[Source and Cause Analysis of High Concentration of Inorganic Aerosol During Two Typical Pollution Processes in Winter over Tianjin].

Inorganic aerosol is the main component of haze days in winter over Tianjin. In this study, two typical high concentrations of secondary inorganic aerosol (SIA) processes, defined as CASE1 and CASE2, were selected during polluted days in January 2020 over Tianjin, and the effects of meteorological factors, regional transport, and chemical processes were comprehensively investigated combined with observations and numerical models (WRF-NAQPMS). The average SIA concentrations in CASE1 and CASE2 were 76.8 µg·m-3 and 66.0 µg·m-3, respectively, and the nitrate concentration was higher than that of sulfate and ammonium, which were typical nitrate-dominated pollution processes. Meteorological conditions played a role in inorganic aerosol formation. The temperature of approximately -6-0℃ and 2-4℃ and the relative humidity of 50%-60% and 80%-100% would be suitable conditions for the high SIA concentration (>80 µg·m-3) in CASE1, whereas the temperature of approximately 2-4℃ and the relative humidity of 60%-70% would be suitable in CASE2. The average contribution rates of external sources to SIA in the CASE1 and CASE2 processes were 62.3% and 22.1%, which were regional transport-dominant processes and local emission-dominant processes, respectively. The contribution of the local emission of CASE1 to nitrate and sulfate was 16.2 µg·m-3 and 8.2 µg·m-3, respectively, higher than that of external sources (31.7 µg·m-3 and 8.8 µg·m-3). the local contribution of CASE2 to nitrate and sulfate was 29.3 µg·m-3 and 25.1 µg·m-3, respectively, whereas the contribution from external sources was 8.1 µg·m-3 and 9.4 µg·m-3, respectively. The quantitative result indicated that local formation and regional transport resulted in higher nitrate concentration than sulfate in CASE1, in contrast to only local sources in CASE2. The gas phase reaction was the main source of inorganic aerosol formation, contributing 48.9% and 57.8% in CASE1 and CASE2, respectively, whereas the heterogeneous reactions were also important processes, with contribution rates of 48.1% and 42.2% to SIA. The effect of aqueous phase reaction was negligible.

Genomic Characterization of the Mycoparasite Pestalotiopsis sp. Strain cr013 from Cronartium ribicola.

The Pestalotiopsis sp. strain cr013 is a mycoparasite of Cronartium ribicola, a potential biocontrol fungus for Armand pine (Pinus armandii) blister rust. A previous study showed that the strain cr013 has great potential to produce new compounds. However, there has been no report of the whole-genome sequence of the mycoparasite Pestalotiopsis sp. In this study, the BGISEQ-500 and Oxford Nanopore GridION X5 sequencing platforms were used to sequence the strain cr013 isolates and assemble the reads to obtain the complete genome. We first report the whole-genome information of the mycoparasite Pestalotiopsis sp. strain cr013 (GenBank accession number: JACFXT010000000, BioProject ID: PRJNA647543, BioSample ID: SAMN15589943), and the genomic components and gene functions related to the mycoparasitism process were analyzed. This study provides a theoretical basis for understanding the lifestyle strategy of the mycoparasite Pestalotiopsis sp. and reveals the mechanisms underlying secondary metabolite diversity in the strain cr013.

The effects of methylphenidate and atomoxetine on Drosophila brain at single-cell resolution and potential drug repurposing for ADHD treatment.

