[Effects of Straw and Fertilizer Managements on Nitrogen Loss in Rice Cultivation in Taihu Lake Basin].

Nitrogen loss from rice systems is an important source of agricultural non-point source pollution. Many studies revolve around reducing the rate of nitrogen fertilizer application. However, studies examining the characteristics of nitrogen loss in multiple loss paths （runoff, leaching, and lateral seepage） under different straw and fertilizer managements are lacking. Therefore, a study was carried out based on a rice field planted for more than 20 years with straw continuously returned to the field for more than 5 years in Taihu lake basin. The effects of straw and fertilizer managements on nitrogen loss in different paths during the whole growth period of rice were studied. Moreover, straw and fertilizer managements were evaluated by their production suitability and environmental friendliness based on crop yield, nitrogen use efficiency, and nitrogen loss. The results showed that straw removal from the field increased the response sensitivity of nitrogen accumulation in plant tissue to nitrogen application. The nitrogen loss in the rice season was 9-17 kg·hm-2, accounting for 5%-7% of the nitrogen application rate. Straw removal increased the risk of nitrogen loss when soaking water discharged. Straw returning could decrease the nitrogen loss by more than 15%, though the effect of straw on nitrogen loss via lateral seepage was not clear. Furthermore, the suitable substitution of organic fertilizer （30% in this study） could respectively reduce the amount of nitrogen loss via runoff, leaching, and lateral seepage by 16%, 26%, and 37% compared with the fertilizer application under the same nitrogen gradient. In conclusion, the implementation of straw returning and fertilizer type optimization measures effectively reduced the nitrogen loss for unit weight of rice production and realized the balance between agricultural production and environmental protection.

[Vertical Distribution Characteristics and Driving Factors of Bacterioplankton and Nitrogen Phosphorus Cycle Genes in Danjiangkou Reservoir].

Danjiangkou Reservoir is a critical water source for the South-to-North Water Diversion Project, which harbors a diverse bacterioplankton community with varying depths, and the understanding of its nitrogen and phosphorus cycle and associated driving factors remains limited. In this study, we selected five ecological sites within Danjiangkou Reservoir and conducted metagenomics analysis to investigate the vertical distribution of bacterioplankton communities in the surface, middle, and bottom layers. Furthermore, we analyzed and predicted the function of nitrogen and phosphorus cycles, along with their driving factors. Our findings revealed the dominance of Proteobacteria, Actinobacteria, and Planctomycetes in the Danjiangkou Reservoir. Significant differences were observed in the structure of bacterioplankton communities across different depths, with temperature （T）, oxidation-reduction potential （ORP）, dissolved oxygen （DO）, and Chla identified as primary factors influencing the bacterioplankton composition. Analysis of nitrogen cycle functional genes identified 39 genes, including gltB, glnA, gltD, gdhA, NRT, etc., which were involved in seven main pathways, encompassing nitrogen fixation, nitrification, denitrification, and dissimilatory nitrate reduction. Phosphorus cycle function gene analysis identified 54 genes, including pstS, ppx-gppA, glpQ, ppk1, etc., primarily participating in six main pathways, including organic P mineralization, inorganic P solubilization, and regulatory. Cluster analysis indicated that different depths were significant factors influencing the composition and abundance of nitrogen and phosphorus cycle functional genes. The composition and abundance of nitrogen and phosphorus cycle functional genes in the surface and bottom layers differed and were generally higher than those in the middle layer. Deinococcus, Hydrogenophaga, Limnohabitans, Clavibacter, and others were identified as key species involved in the nitrogen and phosphorus cycle. Additionally, we found significant correlations between nitrogen and phosphorus cycle functional genes and environmental factors such as DO, pH, T, total dissolved solids （TDS）, electrical conductivity （EC）, and Chla. Furthermore, the content of these environmental factors exhibited depth-related changes in the Danjiangkou Reservoir, resulting in a distinct vertical distribution pattern of bacterioplankton nitrogen and phosphorus cycle functional genes. Overall, this study sheds light on the composition, function, and influencing factors of bacterioplankton communities across different layers of Danjiangkou Reservoir, offering valuable insights for the ecological function and diversity protection of bacterioplankton in this crucial reservoir ecosystem.

