Difference of anterior and posterior orbital development in patients with congenital microphthalmia: a retrospective cohort study from China.

AIM: To evaluate volume differences between anterior and posterior orbit and demographic characteristics of Chinese patients with congenital microphthalmia. METHODS: A retrospective cohort study, involving 169 unilateral congenital microphthalmia patients aged between 1 and 57 years old was conducted. Three-dimensional images of the orbit were generated from past CT scans, and digital orbital volume comprehensive measurement was done. The measured data included orbital volume (OBV), posterior orbital volume (POV), orbital width (OBW), orbital height (OBH), orbital depth (OBD), and posterior orbital area ratio. RESULTS: Significant differences were observed among OBV, POV, OBW, OBH, and OBD of the affected and unaffected eyes in different age-based groups (all P<0.001). Among them, OBH had the greatest different. The mean microphthalmic to contralateral ratio (MCR) of OBV, POV, OBW, and OBH continuously increased from 1 to 3 years old, whereas the MCR of POV decreased from 3 to 17 years old. The MCR of OBD was not found to be correlated to age. There was no significant difference between OBV, POV, OBW, and OBH in ages from 13 years old to adulthood (all P>0.05). The difference in posterior orbital area ratio between the affected and unaffected groups was not statistically significant (P>0.05). CONCLUSION: OBH is maximally affected, whereas OBD is minimally affected by microphthalmia. Posterior orbital retardation began 2y prior to orbital retardation and occurred at 3 years old in the affected eye, suggesting that intervention therapy should be done before the age of 4.

Synovial mesenchymal stem cell-derived exosomal microRNA-320c facilitates cartilage damage repair by targeting ADAM19-dependent Wnt signalling in osteoarthritis rats.

OBJECTIVE: Our previous study revealed that synovial mesenchymal stem cell (SMSC)-derived exosomal microRNA-302c enhanced chondrogenesis by targeting a disintegrin and metalloproteinase 19 (ADAM19) in vitro. This study aimed to validate the potential of SMSC-derived exosomal microRNA-302c for the treatment of osteoarthritis in vivo. METHODS: After 4 weeks of destabilization of the medial meniscus surgery (DMM) to establish an osteoarthritis model, the rats received weekly articular cavity injection of SMSCs with or without GW4869 treatment (exosome inhibitor) or exosomes from SMSCs with or without microRNA-320c overexpression for another 4 weeks. RESULTS: SMSCs and SMSC-derived exosomes reduced the Osteoarthritis Research Society International (OARSI) score, improved cartilage damage repair, suppressed cartilage inflammation, suppressed extracellular matrix (ECM) degradation, and inhibited chondrocyte apoptosis in DMM rats. However, these effects were largely hampered in rats that were injected with GW4869-treated SMSCs. Moreover, exosomes from microRNA-320c-overexpressing SMSCs exerted a better effect than exosomes from negative control SMSCs on decreasing the OARSI score, enhancing cartilage damage repair, suppressing cartilage inflammation, and inhibiting ECM degradation and chondrocyte apoptosis. Mechanistically, exosomes from microRNA-320c-overexpressing SMSCs reduced the levels of ADAM19, as well as ß-catenin and MYC, which are two critical proteins in Wnt signalling. CONCLUSION: SMSC-derived exosomal microRNA-320c suppresses ECM degradation and chondrocyte apoptosis to facilitate cartilage damage repair in osteoarthritis rats by targeting ADAM19-dependent Wnt signalling.

A c-di-GMP binding effector controls cell size in a cyanobacterium.

