Maternal Di-(2-ethylhexyl)-Phthalate exposure during pregnancy altered energy metabolism in immature offspring and caused hyperglycemia.

Di-(2-ethylhexyl)-phthalate (DEHP), as distinctive endocrine disrupting chemicals, has become a global environmental pollutant harmful to human and animal health. However, the impacts on offspring and mothers with maternal DEHP exposure are largely unknown and the mechanism remains elusive. We established DEHP-exposed maternal mice to investigate the impacts on mother and offspring and illustrate the mechanism from multiple perspectives. Pregnant mice were administered with different doses of DEHP, respectively. Metagenomic sequencing used fecal and transcriptome sequencing using placentas and livers from offspring have been performed, respectively. The results of the histopathology perspective demonstrated that DEHP exposure could disrupt the function of islets impact placentas and fetus development for maternal mice, and cause the disorder of glucose and lipid metabolism for immature offspring mice, resulting in hyperglycemia. The results of the metagenome of gut microbial communities indicated that the dysbiosis of gut microbiota in mother and offspring mice and the dominant phyla transformed through vertical transmission. Transcriptome analysis found DEHP exposure induced mutations of Ahcy and Gstp3, which can damage liver cells and affect the metabolism of the host. DEHP exposure harms pregnant mice and offspring by affecting gene expression and altering metabolism. Our results suggested that exposure of pregnant mice to DEHP during pregnancy and lactation increased the risk of metabolic disorders by altering key genes in liver and gut microbiota, and these results provided new insights into the potential long-term harms of DEHP.

Metalloestrogens exposure and risk of gestational diabetes mellitus: Evidence emerging from the systematic review and meta-analysis.

BACKGROUND: Metalloestrogens are metals and metalloid elements with estrogenic activity found everywhere. Their impact on human health is becoming more apparent as human activities increase. OBJECTIVE: Our aim is to conduct a comprehensive systematic review and meta-analysis of observational studies exploring the correlation between metalloestrogens (specifically As, Sb, Cr, Cd, Cu, Se, Hg) and Gestational Diabetes Mellitus (GDM). METHODS: PubMed, Web of Science, and Embase were searched to examine the link between metalloestrogens (As, Sb, Cr, Cd, Cu, Se, and Hg) and GDM until December 2023. Risk estimates were derived using random effects models. Subgroup analyses were conducted based on study countries, exposure sample, exposure assessment method, and detection methods. Sensitivity analyses and adjustments for publication bias were carried out to assess the strength of the findings. RESULTS: Out of the 389 articles identified initially, 350 met our criteria and 33 were included in the meta-analysis, involving 141,175 subjects (9450 cases, 131,725 controls). Arsenic, antimony, and copper exposure exhibited a potential increase in GDM risk to some extent (As: OR = 1.28, 95 % CI [1.08, 1.52]; Sb: OR = 1.73, 95 % CI [1.13, 2.65]; Cu: OR = 1.29, 95 % CI [1.02, 1.63]), although there is a high degree of heterogeneity (As: Q = 52.93, p < 0.05, I2 = 64.1 %; Sb: Q = 31.40, p < 0.05, I2 = 80.9 %; Cu: Q = 21.14, p < 0.05, I2 = 71.6 %). Conversely, selenium, cadmium, chromium, and mercury exposure did not exhibit any association with the risk of GDM in our study. DISCUSSION: Our research indicates that the existence of harmful metalloestrogens in the surroundings has a notable effect on the likelihood of GDM. Hence, we stress the significance of environmental elements in the development of GDM and the pressing need for relevant policies and measures.

Utilizing Integrated UHPLC-Q-Exactive Orbitrap-MS, Multivariate Analysis, and Bioactive Evaluation to Distinguish between Wild and Cultivated Niudali (Millettia speciosa Champ.).

Millettia speciosa Champ. (MSCP) enjoys widespread recognition for its culinary and medicinal attributes. Despite the extensive history of MSCP cultivation, the disparities in quality and bioactivity between wild and cultivated varieties have remained unexplored. In this study, 20 wild and cultivated MSCP samples were collected from different regions in China. We embarked on a comprehensive investigation of the chemical constituents found in both wild and cultivated MSCP utilizing UHPLC-Q-Exactive Orbitrap-MS technology and multivariate analysis such as principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). In total, 62 chemical components were unequivocally identified or tentatively characterized. Via the multivariate statistical analysis, we successfully pinpointed nine compounds with the potential to serve as chemical markers, enabling the differentiation between wild and cultivated MSCP varieties. Moreover, both genotypes exhibited substantial antioxidant and anti-fatigue properties. The bioactivities of wild MSCP were marginally higher when compared to their cultivated counterparts. This study illuminates the impressive antioxidant and anti-fatigue potential present in both wild and cultivated MSCP genotypes, further augmenting the allure of this species and opening new avenues for the economic valorization of MSCP. Hence, this study provides a valuable method for the identification and quality control of MSCP and a method in chemistry and pharmacology to assess an alternative possibility for cultivated MSCP.

