adenocarcinoma patients after surgical resection (n = 123). By analyzing the mRNA and protein levels of GINS2 in tissue samples, we found that GINS2 presented a higher expression in tumor tissues than in adjacent normal stomach tissues. Besides, GINS2 level was positively correlated with tumor size and gastric adenocarcinoma tumor stage, implying its potential role as a tumor promoter. Univariate and multivariate analyses identified that patients with lower GINS2 showed a better overall survival compared to those with higher GINS2 expression. In addition, cellular and xenograft experiments confirmed the role of GINS2 in facilitating tumor proliferation both in vitro and in vivo. To our knowledge, this is the initial finding on GINS2 in promoting gastric adenocarcinoma progression. In conclusion, our study revealed a pro-oncogenic role of GINS2 in gastric cancer.

Colorectal cancer (CRC) liver metastasis is a significant clinical problem for which better therapies are urgently needed. Tumor-associated macrophage, a major cell population in the tumor microenvironment, is a known contributor to primary cancer progression and cancer metastasis. Here, we found TAM recruitment and M2 polarization were increased in the hepatic metastatic lesion compared with the primary site of human CRC tissues. Moreover, Pearson correlation analysis showed that TAM recruitment and polarization were closely correlated with the elevated TCF4 expression in the metastatic site. To investigate the role of TCF4 in CRC liver metastasis, we generated a syngeneic mouse model using MC38 cells splenic injection. Results from in vivo experiments and mouse models revealed that TCF4 deficiency in MC38 cells does not affect their proliferation and invasion; however, it reduces TAM infiltration and M2 polarization in the metastasis site. Further studies indicated that these effects are mediated by the TCF4 regulated CCL2 and CCR2 expression. TCF4 or CCL2 silencing in the tumor cells prevent CRC liver metastasis in the mouse model. Altogether, these findings suggest that the TCF4-CCL2-CCR2 axis plays an essential role in CRC liver metastasis by enhancing TAMs recruitment and M2 polarization., (© 2021. The Author(s).)

Maintaining Na + /K + homeostasis is a critical feature for plant survival under salt stress, which depends on the operation of Na + and K + transporters. Although some K + transporters mediating root K + uptake have been reported to be essential to the maintenance of Na + /K + homeostasis, the effect of K + long-distance translocation via phloem on plant salt tolerance remains unclear. Here, we provide physiological and genetic evidence of the involvement of phloem-localized OsAKT2 in rice salt tolerance. OsAKT2 is a K + channel permeable to K + but not to Na + . Under salt stress, a T-DNA knock-out mutant, osakt2 and two CRISPR lines showed a more sensitive phenotype and higher Na + accumulation than wild type. They also contained more K + in shoots but less K + in roots, showing higher Na + /K + ratios. Disruption of OsAKT2 decreases K + concentration in phloem sap and inhibits shoot-to-root redistribution of K + . In addition, OsAKT2 also regulates the translocation of K + and sucrose from old leaves to young leaves, and affects grain shape and yield. These results indicate that OsAKT2-mediated K + redistribution from shoots to roots contributes to maintenance of Na + /K + homeostasis and inhibition of root Na + uptake, providing novel insights into the roles of K + transporters in plant salt tolerance., (© 2021 John Wiley & Sons Ltd.)

The activity of a gene newly integrated into a chromosome depends on the genomic context of the integration site. This "position effect" has been widely reported, although the other side of the coin, that is, how integration affects the local chromosomal environment, has remained largely unexplored, as have the mechanism and phenotypic consequences of this "externality" of the position effect. Here, we examined the transcriptome profiles of approximately 250 Saccharomyces cerevisiae strains, each with GFP integrated into a different locus of the wild-type strain. We found that in genomic regions enriched in essential genes, GFP expression tended to be lower, and the genes near the integration site tended to show greater expression reduction. Further joint analysis with public genome-wide histone modification profiles indicated that this effect was associated with H3K4me2. More importantly, we found that changes in the expression of neighboring genes, but not GFP expression, significantly altered the cellular growth rate. As a result, genomic loci that showed high GFP expression immediately after integration were associated with growth disadvantages caused by elevated expression of neighboring genes, ultimately leading to a low total yield of GFP in the long run. Our results were consistent with competition for transcriptional resources among neighboring genes and revealed a previously unappreciated facet of position effects. This study highlights the impact of position effects on the fate of exogenous gene integration and has significant implications for biological engineering and the pathology of viral integration into the host genome., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