The stimulant methylphenidate (MPH) and the non-stimulant atomoxetine (ATX) are frequently used for the treatment of attention-deficit/hyperactivity disorder (ADHD); however, the function of these drugs in different types of brain cells and their effects on related genes remain largely unknown. To address these questions, we built a pipeline for the simultaneous examination of the activity behavior and transcriptional responses of Drosophila melanogaster at single-cell resolution following drug treatment. We selected the Drosophila with significantly increased locomotor activities (hyperactivity-like behavior) following the administration of each drug in comparison with the control (same food as the drug-treated groups with 5% sucrose, yeast, and blue food dye solution) using EasyFlyTracker. Subsequently, single cell RNA sequencing (scRNASEQ) was used to capture the transcriptome of 82,917 cells, unsupervised clustering analysis of which yielded 28 primary cell clusters representing the major cell types in adult Drosophila brain. Indeed, both neuronal and glial cells responded to MPH and ATX. Further analysis of differentially expressed genes (DEGs) revealed distinct transcriptional changes associated with these two drugs, such as two well-studied dopamine receptor genes (Dop2R and DopEcR) were responsive to MPH but not to ATX at their optimal doses, in addition to genes involved in dopamine metabolism pathways such as Syt1, Sytalpha, Syt7, and Ih in different cell types. More importantly, MPH also suppressed the expression of genes encoding other neurotransmitter receptors and synaptic signaling molecules in many cell types, especially those for Glu and GABA, while the responsive effects of ATX were much weaker. In addition to monoaminergic neuronal transmitters, other neurotransmitters have also shown a similar pattern with respect to a stronger effect associated with MPH than with ATX. Moreover, we identified four distinct glial cell subtypes responsive to the two drugs and detected a greater number of differentially expressed genes associated with ensheathing and astrocyte-like glia. Furthermore, our study provides a rich resource of candidate target genes, supported by drug set enrichment analysis (P = 2.10E-4; hypergeometric test), for the further exploration of drug repurposing. The whole list of candidates can be found at ADHDrug ( http://adhdrug.cibr.ac.cn/ ). In conclusion, we propose a fast and cost-efficient pipeline to explore the underlying molecular mechanisms of ADHD drug treatment in Drosophila brain at single-cell resolution, which may further facilitate drug repurposing applications.

Unraveling the evolutionary dynamics of the TPS gene family in land plants.

Terpenes and terpenoids are key natural compounds for plant defense, development, and composition of plant oil. The synthesis and accumulation of a myriad of volatile terpenoid compounds in these plants may dramatically alter the quality and flavor of the oils, which provide great commercial utilization value for oil-producing plants. Terpene synthases (TPSs) are important enzymes responsible for terpenic diversity. Investigating the differentiation of the TPS gene family could provide valuable theoretical support for the genetic improvement of oil-producing plants. While the origin and function of TPS genes have been extensively studied, the exact origin of the initial gene fusion event - it occurred in plants or microbes - remains uncertain. Furthermore, a comprehensive exploration of the TPS gene differentiation is still pending. Here, phylogenetic analysis revealed that the fusion of the TPS gene likely occurred in the ancestor of land plants, following the acquisition of individual C- and N- terminal domains. Potential mutual transfer of TPS genes was observed among microbes and plants. Gene synteny analysis disclosed a differential divergence pattern between TPS-c and TPS-e/f subfamilies involved in primary metabolism and those (TPS-a/b/d/g/h subfamilies) crucial for secondary metabolites. Biosynthetic gene clusters (BGCs) analysis suggested a correlation between lineage divergence and potential natural selection in structuring terpene diversities. This study provides fresh perspectives on the origin and evolution of the TPS gene family.

Rho2 involved in development, stress response and pathogenicity of Fusarium oxysporum.

Rho GTPases regulate the activity of cell wall biosynthesis, actin assembly and polar cell secretion. However, the function of Rho GTPase in filamentous fungi is poorly understood. To understand the role of Rho2 GTPase in Fusarium oxysporum, which is one of root rot pathogens of Panax notoginseng, △rho2 mutant was constructed. Phenotypes of △rho2, including conidiation, germination of spores, stresses (osmotic-, cell membrane-, cell wall disturbing-, metal-, and high temperature-) tolerance and pathogenicity were analyzed. The results showed that the growth of △rho2 was destroyed under cell wall disturbing stress and high temperature stress, suggesting that Rho2 regulated the response of F. oxysporum to cell wall synthesis inhibitors and high temperature stress. Germination of spores and pathogenicity to P. notoginseng were reduced in △rho2 mutant. Western blot results showed that rho2 deletion increased the phosphorylation level of Mpk1. To identify genes regulated by Rho2, transcriptome sequencing was carried out. 2477 genes were identified as upregulated genes and 2177 genes were identified as downregulated genes after rho2 was deleted. These genes provide clues for further study of rho2 function.

