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To evaluate the dosimetric benefits and clinical feasibility of deep inspiratory breath-hold (DIBH) combined with volumetric modulated arc therapy (VMAT) in left-sided postmastectomy radiotherapy (PMRT). Eligible patients with left-sided breast cancer undergoing DIBH-based PMRT were prospectively included. Chest wall, supra/infraclavicular fossa, and/or internal mammary node irradiation (IMNI) were planned with a prescription dose of 43.5 Gy in 15 fractions. VMAT plans were designed on free breathing (FB)-and DIBH-CT to compare dosimetric parameters in heart, left anterior descending artery (LAD) and lung. Cone-beam computed tomography (CBCT) was performed before and after treatment to evaluate inter- and intra-fractional setup errors. Heart position and dose variations during treatment were estimated by fusing CBCT with DIBH-CT scans.Twenty patients were included with 10 receiving IMNI. In total, 193 pre-treatment and 39 pairs pre- and post-treatment CBCT scans were analyzed. The D mean , D max , and V 5-40 of the heart, LAD, and left lung were significantly lower in DIBH than FB (p < 0.05 for all), except for V5 of LAD (p = 0.167). The cardiopulmonary dosimetric benefits were maintained regardless of IMNI. The inter- and intra-fractional setup errors were < 0.3 cm; and the overall estimated PTV margins were < 1.0 cm. During treatment, the mean dice similarity coefficient of heart position and the mean ratio of heart D mean between CBCT and DIBH-CT plans was 0.95 (0.88-1.00) and 100% (70.6-119.5%), respectively. DIBH-VMAT could effectively reduce the cardiopulmonary doses with acceptable reproducibility and stability in left-sided PMRT regardless of IMNI., (© 2024. The Author(s).)

Key Message: Hydrogen peroxide promoted leaf senescence by sulfenylating the magnesium chelating protease I subunit (CHLI1) in the chlorophyll synthesis pathway, and inhibited its activity to reduce chlorophyll synthesis. Leaf senescence is the final and crucial stage of plant growth and development, during which chlorophyll experiences varying degrees of destruction. It is well-known that the higher ROS accumulation is a key factor for leaf senescence, but whether and how ROS regulates chlorophyll synthesis in the process are unknown. Here, we report that H 2 O 2 inhibits chlorophyll synthesis during leaf senescence via the I subunit of magnesium-chelatase (CHLI1). During leaf senescence, the decrease of chlorophyll content is accompanied by the increase of H 2 O 2 accumulation, as well as the inhibition of catalase (CAT) genes expression. The mutant cat2-1, with increased H 2 O 2 shows an accelerated senescence phenotype and decreased CHLI1 activity compared with the wild type. H 2 O 2 inhibits CHLI1 activity by sulfenylating CHLI1 during leaf senescence. Consistent with this, the chli1 knockout mutant displays the same premature leaf senescence symptom as cat2-1, while overexpression of CHLI1 in cat2-1 can partially restore its early senescence phenotype. Taken together, these results illustrate that CAT2-mediated H 2 O 2 accumulation during leaf senescence represses chlorophyll synthesis through sulfenylating CHLI1, and thus inhibits its activity, providing a new insight into the pivotal role of chlorophyll synthesis as a participant in orchestrating the leaf senescence., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Previous studies revealed that vitamin K might help maintain muscle homeostasis, but this association has received little attention. We aimed to explore the associations of vitamin K intake with skeletal muscle mass and strength., Methods: We included cross-sectional data from the U.S. National Health and Nutrition Examination Survey (NHANES, 2011-2018). Vitamin K intake was assessed via 24-h recall. Covariate-adjusted multiple linear regression and restricted cubic splines were used to evaluate the associations of dietary vitamin K intake with skeletal muscle mass and strength, measured by dual-energy X-ray absorptiometry and handgrip dynamometer, respectively., Results: Dietary vitamin K intake was positively associated with skeletal muscle mass in males (β = 0.05747, p  = 0.0204) but not in females. We also revealed a positive association between dietary vitamin K intake and handgrip strength within the range of 0-59.871 μg/d ( P nonlinear  = 0.049). However, beyond this threshold, increasing vitamin K intake did not cause additional handgrip strength improvements., Conclusion: We provided evidence for a positive relationship between dietary vitamin K intake and skeletal muscle mass in males. Moreover, our study revealed a nonlinear relationship between dietary vitamin K intake and handgrip strength, highlighting an optimal intake range., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Chen, Guo, Wang, Bao, Zhang and Yu.)