Nowadays, artificial construction of bacteria-algae consortia to enhance microalgal biomass is prevalent in enclosed systems, while few are built in an open culture. In this study, Achromobacter sp. and Rhizobium sp., isolated from an open pond of Chlorella sorokiniana, were the microalgal growth-promotion bacteria and selected to build the bacteria-algae consortia with axenic C. sorokiniana in open cultivation systems. To examine the performance of these two artificial bacteria-algae consortia in open culture under stable cultivation conditions, the co-cultivation experiments were conducted under constant temperature and light intensity indoors. It was found that Achromobacter sp. gradually lost the dominance of the population in the co-culture and failed to promote the growth of C. sorokiniana during open cultivation. However, the Rhizobium sp. maintained its dominant population of bacterial community in open culture and could promote the growth of C. sorokiniana, with an enhancement of 13.76%. To further evaluate the effects of Rhizobium sp. on microalgae under variations of temperature and sunlight intensity conditions, the open co-cultivation experiments were built outdoors. Results showed that the growth of C. sorokiniana could rise 13.29% only when Rhizobium sp. was added to the culture continuously, and addition of bacterial solution in log-phase of microalgae could help Rhizobium sp. dominate in the bacterial community. In this way, addition of Rhizobium sp. in the log-phase of C. sorokiniana should be an effective process to be applied to open ponds cultivation. Our findings are a step toward applying growth-promotion bacteria for C. sorokiniana for applications in open cultivation systems.

Cell alignment plays an essential role in cytoskeleton reorganization, extracellular matrix remodeling, and biomechanical properties regulation of tissues such as vascular tissues, cardiac muscles, and tendons. Based on the natural-oriented features of cells in native tissues, various biomimetic scaffolds have been reported with the introduction of well-arranged ultrafine fibers to induce cell alignment. However, it is still a challenge to fabricate scaffolds with suitable mechanical properties, biomimetic microenvironment, and ability to promote cell alignment. In this paper, we propose an integrated 3D printing system to fabricate multi-scale hierarchical scaffolds combined with meso-, micro-, and nano-fibrous filaments, in which the meso-, micro-, and nano-fibers fabricated via fused deposition modeling, melt electrospining writing, and solution electrospining can provide structural support, promote cell alignment, and create a biomimetic microenvironment to facilitate cell function, respectively. The plasma surface modification was performed improve the surface wettability of the scaffolds by measuring the contact angle. The obtained in vitro biological results validate the ability of multi-scale hierarchical scaffolds to enhance cell adhesion and proliferation, and promote cell alignment with the guidance of the aligned microfibers produced via melt electrospining writing in hierarchical scaffolds., (© 2021 IOP Publishing Ltd.)

Microalgal oil is considered a promising candidate for edible oils. However, investigation of the refining processes of microalgal oil has been limited, especially deacidification. In this work, microcrystalline cellulose (MCC) was pretreated using different methods and utilized for the first time in the deacidification of microalgal oil. Detection results from FTIR and XRD indicated alkali pretreatment had a significant effect on the structure of MCC. Some inter- and intramolecular hydrogen bonds in AMCC (alkali-pretreated MCC) were destroyed, and crystallinity index of cellulose decreased, which increased its adsorption capacity and the reaction of OH groups with free fatty acids. Some NaOH was adsorbed into AMCC through cellulose swelling, which also contributed to deacidification. The interaction with oil was also improved with many cracks and voids on the surface of AMCC. AMCC could reduce the acid value to about 2 mg KOH/g. Comparatively, original MCC and MCC pretreated with microwave or ultrasound did not exhibit the ability to deacidify. Furthermore, the conditions of alkali treatment were optimized. Treatment with 20% NaOH for 20 min was optimal. Compared with other adsorbents, such as sodium silicate and chitosan treated with alkali and resin, only AMCC could effectively reduce acid value while maintaining high lipid recovery. Therefore, AMCC was considered a better adsorbent for the deacidification of microalgal oil.

High-throughput experiment can significantly accelerate the materials research efficiency. Thanks to national efforts, the Materials Genome Initiative further promotes the development of high-throughput experimental technology. A multi-channel fiber optical spectrometer has been designed and developed by us for high-throughput characterization of photoluminescence (PL) properties. It can quickly and automatically detect the PL spectrum, Commission International de l'Eclairage chromaticity, and PL intensity over time for luminescent materials under a given condition. The multi-channel fiber optical spectrometer synergistically combines a sample library holder, multiple modular excitation sources, multiple spectrometers, and Coral software, so it can measure and analyze multiple samples simultaneously. The number of channels in the multi-channel fiber optical spectrometer can be added or subtracted as required. Various modular light-emitting diode or laser diode excitation sources with the wavelength from 370 nm to 980 nm and corresponding filters can be provided according to the measurement need of different luminescent materials. The monitoring wavelength of the currently used fiber optical spectrometer is from 300 nm to 1000 nm. For example, the PL spectral measurement of 54 samples in a {6 × 9} array is completed in only about 30 min by using a representative triple-channel fiber optical spectrometer. The designed multi-channel fiber optical spectrometer facility not only makes PL measurements faster and more intuitive but is also easy to popularize for wide users.

