Prediction method for the tension force of support ropes in flexible rockfall barriers based on full-scale experiments and numerical analysis.

This paper proposes a prediction method for the tension force of support ropes in flexible rockfall barriers. The method is based on two full-scale model tests with an impact energy of 3000 kJ, as well as 36 set numerical models featuring varying lengths and impact energies. From the results of full scale tests and numerical models, it is inferred that the tension force at the end of the support rope is significantly less than that at the point of impact, exhibiting an approximate Gaussian attenuation distribution with propagation distance. To account for the attenuation of tensile forces in support ropes, a tensile attenuation coefficient is defined. Through comparative analysis of data obtained from 36 models with varying impact energies and propagation distances, the average attenuation coefficient for the upper support rope is determined to be approximately 0.7, while the average coefficient for the lower support rope is around 0.8. Utilizing the least squares method, a prediction method for the tension force of support ropes in flexible rockfall barriers is established. This method takes into account both the propagation distance and impact energy, enabling accurate predictions of the tensile behavior of the ropes under different conditions. This prediction model provides valuable insights for engineers in the design and optimization of these flexible barriers for rockfall mitigation.

Ameliorative Effect of Morinda Officinalis Oligosaccharides on LPS-Induced Acute Lung Injury.

Acute lung injury (ALI) is a disease characterized by extensive lung damage and rampant inflammation, with a high mortality rate and no effective treatments available. Morinda officinalis oligosaccharides (MOOs), derived from the root of the traditional Chinese medicinal herb Morinda officinalis, known for its immune-boosting properties, presents a novel therapeutic possibility. To date, the impact of MOOs on ALI has not been explored. Our study aimed to investigate the potential protective effects of MOOs against ALI and to uncover the underlying mechanisms through an integrated approach of network pharmacology, molecular docking, and experimental validation. We discovered that MOOs significantly mitigated the pathological damage and decreased the expression of pro-inflammatory cytokines in LPS-induced ALI in mice. Complementary in vitro studies further demonstrated that MOOs effectively attenuated the M1 polarization induced by LPS. Network pharmacology analysis identified HSP90AA1, HSP90AB1, and NF-κB as key overlapping targets within a protein-protein interaction (PPI) network. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses elucidated the biological processes and signaling pathways implicated in MOOs' therapeutic action on ALI. Subsequently, molecular docking affirmed the binding of MOOs to the active sites of these identified targets. Corroborating these findings, our in vivo and in vitro experiments consistently demonstrated that MOOs significantly inhibited the LPS-induced upregulation of HSP90 and NF-κB. Collectively, these findings suggest that MOOs confer protection against ALI through a multi-target, multi-pathway mechanism, offering a promising new therapeutic strategy to mitigate this severe pulmonary condition.

Neutrophil lncRNA ZNF100-6:2 is a potential diagnostic marker for active pulmonary tuberculosis.

Active pulmonary tuberculosis (PTB) poses challenges in rapid diagnosis within complex clinical conditions. Given the close association between neutrophils and tuberculosis, we explored differentially expressed long non-coding RNAs (lncRNAs) in neutrophils as potential molecular markers for diagnosing active PTB. We employed a gene microarray to screen for lncRNA alterations in neutrophil samples from three patients with active PTB and three healthy controls. The results revealed differential expression of 1457 lncRNAs between the two groups, with 916 lncRNAs upregulated and 541 lncRNAs down-regulated in tuberculosis patients. Subsequent validation tests demonstrated down-regulation of lncRNA ZNF100-6:2 in patients with active PTB, which was restored following anti-tuberculosis treatment. Our findings further indicated a high diagnostic potential for lncRNA ZNF100-6:2, as evidenced by an area under the receiver operating characteristic (ROC) curve of 0.9796 (95% confidence interval: 0.9479 to 1.000; P < 0.0001). This study proposes lncRNA ZNF100-6:2 as a promising and novel diagnostic biomarker for active PTB.

Spontaneous multivessel coronary artery spasm: a case report.

A 60-year-old male presented to the emergency department of our hospital with persistent dull pain in the lower and middle sternum with generalized sweating after a heated argument with another person, and his symptoms did not resolve after 3 hours of onset.