Cyclic-di-GMP (c-di-GMP) is a ubiquitous bacterial signaling molecule. It is also a critical player in the regulation of cell size and cell behaviors such as cell aggregation and phototaxis in cyanobacteria, which constitute an important group of prokaryotes for their roles in the ecology and evolution of the Earth. However, c-di-GMP receptors have never been revealed in cyanobacteria. Here, we report the identification of a c-di-GMP receptor, CdgR, from the filamentous cyanobacterium Anabaena PCC 7120. Crystal structural analysis and genetic studies demonstrate that CdgR binds c-di-GMP at the dimer interface and this binding is required for the control of cell size in a c-di-GMP-dependent manner. Different functions of CdgR, in ligand binding and signal transmission, could be separated genetically, allowing us to dissect its molecular signaling functions. The presence of the apo-form of CdgR triggers cell size reduction, consistent with the similar effects observed with a decrease of c-di-GMP levels in cells. Furthermore, we found that CdgR exerts its function by interacting with a global transcription factor DevH, and this interaction was inhibited by c-di-GMP. The lethal effect triggered by conditional depletion of DevH or by the production of several point-mutant proteins of CdgR in cells indicates that this signaling pathway plays critical functions in Anabaena. Our studies revealed a mechanism of c-di-GMP signaling in the control of cell size, an important and complex trait for bacteria. CdgR is highly conserved in cyanobacteria, which will greatly expand our understanding of the roles of c-di-GMP signaling in these organisms.

The development of visual aesthetic sensitivity in students in China.

To examine the development of visual aesthetic sensitivity in students in China, 2,387 students from age 9 to age 22 (excluding ages 16-17) were tested by the Visual aesthetic Sensitivity Test-Revised. The development of visual aesthetic sensitivity across ages and genders, and the effect of artistic training on students' visual aesthetic sensitivity were examined. The data of primary school and junior middle school students were collected by paper tests completed collectively in class, while the data of university students were collected by distributing and collecting online. Result suggests that students' visual aesthetic sensitivity is relatively stable from age 9 to age 12 and increases at age 13. The visual aesthetic sensitivity of girls is significantly better than that of boys at age 15, 19, and 20 years of age. This study also found that artistic training improves students' visual aesthetic sensitivity.

Lipidomics reveals alterations of lipid composition and molecular nutrition in irradiated marble beef.

Electron beam irradiation can effectively inhibit microbial growth, but the changes of lipid during irradiation have not been comprehensively analyzed in marble beef. Here, UHPLC-MS/MS was used to detect lipids changes of irradiated marble beef. A total of 1032 lipids were identified and classified into 3 lipid classes and 8 subclasses in irradiated marble beef. 9 lipid biomarkers were screened with increasing irradiation dose. 122 differential lipids were generated and involved in 4 metabolic pathways included Glycerophospholipid metabolism, Linoleic acid metabolism, alpha-Linolenic acid metabolism and Arachidonic acid metabolism though PC(18:0/14:0), PE(16:0/16:0) and PE(18:0/16:0) in irradiated. Our results showed that irradiation had effect on the lipid of marbled beef, but the increase of irradiation dose from 2.5 kGy to 4.5 kGy had little effect on lipids. These results help us to understand the dynamic changes of irradiated meat lipids and lay a foundation for the application of irradiation in meat preservation.

Characteristics of key microorganisms and metabolites in irradiated marbled beef.

Insights into changes in microorganisms and metabolites in irradiated marbled beef may help elucidate the beneficial effects of irradiation on prolonging the shelf life of meat. In this study, 16S rRNA gene sequencing, ultra-high-performance liquid chromatography-tandem mass spectrometry, and Pearson's correlation analyses were conducted to detect key microorganisms, core metabolites, and potential correlation between the microbiome and metabolome in marbling beef. Microbiome analysis showed that irradiation effectively eradicated the spoilage bacterium Leuconostoc and reduced the proportions of Carnobacterium and Lactobacillus in marbled beef. Additionally, results of metabolomic analysis involving irradiated marbled beef revealed that metabolites with significant differences were mainly organic acids and their derivatives, lipids, and lipid-like molecules, including six core metabolites. Furthermore, a significant correlation between key bacteria and metabolites was observed. Carnobacterium, Lactobacillus, and Leuconostoc affected the accumulation of core metabolites in irradiated marbled beef by influencing amino acid and lipid metabolism. Characterization of the microbiota and metabolites, as well as clarification of their correlation, can contribute to a better understanding of the mechanisms whereby irradiation helps maintain meat quality.

Prognostic value of baseline 18F-FDG PET/CT in patients with esophageal squamous cell carcinoma treated with definitive (chemo)radiotherapy.