Haplotype-resolved genome assembly of Coriaria nepalensis a non-legume nitrogen-fixing shrub.

Coriaria nepalensis Wall. (Coriariaceae) is a nitrogen-fixing shrub which forms root nodules with the actinomycete Frankia. Oils and extracts of C. nepalensis have been reported to be bacteriostatic and insecticidal, and C. nepalensis bark provides a valuable tannin resource. Here, by combining PacBio HiFi sequencing and Hi-C scaffolding techniques, we generated a haplotype-resolved chromosome-scale genome assembly for C. nepalensis. This genome assembly is approximately 620 Mb in size with a contig N50 of 11 Mb, with 99.9% of the total assembled sequences anchored to 40 pseudochromosomes. We predicted 60,862 protein-coding genes of which 99.5% were annotated from databases. We further identified 939 tRNAs, 7,297 rRNAs, and 982 ncRNAs. The chromosome-scale genome of C. nepalensis is expected to be a significant resource for understanding the genetic basis of root nodulation with Frankia, toxicity, and tannin biosynthesis.

Amplified Spontaneous Emission and Lasing from Zn-Processed AgIn5S8 Core/Shell Quantum Dots.

I-III-VI ternary quantum dots (QDs) have emerged as favorable alternatives to the toxic II-VI QDs for optoelectronic and biological applications. However, their use as optical gain media for microlasers is still limited by a low fluorescence efficiency. Here, we demonstrate amplified spontaneous emission (ASE) and lasing from colloidal QDs of Zn-processed AgIn5S8 (AIS) for the first time. The passivation treatment on the AIS QDs yields a 3.4-fold enhancement of fluorescence quantum efficiency and a 30% increase in the two-photon absorption cross section. ASE is achieved from the AIS/ZnS core/shell QD films under both one- and two-photon pumping with a threshold fluence of ∼84.5 µJ/cm2 and 3.1 mJ/cm2, respectively. These thresholds are comparable to the best optical gain performance of Cd based-QDs reported in the literature. Moreover, we demonstrate a facile whispering-gallery-mode microlaser of the core/shell QDs with a lasing threshold of ∼233 µJ/cm2. The passivated AIS QDs can be promising optical gain media for photonic applications.

Efficacy of invisible advancement correction for mandibular retraction in adolescents based on Pancherz analysis.

BACKGROUND: Mandibular retraction is the main etiological mechanism of class II malocclusion in China and the subsequent distal molar relationship can cause functional discomfort in mastication, breathing and the temporomandibular joint. The use of mandibular advancement (MA) devices has recently emerged as an adolescent mandibular retraction treatment; however, current studies regarding the effect thereof are relatively few, and there is lack of sufficient clinical support. AIM: To investigate the clinical effect of invisalign MA on the treatment of mandibular retraction in adolescents. METHODS: This study included 30 adolescent patients who underwent treatment with the MA appliances from December 2017 to June 2021. The lateral cephalometric data before and after treatment were collected and imported into Dolphin Imaging software. The changes were measured by linear measurement superimposed with lateral cephalometric trajectory based on the Pancherz technology. RESULTS: There was no significant difference in the length and position of maxilla before and after the treatment. The position of the mandible moved 3.13 mm, the length increased 4.14 mm, the mandibular ramus length increased 4.09 mm, the body length increased 4.25 mm, and the position of the condyle moved 1.03 mm forward after treatment. Additionally, changes in the incisor sagittal position and labial inclination were observed. The position of the upper incisor point moved back 1.33 mm, without statistical difference, the inclination and tooth angle decreased by 3.44° and 4.06°, respectively; the position of the lower incisor point was moved 2.98 mm, and the inclination and tooth angle increased by 2.62° and 1.23°, respectively. Furthermore, changes in the incisor overjet and molar relationship were seen. Overjet decreased by 4.31 mm, of which 1.78 mm was due to dental factors, accounting for 41.3% of the effect as opposed to 58.7% due to skeletal factors. Molar relationship improved 3.87 mm, with 1.34 mm due to dental factors, and dental and skeletal factors were accounted for 34.6% and 65.4% of the effect, respectively. CONCLUSION: For adolescent patients with mandible retraction, invisalign MA can effectively promote the mandible growth, and it was proven to be mainly due to skeletal effects.

