Endoplasmic reticulum protein ALTERED MERISTEM PROGRAM 1 negatively regulates senescence in Arabidopsis.

Plant senescence is a highly regulated developmental program crucial for nutrient reallocation and stress adaptation in response to developmental and environmental cues. Stress-induced and age-dependent natural senescence share both overlapping and distinct molecular responses and regulatory schemes. Previously, we have utilized a carbon-deprivation (C-deprivation) senescence assay using Arabidopsis (Arabidopsis thaliana) seedlings to investigate senescence regulation. Here we conducted a comprehensive time-resolved transcriptomic analysis of Arabidopsis wild type seedlings subjected to C-deprivation treatment at multiple time points, unveiling substantial temporal changes and distinct gene expression patterns. Moreover, we identified ALTERED MERISTEM PROGRAM 1 (AMP1), encoding an endoplasmic reticulum protein, as a potential regulator of senescence based on its expression profile. By characterizing loss-of-function alleles and overexpression lines of AMP1, we confirmed its role as a negative regulator of plant senescence. Genetic analyses further revealed a synergistic interaction between AMP1 and the autophagy pathway in regulating senescence. Additionally, we discovered a functional association between AMP1 and the endosome-localized ABNORMAL SHOOT3 (ABS3)-mediated senescence pathway and positioned key senescence-promoting transcription factors downstream of AMP1. Overall, our findings shed light on the molecular intricacies of transcriptome reprogramming during C-deprivation-induced senescence and the functional interplay among endomembrane compartments in controlling plant senescence.

Establishment and validation of a prediction model for nonrecovery of left ventricular ejection fraction in acute myocardial infarction patients combined with decreased left ventricular ejection fraction.

BACKGROUND: This study aimed to investigate the risk factors for nonrecovery of left ventricular ejection fraction (LVEF) during follow-up in patients with acute myocardial infarction (AMI) who underwent percutaneous coronary intervention (PCI) combined with reduced LVEF, and establish and verify a risk prediction model based on these factors. METHODS: In this study, patients with AMI who underwent PCI in a high-volume PCI center between December 2018 and December 2021 were consecutively enrolled, screened, and randomly assigned to the model establishment and validation cohorts. A predictive model method based on least absolute shrinkage and selection operator regression was used for establishment and validation. RESULTS: Cardiac troponin I, myoglobin, left ventricular end-diastolic dimension, multivessel disease, and no-reflow were identified as potential predictors of LVEF recovery failure. The areas under the curve were 0.703 and 0.665 in the model establishment and validation cohorts, respectively, proving that the prediction model had some predictive ability. The calibration curves of the two cohorts showed good agreement with those of the nomogram model. In addition, the decision curve analysis showed that the model had a net clinical benefit. CONCLUSION: This prediction model can assess the risk of nonrecovery of LVEF in patients with AMI undergoing PCI combined with LVEF reduction during follow-up, and conveniently screen high-risk patients with nonrecoverable LVEF early.

Increased GIRK channel activity prevents arrhythmia in mice with heart failure by enhancing ventricular repolarization.

Ventricular arrhythmia causing sudden cardiac death is the leading mode of death in patients with heart failure. Yet, the mechanisms that prevent ventricular arrhythmias in heart failure are not well characterized. Using a mouse model of heart failure created by transverse aorta constriction, we show that GIRK channel, an important regulator of cardiac action potentials, is constitutively active in failing ventricles in contrast to normal cells. Evidence is presented indicating that the tonic activation of M2 muscarinic acetylcholine receptors by endogenously released acetylcholine contributes to the constitutive GIRK activity. This constitutive GIRK activity prevents the action potential prolongation in heart failure ventricles. Consistently, GIRK channel blockade with tertiapin-Q induces QT interval prolongation and increases the incidence of arrhythmia in heart failure, but not in control mice. These results suggest that constitutive GIRK channels comprise a key mechanism to protect against arrhythmia by providing repolarizing currents in heart failure ventricles.

The ideal treatment timing for diabetic retinopathy: the molecular pathological mechanisms underlying early-stage diabetic retinopathy are a matter of concern.