PURPOSE: To investigate the prognostic value of baseline 18F-FDG PET/CT in patients with esophageal squamous cell carcinoma (ESCC) treated with definitive (chemo)radiotherapy. METHODS: A total of 98 ESCC patients with cTNM stage T1-4, N1-3, M0 who received definitive (chemo)radiotherapy after 18F-FDG PET/CT examination from December 2013 to December 2020 were retrospectively analyzed. Clinical factors included age, sex, histologic differentiation grade, tumor location, clinical stage, and treatment strategies. Parameters obtained by 18F-FDG PET/CT included SUVmax of primary tumor (SUVTumor), metabolic tumor volume (MTV), total lesion glycolysis (TLG), SUVmax of lymph node (SUVLN), PET positive lymph nodes (PLNS) number, the shortest distance between the farthest PET positive lymph node and the primary tumor in three-dimensional space after the standardization of the patient BSA (SDmax(LN-T)). Univariate and multivariate analysis was conducted by Cox proportional hazard model to explore the significant factors affecting overall survival (OS) and progression-free survival (PFS) in ESCC patients. RESULTS: Univariate analysis showed that tumor location, SUVTumor, MTV, TLG, PLNS number, SDmax (LN-T) were significant predictors of OS and tumor location, and clinical T stage, SUVTumor, MTV, TLG, SDmax (LN-T) were significant predictors of PFS (all p < 0.1). Multivariate analysis showed that MTV and SDmax (LN-T) were independent prognostic factors for OS (HR = 1.018, 95% CI 1.006-1.031; p = 0.005; HR = 6.988, 95% CI 2.119-23.042; p = 0.001) and PFS (HR = 1.019, 95% CI 1.005-1.034; p = 0.009; HR = 5.819, 95% CI 1.921-17.628; p = 0.002). Combined with independent prognostic factors MTV and SDmax (LN-T), we can further stratify patient risk. CONCLUSIONS: Before treatment, 18F-FDG PET/CT has important prognostic value for patients with ESCC treated with definitive (chemo)radiotherapy. The lower the value of MTV and SDmax (LN-T), the better the prognosis of patients.

Comprehensive Genomics and Proteomics Analysis Reveals the Multiple Response Strategies of Endophytic Bacillus sp. WR13 to Iron Limitation.

Iron (Fe) is an important metal element for the growth of bacteria. Many bacteria respond to Fe limitation through a variety of strategies. We previously isolated an endophyte Bacillus sp. WR13 from wheat root. However, whether and how this strain can cope with Fe-deficient environments remains unclear. In this study, the growth of WR13 under Fe starvation was investigated, and the underlying mechanisms of WR13 in response to Fe starvation were elucidated via genomics and iTRAQ-based proteomics. Under Fe limitation, WR13 showed a growth pattern similar to that of Fe sufficiency. Genomics analysis demonstrated that WR13 had gene clusters related to siderophore synthesis (dhbACEBF), transportation (bcbE), uptake (feuABC-yusV) and hydrolysis (besA). These genes were significantly up-regulated in Fe-starved WR13, which resulted in more siderophore production. Proteomics data revealed that many Fe-containing proteins such as ACO, HemQ, ferredoxin, CNP, and SufD were significantly reduced under Fe limitation. Meanwhile, significant decreases in many proteins involved in glycolysis, TCA cycle, pentose phosphate pathway; asparagine, glutamine, methionine, and serine metabolism; and phospholipid hydrolysis were also observed. Overall, this study shows that Bacillus sp. WR13 was able to respond to Fe limitation via multiple strategies and provides a theoretical basis for the application of WR13 in Fe-deficient soil.

Integrated proteomics and metabolomics analysis revealed the mechanisms underlying the effect of irradiation on the fat quality of Chinese bacon.

Irradiation increases the security and storage period of preserved Chinese bacon; nevertheless, the biological mechanisms underlying the changes in fat quality caused by irradiation are unknown. We investigated the influence of irradiation on Chinese bacon by proteomic and metabolomic. We identified 24 proteins that participated in metabolism and 40 common differential metabolites enriched in 16 signalling pathways. Correlation analysis revealed that irradiation altered 11 pathways shared between the proteome and metabolome, including two lipid metabolism pathways. Acetyl-CoA carboxylase, ACSL, octanoic acid, decanoic acid, palmitic acid, and oleic acid participated in fatty acid biosynthesis. Acyl-CoA thioesterase 1/2/4, enoyl-CoA reductase, acetyl-CoA acyltransferase 1, enoyl-CoA hydratase 2, palmitic acid, and oleic acid participated in unsaturated fatty acid biosynthesis. These findings lay the groundwork for multi-omics research on the effects of irradiation on Chinese bacon quality, assisting in assessing irradiated Chinese bacon quality, and developing effective strategies to standardise quality parameters.