Unique gene duplications and conserved microsynteny potentially associated with resistance to wood decay in the Lauraceae.

Wood decay resistance (WDR) is marking the value of wood utilization. Many trees of the Lauraceae have exceptional WDR, as evidenced by their use in ancient royal palace buildings in China. However, the genetics of WDR remain elusive. Here, through comparative genomics, we revealed the unique characteristics related to the high WDR in Lauraceae trees. We present a 1.27-Gb chromosome-level assembly for Lindera megaphylla (Lauraceae). Comparative genomics integrating major groups of angiosperm revealed Lauraceae species have extensively shared gene microsynteny associated with the biosynthesis of specialized metabolites such as isoquinoline alkaloids, flavonoid, lignins and terpenoid, which play significant roles in WDR. In Lauraceae genomes, tandem and proximal duplications (TD/PD) significantly expanded the coding space of key enzymes of biosynthesis pathways related to WDR, which may enhance the decay resistance of wood by increasing the accumulation of these compounds. Among Lauraceae species, genes of WDR-related biosynthesis pathways showed remarkable expansion by TD/PD and conveyed unique and conserved motifs in their promoter and protein sequences, suggesting conserved gene collinearity, gene expansion and gene regulation supporting the high WDR. Our study thus reveals genomic profiles related to biochemical transitions among major plant groups and the genomic basis of WDR in the Lauraceae.

Mechanism of YAP1 in the senescence and degeneration of endplate chondrocytes induced by intermittent cyclic mechanical tension.

BACKGROUND: This study aimed to investigate the potential mechanism of YAP1 in the senescence and degeneration of endplate chondrocytes induced by intermittent cyclic mechanical tension (ICMT). METHODS: According to the Pfirrmann grade evaluation classification, 30 human endplate cartilage tissues were divided into the lumbar vertebra fracture (LVF) group and lumbar disc herniation (LDH) group. Then, quantitative reverse transcription polymerase chain reaction, western blot, flow cytometry, hematoxylin-eosin staining, and senescence-associated ß-galactosidase staining were performed. The difference in extracellular matrix expression between LVF and LDH endplate cartilage was detected. Second, the effect of ICMT on endplate chondrocytes degeneration was observed. Finally, the key regulatory role of YAP1 in ICMT-induced endplate cartilage degeneration was further verified. RESULTS: In degraded human endplate cartilage and tension-induced degraded endplate chondrocytes, the expression of YAP1, COL-2A, and Sox9 was decreased. Conversely, the expression of p53 and p21 was increased. By regulating YAP1 in vivo and in vitro, we can achieve alleviation of ICMT-induced senescence of endplate chondrocytes and effective treatment of disc degeneration. CONCLUSIONS: ICMT could induce senescence and degeneration of endplate chondrocytes, and ICMT-induced senescence and degeneration of endplate chondrocytes could be alleviated by regulating YAP1 expression.

Gapless genome assembly of azalea and multi-omics investigation into divergence between two species with distinct flower color.