Lung protection of Chimonanthus nitens Oliv. essential oil driven by the control of intestinal disorders and dysbiosis through gut-lung crosstalk.

This work aimed to investigate whether Chimonanthus nitens Oliv. essential oil (CEO)-mediated lung protection was implicated in gut-lung crosstalk. Results showed that CEO attenuated lung and intestinal impairment by improving histopathological changes and inhibiting TLR4/NF-κB signaling pathway in LPS-stimulated rats, suggesting that there might be a mechanism for its lung protection involved in gut-lung interaction through manipulating the overlap in pathological changes via the similar inflammatory response. Furthermore, CEO-triggered intestinal protection was in parallel with the mitigation of ROS production, apoptosis, Ca2+ transport and mitochondrial membrane potential loss in vivo, and its intestinal protection was confirmed in vitro through IEC-6 cells. Importantly, a combination with CEO and LPS significantly remodeled gut microbiota composition compared with LPS alone in rats, while no significant impact on lung microbiota. Therefore, CEO-exerted lung protection was linked to gut and lung interactions involvement with the control of intestinal disorders and dysbiosis.

Dual Antiplatelet Therapy vs Alteplase for Patients With Minor Nondisabling Acute Ischemic Stroke: The ARAMIS Randomized Clinical Trial.

Importance: Intravenous thrombolysis is increasingly used in patients with minor stroke, but its benefit in patients with minor nondisabling stroke is unknown. Objective: To investigate whether dual antiplatelet therapy (DAPT) is noninferior to intravenous thrombolysis among patients with minor nondisabling acute ischemic stroke. Design, Setting, and Participants: This multicenter, open-label, blinded end point, noninferiority randomized clinical trial included 760 patients with acute minor nondisabling stroke (National Institutes of Health Stroke Scale [NIHSS] score ≤5, with ≤1 point on the NIHSS in several key single-item scores; scale range, 0-42). The trial was conducted at 38 hospitals in China from October 2018 through April 2022. The final follow-up was on July 18, 2022. Interventions: Eligible patients were randomized within 4.5 hours of symptom onset to the DAPT group (n = 393), who received 300 mg of clopidogrel on the first day followed by 75 mg daily for 12 (±2) days, 100 mg of aspirin on the first day followed by 100 mg daily for 12 (±2) days, and guideline-based antiplatelet treatment until 90 days, or the alteplase group (n = 367), who received intravenous alteplase (0.9 mg/kg; maximum dose, 90 mg) followed by guideline-based antiplatelet treatment beginning 24 hours after receipt of alteplase. Main Outcomes and Measures: The primary end point was excellent functional outcome, defined as a modified Rankin Scale score of 0 or 1 (range, 0-6), at 90 days. The noninferiority of DAPT to alteplase was defined on the basis of a lower boundary of the 1-sided 97.5% CI of the risk difference greater than or equal to -4.5% (noninferiority margin) based on a full analysis set, which included all randomized participants with at least 1 efficacy evaluation, regardless of treatment group. The 90-day end points were assessed in a blinded manner. A safety end point was symptomatic intracerebral hemorrhage up to 90 days. Results: Among 760 eligible randomized patients (median [IQR] age, 64 [57-71] years; 223 [31.0%] women; median [IQR] NIHSS score, 2 [1-3]), 719 (94.6%) completed the trial. At 90 days, 93.8% of patients (346/369) in the DAPT group and 91.4% (320/350) in the alteplase group had an excellent functional outcome (risk difference, 2.3% [95% CI, -1.5% to 6.2%]; crude relative risk, 1.38 [95% CI, 0.81-2.32]). The unadjusted lower limit of the 1-sided 97.5% CI was -1.5%, which is larger than the -4.5% noninferiority margin (P for noninferiority <.001). Symptomatic intracerebral hemorrhage at 90 days occurred in 1 of 371 participants (0.3%) in the DAPT group and 3 of 351 (0.9%) in the alteplase group. Conclusions and Relevance: Among patients with minor nondisabling acute ischemic stroke presenting within 4.5 hours of symptom onset, DAPT was noninferior to intravenous alteplase with regard to excellent functional outcome at 90 days. Trial Registration: ClinicalTrials.gov Identifier: NCT03661411.

Lower Baseline LDL Cholesterol Affects All-cause Mortality in Patients with First Percutaneous Coronary Intervention.