Diabetic retinopathy (DR) is a prevalent complication of diabetes, significantly impacting patients' quality of life due to vision loss. No pharmacological therapies are currently approved for DR, excepted the drugs to treat diabetic macular edema such as the anti-VEGF agents or steroids administered by intraocular route. Advancements in research have highlighted the crucial role of early intervention in DR for halting or delaying disease progression. This holds immense significance in enhancing patients' quality of life and alleviating the societal burden associated with medical care costs. The non-proliferative stage represents the early phase of DR. In comparison to the proliferative stage, pathological changes primarily manifest as microangiomas and hemorrhages, while at the cellular level, there is a loss of pericytes, neuronal cell death, and disruption of components and functionality within the retinal neuronal vascular unit encompassing pericytes and neurons. Both neurodegenerative and microvascular abnormalities manifest in the early stages of DR. Therefore, our focus lies on the non-proliferative stage of DR and we have initially summarized the mechanisms involved in its development, including pathways such as polyols, that revolve around the pathological changes occurring during this early stage. We also integrate cutting-edge mechanisms, including leukocyte adhesion, neutrophil extracellular traps, multiple RNA regulation, microorganisms, cell death (ferroptosis and pyroptosis), and other related mechanisms. The current status of drug therapy for early-stage DR is also discussed to provide insights for the development of pharmaceutical interventions targeting the early treatment of DR.

A Four-Port MIMO Cylindrical DRA with High Isolation in Ultra-Compact Size for WLAN Applications.

A novel ultra-compact four-port multiple-input-multiple-output (MIMO) cylindrical dielectric resonator antenna (DRA) with improved isolation is proposed for WLAN applications in this paper. The antenna is originally radiated with the assistance of two different excitation mechanisms to generate decoupled orthogonal modes. To further diminish the coupling field and improve the isolation, a suitable U-shaped slot is created on the common ground plane. Two additional rectangular slits are also etched to adjust the impedance matching of other ports. To better reveal the operating mechanism of the decoupling scheme, the common mode (CM) and differential mode (DM) impedance analysis methods between DRA ports are presented. The etched U-shaped slot can tune the impedance of CM and DM to be consistent to realize the decoupling. The antenna is simulated, fabricated, and tested to verify the decoupling mechanism. The results demonstrate that the isolation between ports 1 and 2 is enhanced from 5 dB to 23 dB, and other ports exhibit low coupling of better than 12 dB. Moreover, the antenna with the full size of 30 × 30 × 8.1 mm3 can be used either as a four-port DRA with a bandwidth of 300 MHz or as a two-port DRA with a bandwidth of 700 MHz, at a center frequency of 5.6 GHz.

Effect of cell size distribution on mechanical properties of strawberry fruit tissue.

Strawberry fruit are high value, but also perishable products, because of their soft texture. Better insight on the strawberry mechanics are requested for understanding postharvest decay due to bruising. To gain data on the volumetric cell size distribution of strawberry tissue capturing the volume of 10 * 5 * 5 mm, fruit cells were suspended in 0.3 M mannitol solution. Cell size of 'Flair', 'Malwina', and 'Sonata' strawberry fruit, each in three commercially marketed ripeness stages (N = 135), was measured with particle size analyzer based on laser light scattering density analysis (LSD). The strawberry cell size distribution showed a wide range from 30-500 µm with frequency peak between 200 and 240 µm. The cell size of 'Flair' and 'Malwina' was smaller compared to 'Sonata' strawberry fruit. The volumetric cell size distribution obtained by LSD was correlated to microscopy results (R2 = 0.97-0.99) obtained on single cells (N = 1215), indicating that LSD can be used for measuring the percentages of different cell size ranges of volumetric fruit sample. The three ripeness stages were classified with Gaussian Naïve Bayes approach considering absorption coefficient of anthocyanins at 405 nm (GNBa) and percentage frequency of peak cell size (GNBc). For GNBa classes, ripening stage showed no interaction with failure stress, strain, and elastic modulus. Considering GNBc classes, the failure stress and elastic modulus of strawberry tissue increased with enhanced percentage frequency of peak cell size for all three cultivars. An enhanced percentage frequency of large cells resulted in increased susceptibility of the strawberry tissue. Overall, this study showed that LSD cell size distribution data from a volumetric tissue sample are related to fruit tissue mechanics, which is conducive to a better analysis of the actual stress and damage problems of strawberry fruit tissue specimens during compression in supply chain processes.