Investigation on the Mechanical Properties and Strengthening Mechanism of Solid-Waste-Sulfur-Based Cementitious Composites.

This research used waste ceramic powder (CP) to replace aggregate, fly ash (FA) as filler, and combined them with sulfur to prepare composite cementitious materials. The variations of the mechanical properties with the aggregate proportions (aggregate mass/total mass) of 65%, 70%, and 75%, and the FA contents (FA mass/aggregate and filler mass) of 0%, 10%, 20%, 30%, 40%, and 50% were studied. The correlation evaluation model of sulfur content, CP content, FA content, and mechanical properties was established using the gray correlation theory, and the comprehensive mechanical property evaluation model was established as the foundation of the entropy method. Finally, the optimum proportion of the solid-waste-sulfur-based cementitious composites was determined. Results showed that, without FA, the CP increased from 65% to 75% and the comprehensive mechanical properties of the specimen increased by 60.53%. After FA was added, the peak point of the comprehensive mechanical properties appeared in group S75F10, which was 0.9210. During the hardening of the cementitious material, sulfur was mainly used as a binder, CP played the role of skeleton and part of the filler, whereas, as a crystal nucleus, the FA promoted the transformation of the sulfur crystals. Both the CP and FA can reduce the porosity of the specimen to a certain extent and have potential defect repair ability, thus densifying the matrix and improving the strength. When the proportion of sulfur: CP: FA is 1:2.7:0.3, the flexural (FS), compressive (CS), and splitting tensile (STS) strengths of the specimen are 14.8, 86.2, and 6.8 MPa, respectively. The flexural (FCR) and tensile (TCR) compression ratios are 0.172 and 0.079, respectively.

TRPM8 promotes hepatocellular carcinoma progression by inducing SNORA55 mediated nuclear-mitochondrial communication.

Transient receptor potential melastatin 8 (TRPM8) play crucial roles in solid tumors such as prostate and breast cancers. But the role of TRPM8 in hepatocellular carcinoma (HCC) and its underlying molecular mechanisms remain largely unknown. In this study, the functional roles of TRPM8 in HCC were systematically investigated for the first time. It was found that the expression level of TRPM8 was significantly upregulated in HCC, which was positively correlated with the worse clinicopathological characteristics. Functional studies revealed that pharmacological inhibition or genetic downregulation of TRPM8 ameliorated hepatocarcinogenesis in vitro and in vivo. Mechanistically, the oncogenic role of TRPM8 in HCC was at least partially achieved by affecting mitochondrial function. TRPM8 could modulate the expression of nucleolar relative molecule-small nucleolar RNA, H/ACA box 55 (SNORA55) by inducing transformation of chromatin structure and histone modification type. These data suggest that as a bridge molecule in TRPM8-triggered HCC, SNORA55 can migrate from nucleus to mitochondria and exert oncogenic role by affecting mitochondria function through targeting ATP5A1 and ATP5B. Herein, we uncovered the potent oncogenic role of TRPM8 in HCC by inducing nuclear and mitochondrial dysfunction in a SNORA55 dependent manner, and provided a potential therapeutic target for HCC.

Investigation of contrast visual acuity with rigid gas permeable contact lenses after penetrating Keratoplasty.