The genus Rhododendron (Ericaceae), with more than 1000 species highly diverse in flower color, is providing distinct ornamental values and a model system for flower color studies. Here, we investigated the divergence between two parental species with different flower color widely used for azalea breeding. Gapless genome assembly was generated for the yellow-flowered azalea, Rhododendron molle. Comparative genomics found recent proliferation of long terminal repeat retrotransposons (LTR-RTs), especially Gypsy, has resulted in a 125 Mb (19%) genome size increase in species-specific regions, and a significant amount of dispersed gene duplicates (13 402) and pseudogenes (17 437). Metabolomic assessment revealed that yellow flower coloration is attributed to the dynamic changes of carotenoids/flavonols biosynthesis and chlorophyll degradation. Time-ordered gene co-expression networks (TO-GCNs) and the comparison confirmed the metabolome and uncovered the specific gene regulatory changes underpinning the distinct flower pigmentation. B3 and ERF TFs were found dominating the gene regulation of carotenoids/flavonols characterized pigmentation in R. molle, while WRKY, ERF, WD40, C2H2, and NAC TFs collectively regulated the anthocyanins characterized pigmentation in the red-flowered R simsii. This study employed a multi-omics strategy in disentangling the complex divergence between two important azaleas and provided references for further functional genetics and molecular breeding.

Retrospective Analysis of Paraspinal Muscle-Splitting Microscopic-Assisted Discectomy Versus Percutaneous Endoscopic Lumbar Discectomy for the Treatment of Far-Lateral Lumbar Disc Herniation.

AIM: To compare percutaneous endoscopic lumbar discectomy (PELD) and the microscopic tubular technique, and to evaluate the outcomes of surgery. MATERIAL AND METHODS: We collected information through retrospective analysis of patients with far-lateral lumbar disc herniation (FLLDH) from June 2015 to October 2018. Twenty-six patients underwent paraspinal muscle-splitting microscopicassisted discectomy (MD) and thirty patients underwent PELD surgery by the same surgical team. Data included the duration of the operation, duration of intraoperative radiation exposure, and average duration of hospitalization. Pre- and postoperative pain scores and neurological functions were recorded using the visual analog scale (VAS) score and Oswestry disability index (ODI). RESULTS: Fifty-six patients remained in the study over the 12-24 months period. The mean operating time was 65.83 ± 16.64 min in the PELD group, mean duration of radiation exposure was 154.98 ± 64.26 mGy, and average of hospitalization was 3.43 days. The mean operating time was 44.96 ± 16.87 min in the MD group, duration of radiation exposure was 42.12 ± 17.28 mGy, and duration of hospitalization was 4.12 days. There were two patients with postoperative transient dysesthesia and one underwent reoperation seven months after surgery in the PELD group. One patient had postoperative transient dysesthesia in the MD group. Except low back pain at three months (p > 0.05), all patients in both groups showed significant improvement in VAS and ODI scores compared with pre-operation and until final follow-up (p < 0.05). CONCLUSION: Both techniques are minimally invasive, effective, and safe for treating FLLDH in selected patients. Compared with the PELD technique, the MD procedure offers a wider field of vision during operation, shorter operation time, fewer postoperative complications, and shorter learning curve.

Real-world emission characteristics of carbonyl compounds from agricultural machines based on a portable emission measurement system.