The calanoid copepod, Acartia tonsa, is relatively sensitive to marine pollution. Glutathione S-transferase (GST) multifunctional enzyme, as a biomarker, play an important role in detoxification metabolism of exogenous substances. In the present study, GST-theta and GST-mu class homology genes (designated as AtGSTT1 and AtGSTM2) were identified and characterized from A. tonsa. The coding sequence of AtGSTT1 comprised 726 bp and encoded a putative protein of 241 amino acid residues. AtGSTM2 contained an open reading frame of 678 bp that encoded a putative 227 amino acid polypeptide. Both proteins contained a conserved GST-N domain and a GST-C domain. Structural analysis revealed the characteristic N-terminal G-site. Three-dimensional structure analysis showed that AtGSTT1 and AtGSTM2 have two typical domains of GST family: The βαβαββα topology structure at the N- terminus and the superhelical structure at the C- terminus. Subsequently, the expression levels of the two GST genes were detected in A. tonsa using real-time quantitative PCR after exposure to 1,2-dimethylnaphthalene (C2-NAPH) at different concentrations (0.574, 5.736 and 57.358 μg/L) for 24, 48, 72, and 96 h. AtGSTT1 mRNA expression was significantly up-regulated in a time-dependent manner and the highest mRNA expression occurred at 5.736 μg/L C2-NAPH exposure for 96 h. AtGSTM2 mRNA expression peaked at 72 h in 0.574 μg/L and 5.736 μg/L dose groups. The expression level of AtGSTM2 showed an increasing trend in a time-dependent manner at 57.358 μg/L of C2-NAPH. These results suggested that GST genes may play an important role in protecting A. tonsa from C2-NAPH pollution, and provide a theoretical basis for further study on the molecular mechanism of polycyclic aromatic hydrocarbon (PAHs) pollution on zooplankton., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Cervical cancer induced by human papillomavirus (HPV) causes severe morbidity worldwide. Although cervical conization has been widely accepted as the most conventional surgery against cervical cancer, tissue defects and high recurrence rates have a significant negative impact on women's mental and physical health. Herein we developed an implantable, personalized cervical implant with drug release function using 3D printing technology. The cervical implant was designed in cone-shape with hieratical porous structures according to the clinical data, 3D-printed using polyurethane by low-temperature deposition manufacturing (LDM), and finished by lyophilization. Anti-HPV protein was loaded into the porous structure under negative pressure afterwards. Elastic biomedical polyurethane and the porous structure ensured that these cervical implants were equipped with tailored mechanical properties comparable to physiological cervix tissue. Cytotoxicity and cytocompatibility tests indicated that these 3D-printed cervical implants supported cell adhesion and growth. More importantly, the cervical implants with regulated pores could help to quantitatively control the loading and release of anti-HPV protein to inhibit dissociative viruses near the cervix validly. As a result, the 3D-printed cervical implants in the present study showed considerable potential for use as functional tissue implants against HPV infection after cervical conization.

The plant Shaker K + channel AtAKT2 has been identified as a weakly rectifying channel that can stabilize membrane potentials to promote photoassimilate phloem loading and translocation. Thus, studies on functional characterization and regulatory mechanisms of AtAKT2-like channels in crops are highly important for improving crop production. Here, we identified the rice OsAKT2 as the ortholog of Arabidopsis AtAKT2, which is primarily expressed in the shoot phloem and localized at the plasma membrane. Using an electrophysiological assay, we found that OsAKT2 operated as a weakly rectifying K + channel, preventing H + /sucrose-symport-induced membrane depolarization. Three critical amino acid residues (K193, N206, and S326) are essential to the phosphorylation-mediated gating change of OsAKT2, consistent with the roles of the corresponding sites in AtAKT2. Disruption of OsAKT2 results in delayed growth of rice seedlings under short-day conditions. Interestingly, the lipid second messenger phosphatidic acid (PA) inhibits OsAKT2-mediated currents (both instantaneous and time-dependent components). Lipid dot-blot assay and liposome-protein binding analysis revealed that PA directly bound with two adjacent arginine residues in the ANK domain of OsAKT2, which is essential to PA-mediated inhibition of OsAKT2. Electrophysiological and phenotypic analyses also showed the PA-mediated inhibition of AtAKT2 and the negative correlation between intrinsic PA level and Arabidopsis growth, suggesting that PA may inhibit AKT2 function to affect plant growth and development. Our results functionally characterize the Shaker K + channel OsAKT2 and reveal a direct link between phospholipid signaling and plant K + channel modulation., (© 2020 Society for Experimental Biology and John Wiley & Sons Ltd.)