Photochemical-promoted ZVI reduction for highly efficient removal of 4-chlorophenol and Cr(VI): Catalytic activity, performance and electron transfer mechanisms.

Zero-valent iron (ZVI) reduction represents a promising methodology for water remediation, but its broad application is limited by two critical challenges (i.e., aggregation and passivation). Here, we report a hybrid strategy of photochemical-promoted ZVI reduction with high efficiency and reduction capacity for removing coexisting refractory pollutants in water. A composite material with Pd/Fe bimetallic nanoparticles supported onto semiconducting metal oxide (Pd/Fe@WO3-GO) was prepared and subsequently used as the model catalyst. By using the developed strategy with visible light as light source, this catalyst showed a remarkable catalytic performance for simultaneously eliminating 4-chlorophenol (4-CP) and Cr(VI), with dehalogenation rate as high as 0.43 min-1, outperforming the reported ZVI-based catalysts. A synergistic interaction of photocatalysis and ZVI reduction occurred in this strategy, where the interfacial electron transfer on particles surface were greatly strengthened with light irradiation. The activation was attributed to the dual functions of semiconducting material as support to disperse Pd/Fe nanoparticles and as (photoexcited) electron donor to directly trigger reduction reactions and/or indirectly inhibit the formation of oxides passivation layer. Both direct electron transfer and H*-mediated indirect electron transfer mechanisms were confirmed to participate in the reduction of pollutants, while the later was quantitatively demonstrated as the predominant reaction route. Importantly, this strategy showed a wide pH applicability, long-term durability and excellent catalytic performance in different real-water systems. This work provides new insights into ZVI reduction and advances its applications for the removal of combined organic and inorganic pollutants. The developed photochemical-promoted ZVI reduction strategy holds a great potential for practical applications.

First report of Agroathelia rolfsii causing southern blight on cowpea in China.

Cowpea (Vigna unguiculata L.) is a legume consumed as a high-quality plant protein source in many parts of the world. In August 2023, it was observed that a plant disease affected cowpea growth in Yiyang (28.34°N, 112.55°E), China. The average disease incidence was 10%, resulting in 8.5% economic losses in approximately 3,000 m2. The symptoms initially appeared as brown lesions near the stem-soil interface and the lesions were colonized by white mycelia. As the disease progressed, the disease symptoms included constriction and brown staining at the base of the stem, covered with a small amount of white mycelia. Eventually, the entire plants withered and collapsed and many sclerotia were scattered on the ground around the diseased stem. Twenty samples (10 sclerotia and 10 diseased tissue fragments) were collected from symptomatic plants for causal agent isolation. Samples were disinfected with 70% ethanol for 30 s, 5% NaClO for 1 min, rinsed three times with sterile water, dried and placed on potato dextrose agar (PDA) plates at 28℃ in the dark. In total, 20 isolates were obtained by the hyphal tip method (Terrones et al. 2022) and showed a consistent phenotype of white cottony mycelia on PDA with an growth rate of 12.9 to 21.3 mm/day (n = 20). Sclerotia formed at five to eight days post inoculation, were initially whitish, turning beige and eventually dark brown. The diameter of mature sclerotia ranged from 0.89 to 2.13 mm (mean = 1.64±0.29 mm; n =50). For pathogen identification, ITS1/ITS4 (White et al. 1990) and EF1-983F/EF1-2218R (Rehner and Buckley 2005) primers were used to amplify the internal transcribed spacer regions (ITS) and translation elongation factor-1 alpha gene (TEF-1α), respectively. The sequences of all 20 isolates showed 99% to 100% similarity with Agroathelia rolfsii sequences from GenBank by BLAST analysis. The sequences of two representative strains, ID1 and ID4, were deposited in GenBank. The ITS sequences of ID1 (OR689482) and ID4 (OR689481) were ＞99% similar to A. rolfsii strain QJ7 (593/596 bp; MZ750983) and A. rolfsii strain Kale078 (565/568 bp; MN872304), respectively. Also, TEF-1α sequences of ID1 (OR713735) and ID4 (OR713736) were ＞99% similar to the sequences of A. rolfsii strain HS-Sr (1073/1073 bp; OL416131) and A. rolfsii strain MSB1-2 (1070/1075 bp; MN702790), respectively. Phylogenetic analysis based on ITS and TEF1-α sequences indicated that ID1 and ID4 clustered into the A. rolfsii clade. Based on morphology and sequence analyses, the isolates ID1 and ID4 were identified as A. rolfsii (anamorph Sclerotium rolfsii). Pathogenicity tests were conducted three times on healthy 30-day-old cowpea seedlings. Five plants were inoculated with 6-day-old mycelial discs (6 mm) of ID1 or ID4 at the base of the seedlings (n = 30) while four plants were inoculated with a sterile PDA disc as a control (n = 12). All seedlings were cultivated in a greenhouse with a temperature of 26°C to 28°C and relative humidity 60% to 80% with a 14/10 h light/dark photoperiod. Eight days later, all the fungal inoculated seedlings showed symptoms including brown necrosis and collapse of the stems, and eventual withering of the seedlings. Control plants remained asymptomatic. The causal pathogens were reisolated in PDA plates and identified by ITS sequence analysis, completing Koch's postulates. To our knowledge, this is the first report of A. rolfsii causing southern blight on cowpea in China. Early accurate diagnosis will help farmers to adopt suitable practices to control disease outbreaks and reduce losses.