Ultrasensitive lateral flow biosensor based on PtAu@CNTs nanocomposite catalytic chromogenic signal amplification strategy for the detection of nucleic acid.

A rapid and ultrasensitive lateral flow biosensor was developed, which based on gold and platinum nanoparticles-decorated carbon nanotubes (PtAu@CNTs) nanocomposite catalytic chromogenic signal amplification strategy for the detection of nucleic acid. Independent platinum and gold nanoparticles modified functional carbon nanotubes (PtAu@CNTs) were prepared by in-situ reduction. Sandwich-type hybridization reaction occurred between PtAu@CNTs-labeled DNA probe, target DNA and Biotin-modified DNA probes, which was captured on test zone of the strip. Accumulation of PtAu@CNTs nano-labels formed a characteristic colored band. After systematic optimization and catalytic chromogen, the naked eye detection limit of PtAu@CNTs-LFA was about 2 pM, and the theoretical detection limit of target DNA is calculated to be 0.43 pM according to the standard curve. The results indicates a rapid, sensitive and specific methods for DNA detection in biological samples, showing great promise for biomedical diagnosis in some malignant diseases in clinical application.

Overexpression of lipocalin 2 in PBX1-deficient decidual NK cells promotes inflammation at the maternal-fetal interface.

PROBLEM: Impairment of PBX1 expression in decidual natural killer (dNK) cells is associated with the pathogenesis of unexplained recurrent spontaneous abortion, which results in fetal growth restriction (FGR) by affecting the secretion of downstream growth factors. However, whether other mechanisms limit embryo growth in decidua containing PBX1-deficient natural killer (NK) cells is unknown. METHOD OF STUDY: Pbx1f/f ; Ncr1Cre mice were employed to explore the underlying mechanisms by which PBX1- NK cells affect embryonic development. To simulate the clinical testing of pregnant women, Doppler ultrasound imaging was used to detect embryo implantation and development. Differentially expressed genes (DEGs) in PBX1- NK cells that may affect normal pregnancy were screened using RNA-sequencing and real-time PCR. Immune cell changes caused by DEGs were detected by flow cytometry. Finally, the mechanism of FGR was explored by injecting the protein LCN2, corresponding to the selected DEG, into mice. RESULTS: We verified the embryonic dysplasia in pregnant Pbx1f/f ; Ncr1Cre mice by Doppler ultrasound imaging and found that LCN2 was upregulated in dNK cells. We also observed higher infiltration of neutrophils and macrophages in the decidua of Pbx1f/f ; Ncr1Cre mice. Finally, we found an increase in the number and activation of neutrophils at the maternal-fetal interface after injecting LCN2 into pregnant mice and observed that these mice showed signs of FGR. CONCLUSION: Excessive LCN2 secreted by PBX1- dNK cells at the maternal-fetal interface recruit neutrophils and causes an inflammatory response, which is related to FGR.

Masticadienonic acid from Chios mastic gum mitigates colitis in mice via modulating inflammatory response, gut barrier integrity and microbiota.

BACKGROUND: Chios mastic gum (CMG) is a traditional Greek medicine used to treat a variety of gastrointestinal disorders, including inflammatory bowel disease (IBD). However, the bioactive compounds of CMG and the mechanisms of action for controlling of IBD remain unknown. PURPOSE: Masticadienonic acid (MDA) is one of the most abundant constituents isolated from CMG. This study aims to investigate the potential effects and underlying mechanisms of MDA in the pathogenesis of colitis. METHODS: The effects of MDA were evaluated using a dextran sulphate sodium (DSS)-induced acute colitis mouse model. The body and spleen weight and colon length and weight were measured and the clinical symptoms were analysed. Blood samples were collected to analyse the level of serum inflammatory markers. Colon tissues were processed for histopathological examination, evaluation of the epithelial barrier function, and investigation of the probable mechanisms of action. The gut microbiota composition was also studied to determine the mechanism for the beneficial effects of MDA on IBD. RESULTS: MDA could ameliorate the severity of IBD by increasing the body weight and colon length, reducing spleen weight, disease activity index, and histological score. MDA treatments reduce the release of serum inflammatory cytokines tumour necrosis factor-alpha (TNFα), interleukin 1 beta (IL-1ß), and interleukin 6 (IL-6) via inhibiting the MAPK and NF-κB signalling pathways. MDA supplementation could also improve the intestinal barrier function by activating the NF-E2-related factor-2 (Nrf2) signalling pathway and restoring the expression of tight junction proteins zonula occludens-1 (ZO-1) and occludin. In addition, MDA administration modulates the gut microbiota composition in DSS-induced colitis mice. CONCLUSION: The results indicate that MDA attenuated experimental colitis by restoring intestinal barrier integrity, reducing inflammation, and modulating the gut microbiota. The present study provides novel insights into CMG-mediated remission of IBD and may facilitate the development of preventive and therapeutic strategies for IBD.

