An Ascovirus Utilizes Different Types of Host Larval Regulated Cell Death Mechanisms To Produce and Release Vesicles.

Ascoviruses are insect-specific viruses that are thought to utilize the cellular apoptotic processes of host larvae to produce numerous virion-containing vesicles. In this study, we monitored the in vivo infection processes of Heliothis virescens ascovirus 3h (HvAV-3h) to illustrate the regulated cell death (RCD) of host cells. Transmission electron microscopic observations did not reveal any morphological markers of apoptosis in the fat bodies or hemocytes of HvAV-3h-infected Helicoverpa armigera or Spodoptera exigua larvae. However, several hemocytes showed the morphological criteria for necrosis and/or pyroptosis. Further in vitro biochemical tests were performed to confirm the RCD type of host cells after infection with HvAV-3h. Different morphological characteristics were found between the early (prior to 24 hours post-infection, [hpi]) and later (48 to 120 hpi) stages in both HvAV-3h infected larval fat bodies and hemocytes. In the early stages, the virions could only be found in several adipohemocytes, and the fat bodies were cleaving their contained lipid inclusions into small lipid dots. In the later stage, both fat bodies and hemocytes were filled with numerous virions. According to the morphological characteristics of HvAV-3h infected larval fat bodies or hemocytes, the pathogenic characteristics and infection patterns of HvAV-3h in the host larvae were described, and the systematic pathogenic mode of ascovirus infection was refined in this study. This study details the complete infection process of ascoviruses, which provides insights into the relationship between a pathogenesis of an insect virus and the RCD of different host tissues at different stages of infection. IMPORTANCE Viruses and other pathogens can interrupt host cellular apoptosis to gain benefits, such as sufficient resources and a stable environment that enables them to complete their replication and assembly. It is unusual for viruses to code proteins with homology to caspases, which are commonly recognized as apoptosis regulators. Ascoviruses are insect viruses with special cytopathology, and they have been hypothesized to induce apoptosis in their host larvae via coding a caspase-like protein. This enables them to utilize the process of cellular apoptosis to facilitate vesicle formation and replication. However, our previous studies revealed different trends. The fat bodies and hemocytes of Heliothis virescens ascovirus 3h (HvAV-3h)-infected larvae did not show any morphological markers of apoptosis but did display necrosis and/or pyroptosis morphological characteristics. The pathogenic characteristics and infection patterns of HvAV-3h in the host larvae were described, which can help us understand the relationship between the pathogenesis of an insect virus and host RCD.

Structural basis for the killing of human beta cells by CD8(+) T cells in type 1 diabetes.

The structural characteristics of the engagement of major histocompatibility complex (MHC) class II-restricted self antigens by autoreactive T cell antigen receptors (TCRs) is established, but how autoimmune TCRs interact with complexes of self peptide and MHC class I has been unclear. Here we examined how CD8(+) T cells kill human islet beta cells in type 1 diabetes via recognition of a human leukocyte antigen HLA-A*0201-restricted glucose-sensitive preproinsulin peptide by the autoreactive TCR 1E6. Rigid 'lock-and-key' binding underpinned the 1E6-HLA-A*0201-peptide interaction, whereby 1E6 docked similarly to most MHC class I-restricted TCRs. However, this interaction was extraordinarily weak because of limited contacts with MHC class I. TCR binding was highly peptide centric, dominated by two residues of the complementarity-determining region 3 (CDR3) loops that acted as an 'aromatic-cap' over the complex of peptide and MHC class I (pMHCI). Thus, highly focused peptide-centric interactions associated with suboptimal TCR-pMHCI binding affinities might lead to thymic escape and potential CD8(+) T cell-mediated autoreactivity.

Phylogenomic data exploration with increased sampling provides new insights into the higher-level relationships of butterflies and moths (Lepidoptera).