The modified biochar from wheat straw by the combined composites of MnFe2O4 nanoparticles and chitosan Schiff base for enhanced removal of U(VI) ions from aqueous solutions.

In the last few decades, U(VI) is a significant environmental threat. The innovative and environmentally friendly adsorbent materials for U(VI) removal were urgent. Preparation of the modified biochar from wheat straw by combined composites of MnFe2O4 nanoparticles and chitosan Schiff base (MnFe2O4@CsSB/BC) was characterized, and adsorption experiments were carried out to investigate the performance and interfacial mechanism of U(VI) removal. The results showed that MnFe2O4@CsSB/BC exhibited high adsorption capacity of U(VI) compared with BC. The adsorption process of U(VI) removal by MnFe2O4@CsSB/BC could be ascribed as pseudo-second-order model and Langmuir model. The maximum adsorption capacity of U(VI) removal by MnFe2O4@CsSB/BC reached 19.57 mg/g at pH4.0, 30 mg/L of U(VI), and 25 °C. The possible mechanism was a chemical adsorption process, and it mainly contained electrostatic attraction and surface complexation. Additionally, it also was an economic and environmental friendly adsorbent.

Electrochemical selenocyclization of 2-ethynylanilines with diselenides: facile and efficient access to 3-selenylindoles.

An efficient electrochemical selenocyclization strategy for the synthesis of 3-selenylindoles from 2-ethynylanilines and diselenides has been developed in simple tube- or beaker-type undivided cells under ambient conditions. Notably, these sustainable transformations are completed within a short time with low equivalents of charges, diselenides and electrolytes, exhibiting a broad substrate scope with excellent functional group compatibility. Moreover, a gram-scale electrosynthesis and late-stage functionalization of complex molecules further demonstrate the practical synthetic potential of this facile electrochemical system.

Study on Spontaneous Reactivation and Aging of Acetylcholinesterase Inhibited by Paraoxon and Malaoxon in Ten Species.

Organophosphorus insecticides (OPs), acting as serine phosphorylating agents in acetylcholinesterase (AChE), are highly effective neurotoxic insecticides. In our previous research, we found that six herbivorous pests and four ladybirds howed significantly higher AChE LC50 values than seven parasitoids and a predator (Epistrophe balteate), and that there was a significant correlation with the corresponding bimolecular rate constant (Ki) value. The Ki value of pests was much smaller than that of natural enemies and had a higher LC50 value.Then, we speculated that the low sensitivity of the pest AChE to OPs may be associated with its higher recovery and lower aging ability. In this work, the I50 and I90 were calculated, to determine the sensibility of AChE in ten representative species, including Plutella xylostella, Prodenia litura, Musca domestica, and Cavia porcellus, to paraoxon and malaoxon. The enzyme activities were measured at various time points, and kinetic calculations were used to obtain their spontaneous reactivation (Ks) and aging (Ka) constants, which were comprehensively compared. We conclude that the Ka and Ks of the AChE inhibited by OPs showed primarily species-specific correlations, and little correlation with the sensitivity to OPs. The differences in the AChE sensitivity to paraoxon among the ten species were much greater than in the sensitivity to malaoxon. Compared to paraoxon, malaoxon was more selective for Cavia porcellus. Coleoptera insects showed a stronger dephosphorylation ability than other insect groups. The recovery ability of phospho-AChE was stronger in mammals than in insects, which could be related to the low sensitivity of the AChE site of action to OPs. The Ka of the AChE inhibited by malaoxon was larger than that inhibited by paraoxon with the corresponding biomaterials, indicating that the OP type had a substantial relationship with the Ka of the AChE. We further discovered that, when insects were inhibited by OP, the tendency of AChE to undergo aging was greater than that of dephosphorylation. Overall, the study provides valuable information on the action mechanism of various OPs on AChE in several species, which could be used to further research into AChE and the potential dangers that organophosphates pose to animals.