GPAT3 is a potential therapeutic target to overcome sorafenib resistance in hepatocellular carcinoma.

Background: Sorafenib is the standard treatment for advanced hepatocellular carcinoma (HCC), but acquired resistance during the treatment greatly limits its clinical efficiency. Lipid metabolic disorder plays an important role in hepatocarcinogenesis. However, whether and how lipid metabolic reprogramming regulates sorafenib resistance of HCC cells remains vague. Methods: Sorafenib resistant HCC cells were established by continuous induction. UHPLC-MS/MS, proteomics, and flow cytometry were used to assess the lipid metabolism. ChIP and western blot were used to reflect the interaction of signal transducer and activator of transcription 3 (STAT3) with glycerol-3-phosphate acyltransferase 3 (GPAT3). Gain- and loss-of function studies were applied to explore the mechanism driving sorafenib resistance of HCC. Flow cytometry and CCK8 in vitro, and tumor size in vivo were used to evaluate the sorafenib sensitivity of HCC cells. Results: Our metabolome data revealed a significant enrichment of triglycerides in sorafenib-resistant HCC cells. Further analysis using proteomics and genomics techniques demonstrated a significant increase in the expression of GPAT3 in the sorafenib-resistant groups, which was found to be dependent on the activation of STAT3. The restoration of GPAT3 resensitized HCC cells to sorafenib, while overexpression of GPAT3 led to insensitivity to sorafenib. Mechanistically, GPAT3 upregulation increased triglyceride synthesis, which in turn stimulated the NF-κB/Bcl2 signaling pathway, resulting in apoptosis tolerance upon sorafenib treatment. Furthermore, our in vitro and in vivo studies revealed that pan-GPAT inhibitors effectively reversed sorafenib resistance in HCC cells. Conclusions: Our data demonstrate that GPAT3 elevation in HCC cells reprograms triglyceride metabolism which contributes to acquired resistance to sorafenib, which suggests GPAT3 as a potential target for enhancing the sensitivity of HCC to sorafenib.

SLC10A5 deficiency causes hypercholanemia.

BACKGROUND AND AIMS: Solute Carrier Family 10 Member 5 ( SLC10A5 ) is a member of SLC10, comprising transporters of bile acids, steroidal hormones and other substrates, but its function remains unclear. The aim of the current investigation was to clarify its function in the metabolism of bile acid and hypercholanemia. APPROACH: Whole-exome sequencing and Sanger sequencing were used to identify and confirm the variant in the subjects of hypercholanemia. CRISPR/Cas9-mediated genome engineering was used to establish the knockout and point mutation mice. Primary mouse hepatocytes were isolated and cell lines were cultured. SLC10A5 was silenced by siRNA and overexpressed by wild-type and mutant plasmids. The fluorescent bile acid derivative was used for bile acid uptake assay. Bile acids were assessed with ultra-performance liquid chromatography tandem mass spectrometry. RESULTS: A heterozygous variant SLC10A5 : c.994_995del (p.D332X) was identified in subjects with elevated total bile acid or altered bile acid profiles. Bile acids were increased in the serum and liver of knockout and point mutation mice. The expressions of FXR and SHP , regulators involved in the negative feedback of bile acid synthesis, were downregulated, while the bile acid synthesis genes CYP8B1 and CYP7A1 were upregulated in both gene-edited mice. Both the wild and mutant SLC10A5 protein were localized on the plasma membrane. Knockdown, knockout or targeted mutation of SLC10A5 led to the inhibition of bile acid uptake by cell lines and primary mouse hepatocyte. CONCLUSION: SLC10A5 is involved in the uptake of bile acid and its deficiency causes hypercholanemia.

Surface Coating of NCM523 Cathode Electrodes by the Difunctional Block Copolymer/Lithium Salt Composites.

