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1.
J Asthma Allergy ; 16: 1-8, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36636704

RESUMO

Previously case reports showed dupilumab may benefit for hand eczema treatment, but relatively comprehensive assessments are lacking. A 45-year-old male with multiple severe vesicles, bullae and pustule on the palmar aspects of both hand and foot diagnosed dyshidrotic eczema by pathology was treated with dupilumab at an initial dose of 600 mg subcutaneously, followed by 300 mg every 2 weeks. The physician's assessment of the patient revealed an excellent response to the treatment with dupilumab; the lesions and symptoms achieved dramatic improvement on the third day, and at 6 weeks, the hands and feet became completely normal without relapse in the past 1.5 years of discontinuation. Systematic literature searches were performed, and 6 case reports, 5 case series, 2 prospective observational studies and 1 retrospective review with a total of 150 patients were identified to describing the evaluation of efficacy and safety of dupilumab treatment for hand and foot eczema. Dupilumab appears to be safe and well tolerated with clinical benefit in recalcitrant hand and foot eczema. Larger randomized controlled trials using validated outcome measures and detailed hand eczema type and population classification are needed before dupilumab can be applied in clinical settings.

2.
Cell Rep ; 42(1): 112002, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36662617

RESUMO

Type I interferon (IFN-I) signaling is central to inducing antiviral innate immunity. However, the mechanisms for IFN-I signaling self-regulation are still largely unknown. Here, we report that RNA virus-infected macrophages with UBE2M deficiency produced decreased IFN-I expression in a RIG-I-dependent manner, causing an aggravated viral infection. Mechanistically, UBE2M inhibits RIG-I degradation by preventing the interaction of RIG-I and E3 ligase STUB1, resulting in antiviral IFN-I signaling activation. Simultaneously, IFN-I signaling-activated STAT1 facilitates the transcription of Trim21, leading to increased UBE2M degradation and blunted antiviral immunity. Translationally, oral administration of milk-derived extracellular vesicles containing RING domain-truncated TRIM21 (TRIM21-ΔRING) lacking E3 ligase activity efficiently transfers TRIM21-ΔRING into macrophages. TRIM21-ΔRING suppresses UBE2M degradation by competitively binding to UBE2M with TRIM21, thereby enhancing antiviral immunity. Overall, we reveal a negative feedback loop of IFN-I signaling and develop a reagent to improve innate immunity against RNA viruses.

3.
Antioxidants (Basel) ; 12(1)2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36670986

RESUMO

To determine the anti-heat stress and antioxidant effects of genistein and the underlying mechanisms, lipofuscin, reactive oxygen species (ROS), and survival under stress were first detected in Caenorhabditis elegans (C. elegans); then the localization and quantification of the fluorescent protein was determined by detecting the fluorescently labeled protein mutant strain; in addition, the aging-related mRNAs were detected by applying real-time fluorescent quantitative PCR in C. elegans. The results indicate that genistein substantially extended the lifespan of C. elegans under oxidative stress and heat conditions; and remarkably reduced the accumulation of lipofuscin in C. elegans under hydrogen peroxide (H2O2) and 35 °C stress conditions; in addition, it reduced the generation of ROS caused by H2O2 and upregulated the expression of daf-16, ctl-1, hsf-1, hsp-16.2, sip-1, sek-1, pmk-1, and eat-2, whereas it downregulated the expression of age-1 and daf-2 in C. elegans; similarly, it upregulated the expression of daf-16, sod-3, ctl-1, hsf-1, hsp-16.2, sip-1, sek-1, pmk-1, jnk-1 skn-1, and eat-2, whereas it downregulated the expression of age-1, daf-2, gst-4, and hsp-12.6 in C. elegans at 35 °C; moreover, it increased the accumulation of HSP-16.2 and SKN-1 proteins in nematodes under 35 °C and H2O2 conditions; however, it failed to prolong the survival time in the deleted mutant MQ130 nematodes under 35 °C and H2O2 conditions. These results suggest that genistein promote anti-heat stress and antioxidant effects in C. elegans via insulin/-insulin-like growth factor signaling (IIS), heat shock protein (HSP), mitogen-activated protein kinase (MAPK), dietary restriction (DR), and mitochondrial pathways.