ARF2-PIF5 interaction controls transcriptional reprogramming in the ABS3-mediated plant senescence pathway.

One of the hallmarks of plant senescence is the global transcriptional reprogramming coordinated by a plethora of transcription factors (TFs). However, mechanisms underlying the interactions between different TFs in modulating senescence remain obscure. Previously, we discovered that plant ABS3 subfamily MATE transporter genes regulate senescence and senescence-associated transcriptional changes. In a genetic screen for mutants suppressing the accelerated senescence phenotype of the gain-of-function mutant abs3-1D, AUXIN RESPONSE FACTOR 2 (ARF2) and PHYTOCHROME-INTERACTING FACTOR 5 (PIF5) were identified as key TFs responsible for transcriptional regulation in the ABS3-mediated senescence pathway. ARF2 and PIF5 (as well as PIF4) interact directly and function interdependently to promote senescence, and they share common target genes such as key senescence promoting genes ORESARA 1 (ORE1) and STAY-GREEN 1 (SGR1) in the ABS3-mediated senescence pathway. In addition, we discovered reciprocal regulation between ABS3-subfamily MATEs and the ARF2 and PIF5/4 TFs. Taken together, our findings reveal a regulatory paradigm in which the ARF2-PIF5/4 functional module facilitates the transcriptional reprogramming in the ABS3-mediated senescence pathway.

The role of free fatty acid receptor pathways in a selective regulation of TRPA1 and TRPV1 by resolvins in primary sensory neurons.

Transient receptor potential ankyrin 1 and vanilloid 1 (TRPA1 and TRPV1, respectively) channels contribute to inflammatory and neuropathic pain, indicating that their pharmacological inhibition could be a novel strategy for treating painful diseases. However, the mechanisms of TRPA1/V1 channel modulation have been mostly characterized to be upregulation and sensitization via variety of exogenous stimuli, endogenous inflammatory mediators, and metabolites of oxidative stress. Here we used calcium imaging of dorsal root ganglion neurons to identify an inhibitor signaling pathway for TRPA1 and TRPV1 regulated by resolvins (RvD1 and RvE1), which are endogenous anti-inflammatory lipid mediators. TRPA1 and TRPV1 channel activations were evoked by the TRPA1 agonist allyl isothiocyanate and the TRPV1 agonist capsaicin. Our results show that RvD1-induced selective inhibition of TRPA1 activity was mediated by free fatty acid receptor 4 (FFAR4)-protein kinase C (PKC) signaling. Experiments assessing RvE1-induced TRPV1 inhibition showed that RvE1 actions required both FFAR1 and FFAR4. Combined stimulation of FFAR1/FFAR4 or FFAR1/PKC mimicked TRPV1 inhibition by RvE1, and these effects were blocked by a protein kinase D (PKD) inhibitor, implying that PKD is an effector of the FFAR/PKC signaling axis in RvE1-induced TRPV1 inhibition. Despite selective inhibition of TRPV1 in the nanomolar range of RvE1, higher concentrations of RvE1 also inhibited TRPA1, possibly through PKC. Collectively, our findings reveal FFAR1 and FFAR4 as key signaling pathways mediating the selective targeting of resolvins to regulate TRPA1 and TRPV1, elucidating endogenous analgesic mechanisms that could be exploited as potential therapeutic targets.

Modulation of IKs channel-PIP2 interaction by PRMT1 plays a critical role in the control of cardiac repolarization.