Nickel-rich layered oxide cathodes, such as LiNi0.5Co0.2Mn0.3O2 (NCM523), are prevalent in high-power batteries owing to their high energy density. However, these cathodes suffer from undesirable side reactions occurring at the cathode/liquid electrolyte interface, leading to inferior interface stability and poor cycle life. To address these issues, herein, an amphiphilic diblock copolymer poly(dimethylsiloxane)-block-poly(acrylic acid) (PDMS-b-PAA) along with lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) is utilized for modifying the electrode surface. This modification causes a thin and stable cathode-electrolyte interface (CEI) on the surface of NCM523 particles, as evidenced by XPS, TEM, and EIS analysis. The introduction of this modified interface successfully suppresses the capacity fading of NCM523. After 200 cycles at a rate of 1.0 C, the capacity of the modified NCM523 cathode is 108.7 mAh g-1, with a capacity retention of 82.8%, while the control samples without the polymer modification display a capacity retention of 72.7%. These results outline the distinct advantage of electrode surface modification with diblock copolymers/LiTFSI for the stabilization of Ni-rich layered oxide cathodes.

The Diagnostic Value of Conventional MRI Combined With Diffusion-Weighted Imaging in Microprolactinomas.

BACKGROUND: Turbo spin-echo (TSE) diffusion-weighted imaging (DWI) sequences may reduce susceptibility artifacts and image distortion in sellar region, allowing better visualization of small pituitary lesions, and may be used to assist in the diagnosis of pituitary microadenomas. PURPOSE: To explore the application value of conventional MRI combined with DWI sequences in the diagnosis of microprolactinomas. STUDY TYPE: Prospective. POPULATION: Thirty-four patients in microprolactinomas with high signal on T2WI (HT2-PRL) group (34 females, 34 ± 7 years), 26 patients in microprolactinomas with equal or low signal on T2WI (ELT2-PRL) group (21 females, 34 ± 7 years), 35 patients with hyperprolactinemia (33 females, 32 ± 8 years), and 30 normal controls (25 females, 31 ± 7 years). FIELD STRENGTH/SEQUENCE: TSE sequence at 3 T. ASSESSMENT: Pituitary morphological parameters (such as length and volume), dynamic contrast-enhanced parameters (such as time to peak) and the apparent diffusion coefficients (ADCs) were measured in each group. STATISTICAL TESTS: ANOVA and Mann-Whitney U test were used to compare parameters among groups. Spearman's coefficient was used to evaluate the correlation between variables. ROC analysis was used to assess the performance of the parameters. A P-value <0.05 was considered statistically significant. RESULTS: The pituitary volume of patients in HT2-PRL, ELT2-PRL, and hyperprolactinemia group were 831.00 (747.60, 887.60), 923.63 ± 219.34, and 737.20 (606.40, 836.80) mm3. The pituitary maximum height in these three groups were 7.03 (6.43, 8.63), 8.03 ± 1.41, and 6.63 ± 1.28 mm, respectively. The lesion ADC value was significantly correlated with T2 relative signal intensity (the ratio of signal intensity of microprolactinoma or anterior pituitary to left temporal cortex) (r = 0.821). Compared with patients with hyperprolactinemia, the diagnostic efficacy of T2 relative signal intensity was higher in HT2-PRL group, with an AUC of 0.954, whereas the ADC value was the highest in ELT2-PRL group, with an AUC of 0.924. CONCLUSION: DWI sequences can be used to assist in the diagnosis of pituitary microadenomas. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Effect of NLRP3 gene knockdown on pyroptosis and ferroptosis in diabetic cardiomyopathy injury.