Ram sperm undergo a sequence of physiological and biochemical changes collectively termed as capacitation to perform oocyte fertilization. However, the protein changes induced by capacitation remain in need of further exploration. Thus, the present study investigated the comparative proteomic profiling in ram spermatozoa under non-capacitating (NC) and capacitating (CAP) conditions in vitro using a liquid chromatography-tandem mass spectrometry combined with tandem mass tag labeling strategy. As a results, 2050 proteins were identified and quantified; 348 of them were differentially abundant, with 280 of the proteins upregulated and 68 of the proteins downregulated between the CAP and NC spermatozoa, respectively. Functional enrichment analysis indicated that the differentially abundant proteins Prune Exopolyphosphatase 1, Galactose-1-Phosphate Uridylyltransferase, and ATP Citrate Lyase were strictly related to energy production and conversion, and Phosphoglycolate phosphatase, Glucosamine-6-Phosphate Deaminase 1 and 2 were related to metabolism, RNA processing, and vesicular transport pathways. Furthermore, the networks of protein-protein interaction indicated a strong interaction among these differential proteins in annotated pathways such as ubiquitin and transport metabolism. Our findings indicate that capacitation progress might be regulated through different pathways, providing insights into mechanisms involved in ram sperm capacitation and fertility.

Although selenium (Se) and cadmium (Cd) often coexist naturally in the soil of China, the health risks to local residents consuming Se-Cd co-enriched foods are unknown. In the present study, we investigated the effects of chemical-based selenocystine (SeCys 2 ) on cadmium chloride-induced human hepatocarcinoma (HepG2) cell injury and plant (Cardamine hupingshanensis)-derived SeCys 2 against Cd-induced liver injury in mice. We found that chemical- and plant-based SeCys 2 showed protective effects against Cd-induced HepG2 cell injury and liver damage in mice, respectively. Compared with Cd intervention group, co-treatment with chemical- or plant-based SeCys 2 both alleviated liver toxicity and ferroptosis by decreasing ferrous iron, acyl-CoA synthetase long-chain (ACSL) family member 4, lysophosphatidylcholine acyltransferase 3, reactive oxygen species and lipid peroxide levels, and increasing ACSL3, peroxisome proliferator-activated receptor α, solute carrier family 7 member 11 (SLC7A11) and glutathione and glutathione peroxidase 4 (GPX4) levels. In conclusion, chemical- and plant-based SeCys 2 alleviated Cd-induced hepatotoxicity and ferroptosis by regulating SLC7A11/GPX4 signaling and lipid peroxidation. Our findings indicate that potential Cd toxicity from consuming foods grown in Se- and Cd-rich soils should be re-evaluated. This study offers a new perspective for the development of SeCys 2 -enriched agricultural products., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Xanthomonas oryzae pv. oryzae (Xoo) causes bacterial blight (BB), a globally devastating disease of rice (Oryza sativa) that is responsible for significant crop loss. Sugars and sugar metabolites are important for pathogen infection, providing energy and regulating events associated with defense responses; however, the mechanisms by which they regulate such events in BB are unclear. As an inevitable sugar metabolite, methylglyoxal (MG) is involved in plant growth and responses to various abiotic stresses, but the underlying mechanisms remain enigmatic. Whether and how MG functions in plant biotic stress responses is almost completely unknown. Here, we report that the Xoo strain PXO99 induces OsWRKY62.1 to repress transcription of OsGLY II genes by directly binding to their promoters, resulting in overaccumulation of MG. MG negatively regulates rice resistance against PXO99: osglyII2 mutants with higher MG levels are more susceptible to the pathogen, whereas OsGLYII2-overexpressing plants with lower MG content show greater resistance than the wild type. Overexpression of OsGLYII2 to prevent excessive MG accumulation confers broad-spectrum resistance against the biotrophic bacterial pathogens Xoo and Xanthomonas oryzae pv. oryzicola and the necrotrophic fungal pathogen Rhizoctonia solani, which causes rice sheath blight. Further evidence shows that MG reduces rice resistance against PXO99 through CONSTITUTIVE DISEASE RESISTANCE 1 (OsCDR1). MG modifies the Arg97 residue of OsCDR1 to inhibit its aspartic protease activity, which is essential for OsCDR1-enhanced immunity. Taken together, these findings illustrate how Xoo promotes infection by hijacking a sugar metabolite in the host plant., (Copyright © 2024 The Author. Published by Elsevier Inc. All rights reserved.)