4.
Polymers (Basel) ; 15(2)2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36679241

RESUMO

It is of great significance to develop green, sustainable additives to improve the thermal stability and flame retardancy of biopolymers. In this work, a synergistic modification of P/N elements to bamboo biochar (mBC) was successfully achieved by grafting a reaction of phytic acid and urea with preoxidized bamboo biochar. Fourier transform infrared spectroscopy, X-ray diffraction, nuclear magnetic resonance and scanning electron microscope determinations of the mBC demonstrated a successive grafting of phytic acid and urea to the originally porous surface. The ground mBC was blended with polylactic acid (PLA) to prepare mBC/PLA composites by extrusion and hot pressing. Mechanical strength studies showed a compromise in rigidity, which might originate from the mBC overdose and its limited miscibility with the resin. The thermogravimetric results supported the fact that the enhancement of thermal stability and flame retardancy of the composites with the mBC dosage, which showed that the mBC dosage in the PLA composites was not only lower than that of the conventional flame retardants, but also outperformed the counterparts using BC modified by inorganic phosphoric acid and urea. The mBC was prone to accelerate the earlier decomposition of the composites (30 °C lower in decomposition) and generate a continuous, dense residual carbon layer, which provides an effective shield resisting the mass and heat transfer between the combustion area and the underlying composite matrix. Only 10 wt% of mBC dosage could achieve a V-0 rating (UL94) for the composite, with a higher limiting oxygen index up to 28.3% compared to 20.7% for that of the virgin PLA; the cone colorimetric results also suggested that the flame retardancy had been greatly improved for all composites. In this work, biobased P-/N-containing bamboo biochar would be expected as a nontoxic biochar-based flame retardant that serves as green filler in polymer composites.

5.
Artigo em Inglês | MEDLINE | ID: mdl-36627498

RESUMO

PURPOSE: Human post mortem studies have described the topographical patterns of tau pathology in progressive supranuclear palsy (PSP). Recent advances in tau PET tracers are expected to herald the next era of PSP investigation for early detection of tau pathology in living brains. This study aimed to investigate whether 18F-Florzolotau PET imaging may capture the distribution patterns and regional vulnerability of tau pathology in PSP, and to devise a novel image-based staging system. METHODS: The study cohort consisted of 148 consecutive patients with PSP who had undergone 18F-Florzolotau PET imaging. The PSP rating scale (PSPrs) was used to measure disease severity. Similarities and differences of tau deposition among different clinical phenotypes were examined at the regional and voxel levels. An 18F-Florzolotau pathological staging system was devised according to the scheme originally developed for post mortem data. In light of conditional probabilities for the sequence of events, an 18F-Florzolotau modified staging system by integrating clusters at the regional level was further developed. The ability of 18F-Florzolotau staging systems to reflect disease severity in terms of PSPrs score was assessed by analysis of variance. RESULTS: The distribution patterns of 18F-Florzolotau accumulation in living brains of PSP showed a remarkable similarity to those reported in post mortem studies, with the binding intensity being markedly higher in Richardson's syndrome. Moreover, 18F-Florzolotau PET imaging allowed detecting regional vulnerability and tracking tau accumulation in an earlier fashion compared with post mortem immunostaining. The 18F-Florzolotau staging systems were positively correlated with clinical severity as reflected by PSPrs scores. CONCLUSIONS: 18F-Florzolotau PET imaging can effectively capture the distribution patterns and regional vulnerability of tau pathology in PSP. The 18F-Florzolotau modified staging system holds promise for early tracking of tau deposition in living brains.