Diabetic cardiomyopathy (DCM) is a chronic disease caused by diabetes mellitus, which is recognized as a worldwide challenging disease. This study aimed to investigate the role and the potential mechanism of knocking down the NACHT-, LRR- and PYD domains-containing protein 3 (NLRP3), an inflammasome associated with onset and progression of various diseases, on high glucose or diabetes -induced cardiac cells pyroptosis and ferroptosis, two regulated non-necrosis cell death modalities discovered recent years. In the present study, both in vivo and in vitro studies were conducted simultaneously. Diabetic rats were induced by 55 mg/kg intraperitoneal injection of streptozotocin (STZ). Following the intraperitoneal injection of MCC950 (10 mg/kg), On the other hand, the DCM model in H9C2 cardiac cells was simulated with 35 mmol/L glucose and a short hairpin RNA vector of NLRP3 were transfected to cells. The results showed that in vivo study, myocardial fibers were loosely arranged and showed inflammatory cell infiltration, mitochondrial cristae were broken and the GSDMD-NT expression was found notably increased in the DM group, while the protein expressions of xCT and GPX4 was significantly decreased, both of which were reversed by MCC950. High glucose reduced the cell viability and ATP level in vitro, accompanied by an increase in LDH release. All of the above indicators were reversed after NLRP3 knockdown compared with the HG treated alone. Moreover, the protein expressions of pyroptosis- and ferroptosis-related fators were significantly decreased or increased, consistent with the results shown by immunofluorescence. Furthermore, the protective effects of NLRP3 knockdown against HG were reversed following the mtROS agonist rotenone (ROT) treatment. In conclusion, inhibition of NLRP3 suppressed DM-induced myocardial injury. Promotion of mitochondrial ROS abolished the protective effect of knockdown NLRP3, and induced the happening of pyroptosis and ferroptosis. These findings may present a novel therapeutic underlying mechanism for clinical diabetes-induced myocardial injury treatment.

Exploring potential predictive biomarkers through historical perspectives on the evolution of systemic therapies into the emergence of neoadjuvant therapy for the treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC), a type of liver cancer, ranks as the sixth most prevalent cancer globally and represents the third leading cause of cancer-related deaths. Approximately half of HCC patients miss the opportunity for curative treatment and are then limited to undergoing systemic therapies. Currently, systemic therapy has entered the era of immunotherapy, particularly with the advent of immune-checkpoint inhibitors (ICIs), which have significantly enhanced outcomes for patients with advanced HCC. Neoadjuvant treatment for HCC has become a possibility-findings from the IMbrave 050 trial indicated that ICIs offer the benefit of recurrence-free survival for high-risk HCC patients post-resection or local ablation. However, only a small fraction of individuals benefit from systemic therapy. Consequently, there is an urgent need to identify predictive biomarkers for treatment response and outcome assessment. This study reviewed the historical progression of systemic therapy for HCC, highlighting notable therapeutic advancements. This study examined the development of systemic therapies involving conventional drugs and clinical trials utilized in HCC treatment, as well as potential predictive biomarkers for advanced and/or locally advanced HCC. Various studies have revealed potential biomarkers in the context of HCC treatment. These include the association of dendritic cells (DCs) with a favorable response to neoadjuvant therapy, the presence of enriched T effector cells and tertiary lymphoid structures, the identification of CD138+ plasma cells, and distinct spatial arrangements of B cells in close proximity to T cells among responders with locally advanced HCC receiving neoadjuvant cabozantinib and nivolumab treatment. Furthermore, pathological response has been associated with intratumoral cellular triads consisting of progenitor CD8+ T cells and CXCL13+ CD4+ T helper cells surrounding mature DCs in patients receiving neoadjuvant cemiplimab for resectable HCC. Despite no widely recognized predictive biomarkers for HCC individualized treatment, we believe neoadjuvant trials hold the most promise in identifying and validating them. This is because they can collect multiple samples from resectable HCC patients across stages, especially with multi-omics, bridging preclinical and clinical gaps.

PyBox-La(OTf)3-Catalyzed Enantioselective Diels-Alder Cycloadditions of 2-Alkenoylpyridines with Cyclopentadiene.

The PyBox-La(OTf)3-catalyzed enantioselective Diels-Alder cycloaddition of 2-alk-2-enoylpyridines with cyclopentadiene is realized, producing enantiopure disubstituted norbornenes, which possess four contiguous stereocenters and are biologically relevant structures in up to 92:8 dr and 99:1 er.

Evolution of topological singularities below the light line in momentum space.