A robust and stable phylogenetic framework is a fundamental goal of evolutionary biology. As the third largest insect order in the world following Coleoptera and Diptera, Lepidoptera (butterflies and moths) play a central role in almost every terrestrial ecosystem as indicators of environmental change and serve as important models for biologists exploring questions related to ecology and evolutionary biology. However, for such a charismatic insect group, the higher-level phylogenetic relationships among its superfamilies are still poorly resolved. Compared to earlier phylogenomic studies, we increased taxon sampling among Lepidoptera (37 superfamilies and 68 families containing 263 taxa) and acquired a series of large amino-acid datasets from 69,680 to 400,330 for phylogenomic reconstructions. Using these datasets, we explored the effect of different taxon sampling with significant increases in the number of included genes on tree topology by considering a series of systematic errors using maximum-likelihood (ML) and Bayesian inference (BI) methods. Moreover, we also tested the effectiveness in topology robustness among the three ML-based models. The results showed that taxon sampling is an important determinant in tree robustness of accurate lepidopteran phylogenetic estimation. Long-branch attraction (LBA) caused by site-wise heterogeneity is a significant source of bias giving rise to unstable positions of ditrysian groups in phylogenomic reconstruction. Phylogenetic inference showed the most comprehensive framework to reveal the relationships among lepidopteran superfamilies, and presented some newly relationships with strong supports (Papilionoidea was sister to Gelechioidea and Immoidea was sister to Galacticoidea, respectively), but limited by taxon sampling, the relationships within the species-rich and relatively rapid radiation Ditrysia and especially Apoditrysia remain poorly resolved, which need to increase taxon sampling for further phylogenomic reconstruction. The present study demonstrates that taxon sampling is an important determinant for an accurate lepidopteran tree of life and provides some essential insights for future lepidopteran phylogenomic studies.

CdBi2S4-Decorated Aminated Polyacrylonitrile Nanofiber for Photocatalytic Treatment of Cr(VI) and Tetracycline Wastewater.

The significant threat posed by the high toxicity of heavy metals and antibiotics in water pollutants has prompted a growing emphasis on the development of highly efficient removal methods for these pollutants. In this paper, flexible electrospinning polyacrylonitrile (PAN) nanofiber-supported CdBi2S4 was synthesized via a hydrothermal method, followed by amination treatment with diethylenetriamine (DETA). The as-prepared CdBi2S4/NH2-PAN nanofiber, enriched with sulfur vacancies, demonstrated outstanding visible-light trapping ability and a suitable band gap, leading to efficient separation and transport of photogenerated carriers, ultimately resulting in exceptional photocatalytic capability. The optimal 3-CdBi2S4/NH2-PAN nanofiber achieved impressive reduction rates of 92.26% for Cr(VI) and 96.45% for tetracycline hydrochloride (TCH) within 120 min, which were much higher than those for CdS/NH2-PAN, Bi2S3/NH2-PAN, and CdBi2S4/PAN nanofibers. After five cycles, the removal rate of the CdBi2S4/NH2-PAN nanofiber consistently remained above 90%. Their ease of separation and recovery from the application environment contributes to their practicality. Additionally, compared with conventional suspended particle catalyzers, the composite nanofiber exhibited remarkable flexibility and self-supporting properties.

Highly Emissive and Robust Cd-Based MOF with an Unprecedented Topology for Tetracycline Sensing.

Herein, an unprecedented cadmium-based metal-organic framework (JNU-106) fabricated by utilizing pyrazole-functionalized tetraphenylethylene ligands (Py-TPE) and rod-shaped secondary building units is reported, possessing a new (3,3,3,6,6,8)-connected topological network. Thanks to the ingeniously designed intramolecular charge transfer behavior, which originates from the congruent coplanarity between Py and TPE, JNU-106 exhibits intense green luminescence with a quantum yield increased by 1.5 times. The phenomenon of remarkable fluorescence quenching of JNU-106 reveals that it possesses extremely high anti-interference performance, superior sensitivity, and dedicated selectivity toward tetracycline antibiotics (TCAs) in aqueous solutions, which are comparable to those of the state-of-the-art porous sensing compounds. Taking the theoretical calculations and experimental results into account, the luminescence quenching is mainly attributed to the internal filtration effect and the static quenching effect. Considering the portable and rapid performance of JNU-106-based testing strips for sensing TCAs, the fabricated JNU-106 provides an alternative for ecological monitoring and environmental governance.

Identification of Additives in Disposable Face Masks and Evaluation of Their Toxicity Using Marine Medaka (Oryzias melastigma).