Seed germination is a complex process that is regulated by various exogenous and endogenous factors, in which abscisic acid (ABA) plays a crucial role. The triphosphate tunnel metalloenzyme (TTM) superfamily exists in all living organisms, but research on its biological role is limited. Here, we reveal that TTM2 functions in ABA-mediated seed germination. Our study indicates that TTM2 expression is enhanced but repressed by ABA during seed germination. Promoted TTM2 expression in 35S::TTM2-FLAG rescues ABA-mediated inhibition of seed germination and early seedling development and ttm2 mutants exhibit lower seed germination rate and reduced cotyledon greening compared with the wild type, revealing that the repression of TTM2 expression is required for ABA-mediated inhibition of seed germination and early seedling development. Further, ABA inhibits TTM2 expression by ABA insensitive 4 (ABI4) binding of TTM2 promoter and the ABA-insensitive phenotype of abi4-1 with higher TTM2 expression can be rescued by mutation of TTM2 in abi4-1 ttm2-1 mutant, indicating that TTM2 acts downstream of ABI4 . In addition, TTM1 , a homolog of TTM2 , is not involved in ABA-mediated regulation of seed germination. In summary, our findings reveal that TTM2 acts as a downstream factor of ABI4 in ABA-mediated seed germination and early seedling growth.

We examined the effects of freeze-thaw cycles (0, 1, 3, 5, 7, 15 cycles) on the activities of urease, invertase, and proteinase in the different layers of the soil under the four typical stands in the cold temperate zone, i.e ., Pinus pumila stand, Rhododendron-Betula platyphylla stand, Rhododendron-Larix gmelinii stand, Ledum-Larix gmelinii stand, with the indoor freeze-thaw simulation culture method being used. The relationship between soil enzyme activity and multiple physicochemical variables was analyzed during freeze-thaw alternation. The results showed that the activity of soil urease was firstly increased and then inhibited during freeze-thaw alternation. After freeze-thaw, urease activity did not differ from that without freeze-thaw. Invertase activity was firstly inhibited and then increased during freeze-thaw alternation, and was significantly increased by 8.5%-40.3% after freeze-thaw. Proteinase activity was firstly increased and then inhibited during freeze-thaw alternation, and was significantly decreased by 13.8%-68.9% after freeze-thaw. After freezing and thawing, there was significant positive correlation between urease activity and ammonium nitrogen and soil water content in Ledum-L. gmelinii stand and P. pumila stand, respectively, and proteinase activity had significant negative correlation with inorganic nitrogen concentration in P. pumila stand, Rhododendron-B. platyphylla stand, and Ledum-L. gmelinii stand. Invertase activity had significant positive correlation with organic matter in Rhododendron-L. gmelinii stand and Ledum-L. gmelinii stand.

Few studies have systematically explored the association between cognitive decline and all-cause mortality among oldest old individuals (above 80 years old), and there is limited evidence of blood pressure (BP) as a potential effect modifier. Therefore, this study included 14,891 oldest old individuals (mean age: 90.3 ± 7.5 years); 10,904 deaths and 34,486 person-years were observed. Cognitive scores were calculated using the Chinese version of the Mini-Mental State Examination (MMSE). Cognitive decline was stratified into ten categories (C0-C9). Continuous cognitive scores were used to assess the interactions of modifiers of the cognitive decline and all-cause mortality association and potentially modifiable factors. Potential effect modifiers were explored by age, sex, BP status and hypertension. Cox proportional hazards models were used to evaluate the relationship between cognitive decline and all-cause mortality after adjustments for demographic characteristics, socioeconomic status, lifestyle factors, leisure activities and health conditions. Participants who progressed to severe cognitive impairment from high normal cognitive function (C3), low normal cognitive function (C6), or mild cognitive impairment (C8) had 55%, 56%, and 63% higher mortality risks, respectively, than those who maintained high normal cognitive function (C0). The multivariate-adjusted model indicated that oldest old individuals with a decrease of more than one point in the MMSE score per year had an approximately 4% all-cause mortality risk. The relationship between cognitive decline and mortality was statistically influenced by sex (P = 0.013), high BP in nonagenarians (P = 0.003), and hypertension (P = 0.004) but not by age (P = 0.277). Our findings suggest that periodic screening for cognitive decline and strengthening BP management may be necessary for public health., (© 2022. The Author(s).)