Polarization singularities that exist in momentum space have brought new opportunities in various fields such as enhanced optical nonlinearity, structured laser sources, and light field manipulation. However, previous researches have predominantly focused on the polarization singularities above the light line, because they have no leakage and are referred to bound states in the continuum. Here, by extending the polarization fields to Fourier components of the evanescent field on a dielectric metasurface, polarization singularities of different Fourier orders are discovered below the light line. When continuously changing the geometrical parameters of the metasurface, a Fourier order transition process of the polarization singularity is observed through the bandgap closing at the boundary of the Brillouin zone, which finally leads to the annihilation of two singularities with opposite topological charges below the light line. These findings expand the understanding of polarization singularities in the near-field region and may find applications in light field manipulation and light-matter interaction.

Investigation on the performance of photonics-aided W-band millimeter-wave wireless transmission.

W-band (75-110 GHz) is a potential radio frequency band to provide long-distance wireless links for mobile data transmission. This paper proposes and experimentally demonstrates high-speed wireless transmission at W-band using photonics-aided method, including optical heterodyne, photonics-aided down-conversion without RF oscillator and coherent detection. A comparison between the photonics-aided method and the conventional electronic method employing solid-state electronic devices is conducted for the first time. The photonics-aided method is shown to offer advantages such as lower harmonic components, spur, reduced nonlinearity, and no local oscillator leakage, results in a 2.5 dB better performance of the photonic-aided W-band mm-wave transmitter compared to the electronic one. In the terms of receiver, the photonics-aided method can surpass the electronic method, with the help of larger electro-optical modulator bandwidth and lower drive voltage in the photonic down-conversion stage. Ultimately, using the photonics-aided method, a recorded equivalent transmission distance of 29 km@84 GHz and 45km@75.6GHz is achieved respectively for 1Gbaud QPSK signal.

PGD2/DP1 axis promotes liver regeneration by secreting Wnt2 in Kupffer cells in mice.

BACKGROUND AND AIMS: The liver possesses a remarkable regenerative capacity in response to injuries or viral infections. Various growth factors and cytokines are involved in regulating liver regeneration. Prostaglandin (PG) D2, a pro-resolution lipid mediator, is the most abundant hepatic prostanoid. However, the role of PGD2 in the injury-induced liver regeneration remains unclear. APPROACH AND RESULTS: Two-thirds partial hepatectomy (70% PH), massive hepatectomy (85% resection), and carbon tetrachloride-induced chronic injury were performed in mice to study the mechanisms of live regeneration. Hepatic PGD2 production was elevated in mice after PH. Global deletion of D prostanoid receptor (DP) 1, but not DP2, slowed PH-induced liver regeneration in mice, as evidenced by lower liver weight to body weight ratio, less Ki67+ hepatocyte proliferation, and G2/M phase hepatocytes. Additionally, DP1 deficiency specifically in resident Kupffer cells (KCs), and not in endothelial cells or hepatic stellate cells, retarded liver regeneration in mice post-PH. Conversely, the overexpression of exogenous DP1 in KCs accelerated liver regeneration in mice. Mechanistically, DP1 activation promoted Wnt2 transcription in a PKA/CREB-dependent manner in resident KCs and mediated hepatocyte proliferation through Frizzled8/ß-catenin signaling. Adeno-associated virus vector serotype 8 (AAV8)-mediated Frizzled8 knockdown in hepatocytes attenuated accelerated liver regeneration in KC-DP1 transgenic mice post-PH. Treatment with the DP1 receptor agonist BW245C promotes PH-induced liver regeneration in mice. CONCLUSIONS: DP1 activation mediates crosstalk between KCs and hepatocytes through Wnt2, and facilitates liver regeneration. Hence, DP1 may serve as a novel therapeutic target in acute and chronic liver diseases.

[Damage and changes in expression of autophagy related factors LC3 and p62 of condylar cartilage in fluorosis mouse].