Objective: Foreign studies have reported that coronary artery disease (CAD) patients with high baseline low-density lipoprotein cholesterol (LDL-C) may have a good prognosis, which is called the "cholesterol paradox". This study aimed to examine whether the "cholesterol paradox" also exists in the Chinese population. Methods: A total of 2,056 patients who underwent the first percutaneous coronary intervention (PCI) between 2014 and 2016 were enrolled in this retrospective cohort study and classified into two groups based on baseline LDL-C = 2.6 mmol/L (100 mg/dL). The outcomes of interest included major adverse cardiovascular events (MACE), all-cause mortality, recurrent nonfatal myocardial infarction, unexpected coronary revascularization, or any nonfatal stroke. Results: All-cause mortality occurred in 8 patients (0.7%) from the low-LDL-C group and 12 patients (2.4%) in the high-LDL-C group, with a significant difference between the two groups (adjusted hazard ratio: 4.030, 95% confidence interval: 1.088-14.934; P = 0.037). However, no significant differences existed for the risk of MACE or other secondary endpoints, such as unexpected revascularization, nor any nonfatal stroke in the two groups. Conclusion: In this study, a high baseline LDL-C was not associated with a low risk of clinical outcomes in CAD patients undergoing first PCI, which suggested that the "cholesterol paradox" may be inapplicable to Chinese populations.

Effect of Argatroban Plus Intravenous Alteplase vs Intravenous Alteplase Alone on Neurologic Function in Patients With Acute Ischemic Stroke: The ARAIS Randomized Clinical Trial.

Importance: Previous studies suggested a benefit of argatroban plus alteplase (recombinant tissue-type plasminogen activator) in patients with acute ischemic stroke (AIS). However, robust evidence in trials with large sample sizes is lacking. Objective: To assess the efficacy of argatroban plus alteplase for AIS. Design, Setting, and Participants: This multicenter, open-label, blinded end point randomized clinical trial including 808 patients with AIS was conducted at 50 hospitals in China with enrollment from January 18, 2019, through October 30, 2021, and final follow-up on January 24, 2022. Interventions: Eligible patients were randomly assigned within 4.5 hours of symptom onset to the argatroban plus alteplase group (n = 402), which received intravenous argatroban (100 µg/kg bolus over 3-5 minutes followed by an infusion of 1.0 µg/kg per minute for 48 hours) within 1 hour after alteplase (0.9 mg/kg; maximum dose, 90 mg; 10% administered as 1-minute bolus, remaining infused over 1 hour), or alteplase alone group (n = 415), which received intravenous alteplase alone. Both groups received guideline-based treatments. Main Outcomes and Measures: The primary end point was excellent functional outcome, defined as a modified Rankin Scale score (range, 0 [no symptoms] to 6 [death]) of 0 to 1 at 90 days. All end points had blinded assessment and were analyzed on a full analysis set. Results: Among 817 eligible patients with AIS who were randomized (median [IQR] age, 65 [57-71] years; 238 [29.1%] women; median [IQR] National Institutes of Health Stroke Scale score, 9 [7-12]), 760 (93.0%) completed the trial. At 90 days, 210 of 329 participants (63.8%) in the argatroban plus alteplase group vs 238 of 367 (64.9%) in the alteplase alone group had an excellent functional outcome (risk difference, -1.0% [95% CI, -8.1% to 6.1%]; risk ratio, 0.98 [95% CI, 0.88-1.10]; P = .78). The percentages of participants with symptomatic intracranial hemorrhage, parenchymal hematoma type 2, and major systemic bleeding were 2.1% (8/383), 2.3% (9/383), and 0.3% (1/383), respectively, in the argatroban plus alteplase group and 1.8% (7/397), 2.5% (10/397), and 0.5% (2/397), respectively, in the alteplase alone group. Conclusions and Relevance: Among patients with acute ischemic stroke, treatment with argatroban plus intravenous alteplase compared with alteplase alone did not result in a significantly greater likelihood of excellent functional outcome at 90 days. Trial Registration: ClinicalTrials.gov Identifier: NCT03740958.

Ebastine exerts antitumor activity and induces autophagy by activating AMPK/ULK1 signaling in an IPMK-dependent manner in osteosarcoma.