Evaluation of exogenous therapeutic protein activity under confinement and crowding effects.

Dysfunction of intracellular proteins is frequently associated with various diseases, such as cancer. The exogenous proteins in cells are usually assembled with specific configurations due to physiological confinement/crowding to exhibit novel features in the protein structure, folding or conformational stability, distinguished with their behaviors in buffer solutions. Here, we synthesized exogenous proteins under confined/crowded conditions, to explore protein activity within cells. The findings suggested that the confinement and crowding effects on protein activity are heterogeneous; they showed an inhibitory effect on HRP by decreasing Km from ∼9.5- and ∼21.7-fold and Vmax from ∼6.8- and ∼20.2-fold lower than that of dilute solutions. Interestingly, the effects on Cyt C seem to be more complicated, and crowding exerts a positive effect by increasing Km ∼ 3.6-fold and Vmax ∼ 1.5-fold higher than that of dilute solutions; however, confinement exhibits a negative effect by decreasing Km ∼2.0 and Vmax ∼8.3 times. Additionally, in contrast to traditional nanoparticle-based confinement models, we synthesized a biodegradable nanoparticle to mimic the confined space, and the biggest advantage of this novel model is that the particles can be degraded and thus it can provide more intuitive observations of the properties of the target proteins under confinement and after release. Furthermore, we also evaluated protein activity in different cellular environments, indicating that the exogenous protein activity was closely related to the crowdedness of cellular environments, and the inhibition of protein activity in MDA-MB-231 cancer cells was more obvious than in HEK293 normal cells. Finally, SAXS analysis revealed the correlation between the protein conformation and the different environments. Our work will provide a unique method for precisely assessing whether the target cellular environments are native matrix in which specific exogenous protein drugs are delivered to function or whether they display a therapeutic role, which is of great significance for screening and development of new drugs.

First Report of Southern Blight Caused by Athelia rolfsii on Pepper in Yiyang, China.

Pepper(Capsicum annuum L.) is the vegetable with the largest production area China (Zou and Zou 2021). In the summer of 2020 and 2021, disease symptoms were observed in C. annuum L. cv. bola in a 10-ha field in Yiyang(28.35°N, 112.56°E), Hunan province of China. The disease incidence ranged from 10% to 30%. The symptoms initially appeared as tan lesions, which were colonized by fast-growing white mycelia, at the soil line. Affected plants eventually became wilted. Wilting was accompanied by girdling of the stem at the base, and signs of the pathogen, mycelia and golden-brown colored sclerotia. The spatial distribution of the disease was either single plants or small foci of affected plants. Diseased stem sections (1.0~1.5 cm) of 20 plants from the field in 2021 with typical symptoms were surface sterilized with 75% ethanol for 30 s, followed by 60 s in 2.5% NaClO, rinsed thrice with sterile water, air dried and plated on potato dextrose agar (PDA), and incubated at 28℃ in the dark for 5 days to isolate the causative pathogen. Twenty fungal isolates with similar colony morphology were collected and purified. These isolates formed radial colonies, and abundant sclerotia were observed after 5 to 10 days of incubation at 28℃. The color of the sclerotia with a diameter of 1.39 ± 0.15 mm (1.15 to 1.60, n=50) gradually changed from white to light yellow, and finally to dark brown. The representative isolate YYBJ20 was selected for further molecular identification. The internal transcribed spacer region and elongation factor-1alpha gene were amplified using the primers, ITS1/ITS4 (White et al. 1990) and EF1-983F/EF1-2218R (Rehner and Buckley 2005), respectively. The ITS and EF1α amplicons were sequenced and deposited in GenBank with the accession numbers OQ186649 and OQ221158, respectively. Sequence analysis revealed that the ITS and EF1α sequences of the YYBJ20 isolate exhibited ≥99% of identity with the ITS (MH260413 and AB075300) and EF1α (OL416131 and MW322687) sequences of Athelia rolfsii, respectively. Phylogenetic analysis classified YYBJ20 into a common clade with different A. rolfsii strains, but different from other Athelia or Sclerotium species. For pathogenicity tests, PDA plugs (6 mm diam.) colonized by 3-day-old mycelia were inoculated into the stem bases of 30-day-old pepper seedlings (n=10). Another 10 seedlings were inoculated with noncolonized PDA plugs were used as noninoculated controls. The pepper seedlings were incubated at 28 ± 2℃ and 60 to 80 % relative humidity under a 14h-10h of light-dark cycle. After 10 days of incubation, ten YYBJ20-inoculated plants were wilted with similar symptoms to those observed in the field, while control plants remained healthy. The pathogenicity tests were repeated three times. The fungal strain re-isolated from the infected seedlings (100% re-isolation frequency) showed the same morphological and molecular traits as the original isolates from the diseased plants. No fungi were isolated from the control plants, which is consistent with the Koch's postulates. Based on the morphological and sequencing results, the causative fungus was identified as A. rolfsii (anamorph Sclerotium rolfsii). To our knowledge, this is the first report of A. rolfsii causing southern blight on pepper in China. Due to the broad host range of and serious consequences caused by A. rolfsii (Lei et al. 2021; Zhang et al. 2022; Zhu et al. 2022), this research will be beneficial to develop strategies to mitigate future losses of pepper in China.