The COVID-19 pandemic has resulted in huge amounts of face masks worldwide. However, there is a lack of awareness on the additives and their potential risk to aquatic ecosystems of face masks. To address this issue, the additives and their toxicity in 13 face masks (e.g., polypropylene, polyethylene, and polylactic acid) were determined using nontarget analysis and bioassays. A total of 826 organic additives including intermediates (14.8%), surfactants (9.3%), plasticizers (8.2%), and antioxidants (6.1%) were tentatively identified, with 213 compounds being assigned confidence levels of 1 and 2. Interestingly, polylactic acid masks contained more additives than most polypropylene or polyethylene masks. Among these additives, the concentration of tris(2-ethylhexyl) phosphate in masks was 9.4-978.2 ng/g with a 100% detection frequency. Furthermore, 13 metals such as zinc (up to 202.0 µg/g), copper (32.5 µg/g), and chromium (up to 5.7 µg/g) were detected in the face masks. The methanol extracts of the masks showed the developmental toxicity, swimming behavior, and/or endocrine disruption in embryos/larvae of Oryzias melastigma. The findings demonstrate that face masks contain various toxic additives to marine medaka, which deserves close attention to pollution by face masks.

Global, regional, and national burden of ischemic heart disease attributable to ambient PM2.5 from 1990 to 2019: An analysis for the global burden of disease study 2019.

Information on the spatio-temporal patterns of the burden of ischemic heart disease (IHD) caused by ambient ambient fine particulate matter (PM2.5) in the global level is needed to prioritize the control of ambient air pollution and prevent the burden of IHD. The Global Burden of Disease Study (GBD) 2019 provides data on IHD attributable to ambient PM2.5. The IHD burden and mortality attributable to ambient PM2.5 were analyzed by year, age, gender, socio-demographic index (SDI) level, geographical region and country. Estimated annual percentage change (EAPC) was calculated to estimate the temporal trends of age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life years rate (ASDR) from 1990 to 2019. Globally, the ASMR and ASDR for ambient PM2.5-related IHD tended to level off generally, with EAPC of -0.03 (95% CI: -0.06, 0.12) and 0.3 (95% CI: 0.22, 0.37), respectively. In the past 30 years, there were obvious differences in the trend of burden change among different regions. A highest increased burden was estimated in low-middle SDI region (EAPC of ASMR: 3.73 [95% CI: 3.56, 3.9], EAPC of ASDR: 3.83 [95% CI: 3.64, 4.02]). In contrast, the burden in high SDI region (EAPC of ASMR: -4.48 [95% CI: -4.6, -4.35], EAPC of ASDR: -3.98 [95% CI: -4.12, -3.85]) has declined most significantly. Moreover, this burden was higher among men and older populations. EAPCs of the ASMR (R = -0.776, p < 0.001) and ASDR (R = -0.781, p < 0.001) of this burden had significant negative correlations with the countries' SDI level. In summary, although trends in the global burden of IHD attributable to ambient PM2.5 are stabilizing, but this burden has shifted from high SDI countries to middle and low SDI countries, especially among men and elderly populations. To reduce this burden, the air pollution management prevention need to be further strengthened, especially among males, older populations, and middle and low SDI countries.

Cordycepin delays postovulatory aging of oocytes through inhibition of maternal mRNAs degradation via DCP1A polyadenylation suppression.

Postovulatory aging leads to the decline in oocyte quality and subsequent impairment of embryonic development, thereby reducing the success rate of assisted reproductive technology (ART). Potential preventative strategies preventing oocytes from aging and the associated underlying mechanisms warrant investigation. In this study, we identified that cordycepin, a natural nucleoside analogue, promoted the quality of oocytes aging in vitro, as indicated by reduced oocyte fragmentation, improved spindle/chromosomes morphology and mitochondrial function, as well as increased embryonic developmental competence. Proteomic and RNA sequencing analyses revealed that cordycepin inhibited the degradation of several crucial maternal proteins and mRNAs caused by aging. Strikingly, cordycepin was found to suppress the elevation of DCP1A protein by inhibiting polyadenylation during postovulatory aging, consequently impeding the decapping of maternal mRNAs. In humans, the increased degradation of DCP1A and total mRNA during postovulatory aging was also inhibited by cordycepin. Collectively, our findings demonstrate that cordycepin prevents postovulatory aging of mammalian oocytes by inhibition of maternal mRNAs degradation via suppressing polyadenylation of DCP1A mRNA, thereby promoting oocyte developmental competence.