Numerous studies have confirmed that in addition to interfering with the tumor inflammatory environment, anti-inflammatory agents can directly increase apoptosis and sensitivity to conventional therapies and decrease invasion and metastasis, making them useful candidates for cancer therapy. Here, we first used high-throughput screening and had screened one compound candidate, ebastine (a H1-histamine receptor antagonist), for osteosarcoma therapy. Cell viability assays, colony formation assays, wound healing assays, and Transwell assays demonstrated that ebastine elicited antitumor effects in osteosarcoma cells. In addition, ebastine treatment exerted obvious effects on cell cycle arrest, metastasis inhibition, apoptosis and autophagy induction both in vitro and in vivo. Mechanistically, we observed that ebastine treatment triggered proapoptotic autophagy by activating AMPK/ULK1 signaling in osteosarcoma cells. Treatment with the AMPK inhibitor dorsomorphin reversed ebastine-induced apoptosis and autophagy. More importantly, we found that IPMK interacted with AMPK and functioned as a positive regulator of AMPK protein in osteosarcoma cells. A rescue study showed that the induction of autophagy and activation of the AMPK/ULK1 signaling pathway by ebastine treatment were reversed by IPMK knockdown, indicating that the activity of ebastine was IPMK dependent. We provide experimental evidence demonstrating that ebastine has antitumor activity in osteosarcoma and promotes autophagy by activating the AMPK/ULK1 signaling pathway, which is IPMK dependent. Our results provide insight into the clinical application potential of ebastine, which may represent a new potential therapeutic candidate for the treatment of osteosarcoma.

Special issue "The advance of solid tumor research in China": Participants with a family history of cancer have a higher participation rate in low-dose computed tomography for lung cancer screening.

We aimed to determine participation in low-dose computed tomography (LDCT) of individuals with a family history of common cancers in a population-based screening program to provide timely evidence in high-risk populations in China. The analysis was conducted using data from the Cancer Screening Program in Urban China (CanSPUC), which recruited 282 377 participants aged 40 to 74 years from eight cities in the Henan province. Using the CanSPUC risk score system, 55 428 participants were evaluated to have high risk for lung cancer and were recommended for LDCT. We calculated the overall and group-specific participation rates using family history of common cancers and compared differences in participation rates between different groups. Odds ratios (ORs) and 95% confidence intervals were derived by multivariable logistic regression. Of the 55 428 participants, 22 260 underwent LDCT (participation rate, 40.16%). Family history of lung, esophageal, stomach, liver and colorectal cancer was associated with increased participation in LDCT screening. The odds of participants with a family history of one, two, three and four or more cancer cases undergoing LDCT screening were 1.9, 2.7, 2.8 and 3.5 times, respectively, than those without a family history of cancer. Compared to those without a history of cancer, participation in LDCT gradually increased as the number of cancer cases in the family increased (P < .001). Our findings suggest that there is room for improvement in lung cancer screening given the relatively low participation rate. Lung cancer screening in populations with a family history of cancer may improve efficiency and cost-effectiveness; however, this requires further verification.

[Nutrient uptake strategy selection by first-order roots of Juglans mandshurica under shading and phosphorus limitation]. / 遮阴和磷限制下胡桃楸1çº§æ ¹å »åˆ†å¸æ”¶ç­–ç•¥é€‰æ‹©.

We investigated root growth of 1-year-old Juglans mandshurica seedlings under different light environments and varying doses of phosphorus fertilizer, to understand the relationship between root resource acquisition strategies and the variations of light and phosphorus availability. There were four shading intensities (full light, 65% full light, 35% full light, and 20% full light) along with three doses of phosphate fertilizer (0 (CK), 200% soil background available phosphorus, and 500% soil background available phosphorus). We measured in root morphology characteristics, architectural characteristics, and mycorrhizal colonization rates of first-order roots. The results showed that average diameter, average root length, and mycorrhizal colonization rates of first-order roots gradually decreased, and the specific root length, specific surface area, branching ratio and branching intensity showed a trend of first increasing and then decreasing with the increases of shading degree. As the phosphorus content decreased, the first-order root diameter gradually became thinner, and the mycorrhizal infection rate gradually increased. Root morphology and architecture of J. mandshurica would undergo adaptive changes under shade, adapting to the shading environment by expanding specific root length, specific surface area, branching ratio and branching intensity. Under phosphorus limitation, root system of J. mandshurica would increase phosphorus absorption through symbiosis with mycorrhizal fungi. When J. mandshurica was artificially regenerate in forest land with a light transmittance of 35%, root morphology and architecture would adapt to the shading environment. The symbiosis between J. mandshurica and mycorrhizal fungi would be enhanced under phosphorus limitation, which could improve phosphorus absorption of roots.