Electrocatalytic [3 + 2] Annulation for the Synthesis of Polysubstituted Furans.

In this report we describe an atom-economic, practical strategy for the synthesis of tri/tetra-substituted furans through electrochemical [3 + 2] annulation between alkynes and ß-keto compounds with ferrocene (Fc) as the catalyst. This protocol features the use of a graphite felt (GF) anode and a stainless steel (SST) cathode, mild conditions, and excellent tolerance with various alkynes and ß-keto compounds. Additionally, the application of this method is highlighted by the late-stage functionalization of complex structures and a gram-scale experiment.

Associating phthalate exposure during pregnancy with preschooler's FMI, ABSI and BRI trajectories via putative mechanism pathways.

Phthalates are well-known obesogens, but a few studies have explored their impacts on the childhood fat mass index (FMI), body shape index (ABSI) and body roundness index (BRI). Information from 2950 participants recruited in the Ma'anshan Birth Cohort was analyzed. The relationships between six maternal phthalate metabolites and their mixture and childhood FMI, ABSI and BRI were investigated. FMI, ABSI and BRI in children aged 3.5 y, 4.0 y, 4.5 y, 5.0 y, 5.5 y and 6.0 y were calculated. The latent class trajectory modeling categorized the FMI trajectories into "rapidly increasing FMI" (4.71%) and "stable FMI" (95.29%) groups; ABSI trajectories were categorized as "decreasing ABSI" (32.74%), "stable ABSI" (46.55%), "slowly increasing ABSI" (13.26%), "moderately increasing ABSI" (5.27%) and "rapidly increasing ABSI" (2.18%) groups; BRI trajectories were categorized as "increasing BRI" (2.82%), "stable BRI" (19.85%), and "decreasing BRI" (77.34%) groups. Prenatal MEP exposure was associated with repeated measurements of FMI (ß = 0.111, 95% CI = 0.002-0.221), ABSI (ß = 0.145, 95% CI = 0.023-0.268) and BRI (ß = 0.046, 95% CI = -0.005-0.097). Compared with each stable trajectory group, prenatal MEP (OR = 0.650, 95% CI = 0.502-0.844) and MBP (OR = 0.717, 95% CI = 0.984-1.015) were linked to a decreased risk of "decreasing BRI" in children; there was a negative relationship between MBP and the "decreasing ABSI" group (OR = 0.667, 95% CI = 0.487-0.914), and MEP increased the risks of "slowly increasing ABSI" (OR = 1.668, 95% CI = 1.210-2.299) and "rapidly increasing ABSI" (OR = 2.522, 95% CI = 1.266-5.024) in children. Phthalate mixture during pregnancy showed significant relationships with all anthropometric indicator trajectories, with MEP and MBP always being of the largest importance. In conclusion, this study suggested that prenatal phthalate coexposure increased the childhood probability of being in higher ABSI and BRI trajectory groups. That is, children were more likely to be obese when they were exposed to higher levels of some phthalate metabolites and their mixture. The low-molecular weight phthalates, including MEP and MBP, contributed the greatest weights.