BACKGROUND: To investigate the effects of rigid gas permeable contact lens (RGP-CL) wear on contrast visual acuity in patients after penetrating keratoplasty. METHODS: Nineteen patients (19 eyes), aged 30.45 ± 5.83 years, who had received penetrating keratoplasty and were successfully fitted with RGP-CLs at our hospital from July 2017 to June 2018 were included. Contrast visual acuities at 100%, 25%, and 10% with spectacles and RGP-CLs were analyzed using the Chi-square test. The wavefront aberrations at the anterior surface of the cornea before and 1 month after RGP-CL wear were compared using the matched sample t-test. RESULTS: The mean best spectacle-corrected visual acuities were 0.390 ± 0.135 logMAR, 0.706 ± 0.182 logMAR, and 0.952 ± 0.223 logMAR at the 100%, 25%, and 10% contrast levels, respectively, which were significantly lower than the RGP-CL-corrected visions at the three levels (0.255 ± 0.133 logMAR, 0.488 ± 0.168 logMAR, and 0.737 ± 0.159 logMAR; all P < 0.001). The vision losses with RGP-CLs were 0.231 ± 0.099 logMAR and 0.466 ± 0.094 logMAR at the 25% and 10% contrast levels, respectively. The Zernike spherical aberration Z04 was reduced from 3.734 ± 1.061 µm to 2.622 ± 0.725 µm after wearing the RGP-CLs (P ≤ 0.001). The astigmatism parameters of Z- 22 and Z22 were also reduced from 3.761 ± 2.309 µm and 3.316 ± 2.147 µm to 2.637 ± 1.722 µm and 2.016 ± 1.184 µm, respectively (P < 0.05). CONCLUSION: For post-keratoplasty patients, RGP-CLs can help to improve visual performance, especially low contrast visual acuity. The improvement may be related to the reduction of corneal aberrations, mainly the spherical and astigmatism aberrations.

Control of Cell Size by c-di-GMP Requires a Two-Component Signaling System in the Cyanobacterium Anabaena sp. Strain PCC 7120.

Each bacterial species possesses a specific cell size and morphology, which constitute important and recognizable physical traits. How bacteria maintain their particular cell size and morphology remains an essential question in microbiology. Cyanobacteria are oxygen-evolving photosynthetic prokaryotes. Although monophyletic, these organisms are highly diverse in their cell morphology and cell size. How these physical traits of cyanobacteria are controlled is poorly understood. Here, we report the identification of a two-component signaling system, composed of a histidine kinase CdgK and a response regulator CdgS, involved in cell size regulation in the filamentous, heterocyst-forming cyanobacterium Anabaena sp. PCC 7120. Inactivation of cdgK or cdgS led to reduction of cell length and width with little effect on cell growth capacity. CdgS has a GGDEF domain responsible for the synthesis of the second messenger c-di-GMP. Based on genetic and biochemical studies, we proposed a signaling pathway initiated by CdgK, leading to the phosphorylation of CdgS, and thereby an enhanced enzymatic activity for c-di-GMP synthesis of the latter. The GGDEF domain of CdgS was essential in cell size control, and the reduction of cell size observed in various mutants could be rescued by the expression of a c-di-GMP synthetase from E. coli. These results provided evidence that a minimal threshold of c-di-GMP level was required for maintaining cell size in Anabaena. IMPORTANCE Cyanobacteria are considered the first organisms to produce oxygen on Earth, and their activities shaped the evolution of our ecosystems. Cell size is an important trait fixed early in evolution, with the diversification of micro- and macrocyanobacterial species during the Great Oxidation Event. However, the genetic basis underlying cell size control in cyanobacteria was not understood. Our studies demonstrated that the CdgK-CdgS signaling pathway participates in the control of cell size, and their absence did not affect cell growth. CdgK has multiple domains susceptible to signal input, which are necessary for cell size regulation. This observation suggests that cell size in Anabaena could respond to environmental signals. These studies paved the way for genetic dissection of cell size regulation in cyanobacteria.

Hip centre regression progression: Same equations, better numbers.

Accurate estimation of the hip joint centre (HJC) location is critical for modelling the kinematics and kinetics of the lower limb. Regression equations are commonly used to predict the HJC from anatomical landmarks on the pelvis, such as those published by Tylkowski et al., Andriacchi et al., Bell et al., and Seidel et al. Using a population of 159 CT-segmented pelvises, we assessed the accuracy of these methods as originally reported, and refined their parameters based on our larger cohort. We found the Tylkowski, Bell, and Seidel methods had mean Euclidean errors of 22.5, 26.4, and 17.9 mm, respectively. With new parameters for each method 'back-calculated' from our pelvic population, each method's error was reduced by an average of 69 %, with mean absolute errors of 7.9, 6.6, and 5.9 mm, respectively. For all methods, error has been reduced to below 1 cm, well below published levels for pelvic landmark estimation methods. These results highlight the need to validate and re-calibrate joint centre prediction methods on large, representative datasets to account for natural morphological variations.