Recent studies have shown that protein arginine methyltransferase 1 (PRMT1) is highly expressed in the human heart, and loss of PRMT1 contributes to cardiac remodeling in the heart failure. However, the functional importance of PRMT1 in cardiac ion channels remains uncertain. The slow activating delayed rectifier K+ (IKs ) channel is a cardiac K+ channel composed of KCNQ1 and KCNE1 subunits and is a new therapeutic target for treating lethal arrhythmias in many cardiac pathologies, especially heart failure. Here, we demonstrate that PRMT1 is a critical regulator of the IKs channel and cardiac rhythm. In the guinea pig ventricular myocytes, treatment with furamidine, a PRMT1-specific inhibitor, prolonged the action potential duration (APD). We further show that this APD prolongation was attributable to IKs reduction. In HEK293T cells expressing human KCNQ1 and KCNE1, inhibiting PRMT1 via furamidine reduced IKs and concurrently decreased the arginine methylation of KCNQ1, a pore-forming α-subunit. Evidence presented here indicates that furamidine decreased IKs mainly by lowering the affinity of IKs channels for the membrane phospholipid, phosphatidylinositol 4,5-bisphosphate (PIP2 ), which is crucial for pore opening. Finally, applying exogenous PIP2 to cardiomyocytes prevented the furamidine-induced IKs reduction and APD prolongation. Taken together, these results indicate that PRMT1 positively regulated IKs activity through channel-PIP2 interaction, thereby restricting excessive cardiac action potential.

Textural thermo-mechanical properties of sweet cherry for postharvest damage analysis.

In this study, the textural thermo-mechanical properties of three sweet cherry varieties were systematically investigated by the puncture test of whole fruit, uniaxial tension of the exocarp, and uniaxial compression test of mesocarp. It was found that the puncture test can not only reflect the shear mechanics of the exocarp in vivo at the tissue level, but it can also characterize the resistance level of fruit to puncture damage at the macroscopic level, particularly when the puncture failure stress is used. The environmental temperature had negative and positive significant effects on the puncture failure stress and the puncture failure deformation of the sweet cherry (p < .05), respectively. The environmental temperature showed a negative significant effect on the failure stress and elastic modulus of the sweet cherry exocarp under tension and mesocarp under compression (p < .05). As the environmental temperature increased from 5 to 40°C, the elastic modulus of the Black pearl, Summit, and Tieton sweet cherry exocarp ranged from 2.28 to 1.72, 2.57 to 1.47, and 1.98 to 1.24 MPa, respectively; and that of mesocarp ranged from 0.33 to 0.21, 0.27 to 0.19, and 0.43 to 0.23 MPa, respectively. The obtained exponential function relationships between environmental temperature and each mechanical parameter are useful for predicting the thermo-mechanical properties of sweet cherry across a 5-40°C continuous temperature range. This study provided systematical thermo-mechanical data for predicting the mechanical damage of sweet cherry in postharvest handling using the thermo-mechanical coupling numerical simulation.

A congenital CMV infection model for follow-up studies of neurodevelopmental disorders, neuroimaging abnormalities, and treatment.

Congenital cytomegalovirus (cCMV) infection is the leading infectious cause of neurodevelopmental disorders. However, the neuropathogenesis remains largely elusive due to a lack of informative animal models. In this study, we developed a congenital murine CMV (cMCMV) infection mouse model with high survival rate and long survival period that allowed long-term follow-up study of neurodevelopmental disorders. This model involves in utero intracranial injection and mimics many reported clinical manifestations of cCMV infection in infants, including growth restriction, hearing loss, and impaired cognitive and learning-memory abilities. We observed that abnormalities in MRI/CT neuroimaging were consistent with brain hemorrhage and loss of brain parenchyma, which was confirmed by pathological analysis. Neuropathological findings included ventriculomegaly and cortical atrophy associated with impaired proliferation and migration of neural progenitor cells in the developing brain at both embryonic and postnatal stages. Robust inflammatory responses during infection were shown by elevated inflammatory cytokine levels, leukocyte infiltration, and activation of microglia and astrocytes in the brain. Pathological analyses and CT neuroimaging revealed brain calcifications induced by cMCMV infection and cell death via pyroptosis. Furthermore, antiviral treatment with ganciclovir significantly improved neurological functions and mitigated brain damage as shown by CT neuroimaging. These results demonstrate that this model is suitable for investigation of mechanisms of infection-induced brain damage and long-term studies of neurodevelopmental disorders, including the development of interventions to limit CNS damage associated with cCMV infection.

Shumian capsule improves symptoms of sleep mood disorder in convalescent patients of Corona Virus Disease 2019.