Emissions of carbonyl compounds from agricultural machines cannot be ignored. Carbonyl compounds can cause the formation of ozone (O3) and secondary organic aerosols, which can cause photochemical smog to form. In this study, 20 agricultural machines were tested using portable emission measurement system (PEMS) under real-world tillage processes. The exhaust gases were sampled using 2,4-dinitrophenylhydrazine cartridges, and 15 carbonyl compounds were analyzed by high-performance liquid chromatography. Carbonyl compound emission factors for agricultural machines were 51.14-3315.62 mg/(kg-fuel), and were 2.58 ± 2.05, 0.86 ± 1.07 and 0.29 ± 0.20 g/(kg-fuel) for China 0, China II and China III emission standards, respectively. Carbonyl compound emission factor for sowing seeds of China 0 agricultural machines was 3.32 ± 1.73 g/(kg-fuel). Formaldehyde, acetaldehyde and acrolein were the dominant carbonyl compounds emitted. Differences in emission standards and tillage processes impact ozone formation potential (OFP). The mean OFP was 20.15 ± 16.15 g O3/(kg-fuel) for the China 0 emission standard. The OFP values decreased by 66.9% from China 0 to China II, and 67.4% from China II to China III. The mean OFP for sowing seeds of China 0 agricultural machines was 25.92 ± 13.84 g O3/(kg-fuel). Between 1.75 and 24.22 times more ozone was found to be formed during sowing seeds than during other processes for China 0 and China II agricultural machines. Total carbonyl compound emissions from agricultural machines in China was 19.23 Gg in 2019. The results improve our understanding of carbonyl compound emissions from agricultural machines in China.

ADSC-Exos outperform BMSC-Exos in alleviating hydrostatic pressure-induced injury to retinal ganglion cells by upregulating nerve growth factors.

BACKGROUND: Mesenchymal stem cells (MSCs) have protective effects on the cornea, lacrimal gland, retina, and photoreceptor cell damage, which may be mediated by exosomes (exos) released by MSCs. AIM: To investigate the ameliorating effect of exos derived from different MSCs on retinal ganglion cell (RGC) injury induced by hydrostatic pressure. METHODS: The RGC injury model was constructed by RGC damage under different hydrostatic pressures (40, 80, 120 mmHg). Then RGCs were cultured with adipose-derived stem cell (ADSC)-Exos and bone marrow-derived stem cell (BMSC)-Exos. Cell Counting Kit-8, transmission electron microscopy, flow cytometry, immunofluorescence, real-time quantitative polymerase chain reaction, and western blotting were performed to detect the ameliorating effect of exos on pressure-induced RGC injury. RESULTS: ADSC-Exos and BMSC-Exos were successfully isolated and obtained. The gibbosity of RGCs was lower, the cells were irregularly ellipsoidal under pressure, and the addition of ADSC-Exos and BMSC-Exos significantly restored RGC morphology. Furthermore, the proliferative activity of RGCs was increased and the apoptosis of RGCs was inhibited. Moreover, the levels of lactate dehydrogenase and apoptosis-related proteins were increased, and the concentrations of antiapoptotic proteins and neurotrophic factors were decreased in damaged RGCs. However, the above indicators were significantly improved after ADSC-Exos and BMSC-Exos treatment. CONCLUSION: These findings indicated that ADSC-Exos and BMSC-Exos could ameliorate RGC injury caused by hydrostatic pressure by inhibiting apoptosis and increasing the secretion of neurotrophic factors.

Safety and efficacy analysis of chemoradiotherapy/radiotherapy combined with nimotuzumab for treating unresectable oesophageal squamous cell carcinoma in elderly patients: a retrospective analysis.