The objective of this work was to evaluate the effects of extrusion pretreatment on the efficiency of lipid extraction and the quality of lipid extracted from the microalga Nannochloropsis oceanica. Five processing parameters of extrusion pretreatment using a twin-screw extruder were studied: die configuration, distance from the internal surface of the die to the end of the screw (δ), temperature, screw rotation speed, and the water content of biomass. The results showed that die configuration, δ, and the water content of the biomass were vital factors affecting lipid extraction efficiency. After the pretreatment of extrusion, the extraction time was shortened from 10 h to 20 min, and the amount of solvent used was reduced to one-third of that without pretreatment. The content of polyunsaturated fatty acid (PUFA) in crude lipid increased by over 30 percent of those components without pretreatment, especially for eicosapentaenoic acid (EPA), which increased by 37.45%. In addition, the unsaponifiable content and acid value of the crude lipid extracted from the extruded microalga decreased significantly, which would facilitate further refining processes.

We report a novel Nd 3+ and Eu 3+ co-doped Sr 2 SnO 4 (SSONE) phosphor showing the capability of "write-in" and "read-out" in optical information storage. As-prepared phosphors exhibit a dominant emission (PL) band centered at 596 nm under UV excitation, closely identical with its photo-stimulated luminescence (PSL) spectrum center (595 nm) upon near-infrared (NIR) light and thermal-stimulated luminescence (TSL) spectrum center (595 nm) under heat source. Remarkably, compared with Eu 3+ single-doped phosphors, the co-doping strategy enhances the deep traps and also separates the deep traps with shallow traps, which are very crucial factors for optical information storage in electron trapping materials. Further, a demonstration confirmed the optical information storage capacity by photo- and thermal-stimulating the prepared phosphors filled in the designed patterns.

Propofol is an intravenous anesthetic widely used in clinical surgeries, such as tumor resection. Propofol affects the growth of many cancers, though its effect on melanoma is unknown. Our study aimed to explore how propofol affects melanoma cells. Melanoma cells A2058 and WM793B were cultured with propofol for 24 hr. Propofol significantly suppressed proliferation, migration, and invasion of A2058 and WM793B cells. Lower miR-137 level was observed in A2058 and WM793B cells, compared with normal human epidermal melanocyte HEMa-LP cells. Propofol-induced miR-137 upregulation and decreased proliferation, invasive ability, and migrated ability of A2058 and WM793B cells. Transfection with the miR-137 inhibitor reversed these effects. Additionally, miR-137 was verified to target and negatively regulate fibroblast growth factor 9 (FGF9) expression. Propofol efficiently downregulated FGF9 protein expression by upregulating miR-137. Furthermore, FGF9 overexpression abrogated propofol's repressive effects on the malignant potential of A2058 and WM793B cells. These findings indicate that propofol suppressed melanoma cell proliferation, invasion, and migration by regulating miR-137 and FGF9., (© 2019 Wiley Periodicals, Inc.)

Off-line multi-hyphenated methods including affinity-ultrafiltration mass spectrometry, molecular docking, and reverse-phase high-performance liquid chromatography-fluorescence detection (RP-HPLC-FD) were used to rapidly screen and identify natural inducible nitric oxide synthase (iNOS) inhibitors isolated from Ophiopogon japonicus (Thunb.) Ker-Gawl. Ultrafiltration high-performance liquid chromatography quadrupole time-of-flight mass spectrometry was used to screen and identify the potential ligands with high binding affinity to iNOS. Seven compounds (three saponins and four flavonoids) were found in Radix Ophiopogonis. Molecular docking identified the binding sites and found that the binding affinity of the three ophiopogonis ligands was higher than that of the four homoisoflavonoids. Pre-column derivatization of l-citrulline and RP-HPLC-FD verified that the in vitro inhibition activity of the three ophiopogonis compounds was stronger than that of the four homoisoflavonoids, which was similar to the screened results. In conclusion, combining an in vitro iNOS inhibition assay and affinity-ultrafiltration mass spectrometry with molecular docking was a powerful tool for rapid screening and identification of iNOS inhibitors isolated from this traditional Chinese medicine., (Copyright © 2019 Elsevier B.V. All rights reserved.)