PURPOSE: To study the damage and the expression of LC3 and p62 of condylar cartilage in fluorosis mouse. METHODS: Thirty 4-week-old male C57BL/6 mice were randomly divided into control group and the experimental group with 15 animals in each group. The control group received regular drinking water and the experimental group received a fluoride concentration of 75 mg/L drinking water for 8 weeks. The structure of condylar cartilage was observed through modified safranine O-fast green FCF cartilage stain kit. Immunohistochemistry was used to detect the expression of MMP-13, type Ⅱ collagen and LC3 and p62. Two-way analysis of variance test was conducted for analysis of semi-quantitative results of immunohistochemistry using SPSS 22.0 software package. RESULTS: Compared with the control group, the fibrocartilage layer of the experimental group became thinner, the condrocytes were smaller, and the staining became deeper.Immunohistochemistry results showed that the expression of MMP-13 and LC3 increased; the expression of type Ⅱ collagen and p62 decreased in the experimental group. CONCLUSIONS: There was degeneration of the condylar cartilage and autophagy in mice with drinking water containing 75 mg/L fluoride.

Does a single session of transcranial direct current stimulation enhance both physical and psychological performance in national- or international-level athletes? A systematic review.

Some studies showed that a single session of transcranial direct current stimulation (tDCS) has the potential of modulating motor performance in healthy and athletes. To our knowledge, previously published systematic reviews have neither comprehensively investigated the effects of tDCS on athletic performance in both physical and psychological parameters nor investigated the effects of tDCS on high-level athletes. We examined all available research testing a single session of tDCS on strength, endurance, sport-specific performance, emotional states and cognitive performance for better application in competition and pre-competition trainings of national- or international-level athletes. A systematic search was conducted in PubMed, Web of Science, EBSCO, Embase, and Scopus up until to June 2023. Studies were eligible when participants had sports experience at a minimum of state and national level competitions, underwent a single session of tDCS without additional interventions, and received either sham tDCS or no interventions in the control groups. A total of 20 experimental studies (224 participants) were included from 18 articles. The results showed that a single tDCS session improved both physical and psychological parameters in 12 out of the 18 studies. Of these, six refer to the application of tDCS on the motor system (motor cortex, premotor cortex, cerebellum), five on dorsolateral prefrontal cortex and two on temporal cortex. The most sensitive to tDCS are strength, endurance, and emotional states, improved in 67%, 75%, and 75% of studies, respectively. Less than half of the studies showed improvement in sport-specific tasks (40%) and cognitive performance (33%). We suggest that tDCS is an effective tool that can be applied to competition and pre-competition training to improve athletic performance in national- or international-level athletes. Further research would explore various parameters (type of sports, brain regions, stimulation protocol, athlete level, and test tasks) and neural mechanistic studies in improving efficacy of tDCS interventions. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022326989, identifier CRD42022326989.

Typical emerging contaminants in sewage treatment plant effluent, and related watersheds in the Pearl River Basin: Ecological risks and source identification.

Emerging contaminants pose a potential risk to aquatic ecosystems in the Pearl River Basin, China, owing to the high population density and active industry. This study investigated samples from eight sewage treatment plants, and five surface water bodies of related watersheds. To screen the risk of emerging contaminants (ECs), and clarify their sources, this study calculated the risk quotient of detected chemical and performed source identification/apportionment using the positive matrix factorization method. In total, 149 organic pollutants were identified. Pharmaceuticals showed significant concentrations in sewage treatment plant samples (120.87 ng/L), compared with surface water samples (1.13 ng/L). The ecological risk assessment identified three chemicals with a heightened risk to aquatic organisms: fipronil sulfide, caffeine, and roxithromycin. Four principal sources of contaminants were identified: pharmaceutical wastewater, domestic sewage, medical effluent, and agricultural runoff. Pharmaceutical wastewater was the primary contributor (60.4 %), to the cumulative EC concentration and to ECs in sewage treatment plant effluent. Agricultural drainage was the main source of ECs in surface water. This study provides a strategy to obtain comprehensive information on the aquatic risks and potential sources of EC species in areas affected by artificial activities, which is of substantial importance to pollutant management and control.

Histamine promotes mouse decidualization through stimulating epithelial amphiregulin release.