The impact of ecological restoration on ecosystem services change modulated by drought and rising CO2.

Ecological restoration projects (ERPs) are an indispensable component of natural climate solutions and have proven to be very important for reversing environmental degradation in vulnerable regions and enhancing ecosystem services. However, the level of enhancement would be inevitably influenced by global drought and rising CO2 , which remain less investigated. In this study, we took the Beijing-Tianjin sand source region (which has experienced long-term ERPs), China, as an example and combined the process-based Biome-BGCMuSo model to set multiple scenarios to address this issue. We found ERP-induced carbon sequestration (CS), water retention (WR), soil retention (SR), and sandstorm prevention (SP) increased by 22.21%, 2.87%, 2.35%, and 28.77%, respectively. Moreover, the ecosystem services promotion from afforestation was greater than that from grassland planting. Approximately 91.41%, 98.13%, and 64.51% of the increased CS, SR, and SP were contributed by afforestation. However, afforestation also caused the WR to decline. Although rising CO2 amplified ecosystem services contributed by ERPs, it was almost totally offset by drought. The contribution of ERPs to CS, WR, SR, and SP was reduced by 5.74%, 32.62%, 11.74%, and 14.86%, respectively, under combined drought and rising CO2 . Our results confirmed the importance of ERPs in strengthening ecosystem services provision. Furthermore, we provide a quantitative way to understand the influence rate of drought and rising CO2 on ERP-induced ecosystem service dynamics. In addition, the considerable negative climate change impact implied that restoration strategies should be optimized to improve ecosystem resilience to better combat negative climate change impacts.

Advances in spring leaf phenology are mainly triggered by elevated temperature along the rural-urban gradient in Beijing, China.

Urbanization-induced phenological changes have received considerable attention owing to their implications for determining urban ecosystem productivity and predicting the response of plants and ecosystem carbon cycles to future climate change. However, inconsistent rural-urban gradients in plant phenology remain, and phenological drivers other than temperature are poorly understood. In this study, we simultaneously observed the micro-climate and spring leaf phenology of seven woody plant species at 13 parks along a rural-urban gradient in Beijing, China. The minimum (Tmin) and mean (Tmean) air temperature and the minimum (VPDmin) and mean (VPDmean) vapor pressure deficit increased significantly along the rural-urban gradient, but the maximum air temperature (Tmax) and maximum vapor pressure deficit (VPDmax) did not. All observed leaf phenological phases for the seven species were significantly advanced along the rural-urban gradient by 0.20 to 1.02 days/km. Advances in the occurrence of leaf phenological events were significantly correlated with increases in Tmean (accounting for 57-59% variation), Tmin (21-26%), VPDmin (12-16%), and VPDmean (3-5%), but not with changes in Tmax or VPDmax. Advances in spring leaf phenology along the rural-urban gradient differed between non-native species and native species and between shrubs and trees. The reason may be mainly that the sensitivities of spring leaf phenology to micro-climate differ with species origin and growth form. This study highlights that urbanization-induced increases in Tmean and Tmin are the major contributors to advances in spring leaf phenology along the rural-urban gradient, exerting less influence on native species than on non-native species.

Engineering active heterojunction architecture with oxygenated-Co, Mo bimetallic sulfide heteronanosheet and graphene oxide for peroxymonosulfate activation.

Bimetallic sulfides have distinctive catalytic property in activating peroxymonosulfate (PMS) for water remediation. Polyoxometalates as potential precursors have rarely been reported for the catalytic degradation of refractory organic pollutants. Herein, a composite catalyst of Co-Mo bimetallic sulfides supported onto graphene oxide (O-CoMoS/GO) with a heterojunction architecture was synthesized through a hydrothermal strategy with polyoxometalates ((NH4)4[CoIIMo6O24H6]·6H2O) as the precursor and applied in the PMS activation. This material showed a superior performance for the catalytic degradation of the model organic pollutant, 4-chlorophenol (rapidly removed within 10 min with an apparent reaction rate constant of 0.5458 min-1). O-CoMoS/GO outperformed most of the reported catalysts in terms of activity and had a strong tolerance towards common organic and inorganic compounds in water, and could perform well in different real water systems. Experimental and theoretical results indicated that the introduction of GO could achieve the enrichment of electrons on the metals and reduce the d band center (εd) of Co close to the Fermi level (εF), thereby facilitating the interfacial electron transfer process. The activation mechanism was due to the as-prepared bimetallic sulfides and the formation of heterojunction structure with GO, where Co(II) as the active center could be regenerated by the adjacent Mo element (as co-catalyst) and by gathering electrons from GO through the Co/Mo-O-C coupling. This work provides insights into the design of bimetallic sulfide catalysts in activating PMS for water remediation.