Follistatin mediates learning and synaptic plasticity via regulation of Asic4 expression in the hippocampus.

The biological mechanisms underpinning learning are unclear. Mounting evidence has suggested that adult hippocampal neurogenesis is involved although a causal relationship has not been well defined. Here, using high-resolution genetic mapping of adult neurogenesis, combined with sequencing information, we identify follistatin (Fst) and demonstrate its involvement in learning and adult neurogenesis. We confirmed that brain-specific Fst knockout (KO) mice exhibited decreased hippocampal neurogenesis and demonstrated that FST is critical for learning. Fst KO mice exhibit deficits in spatial learning, working memory, and long-term potentiation (LTP). In contrast, hippocampal overexpression of Fst in KO mice reversed these impairments. By utilizing RNA sequencing and chromatin immunoprecipitation, we identified Asic4 as a target gene regulated by FST and show that Asic4 plays a critical role in learning deficits caused by Fst deletion. Long-term overexpression of hippocampal Fst in C57BL/6 wild-type mice alleviates age-related decline in cognition, neurogenesis, and LTP. Collectively, our study reveals the functions for FST in adult neurogenesis and learning behaviors.

Value of CT in targeted CT-guided epidural blood patching: Predictors for successful epidural punctures.

BACKGROUND AND PURPOSE: Differentiating epidural from intrathecal punctures before computed tomography (CT)-guided epidural blood patching (EBP) is subjective, relying on operator experience. This study aimed to investigate CT findings for epidural and intrathecal punctures and identify reliable predictors for successful epidural punctures before targeted CT-guided EBP. MATERIALS AND METHODS: We included 65 patients with low-cerebrospinal fluid (CSF)-pressure headache receiving targeted CT-guided EBP between January 2021 and October 2022 in this retrospective study. We analyzed clinical data, technical information, and CT features before EBP. Fisher's exact test was used for discrete variables, while Mann-Whitney U test was used for continuous variables. Positive (PLR) and negative likelihood ratios (NLR) were calculated to identify predictors for confirming epidural punctures. RESULTS: We confirmed 43 patients as epidural punctures and 22 patients as intrathecal punctures. Before contrast injection, epidural fat at the needle tip in the epidural group was higher than the intrathecal group (37.2 % [16/43] vs. 4.5 % [1/22], p = 0.006). After contrast injection, the "contrast-needle tip connection" sign was mostly observed in the epidural group than the intrathecal group (95.3 % [41/43] vs. 9.1 % [2/22], p < 0.001). Additionally, the epidural group had significantly higher boomerang-shaped contrast morphology than the intrathecal group (65.1 % [28/43] vs. 9.1 % [2/22], p < 0.001). The "contrast-needle tip connection" sign had the highest PLR (10.49) and lowest NLR (0.05). CONCLUSION: Identifying epidural fat at the needle tip, "contrast-needle tip connection" sign, and boomerang-shaped contrast morphology on CT scans are useful for confirming proper placement of the needle tip within the epidural space.

Unlocking cardiomyocyte renewal potential for myocardial regeneration therapy.

Cardiovascular disease remains the leading cause of mortality worldwide. Cardiomyocytes are irreversibly lost due to cardiac ischemia secondary to disease. This leads to increased cardiac fibrosis, poor contractility, cardiac hypertrophy, and subsequent life-threatening heart failure. Adult mammalian hearts exhibit notoriously low regenerative potential, further compounding the calamities described above. Neonatal mammalian hearts, on the other hand, display robust regenerative capacities. Lower vertebrates such as zebrafish and salamanders retain the ability to replenish lost cardiomyocytes throughout life. It is critical to understand the varying mechanisms that are responsible for these differences in cardiac regeneration across phylogeny and ontogeny. Adult mammalian cardiomyocyte cell cycle arrest and polyploidization have been proposed as major barriers to heart regeneration. Here we review current models about why adult mammalian cardiac regenerative potential is lost including changes in environmental oxygen levels, acquisition of endothermy, complex immune system development, and possible cancer risk tradeoffs. We also discuss recent progress and highlight conflicting reports pertaining to extrinsic and intrinsic signaling pathways that control cardiomyocyte proliferation and polyploidization in growth and regeneration. Uncovering the physiological brakes of cardiac regeneration could illuminate novel molecular targets and offer promising therapeutic strategies to treat heart failure.