Adiponectin receptors activation performs dual effects on regulating myogenesis and adipogenesis of young and aged muscle satellite cells.

OBJECTIVES: Skeletal muscle mass and function deteriorate with ageing. Adiponectin receptors (APNrs), mainly activated by adiponectin, participate in various physiological activities and have varying signalling pathways at different ages. This study aimed to explore whether discrepant performance exists in APNr activation regulating young and aged muscle satellite cells (MUSCs) and whether age-related muscle dysfunction could be alleviated upon APNr activation. METHODS: The gastrocnemius muscle phenotype was observed in male mice aged 2 and 18 months. An APNr agonist (AdipoRon) was used in vitro and in vivo to investigate the changes in cell biological behaviours and whether muscle dysfunction could be retarded after APNr activation. RESULTS: Aged mice exhibited decreased muscle mass and increased fat infiltration. APNr activation inhibited C2C12 cells and young MUSCs (YMUSCs) proliferation but showed no obvious effect on aged MUSCs (AMUSCs). Moreover, APNr activation inhibited the migration of both YMUSCs and AMUSCs. Interestingly, APNr activation hampered the myogenic differentiation but advanced the adipogenic differentiation of YMUSCs, yet exact opposite results were presented in AMUSCs. It was demonstrated that Wnt and PI3K signalling pathways may mediate the phenotypic differences. Furthermore, in vivo experiments verified that APNr activation ameliorated age-related muscle atrophy and excessive fat infiltration. CONCLUSIONS: APNr activation exerted dual effects on the regulation of myogenesis and adipogenesis of YMUSCs and AMUSCs and rescued age-related skeletal muscle dysfunction.

A novel denoising method for CT images based on U-net and multi-attention.

Reducing the radiation dose may lead to increased noise in medical computed tomography (CT), which can adversely affect the radiologists' judgment. Many efforts have been devoted to the denoising of low-dose CT (LDCT) images. However, it is often observed that denoised medical images usually lose some important clinical lesion edge information and may affect doctors' clinical diagnosis. For a denoising neural network, it is expected that the neural network can well retain the detailed features and make the network more anthropomorphic, and to simulate the attention mechanism of observation, being a valuable feature of the thinking process of human brain. Based on U-network (U-Net) and multi-attention mechanism, a novel denoising method for medical CT images is proposed in this study. To obtain different feature information in CT images, three attention modules are proposed in our method. The local attention module is developed to localize the surrounding information of the feature map and calculate each pixel from the context extracted from the feature map. The multi-feature channel attention module can automatically learn and extract features, suppress some invalid information and add different weights to each channel in the feature map according to different tasks. The hierarchical attention module allows the deep neural network to extract a large amount of feature information. This study also introduces an enhanced learning module to learn and retain the detail information in the image by stacking multi-layer convolution layer, batch normalization (BN) layer and activation function layer to increase the network depth. Experimental studies are conducted, and comparisons with the state-of-the-art networks are made, and the results demonstrate that the developed method can effectively remove the noise in CT images and improve the image quality in the evaluation metrics of peak signal to noise ratio (PSNR) and structural similarity (SSIM). Our method achieved 34.7329 of PSNR and 0.9293 of SSIM for σ = 10 on the QIN_LUNG_CT dataset, and achieved 28.9163 of PSNR and 0.8602 of SSIM on the Mayo Clinic LDCT Grand Challenge dataset.

Mutation in a chlorophyll-binding motif of Brassica ferrochelatase enhances both heme and chlorophyll biosynthesis.