Roles of osteoprotegerin in endocrine and metabolic disorders through receptor activator of nuclear factor kappa-B ligand/receptor activator of nuclear factor kappa-B signaling.

Endocrine and metabolic diseases show increasing incidence and high treatment costs worldwide. Due to the complexity of their etiology and mechanism, therapeutic strategies are still lacking. Osteoprotegerin (OPG), a member of the tumor necrosis factor receptor superfamily, appears to be a potential candidate for the treatment of these diseases. Studies based on clinical analysis and rodent animal models reveal the roles of OPG in various endocrine and metabolic processes or disorders, such as bone remodeling, vascular calcification, and ß-cell proliferation, through the receptor activator of nuclear factor kappa-B ligand (RANKL) and the receptor activator of NF-κB (RANK). Thus, in this review, we mainly focus on relevant diseases, including osteoporosis, cardiovascular disease (CVD), diabetes, and gestational diabetes mellitus (GDM), to summarize the effects of the RANKL/RANK/OPG system in endocrine and metabolic tissues and diseases, thereby providing a comprehensive insight into OPG as a potential drug for endocrine and metabolic diseases.

Di-(2-ethylhexyl) phthalate exposure induces liver injury by promoting ferroptosis via downregulation of GPX4 in pregnant mice.

As one kind of endocrine disrupting chemical, di-(2-ethylhexyl) phthalate (DEHP) has been reported to cause liver dysfunction in epidemiological and experimental studies. Abnormal liver function in pregnancy is associated with adverse maternal and perinatal outcomes. Few studies have investigated the potential effect of gestational DEHP exposure on the liver in pregnant mice, and the underlying mechanisms remain unclear. In the present study, pregnant ICR mice were exposed to doses (0, 500, 1,000 mg/kg/day) of DEHP in the presence or absence of 5 mg/kg/day ferrostatin-1 (Fer-1, ferroptosis inhibitor) by oral gavage from gestation day 4 to day 18. HepG2 cells were exposed to different doses of monoethylhexyl phthalate (MEHP, a major metabolite of DEHP) in vitro. Hepatic function and pathologic changes were observed. Oxidative stress, iron metabolism, and ferroptosis-related indicators and genes were evaluated both in vivo and in vitro. The results showed that gestational DEHP exposure induced disordered liver function and hepatocyte morphology changes in pregnant mice, along with increased malondialdehyde (MDA) and Fe2+ content and decreased glutathione (GSH) levels. The expression levels of the selected ferroptosis-related genes Slc7a11, Gpx4, and Nfr2 were significantly decreased, and Ptgs2 and Lpcat3 were significantly increased. Notably, Fer-1 attenuated DEHP-induced liver injury and ferroptosis. Furthermore, MEHP exhibited a synergistic effect with RSL3 (a GPX4 inhibitor) in promoting ferroptosis in vitro. Taken together, the results demonstrated that DEHP induced liver injury and ferroptosis in pregnant mice, probably by inhibiting the GPX4 pathway through lipid peroxidation and iron accumulation.

pH/Redox Dual-Responsive Drug Delivery System with on-Demand RGD Exposure for Photochemotherapy of Tumors.

Purpose: Nanotechnology has been widely used in antitumor research. The complex physiological environment has brought significant challenges to the field of antitumor micelles. The ideal micelles must not only have an invisible surface to extend the circulation time but must also enhance the retention of drugs and cellular internalization at the tumor. Methods: A graded response micelle (RPPssD@IR780/DOC) was designed to self-assemble by cRGD-poly(ß-amino esters)-polyethylene glycol-ss-distearoyl phosphatidylethanolamine (cRGD-PBAE-PEG-ss-DSPE) loaded with docetaxel (DOC) and IR-780 iodide (IR780). The micelles were designed to allow the PEG shell to prolong the blood circulation time in the body and effectively accumulate in the tumor. Subsequently, the acidic microenvironment of the tumor could transform the PBAE to hydrophilic, thereby increasing the size of micelles and exposing cyclic Arg-Gly-Asp (cRGD) peptides to increase the retention and cellular internalization of micelles in the tumor. After tumor cells had captured micelles, the high expression of glutathione in the cells prompted the release of DOC and IR780. Subsequently, the IR780 was stimulated by an 808-nm laser to generate local heat and reactive oxygen species (ROS) to synergize with DOC to treat the tumor. Results: In vitro and in vivo experimental results suggested that RPPssD@IR780/DOC was a potential photochemical effective for the treatment of tumors with non-negligible antitumor activity and good biocompatibility. Conclusion: A dual-response pH/redox delivery system with on-demand RGD exposure was designed to achieve photochemotherapy of tumors with good biosafety and antitumor effects.