Value of Intraplaque Neovascularization on Contrast-Enhanced Ultrasonography in Predicting Ischemic Stroke Recurrence in Patients With Carotid Atherosclerotic Plaque

Objective@#Patients with a history of ischemic stroke are at risk for a second ischemic stroke. This study aimed to investigate the relationship between carotid plaque enhancement on perfluorobutane microbubble contrast-enhanced ultrasonography (CEUS) and future recurrent stroke, and to determine whether plaque enhancement can contribute to risk assessment for recurrent stroke compared with the Essen Stroke Risk Score (ESRS). @*Materials and Methods@#This prospective study screened 151 patients with recent ischemic stroke and carotid atherosclerotic plaques at our hospital between August 2020 and December 2020. A total of 149 eligible patients underwent carotid CEUS, and 130 patients who were followed up for 15–27 months or until stroke recurrence were analyzed. Plaque enhancement on CEUS was investigated as a possible risk factor for stroke recurrence and as a possible adjunct to ESRS. @*Results@#During follow-up, 25 patients (19.2%) experienced recurrent stroke. Patients with plaque enhancement on CEUS had an increased risk of stroke recurrence events (22/73, 30.1%) compared to those without plaque enhancement (3/57, 5.3%), with an adjusted hazard ratio (HR) of 38.264 (95% confidence interval [CI]:14.975–97.767; P < 0.001) according to a multivariable Cox proportional hazards model analysis, indicating that the presence of carotid plaque enhancement was a significant independent predictor of recurrent stroke. When plaque enhancement was added to the ESRS, the HR for stroke recurrence in the high-risk group compared to that in the low-risk group (2.188; 95% CI, 0.025–3.388) was greater than that of the ESRS alone (1.706; 95% CI, 0.810–9.014). A net of 32.0% of the recurrence group was reclassified upward appropriately by the addition of plaque enhancement to the ESRS. @*Conclusion@#Carotid plaque enhancement was a significant and independent predictor of stroke recurrence in patients with ischemic stroke. Furthermore, the addition of plaque enhancement improved the risk stratification capability of the ESRS.

Effects of polysorbates on stability of monoclonal antibody drugs / 中国生物制品学杂志

@#Objective To evaluate the effects of various polysorbates(PS)on the stability of different types of monoclonal antibody(mAb)drugs.Methods Three types of monoclonal antibodies mAbA(IgG1 proantibody drug),mAbB(IgG1 mAb)and mAbC(IgG1 mAb with Fc N297A mutation)were used as model proteins,and different kinds or contents of PS were added into the mAb formulations respectively to investigate the influencing factors.The effects of PS on the stability of mAb drugs were evaluated comprehensively by detecting the changes of quality attributes,such as protein aggregates and insoluble particles.Results PS20 and PS80 showed no significant difference in inhibiting the formation of aggregates and charge variants in the three mAbs(P>0.05),while the addition of PS80 in mAbB and PS20 in mAbC significantly inhibited the increase of insoluble particles respectively(P<0.05);The content of PS20 showed a significant effect on the detection indexes of charge variants and insoluble particles in mAbC(P<0.05).Conclusion Different types of mAbs have different sensitivities to various kinds and contents of PS.Therefore,when designing the formulation of mAbs,it is necessary to select appropriate kinds and contents of PS to further improve the stability of mAb drugs.