Accumulating evidence shows that inflammation is essential for embryo implantation and decidualization. Histamine, a proinflammatory factor that is present in almost all mammalian tissues, is synthesized through decarboxylating histidine by histidine decarboxylase (HDC). Although histamine is known to be essential for decidualization, the underlying mechanism remains undefined. In the present study, histamine had no obvious direct effects on in vitro decidualization in mice. However, the obvious differences in HDC protein levels between day 4 of pregnancy and day 4 of pseudopregnancy, as well as between delayed and activated implantation, suggested that the blastocyst may be involved in regulating HDC expression. Furthermore, blastocyst-derived tumor necrosis factor α (TNFα) significantly increased HDC levels in the luminal epithelium. Histamine increased the levels of amphiregulin (AREG) and disintegrin and metalloproteinase domain-containing protein 17 (ADAM17) proteins, which was abrogated by treatment with famotidine, a specific histamine type 2 receptor (H2R) inhibitor, or by TPAI-1 (a specific inhibitor of ADAM17). Intraluminal injection of urocanic acid (HDC inhibitor) on day 4 of pregnancy significantly reduced the number of implantation sites on day 5 of pregnancy. TNFα-stimulated increases in HDC, AREG and ADAM17 protein levels was abrogated by urocanic acid, a specific inhibitor of HDC. Additionally, AREG treatment significantly promoted in vitro decidualization. Collectively, our data suggests that blastocyst-derived TNFα induces luminal epithelial histamine secretion, and histamine increases mouse decidualization through ADAM17-mediated AREG release.

[Identification of the binding proteins of organic acid metabolites by matrix thermal shift assay].

Organic acid metabolites exhibit acidic properties. These metabolites serve as intermediates in major carbon metabolic pathways and are involved in several biochemical pathways, including the tricarboxylic acid (TCA) cycle and glycolysis. They also regulate cellular activity and play crucial roles in epigenetics, tumorigenesis, and cellular signal transduction. Knowledge of the binding proteins of organic acid metabolites is crucial for understanding their biological functions. However, identifying the binding proteins of these metabolites has long been a challenging task owing to the transient and weak nature of their interactions. Moreover, traditional methods are unsuitable for the structural modification of the ligands of organic acid metabolites because these metabolites have simple and similar structures. Even minor structural modifications can significantly affect protein interactions. Thermal proteome profiling (TPP) provides a promising avenue for identifying binding proteins without the need for structural modifications. This approach has been successfully applied to the identification of the binding proteins of several metabolites. In this study, we investigated the binding proteins of two TCA cycle intermediates, i.e., succinate and fumarate, and lactate, an end-product of glycolysis, using the matrix thermal shift assay (mTSA) technique. This technique involves combining single-temperature (52 ℃) TPP and dose-response curve analysis to identify ligand-binding proteins with high levels of confidence and determine the binding affinity between ligands and proteins. To this end, HeLa cells were lysed, followed by protein desalting to remove endogenous metabolites from the cell lysates. The desalted cell lysates were treated with fumarate or succinate at final concentrations of 0.004, 0.04, 0.4, and 2 mmol/L in the experimental groups or 2 mmol/L sodium chloride in the control group. Considering that the cellular concentration of lactate can be as high as 2-30 mmol/L, we then applied lactate at final concentrations of 0.2, 1, 5, 10, and 25 mmol/L in the experimental groups or 25 mmol/L sodium chloride in the control group. Using high-sensitivity mass spectrometry coupled with data-independent acquisition (DIA) quantification, we quantified 5870, 5744, and 5816 proteins in succinate, fumarate, and lactate mTSA experiments, respectively. By setting stringent cut-off values (i.e., significance of changes in protein thermal stability (p-value)<0.001 and quality of the dose-response curve fitting (square of Pearson's correlation coefficient, R2)>0.95), multiple binding proteins for these organic acid metabolites from background proteins were confidently determined. Several known binding proteins were identified, notably fumarate hydratase (FH) as a binding protein for fumarate, and α-ketoglutarate-dependent dioxygenase (FTO) as a binding protein for both fumarate and succinate. Additionally, the affinity data for the interactions between these metabolites and their binding proteins were obtained, which closely matched those reported in the literature. Interestingly, ornithine aminotransferase (OAT), which is involved in amino acid biosynthesis, and 3-mercaptopyruvate sulfurtransferase (MPST), which acts as an antioxidant in cells, were identified as lactate-binding proteins. Subsequently, an orthogonal assay technique developed in our laboratory, the solvent-induced precipitation (SIP) technique, was used to validate the mTSA results. SIP identified OAT as the top target candidate, validating the mTSA-based finding that OAT is a novel lactate-binding protein. Although MPST was not identified as a lactate-binding protein by SIP, statistical analysis of MPST in the mTSA experiments with 10 or 25 mmol/L lactate revealed that MPST is a lactate-binding protein with a high level of confidence. Peptide-level empirical Bayes t-tests combined with Fisher's exact test also supported the conclusion that MPST is a lactate-binding protein. Lactate is structurally similar to pyruvate, the known binding protein of MPST. Therefore, assuming that lactate could potentially occupy the binding site of pyruvate on MPST. Overall, the novel binding proteins identified for lactate suggest their potential involvement in amino acid synthesis and redox balance regulation.