Aquaporin-8 transports hydrogen peroxide to regulate granulosa cell autophagy.

Aquaporin-8 (AQP8), a member of the aquaporin family, is strongly expressed in follicular granulosa cells, which could affect the hormone secretion level in females. AQP8, as a membrane protein, could mediate H2O2 into cells, thereby triggering various biological events. The deficiency of Aqp8 increases female fertility, resulting from the decrease in follicular atresia. The low cell death rate is related to the apoptosis of granulosa cells. However, the mechanism by which AQP8 regulates the autophagy of granulosa cells remains unclear. Thus, this study aimed to explore the effect of AQP8 on autophagy in follicular atresia. We found that the expression of the autophagy marker light-chain protein 3 was significantly downregulated in the granulosa cells of Aqp8-knockout (Aqp8 -/- ) mice, compared with wild-type (Aqp8 +/+ ) mice. Immunofluorescence staining and transmission electron microscopic examination indicated that the number of autophagosomes in the granulosa cells of Aqp8 -/- mice decreased. Using a follicular granulosa cell autophagy model, namely a follicular atresia model, we verified that the concentration of H2O2 significantly increased during the autophagy of granulosa cells, consistent with the Aqp8 mRNA level. Intracellular H2O2 accumulation was modulated by endogenous AQP8 expression level, indicating that AQP8-mediated H2O2 was involved in the autophagy of granulosa cells. AQP8 deficiency impaired the elevation of H2O2 concentration through phosphorylated tyrosine activation. In addition, we carried out the analysis of transcriptome sequencing datasets in the ovary and found there were obvious differences in principal components, differentially expressed genes (DEGs) and KEGG pathways, which might be involved in AQP8-regulated follicular atresia. Taken together, these findings indicated that AQP8-mediated H2O2 transport could mediate the autophagy of granulosa cells. AQP8 might be a potential target for diseases related to ovarian insufficiency.

The SlTPL3-SlWUS module regulates multi-locule formation in tomato by modulating auxin and gibberellin levels in the shoot apical meristem.

Malformed fruits depreciate a plant's market value. In tomato (Solanum lycopersicum), fruit malformation is associated with the multi-locule trait, which involves genes regulating shoot apical meristem (SAM) development. The expression pattern of TOPLESS3 (SlTPL3) throughout SAM development prompted us to investigate its functional significance via RNA interference (RNAi) and clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9 (Cas9)-mediated gene editing. Lower SlTPL3 transcript levels resulted in larger fruits with more locules and larger SAMs at the 5 d after germination (DAG5) stage. Differentially expressed genes in the SAM of wild-type (WT) and SlTPL3-RNAi plants, identified by transcriptome deep sequencing (RNA-seq), were enriched in the gibberellin (GA) biosynthesis and plant hormone signaling pathways. Moreover, exogenous auxin and paclobutrazol treatments rescued the multi-locule phenotype, indicating that SlTPL3 affects SAM size by mediating auxin and GA levels in the SAM. Furthermore, SlTPL3 interacted with WUSCHEL (SlWUS), which plays an important role in SAM size maintenance. We conducted RNA-seq and DNA affinity purification followed by sequencing (DAP-seq) analyses to identify the genes regulated by SlTPL3 and SlWUS in the SAM and to determine how they regulate SAM size. We detected 24 overlapping genes regulated by SlTPL3 and SlWUS and harboring an SlWUS-binding motif in their promoters. Furthermore, functional annotation revealed a notable enrichment for functions in auxin transport, auxin signal transduction, and GA biosynthesis. Dual-luciferase assays also revealed that SlTPL3 enhances SlWUS-mediated regulation (repression and activation) of SlPIN3 and SlGA2ox4 transcription, indicating that the SlTPL3-SlWUS module regulates SAM size by mediating auxin distribution and GA levels, and perturbations of this module result in enlarged SAM. These results provide novel insights into the molecular mechanism of SAM maintenance and locule formation in tomato and highlight the SlTPL3-SlWUS module as a key regulator.