6.
Nat Microbiol ; 8(1): 162-173, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36604510

RESUMO

The increasing prevalence and expanding distribution of tick-borne viruses globally have raised health concerns, but the full repertoire of the tick virome has not been assessed. We sequenced the meta-transcriptomes of 31 different tick species in the Ixodidae and Argasidae families from across mainland China, and identified 724 RNA viruses with distinctive virome compositions among genera. A total of 1,801 assembled and complete or nearly complete viral genomes revealed an extensive diversity of genome architectures of tick-associated viruses, highlighting ticks as a reservoir of RNA viruses. We examined the phylogenies of different virus families to investigate virome evolution and found that the most diverse tick-associated viruses are positive-strand RNA virus families that demonstrate more ancient divergence than other arboviruses. Tick-specific viruses are often associated with only a few tick species, whereas virus clades that can infect vertebrates are found in a wider range of tick species. We hypothesize that tick viruses can exhibit both 'specialist' and 'generalist' evolutionary trends. We hope that our virome dataset will enable much-needed research on vertebrate-pathogenic tick-associated viruses.


Assuntos
Vírus de RNA , Carrapatos , Vírus , Animais , Vírus de RNA/genética , Genoma Viral/genética , RNA
7.
Adv Sci (Weinh) ; : e2206096, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36594619

RESUMO

The construction of strong interactions and synergistic effects between small metal clusters and supports offers a great opportunity to achieve high-performance and cost-effective heterogeneous catalysis, however, studies on its applications in electrocatalysis are still insufficient. Herein, it is reported that W18 O49 nanowires supported sub-nanometric Ru clusters (denoted as Ru SNC/W18 O49 NWs) constitute an efficient bifunctional electrocatalyst for hydrogen evolution/oxidation reactions (HER and HOR) under acidic condition. Microstructural analyses, X-ray absorption spectroscopy, and density functional theory (DFT) calculations reveal that the Ru SNCs with an average RuRu coordination number of 4.9 are anchored to the W18 O49 NWs via RuOW bonds at the interface. The strong metal-support interaction leads to the electron-deficient state of Ru SNCs, which enables a modulated RuH strength. Furthermore, the unique proton transport capability of the W18 O49 also provides a potential migration channel for the reaction intermediates. These components collectively enable the remarkable performance of Ru SNC/W18 O49 NWs for hydrogen electrocatalysis with 2.5 times of exchange current density than that of carbon-supported Ru nanoparticles, and even rival the state-of-the-art Pt catalyst. This work provides a new prospect for the development of supported sub-nanometric metal clusters for efficient electrocatalysis.

8.
Cancer Sci ; 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36644819

RESUMO

Therapeutic effects of MK-2206 are largely limited due to the complexity of the pathogenesis of nasopharyngeal cancer (NPC). Here, we aimed to investigate whether and how circLASP1 involves in therapeutic effects of MK-2206 on NPC. We showed circLASP1 was increased while miR-625 was decreased in NPC tissues and cell lines. CircLASP1 silence strengthened the therapeutic effects of MK-2206 via suppressing NPC cell proliferation, and inducing autophagy and apoptosis in vitro. In mechanism, we found that circLASP1 indirectly released AKT by directly binding to miR-625 in NPC cells, and miR-625 played as a tumor suppressor in NPC and activated cell autophagy through inhibiting AKT/mTOR pathway. Most importantly, knockdown of circLASP1 was revealed to enhance the therapeutic effects of MK-2206 on NPC in vivo. Our results suggest that circLASP1/miR-625 axis involves the therapeutic effects of MK-2206 on NPC by regulating autophagy, proliferation, and apoptosis through AKT/mTOR pathway.

9.
Nature ; 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36634707

RESUMO

Despite the success of PD-1 blockade in melanoma and other cancers, effective treatment strategies to overcome resistance to cancer immunotherapy are lacking1,2. We identified the innate immune kinase TANK-binding kinase 1 (TBK1)3 as a candidate immune evasion gene in a pooled genetic screen4. Using a suite of genetic and pharmacologic tools across multiple experimental model systems, we confirm a role for TBK1 as an immune evasion gene. Targeting TBK1 enhances response to PD-1 blockade by lowering the cytotoxicity threshold to effector cytokines (TNFα/IFNγ). TBK1 inhibition in combination with PD-1 blockade also demonstrated efficacy using patient-derived tumour models, with concordant findings in matched patient-derived organotypic tumour spheroids (PDOTS) and matched patient-derived organoids (PDOs). Tumour cells lacking TBK1 are primed to undergo RIPK- and caspase-dependent cell death in response to TNFα/IFNγ in a JAK/STAT-dependent manner. Taken together, our results demonstrate that targeting TBK1 is a novel and effective strategy to overcome resistance to cancer immunotherapy.