Lower Baseline LDL Cholesterol Affects All-cause Mortality in Patients with First Percutaneous Coronary Intervention / 生物医学与环境科学（英文）

OBJECTIVE@#Foreign studies have reported that coronary artery disease (CAD) patients with high baseline low-density lipoprotein cholesterol (LDL-C) may have a good prognosis, which is called the "cholesterol paradox". This study aimed to examine whether the "cholesterol paradox" also exists in the Chinese population.@*METHODS@#A total of 2,056 patients who underwent the first percutaneous coronary intervention (PCI) between 2014 and 2016 were enrolled in this retrospective cohort study and classified into two groups based on baseline LDL-C = 2.6 mmol/L (100 mg/dL). The outcomes of interest included major adverse cardiovascular events (MACE), all-cause mortality, recurrent nonfatal myocardial infarction, unexpected coronary revascularization, or any nonfatal stroke.@*RESULTS@#All-cause mortality occurred in 8 patients (0.7%) from the low-LDL-C group and 12 patients (2.4%) in the high-LDL-C group, with a significant difference between the two groups (adjusted hazard ratio: 4.030, 95% confidence interval: 1.088-14.934; P = 0.037). However, no significant differences existed for the risk of MACE or other secondary endpoints, such as unexpected revascularization, nor any nonfatal stroke in the two groups.@*CONCLUSION@#In this study, a high baseline LDL-C was not associated with a low risk of clinical outcomes in CAD patients undergoing first PCI, which suggested that the "cholesterol paradox" may be inapplicable to Chinese populations.

[Construction of Nalm6-Cas9 Cell Line for Genome-Wide Translocation Sequencing].

OBJECTIVE: In order to conduct high-throughput genome-wide translocation sequencing based on CRISPR/Cas9, Nalm6-cas9 monoclonal cell line expressing Cas9 protein was constructed by lentivirus transduction. METHODS: Lentiviral vectors LentiCas9-Blast, pSPAX2, and pMD2.G were used to co-transfect HEK293T cells to obtain recombinant lentivirus. After Nalm6 cells were infected with the recombinant lentivirus, the cells were screened by Blasticidin, and multiple monoclonal cell lines expressing Cas9 protein were obtained by limited dilution. Western blot was used to detect the expression level of Cas9 protein in monoclonal cell lines, and cell count analysis was used to detect the proliferation activity of monoclonal cell lines. LentiCRISPRV2GFP-Δcas9, LentiCRISPRV2GFP-Δcas9-AF4, LentiCRISPRV2GFP-Δ cas9-MLL plasmids were constructed, and transfected with pSPAX2 and pMD2.G, respectively. T vector cloning was used to detect the function of Cas9 protein in Nalm6-Cas9 monoclonal cell line infected with virus. RESULTS: Western blot showed that Nalm6-Cas9_1-6 monoclonal cell line had high expression of Cas9 protein. Cell count analysis showed that high expression of Cas9 protein in Nalm6-Cas9_1-6 monoclonal cell line did not affect cell proliferation activity. The Nalm6-Cas9_1-6 monoclonal cell line had high cleavage activity, and the editing efficiency of AF4 and MLL genes was more than 90% which was determined by T vector cloning. CONCLUSION: Nalm6-Cas9_1-6 monoclonal cell line stably expressing highly active Cas9 protein was obtained, which provided a basis for exploring the translocation of MLL in therapy-related leukemias based on CRISPR/Cas9 genome-wide high-throughput genome-wide translocation sequencing.

LncRNA NEAT1 promoted MPP+­induced ferroptosis via regulating miR­150­5p/BAP1 pathway in SK­N­SH cells.

As widely reported, dysregulated ferroptosis is closely associated with Parkinson's disease (PD) progression. The goal of the present study was to probe the roles of long non­coding RNA (lncRNA) nuclear enriched assembly transcript 1 (NEAT1) in regulating ferroptosis in PD. PD cell model was constructed by subjecting SK­N­SH cells to 1­methyl­4­phenylpyridinium (MPP+) for 24 h. The RNA levels of NEAT1, miRNA (miR)­150­5p, and BRCA1­associated protein 1 (BAP1) were evaluated using qRT­PCR. The protein levels of glutathione peroxidase 4 (GPX4), BAP1, and solute carrier family 7 member 11 (SLC7A11) were determined using western blot. Cell viability was assessed using 3­(4,5­dimethylthiazolyl2)­2, 5­diphenyltetrazolium bromide (MTT) assay. In addition, fluorescent probe 2,7­dichlorodihydrofluorescein diacetate (DCFH­DA) was employed to determine the ROS level. Moreover, the levels of GSH, MDA, and Fe2+ were also measured. Finally, the interactions among NEAT1, miR­150­5p, and BAP1 were identified by dual luciferase reporter gene assay, and/or RIP assay. Upregulated NEAT1 was observed in PD cell model. Knockdown of NEAT1 elevated viability and GSH level in PD cell model and reduced ROS, MDA, and Fe2+ levels. Moreover, NEAT1 functioned as a sponge to suppress miR­150­5p expression. Moreover, miR­150­5p overexpression suppressed ferroptosis in PD cell model. We subsequently found that miR­150­5p regulated SLC7A11 expression by directly binding to BAP1. miR­150­5p inhibition or BAP1 overexpression mitigated the anti­ferroptosis effect meditated by sh­NEAT1. Taken together, knockdown of NEAT1 mitigated MPP+­induced ferroptosis through regulating BAP1/SLC7A11 axis by sponging miR­150­5p, indicating the potential of NEAT1 as a promising therapeutic target for PD.