OBJECTIVE: To investigate the safety and efficacy of chemoradiotherapy or radiotherapy combined with nimotuzumab in the treatment of unresectable oesophageal squamous cell carcinoma (ESCC) in elderly patients. METHODS: This study retrospectively analysed 54 cases of elderly patients (aged over 70 years) with unresectable ESCC in our centre between December 2016 and November 2019. The patients were treated with a radiation dose of 50-61.6 Gy (25-30 fractions) combined with nimotuzumab for targeted therapy with or without chemotherapy according to each patient's condition. The patients were observed for quality of life, safety, side effects and survival before and after the treatment. RESULTS: Among the 54 patients, 26 were treated with nimotuzumab combined with chemoradiotherapy and 28 were treated with nimotuzumab combined with radiotherapy. Toxicities were mainly oesophagitis (≥ Grade 2, 38.9%), myelosuppression (≥ Grade 3, 24.1%) and hypoproteinaemia (any grade, 94.4%). The rates of complete response, partial response, disease stability and disease progression were 11.1% (6/54), 81.5% (44/54), 3.7% (2/54) and 3.7% (2/54), respectively, and the overall objective response rate was 92.6% (50/54). The median follow-up time was 35.1 months, and the 1- and 2-year overall survival (OS) and progression-free survival (PFS) rates were 61.1% (1 year OS) and 35.2% (2 year OS), 42.6% (1 year PFS) and 16.7% (2 year PFS), respectively. The median OS and PFS rates were 16.0 and 10.0 months, respectively. CONCLUSION: Nimotuzumab combined with chemoradiotherapy or radiotherapy was well tolerated in elderly patients with unresectable ESCC. This combination can achieve a good treatment response and enhance survival.

Potential allopolyploid origin of Ericales revealed with gene-tree reconciliation.

Few incidents of ancient allopolyploidization (polyploidization by hybridization or merging diverged genomes) were previously revealed, although there is significant evidence for the accumulation of whole genome duplications (WGD) in plants. Here, we focused on Ericales, one of the largest and most diverse angiosperm orders with significant ornamental and economic value. Through integrating 24 high-quality whole genome data selected from ~ 200 Superasterids genomes/species and an algorithm of topology-based gene-tree reconciliation, we explored the evolutionary history of in Ericales with ancient complex. We unraveled the allopolyploid origin of Ericales and detected extensive lineage-specific gene loss following the polyploidization. Our study provided a new hypothesis regarding the origin of Ericales and revealed an instructive perspective of gene loss as a pervasive source of genetic variation and adaptive phenotypic diversity in Ericales.

CDCA8/SNAI2 Complex Activates CD44 to Promote Proliferation and Invasion of Pancreatic Ductal Adenocarcinoma.

(1) Background: Recently, cell division cycle associated 8 (CDCA8) was found to be overexpressed in pancreatic ductal adenocarcinoma (PDAC). Here, we aimed to explore the specific mechanism of action of CDCA8 in PDAC progression. (2) Methods: All human PDAC samples and clinical data were collected from Huashan Hospital, Fudan University. All experimental studies were carried out using many in vitro and in vivo assays, including lentiviral transfection, real-time quantitative polymerase chain reaction (qPCR), western blotting, co-immunoprecipitation (Co-IP), chromatin IP (ChIP)-qPCR, dual-luciferase reporter, and in vivo imaging assays. (3) Results: Clinical data analysis of human PDAC samples revealed that CDCA8 overexpression were positively and negatively associated with tumor grade (p = 0.007) and overall survival (p = 0.045), respectively. CDCA8 knockdown inhibited PDAC proliferation and invasion in in vitro and in vivo assays. CD44 was also up-regulated by CDCA8 during PDAC progression. CDCA8 could be combined with SNAI2 to form a CDCA8/SNAI2 complex to integrate with the CD44 promoter as indicated through ChIP-qPCR and dual-luciferase reporter assays. (4) Conclusion: We showed that CDCA8-CD44 axis plays a key role in the proliferation and invasion of PDAC, which provides a potential target for treatment.

High Glucose Promotes Pancreatic Ductal Adenocarcinoma Gemcitabine Resistance and Invasion through Modulating ROS/MMP-3 Signaling Pathway.