10.
J Am Chem Soc ; 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36651291

RESUMO

Two-dimensional (2D) nanofluidic membranes have shown great promise in harvesting osmotic energy from the salinity difference between seawater and fresh water. However, the output power densities are strongly hampered by insufficient membrane permselectivity. Herein, we demonstrate that vacancy engineering is an effective strategy to enhance the permselectivity of 2D nanofluidic membranes to achieve high-efficiency osmotic energy generation. Phosphorus vacancies were facilely created on NbOPO4 (NbP) nanosheets, which remarkably enlarged their negative surface charge. As verified by both experimental and theoretical investigations, the vacancy-introduced NbP (V-NbP) exhibited fast transmembrane ion migration and high ionic selectivity originating from the improved electrostatic affinity of cations. When applied in a natural river water|seawater osmotic power generator, the macroscopic-scale V-NbP membrane delivered a record-high power density of 10.7 W m-2, far exceeding the commercial benchmark of 5.0 W m-2. This work endows the remarkable potential of vacancy engineering for 2D materials in nanofluidic energy devices.

11.
EMBO Mol Med ; : e16235, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36652375

RESUMO

Poly-ADP-ribose polymerase (PARP) inhibitors (PARPi) have shown great promise for treating BRCA-deficient tumors. However, over 40% of BRCA-deficient patients fail to respond to PARPi. Here, we report that thioparib, a next-generation PARPi with high affinity against multiple PARPs, including PARP1, PARP2, and PARP7, displays high antitumor activities against PARPi-sensitive and -resistant cells with homologous recombination (HR) deficiency both in vitro and in vivo. Thioparib treatment elicited PARP1-dependent DNA damage and replication stress, causing S-phase arrest and apoptosis. Conversely, thioparib strongly inhibited HR-mediated DNA repair while increasing RAD51 foci formation. Notably, the on-target inhibition of PARP7 by thioparib-activated STING/TBK1-dependent phosphorylation of STAT1, triggered a strong induction of type I interferons (IFNs), and resulted in tumor growth retardation in an immunocompetent mouse model. However, the inhibitory effect of thioparib on tumor growth was more pronounced in PARP1 knockout mice, suggesting that a specific PARP7 inhibitor, rather than a pan inhibitor such as thioparib, would be more relevant for clinical applications. Finally, genome-scale CRISPR screening identified PARP1 and MCRS1 as genes capable of modulating thioparib sensitivity. Taken together, thioparib, a next-generation PARPi acting on both DNA damage response and antitumor immunity, serves as a therapeutic potential for treating hyperactive HR tumors, including those resistant to earlier-generation PARPi.

12.
Sci Adv ; 9(1): eade2493, 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36598987

RESUMO

Auxin and brassinosteroids (BRs) are two major growth-promoting phytohormones that shape hypocotyl elongation; however, the cross-talk between auxin and BR in this process is not fully understood. In this study, we found that auxin-induced hypocotyl elongation is dependent on brassinazole-resistant 1 (BZR1), a core BR signaling component. Auxin promotes BZR1 nuclear accumulation in hypocotyl cells, a process dependent on mitogen-activated protein kinase 3 (MPK3) and MPK6, which are both activated by auxin and whose encoding genes are highly expressed in hypocotyls. We determined that MPK3/MPK6 phosphorylate and reduce the protein stability of general regulatory factor 4 (GRF4), a member of the 14-3-3 family of proteins that retain BZR1 in the cytoplasm. In summary, this study reveals the molecular mechanism by which auxin promotes hypocotyl elongation by enhancing BZR1 nuclear accumulation via MPK3/MPK6-regulated GRF4 protein stability.