The Chromosome-Scale Assembly of the Curcuma alismatifolia Genome Provides Insight Into Anthocyanin and Terpenoid Biosynthesis.

Curcuma alismatifolia, a bulbous flower known for its showy bracts, is widely used around the world as a cut flower, potted, and garden plant. Besides its ornamental value, this species is rich in terpenoid metabolites and could serve as a resource for essential oils. Here, we report a chromosome-level genome assembly of C. alismatifolia and describe its biosynthetic pathways for anthocyanins and terpenoids. This high-quality, assembled genome size is 991.3 Mb with a scaffold N50 value of 56.7 Mb. Evolutionary analysis of the genome suggests that C. alismatifolia diverged from Zingiber officinale about 9.7 million years ago, after it underwent a whole-genome duplication. Transcriptome analysis was performed on bracts at five developmental stages. Nine highly expressed genes were identified, encoding for six enzymes downstream of the anthocyanin biosynthetic pathway. Of these, one gene encoding F3'5'H might be a key node in the regulation of bract color formation. Co-expression network analysis showed that MYB, bHLH, NAC, and ERF transcription factors collectively regulated color formation in the bracts. Characterization of terpenoid biosynthesis genes revealed their dispersal and tandem duplications, both of which contributed greatly to the increase in the number of terpene synthase genes in C. alismatifolia, especially to species-specific expansion of sesquiterpene synthase genes. This work facilitates understanding of genetic basis of anthocyanin and terpenoid biosynthesis and could accelerate the selective breeding of C. alismatifolia varieties with higher ornamental and medicinal value.

Sulfated alginate oligosaccharide exerts antitumor activity and autophagy induction by inactivating MEK1/ERK/mTOR signaling in a KSR1-dependent manner in osteosarcoma.

Alginate oligosaccharide (AOS) has the function to inhibit tumor progression and the sulfated modification can enhance the antitumor activity. To date, the function and mechanism of sulfated AOS (AOS-SO4) in tumors remain largely elusive. We prepared AOS by the enzymatic degradation of alginate, collected AOS-SO4 by sulfating following the canonical procedure. Using these materials, in vitro assays showed that both AOS and AOS-SO4 elicited antitumor effects in osteosarcoma cells. Sulfated modification significantly enhanced the antitumor activity. In addition, AOS-SO4 had obvious effects on cell cycle arrest, apoptosis, and autophagy induction in vitro and in vivo. Mechanistically, we observed that AOS-SO4 treatment triggered proapoptotic autophagy by inhibiting MEK1/ERK/mTOR signaling. The ERK activator reversed AOS-SO4-induced autophagy. More importantly, we found that KSR1 interacted with MEK1 and functioned as a positive regulator of MEK1 protein in osteosarcoma cells. High KSR1 expression was significantly associated with poor survival in osteosarcoma patients. Together, these results suggest that AOS-SO4 has a better antitumor effect in osteosarcoma by inhibiting MEK1/ERK/mTOR signaling, which is KSR1-dependent; thus, AOS-SO4 can be a new potential therapeutic candidate for the treatment of osteosarcoma.

Corrigendum: Construction and Validation of a Lung Cancer Risk Prediction Model for Non-Smokers in China.

[This corrects the article DOI: 10.3389/fonc.2021.766939.].