On-Off Switching of a Photocatalytic Overall Reaction through Dynamic Spin-State Transition in a Hofmann Clathrate System.

Spin-state transition is a vital factor that dominates catalytic processes, but unveiling its mechanism still faces the great challenge of the lack of catalyst model systems. Herein, we propose that the {Fe-Pt} Hofmann clathrates, whose dynamic spin-state transition of metal centers can be chemically manipulated through iodine treatment, can serve as model systems in the spin-related structural-catalytic relationship study. Taking the photocatalytic synthesis of H2O2 as the basic catalytic reaction, when the spin state of Fe(II) in the clathrate is high spin (HS), sacrificial agents are indispensable to the photosynthesis of H2O2 because only the photocatalytic oxygen reduction reaction (ORR) occurs; when it is low spin (LS), both the ORR and water oxidation reaction (WOR) can take place, enabling a high H2O2 photosynthesis rate of 66 000 µM g-1 h-1 under visible-light irradiation. In situ characterizations combined with density functional theory calculations confirmed that, compared with the HS-state counterpart, the LS state can induce strong charge transfer between the LS Fe(II) and the iodide-coordinating Pt(IV) in the polymer and reduce the energy barriers for both the ORR and WOR processes, dominating the on-off switching upon the photosynthesis of H2O2 in O2-saturated water. What's more, the one-pot tandem reactions were conducted to utilize the synthesized H2O2 for transforming the low-value-added sodium alkenesulfonates into value-added bromohydrin products with decent conversion rates. This work provides a pioneering investigation into on-off switching the photocatalytic overall reaction through manipulating the metallic spin-state transition in spin-crossover systems.

X-linked BCOR variants identified in Chinese Han patients with congenital heart disease.

BACKGROUND: Congenital heart disease (CHD) frequently manifests as a complex phenotype and approximately one-third of cases may be caused by genetic factors. BCOR, an X-linked gene encoding the corepressor of BCL6, has been demonstrated to be closely involved in human heart development. However, whether BCOR variants represent the genetic etiology underlying CHD needs further investigation. METHODS: We performed whole exome sequencing on CHD nuclear families and identified a candidate gene, BCOR, by robust bioinformatic analysis and medical literature searches. Targeted DNA sequencing of the candidate gene was conducted and then the association between variants and the risk of developing CHD was analyzed. The effects of BCOR mutations on gene expression, localization, protein interaction, and signaling pathways were evaluated in vitro. RESULTS: We identified a BCOR hemizygous missense variant (c.1448C>T, p.Pro483Leu) in a male proband presented with CHD/heterotaxy. Sanger sequencing confirmed that this variant was inherited from his asymptomatic mother. Interestingly, through literature searches, we observed another novel BCOR hemizygous missense variant (c.1619G>A, p.Arg540Gln) in a CHD patient with heterotaxy, supporting the pathogenic evidence of BCOR variants. Functional experiments conducted in vitro revealed that the variant p.Pro483Leu altered the subcellular localization of BCOR protein, disrupted its interaction with BCL6, and significantly promoted cell proliferation, whereas the variant p.Arg540Gln displayed no obvious effects. Nevertheless, transcriptional analysis revealed that down-regulation of BCOR substantially enhanced the activities of mitogen-activated protein and phosphoinositide 3-kinase-AKT signaling pathways, which are closely attributed to heart development. Targeted sequencing of 932 sporadic CHD patients enriched nine variants of BCOR predicted as likely rare and damaging and a septal defect was present in 81.8% (9/11) of them, including the two probands, which was consistent with the possible phenotype caused by BCOR defects. CONCLUSIONS: The findings of the present study indicate that variants in BCOR may predispose individuals to CHD in the Chinese Han population.

Development of a ZIF-91-Porous-Liquid-Based Composite Hydrogel Dressing System for Diabetic Wound Healing.