13.
J Aging Phys Act ; : 1-13, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36669506

RESUMO

External connectivity refers to the service opportunities provided by community open spaces that are influenced by the factors such as traffic distance, road conditions, residence patterns, and population distribution. It is an important factor in determining access to community open spaces. This has important implications for promoting walking behavior and community physical activity among aging urban populations. Using the accessibility evaluation method, we proposed an external connectivity of the community open spaces model from the community perspective and conducted an empirical study using the Overseas Chinese Town community in Shenzhen as an example. External connectivity of the community open spaces can be used to evaluate the efficiency of community open spaces, serving as a reference for open space optimization. Moreover, it has applicable value in promoting physical activity and healthy aging among older adults.

14.
Nutrients ; 15(2)2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36678243

RESUMO

A frequent chronic liver condition across the world is nonalcoholic fatty liver disease (NAFLD). Oxidative stress caused by lipid accumulation is generally considered to be the main cause of NAFLD. Anthocyanins can effectively inhibit the production of reactive oxygen species and improve oxidative stress. In this work, six major anthocyanins were separated from purple corncob by semi-preparative liquid chromatography. The effects of the 6 kinds of anthocyanins against NAFLD were investigated using a free fatty acid (FFA)-induced cell model. The results showed that peonidin 3-O-glucoside (P3G) can significantly reduce lipid accumulation in the NAFLD cell model. The treatment with P3G also inhibited oxidative stress via inhibiting the excessive production of reactive oxygen species and superoxide anion, increasing glutathione levels, and enhancing the activities of SOD, GPX, and CAT. Further studies unveiled that treatment with P3G not only alleviated inflammation but also improved the depletion of mitochondrial content and damage of the mitochondrial electron transfer chain developed concomitantly in the cell model. P3G upregulated transcription factor EB (TFEB)-mediated lysosomal function and activated the peroxisome proliferator-activated receptor alpha (PPARα)-mediated peroxisomal lipid oxidation by interacting with PPARα possibly. Overall, this study added to our understanding of the protective effects of purple corn anthocyanins against NAFLD and offered suggestions for developing functional foods containing these anthocyanins.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Hepatopatia Gordurosa não Alcoólica/etiologia , Antocianinas/farmacologia , Antocianinas/metabolismo , Fígado/metabolismo , Zea mays/metabolismo , Espécies Reativas de Oxigênio/metabolismo , PPAR alfa/metabolismo , Glucosídeos/farmacologia , Estresse Oxidativo , Inflamação/metabolismo , Ácidos Graxos não Esterificados/metabolismo , Lisossomos/metabolismo
15.
Fish Shellfish Immunol ; 133: 108510, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36608812

RESUMO

Resveratrol (RES) has been found to have immunological enhancement effects on Oreochromis niloticus. In O. nilocticus, the liver, spleen and kidney act as immune target tissues, while intestine works for nutrition sensing organ. In the present study, we determined RES administration on these immune tissues transcriptomic response in genetically improved farmed tilapia (GIFT), and further analyzed the relationship between transcriptomic response and intestinal microbiota. As results, hepatic hemosiderin and intestinal goblet cells significantly increased with RES addition. Kyoto encyclopedia of genes and genomes (KEGG) pathways associated with herpes simplex virus 1 infection, calcium signaling pathway, cell adhesion molecules, apoptosis, and mitogen-activated protein kinase (MAPK)/peroxisome proliferators-activated receptors (PPAR) signaling pathways were enriched. In particular, the differentially enriched genes (DEGs) associated pathways were present in different sampling tissues, times, and comparisons, interestingly, the PPAR signaling pathway was enriched with increasing time of RES addition. The assembled DEGs presented verified expression in the kidney, liver, spleen, and intestine tissues, and fabp6 was highly expressed in the intestine. Serial DEGs of fatty acid-binding proteins (fabp7, fabp7a, fabp10a) decreased in the liver and kidney, and fabp6 significantly increased in the spleen. With time, the pathways of energy metabolism, glycan biosynthesis, and metabolism decreased and increased in the intestinal metagenome. Some Candidatus branches significantly increased (C. cerribacteria and C. harrisonbacteria) and while others decreased (C. glodbacteria, etc.), whereas C. verstraetearchaeota fluctuated with RES addition. slc27a6 and dbi were negatively correlated with bacteria involved in the lipid, energy, and carbohydrate metabolism pathways. The present study suggests that RES supplementation affected lipid metabolism in immune-related organs may be related to the PPAR signaling pathway.