The heme branch of tetrapyrrole biosynthesis contributes to the regulation of chlorophyll levels. However, the mechanism underlying the balance between chlorophyll and heme synthesis remains elusive. Here, we identify a dark green leaf mutant, dg, from an ethyl methanesulfonate (EMS)-induced mutant library of Chinese cabbage. The dg phenotype is caused by an amino acid substitution in the conserved chlorophyll a/b-binding motif (CAB) of ferrochelatase 2 (BrFC2). This mutation increases the formation of BrFC2 homodimer to promote heme production. Moreover, wild-type BrFC2 and dBrFC2 interact with protochlorophyllide (Pchlide) oxidoreductase B1 and B2 (BrPORB1 and BrPORB2), and dBrFC2 exhibits higher binding ability to substrate Pchlide, thereby promoting BrPORBs-catalyzed production of chlorophyllide (Chlide), which can be directly converted into chlorophyll. Our results show that dBrFC2 is a gain-of-function mutation contributing to balancing heme and chlorophyll synthesis via a regulatory mechanism in which dBrFC2 promotes BrPORB enzymatic reaction to enhance chlorophyll synthesis.

TRPM8 contributes to liver regeneration via mitochondrial energy metabolism mediated by PGC1α.

Impairment of liver regeneration leads to severe morbidity in acute and chronic severe liver disease. Transient receptor potential melastain 8 (TRPM8) is involved in a variety of processes, including temperature sensing, ion homeostasis, and cell proliferation. However, whether TRPM8 contributes to liver regeneration is still unclear. We assessed the effect and mechanism of TRPM8 in liver regeneration and hepatocyte proliferation in vivo and in vitro. In this study, we found that TRPM8 deficiency impairs liver regeneration in mice. Mechanistically, the results revealed that mitochondrial energy metabolism was attenuated in livers from TRPM8 knockout (KO) mice. Furthermore, we found that TRPM8 contributes to the proliferation of hepatocytes via PGC1α. Taken together, this study shows that TRPM8 contributes to liver regeneration in mice after hepatectomy. Genetic approaches and pharmacological approaches to regulate TRPM8 activity may be beneficial to the promotion of liver regeneration.

The ERα-NRF2 signalling axis promotes bicalutamide resistance in prostate cancer.

BACKGROUND: Bicalutamide is a nonsteroidal antiandrogen widely used as a first-line clinical treatment for advanced prostate cancer (PCa). Although patients initially show effective responses to bicalutamide treatment, resistance to bicalutamide frequently occurs and leads to the development of castration-resistant PCa (CRPC). This research investigated the roles of the oestrogen receptor α (ERα)-nuclear factor E2-related factor 2 (NRF2) signalling pathway in bicalutamide resistance in PCa cells. METHODS: We performed bioinformatic analysis and immunohistochemical staining on normal and cancerous prostate tissue to evaluate ERα and NRF2 expression and their correlation. Gene expression and localization in PCa cell lines were further investigated using real-time reverse transcription PCR/Western blotting and immunofluorescence staining. We treated PCa cells with the ER inhibitor tamoxifen and performed luciferase reporter assays and chromatin immunoprecipitation (ChIP) assays to understand ERα-dependent NRF2 expression. Overexpression and knockdown of ERα and NRF2 were used to explore the potential role of the ERα-NRF2 signalling axis in bicalutamide resistance in PCa cells. RESULTS: We found that the expression of ERα and NRF2 was positively correlated and was higher in human CRPC tissues than in primary PCa tissues. Treatment with oestrogen or bicalutamide increased the expression of ERα and NRF2 as well as NRF2 target genes in PCa cell lines. These effects were blocked by pretreatment with tamoxifen. ChIP assays demonstrated that ERα directly binds to the oestrogen response element (ERE) in the NRF2 promoter. This binding led to increased transcriptional activity of NRF2 in a luciferase reporter assay. Activation of the ERα-NRF2 signalling axis increased the expression of bicalutamide resistance-related genes. Inhibition of this signalling axis by knockdown of ERα or NRF2 downregulated the expression of bicalutamide resistance-related genes and inhibited the proliferation and migration of PCa cells. CONCLUSIONS: We demonstrated the transcriptional interaction between ERα and NRF2 in CRPC tissues and cell lines by showing the direct binding of ERα to the ERE in the NRF2 promoter under oestrogen treatment. Activation of the ERα-NRF2 signalling axis contributes to bicalutamide resistance in PCa cells, suggesting that the ERα-NRF2 signalling axis is a potential therapeutic target for CRPC. Video Abstract.