Adverse outcome pathway-based approach to reveal the mechanisms of skin sensitization and long-term aging effects of chlorothalonil.

Chlorothalonil (CHT) is a widely used antifungal agent and is reported to be a sensitizer that can cause allergic contact dermatitis (ACD). ACD initiation is associated with various innate immune cell contributions and is usually accompanied by persistent inflammation, which is a potential contributing factor to skin damage. However, detailed information on the mechanisms by which CHT induces skin sensitization and damage is still insufficient. This study focused on investigating the possible sensitization process and mechanism of CHT and the adverse effects of repeated CHT exposure. CHT activates dendritic cells and promotes the proliferation of lymph cells in the skin sensitization phase, causing severe inflammation. Keratinocytes activate the NLRP3 inflammasome pathway to cause inflammation during CHT treatment, and macrophages also secrete inflammatory cytokines. In addition, CHT-induced inflammation triggered skin wrinkles, decreased epidermal thickness and decreased collagen. Cell experiments also showed that repeated exposure to CHT led to cell proliferation inhibition and senescence, and CHT-induced autophagy dysfunction was not only the reason for inflammation but also for senescence. This study defined the possible process through which CHT is involved in the skin sensitization phase and elucidated the mechanism of CHT-induced inflammation in innate immune responses. We also determined that repeated CHT exposure caused persistent inflammation, ultimately leading to skin aging.

Changes in visual performance after implantation of different intraocular lenses.

AIM: To evaluate the trending visual performance of different intraocular lenses (IOLs) over time after implantation. METHODS: Ninety-one patients received cataract surgery with implantations of monofocal (Mon) IOLs, segmental refractive (SegRef) IOLs, diffractive (Dif) IOLs, and extended-depth-of-focus (EDoF) IOLs were included. The aberrations and optical quality collected with iTrace and OQAS within postoperative 6mo were followed and compared. RESULTS: Most of the visual parameters improved over the postoperative 6mo. The postoperative visual acuity (POVA) of the Mon IOL, SegRef IOL, and EDoF IOL groups achieved relative stability in earlier states compared with the Dif IOL group. Nevertheless, the overall visual performance of the 3 IOLs continued to upturn in small extents within the postoperative 6mo. The optical quality initially improved in the EDoF IOL group, then in the Mon IOL, SegRef IOL, and Dif IOL groups. POVA and objective visual performance of the Mon IOL and EDoF IOL groups, as well as POVA and visual quality of the Dif IOL group, improved in the postoperative 1mo and stabilized. Within the postoperative 6mo, gradual improvements were observed in the visual acuity and objective visual performance of the SegRef IOL group, as well as in the postoperative optical quality of the Dif IOL group. CONCLUSION: The visual performance is different among eyes implanted with different IOLs. The findings of the current study provide a potential reference for ophthalmologists to choose suitable IOLs for cataract patients in a personalized solution.