Pancreatic ductal adenocarcinoma (PDA) is often concomitant with diabetes mellitus, which mainly manifests as an increased blood glucose level. Previous studies revealed that diabetic status reduced the survival and blunted gemcitabine sensitivity in PDA patients. This study is aimed at analyzing the mechanism of elevated gemcitabine resistance and cancer invasion ability under high glucose environment. We selected 129 patients with 22 surgical resected samples from 2015 to 2021, who underwent pancreatic surgery in Huashan Hospital. The gene expression and clinical data of PDA were obtained from The Cancer Genome Atlas (TCGA) website and were analyzed by R software. Cell viability assays and flow cytometry were applied to detect gemcitabine sensitivity and apoptosis levels in pancreatic cancer cells. Wound healing and Transwell tests were used to analyze the invasion and metastasis of cancer cells. Streptozotocin (STZ) was used to establish a hyperglycemic mouse model for the in vivo study. In this study, diabetic PDA gemcitabine users showed reduced survival compared to euglycemic PDA gemcitabine users. Clinical samples and laboratory studies revealed that MMP-3 expression was associated with glucose concentration and diabetic status. Elevated MMP-3 expression was positively related to cancer invasion and gemcitabine resistance in PDA cells and gemcitabine resistant PDA cells. Blocking MMP-3 expression inhibited gemcitabine resistance and cancer progression in cellular and animal models. MMP-3 was closely related to the expression of RRM1, a gemcitabine metabolism-related gene. Reactive oxygen species (ROS) level increased under higher glucose concentrations and was mediated by NOX4. ROS determined the MMP-3 expression in pancreatic cancer cells. Inhibiting NOX4 expression effectively suppressed MMP-3 expression, gemcitabine resistance, and cancer invasion. In conclusion, a high glucose environment induces gemcitabine resistance and cancer invasion via ROS/MMP-3 signaling pathway. MMP-3 can be a potential novel target for suppressing gemcitabine resistance and invasion in PDA.

A carbon nanotube-based textile pressure sensor with high-temperature resistance.

Textile pressure sensors capable of withstanding high temperatures have attracted increasing interest due to their potential applications in harsh conditions. In this work, a textile pressure sensor with high-temperature resistance was realized based on multi-wall carbon nanotubes (MWCNTs) and quartz fabrics. The textile pressure sensors exhibited low fatigue over 20 000 cyclic loadings. Owing to the high-temperature resistance of MWCNTs and quartz fabrics, the textile sensor can work at temperatures up to 300 °C and can maintain good sensitivity after calcination at 900 °C in N2 for 30 min. This work provides a simple, facile, and inexpensive method for fabricating textile pressure sensors with high-temperature resistance.

Gemcitabine-Loaded Albumin Nanoparticle Exerts An Antitumor Effect on Gemcitabine-Resistant Pancreatic Cancer Cells Induced by MDR1 and MRP1 Overexpression in Vitro.

Purpose: Gemcitabine (GEM) is the first-line chemotherapeutic drug for pancreatic cancer treatment in clinical practice. However, many reasons can reduce the efficacy of GEM, among which the high expression of ATP-binding cassette (ABC) transporters is a significant factor. In this study, we aimed to investigate the antitumor effect of gemcitabine-loaded human serum albumin nanoparticle (GEM-HSA-NP) on GEM-resistant pancreatic cancer cells induced by the high expression of ABC transporters, namely multidrug resistance protein 1/P-gp/ABCB1 (MDR1) and multidrug resistance-associated protein 1/ ABCC1 (MRP1). Methods: MDR1 and MRP1 were stably overexpressed via lentiviral transduction in the pancreatic cancer cell lines BxPC3 and PANC1. Proliferation inhibition assays, cell cycle arrest and apoptosis analyses were conducted to examine the antitumor effect of GEM-HSA-NP. In addition, intracellular ATP levels were determined to explore the potential mechanisms implicated preliminarily. Results: When administered to GEM-resistant cancer cells, GEM-HSA-NP displayed its antitumor effect by promoting the inhibition of proliferation, cell cycle arrest, and apoptosis induction. Intracellular ATP depletion, caused by the albumin component of GEM-HSA-NP was proposed to be potentially involved in the modulation of ABC transporter activity. Conclusion: GEM-HSA-NP can effectively overcome GEM-resistance induced by MDR1 and MRP1 overexpression, which highlights its potential value in a clinical setting.