Cancer stem cells (CSCs) are highly implicated in the progression of human cancers. Thus, targeting CSCs may be a promising strategy for cancer therapy. Wnt/β-catenin and Sonic Hedgehog pathways play an important regulatory role in maintaining CSC characteristics. Natural compounds, such as curcumin, possess chemopreventive properties. However, the interventional effect of curcumin on lung CSCs has not been clarified. In the present study, tumorsphere formation assay was used to enrich lung CSCs from A549 and H1299 cells. We showed that the levels of lung CSC markers (CD133, CD44, ALDHA1, Nanog and Oct4) and the number of CD133-positive cells were significantly elevated in the sphere-forming cells. We further illustrated that curcumin efficiently abolished lung CSC traits, as evidenced by reduced tumorsphere formation, reduced number of CD133-positive cells, decreased expression levels of lung CSC markers, as well as proliferation inhibition and apoptosis induction. Moreover, we demonstrated that curcumin suppressed the activation of both Wnt/β-catenin and Sonic Hedgehog pathways. Taken together, our data suggested that curcumin exhibited its interventional effect on lung CSCs via inhibition of Wnt/β-catenin and Sonic Hedgehog pathways. These novel findings could provide new insights into the potential therapeutic application of curcumin in lung CSC elimination and cancer intervention. Copyright © 2017 John Wiley & Sons, Ltd., (Copyright © 2017 John Wiley & Sons, Ltd.)

Aim: To investigate the effect of interleukin (IL)-22 on hepatic fibrosis in mice and the possible mechanism involved., Methods: Liver fibrosis was induced in male BALB/c mice by CCl₄. Recombinant IL-22 (rmIL-22) was administered intraperitoneally in CCl₄-treated mice. Fibrosis was assessed by histology and Masson staining. The activation of hepatic stellate cells (HSCs) was investigated by analysis of α-smooth muscle actin expression. The frequencies of T helper (Th) 22 cells, Th17 cells and Th1 cells, the expression of inflammatory cytokines [IL-22, IL-17A, interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), IL-6, IL-1β] and transcription factors [aryl hydrocarbon receptor (AHR), RAR-related orphan receptor (RORγt), T-bet] mRNA in the liver were investigated. In addition, the plasma levels of IL-22, IL-17A, IFN-γ, TNF-α, IL-6 and IL-1β were evaluated., Results: Significant elevations in circulating Th22 cells, Th17 cells, Th1 cells, IL-22, IL-17A, and IFN-γ were observed in the hepatic fibrosis group compared with the control group (P < 0.01). Treatment with rmIL-22 in mice with hepatic fibrosis ameliorated the severity of hepatic fibrosis, which was confirmed by lower hepatic fibrosis pathological scores (P < 0.01). RmIL-22 decreased the frequencies of Th22 cells (6.71% ± 0.97% vs 8.09% ± 0.74%, P < 0.01), Th17 cells (4.34% ± 0.37% vs 5.71% ± 0.24%, P < 0.01), Th1 cells (3.09% ± 0.49% vs 4.91% ± 0.73%, P < 0.01), and the levels of IL-22 (56.23 ± 3.08 vs 70.29 ± 3.01, P < 0.01), IL-17A (30.74 ± 2.77 vs 45.68 ± 2.71, P < 0.01), and IFN-γ (74.78 ± 2.61 vs 124.89 ± 2.82, P < 0.01). Down-regulation of IL-22, IL-17A, IFN-γ, TNF-α, IL-6, IL-1β, AHR RORγt, and T-bet gene expression in the liver was observed in the rmIL-22 group (P < 0.01)., Conclusion: The frequencies of Th22, Th17 and Th1 cells are elevated in hepatic fibrosis. RmIL-22 can attenuate HSC activation and down-regulate the levels of inflammatory cytokines, thereby ameliorating liver fibrogenesis.