OBJECTIVE: To evaluate the clinical effectiveness of Shumian capsule in improving the symptoms of insomnia, anxiety, depression, and other symptoms of convalescent patients of COVID-19. METHODS: Totally 200 patients were collected and randomly divided into experiment group (n = 100) and control group (n = 100). The control group was treated with Shumian capsule simulator, and the experiment group was treated with Shumian capsule. The improvement of TCM symptom score, the total effective rate and symptom disappearance rate of TCM symptoms in the two groups before and after treatment were observed, and the clinical effect was evaluated. RESULTS: One week after treatment, the scores of anxiety symptoms in the experiment group were significantly different from those in the control group (P < 0.05), but there was no significant difference in the scores of insomnia and depression between the experiment group and the control group (P > 0.05). There was no significant difference in the total effective rate and disappearance rate of TCM symptoms of insomnia, anxiety and depression between the experiment group and the control group (P > 0.05). After 2 weeks of treatment, the scores of insomnia, anxiety, depression and the total effective rate of TCM symptoms in the experiment group were significantly different from those in the control group (P < 0.05). There was no significant difference in the disappearance rate of insomnia, anxiety and depression between the experiment group and the control group (P > 0.05). There were no significant differences in heart rate, respiration, systolic blood pressure and diastolic blood pressure between the experiment group and the control group (P > 0.05). CONCLUSION: Shumian capsule can significantly improve the symptoms of insomnia, anxiety and depression in COVID-19's convalescent patients with sleep and mood disorders.

Riverside underwater noise pollution threaten porpoises and fish along the middle and lower reaches of the Yangtze River, China.

The Yangtze River exhibits a high biodiversity and plays an important role in global biodiversity conservation. As the world's busiest inland river in regard to shipping, little attention has been paid to underwater noise pollution. In 2017, the underwater noise level in 25 riverside locations along the middle and lower reaches of the Yangtze River mainly at night time were investigated by using passive acoustic monitoring method. Approximately 88% and 40% of the sampled sites exhibit noise levels exceeding the underwater acoustic thresholds of causing responsiveness and temporary threshold shift, respectively, in cetacean. Noise pollution may impose a high impact on fish with physostomous swim bladders and Weberian ossicles, such as silver carp, bighead carp, goldfish and common carp, whereas it may affect fish with physoclistous swim bladders and without Weberian ossicles, such as lake sturgeon and paddlefish, to a lesser extent. Noise levels reductions of approximately 10 and 20 dB were observed in the middle and lower reaches, respectively, of the Yangtze River over the 2012 level. The green development mode of the ongoing construction of green shipping in the Yangtze River Economic Belt, including the development of green shipping lanes, ports, ships and transportation organizations, may account for the alleviated underwater noise pollution. Follow-up noise mitigation endeavors, such as the extension of ship speed restrictions and the study and implementation of the optimal navigation speed in ecologically important areas, are required to further reduce the noise level in the Yangtze River to protect local porpoises and fish.

Traditional Chinese Medicine Decoctions Significantly Reduce the Mortality in Severe and Critically Ill Patients with COVID-19: A Retrospective Cohort Study.

Coronavirus disease (COVID-19) is a new infectious disease associated with high mortality, and traditional Chinese medicine decoctions (TCMDs) have been widely used for the treatment of patients with COVID-19 in China; however, the impact of these decoctions on severe and critical COVID-19-related mortality has not been evaluated. Therefore, we aimed to address this gap. In this retrospective cohort study, we included inpatients diagnosed with severe/critical COVID-19 at the Tongren Hospital of Wuhan University and grouped them depending on the recipience of TCMDs (TCMD and non-TCMD groups). We conducted a propensity score-matched analysis to adjust the imbalanced variables and treatments and used logistic regression methods to explore the risk factors associated with in-hospital death. Among 282 patients with COVID-19 who were discharged or died, 186 patients (66.0%) received TCMD treatment (TCMD cohort) and 96 (34.0%) did not (non-TCMD cohort). After propensity score matching at a 1:1 ratio, 94 TCMD users were matched to 94 non-users, and there were no significant differences in baseline clinical variables between the two groups of patients. The all-cause mortality was significantly lower in the TCMD group than in the non-TCMD group, and this trend remained valid even after matching (21.3% [20/94] vs. 39.4% [37/94]). Multivariable logistic regression model showed that disease severity (odds ratio: 0.010; 95% CI: 0.003, 0.037; [Formula: see text]¡ 0.001) was associated with increased odds of death and that TCMD treatment significantly decreased the odds of in-hospital death (odds ratio: 0.115; 95% CI: 0.035, 0.383; [Formula: see text]¡ 0.001), which was related to the duration of TCMD treatment. Our findings show that TCMD treatment may reduce the mortality in patients with severe/critical COVID-19.