Porous metal-organic framework (MOF) liquids with permanent porosity, good fluidity, and fine dispersion attract broad attention in catalysis, transportation, gas storage, and chemical separations. Yet, the design and synthesis of porous MOF liquids for drug delivery remain less explored. Herein, a simple and general strategy is reported to prepare ZIF-91 porous liquid (ZIF-91-PL) via surface modification and ion exchange. The cationic nature of ZIF-91-PL not only renders it antibacterial but also with high curcumin loading capacity and sustained release. More importantly, the acrylate group on the grafted side chain of ZIF-91-PL makes it feasible to crosslink with modified gelatin through light curing, and the obtained hydrogel shows a significantly improved healing effect on the wound of diabetes. This work demonstrates for the first time, a MOF-based porous liquid for drug delivery, and the further fabrication of composite hydrogel may have potential applications in biomedical science.

Growth hormone reduces aneuploidy and improves oocytes quality by JAK2-MAPK3/1 pathway in aged mice.

BACKGROUND: The global delay in women's reproductive age has raised concerns about age-related infertility. The decline in oocyte quality is a limiting factor of female fertility, yet there are currently no strategies to preserve oocyte quality in aged women. Here, we investigated the effects of growth hormone (GH) supplementation on aneuploidy of aged oocytes. METHODS: For the in vivo experiments, the aged mice (8-month-old) were intraperitoneally injected with GH daily for 8 weeks. For the in vitro experiments, germinal vesicle oocytes from aged mice were treated with GH during oocyte maturation. The impacts of GH on ovarian reserve before superovulation was evaluated. Oocytes were retrieved to assess oocyte quality, aneuploidy and developmental potential characteristics. Quantitative proteomics analysis was applied to investigate the potential targets of GH in aged oocytes. RESULTS: In this study, we demonstrated that GH supplementation in vivo not only alleviated the decline in oocyte number caused by aging, but also improved the quality and developmental potential of aged oocytes. Strikingly, we discovered that GH supplementation reduced aneuploidy in aged oocytes. Mechanically, in addition to improving mitochondrial function, our proteomic analysis indicated that the MAPK3/1 pathway may be involved in the reduction in aneuploidy of aged oocytes, as confirmed both in vivo and in vitro. In addition, JAK2 may also act as a mediator in how GH regulates MAPK3/1. CONCLUSIONS: In conclusion, our research reveals that GH supplementation protects oocytes against aging-related aneuploidy and enhances the quality of aged oocytes, which has clinical significance for aged women undergoing assisted reproduction technology.

Oxygen Vacancy-Mediated CuWO4/CuBi2O4 Samples with Efficient Charge Transfer for Enhanced Catalytic Activity toward Photodegradation of Pharmacologically Active Compounds.

Photocatalytic degradation is a promising method for controlling the increasing contamination of the water environment due to pharmacologically active compounds (PHACs). Herein, oxygen vacancy (OV)-modulated Z-scheme CuWO4/CuBi2O4 hybrid systems were fabricated via thermal treatment by loading of CuWO4 nanoparticles with OVs on CuBi2O4 surfaces. The synthesized CuWO4/CuBi2O4 hybrid samples exhibited an enhanced photodegradation ability to remove PHACs under visible-light irradiation. More importantly, an optimized sample (10 wt % CuWO4/CuBi2O4) exhibited superior catalytic activity and excellent recycling stability for PHAC photodegradation. In addition, possible degradation paths for PHAC removal over the CuWO4/CuBi2O4 hybrid systems were proposed. The enhanced photocatalytic performance could be attributed to the efficient separation and transfer of photoformed charge pairs via the Z-scheme mechanism. This Z-scheme mechanism was systematically analyzed using trapping experiments of active species, ultraviolet photoelectron spectroscopy, electron spin resonance, and the photodepositions of noble metals. The findings of this study can pave the way for developing highly efficient Z-scheme photocatalytic systems for PHAC photodegradation.

ALKBH5 inhibits thyroid cancer progression by promoting ferroptosis through TIAM1-Nrf2/HO-1 axis.