16.
Artigo em Inglês | MEDLINE | ID: mdl-36674163

RESUMO

BACKGROUND: Since there is little knowledge about the 24-hour movement behaviors of Chinese children and adolescents, the purposes of this study were to investigate the proportion of Chinese children and adolescents meeting the 24-Hour Movement Guidelines and to further evaluate its relationship with overweight and obesity. METHODS: A total of 440 children and adolescents aged 7-18 years from 7 cities in China were selected to measure physical activity using accelerometers, and sleep (SLP) and screen time (ST) using questionnaires. The data were analyzed with the independent T-test, Mann-Whitney U test, Cox-Stuart test, chi-square test, and logistic regression. RESULTS: The proportion of Chinese children and adolescents meeting the overall 24-Hour Movement Guidelines was 7.3%. Boys (11.8%) were higher than girls (3.4%) (p < 0.001) and showed a downward trend with age (Ptrend = 0.03). The rates of overweight and obesity among children and adolescents who met the ST, MVPA + ST, ST + SLP, and MVPA + SLP + ST guidelines were 39%, 15%, and 36%, and 25% did not meet any guidelines. The rates of overweight and obesity among those who met 1, 2, and 3 guidelines were lower than the rate among those who did not meet any guidelines (odds ratio (OR) = 0.51, 95% confidence interval (CI): 0.22-1.17; OR = 0.32, 95% CI: 0.13-0.77; OR = 0.23, 95% CI: 0.07-0.81) and showed a decreasing trend (Ptrend = 0.006). CONCLUSIONS: The proportion of Chinese children and adolescents meeting the overall 24-Hour Movement Guidelines was low. The rate of overweight and obesity among children and adolescents who met the overall 24-Hour Movement Guidelines was the lowest compared with the rates among those who met any one or two. There was a dose-response relationship between the number of guidelines met and the overweight and obesity rate.


Assuntos
Sobrepeso , Masculino , Feminino , Humanos , Criança , Adolescente , Sobrepeso/epidemiologia , Comportamento Sedentário , Obesidade , Inquéritos e Questionários , Sono
17.
J Thromb Haemost ; 21(1): 101-116, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36695374

RESUMO

BACKGROUND: Platelet endothelial aggregation receptor 1 (PEAR1) is a single-transmembrane orphan receptor primarily expressed on platelets and endothelial cells. Genetic variants of PEAR1 have repeatedly and independently been identified to be associated with cardiovascular diseases, including coronary artery disease. OBJECTIVES: We have identified sulfated fucoidans and their mimetics as ligands for PEAR1 and proposed that its endogenous ligand is a sulfated proteoglycan. The aim of this study was to test this hypothesis. METHODS: A heparin proteoglycan-mimetic (HPGM) was created by linking unfractionated heparin (UFH) to albumin. The ability of the HPGM, UFH and selectively desulfated heparins to stimulate platelet aggregation and protein phosphorylation was investigated. Nanobodies against the 12th to 13th epidermal growth factor-like repeat of PEAR1 and phosphoinositide 3-kinase (PI3K) isoform-selective inhibitors were tested for the inhibition of platelet activation. RESULTS: We show that HPGM, heparin conjugated to an albumin protein core, stimulates aggregation and phosphorylation of PEAR1 in washed platelets. Platelet aggregation was abolished by an anti-PEAR1 nanobody, Nb138. UFH stimulated platelet aggregation in washed platelets, but desulfated UFH did not. Furthermore, HPGM, but not UFH, stimulated maximal aggregation in platelet-rich plasma. However, both HPGM and UFH increased integrin αIIbß3 activation in whole blood. By using PI3K isoform-selective inhibitors, we show that PEAR1 activates PI3Kß, leading to Akt phosphorylation. CONCLUSION: Our findings reveal that PEAR1 is a receptor for heparin and HPGM and that PI3Kß is a key signaling molecule downstream of PEAR1 in platelets. These findings may have important implications for our understanding of the role of PEAR1 in cardiovascular disease.