Purpose: To investigate the spectrum of MRI appearances of ovarian serous borderline tumor (SBT)., Materials and Methods: Following ethics approval, 31 patients with 51 histologically proven ovarian SBTs underwent preoperative MRI. Images were evaluated, by two observers for the location, shape, size, internal architecture, signal intensity, and extent or stage of the tumors. The MRI findings were correlated with pathological findings., Results: Twenty of 31 patients (65%) demonstrated bilateral ovarian SBTs on MRI. Three MRI morphological patterns of ovarian SBT were identified: (i) Mainly cystic mass with multiple intracystic papillary projections from the wall and septations was observed in 24 (47%) tumors. (ii) Solid mass with hierarchical branching papillary and fibrous stalk architecture was observed in 8 (16%) tumors. The branching papillary projections were hyperintensity on T2WI, intermediate intense on DWI, and enhanced intensely after the administration of Gd-DTPA. The internal branching fibrous stalks were hypointensity on T2WI and enhanced slightly. (iii) Mixed cystic-solid mass was observed in 19 (37%) tumors. The cystic and solid components had the architecture and signal intensity similar to those of cystic and solid SBTs. Papillary projections were the common architecture of all three types of tumors., Conclusion: On MRI, the ovarian SBT has some morphological distinguishing features. The solid papillary architecture with internal branching fibrous stalk is a somewhat more characteristic MRI appearance., (© 2013 Wiley Periodicals, Inc.)

Purpose: To investigate MRI in differentiating borderline mucinous cystadenoma (MC) from benign MC of the ovary., Materials and Methods: We studied MR images of 26 benign MCs and 24 borderline MCs of the ovary. The following MRI features of tumors were evaluated and compared between two groups: laterality, shape, size, loculation, signal intensity of the fluid, thickness of the septation and the wall, and vegetations. The results of the MRI were then compared with the pathological findings., Results: Honeycomb loculi, high signal intensity on T1WI, and low signal intensity on T2WI of the intracystic content, thickened septation or wall (≥5 mm), and vegetations (≥5 mm) were significantly more common in borderline MC than in benign MC with the sensitivity and specificity of identifying borderline MC of 50.0% and 80.8%, 41.7% and 96.2%, 45.8% and 96.2%, and 62.5% and 96.2%, respectively. The presence of any one of the following features-honeycomb loculi with a low signal intensity on T2WI, thickened septation or wall (≥5 mm), and vegetations (≥5 mm)-yielded the sensitivity, specificity, and accuracy of identifying borderline MC of 91.7%, 92.3%, and 92.0%, respectively., Conclusion: MRI has the ability to accurately demonstrate the morphological characteristics of ovarian MC and reliably differentiate borderline MC from benign MC., (Copyright © 2013 Wiley Periodicals, Inc.)

A novel serine protease with fibrinolytic activity named CSP was purified from the culture supernatant of the fungus Cordyceps sinensis, a kind of Chinese herbal medicine. Analysis of the purified enzyme by SDS-PAGE indicated that CSP was a single polypeptide chain with an apparent molecular weight of 31 kDa, and N-terminal sequencing revealed that the first ten amino acid residues of the enzyme were Ala-Leu-Ala-Thr-Gln-His-Gly-Ala-Pro-Trp-. When casein was used as a substrate, the proteolytic activity of CSP reached its maximum at pH 7.0 and 40 degrees C. The effect of chemical agents on the enzyme activity indicated that CSP is a serine protease with a free cysteine residue near the active site. It hydrolysed fibrinogen, fibrin and casein with a high efficiency, while hydrolysing bovine serum albumin (BSA) and human serum albumin (HSA) to a lesser extent. CSP was found to be a plasmin-like protease, but not a plasminogen activator, and it preferentially cleaved the A alpha chain of fibrinogen and the alpha-chain of fibrin. Therefore, the extracellular protein CSP may represent a potential new therapeutic agent for the treatment of thrombosis., (Copyright (c) 2007 John Wiley & Sons, Ltd.)