As a critical catalytic subunit of N6-methyladenosine (m6A) modification in messenger RNA, ALKBH5 has been reported to affect the progression of numerous tumors. However, the functions and mechanisms of ALKBH5 in thyroid cancer remain largely unknown. Relative mRNA and protein levels in thyroid cancer tissues and cells were detected by qRT-PCR and western blot, respectively. The proliferation and viability were evaluated using colony formation and CCK-8 assays. Intracellular iron level was measured by an iron colorimetric assay kit. ROS level was determined using CellRox Green reagent. TIAM1 mRNA m6A level was detected by MeRIP. Xenograft tumor growth was performed to examine the role of ALKBH5 in thyroid tumor growth in vivo. ALKBH5 was decreased in thyroid cancer tissues and cells. ALKBH5 overexpression inhibited thyroid cancer cell proliferation and increased the levels of Fe2+ and ROS and reduced the proteins expression of GPX4 and SLC7A11. Furthermore, overexpression of ALKBH5 inhibited TIAM1 expression by m6A modification, and overexpression of TIAM1 reversed the regulatory of oe-ALKBH5 on cell proliferation and ferroptosis in thyroid cancer. In addition, TIAM1 was elevated in thyroid cancer, and TIAM1 knockdown repressed thyroid cancer cell proliferation and promoted ferroptosis through regulating Nrf2/HO-1 axis. In addition, in vivo evidences also showed that ALKBH5 suppressed thyroid cancer progression by decreasing the m6A level of TIAM1. Our findings suggested that ALKBH5 inhibited thyroid cancer progression by inducing ferroptosis through m6A-TIAM1-Nrf2/HO-1 axis, suggesting ALKBH5 might be a potential target molecule for the treatment and diagnosis of thyroid cancer.

Palladium/Norbornene Cooperative-Catalyzed Cascade Decarboxylative Cyclization of 4-Iodoisoquinolin-1(2H)-ones with o-Bromobenzoic Acids: Access to Diverse Fused Phenanthridinones and Hepta[1,2-c]isoquinolinones.

A novel three-component Pd/norbornene cooperative catalysis cascade decarboxylative [2+2+2]/[2+2+3]cyclization of 4-iodoisoquinolin-1(2H)-ones and o-bromobenzoic acids or 8-bromo-1-naphthoic acid has been developed. The method affords a range of fused phenanthridinones and hepta[1,2-c]isoquinolinones and displays unique regioselectivity and broad substrate scope. Palladium/norbornene (Pd/NBE)-catalyzed C-H activation and subsequent decarboxylative coupling reactions were involved, and NBE acts as a building block for the construction of rigid nonplanar molecular architectures.

Visible light-induced radical cascade acylmethylation/cyclization of 2-(allyloxy)arylaldehydes with α-bromo ketones: access to cyclic 1,5-dicarbonyl-containing chroman-4-one skeletons.

A novel photocatalytic protocol for effective and efficient synthesis of cyclic 1,5-diketones containing chroman-4-one skeletons in moderate to good yields via radical cascade acylmethylation/cyclization of 2-(allyloxy)arylaldehydes with α-bromo ketones has been described. This reaction features a broad substrate scope, good functional group tolerance, and metal- and oxidant-free conditions. An acylmethyl radical-triggered cascade cyclization was involved.

Toxicity and Estrogenicity of Bisphenol TMC in Oryzias melastigma via In Vivo and In Silico Studies.

Bisphenol 4-[1-(4-hydroxyphenyl)-3,3,5-trimethylcyclohexyl] phenol (BPTMC), as a substitute for bisphenol A, has been detected in environments. However, the ecotoxicological data of BPTMC are extremely scarce. Here, the lethality, developmental toxicity, locomotor behavior, and estrogenic activity of BPTMC at different concentrations (0.25-2000 µg/L) in marine medaka (Oryzias melastigma) embryos were examined. In addition, the in silico binding potentials of O. melastigma estrogen receptors (omEsrs) with BPTMC were assessed by docking study. Low-concentration BPTMC exposure (including an environmentally relevant concentration, 0.25 µg/L) resulted in stimulating effects, including hatching rate, heart rate, malformation rate, and swimming velocity. However, elevated concentrations of BPTMC led to an inflammatory response, changed heart rate and swimming velocity in the embryos and larvae. In the meantime, BPTMC (including 0.25 µg/L) altered the concentrations of estrogen receptor, vitellogenin, and endogenous 17 ß-estradiol as well as the transcriptional levels of estrogen-responsive genes in the embryos or/and larvae. Furthermore, elaborate tertiary structures of omEsrs were built by ab initio modeling, and BPTMC exerted potent binding potential with three omEsrs with -47.23, -49.23, and -50.30 kJ/mol for Esr1, Esr2a, and Esr2b, respectively. This work suggests that BPTMC has potent toxicity and estrogenic effects in O. melastigma.