18.
Nat Plants ; 9(1): 96-111, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36624255

RESUMO

Stem vascular cambium cells in forest trees produce wood for materials and energy. WOX4 affects the proliferation of such cells in Populus. Here we show that PtrWOX4a is the most highly expressed stem vascular-cambium-specific (VCS) gene in P. trichocarpa, and its expression is controlled by the product of the second most highly expressed VCS gene, PtrVCS2, encoding a zinc finger protein. PtrVCS2 binds to the PtrWOX4a promoter as part of a PtrWOX13a-PtrVCS2-PtrGCN5-1-PtrADA2b-3 protein tetramer. PtrVCS2 prevented the interaction between PtrGCN5-1 and PtrADA2b-3, resulting in H3K9, H3K14 and H3K27 hypoacetylation at the PtrWOX4a promoter, which led to fewer cambium cell layers. These effects on cambium cell proliferation were consistent across more than 20 sets of transgenic lines overexpressing individual genes, gene-edited mutants and RNA interference lines in P. trichocarpa. We propose that the tetramer-PtrWOX4a system may coordinate genetic and epigenetic regulation to maintain normal vascular cambium development for wood formation.

19.
Ann Epidemiol ; 77: 103-109, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36496149

RESUMO

PURPOSE: To investigate the relationships between the estimated cardiorespiratory fitness (eCRF) and the incidence of overall, breast, and prostate cancer in a large prospective cohort study. METHODS: We included 46,968 cancer-free adults who participated in the second survey of the Trøndelag Health Study in Norway. Sex-specific non-exercise algorithms were used to estimate CRF. eCRF was classified into sex and age-specific tertiles, that is, into low, medium and high levels. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Over a median of 22.1 years' follow-up, there were 7752 overall, 858 breast and 1376 prostate cancer cases. Medium and high levels of eCRF were associated with a reduced incidence of overall cancer in a dose-response manner in all participants (HR 0.96; 95% CI, 0.90-1.01 and HR 0.85; 95% CI, 0.79-0.91, respectively, and P-value for trend <.001). No association was observed between eCRF and breast cancer incidence in women. Only the high level of eCRF seemed to be associated with a reduced incidence of prostate cancer in men (HR 0.85; 95% CI, 0.72-1.02). CONCLUSIONS: eCRF may be a practical and cost-effective means of investigating the association between the CRF and cancer incidence.


Assuntos
Neoplasias da Mama , Aptidão Cardiorrespiratória , Neoplasias da Próstata , Adulto , Masculino , Humanos , Estudos Prospectivos , Neoplasias da Próstata/epidemiologia , Noruega/epidemiologia , Neoplasias da Mama/epidemiologia , Incidência , Fatores de Risco
20.
J Chin Med Assoc ; 86(2): 135-137, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36524941

RESUMO

The Omicron variant BA.2 is the dominant form of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in many countries, including those that have already implemented the strictest quarantine mandates that effectively contained the spread of the previous variants. Although many individuals were partially or fully vaccinated, confirmed Omicron infections have far surpassed all other variants combined in just a couple of months since the Omicron variant emerged. The ChAdOx1-S (AstraZeneca), BNT162b2 (Pfizer-BioNTech), and mRNA-1273 (Moderna) vaccines offer protection against the severe illness of SARS-CoV-2 infection; however, these currently available vaccines are less effective in terms of preventing Omicron infections. As a result, a booster dose of BNT162b2 or mRNA-1273 is recommended for individuals >12 years old who had received their second dose of the approved vaccines for >5 months. Herein, we review the studies that assessed the clinical benefits of the booster dose of vaccines against Omicron infections. We also analyzed public data to address whether early booster vaccination effectively prevented the surge of the Omicron infections. Finally, we discuss the consideration of a fourth dose of vaccine as a way to prevent possible upcoming infections.


Assuntos
Vacina de mRNA-1273 contra 2019-nCoV , COVID-19 , Humanos , Criança , Vacina BNT162 , COVID-19/prevenção & controle , SARS-CoV-2
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