LncRNA PCGEM1 contributes to malignant behaviors of glioma by regulating miR-539-5p/CDK6 axis.

BACKGROUND: Glioma, one of the most prevalent and aggressive cancers, is regulated by long noncoding RNAs (lncRNAs). This study aims to research the functional mechanism of lncRNA PCGEM1 involved in glioma progression. METHODS: Expression levels of PCGEM1, miR-539-5p and CDK6 were analyzed by qRT-PCR in NHA, U251, U87, and LN229 cells or glioma tissues. shRNAs were used to knock down PCGEM1 in U251 and LN229 cells. Kaplan-Meier curve and log rank test were utilized to examine survival rate. CCK8 (Cell Counting Kit-8) assay, colony formation assay and EdU staining were conducted to detect cell proliferation. Transwell assay was performed to evaluate cell migration and invasion. Luciferase reporter assay was conducted to assess RNA interaction between PCGEM1 and miR-539-5p. Nude mice were used for tumor xenograft assay. RESULTS: LncRNA PCGEM1 was upregulated in glioma tissues and tumor cell lines. PCGEM1 upregulation predicted unsatisfactory prognosis. PCGEM1 knockdown inhibited proliferation, colony formation, migration and invasion. PCGEM1 knockdown delayed tumor growth in vivo. PCGEM1 played as a competing endogenous RNA (ceRNA) for miR-539-5p to promote CDK6 expression. MiR-539-5p mimics repressed glioma progression while CDK6 overexpression reversed the roles of PCGEM1 knockdown. CONCLUSION: PCGEM1 knockdown suppressed glioma progression through sponging miR-539-5p and regulating CDK6 expression, implying PCGEM1 as a potential therapeutic target.

Biotransformation of androst-4-ene-3,17-dione by three fungal species Fusarium solani BH1031, Aspergillus awamori MH18 and Mucor circinelloides W12.

The microbial transformation of androst-4-ene-3,17-dione (4-AD; I) by three fungal species, involved Fusarium solani BH1031, Aspergillus awamori MH18 and Mucor circinelloides W12, has been studied. The latter two fungi were studied for the first time on biotransformation of 4-AD. The main product obtained by Fusarium solani BH1031 was 17α-oxa-D-homo-androst-1,4-diene-3,17-dione (testolactone; IV), which can be used as an anticancer agent. The main derivative yielded by Aspergillus awamori MH18 was 11α-hydroxyandrost-4-ene-3,17-dione (11α-OH-4-AD; VI), which was an important intermediate to produce Eplerenone. Meanwhile, the microbial transformation of 4-AD by Mucor circinelloides W12 produced three derivatives. Possible metabolic pathway of 4-AD via Fusarium solani BH1031 was proposed. Furthermore, the optimization for the production of 11α-OH-4-AD was carried out and the conversion rate reached to 84.0%. In this process, the dextrin and corn flour showed significant effects by response surface analysis.

Trifunctional metasurface based on spoof surface plasmon polaritons.

In this paper, we propose the design of a metasurface that can achieve three functions in different frequency bands. The proposed metasurface is composed of two kinds of unit cells which are designed on the basis of the spatial k-dispersion engineering of spoof surface plasmon polaritons (SSPPs). By arranging these two kinds of unit cells in the chessboard configuration, the three functions of transmission, anomalous refraction and absorption can be integrated into one metasurface. High transmission and strong absorption can be achieved in 2.0-9.0 GHz and 12.6-20.0 GHz, respectively. Meanwhile, anomalous refraction can be achieved in 10-11.7 GHz due to forward scattering cancellation of two unit cells. To verify the design, a prototype was fabricated and measured. The measured results are consistent with the simulation ones. The metasurface can integrate multiple functions into one aperture and therefore has potential application values in multifunctional microwave devices such as shared-aperture antennas, etc.